Cardizem

Action

Inhibits calcium from entering myocardial and vascular smooth-muscle cells, thereby depressing myocardial and smooth-muscle contraction and decreasing impulse formation and conduction velocity. As a result, systolic and diastolic pressures decrease.

Availability

Capsules (extended-release, sustained-release): 60 mg, 90 mg, 120 mg, 180 mg, 240 mg, 300 mg, 360 mg, 420 mg

Injection: 5 mg/ml in 10-ml vials, 100-mg Monovial

Tablets: 30 mg, 60 mg, 90 mg, 120 mg

Indications and dosages

➣ Angina pectoris and vasospastic (Prinzmetal's) angina; hypertension; supraventricular tachyarrhythmias; atrial flutter or fibrillation

Adults: 30 to 90 mg P.O. three to four times daily (tablets), or 60 to 120 mg P.O. b.i.d. (sustained-release), or 180 to 240 mg P.O. once daily (extended-release), adjusted after 14 days as needed, up to a total daily dosage of 360 mg. Or 0.25 mg/kg by I.V. bolus over 2 minutes; if response is inadequate after 15 minutes, may give 0.35 mg/kg over 2 minutes; may follow with continuous I.V. infusion at 10 mg/hour (at a range of 5 to 15 mg/hour) for up to 24 hours.

Dosage adjustment

• Severe hepatic or renal impairment

• Elderly patients

Off-label uses

• Unstable angina, coronary artery bypass graft surgery

• Tardive dyskinesia

• Migraine

• Hyperthyroidism

• Raynaud's phenomenon

Contraindications

• Hypersensitivity to drug

• Atrial flutter or fibrillation associated with shortened refractory period (Wolff-Parkinson-White syndrome, with I.V. use)

• Recent myocardial infarction or pulmonary congestion

• Cardiogenic shock, concurrent I.V. beta-blocker therapy, ventricular tachycardia, neonates (with I.V. use, because of benzyl alcohol in syringe formulation)

• Sick sinus syndrome, second- or third-degree atrioventricular block (except in patients with ventricular pacemakers)

• Hypotension (systolic pressure below 90 mm Hg)

Precautions

Use cautiously in:

• severe hepatic or renal impairment, heart failure

• history of serious ventricular arrhythmias

• concurrent use of I.V. diltiazem and I.V. beta blockers

• elderly patients

• pregnant or breastfeeding patients

• children (safety not established).

Administration

• When giving I.V., dilute in dextrose 5% in water or normal saline solution.

• Give I.V. bolus dose over 2 minutes; a second bolus may be given after 15 minutes.

• Administer continuous I.V. infusion at a rate of 5 to 15 mg/hour.

☞ When giving by continuous I.V. infusion, make sure emergency equipment is available and that patient has continuous ECG monitoring with frequent blood pressure monitoring.

• Don't crush tablets or sustained-release capsules; they must be swallowed whole.

• Withhold dose if systolic blood pressure falls below 90 mm Hg, diastolic pressure is below 60 mm Hg, or apical pulse is slower than 60 beats/minute.

Adverse reactions

CNS: headache, abnormal dreams, anxiety, confusion, dizziness, drowsiness, nervousness, psychiatric disturbances, asthenia, paresthesia, syncope, tremor

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

EENT: blurred vision, tinnitus, epistaxis

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

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

Hematologic: anemia, leukopenia, thrombocytopenia

Metabolic: hyperglycemia

Musculoskeletal: joint stiffness, muscle cramps

Respiratory: cough, dyspnea

Skin: rash, dermatitis, flushing, diaphoresis, photosensitivity, pruritus, urticaria, erythema multiforme

Other: unpleasant taste, gingival hyperplasia, weight gain, decreased appetite, Stevens-Johnson syndrome

Interactions

Drug-drug. Beta-adrenergic blockers, digoxin, disopyramide, phenytoin: bradycardia, conduction defects, heart failure

Carbamazepine, cyclosporine, quinidine: decreased diltiazem metabolism, increased risk of toxicity

Cimetidine, ranitidine: increased blood level and effects of diltiazem

Fentanyl, nitrates, other antihypertensives, quinidine: additive hypotension

HMG-CoA reductase inhibitors, imipramine, sirolimus, tacrolimus: increased blood levels of these drugs

Lithium: decreased lithium blood level, reduced antimanic control

Nonsteroidal anti-inflammatory drugs: decreased antihypertensive effect of diltiazem

Theophylline: increased theophylline effects

Drug-diagnostic tests. Hepatic enzymes: increased levels

Drug-food. Grapefruit juice: increased blood level and effects of diltiazem

Drug-behaviors. Acute alcohol ingestion: additive hypotension

Patient monitoring

• Check blood pressure and ECG before starting therapy, and monitor closely during dosage adjustment period. Withhold dose if systolic pressure is below 90 mm Hg.

☞ Monitor for signs and symptoms of heart failure and worsening arrhythmias.

• Supervise patient during ambulation.

Patient teaching

• Instruct patient to swallow extended-release capsules whole and not to crush or chew them.

• Advise patient to change position slowly to minimize light-headedness and dizziness.

• Caution patient to avoid driving and other hazardous activities until he knows how drug affects concentration and alertness.

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