LAS DOCE DEL PATIBULO, MEDICINAS FUERA DEL MERCADO. /DRUGS OUT FROM THE MARKET, THE DOZEN OF THE PARTY

 

 Doce Medicinas Retiradas Del Mercado. !

Twelve Medicins Withdrawn From The Market. ! 

  

" Particularmente pienso que los laboratorios farmacéuticos, cuando fabrican una medicina, lo hacen para curar o mejorar la salud de la población, no creo que lo hagan con la intención de malograr el estado físico de una persona que necesita esa medicina, pasa que con el tiempo, sea a corto, mediano o largo plazo se descubren sus efectos deletéreos o dañinos y deben ser retiradas del mercado por el bien común..."

EDITORIAL ESPAÑOL
==================
Hola amigos de la red, DERMAGIC EXPRESS hoy con un tema bien caliente, DOCE MEDICINA RETIRADAS DEL MERCADO. LAS DOCE DEL PATIBULO.  

Lo primero que debemos reconocer, es que todo buen laboratorio que fabrica medicinas NO LO HACE para matar gente o disminuir la población, fabrica e inventa medicinas para mejorar nuestra salud y prolongar nuestra existencia.    

Desde este punto de vista estos famosos laboratorios que dia a dia traen al mercado nuevas drogas para mejorar nuestra calidad de vida, son una bendición para la humanidad. Nunca olvidemos esto.  

Por supuesto existen FALSOS LABORATORIOS cuyo único objetico es hacer dinero vendiendo FALSAS MEDICINAS, lo puedes leer AQUI: FALSAS MEDICINAS UNA NUEVA PANDEMIA.  

Pero estas DOCE MEDICINAS que aquí te traigo fueron fabricadas por tremendos laboratorios de reconocida fama mundial. Lamentablemente tuvieron que ser retiradas del mercado por sus efectos adversos. 

Como dato anecdótico desde el año 1.953 hasta el año 2.013 fueron retirados del mercado 462 productos medicinales, la mayoría por tener efectos adversos en el hígado:  TOXICIDAD HEPATICA. Del total  solo 43 fueron retirados a NIVEL MUNDIAL. 

De modo que la ciencia de las medicinas nos ha traído más beneficios que "desastres" y por ello, repito tenemos que estar agradecidos a todos estos científicos que entregan toda una vida para inventar y producir nuevas medicinas para el bienestar de la humanidad. 

Estas DOCE MEDICINAS fueron lanzadas al mercado con grandes expectativas, las cuales no se cumplieron y fueron retiradas del mercado. 

Hay otras medicinas que aun no han sido retiradas y tienen GRANDES EFECTOS ADVERSOS, y están altamente cuestionadas hoy dia, pero no las voy a mencionar porque quizá tu estés utilizándola y no te hace daño. 

Esto debemos aprenderlo, TODO MEDICAMENTO tiene sus efectos adversos, algunos letales. y solo cuando una gran mayoría de personas es afectada con síntomas graves, es cuando se decide retirarlo del mercado. Es la cruda realidad.

Por si no lo sabías, te cuento que ademas de medico dermatologo, programador y fotógrafo soy un especialista en averiguar sobre medicinas. 

Espero que lean atentamente esta revisión, la cual es anecdótica pero que nos enseña que no TODO  LO QUE BRILLA EN EL CIELO ES ORO. 

Siempre debes estar atento de las medicinas que ingieres y sus posibles efectos adversos.

Una vez más felicito a estos laboratorios, pues su intención con estas MEDICINAS HOY DESCONTINUADAS fue mejorar nuestra salud. 

Saludos a todos.

Dr. José Lapenta. 

EDITORIAL ENGLISH

===================

Hello friends of the network, DERMAGIC EXPRESS today with a hot topic, TWELVE MEDICINES WITHDRAWN FROM THE MARKET. THE TWELVE OF THE PARTY. 


The first thing to recognize is that every good laboratory that manufactures medicines DOES NOT do to kill people or reduce population, manufactures and invents medicines to improve our health and prolong our existence. 

From this point of view these famous laboratories that bring new drugs to market to improve our quality of life, are a blessing for humanity. Let's never forget this.

Of course there are FALSE LABORATORIES whose only objective is to make money selling FALSE MEDICINES, you can read it HERE: FALSE MEDICINES A NEW PANDEMIC. 

But these TWELVE MEDICINES that I bring here were manufactured by tremendous laboratories of recognized world-wide fame. Unfortunately they had to be withdrawn from the market due to their adverse effects.

As an anecdotal data from the year 1.953 until the year 2.013, 462 medicinal products were withdrawn from the market, most of them having adverse effects on the liver: HEPATIC TOXICITY. Of the whole only 43 were withdrawn at WORLD LEVEL.

So the science of medicines has brought us more benefits than "disasters" and for that, I repeat we have to be grateful to all these scientists who give a lifetime to invent and produce new medicines for the welfare of humanity.

These TWELVE MEDICINS were released to the market with big expectations, which were not fulfilled and were withdrawn from the market.

There are other medicines that have not yet been withdrawn and have BIG ADVERSE EFFECTS, and are highly questioned today, but I will not mention them because maybe you are using it and it does not hurt you.

This we must learn it, EVERY DRUG has its adverse effects, some lethal. And only when a large majority of people are affected with severe symptoms, is when they decide to withdraw from the market. It is the full reality.

In case you did not know, I tell you that besides a dermatologist, programmer and photographer I am a specialist in finding out about medicines.

I hope you read this review carefully, which is anecdotal but teaches us that not everything that shines in the sky is gold.

You should always be aware of the medicines you take and their possible adverse effects.

Once again I congratulate these laboratories, because their intention with these MEDICINES TODAY DISCOUNTED was to improve our health.

Greetings to all.

Dr. Jose Lapenta.

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 REFERENCIAS BIBLIOGRAFICAS / BIBLIOGRAPHICAL REFERENCES 
 ================================================================
 1.) THE POSICOR (MIFEBRADIL)/ EL POSICOR (MIFEBRADIL), Lab. ROCHE).
-.) ROCHE LABORATORIES ANNOUNCES WITHDRAWAL OF POSICOR FROM THE MARKET
2.) THE BAYCOL, LIPOBAY (CERIVASTATIN), (Lab. BAYER).
-.) EL LIPOBAY, BAYCOL (CERIVASTATINA) Laboratorio BAYER.
-.) BAYER VOLUNTARILY WITHDRAWS BAYCOL- (LIPOBAY)
3.) THE TROVAN/ EL TROVAN (TROVAFLOXACIN), ( Lab. PFIZER).
.) EL TROVAN (TROVAFLOXACINA): Laboratorio PFIZER.)
-.) FDA ISSUES PUBLIC HEALTH ADVISORY ON LIVER TOXICITY ASSOCIATED WITH THE ANTIBIOTIC TROVAN
4.) THE ASTEMIZOLE (HISMANAL), (Lab JANSSEN-CILAG Pharmaceutica).
-.) EL HISMANAL (ASTEMIZOLE): Laboratorio JANSSEN-CILAG Pharmaceutica
-.) JANSSEN PHARMACEUTICA ANNOUNCES THE WITHDRAWAL OF HISMANAL FROM THE MARKET
5.) THE PROPULSID /PREPULSID (CISAPRIDE), (Lab JANSSEN-CILAG). -.) EL PREPULSID (CISAPRIDE): Laboratorio JANSSEN-CILAG Pharmaceutica
-.) New Safety Recommendations for Use of Cisapride (Propulsid)
6.) THE VIOXX (ROFECOXIB), Laboratory MERCK S. and D.
-.) Merck Announces Voluntary Worldwide Withdrawal of VIOXX®
-.) Merck Halts Vioxx Sales on Health Threats
-.) EL VIOXX (ROFECOXIB): Laboratorio MERCK S. and D.
-.) Merck retira ‘Vioxx’ del mercado por incremento del riesgo cardiovascular en uso prolongado.
7.) THE BEXTRA (VALDECOXIB), (Lab. PFIZER).
-.) LA BEXTRA (VALDECOXIB) Laboratorio PFIZER)
-.) THE BEXTRA (VALDECOXIB) SIDE EFFECTS
-.) New Warnings for Bextra (VALDECOXIB).
-.) Valdecoxib-induced toxic epidermal necrolysis in a patient allergic to sulfa drugs.
-.) BEXTRA WITHDRAWN FROM THE MARKET 
8.) SIBUTRAMINE - REDUCTIL Lab. ABBOTT
-.) SIBUTRAMINA- REDUCTIL - Lab. ABBOTT.
-.) They recognize that Reductil for Weight loss was related to 34 deaths
-.) Reconocen que el adelgazante Reductil fue relacionado con 34 muertes
9.) DEXFENFLURAMINE - REDUX Lab. INTERNEURON PHARMACEUTICALS, WYETH- AYERST.
-.) DEXFENFLURAMINA- REDUX Lab. INTERNEURON PHARMACEUTICALS, WYETH-AYERST
10.) TROGLITAZON - REZULIN Lab. SANKYO, PARKE-DAVIS
-.) TROGLITAZON - ReZULIN Lab. SANKYO, PARQUE DAVIS.
11.) THIORIDAZINE  MELLERIL, MALLERIL / MELERIL Lab. NOVARTIS.
-.) TIORIDAZINA - MELERIL Lab. NOVARTIS.
12.) LYMErix VACCINE - Lab. Glaxo-Smith-Kline(GSK).
-.) LYMERrix -VACUNA Lab. Glaxo-Smith-Kline(GSK)
-.) FDA Vaccine Advisory Committee,  LymeRix Vaccine Victim's Stories
-.) Post-marketing withdrawal of 462 medicinal products because of adverse drug reactions: a systematic review of the world literature

==========================================

1.) THE POSICOR (MIFEBRADIL)/ EL POSICOR (MIFEBRADIL), Lab. ROCHE). 

===========================================

In the year 1.997 the house ROCHE throws to the market the DRUG POSICOR (MIBEFRADIL), with blocking effect of the channels of the calcium for the handling of the hypertension and stable chronic angina. Postmarketing surveillance revealed a potential serious interaction between mibefradil and -blockers, digoxin, verapamil, and diltiazem, especially in elderly patients. The manufacturer (ROCHE) voluntarily withdrew mibefradil on June 8, 1998. Some PEOPLE died for the use of POSICOR.

==============================

EL POSICOR (MIFEBRADIL)

==============================

En el año 1.997 la casa ROCHE lanzo al mercado la DROGA POSICOR (MIBEFRADIL), con efecto bloqueador de los canales del calcio para el manejo de la hipertension y angina cronica estable. Estudios de postmercadeo revelaron una potencial y seria interaccion entre esta droga y bloqueadores, digoxina, verapamil y diltiazem especialmente en personas de edad. El laboratorio ROCHE, VOLUNTARIAMENTE retiro del MERCADO EL MIBEFRADIL EL 8 de junio de 1.998. Unos cuantos murieron por el uso de POSICOR.

=========================================

ROCHE LABORATORIES ANNOUNCES WITHDRAWAL

OF POSICOR FROM THE MARKET

=========================================

Source: The FDA.

Roche Laboratories of Nutley, NJ has announced that it is voluntarily withdrawing the heart drug, Posicor (mibefradil), from the market as a result of new information about potentially harmful interactions with other drugs.

In many cases, drug interactions can be addressed by appropriate labeling changes and public education, but due to the complexity of the prescribing information needed in this case, and seriousness of side effects, FDA and Roche agreed that it would be difficult to administer Posicor safely. The following may be used to respond to inquiries.

Posicor is a calcium-channel blocker, chemically unlike the other approved products in this class. Posicor was approved in June of last year, to be used in the treatment of patients with hypertension and chronic stable angina.

