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Vascor (bepridil) Disease Interactions

There are 8 disease interactions with Vascor (bepridil):

Major

Bepridil (applies to Vascor) agranulocytosis

Major Potential Hazard, Low plausibility. Applicable conditions: Neutropenia

According to the manufacturer, there have been two cases of marked leukopenia and neutropenia reported in U.S. clinical trials of over 800 patients treated with bepridil for up to five years. Both involved diabetic and elderly patients, with one case resulting in death and the other recovering after discontinuation of the drug. In a postmarketing report, a 72-year-old man with severe angina pectoris developed fever and chills associated with an absolute neutrophil count of 35/mm3 six weeks after switching from diltiazem and nitrates to bepridil and nitrates. A bone marrow biopsy revealed profound myeloid hypoplasia. The patient recovered after discontinuation of bepridil and institution of granulocyte colony-stimulating factor and broad-spectrum antibiotics. Therapy with bepridil should be administered cautiously in patients with preexisting neutropenia or agranulocytosis. The drug should be withdrawn promptly if these conditions develop during therapy.

References

  1. "Product Information. Vascor (bepridil)." McNeil Pharmaceutical, Raritan, NJ.
  2. Singh BN "Comparative efficacy and safety of bepridil and diltiazem in chronic stable angina pectoris refractory to diltiazem. The Bepridil Collaborative Study Group." Am J Cardiol 68 (1991): 306-12
  3. Weiss RJ "Bepridil and agranulocytosis." Am Heart J 125 (1993): 1819-20
Major

Bepridil (applies to Vascor) arrhythmias

Major Potential Hazard, High plausibility. Applicable conditions: Abnormal Electrocardiogram, Tachyarrhythmia

The use of bepridil is contraindicated in patients with a history of serious ventricular arrhythmias; patients with congenital or acquired QT interval prolongation syndromes; and patients treated concomitantly with class IA or III antiarrhythmic drugs or other medications that are known to produce increases in the QT interval or cause torsade de pointes. Bepridil has class I antiarrhythmic properties and can induce new arrhythmias, including ventricular tachycardia and ventricular fibrillation. Patients with other severe arrhythmias may have increased susceptibility to the proarrhythmic effects of bepridil, but use in such patients has been limited. Bepridil can also cause torsade de pointes type ventricular tachycardia secondary to its ability to prolong the QT interval. In U.S. clinical trials, the mean prolongations of QTc and QT were 8% and 10%, respectively, but increases of 25% or more occurred in 5% of the studied population for QTc and 8.7% for QT. Although the absolute safe upper limit of QT is not known, the manufacturer recommends that the dosage be reduced in patients whose QT interval exceeds 0.52 seconds during treatment. If prolongation remains excessive, the drug should be discontinued.

References

  1. Coumel P "Safety of bepridil: from review of the European data." Am J Cardiol 69 (1992): d75-8
  2. Shapiro W "Comparative efficacy of bepridil versus placebo in angina pectoris: treatment and withdrawal studies." Am J Cardiol 69 (1992): d43-9
  3. Singh BN "Bepridil therapy: guidelines for patient selection and monitoring of therapy." Am J Cardiol 69 (1992): d79-85
  4. "Product Information. Vascor (bepridil)." McNeil Pharmaceutical, Raritan, NJ.
  5. Singh BN "Safety profile of bepridil determined from clinical trials in chronic stable angina in the United States." Am J Cardiol 69 (1992): d68-74
View all 5 references
Major

Bepridil (applies to Vascor) CHF

Major Potential Hazard, High plausibility. Applicable conditions: Myocardial Infarction, Congestive Heart Failure

Bepridil may have a negative inotropic effect, particularly at high dosages. Congestive heart failure has been observed infrequently (approximately 1%) in U.S. controlled clinical trials. However, experience with the use of bepridil in the presence of significantly impaired ventricular function is limited, and there is little information on the effect of concomitant administration with digoxin. Therapy with bepridil should be administered cautiously in patients with congestive heart failure, especially if they have severe left ventricular dysfunction (e.g., ejection fraction < 30%) or if they are receiving a beta-adrenergic blocker. Likewise, bepridil should not be given to patients with acute myocardial infarction and pulmonary congestion documented by X-ray on admission, since associated heart failure may be acutely worsened. Mild symptoms of cardiac failure should be under control, if possible, prior to initiating bepridil therapy.

