diltiazem hydrochloride
Cardizem, Cardizem CD, Cardizem SR, Cartia XT, Dilacor XR, Diltia XT, Tiazac

Available forms
Available by prescription only
Capsules (extended-release): 120 mg, 180 mg, 240 mg, 300 mg, 360 mg
Capsules (sustained-release): 60 mg, 90 mg, 120 mg, 180 mg, 240 mg, 300 mg, 360 mg, 420 mg
Injection: 5 mg/ml (25 mg and 50 mg)
Tablets: 30 mg, 60 mg, 90 mg, 120 mg

Indications and dosages
 Management of Prinzmetal’s or variant angina or chronic stable angina pectoris. Adults: 30 mg P.O. q.i.d. before meals and h.s. Increase dose gradually to maximum of 360 mg daily divided into three to four doses, as indicated. Or, 120 or 180 mg (extended-release) P.O. once daily. Adjust over a 7- to 14-day period as needed and tolerated up to a maximum dose of 480 mg daily.
 Hypertension. Adults: 60 to 120 mg P.O. b.i.d. (sustained-release). Adjust up to maximum recommended dose of 360 mg daily, as needed. Or, give 180 to 240 mg (extended-release) P.O. once daily. Adjust dose based on patient response to a maximum dose of 480 mg daily.
 Atrial fibrillation or flutter, paroxysmal supraventricular tachycardia. Adults: 0.25 mg/kg I.V. as a bolus injection over 2 minutes. Repeat after 15 minutes if response isn’t adequate with a dose of 0.35 mg/kg I.V. over 2 minutes. Follow bolus with continuous I.V. infusion at 5 to 15 mg/ hour (for up to 24 hours).

Pharmacodynamics
Antianginal and antihypertensive actions: By dilating systemic arteries, diltiazem decreases total peripheral resistance and afterload, slightly reduces blood pressure, and increases cardiac index when given in high doses (more than 200 mg). Afterload reduction, which occurs at rest and with exercise, and the resulting decrease in myocardial oxygen consumption account for the effectiveness of diltiazem in controlling chronic stable angina.
 Diltiazem also decreases myocardial oxygen demand and cardiac work by reducing heart rate, relieving coronary artery spasm (through coronary artery vasodilation), and dilating peripheral vessels. These effects relieve ischemia and pain. In patients with Prinzmetal’s angina, diltiazem inhibits coronary artery spasm, increasing myocardial oxygen delivery.
Antiarrhythmic action: By impeding the slow inward influx of calcium at the AV node, diltiazem decreases conduction velocity and increases refractory period, thereby decreasing the impulses transmitted to the ventricles in atrial fibrillation or flutter. The result is a decreased ventricular rate.

Pharmacokinetics
Absorption: About 80% of a dose is absorbed rapidly from the GI tract. However, only about 40% of drug enters systemic circulation because of a significant first-pass effect in the liver.
Distribution: About 70% to 85% of circulating drug is bound to plasma proteins.
Metabolism: Metabolized in the liver.
Excretion: About 35% is excreted in the urine and about 65% in the bile as unchanged drug and inactive and active metabolites. Elimination half-life is 3 to 9 hours. Half-life may increase in geriatric patients; however, renal dysfunction doesn’t appear to affect half-life.

Contraindications and precautions
Contraindicated in patients with sick sinus syndrome or second- or third-degree AV block in the absence of an artificial pacemaker; in patients with supraventricular tachycardias linked to a bypass tract such as in Wolfe-Parkinson-White syndrome or Lown-Ganong-Levine syndrome; and in patients with left ventricular failure, hypotension (systolic blood pressure less than 90 mm Hg), hypersensitivity to the drug, acute MI, and pulmonary congestion (documented by X-ray).
  Use cautiously in elderly patients and patients with heart failure or impaired hepatic or renal function.

Interactions
Drug-drug. Anesthetics: May potentiate effects. Monitor patient.
Beta blockers: May cause heart failure, conduction disturbances, arrhythmias, and hypotension. Use together cautiously.
Carbamazepine: May increase serum carbamazepine levels, leading to toxicity. Monitor serum levels.
Cimetidine, ranitidine: May increase diltiazem level. Monitor patient carefully.
Cyclosporine: Increases serum cyclosporine levels and cyclosporine-induced nephrotoxicity. If used together, monitor cyclosporine levels.
Digoxin: Increases digoxin levels. Monitor patient for toxicity.
Fentanyl: Cause severe hypotension; may increase fluid volume requirements. Monitor vital signs.
Furosemide: Forms a precipitate when mixed with diltiazem injection. Give drugs through separate I.V. lines.
Lithium: May decrease lithium levels. Monitor serum levels.
Theophylline: May enhance drug actions. Monitor patient for increased or adverse effects.

Adverse reactions
CNS: headache, dizziness, asthenia, somnolence, insomnia, gait abnormalities.
CV: peripheral edema,arrhythmias, flushing, bradycardia, hypotension, conduction abnormalities, heart failure, AV block, abnormal ECG.
EENT: amblyopia, eye irritation.
GI: nausea, constipation, abdominal discomfort.
Hepatic: acute hepatic injury.
Skin: rash.

Effects on lab test results
None reported.

Overdose and treatment
Effects of overdose are primarily extensions of adverse reactions of drug, such as nausea, weakness, dizziness, drowsiness, and slurred speech. Heart block, asystole, and hypotension are the most serious effects and require immediate attention.
 If patient is seen shortly after ingestion, emesis or gastric lavage may be instituted. Treatment may involve I.V. isoproterenol, norepinephrine, epinephrine, atropine, or calcium gluconate administered in usual doses. Ensure adequate hydration. Inotropic agents, including dobutamine and dopamine, may be used, if needed. If patient has severe conduction disturbances (such as heart block and asystole) with hypotension that doesn’t respond to drug therapy develop, initiate cardiac pacing immediately with cardiopulmonary resuscitation measures, as indicated.

Special considerations
• S.L. nitroglycerin may be administered concomitantly, as needed, if patient has acute angina symptoms.
• Diltiazem has been used investigationally to prevent reinfarction after non-Q-wave MI; as an adjunct in the treatment of peripheral vascular disorders; and in the treatment of several spastic smooth-muscle disorders, including esophageal spasm.
• Diltiazem may be diluted in D₅W or normal saline solution. It’s incompatible with I.V. furosemide.
• If systolic blood pressure is less than 90 mm Hg or heart rate is less than 60 beats/minute, dose should be withheld until patient is further evaluated.
Breast-feeding patients
• Drug appears in breast milk; women shouldn’t breast-feed during diltiazem therapy.
Pediatric patients
• Safety and efficacy haven’t been established.
Geriatric patients
• Use drug cautiously in elderly patients because the half-life may be prolonged.

Patient education
• Tell patient that nitrate therapy prescribed during adjustment of diltiazem dosage may cause dizzi

Patient education
• Tell patient that nitrate therapy prescribed during adjustment of diltiazem dosage may cause dizziness. Urge patient to continue compliance.
• Inform patient of proper use, dose, and adverse effects of diltiazem.
• Instruct patient to continue taking drug even when feeling better.
• Tell patient to report feelings of light-headedness or dizziness and to avoid sudden position changes.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use