Posicor reduces the activity of certain liver enzymes that are important in helping the body eliminate many other drugs. Inhibiting these enzymes can cause some of these other drugs to accumulate in the body to dangerous levels.

When Posicor entered the market in August of 1997, its enzyme-inhibiting properties were described in the labeling. The labeling specifically listed three drugs (astemizole, cisapride, and terfenadine) that could be expected to accumulate to dangerous levels if Posicor was coadministered.

In December, after learning of several cases in which patients suffered serious adverse reactions after taking Posicor with one or more of the other drugs, FDA strengthened the labeling of Posicor, and two more drugs (lovastatin and simvastatin) were added to the label's list of those that should never be coadministered with Posicor. FDA also issued a public warning about this problem and the company issued a Dear Doctor letter to physicians.

From spontaneous reports and ongoing trials, FDA and Roche have continued to learn of adverse reactions related to coadministration of Posicor with several other drugs. At present, more than 25 drugs are known to be potentially dangerous if used with Posicor -- a number and diversity of drugs that cannot be practically addressed by standard label warnings.

Since Posicor has not been shown to offer special benefits (such as treating patients who do not respond to other antihypertensive and anti-anginal drugs), the drug's problems are viewed as an unreasonable risk to consumers.

Patients now taking Posicor should not simply discontinue treatment because stopping medications can be risky. Instead, patients should promptly consult with their physicians about appropriate alternative therapy. In addition, patients now taking Posicor should not add any new medication to their current treatment without consulting their physicians.

Roche Laboratories is providing information in a "Dear Doctor" letter to physicians, pharmacists, nurse practitioners, and other health care professionals. Questions about the withdrawal of Posicor can be addressed to Roche's 24-hour hotline at 1-800-205-4611.

The following is a list of drugs that depend on the same liver enzyme as Posicor (mibefradil). Use of them in combination with Posicor could be dangerous.

===============================================

2.) THE BAYCOL, LIPOBAY (CERIVASTATIN), (Lab. BAYER)

===============================================

That same year of 1.997 the house BAYER, throws to the WORLD MARKET THE DRUG BAYCOL, LIPOBAY (CERIVASTATIN) a member of the class of drugs that diminish the cholesterol commonly referred as "estatins ". For the year of 1.998 the first deads were reported by the use of this drug, because of a fatal RHABDOMYOLYSIS, mainly when it was used in combination with THE DRUG LOPID (GEMFIBROZIL) another drug used to diminish the cholesterol.

REGRETTABLY the LABORATORY MADE ALL THE POSSIBLE one to COVER THIS RAW REALITY, and the people still dying because of this DRUG, until August 8, 2.001 and after the FDA had reported 31 deads in United States. The laboratory BAYER DECIDES to PUT AN END TO THE DRUG taking OFF from the MARKET TO THE BAYCOL, LIPOBAY. 

THE MONSTER BAYER few days later I BUY FOR 3 thousand million DOLLARS A PART OF THE LABORATORIO AVENTIS. !

==============================================

EL LIPOBAY, BAYCOL (CERIVASTATINA) Laboratorio BAYER.

==============================================

Ese mismo año de 1.997 la CASA BAYER, UNO DE LOS "monstruos" en agroquimicos lanza al MERCADO MUNDIAL LA DROGA BAYCOL, LIPOBAY (CERIVASTATIN) un miembro de la clase de drogas que disminuyen el colesterol comunmente referidas como "estatinas". Para el año de 1.998 se reportaron los primeros muertos por el uso de esta droga, a causa de una RABDOMIOLISIS fatal, sobre todo cuando era usada en combinacion con LA DROGA LOPID (GEMFIBROZIL) otra droga usada para bajar el colesterol.

LAMENTABLEMENTE el LABORATORIO HIZO TODO LO POSIBLE POR "TAPAR" ESTA CRUDA REALIDAD, y la gente siguio muriendo a causa de esta DROGA, hasta que el 8 DE agosto de 2.001 y despues que la FDA habia reportado 31 muertos en Estados Unidos, el laboratorio BAYER DECIDE PONER FIN A esta MEDICINA sacando del MERCADO AL BAYCOL-LIPOBAY. 

EL MOSNTRUO BAYER pocos dias despues COMPRO POR 3 mil millones de DOLARES UNA PARTE DEL LABORATORIO AVENTIS. !

=================================================

BAYER VOLUNTARILY WITHDRAWS BAYCOL- (LIPOBAY)

================================================

T01-34 Print Media: 301-827-6242

August 8, 2001 Broadcast Media: 301-827-3434

Consumer Inquiries: 888-INFO-FDA

FDA today announced that Bayer Pharmaceutical Division is voluntarily withdrawing Baycol (cerivastatin) from the U.S. market because of reports of sometimes fatal rhabdomyolysis, a severe muscle adverse reaction from this cholesterol-lowering (lipid-lowering) product. The FDA agrees with and supports this decision.

Baycol (cerivastatin), which was initially approved in the U.S. in 1997, is a member of a class of cholesterol lowering drugs that are commonly referred to as "statins." Statins lower cholesterol levels by blocking a specific enzyme in the body that is involved in the synthesis of cholesterol. While all statins have been associated with very rare reports of rhabdomyolysis, cases of fatal rhabdomyolysis in association with the use of Baycol have been reported significantly more frequently than for other approved statins.

Fatal rhabdomyolysis reports with Baycol have been reported most frequently when used at higher doses, when used in elderly patients, and particularly, when used in combination with gemfibrozil (LOPID and generics), another lipid lowering drug. FDA has received reports of 31 U.S. deaths due to severe rhabdomyolysis associated with use of Baycol, 12 of which involved concomitant gemfibrozil use.

Rhabdomyolysis is a condition that results in muscle cell breakdown and release of the contents of muscle cells into the bloodstream. Symptoms of rhabdomyolysis include muscle pain, weakness, tenderness, malaise, fever, dark urine, nausea, and vomiting. The pain may involve specific groups of muscles or may be generalized throughout the body.

Most frequently the involved muscle groups are the calves and lower back; however, some patients report no symptoms of muscle injury. In rare cases the muscle injury is so severe that patients develop renal failure and other organ failure, which can be fatal.

Bayer Pharmaceutical Division has announced plans to withdraw Baycol to the pharmacy level. Pharmacies will be instructed to return the product to the manufacturer for a refund.

Patients who are taking Baycol should consult with their physicians about switching to alternate medications to control their cholesterol levels. Patients taking Baycol who are experiencing muscle pain or are also taking gemfibrozil should discontinue Baycol immediately and consult their physician.

There are five other statins available in the U.S. that may be considered as alternatives to Baycol. They are: lovastatin (Mevacor), pravastatin (Pravachol), simvastatin (Zocor), fluvastatin (Lescol), and atorvastatin (Lipitor).

For further information regarding the withdrawal of Baycol, patients and physicians can contact Bayer Customer Service 1-800-758-9794 or the FDA's Drug Information Office at 301-827-4573 or 1-888-INFO-FDA, or go to "Baycol Information" on FDA's Website.

BMJ. 2004 June 26; 328 (7455): 1537

=========================================================

3.) THE TROVAN/ EL TROVAN (TROVAFLOXACIN), ( Lab. PFIZER).

========================================================

The trovafloxacina(TROVAN),antibiotic (fluoroquinolone) relatively new in the market, liberated by the FDA in February of 1.998, with big promotion and marketed by the famous laboratory PFIZER.

One year later 140 CASES OF HEPATIC TOXICITY had already been reported, in some cases requiring of liver transplant, and death in some cases, with SINGLE THREE DAYS OF TREATMENT. THE FDA RECOMMENDED ITS EXIT OF THE MARKET IN JUNE 1.999.

Him but STRANGE of all this it is that TROVAN was THROWN TO THE MARKET with some PRELIMINARY studies where there were NEVER TOXIC EFFECTS IN THE LIVER. In Our country it was HARDLY retired LATER 2 MONTHS OF THEIR LAUNCHING).

==========================================

EL TROVAN (TROVAFLOXACINA): Laboratorio PFIZER.)

===========================================

La trovafloxacina(TROVAN), antibiotico (fluoroquinolona) relativamente nuevo en el mercado, liberado por la FDA en febrero de 1.998, con grandes espectativas y lanzado por el famoso laboratorio PFIZER,

Un año despues ya se habian reportado 140 CASOS DE TOXICIDAD HEPATICA, en algunas casos requiriendo de transplante de higado y muerte con SOLO TRES DIAS DE TRATAMIENTO. LA FDA RECOMENDO SU SALIDA DEL MERCADO EN JUNIO 1.999.

Lo mas RARO de TODO ESTO es que TROVAN FUE LANZADO AL MERCADO con unos estudios PRELIMINARES donde NUNCA HUBO EFECTOS TOXICOS EN EL HIGADO. En Nuestro pais fue retirado APENAS 2 MESES DESPUES DE SU LANZAMIENTO

=============================================================

FDA ISSUES PUBLIC HEALTH ADVISORY ON LIVER TOXICITY ASSOCIATED WITH THE ANTIBIOTIC TROVAN

=============================================================

Source: The FDA

The Food and Drug Administration today issued a public health advisory to

physicians concerning the risks of liver toxicity associated with the use

of Trovan (trovafloxacin, an oral antibiotic) and Trovan-IV

(alatrofloxacin, the intravenous formulation of the drug). This action

follows postmarketing reports of rare but severe liver injuries leading to

transplants and deaths.

In issuing this advisory, FDA is informing physicians that Trovan should be

reserved for use only in patients who meet all of the following criteria:

Patients who have at least one of several specified infections such as

nosocomial (hospital-acquired) pneumonia or complicated intra-abdominal

infections that, in the judgment of the treating physician, is serious and

life- or limb-threatening;

Patients who begin their therapy in in-patient health care facilities

(hospitals or longterm nursing care facilities);

And patients for whom the treating physician believes that even given the

new safety information, the benefit of the product outweighs the potential

risks.

FDA is further informing physicians that, in general, therapy with Trovan

should not continue for longer than 14 days. Therapy should be discontinued

sooner if the patient experiences any clinical signs of liver dysfunction,

including fatigue, loss of appetite, yellowing of the skin and eyes, severe

stomach pain with nausea and vomiting, or dark urine.

FDA is also advising physicians that for most patients who meet the

treatment criteria, therapy would most likely begin with intravenous

Trovan. After clinical stabilization patients may be switched to the oral

dosage form. Although oral therapy might be appropriate in some cases as an

initial therapy, the agency emphasizes that the oral form of Trovan is not

warranted for infections other than those specified.

In addition, the manufacturer has agreed to limit distribution of the

product to hospitals and long-term nursing care facilities. The

manufacturer will be communicating in the near future with other

appropriate pharmacies to provide directions concerning possible return of

their present inventories of Trovan.

FDA is taking this action to reduce the potential risk from Trovan, while

at the same time preserving for physicians and patients alike the clinical

option of an effective broad-spectrum antibiotic for serious and life-

threatening infections. The agency considers this advisory an interim

measure until revised labeling for the product can be approved.

It is estimated that 2.5 million prescriptions have been written for

Trovan, a quinolone antibiotic, since its February 1998 market launch in

oral and intravenous formulations. Trovan was initially approved for

treating a broad range of infections, from minor skin infections to severe

infections in hospitalized patients.

No reports of liver failure, liver transplant, or death due to liver

problems were reported in the 7,000 patients studied in premarketing

clinical trials for Trovan. In July 1998, FDA worked with the manufacturer

to strengthen the product's labeling concerning liver problems after

receiving reports of elevated liver enzymes and symptomatic hepatitis in

patients after short- and long-term therapy. Since then, FDA has continued

to receive reports of liver toxicity, including reports of a more serious

nature.