References

  1. Singh BN "Safety profile of bepridil determined from clinical trials in chronic stable angina in the United States." Am J Cardiol 69 (1992): d68-74
  2. Shapiro W "Comparative efficacy of bepridil versus placebo in angina pectoris: treatment and withdrawal studies." Am J Cardiol 69 (1992): d43-9
  3. "Product Information. Vascor (bepridil)." McNeil Pharmaceutical, Raritan, NJ.
  4. Coumel P "Safety of bepridil: from review of the European data." Am J Cardiol 69 (1992): d75-8
  5. Singh BN "Bepridil therapy: guidelines for patient selection and monitoring of therapy." Am J Cardiol 69 (1992): d79-85
View all 5 references
Major

Bepridil (applies to Vascor) electrolyte imbalance/hypokalemia

Major Potential Hazard, High plausibility. Applicable conditions: Electrolyte Abnormalities, Magnesium Imbalance, Diarrhea

Bepridil can cause torsade de pointes type ventricular tachycardia secondary to its ability to prolong the QT interval. In U.S. clinical trials, the mean prolongations of QTc and QT were 8% and 10%, respectively, but increases of 25% or more occurred in 5% of the studied population for QTc and 8.7% for QT. Electrolyte disturbances such as hypokalemia and hypomagnesemia may augment the prolongation effect of bepridil on the QT interval and should be corrected prior to institution of bepridil therapy. In addition, patients who experience frequent, severe, and/or prolonged diarrhea may be subject to electrolyte losses and should be followed closely and managed accordingly during therapy with bepridil.

References

  1. Coumel P "Safety of bepridil: from review of the European data." Am J Cardiol 69 (1992): d75-8
  2. Singh BN "Bepridil therapy: guidelines for patient selection and monitoring of therapy." Am J Cardiol 69 (1992): d79-85
  3. Shapiro W "Comparative efficacy of bepridil versus placebo in angina pectoris: treatment and withdrawal studies." Am J Cardiol 69 (1992): d43-9
  4. Singh BN "Safety profile of bepridil determined from clinical trials in chronic stable angina in the United States." Am J Cardiol 69 (1992): d68-74
  5. "Product Information. Vascor (bepridil)." McNeil Pharmaceutical, Raritan, NJ.
View all 5 references
Major

Bepridil (applies to Vascor) MI

Major Potential Hazard, High plausibility. Applicable conditions: Myocardial Infarction, Post MI Syndrome, History - Myocardial Infarction

Bepridil has class I antiarrhythmic properties and can induce new arrhythmias, including ventricular tachycardia and ventricular fibrillation. In the National Heart, Lung, and Blood Institute's Cardiac Arrhythmia Suppression Trial involving patients with asymptomatic, non-life-threatening ventricular arrhythmias who have had myocardial infarctions for less than two years previously, an excess rate of mortality/nonfatal cardiac arrest was seen in patients treated with the class I antiarrhythmic agents, encainide and flecainide, compared with that seen in patients assigned to matched placebo-treated groups. Although the applicability of these results to other antiarrhythmic agents is uncertain, the manufacturer recommends generally avoiding the use of bepridil in the post-infarction period. There is also limited experience in the use of bepridil within three months following a myocardial infarction, since it was one of the exclusion criteria in U.S. clinical trials.

References

  1. "Product Information. Vascor (bepridil)." McNeil Pharmaceutical, Raritan, NJ.
Major

CCBs (applies to Vascor) bradyarrhythmia/AV block

Major Potential Hazard, High plausibility. Applicable conditions: Heart Block, Sinus Node Dysfunction

The use of some calcium channel blockers (CCBs) is contraindicated in patients with severe bradyarrhythmia, sick sinus syndrome (unless a functioning pacemaker is present), or heart block greater than the first degree (unless a functioning pacemaker is present). CCBs like bepridil, diltiazem and verapamil have a negative effect on AV conduction and the SA node and may exacerbate these conditions.

