Dear PD Listserv:
I also subscribe to the Pharminfobytes Listerv, which often has very good
resources about pharmaceutical & medical-related research, in my
continuing search for news regarding PD developments.
Pharminfobytes just now posted some very important news about PROPULSID,
which I know that many people with PD may take as a means of helping
counteract a sluggish digestive tract and constipation; even my mother had
taken this, as prescribed by doctors, during her 1996 hospitalization.
I knew that PROPULSID had some drawbacks -- but I think that this new data
makes it even more important to carefully consider the pros & cons of
taking PROPULSID before deciding whether or not to use it.
I have, therefore, obtained permission from the editor of Pharminfobytes
to reprint their file on this here in its entirety.
It's lengthy, but worth reading.
-- SJS
6/30/98
...And here's the file:
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Date: Mon, 29
Jun 1998 18:25:30 -0400 From: John Mack <[log in to unmask]>
Reply-To: PharmInfoBYTES Newsletter and Notification Service
<[log in to unmask]>
To: [log in to unmask]
Subject: PHARMINFOBYTES: Propulsid (cisapride) "Dear Dr Letter"
[U.S. Food andDrug Administration]
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This is the retyped text of a letter from Janssen Pharmacuetica. Contact the
company for a copy of any referenced enclosures.
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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
The following brand names are registered trademarks of the companies listed
below.
Abbott Laboratories BIAXIN (clarithromycin), NORVIR (ritonavir)
Bristol-Myers Squibb SERZONE (nefazodone)
Janssen Pharmaceutica, SPORANOX (itraconazole), NIZORAL
Inc. (ketoconazole)
Merck & Co. Inc. CRIXIVAN (indinavir)
Pfizer, Inc. DIFLUCAN (fluconazole), TAO (troleandomycin)
-------------------
Janssen At Washington Crossing
1125 Trenton-Harbourton Road
PO Box 200
Titusville, New Jersey 08560-0200
[END of message]
