Vascor (bepridil hydrochloride) Side Effects, Warnings, and Drug Interactions

Vascor (bepridil hydrochloride) is used to treat chronic stable angina (classic effort-associated angina) due to coronary artery disease. Vascor may be used alone or in combination with beta-blockers and/or nitrates. 

Controlled clinical studies have shown an added effect when Vascor is administered to patients already receiving propranolol. Because Vascor has caused serious ventricular arrhythmias, including torsades de pointes type ventricular tachycardia, and the occurrence of cases of agranulocytosis associated with its use, it should be reserved for patients who have failed to respond optimally to, or are intolerant of, other anti-anginal medication.

Common side effects of Vascor include:

• flu-like symptoms,
• muscle aches,
• fever,
• nausea,
• vomiting,
• loss of appetite,
• constipation,
• gas,
• stomach ache,
• dry mouth,
• diarrhea,
• headache,
• fatigue,
• nervousness,
• drowsiness,
• dizziness,
• depression,
• inability to sleep (insomnia),
• blurred vision,
• impotence, and
• reduced sex drive.

Serious side effects of Vascor include:

• very serious cardiac arrhythmias,
• increased or decreased heart rate, and
• other abnormal rhythms.

Drug interactions of Vascor include:

• quinidine,
• procainamide,
• disopyramide,
• flecainide,
• verapamil,
• diltiazem, and
• all beta-blockers, which could seriously reduce contraction of the heart and possibly precipitate congestive heart failure if taken with Vascor. 

If Vascor is taken with tricyclic antidepressants it may cause serious problems with abnormal heart rhythms. Vascor may increase levels of digoxin in the blood, thereby increasing the risk of digoxin toxicity. Diuretics may cause a reduction in blood potassium concentrations thereby increasing the risk of Vascor-induced abnormal heart rhythms. 

Vascor crosses the placenta, and should not be used during pregnancy unless the benefit to the mother outweighs the potential but unknown risk to the fetus. 

Vascor is secreted into breast milk and should not be used by breastfeeding mothers unless the benefit to the mother clearly outweighs the potential but unknown risk to the infant.

• Bepridil can cause very serious cardiac arrhythmias. The risk is increased in patients with a specific electrocardiographic abnormality called QT prolongation and in patients with low blood concentrations of potassium or magnesium.
• Bepridil also can cause increased or decreased heart rate and other abnormal rhythms.

Other side effects that can occur among patients taking bepridil include:

• flu-like symptoms,
• muscle aches,
• fever,
• nausea,
• vomiting,
• loss of appetite,
• constipation,
• gas,
• stomach ache,
• dry mouth,
• diarrhea,
• headache,
• fatigue,
• nervousness,
• drowsiness,
• dizziness,
• depression,
• inability to sleep,
• blurred vision,
• impotence, and
• reduction in sexual drive.

Adverse reactions were assessed in placebo and active-drug controlled trials of 4-12 weeks duration and longer-term uncontrolled studies. The most common side effects occurring more frequently than in control groups were upper gastrointestinal complaints (nausea, dyspepsia or GI distress) in about 22%, diarrhea in about 8%, dizziness in about 15%, asthenia in about 10% and nervousness in about 7%. The adverse reactions seen in at least 2% of bepridil patients in controlled trials are shown in the following table.

In one twelve week controlled study, daily doses of 200, 300, and 400 mg were compared to placebo. The following table shows the rates of more common reactions (at least 5% in at least one bepridil group).

Adverse experiences in long-term open studies were generally similar to those seen in controlled trials.

Although adverse experiences were frequent (at least one being reported in 71% of patients participating in controlled clinical trials), most were well-tolerated. About 15% of patients however, discontinued bepridil treatment because of adverse experiences. In controlled clinical trials, these were principally gastrointestinal (1.0%), dizziness (1.0%) ventricular arrhythmias (1.0%) and syncope (0.6%). The major reasons for discontinuation, with comparison to control agents, are shown below.

Across all controlled and uncontrolled trials, Vascor (bepridil) was evaluated in over 800 patients with chronic angina. In addition to the adverse reactions noted above, the following were observed in 0.5 to 2.0% of the Vascor (bepridil) patients or are rarer, but potentially important events seen in clinical studies or reported in post marketing experience. In most cases it is not possible to determine whether there is a causal relationship to bepridil treatment.

Body as a Whole:   Fever, pain, myalgic asthenia, superinfection, flu syndrome.

Cardiovascular/Respiratory:   Sinus tachycardia, sinus bradycardia, hypertension, vasodilation, edema, ventricular premature contractions, ventricular tachycardia, prolonged QT interval, rhinitis, cough, pharyngitis.