FDA is now aware of 14 cases of acute liver failure that it has concluded

are strongly associated with the drug. Six of these patients died: five due

to liver failure and one of four additional patients who received liver

transplants. Three patients recovered without requiring liver transplants,

and for the remaining two patients the final outcome is still pending.

More information about Trovan, including FDA's public health advisory, is

available on the World Wide Web atwww.fda.gov/cder/news/trovan/default.htm

and from Pfizer, the manufacturer of the drug, at 1-800-438-1985.

The FDA asks that any adverse events associated with Trovan be reported to

the agency through MedWatch, FDA's adverse event reporting system. Reports

may be submitted to FDA by telephone (800-332-1088), by fax (800-332-0178)

or by mail to MedWatch, HF-2, FDA, 5600 Fishers Lane, Rockville, Md. 20857.

Reports can also be filed via the internet atwww.fda.gov/medwatch. Reports

may also be filed directly to the manufacturer.

=========================================================

4.) THE ASTEMIZOLE (HISMANAL), (Lab JANSSEN-CILAG Pharmaceutica).

==========================================================

The ASTEMIZOLE, drugs of the ANTIHISTAMINE group, it was thrown to the market in the year 1.998 in the United States. One year later RETIRED OF THE MARKET FOR the same laboratory JANSSEN in June of 1.999, 21 due to the adverse effects reported among them the Heart events being described arrhythmias and deaths mainly.

Astemizole (marketed under the brand name Hismanal, developmental code R43512) was a second-generation antihistamine drug that has a long duration of action. Astemizole was discovered by Janssen Pharmaceutica in 1977. It has been withdrawn from the market in most countries because of rare but potentially fatal side effects (QTc interval prolongation and related arrhythmias due to hERG channel blockade.

===================================================

 EL HISMANAL (ASTEMIZOLE): Laboratorio JANSSEN-CILAG Pharmaceutica

===================================================

El ASTEMIZOLE, droga del grupo de los ANTIHISTAMINICOS, fue lanzado al mercado en el año 1.998 en los Estados Unidos. Un año despues RETIRADO DEL MERCADO POR el mismo laboratorio JANSSEN el 21 de Junio de 1.999, debido a los efectos adversos reportados entre ellos los eventos Cardiacos describiendose principalmente arritmias y muertes.

Astemizole (comercializado bajo el nombre de marca Hismanal, código de desarrollo R43512) fue un fármaco antihistamínico de segunda generación que tiene una larga duración de acción. Astemizole fue descubierto por Janssen Pharmaceutica en 1977. Ha sido retirado del mercado en la mayoría de los países debido a los efectos secundarios raros pero potencialmente fatales (prolongación del intervalo QTc y arritmias relacionadas debido al bloqueo de canal de hERG).

==============================================

JANSSEN PHARMACEUTICA ANNOUNCES THE WITHDRAWAL OF HISMANAL FROM THE MARKET

==============================================

June 21, 1999

Janssen Pharmaceutica, Inc., of Titusville, N.J., has announced that it is

voluntarily withdrawing the prescription antihistamine, Hismanal

(astemizole) 10 mg., from the market.

Since the drugís approval in 1988, new adverse reaction data has required a

series of labeling changes and warnings. In light of the choices of other

prescription antihistamines now available, and the overall risk benefit

profile of this drug, FDA supports the decision of the company to withdraw

the product.

Patients who have been taking Hismanal for their allergy symptoms should

consult with their doctors to determine an appropriate alternative treatment.

================================================================

5.) THE PROPULSID /PREPULSID (CISAPRIDE), (Lab JANSSEN-CILAG).

===============================================================

Another drug of the laboratory Janssen Pharmaceutica, thrown to the market in 1.993 for the treatment of the gastric reflux with big hopes. For December 31 1.999, 341 cases of heart arrhythmias had been reported, including 80 deaths. For January of year 2.000 Janssen makes an effort to inform on the risk of the handling of the drug.

For JULY 2.000, The product licence for cisapride (Prepulsid), a drug used to treat gastric and digestive disorders in adults and children, has been suspended by the Medicines Control Agency after five (5) DEATHS in the United Kingdom and 125 DEATHS WORLDWIDE that are thought to be associated with the drug.

For April 12- 2.001 Janssen Pharmaceutica decides to retire of the market the drug to avoid bigger problems.

================================================

 EL PREPULSID (CISAPRIDE): Laboratorio JANSSEN-CILAG Pharmaceutica

=================================================

Otra droga del laboratorio Janssen Pharmaceutica, lanzada al mercado en 1.993 para el tratamiento del reflujo gastrico con grandes espectativas. Para el 31 de diciembre de 1.999 se habian reportado 341 casos de arritmias cardiacas asociadas al uso de esta droga, incluyendo 80 muertes. Para enero del año 2.000 Janssen hace un esfuerzo para informar sobre los riesgos del manejo de la droga.

La Agencia de Control de Medicinas del Reino Unido decide suspender la licensia para la venta y comercializacion del CISAPRIDE en JULIO del 2.000, producto para tratar desordenes gastricos y digestivos en niños y adultos, despues del reporte de 5 MUERTES, en el REINO UNIDO Y 125 MUERTES REPORTADAS EN EL MUNDO, asociadas al uso de esta droga.

Para el 12 de Abril de 2.001 Janssen Pharmaceutica decide retirar del mercado la droga para evitar mayores problemas.

==========================================

New Safety Recommendations for Use of Cisapride (Propulsid)

==========================================

Source: Harvard Heart Letter

April 2000

Heart Lines

This month the Food and Drug Administration will hold a public advisory committee meeting to further discuss the safety of cisapride (Propulsid) and how to reduce the chances that someone will experience a severe adverse event from this drug.

The FDA first approved cisapride in tablet form in 1993 and then in liquid form in 1995. It is used to treat severe nighttime heartburn, usually due to gastroesophageal reflux disease (a condition where the band of muscle that prevents stomach acid from leaking back into the esophagus relaxes spontaneously, creating a painful heartburn-like sensation). Many drugs used to treat this condition suppress production of stomach acids. Cisapride works a little differently, moving the harmful acids through the digestive tract thereby preventing their painful reflux into the esophagus. Because this drug can be risky, it is generally reserved for use in patients who have not responded well to lifestyle changes or other medications used to manage gastroesophageal reflux disease.

In June 1998, several reports of serious adverse reactions in patients taking cisapride prompted the FDA to issue a warning about the drug. The medical problems included heart-rhythm disorders and death (most often occurring in people with certain health problems or who were taking other medications). Although it could not find a direct link between the reported problems and cisapride, the FDA did strengthen the precautions for use of this drug. A more recent analysis of 270 adverse event reports (including 70 deaths) suggests that roughly 85% of these cases were patients with these identifiable risks.

In January 2000, the FDA bolstered its efforts to reduce the likelihood of complications from cisapride by recommending that physicians consider performing an electrocardiogram and certain blood tests before prescribing it. New labeling lists drugs and underlying conditions that put patients at increased risk. Cisapride should not be used by patients taking some of the following types of medications: anti-allergy, anti-angina, anti-arrhythmics (to treat an irregular heart rhythm), antibiotics, antidepressants, anti-fungals, anti-nausea, antipsychotics, and protease inhibitors (to treat HIV infection). Also, patients with any of the following conditions should not take the drug: history of irregular heartbeats; abnormal electrocardiogram; heart disease; kidney disease; lung disease; low potassium, calcium, or magnesium levels; an eating disorder (such as bulimia or anorexia); dehydration or persistent vomiting.

===============================================

6.) THE VIOXX (ROFECOXIB), Laboratory MERCK S. and D.

===============================================

The drug VIOXX ROFECOXIB) rushed to the market in the years 2.000, after one year it presents 1.000 reports of adverse reactions for their use including 11 deaths reported in ENGLAND. The effects but commonly reported they were:

Gastrointestinal adverse reactions account for almost half (554) of the reports, of which the majority (84%) were nauseates, dyspepsia, diarrhoea and abdominal pain, the agency said. However there have been 68 reports (12%) of upper GI perforations, ulceration and bleeds (PUBs). Forty-four (65%) of the patients with PUBs recovered, although five had to fatal outcome."

The agencies also received 177 reports of cardiovascular suspected reactions, including 101 reports of oedema, 31 reports of hypertension and 19 reports of palpitations. There were 15 reports of cardiac failure, three of which had to fatal outcome, and nine reports of myocardial infarction, three of them fatal. In the majority of these, the patient had risk factors for

cardiovascular disease.

Psychiatric reactions were also reported, including 28 reports of depression, 14 reports of confusion and 11 reports of hallucinations. Adverse reactions recognised with other NSAIDs were also reported with rofecoxib. These included angioedema (35 reports), bronchospasm or exacerbation of asthma (25), renal failure (16), and abnormal hepatic function (12).

THE FDA ALSO RECENTLY NOTICED TO THE LABORATORY MERCK S. AND D. the problems of their molecule VIOXX it was CAUSING IN THE HEALTH OF THE PATIENTS, MAINLY MYOCARDIAL INFARCTION.

But NOBODY PAID ATTENTION TO THESE WARNINGS until 30 SEPTEMBER 2.004 when the SAME LABORATORY already DECIDED to take it out of the market for the problems mentioned.

By the way MERCK one comes WITH A NEW MOLECULE: ARCOXIA, not yet approved by the FDA, if it is a COX-2 molecule, it will BE MORE OF THE SAME thing. ?

The new molecule that replaces the retired rofecoxif (VIOXX) is etoricoxib with the name of ARCOXIA, nowadays 2.017 not approved yet in the United States. In Europe, their use was approved.

======================================================

Merck Announces Voluntary Worldwide Withdrawal of VIOXX®

======================================================

SourceHttp://healthorbit.ca/

journal@lists.healthorbit.ca <journal@lists.healthorbit.ca>

WHITEHOUSE STATION, N.J., Sept. 30, 2004 - Merck &. Co., Inc. today

announced a voluntary worldwide withdrawal of VIOXX® (rofecoxib), its arthritis

and acute pain medication. The company's decision, which is effective immediately,

is based on new, three-year data from a prospective, randomized, placebo-

controlled clinical trial, the APPROVe (Adenomatous Polyp Prevention on

VIOXX) trial.

=============================================

- Merck Halts Vioxx Sales on Health Threats

==============================================

Sourcehttp://www.abcnews.go.com/

Merck Pulls Vioxx Arthritis Drug From Market on Heart Attack, Stroke

Concerns; Stock Plunges

The Associated Press

TRENTON, N.J. Sept. 30, 2004 — Merck & Co. is pulling its blockbuster Vioxx

from the market after new data found the arthritis drug doubled the risk of heart

attacks and strokes. Merck's stock plunged almost 27 percent as the

pharmaceutical giant said the recall will hurt its earnings.

Merck said Thursday the clinical trial data showed an increased risk of heart attack

and other cardiovascular complications 18 months after patients started taking

Vioxx, which also is prescribed for acute pain and disorders such as carpal tunnel

syndrome.

The three-year study aimed at showing that Vioxx could prevent the recurrence of

polyps, which can turn cancerous, in the colon and rectum was stopped after

Merck discovered participants had double the risk of a heart attack compared to

those taking a placebo.

By Thursday afternoon, at least one plaintiffs' attorney announced plans for a class

-action lawsuit against Merck. Another claimed to represent 58 patients around the

country allegedly harmed by Vioxx, including people who suffered a heart attack,

stroke, internal bleeding or kidney failure.

"It's a disaster for Merck, coming at the worst time," said independent health care

analyst Hemant Shah of HKS & Co. in Warren, N.J.

About 2 million people worldwide use Vioxx, Merck said, and 84 million have

taken it since it came on the market with great fanfare in 1999. It is one of Merck's

most important drugs, with $1.8 billion in U.S. sales in 2003 and global sales of $2

.5 billion 11 percent of the company's $22.49 billion in revenue that year.

