abril 2017 - DERMAGIC EXPRESS / Dermatologia y Bibliografia - Dermatology & bibliography DERMAGIC EXPRESS / Dermatologia y Bibliografia - Dermatology & bibliography: abril 2017

domingo, 30 de abril de 2017

THE NEW MEDICINE AND CANCER. / LA NUEVA MEDICINA Y EL CANCER

The New Medicine, A New vision to Treat Cancer. ! 

 

La Nueva Medicina, Una Nueva vision para tratar el Cancer. !

 


 

 


EDITORIAL ENGLISH 
=======================
Hello friends of the network, DERMAGIC EXPRESS brings you a very interesting topic today and perhaps not known by many of you: THE NEW MEDICINE AND CANCER, by DR RYKE GEERD HAMER. born in Frisia Germany in 1935.

Dr. Hamer at 19 years of age passes the state test in Alemenia to study medicine, in 1.961 he obtains the degree of Dr. in Medicine, in 1.972 he specializes in INTERNAL MEDICINE. At 20 years of  age get married with Sigrid Oldenburg, also medicine student in Germany. In addition to obtaining the Diploma of Internal Medicine, he also obtained the RADIOLOGIST, studying ANGIOMETRY of CEREBRAL TUMORS.

The life of this Dr. who lives today (82 years) changed radically on August 18, 1978, when his son Dirk Hamer, 19, was hit by a bullet at a party, dying 4 months after the 7th of December. 1.978.

Four months later, Dr. HAMER developed  TESTIS CANCER,  his wife also relapsed from cancerous diseases and died of heard attack in 1.985.

The Death of His son and the development of cancers in him and his wife led him to investigate this fact and issue the HYPOTHESIS that both the CANCER of him and his wife MAY BE RELATED to the GREAT CONFLICT that they lived by the great event Who lived.

His studies and investigations led him to formulate THE IRON LAW OF CANCER, which is the basis of the NEW MEDICINE. In 1981 he presented the thesis on his "DISCOVERY", and the jury unexpectedly denied the work and placed him before the possibility of leaving the Thesis or his PROFESSION of MEDICAL.

In 1.982 The University of TUBINGEN, returns his work on THE PSYCHOLOGY AND THE CANCER without having verified it. In 1.986 a judicial process is applied to CONDEMN to Dr. Hamer and to prohibit the exercise of Medicine for "DO NOT WANT TO LEAVE HIS WORK ABOUT THE IRON LAW OF CANCER" he was barred from attending patients.

In 1.990 Dr. Hamer is declared "INCOMPETENT" regarding the treatment of CANCER. In 1.994, 13 years after the presentation of his work, it is denied the verification of the same. In 1.997, May 21 Dr. Hamer was arrested and after spending time in jail, he was released and went to SPAIN, where he resides and lives now.

His Work on the CANCER'S IRON LAW was verified at the University of VIena on December 9, 1988.

I am telling you this HISTORY so that you understand it, and why in MODERN AND CIVILIZED WORLD. "Supposedly, in which we live, a Dr. asks the" ALTERNATIVE "that CANCER is related to psychic" EVENTS ", based on his own experience, His study and investigation AND IS PERSECUTED LIKE A CRIMINAL.

To summarize,  Dr. Hamer "THROW AWAY" all classical medical concepts about CANCER and raises THE NEW MEDICINE as an alternative: CANCER IS PRODUCED BY A GREAT CONFLICT which provokes the disordered proliferation of the cells, once it has passed, it stops the proliferation and The same body is regenerated.

Here I leave you the ALL the review of Dr. Hamer, his Biography and the explanation with graphs on his work. By the way I found on the web a book called THE BIONEUROEMOTION, BASIC LESSONS  by ENRIC CORBERA and MONSERRAT BATLLo, which deals with this topic.

BIONEUROEMOTION studies the correlation between the unconscious emotions triggered by situations that the individual lives as an IMPACT, their expression and location at the level of the nervous system and the changes it causes in their biology, a theme highly related to Dr. Hamer's NEW MEDICINE.

Surprisingly FIND that the DERMAGIC EXPRESS is in the bibliographical references of the book, there I put the photo. Once again I feel grateful and proud to contribute to SPREAD the knowledge in the world, that was the reason for this publication that I THROW TO THE NET on October 2, 2.002 and I am RELEASING today, for patients with CANCER.


In 2.003 Dr. Hamer tried to patent the name of NEW MEDICINE, and could not, later I call it THE GERMAN NEW MEDICINE, finally achieving the patent and copyright.

In 1994, Hamer expanded his system to the 5 biological laws that cover all diseases in the entire field of medicine, based on research of 20,000 cases.

Dr. Hamer still lives and continues to teach courses and conferences, certainly the last ones on April 22 and 23, 2017 in TORONTO, canada, here his WEBSITE: newmedicine.ca (www)

I leave this graffiti painted by cancerous patients on the walls of the Villejuif Hospital in Paris in 1.956:

                       "... Of The Cancer lives much more people than we die ..."

Greetings to all.

Dr. Jose Lapenta



EDITORIAL ESPAÑOL
==================
Hola amigos de la red, DERMAGIC EXPRESS te trae hoy un tema bien interesante y quizá NO CONOCIDO por muchos de ustedes: LA NUEVA MEDICINA Y EL CANCER, por el DR RYKE GEERD HAMER. Medico nacido en Frisia Alemania en 1.935.

El Dr. Hamer a los 19 años de edad aprueba el examen estatal en Alemania para estudiar Medicina, en 1.961 obtiene el grado de Dr. en Medicina, en 1.972 se especializa en MEDICINA INTERNA. A los 20 años de casa con Sigrid Oldenburg, también estudiante de Medicina en Alemania. Además de obtener el Diploma de Medicina Interna, Obtuvo también el de RADIOLOGO,  estudiando ANGIOMETRIA de los TUMORES CEREBRALES.

La vida de este Dr. quien hoy día todavía vive (82 años) cambio radicalmente el 18 de agosto de 1.978, cuando su hijo Dirk Hamer de 19 años fue alcanzado por una bala en una fiesta, muriendo 4 meses después el 7 de Diciembre de 1.978.

Cuatro meses después el Dr. HAMER desarrollo CANCER DE TESTICULO, su esposa también recae de enfermedades cancerosas y murió de un infarto agudo de MIOCARDIO EN 1.985.

La Muerte de Su Hijo y el desarrollo de los canceres en el y su esposa lo llevaron a investigar este hecho y emite la HIPOTESIS de que tanto el CANCER de el como de su esposa PUEDEN ESTAR RELACIONADOS con el GRAN CONFLICTO que vivieron por el acontecimiento grave que vivieron.

Sus estudios e investigaciones lo llevaron a formular LA LEY DE HIERRO DEL CANCER,  hecho en que se basa la LA NUEVA MEDICINA. En 1.981 presenta la tesis sobre su "DESCUBRIMIENTO",  y sorpresivamente el jurado NIEGA el trabajo y lo colocan ante la posibilidad de abandonar la TESIS o su PROFESION de MEDICO.

En 1.982 La Universidad de TUBINGEN, le devuelve su trabajo sobre EL PSIQUISMO Y EL CANCER sin haberlo verificado. En 1.986 se le aplica un proceso judicial para CONDENAR al Dr. Hamer y prohibirle el ejercicio de la Medicina por "NO QUERER ABANDONAR SU TRABAJO SOBRE LA LEY DE HIERRO DEL CANCER"  se le prohibió atender pacientes.

En 1.990 Se declara al Dr. Hamer "INCOMPETENTE"  en relación al tratamiento del CANCER.  En 1.994, 13 años después de la presentación de su trabajo, se vuelve a negar la verificación del mismo. En 1.997, 21 de Mayo el Dr. Hamer Fue arrestado y luego de pasar un tiempo en la cárcel, fue liberado y se fue a ESPAÑA, donde residencio y vive actualmente.

Su Trabajo sobre la LEY DE HIRERO DEL CANCER fue verificado EN LA UNIVERSIDAD DE VIENA EL 9 DE DIEMBRE DE 1.988.

Te estoy contando esta HISTORIA para que entiendas como en un MUNDO MODERNO Y CIVILIZADO "SUPUESTAMENTE, en el que vivimos un Dr. se plantea la "ALTERNATIVA" de que el CANCER está relacionado con "EVENTOS" psíquicos, basado en su propia experiencia, hace su estudio e investigación Y ES PERSEGUIDO CUAL CRIMINAL.

Para resumirte su trabajo, el DR. Hamer "ECHA POR TIERRA" todos los conceptos clásicos médicos sobre el cáncer y plantea LA NUEVA MEDICINA  como alternativa: EL CANCER ES PRODUCIDO POR UN GRAN CONFLICTO el cual provoca la proliferación desordenada de las células, una vez superado este, se detiene la proliferación y el mismo cuerpo se regenera.

Aquí te dejo TODA la revisión DEL Dr. Hamer, su Biografía y la explicación con graficas sobre su trabajo. Por cierto encontré en la web un libro denominado LA BIONEUROEMOCION por ENRIC CORBERA Y MONSERRAT BATLLo, el cual trata este tema.

La BIONEUROEMOCION estudia la correlación entre las emociones inconscientes desencadenadas por situaciones que el individuo vive como un IMPACTO, su expresión y localización a nivel del sistema nervioso y las modificaciones que provoca en su biología, tema altamente relacionado con la NUEVA MEDICINA del Dr. Hamer.

Sorpresivamente ENCONTRE que el DERMAGIC EXPRESS esta en las referencias bibliográficas del libro, allí te pongo la foto. Una vez más me siento agradecido y orgulloso por contribuir a DISEMINAR el conocimiento en el mundo, esa fue la razón y motivo de esta publicación que LANCE A LA RED el 2 de OCTUBRE de 2.002 y  estoy RELANZANDO hoy día, para los pacientes con CANCER.

En 2.003 el Dr. Hamer trato de patentar el nombre de NUEVA MEDICINA,  y no pudo, posteriormente la denomino LA NUEVA MEDICINA ALEMANA, logrando finalmente la patente y derechos de autor.

En 1.994, Hamer amplió su sistema a las 5 leyes biológicas que cubren todas las enfermedades en el campo entero de la medicina, basado en la investigación de 20.000 casos.

El Dr. Hamer aun vive y sigue dictando cursos y conferencias, por cierto las ultimas en abril 22 Y 23, 2.017 en TORONTO, Canadá, aquí su WEB SITE: newmedicine.ca (www)

Te dejo este grafiti pintado por pacientes cancerosos en los muros del Hospital Villejuif  de Paris en 1.956

                 " ...Del cáncer vive mucha más gente de los que morimos..."

Saludos a Todos.

Dr. Jose Lapenta


Dr. Hamer - Biography


Ryke Geerd Hamer, M.D. was born in 1935 and grew up in Frisia, Germany. He received his high school diploma at age 18 and started medical and theological studies in Tubingen, where he met Sigrid Oldenburg, a medical student who later became his wife. At age 20, he passed the preliminary examination in medicine, married a year later, and completed his theological examinations at 22. A daughter was born to the young family and a son, DIRK, who would later play a large role in their lives. At 24, Hamer passed his medical state examination in Marburg. After his residency two years later, he was granted a professional license as a doctor of medicine. There followed a number of years at the University Clinics of Tubingen and Heidelberg. In 1972, Hamer completed his specialization in internal medicine. He also worked in a practice with his wife 

Dr. Sigrid Hamer. He had always had a specific hobby: patenting his inventions, examples of which are the non-traumatic Hamer-scalpel for plastic surgery which cuts twenty times more sharply than a razor; a special bone saw, also for plastic surgery; a massage table that automatically adjusts to the contours of the body, and a device for transcutaneous serum diagnosis. The Hamers were a normal family with four children (two girls and two boys), until August, 1978, when a terrible event shook their lives: an Italian prince of the House of Savoy accidentally shot Dirk Hamer while he was asleep on a boat anchored on the island of Cavallo.  Dirk’s battle with death lasted for almost four months, while his father watched over him day and night. Dirk finally died on December 7th, 1978. As became clear three years later, this resulted in a loss conflict for Dr. Hamer, which caused a testicular carcinoma. He later named this conflict the "Dirk Hamer Syndrome", a biological conflict shock that catches one unexpectedly "on the wrong foot".

In 1981, Hamer thought that these connections applied only to cancer and had no idea that the IRON RULE OF CANCER would become the central discovery for all of medicine. He submitted his discovery to the University in Tubingen in October, 1981 as a post-doctoral thesis for qualification as a university lecturer. The main objective of the thesis was to provide his results to the University so that they could be tested on the next available cases as quickly as possible and benefit patients! In May 1982 the University rejected the work on the interconnections between the psyche and cancer, without testing a single case for reproduction, something they later admitted to in court.  In the next few years, Hamer tried repeatedly to open a hospital or a clinic as a refuge for his patients so that they could benefit from his knowledge. This was always made impossible by concerted action against it. Sigrid Hamer died in 1985, clearly from sorrow over the death of her son, and demoralized by the ceaseless intimidation inflicted by the powerful Savoy family.

The persecution reached a high point in 1986 when the District of Koblenz initiated an action to stop Hamer from practicing medicine on the basis that he "failed to deny the Iron-Rule-of-Cancer and failed to convert to the tenets of official medicine". This was established in one hearing. Forcefully implemented, it was determined that Hamer lacked the "maneuverability" and the "necessary insight with regard to the required cancer therapy". Since then, (1986) Hamer has not been allowed to talk to any patients. A presiding judge of the District Court of Cologne advised him, by warrant, to find (at age 51) another calling, unrelated to medicine.

This made it impossible for Hamer to continue scientific research. With no financial means, a secretary or other co-workers, he had to obtain CT’s and the corresponding records for his research with great difficulty, and with the help of other doctors. This led to some cases being not as well documented as he would have liked. Much was left to chance. Had he had a clinic and some financial support, one can hardly imagine...

In 1986, a court ordered that the University of Tubingen continue the post-doctoral thesis proceedings. Nothing happened until January 3, 1994 when the judgment to validate Hamer's thesis was executed, a unique process in the history of universities! However, after 13 years, it was unlikely that the University would test the New Medicine on the next available cases. On the 22nd April, the University announced that "a verification within the framework of the post-doctoral thesis is not planned". (Readers who would like more current information regarding the events associated with the thesis may request documentation from the Amici di Dirk Publishers). In 1994, Hamer expanded his system to the 5 biological laws that cover all diseases in the entire field of medicine, based on research of 20,000 cases.

Since the underlying criteria are completely scientific, it is very easy to test the New Medicine, as it has been named since then. Physicians and physicians' associations all over the world are constantly attesting to its veracity through signed documentation.


Introduction to the Inflexible Law of Cancer, discovered by Doctor Ryke Geerd Hamer, and verified on the 9th of December 1988 in the University of Vienna.

Until now, medical research into cancer has concentrated its investigations on the site of the cancerous growth: lungs, liver, breasts, bones, etc. The problem under consideration was: why do the body's cells suddenly start to proliferate in such an anarchic fashion? A virus? External agents such as tobacco, chemical products in foods, etc.?

Treatments were focussed on finding new ways to arrest the cellular proliferation: operations, X-rays, cobalt, chemotherapy...

Doctor Hamer re-examined the problem from another perspective. From his own experience –he himself suffered cancer-, and that of the patients under his charge, he has noticed over the years that there is always a well-defined syndrome behind the appearance of a cancer, and this is not simply any case of stress. A powerful stimulus is needed, a brutal psychic shock that the victim perceives as the principal event in his life; an acute, dramatic conflict, lived in psychic isolation. He has named this initial syndrome, which he discovered and which he has carefully checked in each of the thousands of cases so far examined (11,000 by 1988), the Dirk Hamer Syndrome (D.H.S.), in memory of his son

Dirk whose tragic death in 1978 was the origin of his own cancer.The experience of these thousands of individual cases, diagnosed and treated in the course of the last several years, has enabled him little by little to pick out the common factors, and to formulate a law, which is always precisely obeyed, the Inflexible Law of Cancer, that has never been refuted.

This law, in which the Dirk Hamer Syndrome is the keystone, the foundation, is expressed as follows:

Every cancer is triggered by a Dirk Hamer Syndrome, i.e., by an extremely brutal shock, an acute, dramatic conflict suffered in isolation and perceived by the victim as the worst he has ever experienced.

The subjective degree of the conflict, the manner in which the victim feels it at the moment of the Dirk Hamer syndrome, its exact form, is what determines:

The Hamer Focus, i.e., the specific zone of the brain that, under the impact of the psychic shock, suffers a breakdown in its field and issues anarchic commands to the body's cells that depend on this zone. the part of the body where the cancer grows.

There is an exact correlation between the evolution of the conflict and that of the cancer, on the twin cerebral and organic levels.

If the conflict becomes complicated by new, secondary conflicts (for example, by the anguish of knowing that you have a cancer), another zone of the brain may be affected, and another tumour will appear in the corresponding organ (classical medicine calls this metastasis).

Once the conflict disappears, the zone of the brain that was affected stops issuing anarchic commands. It resumes the functions that it was previously performing. The cells cease their anarchic growth. The cancer stops growing.

After the conflict ends, the perturbed zone of the brain needs some time to recover. To heal itself, it surrounds itself with an intra- and perifocal edema. This edema, which can be detected by scanners, is what allowed Doctor Hamer to determine precisely which zones had been affected by each type of conflict, and which were the corresponding affected organs.

At the end of the conflict, the brain also orders the regeneration of the diseased organ. The tumour is repaired (peritumoural edema, ascites, pleural or pericardial effusions), it forms a cyst, it changes in a way determined by its location, sometimes contracting via scar formation (breasts, abdomen), sometimes by reconstitution (recalcification of osteolytic lesions), sometime by expulsion (oral, rectal and vaginal cavities, etc.).

The reparation, or healing, phase, lasts exactly as long as the conflict phase. If, during this phase, there is a recurrence of the conflict, the phase will be prolonged. This healing phase is accompanied by fatigue, pains and edemas, symptoms that can be eased using the therapies recommended by Doctor Hamer.

At the end of this healing phase, which progresses synchronously on the three levels, psychic, cerebral and organic, the localised swelling due to the cerebral edematization disappears and the organism recovers its good health.

Painstakingly developed year by year by empirical methods, the Inflexible Law of Cancer now allows many doors to be opened. In fact, Doctor Hamer has determined that leukaemia obeys this law exactly: its origin is in a serious conflict caused by a loss of self-esteem. And when there is no cerebral trauma or congenital malformation involved, epileptic attacks are, so to speak, a brutal sympaticotonic oscillation intended to stop excessive edamatization caused by vagotonia.

