Propulsid (cisapride) Dear Healthcare Professional Letter Jan 2000
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This is the retyped text of a letter from Janssen Pharmaceutica Research Foundation. Contact the company for a copy of any referenced enclosures.
IMPORTANT DRUG WARNING
January 24, 2000
Janssen Pharmaceutica would like to inform you of important changes made in the PROPULSID (cisapride) labeling. We wish to draw your attention to the Boxed Warning, Drug Interactions and Dosage and Administration sections that contain the essential changes. Other sections of the labeling including Contraindications, Warnings, Precautions, and Adverse Reactions, have also been revised to reflect these changes. In addition, similar changes have been incorporated into the PROPULSID Patient Medication Guide. Highlights of the changes include the following:
- A 12-lead ECG should be obtained before PROPULSID is administered.
- PROPULSID should not be initiated if the QTc value exceeds 450 milliseconds.
- PROPULSID is contraindicated in patients with electrolyte disorders (hypokalemia, hypocalcemia and hypomagnesmia). Serum electrolytes should be assessed in diuretic-treated patients before initiating PROPULSID and periodically thereafter.
Revised information is highlighted in red:
This section has been expanded and reorganized.
Warning: Serious cardiac arrhythmias including ventricular tachycardia, ventricular fibrillation, torsades de pointes, and QT prolongation have been reported in patients taking PROPULSID. From July 1993 through May 1999, more than 270 such cases have been spontaneously reported, including 70 fatalities. In approximately 85% of these cases the events occurred when PROPULSID was used in patients with known risk factors. These risk factors included the administration of other drugs which caused QT prolongation, inhibited the cytochrome P450 3A4 enzymes that metabolize cisapride, or depleted serum electrolytes: or the presence of disorders that may have predisposed patients to arrhythmias. In approximately 0.7% of these cases, the events occurred in the absence of identified risk factors: in the remaining cases, risk factor status was unknown. Because the cases were reported voluntarily from a population of unknown size, estimates of adverse events frequency cannot be made (See CONTRAINDICATIONS, WARNINGS, PRECAUTIONS and Drug Interactions.)
Numerous drug classes and agents increase the risk of developing serious cardiac arrhythmias. PROPULSID is contraindicated in patients taking certain macrolide antibiotics (such as clarithromycin, erythromycin, and troleandomycin), certain antifungals (such as fluconazole, itraconazole, and ketoconazole), protease inhibitors (such as indinavir and ritonavir), phenothiazines (such as prochlorperazine and promethazine); Class IA and Class III antiarrhythmics (such as quinidine, procainamide, and sotalol); tricylic antidepressants (such as amitriptyline); certain antidepressants (such as nefazodone and maprotiline); certain antipsycotic medications (such as sertindole) as well as other agents (such as bepridil, sparfloxacin, and grapefruit juice). See PRECAUTIONS: Drug Interactions.) The preceding list is not comprehensive.
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 PROPULSID. These include history of prolonged electrocardiographic QT intervals or known family history of congenital long QT syndrome; history of ventricular arrhythmias, ischemic or vascular heart disease; other structural heart defects; cardiomyopathy; congestive heart failure: clinically significant bradycardias; sinus node dysfunction; second or third degree atrioventricular block; respiratory failure; or conditions that result in electrolyte disorders (hypokalemia, hypocalcemia, and hypomagnesemia), such as severe dehydration, vomiting, or malnutrition, eating disorders: renal failure; or the administration of potassium-wasting diuretics or insulin in acute settings. PROPULSID is contraindicated in patients with these conditions.
A 12-lead ECG should be performed prior to administration of PROPULSID. Treatment with PROPULSID should not be initiated if the QTc value exceeds 450 milliseconds. Serum electrolytes (potassium, calcium, and magnesium) and creatinine should be assessed prior to administration of PROPULSID and whenever conditions develop that may affect electrolyte balance or renal function (See DOSAGE AND ADMINISTRATION.)
If syncope, rapid or irregular heartbeat develop, patients should immediately stop taking PROPULSID and seek the attention of a physician.
Recommended doses of PROPULSID should not be exceeded.
This section has been revised as follows to include:
DOSAGE AND ADMINISTRATION
This section has been expanded to include:
Janssen Pharmaceutica is committed to providing you with the most current product information available for the management of your patients receiving PROPULSID. You 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 1-800-FDA-1088, by fax 1-800-FDA-0178, by mail (using postage-paid form) MedWatch, HF-2, FDA, 5600 Fishers Lane, Rockville, MD 20852-9787, or via www.fda.gov/medwatch.
Please refer to the enclosed revised package insert for full prescribing information, including Boxed Warning, and the medication guide. For additional medical information concerning PROPULSID, please call the Janssen One to One Customer Action Center at 1-800-JANSSEN (526-7736) from 8AM to 8PM Eastern Time, Monday through Friday.
Jan Gheuens, MD
Vice President, Medical Affairs
Janssen at Washington Crossing
1125 Trenton Harbouton Road
Post Office Box 200
Titusville, New Jersey 08500-0200