|
Use this link to order from Amazon.com and IARP will
receive a donation.
| |
Propulsid Warning Letter Sent
To Doctors.
JANSSEN
PHARMACEUTICA
RESEARCH FOUNDATION
IMPORTANT SAFETY AND EFFICACY INFORMATION
June 26, 1998
Dear Doctor,
Janssen Pharmaceutica would like to inform you of labeling changes concerning new
CONTRAINDICATIONS, WARNINGS, PRECAUTIONS, ADVERSE REACTIONS, and DRUG INTERACTIONS with
PROPULSID (cisapride). In addition, revisions have been made in the PEDIATRIC USE,
INDICATIONS AND USAGE, and DOSAGE AND ADMINISTRATION sections.
We wish to draw your attention to the following sections of the revised PROPULSID labeling
which contain the essential changes.
Warning: Serious cardiac arrhythmias including ventricular tachycardia, ventricular
fibrillation, torsades de pointes, and QT prolongation have been reported in patients
taking PROPULSID. Many of these patients also took drugs expected to increase cisapride
blood levels by inhibiting the cytochrome P450 3A4 enzymes that metabolize cisapride.
These drugs include clarithromycin, erythromycin, troleandomycin, nefazodone, fluconazole,
itraconazole, ketoconazole, indinavir and ritonavir. Some of these events have been fatal.
PROPULSID is contraindicated in patients taking any of these drugs. (See
CONTRAINDICATIONS, WARNINGS, PRECAUTIONS, and DRUG INTERACTIONS).
QT prolongation, torsades de pointes (sometimes with syncope), cardiac arrest and sudden
death have been reported in patients taking PROPULSID without the above-mentioned
contraindicated drugs. Most patients had disorders that may have predisposed them to
arrhythmias with cisapride. PROPULSID is contraindicated for those patients with: history
of prolonged electrocardiographic QT intervals; renal failure; history of ventricular
arrhythmias, ischemic heart disease, and congestive heart failure; uncorrected electrolyte
disorders (hypokalemia, hypomagnesemia); respiratory failure; and concomitant medications
known to prolong the QT interval and increase the risk of arrhythmia, such as certain
antiarrhythmics, including those of Class 1A (such as quinidine and procainamide) and
Class III (such as sotalol); tricyclic antidepressants (such as amitriptyline); certain
tetracyclic antidepressants (such as maprotiline); certain antipsychotic medications (such
as certain phenothiazines and sertindole), astemizole, bepridil, sparfloxacin and
terodiline. (The preceding lists of drugs are not comprehensive.)
Recommended doses of PROPULSID should not be exceeded.
INDICATIONS & USAGE
PROPULSID (cisapride) is indicated for the symptomatic treatment of adult patients with
nocturnal heartburn due to gastroesophageal reflux disease. Because of the risk of
serious, and sometimes fatal, ventricular arrhythmias (see Boxed Warning), PROPULSID
should generally be reserved for patients who do not respond adequately to lifestyle
modifications (See PRECAUTIONS: Information for Patients), antacids and gastric acid
reducing agents.
CONTRAINDICATIONS
Serious cardiac arrhythmias including ventricular tachycardia, ventricular fibrillation,
torsades de pointes, and QT prolongation have been reported in patients taking PROPULSID
(cisapride) with other drugs that inhibit cytochrome P450 3A4. Some of these events have
been fatal.
Concomitant oral or intravenous administration of the following drugs with cisapride may
lead to elevated cisapride blood levels and is contraindicated (See WARNINGS, PRECAUTIONS
and DRUG INTERACTIONS):
Antibiotics: Oral or i.v. erthromycin, clarithromycin (BIAXIN), troleandomycin (TAO)
Antidepressants: Nefazodone (SERZONE)
Antifungals: Oral or i.v. fluconazole (DIFLUCAN), itraconazole (SPORANOX), oral
ketoconazole (NIZORAL)
Protease inhibitors: Indinavir (CRIXIVAN), ritonavir (NORVIR)
PROPULSID is also contraindicated for patients with: history of prolonged
electrocardiographic QT intervals; renal failure; history of ventricular arrhythmias,
ischemic heart disease, and congestive heart failure; uncorrected electrolyte disorders
(hypokalemia, hypomagnesemia); respiratory failure; and concomitant medications known to
prolong the QT interval and increase the risk of arrhythmia, such as certain
antiarrhythmics, certain antipsychotics, certain antidepressants , astemizole, bepridil,
sparfloxacin and terodiline. The preceding lists of drugs are not comprehensive.
PROPULSID should not be used in patients with uncorrected hypokalemia or hypomagnesemia or
who might experience rapid reduction of plasma potassium such as those administered
potassium-wasting diuretics and/or insulin in acute settings.
