Isoptin

Action

Decreases conduction of sinoatrial and atrioventricular (AV) nodes by inhibiting calcium influx into cardiac and vascular smooth muscle cells, inhibiting excitatory contraction. These effects prolong AV node refractoriness and decrease myocardial oxygen consumption.

Availability

Capsules (extended-release): 100 mg, 120 mg, 180 mg, 200 mg, 240 mg, 300 mg, 360 mg

Capsules (sustained-release): 120 mg, 180 mg, 240 mg, 360 mg

Injection: 2.5 mg/ml in 2- and 4-ml vials, ampules, and syringes

Tablets (extended-release): 120 mg, 180 mg, 240 mg

Tablets (immediate-release): 40 mg, 80 mg, 120 mg

Indications and dosages

➣ Angina

Adults: Initially, 80 mg (immediate-release) P.O. t.i.d.; may titrate at daily or weekly intervals to 360 mg/day. Or initially, 180 mg (extended-release) P.O. once daily at bedtime, titrated up to 480 mg/day at bedtime.

➣ Supraventricular tachyarrhythmias (SVTs)

Adults: 5 to 10 mg (0.075 to 0.15 mg/kg) I.V. bolus over 2 minutes; may give additional 10 mg after 30 minutes if response inadequate. Or 240 to 480 mg (immediate-release) P.O. daily in three or four divided doses.

➣ To control ventricular rate in chronic atrial flutter or atrial fibrillation in patients receiving digoxin

Adults: 240 to 320 mg P.O. daily in three or four divided doses

➣ Hypertension

Adults: Initially, 180 mg (extended-release tablet) or 200 mg (extended-release capsule) P.O. daily at bedtime. For maintenance, may titrate up to 480 mg (extended-release tablet) or 400 mg (extended-release capsule) P.O. daily at bedtime. Or initially, 80 mg (immediate-release tablet) P.O. t.i.d.; may titrate at daily or weekly intervals up to 360 to 480 mg/day. Or initially, 240 mg (sustained-release capsule) P.O. q day in morning; for maintenance, may titrate up to 240 mg P.O. b.i.d. or 480 mg P.O. once daily in morning. Titrate based on response.

Dosage adjustment

• Renal or hepatic impairment

• Concurrent digoxin therapy

Off-label uses

• Ventricular tachycardia

• Migraine headache prophylaxis

• Neurogenic bladder

• Premature labor

Contraindications

• Hypersensitivity to drug or other calcium channel blockers

• Sick sinus syndrome

• Second- or third-degree AV block (except in patients with artificial pacemakers)

• Hypotension

• Heart failure, severe ventricular dysfunction, or cardiogenic shock (except when associated with SVTs)

• Atrial flutter or atrial fibrillation associated with accessory bypass tracts (such as Wolff-Parkinson-White or Lown-Ganong-Levine syndrome)

Precautions

Use cautiously in:

• renal or severe hepatic impairment; first-degree AV block; idiopathic hypertrophic cardiomyopathy; neuromuscular transmission defects (such as Duchenne's muscular dystrophy); respiratory depression; digital ulcers, ischemia, or gangrene

• elderly patients

• pregnant or breastfeeding patients.

Administration

• Give I.V. over at least 2 minutes.

• Discontinue disopyramide 48 hours before starting verapamil. Don't restart disopyramide for at least 24 hours after verapamil therapy ends.

Adverse reactions

CNS: anxiety, confusion, dizziness, syncope, drowsiness, headache, jitteriness, abnormal dreams, disturbed equilibrium, psychiatric disturbances, asthenia, paresthesia, tremor, fatigue

CV: chest pain, hypotension, palpitations, peripheral edema, tachycardia, arrhythmias, heart failure, bradycardia, AV block

EENT: blurred vision, epistaxis, tinnitus

GI: nausea, vomiting, diarrhea, constipation, dyspepsia, dry mouth, anorexia

GU: dysuria, urinary frequency, nocturia, polyuria, sexual dysfunction, gynecomastia

Hematologic: anemia, leukopenia, thrombocytopenia

Metabolic: hyperglycemia

Musculoskeletal: joint stiffness, muscle cramps

Respiratory: cough, dyspnea, shortness of breath, pulmonary edema

Skin: dermatitis, flushing, diaphoresis, photosensitivity, pruritus, urticaria, rash, erythema multiforme, Stevens-Johnson syndrome

Other: gingival hyperplasia, edema, weight gain

Interactions

Drug-drug. Antihypertensives: additive hypotension

Aspirin: increased risk of bleeding

Beta-adrenergic blockers, other antiarrhythmics: additive adverse cardiovascular reactions

Carbamazepine, cyclosporine: increased blood levels of these drugs

CYP450-3A4 inducers (such as rifampin): decreased verapamil blood level

CYP450-3A4 inhibitors (such as erythromycin, ritonavir): increased verapamil blood level

Digoxin: increased digoxin blood level, greater risk of toxicity

Lithium: increased or decreased lithium blood level

Neuromuscular blockers (succinylcholine, tubocurarine, vecuronium): prolonged neuromuscular blockade

Theophylline: decreased verapamil clearance, increased blood level, and possible toxicity

Drug-diagnostic tests. Alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, blood urea nitrogen, glucose, lactate dehydrogenase: increased levels

Granulocytes: decreased count

Drug-food. Coffee, tea: increased caffeine blood level

Grapefruit juice: increased verapamil blood level and effects

Drug-herbs. Black catechu: increased drug effects

Cola nut, guarana: increased caffeine blood level

Ephedra (ma huang), St. John's wort: reduced hypotensive effect of verapamil

Yerba maté: decreased clearance of this herb

Drug-behaviors. Alcohol use: additive hypotension

Patient monitoring

• With I.V. use, monitor vital signs and ECG continuously.

• Assess blood pressure when therapy begins and when dosage is adjusted.

• Watch closely for signs and symptoms of heart failure.

Monitor for signs and symptoms of erythema multiforme (fever, rash, sore throat, mouth sores, cough, iris lesions). Report early indications immediately, before condition can progress to Stevens-Johnson syndrome.

• Assess CBC. Watch for blood dyscrasias.

• Monitor blood glucose level. Stay alert for hyperglycemia in diabetic patients.

Patient teaching

• Instruct patient to avoid chewing, breaking, or crushing extended-release form.

Advise patient to immediately report rash, unusual bleeding or bruising, fainting, and (in long-term use) fatigue, nausea, or yellowing of skin or eyes.

• Caution patient not to take with grapefruit juice.

• Instruct patient to limit caffeine intake and avoid alcohol.

• Advise patient to seek medical advice before using over-the-counter medications or herbs.

• Tell patient to avoid sun exposure and to wear sunscreen and protective clothing when going outdoors.

• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs, tests, foods, herbs, and behaviors mentioned above.