boxed warning
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 event 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); tricyclic antidepressants (such as amitriptyline); certain antidepressants (such as nefazodone and maprotiline); certain antipsychotic 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 valvular heart disease; other structural heart defects; cardiomyopathy; congestive heart failure; clinically significant bradycardia; 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.