But Vioxx sales dipped 18 percent in the second quarter of this year to $653

million, partly due to increasing concerns about an elevated risk of heart

complications.

Medical experts advised patients Thursday to stop taking Vioxx and consult their

doctor about alternatives.

Merck said the recall will slash about 50 cents to 60 cents a share from its earnings

for the rest of this year. That includes foregone sales, writeoffs of inventory held by

Merck, customer returns of product previously sold and other costs of the

pullback. Merck expects foregone fourth quarter sales of Vioxx of $700 million to

$750 million alone.

Merck, based in Whitehouse Station, N.J., had previously been expecting 2004

earnings per share of $3.11 to $3.17.

"We're taking this action because we believe it best serves the interest of patients,"

Ray V. Gilmartin, Merck's chairman, president and chief executive, said in a

statement.

Shares in Merck, the world's third-biggest drug maker, plunged $12.07, nearly 27

percent, to close at $33.00 on the New York Stock Exchange. That wiped out $

28 billion in market value. More than 140 million shares were traded, compared to

a daily average below 10 million.

Shah said for Merck, the Vioxx withdrawal comes "at a time when they really need

to get ready for expiration" of its patent for Zocor, the cholesterol treatment that is

the company's top-selling drug.

Zocor loses patent protection early in 2006 and sales are expected to plunge

against generic competition. In an effort to replace those revenues, Merck recently

launched a drug with Schering-Plough Corp., Vytorin, that combines Zocor and

Schering-Plough's Zetia to attack cholesterol levels in two complementary ways.

The Vioxx recall stands to benefit Pfizer Inc., the world's biggest drugmaker.

Merck and Pfizer have been battling for market share, with Pfizer's Celebrex

arthritis drug dominating the market with about $5 billion in U.S. sales alone last

year. Pfizer shares were up 35 cents to $30.53 in afternoon trading on the NYSE.

Pfizer issued a statement Thursday citing the "outstanding long-term safety profile"

of Celebrex and saying that in a recent FDA-sponsored study of 1.4 million

patients, those who received Celebrex demonstrated no increased risk of cardiac

trouble.

Vioxx was labeled with a warning about heart risks in 2001 after Merck's own

study in 2000 uncovered the increased risk of heart attack and other complications.

The Food and Drug Administration has been monitoring problems reported to it

since then.

"This is not a total surprise," said Dr. Steven Galson, acting director of the FDA's

Center for Drug Evaluation and Research.

Dr. Steven Abramson, director of rheumatology at New York University Hospital

for Joint Diseases, said "there are very few patients for whom there won't be a

good alternative drug."

Besides generic anti-inflammatory drugs such as ibuprofen, naproxen and aspirin,

those include Celebrex, which Abramson said has not been linked to heart

complications.

Celebrex and its successor drug, Bextra, as well as Vioxx and a successor drug

called Arcoxia that is awaiting FDA approval, are part of a class of anti-

inflammatory drugs touted by the pharmaceutical industry as being more effective

and having less side effects, particularly on the gastrointestinal system, than older

drugs.

Vioxx's removal will be a blow to hopes that it and other drugs in the class known

as COX-2 inhibitors could be used to prevent cancer in people at high risk of

developing it. A landmark study in 2002 showed that small, daily doses of aspirin

could prevent colon cancer, and studies hinted that COX-2 inhibitors might do the

same possibly without aspirin's side effects.

All COX-2 inhibitors can raise blood pressure, but Vioxx appears to be the only

one that's been linked to higher risk of heart attacks and strokes, Galson said.

Merck is scheduled to release financial results for the third quarter, which ends

today, on Oct. 21.

===========================================

EL VIOXX (ROFECOXIB): Laboratorio MERCK S. and D.

============================================

La droga VIOXX ROFECOXIB) lanzada al mercado en el años 2.000, despues de un año presenta 1.000 reportes de reacciones adversas por su uso incluyendo 11 muertes reportadas en INGLATERRA. Los efectos mas comunmente reportados fueron:

Gastrointestinales: nausea, dispepsia, diarrea, dolor abdominal, ulceras y sangramientos del tracto gastrointestinal superior, (68) reportes (12%) con 5 muertes.

Las agencias recibieron tambien 177 reportes de reacciones cardiovasculares, incluyendo 101 reportes de edema, 31 reportes de hipertension y 19 reportes de palpitaciones. Hay 15 reportes de falla cardiaca, 3 de ellos murieron, y 9 reportes de infarto al miocardio, 3 de ellos murieron.

Tambien han sido reportados recciones psiquiatricas: 14 reportes de confusion y 11 reportes de halucinaciones. Otros: angiodema, 35 reportes, broncoespasmo o exacerbacion de asma, 25 reportes, 16 reportes de falla renal y 12 de funcion hepatica anormal.

LA FDA TAMBIEN RECIENTEMENTE ADVIRTIO AL LABORATORIO MERCK S. AND D. los problemas qu su molecula VIOXX ESTABA PROVOCANDO EN LA SALUD DE LOS PACIENTES principalmente el INFARTO AL MIOCARDIO.

Pero NADIE HIZO CASO A ESTAS ADVERTENCIAS  hasta que     el 30 SEPTIEMBRE 2.004 el MISMO LABORATORIO DECIDIO sacarlo del mercado por los problemas ya antes mencionado.

POR CIERTO MERCK se viene CON UNA NUEVA MOLECULA: ARCOXIA,,,, no esta aprobada aun por la FDA, si es una MOELCULA COX-2,,, SERA MAS DE LO MISMO ?

La nueva molecula que sustituye al retirado rofecoxif (VIOXX) es el etoricoxib con el nombre de ARCOXIA, hoy dia 2.017 no aprobada aun en los Estados Unidos. En Europa se aprobo su uso.

=====================================================

Merck retira ‘Vioxx’ del mercado por incremento del riesgo cardiovascular en uso prolongado.

===================================================

Source:ww.correofarmaceutico.com/

La multinacional Merck, que opera como MSD en Europa, retiró ayer del

mercado su fármaco superventas Vioxx (rofecoxib), inhibidor selectivo de la

COX-2, indicado para el tratamiento sintomático de la artritis reumatoide y de la

artrosis y comercializado como Ceoxx en España para el tratamiento sintomático

del dolor agudo a corto plazo, por su riesgo incrementado de accidente

cardiovascular grave en tratamientos prolongados.

Valvanera Valero

Los nuevos datos del perfil de seguridad del Vioxx se han obtenido en un ensayo

clínico de rofecoxib frente a placebo para estudiar si previene la recurrencia de pó

lipos colorrectales en pacientes con historia de adenomas colorrectales. A partir de

los 18 meses de toma diaria de 25 mg de rofecoxib, los pacientes presentaron un

número de eventos cardiovasculares superior a placebo (45 frente a 25).

La Agencia Española del Medicamento y Productos Sanitarios (Aemps) recuerda

en una nota informativa de comunicación de riesgos de medicamentos para los

profesionales sanitarios que “la seguridad cardiovascular de rofecoxib y de otros

coxibs ha sido revisada en repetidas ocasiones por las agencias reguladoras

nacionales desde la publicación del ensayo clínico Vigor, en el que se observó que

rofecoxib, a dosis de 50 mg (entre 2 y 4 veces la recomendada) se asocia a un

incremento de riesgo de infarto agudo de miocardio comparado con naproxeno,

AINE no selectivo”. Entonces, dice la Aemps, “aunque no pudo resolverse si este

resultado se debía a un incremento de riesgo de rofecoxib o a un efecto protector

de naproxeno, se procedió a modificar la información del medicamento dirigida a

los profesionales y los pacientes para advertir de estos resultados”. Posteriormente,

según la agencia, se han publicado varios estudios donde se observaba un

incremento de riesgo pero solo a dosis superiores a 25 mg.

La AEMPS insiste en que “los datos se refieren únicamente a rofecoxib y que no

pueden generalizarse a otros inhibidores selectivos de la COX-2”. Y aconseja que

aunque los riesgos detectados sólo ocurren tras un tratamiento prolongado (más de

1 año) con Vioxx, se recomienda la suspensión del mismo puesto que es fácilmente

sustituible por tratamientos alternativos sobre los cuales el médico de familia podrá

determinar la alternativa más adecuada a las necesidades de los pacientes.

Vioxx facturó en 2003 2.300 millones de euros en el mundo y desde enero de

2004, 20 millones de euros en España. En los últimos doce meses se han tratado

en España 277.000 pacientes con el fármaco, aunque no necesariamente en uso

crónico. Actualmente Sanidad estima que podría haber entre 70.000 y 100.000

pacientes en tratamiento con este fármaco, que requiere como otros coxibs visado

de inspección desde julio de 2002 en España. Ceoxx, sin embargo, no está

cubierto por la seguridad social.

===============================================================

7.) THE BEXTRA (VALDECOXIB), (Lab. PFIZER).

=============================================================

THE BEXTRA (VALDECOXIB), another molecules but representative of the the feared molecules COX-2, the same as ROFECOXIB,(VIOXX - already retired of the market),and he new clone that he comes over there from the same laboratory Merck (ARCOXIA.

To the BEXTRA, THERE you HAVE about 250 adverse effects attributed to her and the warnings of the FDA...and the WITHDRAWN OF THE MARKET YEAR 2.005

=======================================

LA BEXTRA (VALDECOXIB) Laboratory PFIZER)

=======================================

LA BEXTRA (VALDECOXIB), otra moleculas mas representante del las temidas moleculas COX-2, al igual que ROFECOXIB,(VIOXX- ya retirado del mercado), y el nuevo clon que viene por alli del mismo laboratorio Merck (ARCOXIA).

ALLI TIENEN unos 250 efectos adversos atribuidos a ella y las advertencias de la FDA. Y SU RETIRO DEL MERCADO AÑO 2.005.

====================================

THE BEXTRA (VALDECOXIB) SIDE EFFECTS

====================================

Source:ttp://www.rxlist.com/

Of the patients treated with BEXTRA Tablets in controlled arthritis trials,2665 were patients with OA,and 2684 were patients with RA.More than 4000 patients have received a chronic total daily dose of BEXTRA 10 mg or more.More than 2800 patients have received BEXTRA 10 mg/day,or more,for at least 6 months and 988 of these have received BEXTRA for at least 1 year.

Osteoarthritis and Rheumatoid Arthritis

Table 4 lists all adverse events,regardless of causality,that occurred in ³ 2.0% of patients receiving BEXTRA 10 and 20mg/day in studies of three months or longer from 7 controlled studies conducted in patients with OA or RA that included a placebo and/or a positive control group.

In these placebo- and active-controlled clinical trials, the discontinuation rate due to adverse events was 7.5% for arthritis patients receiving valdecoxib 10 mg daily, 7.9% for arthritis patients receiving valdecoxib 20 mg daily and 6.0% for patients receiving placebo.

In the seven controlled OA and RA studies, the following adverse events occurred in 0.1–1.9% of patients treated with BEXTRA 10 –20 mg daily, regardless of causality.