A myocardial infarction always develops during the phase following the resolution of a territorial conflict, providing this conflict has lasted at least two or three months.

At the present time, there are a large number of diseases that can be deduced from the Inflexible Law: sclerotic plaques, Parkinson's disease, polyarthritis, diabetes, eczema, asthma, zoster, ulcers, nervous depression, mental illness, etc. There is always a conflict of a precise type behind each of these diseases, and a cure is possible after the conflict is eliminated.


THE "NEW MEDICINE" by Dr. Ryke Geerd Hamer

The 5 Bilogical Laws of Nature in New Medicine from Dr. Hamer


1. The Iron Rules of Cancer

1.Criterion

Every cancer and cancer-equivalent disease starts as an DHS(=Dirk Hamer syndrome), i.e. serious, acute-dramatic and isolating conflict-shock-experience, simultaneous on all three levels:
psyche
brain
organ

2.Criterion
The theme of the conflict determines, in the moment the DHS happens, the location of the HAMER focus in the brain, and the location of the cancer or cancer equivalent process in the organ.

3.Criterion
The course of the conflict correlates with particular development of the HAMER focus in the brain, and the course of the cancer or the cancer-equivalent process of the organ.

Example: HAMER focus in the brain





 HAMER FOCUS ON THE BRAIN
















2. The Two Phases of All Diseases




Every disease in medicine goes in two phases, i.e.

1.=conflict active, cold, sympathicotonic phase starting with a DHS (ca-phase) and
2.=conflict solved or healing phase, warm or vagotonic phase, if there is a solution of the conflict. This phase is also called "post conflictolytic phase" (pcl-phase).

Every disease with a solution of the conflict has a ca-phase and a pcl-phase. Every pcl-phase has, if it is not cancelled by a resumption of the conflict, a epileptic or epileptoid crises at the bottom of the vagotonia. This epileptic or epileptoid crises is the turning point in the pcl-phase, where the individual is in its upward trend back to normotonia.

In medicine so far not so much as one disease has been correctly recognized: In so-called "cold diseases" the following healing phase has been ignored or has been misinterpreted as a new disease, in so-called "hot diseases" the previous cold phase (ca-phase) has been ignored or has been misinterpreted as a new disease.

In the brain both phases of course have the HAMER's focus on the same place, however, in a different condition:

ca-phase: with sharply marked circles.
pcl-phase: HAMER's focus swollen, oedematic, circles disappear.
ca-phase - conflict active, e.g.:
conflict thinking under compulsion
stress to solve the conflict
sympathicotonia
loss of weight
contraction of vessels: cold hands and feet
insomnia (often waking up shortly after falling asleep)

pcl-phase - conflict solved, e.g.:
vagotonia
appetite
well-being
fever
trouble with falling asleep until 3 am (=biological daybreak)
expansion of vessels: warm hands and feet

Duration and seriousness of the ca-phase determine the duration of the pcl-phase and the seriousness of the epileptic crisis, resp. the complications during the healing-phase.


3.The Ontogenetic System of Tumors and Cancer-Equivalent Diseases




According to Hamer the different conflict-themes can be understood and classified by their evolutionary background. Diagnosis is possible by means of a CCT (computer tomograph of the brain) long before cancerous growth can be found with conventional examination methods. The CCT can be used also as means of progress control because it shows changes in the Hamer circular focuses, that indicate which phase of conflict the patient is in.

The localization in the brain, where the Hamer focus appears, determines the kind of conflict and the resulting localization of cancerous growth in the organ.
Since all conflict themes must be understood from an evolutionary point of view, the original elementary survival-functions must be seen metaphorically due to our civilization and alienation from nature.

Localization of conflict in the brain stem: the involved tissue is the endoderm, the Hamer circular focuses are found in the pons of the brain stem.
Localities of cancer are ear, mouth, stomach, liver, pancreas, small intestine, large intestine, uterus, prostate, urinary bladder.

Themes of conflict: 
Conflict: "not having been able to get hold of a vital information": Adeno-carcinoma of the middle ear.
Conflict: "not being able to swallow a chunk": Adeno-ca of the palate.
Archaic fear-of-death-conflict, fear of suffocation: Adeno-ca of the alveoli.
Conflict: "not being able to digest the chunk" indigestible anger: Adeno-ca of the small or large intestines.
...
Localization of conflict in the cerebellum and the medulla of the cerebrum; involved tissue is the mesoderm; the Hamer circular focuses are found in the cerebellum and in the medulla of the cerebrum.

Localities of cancer are adrenals, testes, ovaries, kidneys, bones (osteolysis).
Themes of conflict:
Loss of self-respect ("I was a bad mother"): Osteolysis of the shoulder.
Water or liquid conflicts (almost drowning): parenchymatous-necrosis of the kidneys.
Conflict of loss: necrosis of ovaries, necrosis of testes.
Conflict of having gone into the wrong direction (gone a stray): necrosis of the adrenal cortex.
Conflict of being wounded: necrosis of the spleen.
...
Localization of conflict in the cerebral cortex; involved tissue is the ectoderm; the Hamer circular focuses are found in the cortex.
Localities of cancer are thyroid gland, larynx, coronary veins, uterus, vagina, rectum, epidermis, nose, sinuses ...

Themes of conflict:

Conflict of fear and fright: Ca of the epithelium of the larynx
Territorial conflict: Ulcus of the bladder, the renal pelvis, the ureterus ...
Loss of teritorium conflict: Epithelic ulcer, ulcer of the coronary veins ...
Conflict of separation: Vitiligo, intracutaneous mamma ca ...
...
The cancer-and cancer-equivalent diseases run particular courses, depending on their relation to the three primary germ layers.

The tissue, that has originated from the inner germ layer (endoderm), produces adeno-carcinoma. In the parasympathetic relaxation (healing) phase the compact tumors are removed by fungi and mycobacteria (e.g. tuberculosis).

The tissue that originated from the middle germ layer (mesoderm), can be divided according to the mesoderm related to the cerebellum, and the mesoderm related to the white matter of the cerebrum.
Histological formations related to the cerebellum produce compact adeno-carcinomas, which are removed by fungi and mycobacteria.

Histological formations related to the white matter of the cerebrum are tissue necroses and osteolyses, which are restituted by bacteria during the course of healing (at first they form abscesses, that will be filled up with scar- and later with granulating-tissue (e.g. callusforming osteosarcoma, lymphoma, fibroma, healing-cysts with consecutive induration).

Histological formations related to the cortex cerebri (ectoderm) form cancerous ulcers and functional failure (e.g. motoric paralysis, diabetes etc.). In the course of healing the restitution of tissue is supported by viruses (e.g. hepatitis a).



4. The Ontogenetic System of Microbes






Further more the ontogenetic system of microbes classifies the microbes according to the three primary germ layers as follows:

The most ancient microbes, the fungi and mycobacteria are related to the endoderm and to the organs that are controlled by the brain stem.

The less ancient microbes (bacteria) are related to the mesoderm and to all organs, that developed out of the mesoderm and that are controlled by the cerebellum and the medulla of the cerebrum.

The more recent microbes (viruses) are concerned solely with the ectoderm and the organs controlled by the cerebral cortex.


5.The Biological Meaning of Diseases


Every disease has to be understood as an useful biological special program of nature to solve an extraordinary, unsuspected, biological conflict.
 

Overview of the New Medicine of the discoveries of Dr. Ryke Geerd Hamer 


Dr. Ryke Geerd Hamer, formerly of the Universities of Munich and Tubingen in Germany, founded the New Medicine after extensive research and a therapeutic practice dating back to 1979. The New Medicine is a set of findings and principles that solidly bases the nature of disease on universal biological principles and on the interaction between the three levels that make up the organism: the psyche, the brain and the organ. In New Medicine, diseases have a biological meaning and are not mistakes of nature. In fact, we can now categorize most of the diseases known to medicine in pairs of events. These pairs are actually programs of nature relating psychological and biological events. The programs are designed by Nature to either help the individual to cope or as a selection mechanism to serve the group.

Dr. Hamer realized that his wife’s death and his own cancer had to be connected somehow with the tragic shooting and eventual death of their son, Dirk. As a medical doctor, scientific researcher and head internist of an oncology clinic in Munich, Dr. Hamer was in the position to be able to come to the conclusion that a physical event can create a biological conflict shock that manifests in a visible physical transformation in the brain, and leads to a measurable change in physical-nervous parameters and to the development of cancerous growths, ulcerations, necroses and functional disturbances in specific organs of the body.

After twenty years of research and therapy with over 31,000 patients, Dr. Hamer finally established firmly, logically and empirically how biological conflict-shock results in a cold cancerous or necrotic phase and how, if the conflict is resolved, the cancerous or necrotic process is reversed to repair the damage and return the individual to health.

Disease, or the meaningful biological program of nature (as Dr. Hamer likes to call it), is divided into five biological events, all of which can be identified, measured, observed and are part of a system that makes possible a definite (not just statistically probable) prediction of events and development.

A biological conflict-shock - called a DHS (Dirk Hamer Syndrome in honour of his son) - causes the appearance of a focus of activity in the brain - called an HH (Hamerschenherd). This set oof concentric rings that can be seen in a computerized tomography scan (CT) is centred on a precise point of the brain. The location of the focus depends on the nature of the shock-conflict or conflict contents. As soon as the HH appears, the organ controlled by that specific brain centre registers a functional transformation. This transformation can manifest as a growth, as tissue loss or as a loss of function.

Dr. Hamer further discovered that the program that is initiated after a conflict-shock is dependent on the layer of the brain that is affected, something to be understood and explained from the point of view of evolution. The system makes sense both from a phylogenetic and an ontogenetic point of view. Dr. Hamer prefers to keep theory to a minimum and grounds all his observations and conclusions on hard, rock-solid empirical evidence, so we will be referring to ontogenesis in this summary.

For man and mammal, the oldest conflicts originate from the brain stem and result in cancerous growths - tumours. The resolution of these conflicts leads to a breakdown of the tumour and restoration of health. The old brain controls the organs of the endoderm, the innermost germ layer in our organism. This was the first system to appear in the embryo, later to be covered by the mesoderm and the ectoderm over several million years of evolution.

All diseases start with a cold phase, activity of the parasympathetic nervous system predominates, the shock is a constant preoccupation, nights seem long, extremities are cold and meanwhile the organ lesion extends. With the brain stem (the old-brain - controller of the endodermal organs), a tumour is growing. If and when there is a conflict resolution or lysis (CL), the process will be reversed. The HH in the brain begins to heal, as does the organ. All physicians know that healing is accompanied by oedema. The oedema that develops around the focus ring in the brain becomes visible on X-rays or CT's and is usually misdiagnosed as a brain tumour. Dr. Hamer has firmly established that brain tumours do not exist in the traditional sense. All so-called brain tumours are oedematous HH’s, the oedema remaining until healing of the tissue, after which the oedema is reabsorbed and final healing is complete. The oedematous nodes in the brain are concentrations of glia --neuroglia-- used to repair the brain and neural tissue, not only in the brain, but also in many tissues. When healing is complete, after the healing crisis, the oedematous node is pressed out, a diuretic phase eliminates excess liquid from the organism and normal health is re-established.

The warm phase is the healing stage of disease, what we usually identify as infectious disease. During this stage, the transformations of the first stage are reversed. Cancers are broken down or encapsulated (depending on whether or not the microbes needed for caseating the tumour are available to the organism). Necroses or ulcers are filled up again. The filling of necroses or ulcers also tends to be misdiagnosed as accelerated highly malignant growths. Nothing is further from the truth, affirms Dr. Hamer, after several thousand successful cases of healing and restoration of health for terminally ill patients.

The cerebellum and the cerebral medulla control the mesoderm. Organs controlled by the cerebellum show tumours -- growths, cell multiplication in the conflict active phase and, as with the endoderm, tumour destruction in the healing stage. Mesodermal organs controlled by the cerebral medulla show ulcerations and necroses in the conflict active phase and cell-multiplication during healing. All the organs and tissues of the ectoderm, controlled by the cerebral cortex, the latest of the dermal layers in ontogenesis and phylogenesis, show ulceration or functional loss during the conflict active phase. Conflict resolution brings on tissue repair and restoration of functional loss.

Observing the diseases of the different germ layers separately, Dr. Hamer established that there was obviously a biological meaning. He realized that "diseases" were not meaningless mistakes of nature that should be fought, but meaningful events that serve to restore equilibrium.

Biological conflict-shocks exist throughout the animal kingdom but acquire special meaning for human beings. The conflicts of the endoderm, the first and most primitive of the dermic layers, come from the basic functions of survival, food and reproduction. If an animal experiences a conflict-shock, it usually has something to do with a plain fact: it can be that a morsel of food is too big to swallow, that there is an obstruction in the intestine, or that there is a life- or procreative-threatening injury. The types of tumours that develop often increase the ability of the organism to deal with the specific crisis within a given time frame. If the crisis remains unresolved, the individual often dies as a result of the transformation brought about by the growth (increased hormonal release, increased digestive activity, increased strength of a tissue, etc.). If the crisis is resolved, healing sets in and the tissue or organ is often left stronger than it was before.

For humans, these same conflicts are mediated by language and symbol systems - conflicts of swallowing, as in: I can't accept this, I can't swallow it; of inability to obtain sustenance; of uncontrollable anger; of loss of territory: a lay-off at work, dismissal; of separation from child, partner, etc. - all conflicts which have their natural analogies but, mediated by man's symbolic meaning system, are transposed into human terms. Biological-conflict-shock is not a complex Freudian abstraction; it is a real life conflict that is very acute, traumatic and usually isolating (not easy to discuss or mull over with others). As well, the conflict catches us unaware, without any time to prepare ourselves (sometimes even a few seconds would avoid the formation of the HH and the unleashing of the organic program – as, for example, the expected death of a loved one). Typically, it is life threatening or fear-inducing news that causes this kind of shock. Hence, the sadly self-fulfilling aspect of a cancer diagnosis. The patient goes to the doctor with a set of symptoms and ends up with a prognosis of cancer. The patient instantly develops another HH in the brain as a consequence of the fear of death. This normally starts out as a carcinoma of the lung. The second cancer (the first one leading to the diagnosis and the second one resulting from it) is interpreted as metastasis. If the first cancer was already in remission and therefore accompanied by the typical brain node swelling misdiagnosed as a brain tumour, the patient is given a limited life expectancy and subjected to different surgical and chemical interventions. Each one of the interventions also has the potential of producing other shocks and of adding to the burden.

In fact, brain tumours as such do not exist; brain cells cannot multiply, only the glia does (connective tissue of the brain) to generate repair. Metastases do not exist either. There are cancers and cancer-equivalent developments obeying the same rule, all as associations of HH’s with their corresponding organ developments. There is in fact no mechanism for cancer cells to travel from one part of the body to another, nor any way of explaining how one cancer in one tissue learns to mutate and produce the exact correct, histologically different development appropriate to another tissue. As every oncologist knows, each organ, tissue, layer or cell group shows very specific types of growths, necroses or ulcerations, because they are histologically quite distinct. The travelling cell theory would not be able to explain the precise changes needed to account for each separate incident.

Since some of the supposed "metastases" appear locally in the vicinity of an amputated breast, it was commonly thought (working hypothesis) that cancerous cells must have somehow migrated to the new location. These local foci were designated as "proximal metastases". If the corresponding HH is found in the brain, it was supposed that the "malignant cells" had travelled via the (arterial) blood to the brain. These were called "distant metastases". These hypotheses became dogma in spite of the fact that there has never been a single observation of cancerous cells in the arterial blood stream.

There is another difficulty to overcome in the case of ulcers and necroses: from where are the "malignant cells" emitted, given that in cell loss there are none to be found? We were always looking for a "primary" tumour of the old brain type (another hypothesis) that could play the role of the "primary" focus. Yet nobody noticed that essentially benign ulcers or necroses of various organs (stomach ulcers, for example) would all of a sudden become "malignant" (in the PCL phase), as if by a stroke of bad luck. Continuing this train of hypothesis, the "metastatic" benign osteolysis would become a raging "malignant" osteosarcoma.


In summary, Dr. Hamer's discoveries can be presented as follows: 

1. The first biological law 
The Iron Rule of Cancer 

Criterion 1: Every cancer or cancer-equivalent disease originates with a (Dirk Hamer Syndrome) DHS, i.e. a
very difficult
highly acute, dramatic and
isolating shock

The experience of shock conflict is simultaneous or virtually simultaneous on all three levels:

1. on the psyche
2. on the brain
3. in the organ

Criterion 2: The conflict content determines at the moment of the DHS the location of the HH in the brain as well as the corresponding location of the cancer or cancer-equivalent disease in the organ (body).

Criterion 3: The development of the conflict determines a definite development of the HH in the brain and a very definite development of the cancer or cancer-equivalent disease in the organ.


2. The second biological law 


Every disease in medicine, inasmuch as there is a resolution of the conflict, is a two-phased occurrence.

Of the few hundred diseases known --at a rough estimate-- we find that in about half of them patients have cold hands and a cold periphery, while in the other half, the warm or hot diseases, patients have warm or hot hands and, in most cases, fever. In reality, there are only about 500 tandems: at the beginning (after the DHS) a cold, conflict-active, sympathicotonic phase and then, a warm, conflict-resolved, vagotonic healing-phase. This scheme of the two phases is a biological natural law.

All diseases known to us follow this course – as long as there is a resolution to the conflict. When we look back, we see that traditional medical practice has not correctly recognized a single disease. The healing-phase (e.g. "grippe" or flu) in the cold diseases was either overlooked or misdiagnosed as a separate disease, while the first phase in the so-called "warm diseases" was usually overlooked or misdiagnosed as a completely separate disease.

Patients with cold diseases present with cold skin and cold extremities, they are in protracted stress, they lose weight, have difficulty falling asleep and have sleep disorders. For examples we have cancer, MS, angina pectoris, neurodermatitis, diabetes and mental and mood disorders, etc. The warm diseases, especially those of an exanthematous nature, were defined as rheumatic, infectious, allergic, etc.

We now have to conclude that this was not correct. These cold and warm diseases were not individual diseases but actually one of the two phases of one illness. Moreover, the cold phase is always the first and the warm is always the second.


3. The third biological law: 

The ontogenetic system of tumours and cancer-equivalent diseases includes the following criteria:

Criterion 1:

Conflicts related at the embryonic-layer level also have
-embryonic-layer related cerebral relays
-in cases of conflict, so-called HH’s
-embryonic-layer related organs which are affected and have
-embryonic-layer related histological formations.