References

  1. Aromatorio GJ, Uretsky BF, Reddy PS "Hypotension and sinus arrest with nifedipine in pulmonary hypertension." Chest 87 (1985): 265-7
  2. Colombo G, Zucchella G, Planca E, Grieco A "Intravenous diltiazem in the treatment of unstable angina: a study of efficacy and tolerance." Clin Ther 9 (1987): 536-47
  3. Baky SH, Singh BN "Verapamil hydrochloride: pharmacological properties and role in cardiovascular therapeutics." Pharmacotherapy 2 (1982): 328-50
  4. Gobel EJAM, Hautvast RWM, Vangilst WH, Spanjaard JN, Hillege HL, Dejongste MJL, Molhoek GP, Lie KI "Randomised, double-blind trial of intravenous diltiazem versus glyceryl trinitrate for unstable angina pectoris." Lancet 346 (1995): 1653-7
  5. Andrivet P, Beaslay V, Kiger JP, Gnoc CV "Complete sinus arrest during diltiazem therapy - clinical correlates and efficacy of intravenous calcium." Eur Heart J 15 (1994): 350-4
  6. Imamura T, Koiwaya Y, Nakamura M "Sinoatrial block induced by oral diltiazem." Clin Cardiol 9 (1986): 33-4
  7. Reams GP, Lau A, Messina C, et al "Efficacy, electrocardiographic and renal effects of intravenous diltiazem for essential hypertension." Am J Cardiol 60 (1987): i78-84
  8. "Product Information. Vascor (bepridil)." McNeil Pharmaceutical, Raritan, NJ.
  9. Pahor M, Manto A, Pedone C, Carosella L, Guralnik JM, Carbonin P "Age and severe adverse drug reactions caused by nifedipine and verapamil." J Clin Epidemiol 49 (1996): 921-8
  10. "Product Information. Calan (verapamil)." Searle, Skokie, IL.
  11. "Product Information. Covera-HS (verapamil)." Searle, Skokie, IL.
  12. Nagle RE, Low-Beer T, Horton R "Diltiazem and heart block." Lancet Apr (1989): 907
  13. "Product Information. Cardizem (diltiazem)." Hoechst Marion-Roussel Inc, Kansas City, MO.
  14. Woehler TR, Eff J, Graney W, et al "Multicenter evaluation of the efficacy and safety of sustained-release diltiazem hydrochloride for the treatment of hypertension." Clin Ther 14 (1992): 148-57
View all 14 references
Major

CCBs (applies to Vascor) cardiogenic shock/hypotension

Major Potential Hazard, High plausibility.

In general, calcium channel blockers (CCBs) should not be used in patients with hypotension (systolic pressure < 90 mm Hg) or cardiogenic shock. Due to potential negative inotropic and peripheral vasodilating effects, the use of CCBs may further depress cardiac output and blood pressure, which can be detrimental in these patients. The use of verapamil and diltiazem is specifically contraindicated under these circumstances.

References

  1. "Product Information. Calan (verapamil)." Searle, Skokie, IL.
  2. Stehle G, Buss J, Eibach J, et al "Cardiogenic shock associated with verapamil in a patient with liver cirrhosis." Lancet 336 (1990): 1079
  3. "Product Information. Cardizem (diltiazem)." Hoechst Marion-Roussel Inc, Kansas City, MO.
  4. "Product Information. Vascor (bepridil)." McNeil Pharmaceutical, Raritan, NJ.
  5. Kubota K, Pearce GL, Inman WHW "Vasodilation-related adverse events in diltiazem and dihydropyridine calcium antagonists studied by prescription-event monitoring." Eur J Clin Pharmacol 48 (1995): 1-7
  6. Pahor M, Manto A, Pedone C, Carosella L, Guralnik JM, Carbonin P "Age and severe adverse drug reactions caused by nifedipine and verapamil." J Clin Epidemiol 49 (1996): 921-8
View all 6 references
Major

CCBs (applies to Vascor) liver disease

Major Potential Hazard, High plausibility.

Calcium channel blockers (CCBs) are extensively metabolized by the liver. The half-lives of CCBs may be prolonged substantially in patients with severe hepatic impairment, with the potential for significant drug accumulation. In addition, the use of some CCBs has been associated with elevations in serum transaminases, both with and without concomitant elevations in alkaline phosphatase and bilirubin. While these effects may be transient and reversible, several patients have developed cholestasis or hepatocellular injury that was proven by rechallenge. Therapy with CCBs should be administered cautiously and often at reduced dosages in patients with significantly impaired hepatic function. Periodic monitoring of liver function and for excessive pharmacologic effects (e.g., abnormal prolongation of PR interval) is advised, and the dosage adjusted if necessary.