Application site disorders: Cellulitis, dermatitis contact

From Our Sponsors

Cardiovascular:Aggravated hypertension, aneurysm, anginapectoris, arrhythmia, cardiomyopathy, congestive heart failure, coronary artery disorder, heart murmur, hypotension

Central, peripheral nervous system: Cerebrovascular disorder, hypertonia, hypoesthesia, migraine, neuralgia, neuropathy, pares-thesia, tremor, twitching, vertigo

Endocrine: Goiter

Female reproductive: Amenorrhea, dysmenorrhea, leukorrhea, mastitis, menstrual disorder, menorrhagia, menstrual bloating, vaginal hemorrhage

Gastrointestinal: Abnormal stools, constipation, diverticulosis, dry mouth, duodenal ulcer, duodenitis, eructation, esophagitis, fecal incontinence, gastric ulcer, gastritis, gastroenteritis, gastroe-sophageal reflux, hematemesis, hematochezia, hemorrhoids, hemorrhoids bleeding, hiatal hernia, melena, stomatitis, stool frequency increased, tenesmus, tooth disorder, vomiting

General: Allergy aggravated, allergic reaction, asthenia, chest pain, chills, cyst NOS, edema generalized, face edema, fatigue, fever, hot flushes, halitosis, malaise, pain, periorbital swelling, peripheral pain Hearing and vestibular: Ear abnormality, earache, tinnitus

Heart rate and rhythm: Bradycardia, palpitation, tachycardia

Hemic: Anemia

Liver and biliary system: Hepatic function abnormal, hepatitis, ALT increased, AST increased

Male reproductive: Impotence, prostatic disorder

Metabolic and nutritional: Alkaline phosphatase increased, BUN increased, CPK increased, creatinine increased, diabetes mellitus, glycosuria, gout, hypercholesterolemia, hyperglycemia, hyperkalemia, hyperlipemia, hyperuricemia, hypocalcemia, hypokalemia, LDH increased, thirst increased, weight decrease, weight increase, xerophthalmia

Musculoskeletal: Arthralgia, fracture accidental, neck stiffness, osteoporosis, synovitis, tendonitis

Neoplasm: Breast neoplasm, lipoma, malignant ovarian cyst

Platelets (bleeding or clotting): Ecchymosis, epistaxis, hematoma NOS, thrombocytopenia

Psychiatric: Anorexia, anxiety, appetite increased, confusion, depression, depression aggravated, insomnia, nervousness, morbid dreaming, somnolence

Resistance mechanism disorders: Herpes simplex, herpes zoster, infection fungal,infection soft tissue, infection viral, moniliasis, moniliasis genital, otitis media

Respiratory: Abnormal breath sounds, bronchitis, bronchospasm, coughing, dyspnea, emphysema, laryngitis, pneumonia, pharyngitis, pleurisy, rhinitis

Skin and appendages: Acne, alopecia, dermatitis, dermatitis fungal, eczema, photosensitivity allergic reaction, pruritus, rash erythematous, rash maculopapular, rash psoriaform, skin dry, skin hypertrophy, skin ulceration, sweating increased, urticaria

Special senses: Taste perversion

Urinary system: Albuminuria, cystitis, dysuria, hematuria, micturition frequency increased, pyuria, urinary incontinence, urinary tract infection

Vascular: Claudication intermittent, hemangioma acquired, varicose vein

Vision: Blurred vision, cataract, conjunctival hemorrhage, conjunctivitis, eye pain, keratitis, vision abnormal

White cell and RES disorders: Eosinophilia, leukopenia, leukocytosis, lymphadenopathy, lymphangitis, lymphopenia

Other serious adverse events that were reported rarely (estimated <0.1%) in clinical trials, regardless of causality, in patients taking BEXTRA:

Autonomic nervous system disorders: Hypertensive encephalopathy, vasospasm

Cardiovascular: Abnormal ECG,aortic stenosis, atrial fibrillation, carotid stenosis, coronary thrombosis, heart block,heart valve disorders, mitral insufficiency, myocardial infarction, myocardial ischemia, pericarditis, syncope, thrombophlebitis, unstable angina, ventricular fibrillation

Central, peripheral nervous system: Convulsions

Endocrine: Hyperparathyroidism

Female reproductive: Cervical dysplasia

Gastrointestinal: Appendicitis, colitis with bleeding, dysphagia, esophageal perforation, gastrointestinal bleeding, ileus, intestinal obstruction, peritonitis

Hemic: Lymphoma-like disorder, pancytopenia

Liver and biliary system: Cholelithiasis

Metabolic: Dehydration

Musculoskeletal: Pathological fracture, osteomyelitis

Neoplasm: Benign brain neoplasm, bladder carcinoma, carcinoma, gastric carcinoma, prostate carcinoma, pulmonary carcinoma

Platelets (bleeding or clotting): Embolism, pulmonary embolism, thrombosis

Psychiatric: Manic reaction, psychosis

Renal: Acute renal failure

Resistance mechanism disorders: Sepsis

Respiratory: Apnea, pleural effusion, pulmonary edema, pulmonary fibrosis, pulmonary infarction, pulmonary hemorrhage, respiratory insufficiency

Skin: Basal cell carcinoma, malignant melanoma

Urinary system: Pyelonephritis, renal calculus

Vision: Retinal detachment

Postmarketing Experience

The following reactions have been identified during postmarketing use of BEXTRA. These reactions have been chosen for inclusion either due to their seriousness, reporting frequency, possible causal relationship to BEXTRA, or a combination of these factors. Because these reactions were reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

General: Hypersensitivity reactions (including anaphylactic reactions and angioedema)

Skin and appendages: Erythema multiforme, exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis

DRUG INTERACTIONS

The drug interaction studies with valdecoxib were performed both with valdecoxib and a rapidly hydrolyzed intravenous prodrug form. The results from trials using the intravenous prodrug are reported in this section as they relate to the role of valdecoxib in drug interactions.

General: In humans,valdecoxib metabolism is predominantly mediated via CYP 3A4 and 2C9 with glucuronidation being a further (20%) route of metabolism.In vitrostudies indicate that valdecoxib is a moderate inhibitor of CYP 2C19 (IC50 = 6 µg/mL),and a weak inhibitor of both 3A4 (IC50 = 44µg/mL) and 2C9 (IC50 = 13 µg/mL).In view of the limitations of in vitrostudies and the high valdecoxib IC50 values,the potential for such metabolic inhibitory effects in vivoat therapeutic doses of valdecoxib is low.

Aspirin: Concomitant administration of aspirin with valdecoxib may result in an increased risk of GI ulceration and complications compared to valdecoxib alone.Because of its lack of anti-platelet effect valdecoxib is not a substitute for aspirin for cardiovascular prophylaxis.

In a parallel group drug interaction study comparing the intravenous prodrug form of valdecoxib at 40 mg BID (n=10) vs placebo (n=9),valdecoxib had no effect on in vitroaspirin-mediated inhibition of arachidonate- or collagen-stimulated platelet aggregation.

Methotrexate: Valdecoxib 10 mg BID did not show a significant effect on the plasma exposure or renal clearance of methotrexate.

ACE-inhibitors: Reports suggest that NSAIDs may diminish the antihypertensive effect of ACE-inhibitors.This interaction should be given consideration in patients taking BEXTRA concomitantly with ACE-inhibitors.

Furosemide: Clinical studies,as well as post-marketing observations, have shown that NSAIDs can reduce the natriuretic effect of furosemide and thiazides in some patients.This response has been attributed to inhibition of renal prostaglandin synthesis.

Anticonvulsants: Anticonvulsant drug interaction studies with val-decoxib have not been conducted.As with other drugs,routine monitoring should be performed when therapy with BEXTRA is either initiated or discontinued in patients on anticonvulsant therapy.

Dextromethorphan: Dextromethorphan is primarily metabolized by CYP 2D6 and to a lesser extent by 3A4.Coadministration with val-decoxib (40 mg BID for 7 days) resulted in a significant increase in dextromethorphan plasma levels suggesting that,at these doses,val-decoxib is a weak inhibitor of 2D6.Dextromethorphan plasma concentrations in the presence of high doses of valdecoxib were almost 5-fold lower than those seen in CYP 2D6 poor metabolizers.

Lithium: Valdecoxib 40 mg BID for 7 days produced significant decreases in lithium serum clearance (25%) and renal clearance (30%) with a 34% higher serum exposure compared to lithium alone. Lithium serum concentrations should be monitored closely when initiating or changing therapy with BEXTRA in patients receiving lithium.Lithium carbonate (450mg BID for 7 days) had no effect on valdecoxib pharmacokinetics.

Warfarin: The effect of valdecoxib on the anticoagulant effect of warfarin (1 – 8 mg/day) was studied in healthy subjects by coadminis-tration of BEXTRA 40 mg BID for 7 days.Valdecoxib caused a statistically significant increase in plasma exposures of R-warfarin and S-warfarin (12% and 15%,respectively),and in the pharmacodynamic effects (prothrombin time,measured as INR) of warfarin.While mean INR values were only slightly increased with coadministration of valdecoxib,the day-to-day variability in individual INR values was increased.Anticoagulant therapy should be monitored,particularly during the first few weeks,after initiating therapy with BEXTRA in patients receiving warfarin or similar agents.

Fluconazole and Ketoconazole: Ketoconazole and fluconazole are predominantly CYP 3A4 and 2C9 inhibitors, respectively. Concomitant single dose administration of valdecoxib 20 mg with multiple doses of ketoconazole and fluconazole produced a significant increase in exposure of valdecoxib.Plasma exposure (AUC) to valdecoxib was increased 62% when coadministered with flucona-zole and 38% when coadministered with ketoconazole.

Glyburide: Glyburide is a CYP 3A4 substrate.Coadministration of valdecoxib (10 mg BID for 7 days) with glyburide (5 mg QD or 10 mg BID) did not affect the pharmacokinetics (exposure) of glyburide.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Valdecoxib was not carcinogenic in rats given oral doses up to 7.5mg/kg/day for males and 1.5mg/kg/day for females (equivalent to approximately 2- to 6-fold human exposure at 20 mg QD as measured by the AUC(0-24hr)) or in mice given oral doses up to 25mg/kg/day for males and 50mg/kg/day for females (equivalent to approximately 0.6- to 2.4-fold human exposure at 20 mg QD as measured by the AUC(0-24hr)) for two years..

Valdecoxib was not mutagenic in an Ames test or a mutation assay in Chinese hamster ovary (CHO) cells,nor was it clastogenic in a chromosome aberration assay in CHO cells or in an in vivomicronucleus test in rat bone marrow.

Valdecoxib did not impair male rat fertility at oral doses up to 9.0mg/kg/day (equivalent to approximately 3- to 6-fold human exposure at 20 mg QD as measured by the AUC (0-24hr)).In female rats,a decrease in ovulation with increased pre- and post-implantation loss resulted in decreased live embryos/fetuses at doses ³ 2 mg/kg/day (equivalent to approximately 2-fold human exposure at 20mg QD as measured by the AUC (0-24hr) for valdecoxib).The effects on female fertility were reversible.This effect is expected with inhibition of prostaglandin synthesis and is not the result of irreversible alteration of female reproductive function.

Pregnancy

Teratogenic Effects: Pregnancy Category C.

The incidence of fetuses with skeletal anomalies such as semi-bipartite thoracic vertebra centra and fused sternebrae was slightly higher in rabbits at an oral dose of 40 mg/kg/day (equivalent to approximately 72-fold human exposures at 20mg QD as measured by the AUC(0-24hr)) throughout organogenesis.Valdecoxib was not teratogenic in rabbits up to an oral dose of 10 mg/kg/day (equivalent to approximately 8-fold human exposures at 20 mg QD as measured by the AUC(0-24hr)).