Criterion 2:

Old-brain directed conflicts (brain-stem directed endoderm and cerebellar directed mesoderm) show cell multiplication in the conflict active phase (CA phase) and destruction or caseation of the tumours by the appropriate microbes, if they exist, in the healing phase (pcl phase). Cerebral directed conflicts (mesodermal organs directed by loci in the cerebrum and ectodermal organs directed by the cerebral cortex) show cell decrease in the CA phase (necroses, ulcers) or just impairment or interruption of function in the so-called cancer-equivalent diseases.

Criterion 3:

In reference both to the CA-phase and to the pcl-phase, every illness is a meaningful biological occurrence to be understood in a different way through embryology and behavioural research. This means that all illnesses present a special challenge to solve an unusual, unexpected biological problem.

4. The fourth biological law 
There is a correspondence between embryonic-layer related organ groups - without exception in the pcl phase - and embryonically related groups of microbes. Microbes are not the harbingers of the symptoms but rather the optimizers of the healing phase.

The brain directs all microbes. The immune system, traditionally imagined as a sort of army in the body fighting malignant cancerous cells and malignant microbes in a great battle, does not exist in this sense. Following instructions from the brain, the pathogenic microbes become benign apathogenic microbes and retreat into a part of the organism where they are no bother. They can be recalled only in the pcl phase and sent to and reactivated only in the specific organs. Possessed of our anti-bacteria, hygienic thinking, we have tried to stamp out these part-time workers of our organism.

We have pushed TB back, but at the cost of preventing breast and intestinal tumours from being caseated by the little souring rods in the pcl phase, thus precluding the consequent tumour destruction. It has helped surgery and oncology, but is wrong biologically and medically.

The DHS embodies the acute-dramatic conflict shock that caught us on the wrong foot as well as the contents of the conflict that, in turn, determine the location of the HH in the brain and also the location of the cancerous tumour or necrosis in the organ. However, even more can happen in the moment of the DHS: in the moment of the DHS, tracks are laid on which the train of events rolls again and again in the aftermath. The environment or circumstances that existed at the moment of the DHS become like a set of tracks, replaying by association some of the physical elements of the conflict again and again. An allergist professor once put it in a very informal way: "If you suffer a DHS with a biological conflict and a cow happens to be passing, you’ll develop an allergy to cows, but if you’re nibbling on an orange, then you’ll develop an allergy to oranges."


5. The fifth biological law, the "quintessence" 

The Biological Meaning of Each Special Program of Nature 

This law can be paraphrased as: each special program of nature (pair of diseases as described above) has a special biological meaning. The Spanish have coined a term for the New Medicine; they call it La Medicina Sagrada (the Sacred Medicine); this poetic name encompasses the enormous and breathtaking significance encapsulated in the fifth law. Disease is not a meaningless "error" of nature or biology but a special program created by nature over millions of years of evolution to allow organisms to override everyday functioning and to deal with particular emergency situations; they are wonderful programs and, if understood correctly, provide the individual and the group with a way to deal with "out of the ordinary" circumstances.

We can become humble once more and understand for the first time that nature is orderly, that every occurrence in nature is meaningful even in the framework of the whole, and that the events we have called "diseases" are not senseless disturbances to be repaired by magicians. We are entitled to call this meaningful interplay of nature, of the whole inhabited cosmos, "divine". Before the birth of the major religions, the physician’s profession was always that of a priest. Profit-oriented commercial medicine took a gruesome and merciless wrong turn, eventually to be put right by our new awareness.

Not understanding disease as a sequential organization of two, usually opposing phases has prevented our recognizing the "meaning" of these special programs and their essential "goodness". A few examples: bone cancer is the healing stage of bone necrosis that accompanies many self-devaluation conflicts. During the cell reduction phase (osteolysis), there is bone loss and loss of structural stability. When the conflict is resolved, anemia prevents over-activity, reducing the chances of bone breakage. In the re-calcification stage, usually misdiagnosed as bone cancer, the persistent anemia, the pains of the periosteum and the leukaemic stage that sets in, all serve to practically immobilize the body until the healing is complete and comes to a stop (without treatment, so-called bone cancer stops naturally with the complete re-growth and a bone stronger than before!). It is thus that the post-conflict resolution stage gives the organism a much improved chance for survival, while the pre-resolution stage weakens the organism and improves the chances of the group or the pack: Nature takes "loss of self worth" conflicts very seriously!


Another example: 

In a territorial-loss conflict, the intima ulcerate (the innermost layer of the vessels supplying the heart). This allows the individual a greater vessel lumen, meaning that the heart can pump more blood to the body. This process goes on during the conflict active phase. The healing phase, as all other healing in biology, is mediated by oedema. In cases of resolution from a territorial conflict, there is a high risk of heart infarction if the conflict has lasted more than six to eight months. Nature has provided for conflict constellations, where the mass of one conflict is kept in check by the presence of a conflict located on the opposite brain hemisphere. Crazy wolves in the animal kingdom or schizophrenics in the human context tend to be survivors against impossible odds. Nature protects them by using mechanisms that can also kill. The role of the therapist is to help healing processes along by understanding them correctly in the first place.

Dr. Hamer’s New Medicine is empirical and testable at every step: three levels where events run their course synchronously and two phases of disease (as long as there is resolution of the conflict). In addition, there is a phase of normalcy before the sympathicotonia, and a phase of returning to normal at the end of the vagotonia - the healing-phase - which can, given the scars remaining at the psychic, cerebral and organic level, be distinguished from the previous, "virginal" normal phase.

We therefore have not only the four phase cut-offs on the three levels in question, but also three marking points (the DHS, CL and the epileptoid crisis) on the said three levels, giving us 21 criteria which can be tested in the five biological laws.

Since the five biological laws altogether contain at least six criteria - the histological, cerebral-topographic, organ-topographic, conflict-contents and microbial - we are able to investigate the three levels in detail, giving us 126 testable and reproducible facts for one single case!
The single most important rule in the calculations is that the localization of the HH in the brain is predetermined. This means that the relay - one of many hundreds of possible relays -- is already established. For this relay, in case of a disease, the HH must have the precise appearance corresponding to the specific phase. The likelihood of finding corroboration for a single case is already astronomically high. All the patients in each of the experiments conducted in Trnva, where tests of the provability of the New Medicine were conducted, had several cancers or paralyses, diabetes or equivalents, and for each disease, all the conditions and criteria had to be fulfilled.

There will have to be radical changes in therapeutic practice and in the way interventions are made. The first thing we realize from this system is that no disease need be fatal. The second is the necessity to identify and deal with the biological conflict-shock that brought about the first currently active DHS. Occasionally, it is necessary to deal with the healing phase and the risks that come with the reversal processes and the infectious stages appropriate to the latter phases.


Biological conflict is thus defined:


Any conflict of man or mammal resulting in a DHS. From a merely evolutionary point of view, biological conflicts are identifiable as archaic conflicts, analogous, in principle, for man and mammal. Animals experience most of these conflicts in real, physical terms, while man often does so in a transposed sense. An animal genuinely finds a morsel that it cannot swallow, a real chunk of food. For a person, this may be a valuable coin or a lottery ticket.

All relays in the brain stem refer to conflicts regarding grabbing a morsel, getting the morsel, swallowing it, digesting it, being able to separate it from the surrounding dirt, etc.
As an example, cancer of the collecting tubules of the kidneys is warning the organism against drying out - in cases of "refugee" conflicts, specifically "existence or isolation" conflicts - the urine becomes highly concentrated.

The New Medicine has been extremely successful in understanding the organism, in its diagnostic abilities and its therapeutic discipline. However, this success is perceived as a threat by the established profession and many roadblocks will have to be overcome before patients can reap these benefits.


Implications and testable findings of The New Medicine: 

Allergies: 

In the moment of the DHS, both men and animals are unconsciously aware of the circumstances surrounding the DHS. These accompanying circumstances later create so-called allergies.
Inactive Tumours:

Most of the time, patients come with a variety of symptoms or even a diagnosis on the organic level, in which case it is preferable to start at the organic level. It is obvious that the organic symptoms must be evaluated with great care because of the possibility of old carcinomas which were not caseated in the healing phase for lack of tuberculosis bacteria and which have been found by accident. For example, a solitary liver carcinoma is easy to discover today with CT’s when the patient complains of hepatic, specifically ulcerating bile duct disorders.

Brain Foci (HH’s)

In fact, a start can be made on any of the three levels and there should be no limit to one level unless forced by circumstances. Since the cerebral level is very expressive and revealing at the time of the examination, it is always useful, if possible, to conduct a brain CT in standard layers (duration four minutes, irradiation by X-rays minimal). We have to be clear here that the brain CT is only a picture of a specific moment that may indicate an earlier event from the evidence of scar tissue build-up. It also refers to a new DHS as long as the conflict has been continuous and steady in the conflict-active phase.

The conflictolysis (conflict resolution).
The conflictolysis (conflict resolution) is a very distinctive point that must not be ignored, even though it has been until now, with fatal results. The change in the vegetative innervation from lasting sympathicotonia to lasting vagotonia is a powerful seizure, psychically, vegetative-cerebrally and organically. Organically, one often diagnoses fever, "grippe" or "flu".

Every sickness has its very definite conflictolysis (conflict resolution) (CL). In a one-cycle sickness, Hamer thinks it will be easy to definitively find the CL in the future. It will be difficult when the situation is a "hanging conflict" where there is no CL (yet). It is also difficult where there are constant relapses and accompanying conflict resolutions. We then speak of "hanging healing". An example of "hanging healing" is Parkinson's disease, where the trembling (mostly of hands) indicates a healing phase, and the patient suffers a conflict relapse most nights in a dream state.


The patient is in the healing-phase:


The outer symptoms are: warm hands, listlessness and fatigue, good appetite, eventually possible fever, lasting vagotonia. As soon as the doctor determines that the patient is in the healing phase, all the little wheels in his head must work overtime to find out as fast as possible in what stage of the healing-phase. He must find out as quickly as possible the exact moment of the DHS and trace the duration of the conflict to be able to answer the following questions:

Is the patient pre-epileptoid crisis or is he already at a point after the epileptoid crisis? Does the epileptoid crisis have a high mortality risk for this specific instance of the disease? If it is a disease steered by the old-brain, then there is the question of whether or not the patient is suffering tuberculosis infection or if he should be helped to develop a tuberculosis infection.

It may also be that the healing is already well advanced, and specifically without tuberculosis bacteria. In the case of an intestinal cancer, for example, an operation may be advisable in order to avoid an intestinal obstruction. However, one should only extirpate the minimum in such an operation, no more than 15 cms of the thick intestine or, if technically possible without risk of bleeding, cut back the tumour. The earlier motto of cutting far into the healthy tissue to avoid a metastasis has proven to be unfounded and absurd.

Brain Tumours:

Both phases have their HH in the same place on the brain, but show different conditions: as a so-called target configuration in the conflict-active phase (CA-phase), with marked crises always; as a swollen oedema in the conflict-solved configuration (pcl-phase). The oedema of the inner ring is called "intra-focal", and the oedema around the outer one is called "perifocal". These are however, imprecise designations for a thing that is very clear in itself. From the beginning of the healing-phase, it is normally possible to dye the brain to some extent with a contrast dye. At the end of the healing-phase, we find varying amounts of (neuro)glia in the HH stored there as a sign of the restoration of the nerve cells and synapses. These basically innocent (neuro)glioma were usually designated as brain tumours or brain metastases, but, in fact, they are healing HH’s.

Cancer-equivalent diseases:

For old-brain organs there is no cancer-equivalent, but only cancers and a healing phase after resolution of the conflict when the tumour stops growing and fungi and mycobacteria start breaking it down.

For mesodermal cerebrum directed organs (bones, cartilage tissues, lymph-nodes, etc.) there are no cancer-equivalents either, but only cancers in the form of necroses, osteolysis, tissue-holes, in brief; cell melt-down or degeneration, as well, in positive cases of conflicto-lysis (conflict resolution), a healing phase with replenishment of the substance-deficiency.

We only find cancer-equivalent diseases in the ectodermal cortically directed organ diseases and even there, only for a portion of these organs. In spite of this, there are many of them.


 The definition states:


Cancer equivalent diseases are ectodermal cortically directed diseases that occur precisely according to the five biological natural laws, but instead of showing a cellular or parenchymatous substance defect (specifically, instead of cell meltdown), they show a functional impairment. Motor paralyses fall into this category, as does diabetes, glucagon insufficiency and visual and hearing impairments with their corresponding conflicts. They have HH’s in the brain and if there is a conflict resolution, a healing phase with its symptoms and (occasionally even deadly) complications.


Restoration of Function:


Even if the cells of the organ do not dissolve during cancer-equivalent diseases, they do seem to be changed from a given point of view as are the corresponding brain (HH) locations. (E.g. Insuloma in the pancreas or glucagon insufficiency). In spite of these changes, and despite years of conflict, these cells seem to be functionally restorable after a conflict resolution.


The Ontogenetic System of Microbes


Dr. Hamer states that the biology of humans or animals is neither senseless nor without a system; there are no meaningless or random cancerous growths and no senseless or randomly occurring microbes. His research uncovered the following natural laws:

1. The division of microbes: fungi - bacteria - viruses - correspond to their phylogenetic age: the oldest are the fungi, then the bacteria and the phylogenetically youngest are the viruses.

2. The division of microbes conforms to the germ-layer-correspondence of the organs in which they function:

a) fungi and myco-bacteria work in the brain stem directed endodermal organs

b) the myco-bacteria and bacteria work in the mesodermal, cerebellar directed organs, and the bacteria work in the cerebral medullar directed mesodermal organs

c) viruses work exclusively in the ectodermal organs directed by the cerebral cortex.

3. All microbes without exception become active exclusively in the second phase, the healing phase, starting with the conflicto-lysis (conflict resolution) and ending with the completion of the healing phase; they work neither before nor after. Before, they existed as a-pathogenic germs. During the healing phase, they can be considered virulent, and after the healing phase, as a-pathogenic germs again.

4. All microbes are more or less specialized, not only in view of the organs they work on, but also in the way and style in which they work.

a) Fungi and myco-bacteria are a destruction crew, i.e. they destroy brain stem directed tumours (adeno-carcinomas) and mesodermal, cerebellar directed tumours (adenoid-carcinomas); more precisely: they caseate tumours controlled by the old-brain starting at the moment of the conflicto-lysis (conflict resolution), if it happens.

During the normotonia, the conflict-active sympathicotonic phase and in the renewed normotonia (at the end of the healing phase), they are apathogenic, therefore harmless. In the same way, they are harmless for all other organs!

b) Bacteria function as clean-up workers for organs directed by the cerebellar-mesoderm and for mesodermal organs directed by the cerebral-medulla, i.e. they work on the entire mesodermal organ domain, but with differentiable function. They destroy the adenoidal tumours of the cerebellar mesoderm but they rebuild the cerebral-mesoderm (medulla) directed cellular melt down of organs such as necroses (osteolyses, etc. - suppurating-granulating-scarring). Their work also begins with conflicto-lysis (conflict resolution) and ends at the end of the healing phase, specifically with the beginning of the renewed normotonia.

c) Viruses are simply construction or reconstruction workers. They bring about significant swelling and re-fill the ulcers and cellular substance losses of organs directed by the cerebral cortex. Like the other microbes, they are only active during the healing phase. In the case of squamous epithelium ulcers, cures are brought about by viruses, as in tubular organs (i.e., bronchia, coronary arteries or coronary veins, branchial arch ducts of the neck, the milk ducts or intra-hepatic bile-ducts) and they become temporarily blocked by swelling. In principle, the same occurs, but less drastically without virus such as non-viral hepatitis.

5. Microbes, our helpers and companions, are directed by the brain. Microbes have worked for us, not against us, as faithful servants over umpteen billions of years of evolution.


Therapy:


As stated above, the system Dr. Hamer has pieced together has extraordinary diagnostic and therapeutic success. Although the system stands traditional medicine on its head, it does not invalidate many of its practices or most of the knowledge that has been accumulated. We now have a good understanding of the interconnections of all the knowledge and have reached sound and supportive conclusions for patients.

The CT of a patient's brain in standard layers is currently one of the powerful methods of diagnosis. Equipped with that, the few doctors who practise or are allowed to practise New Medicine can interpret a person’s current state of events. Further dialogue between the person and the physician or attending practitioner can lead to working on the resolution of whatever conflicts may still be in development.

For a situation arising with the conflict resolution or the healing phase, the physician will be able to determine the seriousness of the potential healing crisis and will assist with therapy during the recovery phase that may pose dangers in many cases. Both medicine and alternative therapies are very well equipped to help in these stages, aiming to restore the body to health with only the absolutely necessary intervention required to prevent life threatening situations.

It is fundamentally important that patients understand the way the body really works, and how they can work with their practitioner-friend to restore health.
=========================================================================

 

   Produced by Dr. Jose Lapenta R. Dermatologist

                 Maracay Estado Aragua Venezuela 2.017  

           Telf: 02432327287-02432328571   

 

         

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sábado, 29 de abril de 2017

THE LORATADINE AND THEIR 110 ADVERSE EFFECTS. / LA LORATADINA Y SUS 110 EFECTOS ADVERSOS.

 

The Loratadine and their 110 adverse effects. ! 

 

La Loratadina y sus 110 efectos adversos. !














EDITORIAL ENGLISH 
===================
HELLO friends of the network, DERMAGIC EXPRESS give you today a very interesting topic, THE LORATADINE AND ITS 110 ADVERSE EFFECTS. I begin by telling the whole audience that this topic that I am updating today was published ORIGINARILY by DERMAGIC EXPRESS many years ago, exactly 27 September 2001, 16 years have passed.
 

And you ask yourself why today I am RELAUNCHING the theme, and I will explain why, first telling you the HISTORY OF THIS MOLECULE or drug widely used as antiallergic, antihistamine at WORLD level. Both adults, children 6 to 12 years and older, and children under 2 years. 

The goal is to remind you that every medicine has its ADVERSE EFFECTS, but this call my attention given the amount of them, secondarily show you as a simple antihistamine 16 days later is being used as a therapy to relieve BONE PAIN in cancer. Yes, this is how you read it. 

I explain that, what led me to investigate this MEDICIN, was the fact that I met a patient who presented INCREASED HEPATIC ENZYMES by the use of LORATADINE in a short period of time.

I also tell you that this publication I am RELEASING today because after so many years of the first publication DID NOT FIND ARGUMENTS THAT OPPOSE THE 110 ADVERSE AFFECTS described originally, in fact have been described other adverse effects with this drug NOT DOCUMENTED originally as HEMOLYTIC ANEMIA, and may be others. 