Gastrointestinal:   Flatulence, gastritis, appetite increase, dry mouth, constipation.

Musculoskeletal:   Arthritis.

Central Nervous System:   Fainting, vertigo, akathisia, drowsiness, insomnia, tremor.

Psychiatric:   Depression, anxiousness, adverse behavior effect.

Skin:   Rash, sweating, skin irritation.

Special Senses:   Blurred vision, tinnitus, taste change.

Urogenital:   Loss of libido, impotence.

Abnormal Lab Values:   Abnormal liver function test, SGPT increase.

In postmarketing experience with other calcium blockers, gynecomastia has been rarely observed.

Certain cardiovascular events, such as acute myocardial infarction (about 3% of patients) worsened heart failure (1.9%), worsened angina (4.5%), severe arrhythmia (about 2.4% VT/VF) and sudden death (1.6%) have occurred in patients receiving bepridil, but have not been included as adverse events because they appear to be, and cannot be distinguished from, manifestations of the patient's underlying cardiac disease. Such events as torsades de pointes arrhythmias, prolonged QT/QTc, bradycardia, first degree heart block, which are probably related to bepridil, are included in the tables.

Nitrates:   The concomitant use of Vascor (bepridil) with long- and short-acting nitrates has been safely tolerated in patients with stable angina pectoris. Sublingual nitroglycerin may be taken if necessary for the control of acute angina attacks during Vascor (bepridil) therapy.

Beta-blocking Agents:   The concomitant use of Vascor (bepridil) and beta-blocking agents has been well tolerated in patients with stable angina. Available data are not sufficient, however, to predict the effects of concomitant medication on patients with impaired ventricular function or cardiac conduction abnormalities.

Digoxin:   In controlled studies in healthy volunteers, bepridil hydrochloride either had no effect (one study) or was associated with modest increases, about 30% (two studies) in steady-state serum digoxin concentrations. Limited clinical data in angina patients receiving concomitant bepridil hydrochloride and digoxin therapy indicate no discernible changes in serum digoxin levels. Available data are neither sufficient to rule out possible increases in serum digoxin with concomitant treatment in some patients, nor other possible interactions, particularly in patients with cardiac conduction abnormalities.

Oral Hypoglycemics:   Vascor (bepridil) has been safely used in diabetic patients without significantly lowering their blood glucose levels or altering their need for insulin or oral hypoglycemic agents.

General Interactions:   Certain drugs could increase the likelihood of potentially serious adverse effects with bepridil hydrochloride. In general, these are drugs that have one or more pharmacologic activities similar to bepridil hydrochloride, including anti-arrhythmic agents such as quinidine and procainamide, cardiac glycosides and tricyclic anti-depressants. Anti-arrhythmics and tricyclic anti-depressants could exaggerate the prolongation of the QT interval observed with bepridil hydrochloride. Cardiac glycosides could exaggerate the depression of AV nodal conduction observed with bepridil hydrochloride.

Nitrates:   The concomitant use of Vascor (bepridil) with long- and short-acting nitrates has been safely tolerated in patients with stable angina pectoris. Sublingual nitroglycerin may be taken if necessary for the control of acute angina attacks during Vascor (bepridil) therapy.

Beta-blocking Agents:   The concomitant use of Vascor (bepridil) and beta-blocking agents has been well tolerated in patients with stable angina. Available data are not sufficient, however, to predict the effects of concomitant medication on patients with impaired ventricular function or cardiac conduction abnormalities.

Digoxin:   In controlled studies in healthy volunteers, bepridil hydrochloride either had no effect (one study) or was associated with modest increases, about 30% (two studies) in steady-state serum digoxin concentrations. Limited clinical data in angina patients receiving concomitant bepridil hydrochloride and digoxin therapy indicate no discernible changes in serum digoxin levels. Available data are neither sufficient to rule out possible increases in serum digoxin with concomitant treatment in some patients, nor other possible interactions, particularly in patients with cardiac conduction abnormalities.

Oral Hypoglycemics:   Vascor (bepridil) has been safely used in diabetic patients without significantly lowering their blood glucose levels or altering their need for insulin or oral hypoglycemic agents.

General Interactions:   Certain drugs could increase the likelihood of potentially serious adverse effects with bepridil hydrochloride. In general, these are drugs that have one or more pharmacologic activities similar to bepridil hydrochloride, including anti-arrhythmic agents such as quinidine and procainamide, cardiac glycosides and tricyclic anti-depressants. Anti-arrhythmics and tricyclic anti-depressants could exaggerate the prolongation of the QT interval observed with bepridil hydrochloride. Cardiac glycosides could exaggerate the depression of AV nodal conduction observed with bepridil hydrochloride.