Thought you might be interested.

In a message dated 98-06-30 00:51:38 EDT, you write:

> 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:
> *********************
>
> 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]
>
----------------------------------------------------------------------------
> This is the retyped text of a letter from Janssen Pharmacuetica. Contact
the
> company for a copy of any referenced enclosures.
>
----------------------------------------------------------------------------
> 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]
>
>
>