For year 2.008, Jun 27, the FDA denied the approval of a combined medication: LORATADINE plus SODIUM MONTELUKAST for allergic rhinitis. However, for 2,015, MONTACLAR a medicin made up of 10 Mgr of LORATADINE plus 10 Mgr of MONTELUKAST, in tablets was released to the MARKET by the MSD laboratory (Merck Sharp and Dohme).

For the year 2.015, 109 cases of cardiotoxic effects attributed to the anthistamines cetirizine, desloratadine, diphenhydramine, fexofenadine, LORATADIN, including Torsades de Pointes (TdP), QT abnormalities (QTabn), ventricular arrhythmia (VA) And sudden cardiac death / cardiac arrest (SCD / CA), were reported in 13 European countries.  

This confirms the non-solitary CARDIOTOXICITY OF LORATADINE, also DESLORATADINE, FEXOFENADINE, DIFENHYDRAMINE AND CETIRIZINE. 

HISTORY OF THE LORATADINE PRODUCT:
=====================================
 

THE LORATADINE MOLECULE is born for the years 1.986-1987 with the name code of SCH 29851, and the first country that put it the market it was BELGIUM in February of 1.998, then Canada in June of 1.988. For the year of 1.999 the product had been approved in 94 countries including 17 as non prescription product. (OTC= Over The Country). 

In United States it was approved in the year 1.993 FOR EXCLUSIVE USE in children bigger than
12 YEARS of AGE and ADULTS. (1996). Then their USE extended to children between 6 AND 12Years OLD, AND between 2-5 years old. And it was IN SEPTEMBER 26, YEAR 2.000 when it was approved for their use in children minors to 2 years of age.
 

There are five formulations that were approved in those years FOR THE USE OF loratadine by the FDA (Food and Drug Administration): 

1.) Loratadine 10 mg (Claritin) tablets, approved April, 1993.
2.) Loratadine Zydis (Claritin RediTabs), approved December, 1993.
3.) Loratadine 5 mg/pseudoephedrine 120 mg (Claritin-D 12 Hour Extended Release tablets, approved  November, 1994.
4.) Loratadine 10 mg/pseudoephedrine 240 mg (Claritin-D 24 Hour Extended Release) tablets, approved August, 1996.
5.) Loratadine 10 mg/10 mL (Claritin) Syrup, approved October, 1996.  

The single ingredient Claritin tablet products are currently labeled for use in children age 6 years and above. Claritin Syrup was recently approved (September 26, 2.000) for use in children down to age 2 years. The two Claritin- D formulations are approved for use in adults and children 12 years of age and older. 

I now place what the FDA (Food And Drug Administration) PUBLISHED about LORATADINE in those years and still valid today:

1.) for the year 2.000 55 cases of deaths are reported by the use of Loratadine.  

2.) 86 cases of ventricular arrhythmias have been reported of which 16 died.  

3.) 43 cases of convulsions associated to the loratadine use have been reported.  

4.) 103 cases of hepatic injury associated to the loratadine use have been reported that includes abnormal function of the liver, jaundice, hepatitis and hepatic necrosis.  

5.) 5 cases of hepatic failure have been reported of which 4 needed liver transplant.  

6.) For the year 2.000 day 26 of September is that the FDA approves its use in children MINORS than 2 years.  

7.) 10 different types of adverse effects have been reported in relation to the loratadine use in 2-5 year-old children: diarrhea, epistaxis, pharyngitis, influenza-like symptoms, fatigue, stomatitis, tooth disorder, earache, viral infection and rash.  

8.) For the year 1.996 THE 110 ADVERSE EFFECTS had already BEEN REPORTED, described in the Review, and from that same years THE EDVERSE EFFECTS had already BEEN REPORTED ON THE LIVER.  

9.) The loratadinE has effects on the CENTRAL and PERIFERIC nervous system: somnolence, blepharospasm, dizziness, dysphonia, hypertonia, migraine, paresthesia, tremor and vertigo.  

10.) These 110 adverse effects were not INVENTED, and they were reported in patients that were taking the product. The FDA forces the LABORATORIES to place them in the packing of the product from 1.996.  

This publication, once LAUNCHED TO THE NET in those years caused a great impact, in fact today is still on the internet and I put the reference pictures.




Finally, as I said at the beginning, NOT ALL IS "SHADOW" for LORATADINE, Today 2.017, This Medicine has been discovered the property of alleviating BONE PAIN caused by the drug PEGFILGRASTIN (NEULASTA) used for cancer.

In my opinion LORATADINE is a good MEDICINE, and one of the most popular today as antihistamine, but you must know its ADVERSE EFFECTS, especially those who use it continuously and indiscriminately.

The most commonly observed ADVERSE EFFECTS during these years, in my dermatology practice are: drowsiness, dizziness, tachycardia, jaundice, seizures, ineffectiveness and increased liver enzymes. I have not observed DEATHS due to its use in 16 years. 

I am really proud that my articles are mentioned on other Websites. In this case the publication is still on the internet 16 years later. Which shows that many articles like this DO NOT PRESCRIBE, are still useful and updated.

In the references the facts... in the attach the evidence.

Greetings to all 

Dr. Jose Lapenta R. 
  


EDITORIAL ESPANOL 
===================
HOLA amigos de la red, DERMAGIC EXPRESS les pera un tema bien interesante, LA LORATADINA Y SUS 110 EFECTOS ADVERSOS. Comienzo por decirle a toda la audiencia que este tema que hoy estoy actualizando fue publicado ORIGINARIAMENTE por el DERMAGIC EXPRESS hace muchos años, exactamente el 27 de Septiembre de 2.001, han transcurrido 16 años.

Y te preguntaras porque hoy lo estoy RE-LANZANDO, y te voy a explicar el porqué, primero contándote la HISTORIA DE ESTA MOLECULA o droga ampliamente utilizada como antialérgico, antihistamínico a nivel MUNDIAL. tanto en adultos como niños de 6 a 12 años y mayores, y niños menores de 2 años.

El objetivo, recordarte que toda medicina tiene sus EFECTOS ADVERSOS, pero esta llamo mi atención dada la cantidad de ellos, secundariamente mostrarte como un simple antihistamínico hoy día 16 años después está siendo utilizado como terapia para aliviar el DOLOR OSEO en el cáncer. Si, así como lo lees.

Te explico que lo que me llevo a investigar esta MOLECULA, fue el hecho que conocí un paciente que presento AUMENTO DE LAS ENZIMAS HEPATICAS por la utilización de LORATADINA en un corto periodo de tiempo.

También te cuento que esta publicación la estoy LANZANDO nuevamente porque luego de tantos años de la primera publicación NO ENCONTRE ARGUMENTOS QUE CONTRADIGAN LOS 110 EFECTOS ADVERSOS descritos originalmente, de hecho se han descrito otros efectos adversos con este medicamento NO DOCUMENTADOS originalmente como ANEMIA HEMOLITICA.y quiza otros mas.

Para el año 2.008, Junio 27, la FDA nego la aprobacion de un medicamento combinado: LORATADINA mas MONTELUKAST SODICO para la rinitis alergica. Sin embargo para 2.015 es lanzado al MERCADO la medicina MONTACLAR compuesto por 10 Mgrs de LORATADINA mas 10 Mgr de MONTELUKAST, en tabletas por el laboratorio MSD (Merck Sharp and Dohme).

Para él año 2.015 se reportaron en 13 países de Europa 109 casos de afectos cardiotóxicos atribuidas a los antihistamínicos cetirizina, desloratadina, difenhidramina, fexofenadina y LORATADINA, que incluyen: Torsades de Pointes (TdP), anomalías QT (QTabn), arritmia ventricular (VA) y muerte cardiaca súbita / paro cardiaco (SCD / CA). 

Lo cual confirma la CARDIOTOXICIDAD NO SOLO DE LA LORATADINA, también DESLORATADINA, FEXOFENADINA, DIFENHIDRAMINA Y CETIRIZINA. 

HISTORIA DEL MEDICAMENTO LORATADINA: 
======================================== 

LA MOLECULA LORATADINA nace para los años 1.986-1987 con el nombre código de SCH 29851 y el primer país que la puso el mercado FUE BELGICA en febrero de 1.998, luego Canada en junio de 1.988. Para el año de 1.999 el producto había sido aprobado en 94 países incluyendo 17 como producto de no prescripción medica. 

Hay cinco formulaciones que se aprobaron en esos años PARA EL USO de la loratadina, por la FDA (Administración de Alimentos y medicinas):

1.) Loratadina 10 mg comprimidos (Claritin), aprobado en abril de 1.993.
2.) Loratadina Zydis (Claritin RediTabs), aprobado en diciembre de 1.993.
3.) LoratadinA 5 Mg / pseudoefedrina 120 mg (Claritin-D comprimidos de liberación prolongada de 12 horas, aprobado en noviembre de 1.994.
4.) comprimidos de Loratadina 10 mg / pseudoefedrina 240 mg (Claritin-D 24 Hour Extended Release) aprobado en agosto de 1.996.
5.) Loratadina 10 mg / 10 ml (Claritin) jarabe, aprobado en octubre de 1.996.

La LORATADINA como ingrediente único se aprobó para su uso en NIÑOS de 6 AÑOS Y MAS. El jarabe de LORATADINA fue aprobado el 26 de septiembre, 2.000 para el uso en NIÑOS MENORES DE 2 AÑOS. Las dos formulaciones LORATADINA-D están aprobadas para su uso en ADULTOS Y NIÑOS DE 12 AÑOS DE EDAD Y MAYORES.
 

TE coloco ahora lo que PUBLICO LA FDA (Administracion de Alimentos y Medicinas) sobre la LORATADINA en esos años y todavía vigentes hoy día:

1.) Para el año 2.000 se reportaron 55 casos de muertes por el uso de Loratadina. 

2.) Se reportaron 86 casos de arritmias ventriculares de los cuales 16 murieron. 

3.) Se reportaron 43 casos de convulsiones asociadas al uso de loratadina. 

4.) Se han reportado 103 casos de injuria hepática asociada al uso de loratadina, que incluye anormal funcionamiento del hígado, ictericia, hepatitis y necrosis hepática. 

5.) Se reportaron 5 casos de insuficiencia hepática de los cuales 4 necesitaron trasplante de hígado. 

6.) Para el año 2.000 día 26 de septiembre es que la FDA aprueba su uso en niños menores de 2 años. 

7.) Se han reportado 10 diferentes tipos de efectos adversos en relación al uso de loratadina en niños de 2-5 años, a saber: Diarrea, Epistaxis, Faringitis, Influenza-like síntomas, Fatiga, Estomatitis, Desordenes dentales, Dolor de oídos, Infecciones virales, Rash. 

8.) Para el año 1.996 ya se habían REPORTADO LOS 110 EFECTOS ADVERSOS descritos en la revisión y desde ese mismo años ya SE HABIAN REPORTADO LOS EFECTOS EDVERSOS SOBRE EL HIGADO. 

9.) La loratadina SI TIENE EFECTOS ADVERSOS sobre el sistema nervioso CENTRAL Y PRERIFERICO: a saber: somnolencia, Blefarospasmo, Vahídos, Disfonía, Hipertonía, Migraña, Parestesia, Tremor y vértigo. 

10.) Estos 110 efectos adversos NO FUERON INVENTADOS, y se reportaron en pacientes que estaban tomando el producto. La FDA obligo a los fabricantes a colocarlos en el empaque del producto desde 1.996.  

Esta publicación, una vez LANZADA A LA RED en esos años causo gran IMPACTO, de hecho hoy día sigue en la internet y te pongo las fotos referenciales. 

Para finalizar, como te dije al principio, NO TODO ES "SOMBRA" para la LORATADINA, Hoy día 2.017 A Esta Medicina se le ha descubierto la propiedad de aliviar el DOLOR OSEO ocasionado por la droga PEGFILGRASTIN (NEULASTA) utilizada para el cáncer. 

En mi opinión la LORATADINA es una buena MEDICINA, y una de las más populares hoy día como antihistamínico, pero debes conocer sus EFECTOS ADVERSOS, sobre todo aquellos que la utilizan en forma continua, e indiscriminada.

Los EFECTOS ADVERSOS mas comunmente observados durante estos años, en mi ejercicio como dermatologo son: somnolencia, mareos, taquicardia, ictericia, convulsiones, inefectividad y aumento de las enzimas hepaticas. No he observado MUERTES por su uso en 16 años.
 
 Realmente me siento orgulloso que mis articulos sean mencionados en otros Sitios Web. En este caso la publicacion sigue en la internet 16 años despues. Lo cual demuestra que muchos articulos como este  NO PRESCRIBEN, siguen siendo utiles y se actualizan.

 
En las referencias los hechos.
.. en las fotos la evidencia.

Saludos a Todos. 

Dr. Jose Lapenta.


==================================================================
REFERENCIAS BIBLIOGRAFICAS / BIBLIOGRAPHICAL REFERENCES 
==================================================================
1.) THE 110 ADVERSE EFFECTS OF THE LORATADINE / ENGLISH
1.) LOS 110 EFECTOS ADVERSOS DE LA LORATADINA / SPANISH
2.) PEDIATRIC USE OF THE LORATADINE / ENGLISH
2.) USO PEDIATRICO DE LA LORATADINA / SPANISH
3.) LORATADINE, EXECUTIVE SUMMARY FDA REPORT
4.) Loratadine toxicity.
5.) Double-blind comparison of cetirizine and loratadine in children ages 2 to 6 years with perennial allergic rhinitis.
6.) Clinical pharmacology of the H1-receptor antagonists cetirizine and loratadine in children.
7.) Risk of ventricular arrhythmias associated with nonsedating antihistamine drugs.
8.) Clinical prescribing of allergic rhinitis medication in the preschool and young school-age child: what are the options?
9.) The pharmacokinetics, electrocardiographic effects, and tolerability of loratadine syrup in children aged 2 to 5 years.
10.) Comparison of once-daily ebastine 20 mg, ebastine 10 mg, loratadine 10 mg, and placebo in  the treatment of seasonal allergic rhinitis. The Ebastine Study Group.
11.) Comparison of the efficacy, safety and quality of life provided by fexofenadine hydrochloride 120 mg, loratadine 10 mg and placebo administered once daily for the treatment of seasonal allergic rhinitis.
12.) Cetirizine, loratadine, or placebo in subjects with seasonal allergic rhinitis: effects after
controlled ragweed pollen challenge in an environmental exposure unit.
13.) Brompheniramine, loratadine, and placebo in allergic rhinitis: a placebo-controlled comparative clinical trial.
14.) Evaluation of the potential cardiotoxicity of the antihistamines terfenadine, astemizole, loratadine, and cetirizine in atopic children.
15.) Onset of action and efficacy of terfenadine, astemizole, cetirizine, and loratadine for the relief of symptoms of
16.) Comparative outdoor study of the efficacy, onset and duration of action, and safety of cetirizine, loratadine, and placebo for seasonal allergic rhinitis.
17.) [Severe adverse effect of the anti-allergy drug loratadine--warning against prolonged use of non-prescription drugs].
18.) Loratadine (SCH29851) 40 mg once daily versus terfenadine 60 mg twice daily in the treatment of seasonal allergic rhinitis.
19.) Suppression of histamine-induced wheal response by loratadine SCH 29851) over 28 days in man.
20.) loratadine in childrens with skin alergic diseases. 
21.) [Fixed pigmented erythema antihistamine H1: about 2 cases and review of the literature].
22.) Drowsiness and motor responses to consecutive daily doses of promethazine and loratadine.
23.) Low dosage promethazine and loratadine negatively affect neuromotor function.
24.) Severe pegfilgrastim-induced bone pain completely alleviated with loratadine: A case report.
25.) [Drug-induced immune hemolytic anemia: a retrospective study of 10 cases].
[Article in French]
26.) When Hydromorphone Is Not Working, Try Loratadine: An Emergency Department Case of Loratadine as Abortive Therapy for Severe Pegfilgrastim-Induced Bone Pain.
27.) Pegfilgrastim-Induced Bone Pain: A Review on Incidence, Risk Factors, and Evidence-Based Management.
28.) Pegfilgrastim use and bone pain: a cohort study of community-based cancer patients.
29.) Prevention of granulocyte-colony stimulating factor (G-CSF) induced bone pain using double histamine blockade.
30.) Pro-arrhythmic potential of oral antihistamines (H1): combining adverse event reports with drug utilization data across Europe.
31.) Histamine H1-receptor antagonists against Leishmania (L.) infantum: an in vitro and in vivo
32.) Investigation of cytotoxic and genotoxic effects of the antihistaminic drug, loratadine, on human lymphocytes.
=============================================================
=============================================================
1.) THE 110 ADVERSE EFFECTS OF THE LORATADINE /ENGLISH
=============================================================
Sources:
1.) The Mosby year book 1.996.
2.) Information given by the laboratory inside the box(1.999-2.000) 

REPORTED ADVERSE EVENTS WITH AN INCIDENCE OF MORE THAN 2% IN
PLACEBO-CONTROLLED ALLERGIC RHINITIS CLINICAL TRIALS IN PATIENTS 12
YEARS OF AGE AND OLDER 

1.) Headache.
2.) Somnolence.
3.) Fatigue.
4.) Dry Mouth. 

Adverse events reported in placebo-controlled chronic idiopathic urticaria trials were
similar to those reported in allergic rhinítis studies. 


ADVERSE EVENTS OCCURRINg WITH A FREOUENCY OF =2 > 2% IN LORATADINE
SYRUP-TREATED PATIENTS (6-12 YEARS 0LD IN LACEBO-CONTROLLED TRIAL
AND MORE FHEOUENTLY THAN THE PLACEBO GROUP 

5.) Nervousness.
6.) Wheezing.
7.) Fatigue.
8.) Hyperkinesia.
9.) Abdominal Pain.
10.) Conjunctivitis.
11.) Dysphonia.
12.) Malasise.
13.) Upper Respirator Tract Infection. 

In addition to those adverse events the folloving adverse events nave been reported in loratadine
clinical trials in adult and padiatric palients: 

AUTONOMIC NERVOUS SYSTEM: 

14.) alterad lacrimation.
15.) alterad salivation.
16.) flushing.
17.) hypoesthesia.
18.) impotence.
19.) Increased sweating
20.) thirst. 

BODY AS A WHOLE: 

21.) angioneutotic edema.
22.) asthenia.
23.) back pain.
24.) blurred vision.
25.) chest pain.
26.) earache.
27.) eye pain.
28.) fever.
29.) leg cramps.
30.) malaise.
31.) rigors.
32.) tinnitus.
33.) viral infection.
34.) weight gain. 