References

  1. "Product Information. Procardia (nifedipine)." Pfizer US Pharmaceuticals, New York, NY.
  2. Regardh CG, Edgar B, Olsson R, Kendall M, Collste P, Shansky C "Pharmacokinetics of felodipine in patients with liver disease." Eur J Clin Pharmacol 36 (1989): 473-9
  3. Stern EH, Pitchon R, King BD, Wiener I "Possible hepatitis from verapamil." N Engl J Med 306 (1982): 612-3
  4. Giacomini KM, Massoud N, Wong FM, Giacomini JC "Decreased binding of verapamil to plasma proteins in patients with liver disease." J Cardiovasc Pharmacol 6 (1984): 924-8
  5. Elliott HL, Meredith PA "The clinical consequences of the absorption, distribution, metabolism and excretion of amlodipine." Postgrad Med J 67 (1991): s20-3
  6. Graham D, Dow R, Hall D, Alexander O, Mroszczak E, Freedman A "The metabolism and pharmacokinetics of nicardipine hydrochloride in man." Br J Clin Pharmacol 20 (1985): s23-8
  7. Guarascio P, D'Amato C, Sette P, et al "Liver damage from verapamil." Br Med J 288 (1984): 362-3
  8. Rush WR, Alexander O, Hall DJ, Cairncross L, Dow RJ, Graham DJ "The metabolism of nicardipine hydrochloride in healthy male volunteers." Xenobiotica 16 (1986): 341-9
  9. Babany G, Uzzan F, Larrey D, et al "Alcoholic-like liver lesions induced by nifedipine." J Hepatol 9 (1989): 252-5
  10. Ramsch KD, Graefe KH, Scherling D, et al "Pharmacokinetics and metabolism of calcium-blocking agents nifedipine, nitrendipine, and nimodipine." Am J Nephrol 6 (1986): 73-80
  11. "Product Information. DynaCirc (isradipine)." Sandoz Pharmaceuticals Corporation, East Hanover, NJ.
  12. Dunselman PH, Edgar B "Felodipine clinical pharmacokinetics." Clin Pharmacokinet 21 (1991): 418-30
  13. McAllister RG Jr, Hamann SR, Blouin RA "Pharmacokinetics of calcium-entry blockers." Am J Cardiol 55 (1985): b30-40
  14. Brodsky SJ, Cutler SS, Weiner DA, Klein MD "Hepatotoxicity due to treatment with verapamil." Ann Intern Med 94 (1981): 490-1
  15. Woodcock BG, Rietbrock N "Verapamil bioavailability and dosage in liver disease." Br J Clin Pharmacol 13 (1982): 240-1
  16. Stopher DA, Beresford AP, Macrae PV, Humphrey MJ "The metabolism and pharmacokinetics of amlodipine in humans and animals." J Cardiovasc Pharmacol 12 (1988): s55-9
  17. "Product Information. Vascor (bepridil)." McNeil Pharmaceutical, Raritan, NJ.
  18. Kumar KL, Colley CA "Verapamil-induced hepatotoxicity." West J Med 160 (1994): 485-6
  19. "Product Information. Calan (verapamil)." Searle, Skokie, IL.
  20. Traverse JH, Swenson LJ, Mcbride JW "Acute hepatic injury after treatment with diltiazem." Am Heart J 127 (1994): 1636-9
  21. Abramson M, Littlejohn GO "Hepatic reactions to nifedipine." Med J Aust 142 (1985): 47-8
  22. Benet LZ "Pharmacokinetics and metabolism of bepridil." Am J Cardiol 55 (1985): c8-13
  23. Razak TA, McNeil JJ, Sewell RB, Drummer OH, Smallwood RA, Conway EL, Louis WJ "The effect of hepatic cirrhosis on the pharmacokinetics and blood pressure response to nicardipine." Clin Pharmacol Ther 47 (1990): 463-9
  24. Toft E, Vyberg M, Therkelsen K "Diltiazem-induced granulomatous hepatitis." Histopathology 18 (1991): 474-5
  25. Toner M, White A, Moriarty J, Clancy L "Allergic urticarial eruption, leukocytosis and abnormal liver function tests following nifedipine administration." Chest 93 (1988): 1320-1
  26. Colombo G, Zucchella G, Planca E, Grieco A "Intravenous diltiazem in the treatment of unstable angina: a study of efficacy and tolerance." Clin Ther 9 (1987): 536-47
  27. Hare DL, Horowitz JD "Verapamil hepatotoxicity: a hypersensitivity reaction." Am Heart J 111 (1986): 610-11
  28. Raemsch KD, Sommer J "Pharmacokinetics and metabolism of nifedipine." Hypertension 5 (1983): 18-24
  29. Shallcross H, Padley SP, Glynn MJ, Gibbs DD "Fatal renal and hepatic toxicity after treatment with diltiazem." Br Med J 295 (1987): 1256-7