Valdecoxib was not teratogenic in rats up to an oral dose of 10mg/kg/day (equivalent to approximately 19-fold human exposure at 20 mg QD as measured by the AUC (0-24hr)).There are no studies in pregnant women.However,valdecoxib crosses the placenta in rats and rabbits.BEXTRA should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Non-teratogenic Effects: Valdecoxib caused increased pre-and post-implantation loss with reduced live fetuses at oral doses

³ 10mg/kg/day (equivalent to approximately 19-fold human exposure at 20 mg QD as measured by the AUC (0-24hr)) in rats and an oral dose of 40 mg/kg/day (equivalent to approximately 72-fold human exposure at 20 mg QD as measured by the AUC (0-24hr)) in rabbits throughout organogenesis.In addition,reduced neonatal survival and decreased neonatal body weight when rats were treated with valdecoxib at oral doses ³ 6 mg/kg/day (equivalent to approximately 7-fold human exposure at 20 mg QD as measured by the AUC(0-24hr)) throughout organogenesis and lactation period.No studies have been conducted to evaluate the effect of valdecoxib on the closure of the ductus arteriosus in humans.Therefore,as with other drugs known to inhibit prostaglandin synthesis,use of BEXTRA during the third trimester of pregnancy should be avoided.

Labor and Delivery

Valdecoxib produced no evidence of delayed labor or parturition at oral doses up to 10 mg/kg/day in rats (equivalent to approximately 19-fold human exposure at 20 mg QD as measured by the AUC (0-24hr)). The effects of BEXTRA on labor and delivery in pregnant women are unknown.

Nursing Mothers

Valdecoxib and its active metabolite are excreted in the milk of lactating rats.It is not known whether this drug is excreted in human milk.Because many drugs are excreted in human milk,and because of the potential for adverse reactions in nursing infants from BEXTRA,a decision should be made whether to discontinue nursing or to discontinue the drug,taking into account the importance of the drug to the mother and the importance of nursing to the infant.

Pediatric Use

Safety and effectiveness of BEXTRA in pediatric patients below the age of 18 years have not been evaluated.

Geriatric Use

Of the patients who received BEXTRA in arthritis clinical trials of three months duration,or greater,approximately 2100 were 65 years of age or older,including 570 patients who were 75 years or older.No overall differences in effectiveness were observed between these patients and younger patients.

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New Warnings for Bextra (VALDECOXIB).

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SourceHttp://www.fda.gov/

The FDA and Pharmacia Corporation are advising health-care professionals about new warnings and information in the product labeling of Bextra (valdecoxib), a drug approved for treatment of osteoarthritis, rheumatoid arthritis and menstrual pain (dysmenorrhea). The labeling is being updated with new warnings following postmarketing reports of serious adverse effects, including serious allergic reactions (anaphylactoid reactions). As these reactions can be life-threatening, people who start Bextra and experience a rash should discontinue the drug immediately. In addition, the labeling will state that the drug is contraindicated--not to be used--in patients allergic to sulfa-containing products.

Health-care professionals are encouraged to report any unexpected adverse or serious events associated with the use of Bextra directly to Pharmacia Corporation, Peapack, N.J. at 1-800-323-4204 or to the FDA MedWatch program at 1-800-FDA-1088.

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Valdecoxib-induced toxic epidermal necrolysis in a patient allergic to sulfa drugs.

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Pharmacotherapy. 2003 Apr; 23(4): 551-3.

Glasser DL, Burroughs SH.

Department of Pharmacy Practice, Bernard J. Dunn School of Pharmacy, Shenandoah University, 1460 University Drive, Winchester, VA 22601, USA. dglasser@su.edu

A 55-year-old Caucasian woman with a previously documented sulfa allergy was admitted to the hospital after she developed toxic epidermal necrolysis; she had been taking valdecoxib for 8 days for knee pain. Four days later, her bullous lesions had progressed to 45-50% of her body surface area. She was transferred to a burn unit for aggressive wound care and fluid hydration. Valdecoxib, a cyclooxygenase-2 inhibitor, is a benzenesulfonamide prescribed for arthritis pain and inflammation, and dysmenorrhea. Clinicians should exercise caution when prescribing valdecoxib to patients who are allergic to sulfa drugs.

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BEXTRA WITHDRAWN FROM THE MARKET

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Source:     medscape.com and fda.gov

April 7, 2005

— At the request of the U.S. Food and Drug Administration (FDA), Pfizer, Inc, has agreed to suspend sales and marketing of valdecoxib (Bextra) pending further discussions with the agency. The FDA claims that the drug's overall risks outweigh the potential benefits, according to an alert sent today from MedWatch, the FDA's safety information and adverse event reporting program.

The decision follows a joint public meeting of the FDA’s Arthritis Drugs/Drug Safety and Risk Management Advisory committees, held in February to review safety data compiled from clinical trials and postmarketing reports.

According to the FDA, the request was based on a lack of adequate data regarding the cardiovascular (CV) safety of long-term valdecoxib use and the increased risk of adverse CV events observed in trials of valdecoxib in coronary artery bypass postsurgical patients that may be relevant to chronic use.

In addition, the FDA has received reports of serious and potentially life-threatening skin reactions causing some fatalities in patients receiving valdecoxib therapy. The risk of these reactions is considered unpredictable; the reactions have occurred with both short- and long-term use and in patients with and without a history of sulfa allergy.

Patients receiving valdecoxib therapy are advised to contact their healthcare providers to arrange for alternative therapy. The FDA notes that valdecoxib has not been associated with any advantages compared with other nonsteroidal anti-inflammatory drugs (NSAIDs).

As a result of the meeting, the FDA has also asked manufacturers to revise the labeling for all prescription NSAIDs, including celecoxib (Celebrex, made by Pfizer, Inc), to include stronger warnings on the increased risk of CV events and potentially life-threatening gastrointestinal (GI) bleeding associated with their use. Medication guides are to be dispensed with each prescription to inform patients of the potential CV and GI risks and to advise on safe use of the drug.

Labels for over-the-counter NSAIDs will also include more specific information concerning CV and GI risks, and they will warn of potential skin reactions. The labeling revisions do not apply to aspirin because it has been shown in clinical trials to reduce the risk of serious adverse CV events in certain populations.

Additional information, including a list of affected NSAIDs, is available on the FDA's Web site ahttp://www.fda.gov/cder/drug/infopage/cox2/default.htm. Information can also be obtained by calling 1-888-INFO-FDA (888-463-6332).

Adverse events related to use of valdecoxib and other NSAIDs can be reported to the FDA's MedWatch program by phone at 1-800-FDA-1088, by fax at 1-800-FDA-0178, online athttp://www.fda.gov/medwatch, or by mail to 5600 Fishers Lane, Rockville, MD 20852-9787.

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8.) SIBUTRAMINE - REDUCTIL Lab. ABBOTT

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 Source: fda.gob, wikipedia.

Sibutramine (usually in the form of the hydrochloride monohydrate salt) is an oral anorexiant.  was marketed and prescribed as an adjunct in the treatment of exogenous obesity along with diet and exercise. It has been associated with increased cardiovascular events and strokes and has been withdrawn from the market in the year 2.010.

Sibutramine was originally developed in 1988 by Boots in Nottingham, UK, and marketed by Knoll Pharmaceuticals, and was most recently manufactured and marketed by Abbott Laboratories before its withdrawal from the market. It was sold under a variety of brand names including Reductil, Meridia, Siredia, and Sibutrex. It is classified as a Schedule IV controlled substance in the United States.

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SIBUTRAMINA- REDUCTIL - Lab. ABBOTT.

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La sibutramina (generalmente en forma de la sal de hidrocloruro monohidrato) es un anorexigeno oral. Fue comercializado y prescrito como un complemento en el tratamiento de la obesidad exógena, junto con la dieta y el ejercicio. Se ha asociado con el aumento de eventos cardiovasculares y accidentes cerebrovasculares y se ha retirado del mercado en el año 2.010.

La sibutramina fue desarrollada originalmente en 1988 por Boots en Nottingham, Reino Unido [12] y comercializada por Knoll Pharmaceuticals, y fue fabricada y comercializada por Abbott Laboratories antes de su retirada del mercado . Se vendió bajo una variedad de marcas como Reductil, Meridia, Siredia y Sibutrex. Se clasifica como una sustancia controlada de la Lista IV en los Estados Unidos.

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They recognize that Reductil for Weight loss was related to 34 deaths

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Source:http://www.healthig.com

A newspaper in London, on 18 March, reports that a total of 34 patients have died after taking the anti-obesity drug Reductil, belonging to Abbott Laboratories. Eugene Sun, vice president of pharmaceutical development for the company, released the death toll after the British Health Department reported the death of two patients in that country and indicated that more than 200 people have been observed adverse reactions to the drug in the United Kingdom.

Sun said the company has 28 deaths in the United States, two in Italy, two in the United Kingdom, one in South Africa and one in Switzerland. Italy suspended the sale of Reductil (sibutramine) last week after receiving 50 reports of adverse reactions in patients, including the two deaths. In Spain the drug has been sold since last year.

Abbot noted that the death rate associated with Reductil is less than 1% of obesity-related mortality, which often suffer from conditions such as diabetes and cardiovascular disease.

Nearly nine million people have taken the drug in the world, Sun said. The 34 deaths represent an incidence of two deaths per 100,000 people treated annually with this drug, said the Abbot vice president. Studies on obesity indicate that 400 people per 100,000 die each year because of this.

Reductil came on the market in 1997, after several years in human trials. Following the suspension of the sale of the drug in Italy, Abbot reviewed data related to sibutramine worldwide and sent all information on adverse reactions to regulatory authorities.

The two died in the United Kingdom, according to the laboratory, suffered serious cardiac complications. One of them, moreover, had diabetes and a thyroid problem; Died two days after being treated with sibutramine. The other had been on treatment with this drug for four months but stopped taking it five days before dying for a heart failure.

The British Department of Health stated: 'As of 13 March 2002, 212 reports of suspected adverse reactions to sibutramine have been received.' Of these reports, 93 were considered serious. The official statement states that patients currently being treated with Reductil can continue to do so, 'but if they feel bad they should talk to their doctor'.

In other countries the authorities are studying the documentation on adverse drug reactions to prepare a report from the European Agency for Drug Evaluation.

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 Reconocen que el adelgazante Reductil fue relacionado con 34 muertes

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Sourcehttp://www.healthig.com

Un despacho periodístico fechado en Londres, el 18 de marzo pasado, comunica que un total de 34 pacientes han muerto tras tomar el medicamento antiobesidad Reductil, perteneciente a Laboratorios Abbott. Eugene Sun, vicepresidente de desarrollos farmacéuticos de la compañía, hizo pública la cifra de fallecidos después de que el Departamento de Salud británico informara de la muerte de dos pacientes en ese país e indicara que en más de 200 personas se han observado reacciones adversas al fármaco en el Reino Unido.

Sun dijo que la empresa tiene información de 28 muertes en Estados unidos, dos en Italia, dos en el Reino unido, una en Sudáfrica y una en Suiza. Italia suspendió la venta de Reductil (sibutramina) la semana pasada tras recibir 50 informes sobre reacciones adversas en pacientes, incluidos los dos fallecimientos. En España se vende el medicamento desde el año pasado.

Abbot señaló que la tasa de muerte relacionada con Reductil es inferior a un 1% de la mortalidad relacionada con la obesidad, que a menudo sufren afecciones como diabetes y enfermedades cardiovasculares.

Casi nueve millones de personas han tomado la droga en el mundo, aclaró Sun. Los 34 fallecimientos suponen una incidencia de dos muertos por cada 100.000 personas tratadas anualmente con este fármaco, señaló el vicepresidente de Abbot. Los estudios sobre la obesidad indican que 400 personas por cada 100.000 mueren cada año por esta causa.

Reductil salió al mercado en 1997, después de varios años en ensayos en humanos. Tras la suspensión de la venta del fármaco en Italia, Abbot repasó los datos relacionados con la sibutramina en todo el mundo y envió toda la información sobre las reacciones adversas a las autoridades reguladoras.

Los dos fallecidos en el Reino Unido, según indicó el laboratorio, sufrían complicaciones cardíacas graves. Uno de ellos, además, padecía diabetes y un problema de tiroides; murió a los dos días de ser tratado con sibutramina. El otro había estado en tratamiento con este fármaco cuatro meses pero dejó de tomarlo cinco días antes de morir por un fallo en el corazón.

