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:
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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.

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REFERENCIAS BIBLIOGRAFICAS / BIBLIOGRAPHICAL REFERENCES 
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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.
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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. 

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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.
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30.) Pro-arrhythmic potential of oral antihistamines (H1): combining adverse event reports with drug utilization data across Europe.
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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.
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31.) Histamine H1-receptor antagonists against Leishmania (L.) infantum: an in vitro and in vivo
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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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