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Bepridil Disease Interactions

There are 8 disease interactions with bepridil:

Major

Bepridil (Includes Bepridil) ↔ Agranulocytosis

Severe Potential Hazard, Low plausibility

Applies to: 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 The drug should be withdrawn promptly if these conditions develop during therapy.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 (Includes Bepridil) ↔ Arrhythmias

Severe Potential Hazard, High plausibility

Applies to: 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 "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 (Includes Bepridil) ↔ Chf

Severe Potential Hazard, High plausibility

Applies to: 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. "Product Information. Vascor (bepridil)." McNeil Pharmaceutical, Raritan, NJ.
  3. Shapiro W "Comparative efficacy of bepridil versus placebo in angina pectoris: treatment and withdrawal studies." Am J Cardiol 69 (1992): d43-9
View all 5 references
Major

Bepridil (Includes Bepridil) ↔ Electrolyte Imbalance/Hypokalemia

Severe Potential Hazard, High plausibility

Applies to: Electrolyte Abnormalities, Hypokalemia, 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. 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. Coumel P "Safety of bepridil: from review of the European data." Am J Cardiol 69 (1992): d75-8
  3. "Product Information. Vascor (bepridil)." McNeil Pharmaceutical, Raritan, NJ.
View all 5 references
Major

Bepridil (Includes Bepridil) ↔ Mi

Severe Potential Hazard, High plausibility

Applies to: 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 (Includes Bepridil) ↔ Bradyarrhythmia/Av Block

Severe Potential Hazard, High plausibility

Applies to: 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. 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
  2. Aromatorio GJ, Uretsky BF, Reddy PS "Hypotension and sinus arrest with nifedipine in pulmonary hypertension." Chest 87 (1985): 265-7
  3. 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
View all 14 references
Major

Ccbs (Includes Bepridil) ↔ Cardiogenic Shock/Hypotension

Severe Potential Hazard, High plausibility

Applies to: Cardiogenic Shock, Hypotension

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. Vascor (bepridil)." McNeil Pharmaceutical, Raritan, NJ.
View all 6 references
Major

Ccbs (Includes Bepridil) ↔ Liver Disease

Severe Potential Hazard, High plausibility

Applies to: Liver Disease

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. Stern EH, Pitchon R, King BD, Wiener I "Possible hepatitis from verapamil." N Engl J Med 306 (1982): 612-3
  2. 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
  3. "Product Information. Calan (verapamil)." Searle, Skokie, IL.
View all 53 references

bepridil drug Interactions

There are 765 drug interactions with bepridil

bepridil alcohol/food Interactions

There are 3 alcohol/food interactions with bepridil

Drug Interaction Classification

The classifications below are a general guideline only. It is difficult to determine the relevance of a particular drug interaction to any individual given the large number of variables.

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.

Do not stop taking any medications without consulting your healthcare provider.

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