CARDIOVASCULAR SYSTEM: 

35.) hypertension
36.) hypotension.
37.) palpitations.
38.) supraventricular tachyarrhythmias.
39.) syncope.
40.) tachycardia. 

CENTRAL AND PERIPHERAL NERVOUS SYSTEM: 

41.) blepharospasm.
42.) dizziness.
43.) dysphonia
44.) hypertonia
45.) migraine.
46.) paresthesia.
47.) tremor.
48.) vertigo. 

GASTROINTESTINAL SYSTEM: 

49.) alterad taste.
50.) anorexia.
51.) constipation
52.) diarrhea
53.) dyspepsia.
54.) flatulence.
55.) gastritis.
56.) hiccup.
57.)increased appetite.
58.) nausea.
59.) stomatitis.
60.) toothache.
61.) vomiting. 

MUSCULOSKELETAL SYSTEM: 

62.) arthralgia
63.) myalgia. 

PSYCHIATRICS: 

64.) agitation
65.) amnesia.
66.) anxiety.
67.) confusion.
68.) decreased libido.
69.) depression.
70.) impaired concentration.
71.) insomnia.
72.) irritability.
73.) paroniria. 

REPRODUCTIVE SYSTEM: 

74.) Breast pain.
75.) dysmenorrhea.
76.) menorrhagia.
77.) vaginitis. 

RESPIRATORY SYSTEM: 

78.) bronchitis.
79.) bronchospasm.
80.) coughinq.
81.) dyspnea.
82.) epistaxis.
83.) hemoptisis.
84.) laryngitis.
85.) nasal dryness.
86.) pharyngitis.
87.) sinusitis.
88.) sneezing. 

SKIN AND APPENDAGES: 

89.) dermatitis.
90.) dry hair.
91.) dry skin.
92.) photosensitivity reaction.
93.) pruritus.
94.) purpura.
95.) rash.
96.) urticaria. 

URINARY SYSTEM: 

97.) altered micturition.
98.) urinary discoloration.
99.) urirary incontinence.
100.) urinary retention. 

Ir addilion, Ihe following spontaneous adverse avents have been reported rarely during file marketing
of loratadine:
(not reported percentages) 

101.) abnormal hepatic function.
102.) jaundice.
103.) hepatitis.
104.) hepatic necrosis 

OTHERS: 

105.) alopecia.
106.) anaphylaxis.
107.) breast enlargement.
108.) erythema multiforme.
109.) peripheral edema.
110.) seizures. 

ADVERSE EFFECTS IN CHILDRENS BETWEEN 2-5 YEARS OLD
--------------------------- 

Sixty pediatric patients 2 to 5 years of age received 5 mg loratadine once daily in a double-blind,
placebo-controlled
clinical trial for a period of 14 days. No unexpected adverse events were seen given the known
safety profile of loratadine
and likely adverse reactions for this patient population. The following adverse events occurred with a
frequency of 2 to 3
percent in the loratadine syrup-treated patients (2 to 5 years old) during the placebo-controlled trial,
and more frequently
than in the placebo group: 

1.) diarrhea.
2.) epistaxis.
3.) pharyngitis.
4.) influenza-like symptoms.
5.) fatigue.
6.) stomatitis.
7.) tooth disorder.
8.) earache.
9.) viral infection.
10.)rash. 


============================================================
1.) LOS 110 EFECTOS ADVERSOS DE LA LORATADINA / SPANISH
============================================================
Fuentes:
1.) THe Mosby Year Book. (1.996)
2.) Informacion suministrada por el fabricante dentro de las cajas del producto (1.999 - 2.001) 

EFECTOS ADVERSOS REPORTADOS CON UNA INCIDENCIA MAYOR AL 2% EN
ESTUDIOS PLACEBO-CONTROL SOBRE RINITIS ALERGICA EN PACIENTES DE 12
AÑOS DE EDAD Y MAYORES. 

1.) Dolor de Cabeza.
2.) Somnolencia
3.) Fatiga.
4.) Sequedad bucal. 

Estos efectos adversos fueron similares en el grupo de Urticaria cronica tratados con loratadina. 


EFECTOS ADVERSOS PRESENTADOS CON INCIDENCIA DE 2% O MAYOR EN
PACIENTES ENTRE 6 Y 12 AÑOS DE EDAD, ESTUDIOS PLACEBO-CONTROL, CON
JARABE DE LORATADINA, ( MAS FRECUENTEMENTE PRESENTADOS QUE EN EL
GRUPO PLACEBO) 


5.) Nerviosismo.
6.) Fatiga.
7.) Jadeos.
8.) Hiperquinesia.
9.) Dolor Abdominal.
10.) Conjuntivitis.
11.) Disfonia.
12.) Malestar
13.) Infeccion del tracto respiratorio superior. 

Otros efectos adversos presentados en estudios de pacientes adultos y niños con el uso de la
loratadina: 

SISTEMA NERVIOSO AUTONOMO: 

14.) Alteracion lacrimal.
15.) Salivacion Alterada.
16.) Flushing.
17.) Hipoestesia.
18.) Impotencia.
19.) Incremento de la Sudoracion
20.) sed 

CUERPO como TOTALIDAD: 

21.) Edema angioneurotico.
22.) Astenia.
23.) Dolor de espalda.
24.) Vision Borrosa.
25.) Dolor en el pecho.
26.) Dolor de oidos.
27.) Dolor Ocular.
28.) Fiebre.
29.) Calambre en las piernas.
30.) Malestar general.
31.) Rigores.
32.) Tinitus.
33.) Infeccion Viral.
34.) Aumento de peso. 

SISTEMA CARDIOVASCULAR: 

35.) Hipertension.
36.) Hipotension.
37.) Palpitaciones.
38.) Taquiarritmias supraventriculares.
39.) Sincope.
40.) Taquicardia. 

SISTEMA NERVIOSO CENTRAL Y PERIFERICO: 

41.) Blefarospasmo.
42.) Vahidos.
43.) Disfonia.
44.) Hipertonia.
45.) Migraña.
46.) Parestesia.
47.) Tremor.
48.) Vertigo. 

SISTEMA GASTROINTESTINAL: 

49.) Alteracion del gusto.
50.) Anorexia.
51.) Constipacion.
52.) Diarrea.
53.) Dispepsia.
54.) Flatulencia.
55.) Gastritis.
56.) Hipo.
57.) Aumento del apetito.
58.) Nauseas.
59.) Estomatitis.
60.) Dolor en los dientes.
61.) Vomitos. 

SISTEMA MUSCULO-ESQUELETICO: 

62.) Artralgia.
63.) Milgia. 

PSIQUIATRICOS: 

64.) Agitacion.
65.) Amnesia.
66.) Ansiedad.
67.) Confusion.
68.) Disminucion de la libido.
69.) Depresion.
70.) Disminucion de la concentracion.
71.) Imsonio.
72.) Irritabilidad.
73.) Paroniria. 

SISTEMA REPRODUCTIVO: 

74.) Dolor en las mamas.
75.) Dismenorrea.
76.) Menorragia.
77.) Vaginitis. 

SISTEMA RESPIRATORIO: 

78.) Bronquitis.
79.) Broncoespasmo.
80.) tos.
81.) Disnea.
82.) Epistaxis.
83.) Hemoptisis.
84.) Laringitis.
85.) Sequedad nasal.
86.) Faringitis.
87.) Sinusitis.
88.) Estornudos. 

PIEL Y APENDICES: 

89.) Dermatitis.
90.) Cabello seco.
91.) Piel seca.
92.) Reaccion de fotosensibilidad.
93.) Prurito.
94.) Purpura.
95.) Rash.
96.) Urticaria. 

SISTEMA URINARIO: 

97. Alteracion en la miccion.
98.) Decoloracion de la orina.
99.) Incontinencia urinaria.
100.) Retencion de orina. 

En adicion, los siguientes efectos adversos espontaneos han sido reportados raramente (no se
reportan porcentajes) con el uso de loratadina: 

101.) Funcion hepatica anormal.
102.) Ictericia.
103.) Hepatitis.
104.) Necrosis Hepatica. 

OTROS: 

105.) Alopecia.
106.) Anafilaxia.
107.) Agrandamiento de las mamas.
108.) Eritema multiforme.
109.) Edema periferico.
110.) Convulsiones. 

EFECTOS ADVERSOS EN NIÑOS DE 2 A 5 AñOS DE EDAD: 

66 pacientes pediatricos entre 2 y 5 años de edad recibieron 5 mgrs de loratadina 1 vez al dia en un
estudio placebo-control, doble ciego durante 14 dias, no se encontraron efectos adversos
inesperados en el perfil de seguridad de la loratadina. Las reacciones adversas mas comunmente
encontradas mas que el el grupo placebo en el 2-3 % de los pacientes fueron: 

1.) Diarrea.
2.) Epistaxis.
3.) Faringitis.
4.) Influenza-like sintomas.
5.) Fatiga.
6.) Estomatitis.
7.) Desordenes dentales.
8.) Dolor de oidos.
9.) Infeciones virales.
10.) Rash. 


=============================================================
2.) PEDIATRIC USE OF THE LORATADINE / ENGLISH
=============================================================
Source:
1.) Information given by the laboratory inside the box. (2.000) 

Pediatric Use: 

The satety of LORATADINE Syrup at a daily dose of 10 mg has been demonstrated in 188
pediatric patients 6 to 12 years of age in placebo-controlled 2-week trials. The effectiveness of
LORATADIN for the treatment of seasonal allergic rhinitis and chronic idiopathic urticaria in this
pediatric age group is based on an extrapolation of the demonstrated efficacy of LORATADINE in
adults in these conditions and the likelihood that the disease course, pathophysiology and the drug's
effect are substantially similar to that on the adults. The recommended dose for the pediatric
population is based on cross study comparison of the pharmacokinetics of LORATADINE in adults
and pediatric subjects and on the safety profile of loratadine in both adults and pediatric patients at
doses equal
to or higher than the recommended doses. 

The safety and effectiveness of LORATADIN in pediatric patients under 2 years of age nave not
been established. 

=============================================================
2.) USO PEDIATRICO DE LA LORATADINA / SPANISH
=============================================================
Fuente:
1.) Informacion suministrada por uno de los fabricantes dentro de la caja. (2.000) 

Uso pediatrico: 

La seguridad del Jarabe de LORATADINA a una dosis de 10 mgrs ha side demostrada en 188
pacientes pediatricos entre 6 y 12 años de edad en estudios placebo control de 2 semanas de
duracion. La efectividad de la LORATADINA para el tratamiento de la rinotis alergica estacional y
urticaria idiopatica cronica en este grupo de edad pediatrico esta basado en una extrapolacion de la
eficacia demostrada de la LORATADINA en adultos en estas condiciones y la probabilidad que el
curso de la enfermedad,
fisiopatologia, y efecto de la droga es similar que en el adulto. La dosis recomendada para la
poblacion pediatrica esta basada en un estudio cruzado comparativo de la farmacoquinetica de la
LORATADINA en adultos y niños y en el perfil de seguridad en ambos grupos, adultos y niños a
dosis iguales o superiores que las recomendadas 

La seguridad y efectividad de la LORATADINA en pacientes pediatricos por debajo de 2 años no
ha sido aun establecida. 

=============================================================
3.) LORATADINE, FDA REPORT
=============================================================
Source: The FDA 

EXECUTIVE SUMMARY 

ABBREVIATIONS:
-------------
AE= Adverse Event
BID= Twice Daily
CDER= Center for Drug Evaluation and Research
NDA= New Drug Application
OTC=Over-The-Counter
OPDRA=Office Of Post-Marketing Drug Assessment
QD=Once Daily
SAE=Serious Adverse Event
WR=Written Request
AERS=Adverse Event Reporting System 

LORATADINE
----------
There are five approved formulations of loratadine: 

NDA 19-658: Loratadine 10 mg (Claritin) tablets, approved April, 1993. 

NDA 20-704: Loratadine Zydis (Claritin RediTabs), approved December, 1993. 

NDA 19-670: Loratadine 5 mg/pseudoephedrine 120 mg (Claritin-D 12 Hour Extended Release
tablets, approved November, 1994. 

NDA 20-470: Loratadine 10 mg/pseudoephedrine 240 mg (Claritin-D 24 Hour Extended Release)
tablets, approved August, 1996. 

NDA 20-641: Loratadine 10 mg/10 mL (Claritin) Syrup, approved October, 1996. 

The single ingredient Claritin tablet products are currently labeled for use in children age 6 years and
above. Claritin Syrup was recently approved (September 26, 2000) for use in children down to age
2 years. The two Claritin-D formulations are approved for use in adults and children 12 years of age
and older. 

The NDA reviews for the single ingredient loratadine formulations showed that at the labeled dose of
10 mg once daily, the most commonly reported events from placebo-controlled clinical trials
included headache, dry mouth, and somnolence (8% for loratadine vs. 6% for placebo vs. 22% for
clemastine4 1 mg BID). Other safety information in the prescription package insert of potential
relevance in an OTC setting include recommendations for dosing adjustment in renal failure (because
of reduced loratadine clearance) and avoidance of the combination loratadine- pseudoephedrine
products (Claritin-D) in patients with cardiac disease as well as hepatic insufficiency. Clinical
pharmacology studies reported in the package insert and conducted in normal volunteers revealed no
evidence of QTc prolongation at doses of loratadine up to four times the labeled dose. Drug
interaction studies reported in the package insert have demonstrated increased plasma loratadine and
descarboethoxyloratadine5 levels associated with coadministration of erythromycin, cimetidine, and
ketoconazole. No significant effects on the QTc interval were observed in these studies. 

As of April, 2000, the AERS database contained 4081 adverse event reports in association with
products containing loratadine,including 55 reports with death as an outcome. The most prevalent
event categories were for "drug ineffectiveness," "drug interaction," "headache," and "palpitations."
Among the serious events, three categories were identified as potential areas of concern: ventricular
arrhythmias and sudden death, seizures, and hepatotoxicity. These adverse events are further
evaluated below. 

There were a total of 86 cases of ventricular arrhythmias, including 16 deaths, reported in
association with loratadine use. Careful review of these reports by FDA staff revealed that there
were confounding factors present in the majority of cases that precluded a definitive conclusion that
loratadine was causally related to the reported adverse event. These confounding factors included
use of concomitant medications that might be associated with arrhythmias and pre-existing
cardiovascular disease. It remains unclear whether concomitant cardiovascular disease is predictive
of an arrhythmic event in association with loratadine or simply reflects the type of patient more likely
to have been prescribed loratadine, given the known association of other "non-sedating"
antihistamines (i.e, terfenadine and astemizole) with ventricular arrhythmias. 

There were a total of 43 cases of seizures reported in association with loratadine use. Careful review
of these reports by FDA staff suggested that a causal association with loratadine was possible or
likely in 26 of the cases. Seizures are currently included as an adverse event in the loratadine
prescription package insert. A review of the professional labeling of several currently marketed OTC
antihistamines suggests that as a class, antihistamine products may rarely be associated with
seizures. 

Rare occurrences of liver-related events have been reported, including abnormal hepatic function,
jaundice, hepatitis, and hepatic necrosis, and are currently included in the loratadine prescription
package insert. In AERS, there were a total of 103 cases of hepatic injury reported in association
with loratadine use. Of these, there were five cases of hepatic failure, of which four required liver
transplantation. Careful review of these reports by FDA staff revealed that there were confounding
factors in 3 of the 5 cases of hepatic failure that precluded a definitive conclusion that loratadine was
causally related. These confounding factors included use of concomitant medications that might be
associated with liver failure and recent foreign travel. To further evaluate the potential association
between loratadine and hepatic failure, OPDRA reviewers undertook substantial efforts to establish
a comparative background rate for occurrence of hepatic failure, which is known to occur
"spontaneously" (i.e., without an identifiable cause) and which is not uncommonly reported in
association with use of a wide variety of drugs. The reporting rate for hepatic failure in association
with use of loratadine was several fold lower than the calculated background rate of hepatic failure
(i.e., 1 per million person years). In considering these data, it is important to remember that
underreporting of adverse events is a well recognized limitation of spontaneous reporting systems.
Although there is no clear causal relationship between loratadine use and the occurrence of hepatic
failure, the possibility that loratadine use may very rarely result in hepatic failure cannot be excluded. 

Soon after approval and marketing of Claritin-D 24 Hour Extended Release Tablets in 1996,
numerous reports of tablets becoming lodged in the patient’s esophagus were received. Some of
these cases were serious in nature and required endoscopic removal of the tablet, which had
adhered tightly to the esophageal mucosa. This problem was thought to be related to the tablet
coating and possibly the shape and size of the tablet. The tablet coating and shape were changed in
December 1998. No such serious adverse events have been reported for the new formulation. 

A careful review of the published literature for loratadine did not provide additional insight regarding
the primary areas of safety concern, nor did it identify new adverse events that were not observed in
the other safety databases. 

For loratadine, a report prepared by the Therapeutic Products Programme of the Bureau of
Licensed Products Assessment (Canadian regulatory authorities) dated June 22, 2000 was reviewed
by the FDA review team.6 This document was prepared as part of an ongoing, comprehensive
surveillance inquiry of all newer generation antihistamines presently marketed in Canada. A safety
analysis of loratadine was included in this report, with the focus primarily being on cardiovascular
risk. The data reviewed in the report included global safety data submitted by the drug sponsor,
including all Canadian domestic as well as foreign adverse event reports, published case reports and
clinical trials, and any new scientific information relevant to a benefit-risk assessment. The current
marketing status of loratadine in Canada as well as internationally was also reviewed. A summary of
the findings and conclusions of this report are provided below. 

Loratadine was first marketed in February, 1988 in Belgium. Approval was granted in June, 1988 in
Canada, where it became a non-prescription product in December, 1989. As of March, 1999,
loratadine in some formulation had been approved and marketed in 94 countries worldwide,
including in 17 as a non-prescription product. With the exception of the switch to non-prescription
status in 1989, no significant regulatory action related to safety has been taken regarding loratadine in
Canada since its approval. 

The most commonly reported cardiac-related adverse events in the databases reviewed in the
Canadian report were palpitations and/or tachycardia. There were cases of documented cardiac
arrhythmias, although most were confounded by concomitant medications and underlying cardiac
disease. The report noted that loratadine does not significantly block HERG potassium channels
under the same in vitro conditions in which terfenadine has been shown to block these important
channels that are involved in cardiac repolarization. Therefore, the authors of this report concluded
that a causal association of loratadine with ventricular arrhythmias was unlikely, both from a clinical
as well as a scientific standpoint. 

