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]
>
>
>