El Departamento de Salud británico declaró: 'Hasta el 13 de marzo de 2002 se han recibido 212 informes de lo que se sospecha son reacciones adversas, relacionadas con la sibutramina'. De estos informes, 93 fueron considerados graves. La declaración oficial indica que los pacientes que actualmente están siendo tratados con Reductil pueden continuar haciéndolo, 'pero si se sienten mal deben hablar con su médico'.

En otros países las autoridades están estudiando la documentación sobre reacciones adversas del fármaco para preparar un informe de la Agencia Europea de Evaluación de Medicamentos.

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9.) DEXFENFLURAMINE - REDUX Lab. INTERNEURON PHARMACEUTICALS, WYETH- AYERST.

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Source: Fda.gov, wikipedia.

It is important that you know that this drug (Dexfenfluramine-redux) is THE PRECURSOR OF SIBUTRAMINE. ALSO ELIMINATED FROM THE MARKET. A whole story exists behind this medicine to lose weight. I'm telling you.

Dexfenfluramine, marketed as dexfenfluramine hydrochloride under the name Redux, is a serotonergic anorectic drug: it reduces appetite by increasing the amount of extracellular serotonin in the brain.It is the d-enantiomer of fenfluramine and is structurally similar to amphetamine, but lacks any psychologically stimulating effects.

Dexfenfluramine was, for some years in the mid-1990s, approved by the United States Food and Drug Administration for the purposes of weight loss. However, following multiple concerns about the cardiovascular side-effects of the drug, the FDA withdrew the approval in 1997. After it was removed in the US, dexfenfluramine was also pulled out in other global markets. It was later superseded by sibutramine, which, although initially considered a safer alternative to both dexfenfluramine and fenfluramine[citation needed], was likewise removed from the US market in 2010.

The drug was developed by Interneuron Pharmaceuticals, Interneuron licensed the patent to Wyeth-Ayerst Laboratories.

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DEXFENFLURAMINA- REDUX Lab. INTERNEURON PHARMACEUTICALS, WYETH-AYERST

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Es importante que sepas que esta droga (Dexfenfluramina-redux) es LA PRECURSORA DE LA SIBUTRAMINA. TAMBIEN ELIMINADA DEL MERCADO. Toda una historia existe detras de esta medicina para perder peso. Yo te la estoy contando.

La dexfenfluramina, comercializada como clorhidrato de dexfenfluramina con el nombre de Redux, es un fármaco anorexígeno serotonérgico: reduce el apetito al aumentar la cantidad de serotonina extracelular en el cerebro. Es el d-enantiómero de la fenfluramina y es estructuralmente similar a la anfetamina, pero carece de efectos psicológicamente estimulantes.

La dexfenfluramina fue, durante algunos años a mediados de la década de 1990, aprobada por la Administración de Alimentos y Medicamentos de los Estados Unidos con el propósito de perder peso. Sin embargo, después de múltiples preocupaciones sobre los efectos secundarios cardiovasculares de la droga, la FDA retiró la aprobación en 1997. Después de que fue eliminado en los EE.UU., la dexfenfluramina también se retiró en otros mercados mundiales. Posteriormente fue reemplazada por la sibutramina, que, aunque inicialmente considerada una alternativa más segura a la dexfenfluramina ya la fenfluramina, también fue retirada del mercado estadounidense en 2010.

La droga fue desarrollada por Interneuron Pharmaceuticals, Interneuron licenció la patente al laboratorio Wyeth-Ayerst.

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10.) TROGLITAZON - REZULIN Lab. SANKYO, PARKE-DAVIS

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Solurce: Fda.gob, wikipedia, medscape.com

This drug is a classic example that good behavior is sometimes punished, the person in charge of evaluating the medicine at the FDA did not approve it, the laboratory complained about the man and then removed him from his position. Time showed that he was right. The facts:

Troglitazon (Rezulin, Resulin, Romozin, Noscal) is an antidiabetic and anti-inflammatory drug, and a member of the drug class of the thiazolidinediones. It was prescribed for patients with diabetes mellitus type 2. It was developed by Daiichi Sankyo (Japan). In the United States, it was introduced and manufactured by Parke-Davis in the late 1990s, but turned out to be associated with an idiosyncratic reaction leading to drug-induced hepatitis.

The F.D.A. medical officer assigned to evaluate troglitazone, John Gueriguian, did not recommend its approval due to potential high liver toxicity; Parke-Davis complained to the FDA and Gueriguian was subsequently removed from his post] A full panel of experts approved it in January 1997. Once the prevalence of adverse liver effects became known, troglitazone was withdrawn from the British market in December 1997, from the United States market in 2000, and from the Japanese market soon afterwards. It did not get approval in the rest of Europe.

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TROGLITAZON - RAZULIN Lab. SANKYO, PARQUE DAVIS.

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Esta droga es un clasico ejemplo de que el buen proceder a veces es castigado, el encargado de evaluar la medicina en la FDA no la aprobo, el laboratorio se quejo del hombre y entonces  lo removieron de su cargo. El tiempo demostro que tenia la razon. Los Hechos:

La troglitazona (Rezulin, Resulin, Romozin, Noscal) es un fármaco antidiabético y anti-inflamatorio, y un miembro de la clase de fármacos de las tiazolidinedionas. Se prescribió para pacientes con diabetes mellitus tipo 2. Fue desarrollado por Daiichi Sankyo (Japón). En los Estados Unidos, fue introducido y fabricado por Parke-Davis a finales de los años noventa, pero resultó estar asociado con una reacción idiosincrásica que condujo a la hepatitis inducida por fármacos.

El F.D.A. Médico encargado de evaluar la troglitazona, John Gueriguian, no recomendó su aprobación debido a una posible toxicidad hepática alta; Parke Davis se quejó a la FDA y Gueriguian fue posteriormente retirado de su puesto. Un grupo completo de expertos lo aprobó en enero de 1997. Una vez que se conoció la prevalencia de efectos adversos hepáticos, la troglitazona fue retirada del mercado británico en diciembre de 1997, del mercado de los Estados Unidos en 2000 y del mercado japonés poco después. No obtuvo la aprobación en el resto de Europa.

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11.)THIORIDAZINE  MELLERIL/ MELERIL Lab. NOVARTIS.

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 Source: Fda.gob, medscape.com, wikipedia

Thioridazine (Mellaril or Melleril) is a piperidine typical antipsychotic drug belonging to the phenothiazine drug group and was previously widely used in the treatment of schizophrenia and psychosis; the branded product was withdrawn worldwide in 2005 because it caused severe cardiac arrhythmias, however, generic versions are available in the US.

Thioridazine was voluntarily discontinued by its manufacturer, Novartis, worldwide because it caused severe cardiac arrhythmias.

Its primary use in medicine was the treatment of schizophrenia. It was also tried with some success as a treatment for various psychiatric symptoms seen in people with dementia, but chronic use of thioridazine and other anti-psychotics in people with dementia is not recommended.

Side effects

 

Thioridazine prolongs the QTc interval in a dose-dependent manner. It produces significantly less extrapyramidal side effects than most first-generation antipsychotics. Its use, along with the use of other typical antipsychotics, has been associated with degenerative retinopathies. It has a higher propensity for causing anticholinergic side effects coupled with a lower propensity for causing extrapyramidal side effects and sedation than chlorpromazine, but also has a higher incidence of hypotension and cardiotoxicity. It is also known to possess a relatively high liability for causing orthostatic hypotension compared to other antipsychotics. Similarly to other first-generation antipsychotics it has a relatively high liability for causing prolactin elevation. It is moderate risk for causing weight gain. As with all antipsychotics thioridazine has been linked to cases of tardive dyskinesia (an often permanent neurological disorder characterised by slow, repetitive, purposeless and involuntary movements, most often of the facial muscles, that is usually brought on by years of continued treatment with antipsychotics, especially the first-generation (or typical) antipsychotics such as thioridazine) and neuroleptic malignant syndrome (a potentially fatal complication of antipsychotic treatment).Blood dyscrasias such as agranulocytosis, leukopenia and neutropenia are possible with thioridazine treatment.

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TIORIDAZINA - MELERIL Lab. NOVARTIS.

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La tioridazina (Mellaril o Melleril) es un fármaco antipsicótico típico de piperidina perteneciente al grupo de fármacos de fenotiazina y que se utilizó anteriormente ampliamente en el tratamiento de la esquizofrenia y la psicosis; El producto de marca fue retirado en todo el mundo en 2005 debido a que causó severas arritmias cardíacas, sin embargo, las versiones genéricas están disponibles en los EE.UU.

Thioridazine fue interrumpido voluntariamente por su fabricante, Novartis, en todo el mundo, ya que causó severas arritmias cardíacas.

Su principal uso en medicina fue el tratamiento de la esquizofrenia. También se intentó con cierto éxito como tratamiento para varios síntomas psiquiátricos observados en personas con demencia, pero no se recomienda el uso crónico de tioridazina y otros antipsicóticos en personas con demencia.

Efectos secundarios

La tioridazina prolonga el intervalo QTc de una manera dependiente de la dosis. Produce significativamente menos efectos secundarios extrapiramidales que la mayoría de los antipsicóticos de primera generación. Su uso, junto con el uso de otros antipsicóticos típicos, se ha asociado con retinopatías degenerativas. Tiene una mayor propensión a causar efectos secundarios anticolinérgicos, junto con una menor propensión a causar efectos secundarios extrapiramidales y sedación que la clorpromazina, pero también tiene una mayor incidencia de hipotensión y cardiotoxicidad. También se sabe que posee una responsabilidad relativamente alta de causar hipotensión ortostática en comparación con otros antipsicóticos. Al igual que otros antipsicóticos de primera generación, tiene una responsabilidad relativamente alta para provocar la elevación de la prolactina. Es un riesgo moderado de causar aumento de peso. Al igual que con todos los antipsicóticos, la tioridazina se ha relacionado con casos de discinesia tardía (un trastorno neurológico frecuentemente permanente caracterizado por movimientos lentos, repetitivos, sin propósito e involuntarios, más frecuentemente de los músculos faciales, que suele provocar años de tratamiento continuado con antipsicóticos, Especialmente los antipsicóticos de primera generación (o típicos) como la tioridazina) y el síndrome neuroléptico maligno (una complicación potencialmente fatal del tratamiento antipsicótico). Las disacrasias del bazo como la agranulocitosis, la leucopenia y la neutropenia son posibles con el tratamiento con tioridazina.

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12.) LYMErix VACCINE - Lab. Glaxo-Smith-Kline(GSK).

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You can read the full story about LYME DISEASE AND VACCINE HERE.

In the year 1998, December 21, the FDA approved the use of the LYMErix vaccine manufactured by the laboratory SmithKline Beecham, today GlaxoSmithKline (GSK) and promised to be a good way to Stop the progression of this pathology, shortly afterwards began to report adverse effects by the application of the same, also did not have much acceptance in the population and was withdrawn from the market in year 2.002.

Nearly 15 years after the withdrawal of the LYMErix vaccine, there is now no vaccine against the disease, caused by the causative agent Borrelia burgorferi, which is transmitted by a tick bite! In the reference  you can read the testimonial of 3 people who were SEVERELY affected by the LIMERix vaccine, and requested for its discontinuation.

Today a year 2.017, I show you a study about of the safety of ospA vaccine !!! The same LYMErix [Lyme Disease Vaccine (Recombinant OspA)]  ???.

To finish I put this paragraph extracted from the monograph of the product LYMErix ...

