Bepridil is a long-acting calcium-blocking agent with significant anti-anginal activity. The drug produces significant coronary vasodilation and modest peripheral effects. It has antihypertensive and selective anti-arrhythmia activities and acts as a calmodulin antagonist.
Mechanism of action of Bepridil
Bepridil has inhibitory effects on both the slow calcium (L-type) and fast sodium inward currents in myocardial and vascular smooth muscle, interferes with calcium binding to calmodulin, and blocks both voltage and receptor operated calcium channels. Bepridil inhibits the transmembrane influx of calcium ions into cardiac and vascular smooth muscle. This has been demonstrated in isolated myocardial and vascular smooth muscle preparations in which both the slope of the calcium dose response curve and the maximum calcium-induced inotropic response were significantly reduced by bepridil. In cardiac myocytes in vitro, bepridil was shown to be tightly bound to actin. Bepridil regularly reduces heart rate and arterial pressure at rest and at a given level of exercise by dilating peripheral arterioles and reducing total peripheral resistance (afterload) against which the heart works.
Indications of Bepridil
- Angina pectoris
- Stable & unstable angina
- High blood pressure
- Migraine prevention
- Coronary artery disease
- Heart failure
- Chronic stable angina pectoris
- Angina Pectoris Prophylaxis
- Chronic stable angina
- Manifest atherothrombotic cardiovascular disease (history of coronary heart disease, stroke, or peripheral arterial disease)
- Cardiovascular Risk Reduction
- Prevention of Cardiovascular Disease
- For the treatment of hypertension, and chronic stable angina (classic effort-associated angina).
Contra-Indications of Bepridil
- Extreme loss of body water
- The high amount of potassium in the blood
- Renal artery stenosis
- Liver problems
- Blockage of a bile duct
- Kidney disease with the reduction in kidney function
- Second and third trimester of pregnancy
- Biliary obstructive disorders.
- Severe hepatic impairment.
- Hypersensitivity to the active substance or to any of the excipients
Hypersensitivity, history of serious ventricular or atrial arrhythmias, uncompensated cardiac insufficiency, congenital QT interval prolongation.
Dosage of Bepridil
Strengths: 200 mg ,300mg , 400 mg
- Initially, 200 mg/day.
- If necessary, increase to 300 mg/day after 10 days.
- Max dose: 400 mg once daily.
Side Effects of Bepridil
The most common
- Bepridil also can cause increased or decreased heart rate and other abnormal rhythms.
- cardiac arrhythmia
- Dizziness and light-headedness due to low blood pressure
- Fatigue, especially in the early stages
- Mouth dryness in the early stages
- The most commonrn (a burning feeling in the chest, behind the breastbone or gullet)
- Abdominal or stomach pain
- High blood pressure
- Nausea, vomiting,
- painful or swollen gums
- numbness or heavy feeling in the jaw
- dull, aching pain in the hip, groin, or thigh
- stomach pain,
- a headache,
- reversible hair loss or thinning, and
- chills or fever
- a headache, severe and throbbing
- joint or back pain
- muscle aching or cramping
- muscle pains or stiffness
- chest pressure or squeezing pain in the chest
- excessive sweating
- sudden drowsiness or need to sleep
- coughing up blood
- liver problems–nausea, upper stomach pain, itching, tired feeling, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes)
- decreased amount of urine
- change in vision
- chest pain or tightness
- a cough
- arm, back, or jaw pain
- blurred vision
- chest pain or discomfort
- extra heartbeats
- a headache
- cold and clammy skin
- fast and shallow breathing
- swelling of your feet, legs, or hands purple spot on your skin caused by internal bleeding
- fast or abnormal heart rate or palpitations
- loss of appetite
- lower back, side, or stomach pain
- mental depression
- muscle pain or cramps
- fast, irregular, pounding or racing heartbeat or pulse
- redness of the face, neck, arms, and occasionally, upper chest
- shortness of breath
- tightness in the chest
Drug Interactions of Bepridil
Bepridil may interact with following drugs, supplyments, & may change the efficacy of drugs
- antidiabetes medications (e.g., insulin, metformin, gliclazide)
- beta-2 agonists (e.g., formoterol, salmeterol, salbutamol)
- calcium channel blocking agents (e.g., diltiazem, verapamil)
- MAO inhibitors (e.g., phenelzine, tranylcypromine)
- medications that affect heart rhythm
- medications that lower blood pressure
- tricyclic antidepressants (e.g., amitriptyline, nortriptyline)
- Diuretics, for example, furosemide , bumetanide ,hydrochlorothiazide, chlorthalidone, metolazone may cause a reduction in blood potassium concentrations thereby increasing the risk of bepridil-induced abnormal heart rhythms.
FDA Pregnancy Category C
Reproductive studies (fertility and peri-postnatal) have been conducted in rats. Reduced litter size at birth and decreased pup survival during lactation was observed at maternaldosages 37 times (on a mg/kg basis) the maximum daily recommended therapeutic dosage.In teratology studies, no effects were observed in rats or rabbits at these same dosages.
Bepridil is excreted in human milk. Bepridil concentration in human milk is estimated to reach about one third the concentration in serum. Because of the potential for serious adverse reactions in nursing infants from bepridil a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.The safety and effectiveness of bepridil in children have not been established.