On the other hand, new information regarding the in vitro affinity of loratadine for an atrial ion
channel was discussed in the report. Although considered very preliminary, the possibility that a
primary atrial tachycardia could be triggered under certain rare conditions was discussed as an
explanation for the confirmed cases of atrial arrhythmia in the database. The authors of this report
concluded that these data alone could not support a labeling change. 

After careful consideration of the available data, the Canadian regulatory authorities recommended a
risk management plan for loratadine. Specifically, the loratadine product monograph would be
updated to include "tachycardia" under "Adverse Reactions," the adverse event databases would
continue to be closely monitored by both the sponsor as well as the regulators, and the sponsor
would be required to formally investigate the confounders "concomitant medications" and "underlying
cardiac disease" on the cardiovascular safety of this drug product. Loratadine would remain a
nonprescription product in Canada. 

In conclusion, a thorough review of all available safety data for loratadine failed to identify conclusive
evidence of a causal relationship between use or loratadine and serious adverse events. Potential
safety signals were noted for ventricular arrhythmias and liver failure; however, as described above,
the data are inconclusive and suggest that if such events were causally-related to loratadine, they are
extremely unusual . A potential association between loratadine use and seizures was observed,
consistent with information contained in the current package insert, and likely consistent with a class
effect. 

=============================================================
4.) Loratadine toxicity.
=============================================================
Am J Emerg Med 2000 Sep;18(5):639-40 

Gokel Y, Satar S, Sebe A. 

Publication Types:
Letter
=============================================================
=============================================================
5.) Double-blind comparison of cetirizine and loratadine in children ages 2 to 6 years with perennial
allergic rhinitis.
=============================================================
Am J Ther 1999 May;6(3):149-55 

Sienra-Monge JJ, Gazca-Aguilar A, Del Rio-Navarro B. 

Pulmonology and Allergy Department, Hospital Infantil de Mexico Federico Gomez, Mexico. 

Antihistamines are the pharmacologic cornerstone of treatment for allergic rhinitis. The comparative
effects of the newer, more specific H (1) -antagonists cetirizine and loratadine among younger
patients are not well characterized. The efficacy and safety of cetirizine and loratadine were
compared in a prospective, randomized, double-blind, longitudinal, parallel-group study of 80
children, 2 to 6 years of age, with perennial allergic rhinitis caused by house dust mites or plant
pollens (verified by a radioallergosorbent or skin test). Patients received cetirizine or loratadine at
0.2 mg/kg once daily in the morning for 28 days. Histamine skin tests and eosinophil counts from
nasal smears were performed at baseline and at the end of treatment. Individual rhinitis symptoms
were assessed by the investigator at baseline and on day 28 and by parents at baseline and daily in
symptom diaries. Global assessments were made by using a visual analog scale at baseline and at the
end of treatment. Cetirizine produced significantly greater inhibition of the wheal response compared
with loratadine (P <.0001). Eosinophil counts were improved to a comparable degree with both
agents. Cetirizine and loratadine produced comparable improvements in symptoms and according to
a global evaluation as assessed by the investigator at the end of treatment. Both agents produced
substantial symptomatic relief according to patients' daily diary assessments; however, cetirizine was
more effective than loratadine in relieving the symptoms of rhinorrhea, sneezing, nasal obstruction,
and nasal pruritus (P <. 0001). Both treatments were well tolerated; two patients receiving cetirizine
were dropped from the study because of adverse events. Cetirizine and loratadine provided
effective, well-tolerated relief of the symptoms of perennial allergic rhinitis in small children. Cetirizine
was more effective than loratadine in inhibiting the wheal response to histamine challenge and
afforded greater reductions in most individual symptoms assessed daily by the parent. 

=============================================================
6.) Clinical pharmacology of the H1-receptor antagonists cetirizine and loratadine in children.
=============================================================
Pediatr Allergy Immunol 2000 May;11(2):116-9 

Simons FE, Johnston L, Simons KJ. 

Health Sciences Clinical Research Center, Faculty of Medicine, University of Manitoba, Winnipeg,
Canada. 

H1-receptor antagonists are widely used in children but are not as well-studied in children as they
are in adults. Our objective was to determine the onset and duration of action and the relative
potency of the H1-receptor antagonists cetirizine and loratadine in children. We performed a
prospective, randomized, placebo-controlled, double-blind, crossover, single-dose study of
cetirizine and loratadine using suppression of the histamine-induced wheal and flare as the primary
outcome. In 15 allergic children, mean age 9 years, compared with baseline, cetirizine (10 mg)
suppressed the wheals and flares significantly from 0.25 to 24 h, achieving nearly 100% of flare
suppression from 2 to 24 h, inclusive, and loratadine (10 mg) suppressed the wheals and flares
significantly from 0.75 to 24 h, inclusive. Cetirizine suppressed the wheals and flares significantly
more than loratadine from 0.25 to 1 h, inclusive, and at 0.5, 1, 2, 3, 5, 6, 7, and 24 h, respectively.
Placebo also suppressed the wheal and flare significantly at some assessment times. Cetirizine and
loratadine both have excellent antihistaminic activity in children, with a rapid onset of action and a
24-h duration of action in this population. 

=============================================================
7.) Risk of ventricular arrhythmias associated with nonsedating antihistamine drugs.
=============================================================
Br J Clin Pharmacol 1999 Mar;47(3):307-13 

Comment in:
Br J Clin Pharmacol. 2000 Apr;49(4):379-80 

de Abajo FJ, Rodriguez LA. 

Area de Farmacovigilancia, Centro Nacional de Farmacobiologia, Madrid, Spain. 

AIMS: To quantify and compare the incidence of ventricular arrhythniias associated with the use of
five nonsedating antihistamines: acrivastine, astemizole, cetirizine, loratadine and terfenadine. The
effects of age, sex, dose, duration of treatment, and the interaction with P450 inhibitor drugs were
also examined. METHODS: We carried out a cohort study with a nested case-control analysis using
the UK-based General Practice Research database (GPRD). The study cohort included persons
aged less than 80 years old who received their first prescription for any of the five study drugs
between January 1, 1992 and September 30, 1996. We estimated relative risks and 95%
confidence intervals of idiopathic ventricular arrhythmias with current use of antihistamines as
compared with non use. RESULTS: The study cohort included 197425 persons who received
513012 prescriptions. Over the study period 18 valid cases of idiopathic ventricular arrhythmias
were detected. Nine occurred during the current use of any antihistamine, resulting in a crude
incidence of 1.9 per 10000 person-years (95%CI: 1.0-3.6) and a relative risk of 4.2 (95%CI:
1.5-11.8) as compared with non use. Astemizole presented the highest relative risk (RR= 19.0;
95%CI: 4.8-76.0) of all study drugs, while terfenadine (RR=2.1; 95%CI:0.5-8.5) was in the range
of other nonsedating antihistamines. Older age was associated with a greater risk of ventricular
arrhythmias (RR=7.4; 95%CI: 2.6-21.4) and seemed to increase the effect of antihistamines
(RR=6.4; 95%CI: 1.7-24.8). The proportions of high dose terfenadine and the concomitant use with
P450 inhibitors among current users of terfenadine were 2.7% and 3.4%, respectively over the study
period with no single case of ventricular arrhythmias occurring in the presence of these two risk
factors. CONCLUSIONS: The use of nonsedating antihistamines increases the risk of ventricular
arrhythmias by a factor of four in the general population. Yet, the absolute effect is quite low
requiring 57000 prescriptions, or 5300 person-years of use for one case to occur. The risk
associated with terfenadine was no different from that with other nonsedating antihistamines. 

=============================================================
8.) Clinical prescribing of allergic rhinitis medication in the preschool and young school-age child:
what are the options?
=============================================================
BioDrugs 2001;15(7):453-63 


Galant SP, Wilkinson R. 

Department of Paediatric Allergy/Immunology, University of California, Irvine, California, USA. 

Allergic rhinitis (AR) is the most common chronic condition in children and is estimated to affect up
to 40% of all children. It is usually diagnosed by the age of 6 years. The major impact in children is
due to co-morbidity of sinusitis, otitis media with effusion, and bronchial asthma. AR also has
profound effects on school absenteeism, performance and quality of life. Pharmacotherapy for AR
should be based on the severity and duration of signs and symptoms. For mild, intermittent
symptoms lasting a few hours to a few days, an oral second-generation antihistamine should be used
on an as-needed basis. This is preferable to a less expensive first-generation antihistamine because of
the effect of the latter on sedation and cognition. Four second-generation antihistamines are currently
available for children under 12 years of age: cetirizine, loratadine, fexofenadine and azelastine nasal
spray; each has been found to be well tolerated and effective. There are no clearcut advantages to
distinguish these antihistamines, although for children under 5 years of age, only cetirizine and
loratadine are approved. Other agents include pseudoephedrine, an oral vasoconstrictor, for nasal
congestion, and the anticholinergic nasal spray ipratropium bromide for rhinorrhoea. Sodium
cromoglycate, a mast cell stabiliser nasal spray, may also be useful in this population. For patients
with more persistent, severe symptoms, intranasal corticosteroids are indicated, although one might
consider azelastine nasal spray, which has anti- inflammatory activity in addition to its antihistamine
effect. With the exception of fluticasone propionate for children aged 4 years and older, and
mometasone furoate for those aged 3 years and older, the other intranasal corticosteroids including
beclomethasone dipropionate, triamcinolone, flunisolide and budesonide are approved for children
aged 6 years and older. All are effective, so a major consideration would be cost and safety. For
short term therapy of 1 to 2 months, the first-generation intranasal corticosteroids (beclomethasone
dipropionate, triamcinolone, budesonide and flunisolide) could be used, and mometasone furoate
and fluticasone propionate could be considered for longer-term treatment. Although somewhat more
costly, these second-generation drugs have lower bioavailability and thus would have a better safety
profile. In patients not responding to the above programme or who require continuous medication,
identification of specific triggers by an allergist can allow for specific avoidance measures and/or
immunotherapy to decrease the allergic component and increase the effectiveness of the
pharmacological regimen. 

=============================================================
9.) The pharmacokinetics, electrocardiographic effects, and tolerability of loratadine syrup in children
aged 2 to 5 years.
=============================================================
Clin Ther 2000 May;22(5):613-21 

Salmun LM, Herron JM, Banfield C, Padhi D, Lorber R, Affrime MB. 

Allergy/Respiratory Diseases Clinical Research, Schering-Plough Research Institute, Kenilworth,
New Jersey 07033-0539, USA. luis.salmun@spcorp.com 

OBJECTIVE: We assessed the pharmacokinetics and tolerability of 5 mg loratadine syrup (1
mg/mL) in children aged 2 to 5 years. METHODS: Two studies were undertaken. A single-dose,
open-label bioavailability study was performed to characterize the pharmacokinetic profiles of
loratadine and its metabolite desloratadine. Plasma concentrations of loratadine and desloratadine
were determined at 0, 1, 2, 4, 8, 12, 24, 48, and 72 hours after a single administration of 5 mg
loratadine syrup to 18 healthy children (11 male, 7 female; 12 black, 5 white, 1 other; mean age +/-
SD, 3.8 +/- 1.1 years; mean weight +/- SD, 17.4 +/- 4.4 kg). In addition, a randomized,
double-blind, placebo-controlled, parallel-group study was performed to assess the tolerability of 5
mg loratadine syrup after multiple doses. Loratadine (n = 60) or placebo (n = 61) was given once
daily for 15 days to children with a history of allergic rhinitis or chronic idiopathic urticaria. In the
loratadine group, 27 boys and 33 girls (52 white, 8 black) were enrolled, with a mean age +/- SD of
3.67 +/- 1.13 years and a mean weight +/- SD of 17.2 +/- 3.8 kg. In the placebo group, 27 boys
and 34 girls (53 white, 7 black, 1 Asian) were enrolled, with a mean age +/- SD of 3.52 +/- 1.12
years and a mean weight +/- SD of 17.3 +/- 2.9 kg. Tolerability was assessed based on
electrocardiographic results, occurrence of adverse events, changes in vital signs, and results of
laboratory tests and physical examinations. RESULTS: The peak plasma concentrations of
loratadine and desloratadine were 7.78 and 5.09 ng/mL, respectively, observed 1.17 and 2.33
hours after administration of loratadine; the areas under the plasma concentration-time curve to the
last quantifiable time point for loratadine and desloratadine were 16.7 and 87.2 ng x h/mL,
respectively. Single and multiple doses were well tolerated, with no adverse events occurring with
greater frequency after multiple doses of loratadine than after placebo. Electrocardiographic
parameters were not altered by loratadine compared with placebo. There were no clinically
meaningful changes in other tolerability assessments. CONCLUSION: Loratadine was well tolerated
in this small, selected group of children aged 2 to 5 years at a dose providing exposure similar to that
with the adult dose (ie, 10 mg once daily). 

=============================================================
10.) Comparison of once-daily ebastine 20 mg, ebastine 10 mg, loratadine 10 mg, and placebo in
the treatment of seasonal allergic rhinitis. The Ebastine Study Group.
=============================================================
J Allergy Clin Immunol 2000 Jun;105(6 Pt 1):1101-7 

Ratner PH, Lim JC, Georges GC. 

Sylvana Research, San Antonio, TX, USA. 

BACKGROUND: Ebastine and loratadine are 2 nonsedating second-generation H(1) antihistamines
with once-daily dosing. OBJECTIVE: We compared the efficacy and safety of ebastine 20 mg and
10 mg, loratadine 10 mg, and placebo administered once daily for 4 weeks in controlling the
symptoms of seasonal allergic rhinitis (SAR). METHODS: In a double-blind, placebo-controlled,
randomized, parallel-group study, 565 patients with ragweed SAR, ages 12 to 70 years, received
either ebastine 20 mg, ebastine 10 mg, loratadine 10 mg, or placebo once daily for 4 weeks.
Patients recorded morning and evening reflective scores (past 12 hours) as well as snapshot scores
(at time of recording) for nasal discharge, congestion, sneezing, itching, and total eye symptoms.
Total symptom score (TSS) is the sum of these 5 scores. RESULTS: Ebastine 20 mg produced
significantly greater (P <.05) reductions from baseline compared with loratadine 10 mg over the
entire treatment period in the mean daily reflective (42.5% vs 36.3%) and mean morning snapshot
(40.3% vs 31.3%) TSS. The overall improvement in daily reflective and morning snapshot TSS was
comparable between ebastine 10 mg and loratadine 10 mg and significantly better than placebo (P
<.05). The total percent of patients with adverse events was similar among all 4 treatment groups (P
=.78). CONCLUSION: Ebastine 20 mg given once daily was significantly superior to loratadine 10
mg given once daily at improving the rhinitis total symptom score throughout the day and at
awakening over a 4-week period. Ebastine 20 mg and 10 mg doses were both efficacious and well
tolerated in the treatment of SAR. 

=============================================================
11.) Comparison of the efficacy, safety and quality of life provided by fexofenadine hydrochloride
120 mg, loratadine 10 mg and placebo administered once daily for the treatment of seasonal allergic
rhinitis.
=============================================================
Clin Exp Allergy 2000 Jun;30(6):891-9 

Van Cauwenberge P, Juniper EF. 

Department of Otorhinolaryngology, University Hospital, Ghent, Belgium.
paul.vancauwenberge@rug.ac.be 

BACKGROUND: As there have been no previously published studies, this multinational,
double-blind, randomized, placebo-controlled, parallel group study compared the efficacy, safety
and impact on quality of life (QoL) in seasonal allergic rhinitis patients (SAR) of fexofenadine and
loratadine (with placebo), when administered once daily. METHODS: Six hundred and eighty-eight
SAR patients were randomized to receive fexofenadine HCl 120 mg, loratadine 10 mg or placebo,
once daily for 2 weeks. The key parameters were the change from baseline in: mean 24-h reflective
total symptom scores (TSS); sum of four individual symptom scores, excluding nasal congestion;
instantaneous TSS; individual symptom scores including nasal congestion; and Rhinoconjunctivitis
Quality of Life Questionnaire (RQLQ). Adverse events were recorded. RESULTS: Mean 24-h
reflective and instantaneous TSS were significantly reduced by both fexofenadine HCl (both P </=
0.0001) and loratadine (P </= 0.001 and P </= 0.005, respectively) compared with placebo (n =
639). Among individual symptom scores, fexofenadine HCl was significantly better than loratadine in
improving 24-h reflective itchy, watery, red eyes, as well as relieving nasal congestion (P </= 0.05
for both). Fexofenadine HCl was also significantly better than loratadine (P </= 0.03) and placebo
(P </= 0.005) in improving QoL, and the differences were of a magnitude considered to be clinically
relevant. Loratadine had no statistically significant effect on QoL compared with placebo. The
incidence of adverse events was low and similar across all treatment groups. CONCLUSION:
Fexofenadine HCl and loratadine administered once daily are effective and well tolerated in SAR. In
this study, fexofenadine HCl was significantly more effective than loratadine in relieving eye
symptoms and nasal congestion. Furthermore, fexofenadine was significantly better than loratadine in
improving QoL. 

=============================================================
12.) Cetirizine, loratadine, or placebo in subjects with seasonal allergic rhinitis: effects after
controlled ragweed pollen challenge in an environmental exposure unit.
=============================================================
J Allergy Clin Immunol 1998 May;101(5):638-45 

Comment in:
J Allergy Clin Immunol. 1999 Apr;103(4):715 

Day JH, Briscoe M, Widlitz MD. 

Department of Medicine, Queens University, Kingston, Ontario, Canada. 

BACKGROUND: Allergic rhinitis affects nearly one in 10 Americans. Cetirizine is a newer
once-daily selective H1-antagonist. In traditional clinical trials, cetirizine has been shown to be safe
and effective for the treatment of seasonal and perennial allergic rhinitis and chronic idiopathic
urticaria. OBJECTIVE: To better characterize the efficacy and onset of action of cetirizine in a more
controlled but clinically relevant setting, this agent was compared with loratadine and placebo in
patients with symptomatic seasonal allergic rhinitis undergoing controlled pollen challenge in an
environmental exposure unit (EEU). METHODS: This was a double-blind, randomized,
parallel-group study. After screening, patients were exposed to ragweed pollen (primed) in the EEU
(up to six exposures), and those with qualifying symptom scores were randomized to controlled
pollen exposure (two periods of 5.5 to 6.5 hours over 2 days) and once-daily treatment with 10 mg
cetirizine (n = 67), 10 mg loratadine (n = 67), or placebo (n = 68). The mean ragweed pollen level
was 3480 +/- 350 grains/m3 (standard deviation). The primary efficacy variables were the total
symptom complex (TSC) and the major symptom complex (MSC) scores. Symptoms were
evaluated every half hour in the EEU throughout the study. RESULTS: Cetirizine produced a 36.7%
mean reduction in TSC scores overall versus 15.4% with loratadine and 12.0% with placebo (p < or
= 0.01). Cetirizine also produced a 37.4% mean reduction in MSC scores overall versus 14.7%
with loratadine and 6.7% with placebo (p < or = 0.01). Onset of action as assessed by reductions in
TSC and MSC scores versus placebo was evident within 1 hour with cetirizine (p < or = 0.02) and
3 hours with loratadine (p < or = 0.03). The incidence of treatment-related side effects was similar
among groups, with headache reported most commonly in each group. CONCLUSION: Cetirizine
is well tolerated and effective in reducing symptoms of seasonal allergic rhinitis in patients undergoing
controlled pollen challenge. 