..."Among the 10,936 subjects enrolled in the efficacy trial and followed for 20 months, a total of 15 deaths occurred (10 vaccine, 5 placebo). None of these deaths were judged to be treatment-related by investigators. In the vaccine group, causes of death included: cancer (5), myocardial infarction (3), sudden death (1),cardiac arrest (1). In the placebo group, causes of death included:cancer (1), sudden cardiac death (1), cardiac arrest (1), septicshock (1), homicide (1)...."

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LYMERrix -VACUNA Lab. Glaxo-Smith-Kline(GSK)

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Puedes leer la historia completa sobre la enfermedad de LYME Y VACUNA AQUI...

En el año 1.998, 21 de diciembre la FDA aprobo el uso de la vacuna LYMErix fabricada por el laboaratorio  SmithKline Beecham,  hoy GlaxoSmithKline (GSK) y que prometio ser un buen medio para detener el avance de esta patologia, poco despues comenzaron a reportarse efectos adversos por la aplicacion de la misma, ademas no tuvo mucha aceptacion en la poblacion y fue retirada del mercado en el ano 2.002.

Han pasado casi 15 años luego de retirada del mercado la vacuna LYMErix y hoy en dia no existe vacuna alguna contra esta enfermedad, causada por el agente causal Borrelia burgdorferi, la cual es transmitida por la picadura de una garrapata !. En la referencia puede leer el testimonial de 3 personas QUE FUERON SEVERAMENTE afectadas por la vacuna LIMERix, y pidieron su descontinuacion.

Hoy dia se publica un estudio año 2.017 donde se habla de la seguridad de la vacuna ospA,!!! La misma vacuna LYMErix [Enfermedad de Lyme  (Recombinante OspA)]  ???.

Para terminar les pongo este parrafo extraido de la monografia del producto LYMErix...

......"Entre los 10.936 sujetos inscritos en el ensayo de eficacia y Seguido durante 20 meses, se produjeron un total de 15 muertes (10 vacunas, 5

placebo). Ninguna de estas muertes se juzgó como tratamiento-Relacionados por los investigadores. En el grupo de vacunas, las causas de muerte

Incluidos: cáncer (5), infarto de miocardio (3), muerte súbita (1),Paro cardiaco (1). En el grupo placebo, las causas de muerte incluyeron:Cáncer (1), muerte cardíaca súbita (1), paro cardiaco (1), septicemia Shock (1), homicidio (1)...."

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FDA Vaccine Advisory Committee,  LymeRix Vaccine Victim's Stories

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To Whom It May Concern:

I am unable to attend the January 3 1 FDA Vaccine Advisory Committee meeting due to a

restrictive condition, Transverse Myelitis, resulting from the Lymerix vaccine. In the spring of

1999, I decided to get the series of Lymerix shots, after, viewing a verv convincing TV

commercial touting the importance of protecting oneself from Lyme Dise:ase. I felt this would be

a good thing to take advantage of since I had had numerous bites from the ticks which cause

Lyme Disease.

I was given the fust shot of the series on April 20, 1999. Thirteen days later, I collapsed,

completely paralyzed. Many tests at the hospital confirmed the di&nosis of Transverse Myelitis

- inflammation of the myelin sheath around the spinal cord. After days in Intensive Care at the

hospital, I was transferred to the Rehabilitation Center where I spent six months. After intensive

physical and occupational therapy, some mobility returned, but I am in a wheelchair most of the

time. My life has been drastically changed for the past 21 months. Up to the day I collapsed, I

was constantly on the go with meetings of historical societies and community organizations,

church activities, house tours, dinner parties, exercise classes, bus trips, theater outings, concerts,

etc. I used to wear my daughters out, just telling them about all of the running around I did. I

used to be a world traveler, but now because of physical liitations, I stay close to home. I am

able to live at home onlv with sunport from family and friends, and a paid nighttime caregiver.

For the first nine months after coming home from the Rehabilitation Center, I required round-

the-clock caregivers.

Prior to the Lymerix vaccine, I was in excellent health and completely independent. I

strongly urge you to take Lymerix off the market to spare others the pain and suffering it can

cause.

Very truly yours,

=================================================================

My name is

and I have been asked to speak on behalf of

my daughter,

‘. had a pretty normal childhood and

adolescence until the year 1999. Until that point in time, she had a very

active life. She had a horse that she used for exercise and enjoyment. She

had competed on him in various venues. They enjoyed jumping and dressage.

She volunteered in a therapeutic riding barn and worked with multiply

handicapped children. Her plans were to get her degree in veterinary medicine

and have a small animal practice. She held down a job at a vet’s office and

loved going to work and facing the challenges there.ln the !spring of that

year, I decided to get her the lyme vaccine. She was in contact with various

animals daily and spent a lot of time in the woods with horses. It seemed like

a good idea at the time. She had had a simple case of unconfirmed Lyme

Disease when she was around 12 years old and it seemed to respond to

antibiotics, so I thought Lymerix would be a good idea. My primary doctor

looked over the literature and agreed to give this series of injections. Our

lives have never been the same. After the 2nd injection, --

complained

of ankle pain. I took her to an orthopedic surgeon who couldn’t find anything

wrong at the time. We sent her for physical therapy and gave her

medication. She made the best of it and never really got much better. She

had vague complaints of other joints bothering her, but again she kept

plugging along. She developed flulike symptoms, a rash, and woke up on

October 3 1 st, 1999 with peripheral blindness. She was having terrible muscle

aches and joint swelling and pain. We went to many specialists. Finally, we

decided to test her for HLA-dr4 ad lo and behold we had a positive. We also

had a positive ANA. To this day, she continues to test negative for Lyme,

MS, Lupus, Crohn’s Disease and all of the other autoimmune illnesses that

our doctors assumed were the possible cause. Their is no history of juvenile

arthritis in either side of the family. Her ar!

thritis just kept getting worse, even with treatments of anti inflammatories

and all of the arthritis medications on the market. She spent her entire

senior year at home, too ill to even walk through the hallways and put in a full

day at school. She missed her senior prom and any social activities that a

.

normal senior in high school participates in. Her horse coulcl not be exercised

or jumped by her for a very long period of time. We have taken -

to

many specialists in the New York area. They have no explanations for this

sudden dramatic change in her health except the probability that she had a

reaction to Lymerix which somehow caused an autoimmune reaction (because

of the bodies exposure to OspA). I am not as knowledgeable as this

distinguished panel of experts that I speak-to today, but I krnow one thing

with all of my being. It was Lymerix which somehow had this devastating

affect on my 17 year-old child. I think you have all considered that possibility

before today. Maybe after today you will think it is more than just a

possibility, you will see this drug can have some longlasting,dangerous side

effects. Just remember, I have been told this by many a doctor in the last

year and a half, they can treat and cure Lyme Disease but they cannot cure

an autoimmune arthritis. This is an 18year old who will never again be able to

run to catch a bus, or jump her horse with abandon. Her life will be forever

changed by Lymerix. Please consider this very carefully when making your

decisions about giving this to children

=======================================================

To Whom It May Concern,

January 23,200l

In 1999 I was a very healthy 40 year old. Very active with my 10 year

old son, skating, bowling and biking. My only health complaint was

migraines and daily headaches. On May 21 ,I 999 I received the Lymetix

vaccine. With 24 hours I had flu like symptoms, body aches and low

grade fever. I did not think much of it being a nurse and knowing that this

is a common reaction to vaccines. Two weeks after the shot I woke up

and my right elbow was hurting and with a few days the body aches

returned. By the time I went for my second injection I had complained to

my doctor that I was hurting from head to toe and the fatigue was

unbearable. He did not think it was related to the vaccine, because he had

heard nothing about any adverse reactions. I had the second injection

that day and my life has been a living hell since. Within 48 hours I was in

severe joint and body pain, that has not stopped. I tried seeing doctors

and no one knew anything about this vaccine and the realctions it was

causing. I was diagnosed with CFS, fibromalagia, and was even told it

could be stress from my job. I am a Hospice nurse and love what I do.

For months I went through this pain without any help from1 the medical

field. I wake up in the mornings and my husband has to help me out of

bed because the pain is so severe. Four times I have been paralyzed,

three from my wrist down and once from my neck down for up to 20

minutes. I am scared that I my wake up one day and not be able to move

ever again.

I have since seen a doctor that told me I have an auto-immune reaction to

the vaccine that is untreatable and incurable. I am presently under the

care of a pain management doctor. If it was not for the pa.in medicine I

.

would not be able to get through my day. I still wake in the mornings with

severe, debilitating pain. I have to keep the pain medicine by my bed to

get up.

I have had very odd occurrences of unexplained symptoms. I have small

areas on my body that become red and feel as if they are burning, like fire,

from the inside. The fatigue is unbearable at times, especially with having a

10 year old. I am unable to enjoy being active with him like before.

I have been in contact with nearly 75 people that have been harmed by

this vaccine. It is destroying peoples life’s. It is hurting our most healthy

population. The population that goes out doors for different activities, they

are now bedridden or in such severe pain they are unable to move about

with daily activities without difficulty.

This reaction is not just hurting a certain age group. I have been contacted

by people from the age of 17 and up. I ask the committee to recommend

that this vaccine be taken off the market before more people are hurt.

As of May 8, 2000 there were 467 adverse reactions reported to VAERS,

and of them 144 had complained of some sort of joint pain. Please do not

let this vaccine hurt anymore people. I know SmithKline is trying to get it

approved for children, PLEASE DO NOT LET THEM HURT ANYMORE

KIDS.

Thank you

===============================================

Post-marketing withdrawal of 462 medicinal products because of adverse drug reactions: a systematic review of the world literature

===============================================

BMC Med. 2016; 14: 10.

Published online 2016 Feb 4. doi:  10.1186/s12916-016-0553-2

Igho J. Onakpoya,corresponding author Carl J. Heneghan, and Jeffrey K. Aronson

Centre for Evidence-based Medicine, Nuffield Department of Primary Care Health Sciences, University of Oxford, New Radcliffe House, Radcliffe Observatory Quarter, Oxford, OX2 6GG UK

Igho J. Onakpoya, Phone: +44 (0) 1865289672, Email: ku.ca.xo.chp@ayopkano.ohgi.

corresponding authorCorresponding author.

Abstract

Background

There have been no studies of the patterns of post-marketing withdrawals of medicinal products to which adverse reactions have been attributed. We identified medicinal products that were withdrawn because of adverse drug reactions, examined the evidence to support such withdrawals, and explored the pattern of withdrawals across countries.

Methods

We searched PubMed, Google Scholar, the WHO’s database of drugs, the websites of drug regulatory authorities, and textbooks. We included medicinal products withdrawn between 1950 and 2014 and assessed the levels of evidence used in making withdrawal decisions using the criteria of the Oxford Centre for Evidence Based Medicine.

Results

We identified 462 medicinal products that were withdrawn from the market between 1953 and 2013, the most common reason being hepatotoxicity. The supporting evidence in 72 % of cases consisted of anecdotal reports. Only 43 (9.34 %) drugs were withdrawn worldwide and 179 (39 %) were withdrawn in one country only. Withdrawal was significantly less likely in Africa than in other continents (Europe, the Americas, Asia, and Australasia and Oceania). The median interval between the first reported adverse reaction and the year of first withdrawal was 6 years (IQR, 1–15) and the interval did not consistently shorten over time.

Conclusion

There are discrepancies in the patterns of withdrawal of medicinal products from the market when adverse reactions are suspected, and withdrawals are inconsistent across countries. Greater co-ordination among drug regulatory authorities and increased transparency in reporting suspected adverse drug reactions would help improve current decision-making processes.

=============================================================

Producido por Dr. José Lapenta R. Dermatólogo

  Maracay Estado Aragua Venezuela 2.017-2.023  

 Telf:  04142976087 - 04127766810

04166401045

 

 Follow @dermagicexpr

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