  30. Tse FL, Jaffe JM "Pharmacokinetics of PN 200-110 (isradipine), a new calcium antagonist, after oral administration in man." Eur J Clin Pharmacol 32 (1987): 361-5
  31. Gengo FM, Fagan SC, Krol G, Bernhard H "Nimodipine disposition and haemodynamic effects in patients with cirrhosis and age-matched controls." Br J Clin Pharmacol 23 (1987): 47-53
  32. Saracheck NS, London RL, Matulewicz TJ, et al "Diltiazem and granulomatous hepatitis." Gastroenterology 88 (1985): 1260-2
  33. Meredith P, Elliott H "Clinical pharmacokinetics of amlodipine." Clin Pharmacokinet 22 (1992): 22-31
  34. Somogyi A, Albrecht M, Kliems G, et al "Pharmacokinetics, bioavailability and ECG response of verapamil in patients with liver cirrhosis." Br J Clin Pharmacol 12 (1981): 51-60
  35. Challenor VF, Waller DG, Renwick AG, et al "The trans-hepatic extraction of nifedipine." Br J Clin Pharmacol 24 (1987): 473-7
  36. Abernathy DR, Schwrtz JB "Calcium-antagonist drugs." N Engl J Med 341 (1999): 1447-57
  37. Finucci GF, Padrini R, Piovan D, et al "Verapamil pharmacokinetics and liver function in patients with cirrhosis." Int J Clin Pharmacol Res 8 (1988): 123-6
  38. Cotting J, Reichen J, Kutz K, Laplanche R, Nuesch E "Pharmacokinetics of isradipine in patients with chronic liver disease." Eur J Clin Pharmacol 38 (1990): 599-603
  39. "Product Information. Plendil (felodipine)." Merck & Co, Inc, West Point, PA.
  40. Johnson KE, Balderston SM, Pieper JA, Mann DE, Reiter MJ "Electrophysiologic effects of verapamil metabolites in the isolated heart." J Cardiovasc Pharmacol 17 (1991): 830-7
  41. Woodcock BG, Rietbrock I, Vohringer HF, Rietbrock N "Verapamil disposition in liver disease and intensive-care patients: kinetics, clearance, and apparent blood flow relationships." Clin Pharmacol Ther 29 (1981): 27-34
  42. Echizen H, Eichelbaum M "Clinical pharmacokinetics of verapamil, nifedipine and diltiazem." Clin Pharmacokinet 11 (1986): 425-49
  43. Scherling D, Karl W, Ahr G, Ahr HJ, Wehinger E "Pharmacokinetics of nisoldipine. III. Biotransformation of nisoldipine in rat, dog, monkey, and man." Arzneimittelforschung 38 (1988): 1105-10
  44. Kurosawa S, Kurosawa N, Owada E, et al "Pharmacokinetics of diltiazem in patients with liver cirrhosis." Int J Clin Pharmacol Res 10 (1990): 311-8
  45. "Product Information. Cardizem (diltiazem)." Hoechst Marion-Roussel Inc, Kansas City, MO.
  46. Kleinbloesem CH, van Harten J, Wilson JP, et al "Nifedipine: kinetics and hemodynamic effects in patients with liver cirrhosis after intravenous and oral administration." Clin Pharmacol Ther 40 (1986): 21-8
  47. Kates RE "Calcium antagonists: pharmacokinetic properties." Drugs 25 (1983): 113-24
  48. "Product Information. Norvasc (amlodipine)." Pfizer US Pharmaceuticals, New York, NY.
  49. "Product Information. Sular (nisoldipine)." Zeneca Pharmaceuticals, Wilmington, DE.
  50. Stehle G, Buss J, Eibach J, et al "Cardiogenic shock associated with verapamil in a patient with liver cirrhosis." Lancet 336 (1990): 1079
  51. "Product Information. Cardene (nicardipine)." Syntex Laboratories Inc, Palo Alto, CA.
  52. "Product Information. Nimotop (nimodipine)." Bayer, West Haven, CT.
  53. Dow RJ, Graham DJM "A reveiw of the human metabolism and pharmacokinetics of nicardipine hydrochloride." Br J Clin Pharmacol 22 (1986): s195-202
View all 53 references

Vascor (bepridil) drug interactions

There are 523 drug interactions with Vascor (bepridil)

Vascor (bepridil) alcohol/food interactions

There are 3 alcohol/food interactions with Vascor (bepridil)

Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.
Unknown No interaction information available.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.