=============================================================
13.) Brompheniramine, loratadine, and placebo in allergic rhinitis: a placebo-controlled comparative
clinical trial.
=============================================================
J Clin Pharmacol 1998 Apr;38(4):382-9 

Druce HM, Thoden WR, Mure P, Furey SA, Lockhart EA, Xie T, Galant S, Prenner BM,
Weinstein S, Ziering R, Brandon ML. 

Department of Clinical Research, Whitehall-Robins Healthcare, Madison, New Jersey 07940-0871,
USA. 

A double-blind, randomized, placebo-controlled, parallel-group, multicenter study was conducted to
compare the effectiveness of an extended-release formulation of a classical antihistamine,
brompheniramine, and a second-generation compound, loratadine, in the treatment of allergic rhinitis.
Subjects with symptoms of allergic rhinitis received brompheniramine 12 mg twice daily (n = 112),
loratadine 10 mg once daily (n = 112), or placebo twice daily (n = 114) for 7 days. Study
medications were blinded using a double-dummy technique. Subjects completed an overall
evaluation of symptom relief on a daily basis and returned on treatment days 3 and 7, at which times
the investigator assessed symptom severity. The investigator and subject each completed a global
efficacy evaluation, and subjects were interviewed regarding adverse experiences. The primary
efficacy variable was the physicians' global efficacy evaluation on day 3. Symptoms also were
analyzed as summed severity scores for all symptoms and for the nasal symptom cluster of
rhinorrhea, sneezing, and nasal blockage. At all post-baseline evaluations (days 3, 7, and averaged
over the two days), brompheniramine was significantly better than loratadine and placebo for both
sets of summed symptom scores and all three global assessments. Loratadine was significantly better
than placebo for physician ratings of total symptom severity averaged over the two days and for the
physician and subject ratings of the nasal cluster on day 3. Central nervous system-related symptoms
were the most frequently reported adverse experiences; somnolence was reported most frequently
by patients taking brompheniramine, and its occurrence was less frequent as treatment continued. A
nonprescription, extended-release formulation of brompheniramine 12 mg twice daily provided
significantly better relief of symptomatic allergic rhinitis than loratadine 10 mg once daily. 

=============================================================
14.) Evaluation of the potential cardiotoxicity of the antihistamines terfenadine, astemizole, loratadine,
and cetirizine in atopic children.
=============================================================
Ann Allergy Asthma Immunol 1998 Apr;80(4):333-7 

Comment in:
Ann Allergy Asthma Immunol. 1999 Nov;83(5):422 

Delgado LF, Pferferman A, Sole D, Naspitz CK. 

Department of Pediatrics, Paulista School of Medicine, Federal University of Sao Paulo, SP, Brazil. 

BACKGROUND: Adverse cardiac effects have been related to the use of H1-receptor antagonists
terfenadine and astemizole. OBJECTIVE: We have investigated the cardiac effects of the
H1-receptor antagonists terfenadine, astemizole, loratadine and cetirizine, used in recommended
doses, concomitantly or not with the antibiotic erythromycin. METHODS: A group of 80 children
aged 5 to 12 years was studied. All children had been diagnosed with perennial allergic rhinitis based
on symptoms, clinical signs and a positive immediate skin test to Dermatophagoides pteronyssinus.
The children had no personal history of cardiac disease or hepatic dysfunction, and they had a
normal electrocardiogram (ECG) at the beginning of the study. Forty children had allergic rhinitis and
sinusitis, and were assigned to subgroups of ten children who received terfenadine, astemizole,
loratadine, or cetirizine, concomitantly with erythromycin, for 14 days. Erythromycin was started to
treat presumed bacterial infection in children with complete radiologic opacification of the maxillary
sinus(es). The remaining 40 children had no sinusitis, and were assigned to subgroups of 10 children
who received terfenadine, astemizole, loratadine, or cetirizine for 14 days. RESULTS: No significant
changes in the QT interval and QTc (QT corrected by Bazzett's equation) were observed among
children who received astemizole, loratadine or cetirizine, with or without erythromycin. Children
who have received terfenadine and erythromycin showed significantly prolonged QT interval (mean
pretreatment and posttreatment values 0.32s and 0.34s, respectively). Analysis of the QTc interval,
however, showed no significant differences in the group treated with terfenadine and erythromycin
(mean values 0.39s and 0.39s, respectively). CONCLUSIONS: Our results show that H1-receptor
antagonists terfenadine, astemizole, loratadine and cetirizine, administered with or without
erythromycin, to atopic children in recommended doses, do not induce adverse cardiac effects.
Although the association between terfenadine and erythromycin has caused a statistically significant
increase in QT interval measurements, the magnitude of these changes was below levels considered
cardiotoxic or clinically relevant. 

=============================================================
15.) Onset of action and efficacy of terfenadine, astemizole, cetirizine, and loratadine for the relief of
symptoms of
=============================================================
allergic rhinitis. 

Ann Allergy Asthma Immunol 1997 Aug;79(2):163-72 

Day JH, Briscoe MP, Clark RH, Ellis AK, Gervais P. 

Division of Allergy and Immunology, Kingston General Hospital, Ontario, Canada. 

BACKGROUND: Terfenadine, astemizole, cetirizine, and loratadine are compared in their abilities
to produce relief of symptoms of allergic rhinitis. OBJECTIVE: The aim of this study was to
compare the onset of action and efficacy of the study medications. METHODS: 111
ragweed-sensitive subjects were primed with pollen in the Environmental Exposure Unit. Study entry
required adequate symptoms over a 3 hour exposure to 5000 +/- 300 grains/m3 of ragweed pollen.
On the test day, subjects were given a single dose of either terfenadine 60 mg (22), astemizole 10
mg (22), cetirizine 10 mg (23), loratadine 10 mg (22), or placebo (22) when sufficiently symptomatic
after a 60-minute exposure. Allergen levels were maintained and symptoms recorded every 30
minutes. RESULTS: Proportions of subjects with clinically important relief were cetirizine, 69.6%;
terfenadine, 54.5%; loratadine, 50.0%; astemizole, 40.9%; and placebo, 31.8% but differences
weren't significant between treatment groups (P = .119). Survival curves for times to onset of
clinically important relief for the four treatment groups were not different (P = .119). Subjects
realizing definitive relief were cetirizine, 65.2%; terfenadine, 45.5%; loratadine, 31.8%; placebo,
27.3%; and astemizole, 22.7% (P = .023). Survival analysis of onset time for definitive relief found
significant differences (P = .010). The ranking was cetirizine --> terfenadine --> loratadine -->
astemizole (quickest to slowest). Global evaluation based on subject willingness to take the
medication again yielded percentages: cetirizine, 82.6%; terfenadine, 66.7%; astemizole, 63.6%;
loratadine, 40.9%; and placebo, 36.4% (P = .036). CONCLUSION: Cetirizine and terfenadine
continuously ranked higher in terms of onset of action and efficacy, while loratadine and astemizole
ranked lower. Significance was detected in definitive relief and relative efficacy. 

=============================================================
16.) Comparative outdoor study of the efficacy, onset and duration of action, and safety of cetirizine,
loratadine, and placebo for seasonal allergic rhinitis.
=============================================================
J Allergy Clin Immunol 1996 Feb;97(2):617-26 

Meltzer EO, Weiler JM, Widlitz MD. 

Allergy and Asthma Medical Group and Research Center, San Diego, CA 92123, USA. 

BACKGROUND: Cetirizine, a new once-daily highly specific H1-antagonist, has been shown in
conventional studies to be efficacious in the treatment of seasonal and perennial allergic rhinitis and
chronic idiopathic urticaria. OBJECTIVE: The efficacy, duration and onset of action, and safety of
cetirizine, 10 mg once daily, was compared with that of loratadine, 10 mg once daily, and placebo in
a field study of patients with seasonal allergic rhinitis. METHODS: This was a randomized,
double-blind, parallel, double-dummy study conducted over 2 days in spring allergy season at
outdoor parks in San Diego and Iowa City. Study medication was administered at 10:00 AM on
both days. After screening, eligible patients completed rhinitis symptom diaries in the park hourly
from 7:30 to 9:30 AM (baseline); at 10:30 AM and hourly from 11:00 AM to 4:00 PM (period I);
at 6:00, 8:00, and 10:00 PM at home (period II); and the next day in the park hourly from 8:00 to
10:00 AM (period III), and from 11:00 AM to 4:00 PM (period IV). Major and total symptom
complex scores, global efficacy and overall satisfaction, and adverse events were assessed.
RESULTS: Of the 279 patients (140 men and 139 women; mean age, 29 years) randomized to
treatment, 278 were included in the efficacy analysis. Cetirizine produced significantly greater mean
reductions than loratadine or placebo in major symptom complex severity scores at all periods (p <
or = 0.05), except period I for placebo. Cetirizine also produced mean reductions in total symptom
complex severity scores that were superior to loratadine at every evaluation period (p < 0.05) and
were statistically different from placebo at period II (p < 0.01). A rapid onset of action was
observed with cetirizine, as was a better response pattern in the patient global assessment of efficacy
compared with loratadine. Study medications were well tolerated; no patient stopped treatment
because of side effects. The incidence of somnolence with cetirizine was 13% versus 2% with
placebo (p < 0.05); headache occurred more frequently with loratadine (23%) than with cetirizine
(11%, p = 0.03). CONCLUSIONS: Cetirizine relieved rhinitis symptoms more effectively and
quickly than loratadine and placebo in this field study of seasonal allergic rhinitis. Both active agents
were generally well tolerated. 

=============================================================
17.) [Severe adverse effect of the anti-allergy drug loratadine--warning against prolonged use of
non-prescription drugs].
=============================================================
Lakartidningen 1992 Jun 17;89(25):2281 

[Article in Swedish] 

Nyman K, Bergman U. 

Lisebergs vardcentral, Alvsjo.
=============================================================
=============================================================
18.) Loratadine (SCH29851) 40 mg once daily versus terfenadine 60 mg twice daily in the treatment
of seasonal allergic rhinitis.
=============================================================
J Int Med Res 1987 Mar-Apr;15(2):63-70 

Bruttmann G, Pedrali P. 

Seventy patients received loratadine 40 mg once daily, terfenadine 60 mg twice daily, or placebo in
a 14-day, double-blind, randomized study. Four nasal and four non-nasal symptoms associated with
allergic rhinitis were evaluated. At the endpoint (the last evaluable visit), the mean total scores of
combined nasal and non-nasal symptoms decreased (improved) from the baseline by 51.8% and
55.7% with loratadine and terfenadine, respectively, but increased (worsened) by 6.1% with
placebo. There was a significant difference between both the loratadine and terfenadine treatment
groups and the placebo group (P = 0.001) but not between the active medication groups (P =
0.608). Overall therapeutic response was good or excellent in 14 of the 23 patients given loratadine,
in 18 of the 24 given terfenadine and in none of the 23 given placebo. The difference between each
active medication group and the placebo group was significant (P less than or equal to 0.01) but
there was no significant difference between the two active treatment groups (P greater than 0.35).
No loratadine patient had any adverse side-effects. Sedating effects occurred in one terfenadine
patient, headache in one placebo patient and two terfenadine patients (one terfenadine patient with
severe headache discontinued treatment), and dyspepsia in two placebo patients. No anti-cholinergic
effects occurred in this study. Loratadine 40 mg once daily was effective and safe in the relief of
symptoms of allergic rhinitis. 

=============================================================
19.) Suppression of histamine-induced wheal response by loratadine SCH 29851) over 28 days in
man.
=============================================================
Ann Allergy 1986 Oct;57(4):253-6 

Roman IJ, Kassem N, Gural RP, Herron J. 

Five groups of 12 healthy volunteers each received in double-blind, randomized fashion oral b.i.d.
doses of 10, 20, or 40 mg loratadine, 12 mg chlorpheniramine maleate (CTM), or placebo for 28
days. Histamine and saline were injected intradermally into opposite arms at baseline and at specified
times following treatment on days 1, 3, 7, 14, 21, and 28. Notable suppression of adjusted wheal
formation (histamine-induced minus saline-induced) occurred within two hours after the first dose of
each active treatment on day 1. In general, throughout the treatment period, suppression of adjusted
wheal formation by all doses of loratadine was significantly greater than by placebo. Suppression by
10 mg loratadine was comparable to CTM, and 20 and 40 mg loratadine were significantly greater
than CTM. Suppression of wheal formation by loratadine during the treatment period and during five
days posttreatment were dose related. The continued effectiveness of loratadine throughout the 28
days suggests that tolerance to loratadine did not develop in this study. Sedation occurred in 8 of 12
subjects receiving CTM, 1 of 12 receiving 10 mg loratadine, and 1 of 12 receiving placebo. 

=============================================================
20.) Loratadine in childrens with skin alergic diseases
=============================================================
Der Kinderarzt 20/12, 1818-1821(1989) 

Sitzmann, F.C, Neumann Y 
====================================
21.) [Fixed pigmented erythema antihistamine H1: about 2 cases and review of the literature].
====================================
Therapie. 2014 May-Jun;69(3):243-4. doi: 10.2515/therapie/2014001. Epub 2014 Jun 18.

[Article in French]
Lakhoua G, El Aidli S, Zaïem A, Sahnoun R, Kastalli S, Hedi Loueslati M, Daghfous R.
Abstract

We describe two cases of fixed drug eruptions induced by pheniramine (1(st) case) and loratadine (2(nd) case)
===========================================================
22.) Drowsiness and motor responses to consecutive daily doses of promethazine and loratadine.
==========================================================
Clin Neurophysiol. 2014 Dec;125(12):2390-6. doi: 10.1016/j.clinph.2014.03.026. Epub 2014 Apr 12.

Baumann-Birkbeck L1, Grant GD1, Anoopkumar-Dukie S1, Kavanagh JJ2.
Author information

1
School of Pharmacy, Griffith University, Gold Coast, Australia; Griffith Health Institute, Griffith University, Gold Coast, Australia.
2
Centre for Musculoskeletal Research, Griffith University, Gold Coast, Australia; Griffith Health Institute, Griffith University, Gold Coast, Australia. Electronic address: j.kavanagh@griffith.edu.au.

Abstract
OBJECTIVES:

Limited information is available regarding sedation and motor function following repeat dosing of antihistamines. This study examined how promethazine and loratadine affect day-time drowsiness, the commencement of voluntary movement, and involuntary movement when administered on consecutive days.
METHODS:

Ten healthy young subjects (24±5years) were recruited into a double-blind, placebo-controlled, three-way crossover study. Subjects ingested either promethazine, loratadine or a placebo, and ingested the same drug 24h later. Measures of drowsiness, simple reaction time (SRT), choice reaction time (CRT), and postural tremor were obtained pre-ingestion, 1h post-ingestion and 2h post-ingestion on each day.
RESULTS:

Consecutive daily doses of promethazine and loratadine affected SRT and CRT, respectively, whereby reaction time deficits were less pronounced following the repeat dose. A reduced tremor response was also observed following consecutive daily dosing of promethazine, in contrast to loratadine which caused an increase in tremor amplitude with the consecutive daily dose.
CONCLUSIONS:

Reaction time and tremor responses differed following the single dose compared to consecutive doses.
SIGNIFICANCE:

Sufferers of allergic rhinitis often require antihistamine dosing regimens that continue over multiple days. Future studies will benefit from examining drowsiness and movement responses following single doses as well as consecutive dosing.
=============================================
23.) Low dosage promethazine and loratadine negatively affect neuromotor function.
============================================
Clin Neurophysiol. 2012 Apr;123(4):780-6. doi: 10.1016/j.clinph.2011.07.046. Epub 2011 Aug 30.

Kavanagh JJ1, Grant GD, Anoopkumar-Dukie S.
Author information

1
School of Physiotherapy and Exercise Science, Griffith University, Gold Coast, Australia. j.kavanagh@griffith.edu.au

Abstract
OBJECTIVES:

Determine how the sedating antihistamine promethazine and non-sedating antihistamine loratadine at a dose of 10mg influence voluntary and involuntary motor processes in the hours following ingestion and the morning after ingestion.
METHODS:

Eight healthy young adults were recruited into a human double-blind, placebo-controlled, three-way crossover study. Neuromotor function was examined using a battery of controlled reaction time, postural tremor, and heart rate variability measures. Neuromotor function was assessed 4 times for each of the promethazine, loratadine and placebo interventions; pre-ingestion, 1h post-ingestion, 2h post-ingestion, and the following day.
RESULTS:

Self-perceived levels of drowsiness increased only after ingestion of promethazine. However, both antihistamines had negative effects on simple reaction time, choice reaction time, the RMS and peak power amplitude of postural tremor, and autonomic cardiac regulation.
CONCLUSIONS:

The presence of selective neuromotor deficits following ingestion of promethazine and loratadine suggest that sedating and non-sedating antihistamines alter neuromotor function. It is possible that the H(1) antagonists used in this study have antimuscarinic effects, which may impact on the central dopaminergic system that plays a role in modulating several CNS processes associated with movement.
SIGNIFICANCE:

Antihistamines are one of the most commonly procured over-the-counter medications. The current study suggests that taking non-sedating antihistamines to avoid the adverse drug reaction of drowsiness may not avoid unwanted motor control side-effects.
============================================
24.) Severe pegfilgrastim-induced bone pain completely alleviated with loratadine: A case report.
============================================
J Oncol Pharm Pract. 2015 Aug;21(4):301-4. doi: 10.1177/1078155214527858. Epub 2014 Mar 24.

Romeo C1, Li Q2, Copeland L3.
Author information

1
College of Pharmacy, The Ohio State University, Columbus, OH, USA.
2
James Cancer Hospital, The Ohio State University, Columbus, OH, USA Quan.Li@osumc.edu.
3
College of Medicine, The Ohio State University, Columbus, OH, USA.