WARNINGS
ECG should be considered prior to initiation of cisapride. Cisapride should not be used in
patients with a prolonged QT interval at baseline, those with a history of torsades de
pointes, or those with long QT syndrome. Cisapride should also be avoided in patients with
sinus node dysfunction, and in those with second or third degree atrioventricular block.
Cisapride should not be used concomitantly with other drugs known to prolong the QT
interval; certain antiarrhythmics, including those of Class 1A (such as quinidine and
procainamide) and Class III (such as sotalol): tricyclic antidepressants (such as
amitriptyline); certain tetracyclic antidepressants (such as maprotiline); certain
antipsychotic medications (such as certain phenothiazines and sertindole); astemizole,
bepridil, sparfloxacin and terodiline. (See CONTRAINDICATIONS, PRECAUTIONS and DRUG
INTERACTIONS.) The preceding lists of drugs are not comprehensive.
PRECAUTIONS
General: Potential benefits should be weighed against risks prior administration of
cisapride to patients who have or may develop prolongation of cardiac conduction
intervals, particularly QTc. These include patients with conditions that could predispose
them to the development of serious arrhythmias, such as multiple organ failure, COPD,
apnea and advanced cancer. (See CONTRAINDICATIONS.)
PROPULSID (cisapride) should not be used in patients with uncorrected hypokalemia or
hypomagnesemia, such as those with severe dehydration, vomiting or malnutrition, or those
taking potassium-wasting diuretics. PROPULSID should not be used in patients who might
experience rapid reduction of plasma potassium, such as those administered
potassium-wasting diuretics and/or insulin in acute settings.
Pediatric Use: Safety and effectivenesss in pediatric patients have not been established.
Although causality has not been established, serious adverse events, including death, have
been reported in infants and children treated with cisapride. Several pediatric deaths
were due to cardiovascular events (third degree heart block and ventricular tachycardia).
Pediatric deaths have been associated with seizures and there has been at least one case
of "sudden unexplained death" in a 3-month-old infant. Other unlabeled
potentially serious events which have been reported in pediatric patients include:
antinuclear antibody (ANA) positive, anemia, hemolytic anemia, methemoglobinemia,
hyperglycemia, hypoglycemia with acidosis, unexplained apneic episodes, confusion,
impaired concentration, depression, apathy, visual changes accompanied by amnesia, and
severe photosensitivity reaction.
A one-month-old male infant received 2 mg/kg of cisapride four times per day for 5 days.
The patient developed third degree heart block and subsequently died of right ventricular
perforation caused by pacemaker wire insertion.
ADVERSE REACTIONS
Postmarketing Reports: In addition to the cardiovascular adverse events, the following
events have been identified during post-approval use of cisapride in clinical practice.
Because they are reported voluntarily from a population of unknown size, estimates of
frequency cannot be made. These events have been chosen for inclusion in this insert due
to a combination of their seriousness, frequency of reporting, or potential causal
connection to cisapride: allergic reactions, including bronchospasm, urticaria, and
angioedema; possible exacerbation of asthma; psychiatric events, including confusion,
depression, suicide attempt, and hallucinations; gynecomastia, female breast enlargement,
urinary incontinence, hyperprolactinemia and galactorrhea.
The following events were specifically reported in the pediatric population: antinuclear
antibody (ANA) positive, anemia, hemolytic anemia, methemoglobinemia, hyperglycemia,
hypoglycemia with acidosis, unexplained apneic episodes, confusion, impaired
concentration, depression, apathy, visual changes accompanied by amnesia, and severe
photosensitivity reactions.
DOSAGE AND ADMINISTRATION
PROPULSID should be discontinued if relief of nocturnal heartburn does not occur. The
minimum effective dose should be used. Recommended doses of PROPULSID should not be
exceeded.
It is recommended that the daily dose be halved in patients with hepatic insufficiency.
We at Janssen want you to be aware of this important information to ensure the proper use
of PROPULSID in your patients. Please refer to the enclosed revised package insert for
full prescribing information. The Medical Community can further our understanding of
adverse events by reporting all cases to Janssen at 1-800-Janssen (526-7736) or to the FDA
MedWatch program by phone at 1-800-FDA-1088, by fax at 1-800-FDA-0178, or by mail to
MedWatch, HF-2, FDA, 5600 Fishers Lane, Rockville, MD 20857. For additional medical
information, please call 1-800-Janssen from 8 AM to 8 PM Eastern Time, Monday through
Friday.
Sincerely,
Mark A. Klausner, M.D.
Vice President, Medical Affairs
Send us Email: 
[ Reflux Support ] [ Reflux Child ] [ Reflux Information ] [ Dealing With GERD ] [ Doctor Referrals ] [ Donation Form ] [ Reflux Products ] [ July Newsletter ][ Testing ] [ Propulsid Warning ] [ Reflux Meds ]
|
