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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] > > >