Abstract

Febrile neutropenia is an oncologic emergency that can result in serious consequences. Granulocyte colony stimulating factors (G-CSFs) are often used as prophylaxis for febrile neutropenia. Bone pain is the most notorious adverse effect caused by G-CSFs. Specifically, with pegfilgrastim (Neulasta(®)), the incidence of bone pain is higher in practice than was observed during clinical trials. Traditional analgesics, such as non-steroidal anti-inflammatory drugs (NSAIDs) and opioids, can be ineffective in severe pegfilgrastim-induced bone pain. With the high frequency of this adverse effect, it is clear that health practitioners need additional treatment options for patients who experience severe pegfilgrastim-induced bone pain. The mechanisms of bone pain secondary to G-CSFs are not fully known, but research has shown that histamine release is involved in the inflammatory process. There is scant previous clinical data on antihistamine use in the management of G-CSF-induced pain. We present the first case report in which loratadine prophylaxis completely alleviated NSAID-resistant severe pain secondary to pegfilgrastim. The result showed that loratadine may be a promising option for severe, resistant pegfilgrastim-induced bone pain. Further clinical studies are warranted and ongoing.
=============================================================
25.) [Drug-induced immune hemolytic anemia: a retrospective study of 10 cases].
[Article in French]
=============================================================
Bollotte A1, Vial T2, Bricca P3, Bernard C1, Broussolle C1, Sève P4.
Author information

1
Service de médecine interne, hôpital de la Croix-Rousse, 1, place de l'Hôpital, 69317 Lyon, France.
2
Centre régional de pharmacovigilance et d'information sur les médicaments, 69424 Lyon cedex 3, France.
3
Laboratoire d'immuno-hématologie, EFS, groupement hospitalier est, hôpital Louis-Pradel, 69677 Bron cedex, France.
4
Service de médecine interne, hôpital de la Croix-Rousse, 1, place de l'Hôpital, 69317 Lyon, France. Electronic address: pascal.seve@chu-lyon.fr.

Abstract
PURPOSE:

Drug-induced immune haemolytic anemia occurs in one case per million and can be fatal. Our aim was to describe the main characteristics and the type of drug involved.
METHODS:

Cases were retrospectively identified using spontaneous notifications collected by our pharmacovigilance centre and the results of immuno-hematological investigations performed by the laboratory of French blood establishment of Lyon between 2000 and 2012. Inclusion criteria were: an immune (positive direct antiglobulin test), hemolytic, anemia (haemoglobin <100 g/L), with at least a plausible causal relationship with drug exposure according to the French method of imputability or the presence of drug-dependent antibodies, and exclusion of other causes of hemolysis.
RESULTS:

Ten cases (5 men and 5 women, median age 54.4 years) were identified. Causal drugs were ambroxol, beta-interferon, cefotetan, ceftriaxone, loratadine, oxacillin, oxaliplatine, piperacillin-tazobactam, pristinamycin, and quinine. The median time to onset of anemia after starting the culprit drug was 6 days (2 hours to 16 days). The median nadir of hemoglobin was 57.9 g/L (range: 34-78). The direct antiglobulin test was positive in 8 patients: IgG only (n=4), IgG and complement (n=3), and IgA (n=1). Drug-induced immune haemolytic anemia was considered as definite in 5 cases with positive drug-induced antibodies, probable in 4 cases negative for the detection of drug-induced antibodies but with plausible or likely causal relationship with drug exposure, and probable with an autoimmune mechanism in 1 case.
CONCLUSION:

The diagnosis of DIIHA is often difficult because of the similarities with autoimmune haemolytic anemia and the inconstant sensitivity of immunologic tests that sometimes required repetitive assessmen
=======================================
26.) When Hydromorphone Is Not Working, Try Loratadine: An Emergency Department Case of Loratadine as Abortive Therapy for Severe Pegfilgrastim-Induced Bone Pain.
=======================================
J Emerg Med. 2017 Feb;52(2):e29-e31. doi: 10.1016/j.jemermed.2016.08.018. Epub 2016 Oct 14.

Moore K1, Haroz R2.
Author information

1
Department of Emergency Medicine, Medical Toxicology, Cooper University Hospital, Camden, New Jersey.
2
Department of Emergency Medicine, Medical Toxicology, Cooper University Hospital, Camden, New Jersey; Cooper Medical School of Rowan University, Medical Toxicology, Cooper University Hospital, Camden, New Jersey.

Abstract
BACKGROUND:

Intractable bone pain is a notorious adverse effect of granulocyte-colony stimulating factors (G-CSFs), such as pegfilgrastim and filgrastim, which are given to help prevent neutropenia in patients who are undergoing chemotherapy. G-CSF-induced bone pain is surprisingly common and often refractory to treatment with conventional analgesics.
CASE REPORT:

This article describes an emergency department case of opiate and nonsteroidal anti-inflammatory drug-resistant pegfilgrastim-induced bone pain that was successfully alleviated with 10 mg of oral loratadine, allowing for discharge home. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: This case suggests that loratadine may be an easy to implement, safe, and effective therapy in the emergency department management of intractable bone pain caused by G-CSF use. Emergency physicians should be aware that loratadine may successfully relieve otherwise intractable G-CSF-induced bone pain and allow for discharge home.
=======================================
27.) Pegfilgrastim-Induced Bone Pain: A Review on Incidence, Risk Factors, and Evidence-Based Management.
========================================
Ann Pharmacother. 2017 Apr 1:1060028017706373. doi: 10.1177/1060028017706373. [Epub ahead of print]

Moore DC1, Pellegrino AE1.
Author information

1
1 Levine Cancer Institute, Carolinas HealthCare System, Charlotte, NC, USA.

Abstract
OBJECTIVE:

To review the incidence, risk factors, and management of pegfilgrastim-induced bone pain (PIBP).
DATA SOURCES:

PubMed was searched from 1980 to March 31, 2017, using the terms pegfilgrastim and bone pain.
STUDY SELECTION AND DATA EXTRACTION:

English-language, human studies and reviews assessing the incidence, risk factors, and management of PIBP were incorporated.
DATA SYNTHESIS:

A total of 3 randomized, prospective studies and 2 retrospective studies evaluated pharmacological management of PIBP. Naproxen compared with placebo demonstrated a reduction in the degree, incidence, and duration of bone pain secondary to pegfilgrastim. Loratadine was not effective in reducing the incidence of bone pain prophylactically, but a retrospective study evaluating dual antihistamine blockade with loratadine and famotidine demonstrated a decreased incidence in bone pain when administered before pegfilgrastim.
CONCLUSION:

Naproxen is effective at managing PIBP. Although commonly used, antihistamines have a paucity of data supporting their use. Dose reductions of pegfilgrastim and opioids may also be potential management options; however, data supporting these treatment modalities are scarce.
=======================================
28.) Pegfilgrastim use and bone pain: a cohort study of community-based cancer patients.
=======================================
Pawloski PA1, Larsen M2, Thoresen A3, Giordana MD4.
Author information

1
HealthPartners Institute for Education and Research, Minneapolis, MN, USA Regions Hospital Cancer Care Center, St. Paul, MN, USA pamala.a.pawloski@healthpartners.com.
2
University of Minnesota College of Pharmacy, Minneapolis, MN, USA.
3
United Hospital, St. Paul, MN, USA.
4
Regions Hospital Cancer Care Center, St. Paul, MN, USA.

Abstract
PURPOSE:

Bone pain is a common adverse effect of the granulocyte colony-stimulating factors filgrastim and pegfilgrastim. However, the incidence of reported bone pain varies and therapies to mitigate this adverse effect are limited to case reports and one randomized controlled trial. The purpose of this study was to describe pegfilgrastim use, the incidence and treatment of bone pain, and rate of severe or febrile neutropenia among cancer patients receiving pegfilgrastim at a metropolitan, hospital-based, community cancer center.
METHODS:

This retrospective chart review included the first 100 adult oncology patients who received at least one dose of pegfilgrastim from 1 January 2012 to 31 December 2012. Descriptive analyses were used to evaluate the primary and secondary outcomes.
RESULTS:

Of the identified cases, 69 cancer patients were evaluable. Most patients (74%) received pegfilgrastim for primary prophylaxis. Pegfilgrastim-associated bone pain occurred in 19% and loratadine was the most common medication used to treat it. Among the patients who received pegfilgrastim for primary prophylaxis, 8% were hospitalized for febrile neutropenia. Among those hospitalized for febrile neutropenia, 64% had not received pegfilgrastim for primary prophylaxis.
CONCLUSIONS:

Pegfilgrastim is commonly used for primary prophylaxis during the first cycle of chemotherapy. Hospitalizations for febrile neutropenia occurred most commonly among patients without primary prophylaxis. Pegfilgrastim-associated bone pain occurred in a similar percentage, as reported in randomized controlled trials but less than that reported by survey. Loratadine was the most commonly employed medication to mitigate this adverse effect.
=======================================
29.) Prevention of granulocyte-colony stimulating factor (G-CSF) induced bone pain using double histamine blockade.
======================================
Support Care Cancer. 2017 Mar;25(3):817-822. doi: 10.1007/s00520-016-3465-y. Epub 2016 Nov 5.

Gavioli E1, Abrams M2,3.
Author information

1
Department of Pharmacy, Indiana University Health, 601 W. Second St., Bloomington, IN, 47403, USA. egavioli@kingsbrook.org.
2
Indiana University Health Cancer Care Infusion, 508 W. 2nd St., Bloomington, IN, 47403, USA.
3
Indiana University Health Infusion Therapy, 601 W 2nd St., Bloomington, IN, 47403, USA.

Abstract
PURPOSE:

Febrile neutropenia (FN) is an oncological emergency that may reduce patient survival due to chemotherapy dose delays or reductions. It is recommended that patients at risk for FN receive prophylaxis with granulocyte-colony stimulating factor (G-CSF). Bone pain is a common side effect through a mechanism not fully understood. It is thought to be due to histamine release from an inflammatory response.
METHODS:

This was a retrospective cohort from January to November 2015. Oncology patients receiving an initial dose of G-CSFs rated their bone pain on a 0-10 scale prior to starting each cycle of chemotherapy and at least 1 day after G-CSF had been given. Those who developed bone pain received prophylaxis at their next G-CSF dose with a combination of famotidine and loratadine. The primary endpoint was to determine the analgesic effects of double histamine blockade for G-CSF induced bone pain. The secondary endpoint was to determine potential risk factors for the development of bone pain.
RESULTS:

Thirty percent of patients developed bone pain within this cohort, and 17 patients were included in the final analysis. Bone pain scores were lower by a mean of 1.21[(0.20-2.23), p = 0.019] in patients who were prophylaxed with the double histamine blockade. Type of cancer, treatment, age, and BMI were not significant predictors of bone pain.
CONCLUSION:

The use of a double histamine blockade is an inexpensive, safe, and effective way to alleviate bone pain symptoms secondary to G-CSF agents. Further investigation is warranted for prospective larger studies to confirm these results.
=================================================
30.) Pro-arrhythmic potential of oral antihistamines (H1): combining adverse event reports with drug utilization data across Europe.
==================================================
Poluzzi E1, Raschi E1, Godman B2, Koci A1, Moretti U3, Kalaba M4, Wettermark B5, Sturkenboom M6, De Ponti F1.
Author information

1
Department of Medical and Surgical Sciences, Alma Mater Studiorum-University of Bologna, Bologna, Italy.
2
Division of Clinical Pharmacology, Karolinska Institutet, Stockholm, Sweden; Strathclyde Institute of Pharmacy and Biomedical Sciences, Strathclyde University, Glasgow, United Kingdom.
3
Clinical Pharmacology Unit, University of Verona, Verona, Italy.
4
Republic Fund for Health Insurance, Belgrade, Serbia.
5
Division of Clinical Pharmacology, Karolinska Institutet, Stockholm, Sweden; Centre for Pharmacoepidemiology, Karolinska University Hospital, Solna, Stockholm, Sweden; Stockholm, County Council, Stockholm, Sweden.
6
Erasmus University Medical Centre, Rotterdam, Netherlands.

Abstract
BACKGROUND:

There is appreciable utilisation of antihistamines (H1) in European countries, either prescribed by physician and purchased by patients for self-medication. Terfenadine and astemizole underwent regulatory restrictions in '90 because of their cardiac toxicity, but only scarce clinical data are available on other antihistamines.
AIM:

To investigate the pro-arrhythmic potential of antihistamines by combining safety reports of the FDA Adverse Event Reporting System (FAERS) with drug utilization data from 13 European Countries.
METHODS:

We identified signals of antihistamine arrhythmogenic potential by analyzing FAERS database for all cases of Torsades de Pointes (TdP), QT abnormalities (QTabn), ventricular arrhythmia (VA) and sudden cardiac death/cardiac arrest (SCD/CA). Number of cases ≥3 and disproportionality were used to define alert signals: TdP and QTabn identified stronger signals, whereas SCD/CA identified weaker signals. Drug utilization data from 2005 to 2010 were collected from administrative databases through health authorities and insurance.
RESULTS:

Antihistamines were reported in 109 cases of TdP/QT prolongation, 278 VA and 610 SCD/CA. Five agents resulted in stronger signals (cetirizine, desloratadine, diphenhydramine, fexofenadine, loratadine) and 6 in weaker signals (alimemazine, carbinoxamine, cyclizine, cyproeptadine, dexchlorpheniramine and doxylamine). Exposure to antihistamines with stronger signal was markedly different across European countries and was at least 40% in each Country. Cetirizine was >29 Defined Daily Doses per 1000 inhabitants per day (DID) in Norway, desloratadine >11 DID in France and loratadine >9 DID in Sweden and Croatia. Drugs with weaker signals accounted for no more than 10% (in Sweden) and in most European countries their use was negligible.
CONCLUSIONS:

Some second-generation antihistamines are associated with signal of torsadogenicity and largely used in most European countries. Although confirmation by analytical studies is required, regulators and clinicians should consider risk-minimisation activities. Also antihistamines without signal but with peculiar use in a few Countries (e.g., levocetirizine) or with increasing consumption (e.g., rupatadine) deserve careful surveillance.
==================================================
31.) Histamine H1-receptor antagonists against Leishmania (L.) infantum: an in vitro and in vivo
==================================================
evaluation using phosphatidylserine-liposomes.
Pinto EG1, da Costa-Silva TA2, Tempone AG3.
Author information

1
Center for Parasitology and Mycology, Instituto Adolfo Lutz, Av. Dr. Arnaldo, 351, 01246-900, São Paulo SP, Brazil; Instituto de Medicina Tropical de São Paulo, Universidade de São Paulo, Av. Dr. Enéas de Carvalho Aguiar, 470, 05403-000, São Paulo SP, Brazil.
2
Center for Parasitology and Mycology, Instituto Adolfo Lutz, Av. Dr. Arnaldo, 351, 01246-900, São Paulo SP, Brazil.
3
Center for Parasitology and Mycology, Instituto Adolfo Lutz, Av. Dr. Arnaldo, 351, 01246-900, São Paulo SP, Brazil. Electronic address: atempone@usp.br.

Abstract

Considering the limited and toxic therapeutic arsenal available for visceral leishmaniasis (VL), the drug repositioning approach could represent a promising tool to the introduction of alternative therapies. Histamine H1-receptor antagonists are drugs belonging to different therapeutic classes, including antiallergics and anxyolitics. In this work, we described for the first time the activity of H1-antagonists against L. (L.) infantum and their potential effectiveness in an experimental hamster model. The evaluation against promastigotes demonstrated that chlorpheniramine, cinnarizine, hydroxyzine, ketotifen, loratadine, quetiapine and risperidone exerted a leishmanicidal effect against promastigotes, with IC50 values in the range of 13-84μM. The antihistaminic drug cinnarizine demonstrated effectiveness against the intracellular amastigotes, with an IC50 value of 21μM. The mammalian cytotoxicity was investigated in NCTC cells, resulting in IC50 values in the range of 57-229μM. Cinnarizine was in vivo studied as a free formulation and entrapped into phosphatidylserine-liposomes. The free drug was administered for eight consecutive days at 50mg/kg by intraperitoneal route (i.p.) and at 100mg/kg by oral route to L. infantum-infected hamsters, but showed lack of effectiveness in both regimens, as detected by real time PCR. The liposomal formulation was administered by i.p. route at 3mg/kg for eight days and reduced the parasite burden to 54% in liver when compared to untreated group; no improvement was observed in the spleen of infected hamsters. Cinnarizine is the first antihistaminic drug with antileishmanial activity and could be used as scaffold for drug design studies for VL.
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32.) Investigation of cytotoxic and genotoxic effects of the antihistaminic drug, loratadine, on human lymphocytes.
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Drug Chem Toxicol. 2015 Jan;38(1):57-62. doi: 10.3109/01480545.2014.900074. Epub 2014 Mar 18.

Kontaş S1, Atlı Şekeroğlu Z.
Author information

1
Department of Biology, Faculty of Science and Letters, Ordu University , Ordu , Turkey.

Abstract
CONTEXT:

Loratadine (LOR) is a new generation antihistamine used in the treatment of allergic disorders.
OBJECTIVE:

The aim of this study was to evaluate the cytogenotoxic effect of LOR on human peripheral blood lymphocytes.
MATERIALS AND METHODS:

We investigated the genotoxic effect of this drug in cultured human peripheral blood lymphocytes using sister chromatid exchange (SCE), chromosomal aberrations (CA) and micronucleus (MN) assay in culture conditions. Proliferation index (PI), mitotic index (MI) and nuclear division index (NDI) were also calculated to determine the cytotoxic/cytostatic effect. Cultures were treated with LOR at three concentrations (5, 15 and 25 µg/ml) for 48 h.
RESULTS:

Although the MI significantly decreased at the higher concentrations (15 and 25 µg/ml) compared with negative (solvent) control, LOR indicated weaker cytotoxic potential in PI and NDI values at all the tested concentrations. LOR increased the frequencies of SCE, CA and MN in all lymphocyte cultures. However, significant increase was observed in MN at the medium and highest doses (15 and 25 µg/ml) and in CA at the medium dose (15 µg/ml) compared with negative (solvent) control culture. Our results indicate that LOR has cytotoxic and genotoxic effects on human peripheral blood lymphocyte cultures.
DISCUSSION:

Although most of previously findings have shown that LOR does not reflect genotoxicity, our results indicated that it may be a genotoxic drug.
CONCLUSION:

More studies are necessary to elucidate the relationship between cytotoxic, genotoxic and apoptotic effects, and to make a possible risk assessment in patients receiving therapy with this drug.
 


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