/publications/issue/2004/2004-12/2004-12-9089

RxPRODUCT NEWS: PROFILE: Cardizem LA (diltiazem hydrochloride)

Author: Monica Holmberg, PharmD

The treatment of chronic stable angina recently expanded to include Biovail's Cardizem LA, a long-acting tablet formulation of diltiazem hydrochloride, which received approval from the FDA in April 2004.1

In the United States alone, approximately one half of emergency department patients who present with myocardial infarction have preexisting angina. Each hospitalization extrapolates to ~30 patients with chronic stable angina. Mortality rates from chronic stable angina remain high: ischemic heart disease is still the leading cause of death in the Western world. Its morbidity is significant, too, resulting in millions of hospitalizations each year. Its impact on quality of life is equally important; chronic chest pain syndrome impairs daily activities, sometimes for days at a time. Although cardiovascular mortality has been declining overall, the treatment of chronic stable angina remains worthy of concern.2

Described by Biovail as a "gradedrelease formulation" of diltiazem hydrochloride, Cardizem LA is identified by the FDA as a distinct dosagedelivery system and is not therapeutically equivalent to the various other extended-release diltiazem products on the market.3 Biovail promotes Cardizem LA as providing 24-hour antianginal and antihypertensive control and asserts that other diltiazem formulations do not achieve morning peak-plasma concentrations comparable with those of Cardizem LA. Although evening administration is advertised to result in peak levels "when patients need it most"—between 6 AM and noon—the manufacturer admits that the clinical significance of administration time is unknown.4 Cardizem LA was previously approved for the treatment of hypertension.

Pharmacology

As a calcium channel blocking agent, Cardizem LA exerts its effect by inhibiting the calcium ion influx during membrane depolarization in cardiac and smooth muscle. This action results in a decrease in heart rate and systemic blood pressure, which leads to increased exercise tolerance and decreased myocardial oxygen demand. Additionally, Cardizem has been shown to dilate and relax coronary arteries.5

Clinical Studies

Cardizem LA and its impact on angina were studied in a randomized, double-blind, parallel-group, dose-response trial of 311 patients with chronic angina. Treatment with doses of 180, 360, and 420 mg administered in the evening was compared with the administration of 360 mg in the morning and with placebo. Compared with placebo, all 3 evening doses increased exercise tolerance 21 hours after administration. At 25 hours after administration, the morning 360-mg dose also was shown to increase exercise tolerance, although to a smaller extent than the evening doses.5

Contraindications

Cardizem LA is contraindicated in patients with sick sinus syndrome or with second- or third-degree atrioventricular (AV) block, unless a functioning ventricular pacemaker is present. The drug also is contraindicated in hypotensive patients with a systolic pressure of<90 mm Hg, in patients with documented acute myocardial infarction and pulmonary congestion, and in patients with a hypersensitivity to diltiazem.5

Precautions

Cardizem is metabolized hepatically and excreted renally. Caution should be used with patients with impaired hepatic or renal function. Prescribers should be advised that concurrent use of Cardizem LA with cimetidine may increase diltiazem levels. Other potential drug interactions include those with digitalis, anesthetics, benzodiazepines, cyclosporine, carbamazepine, lovastatin, and rifampin. Use with known CYP 3A4 inducers should be avoided when possible.5

Dosing

Treatment of angina should be initiated at 180 mg once a day, with dose increases every 7 to 14 days if needed. Total daily doses should not exceed 360 mg.6

Adverse Reactions

In the angina study, side effects were similar to those previously reported from diltiazem. They included lowerlimb edema, dizziness, fatigue, bradycardia, first-degree AV block, and cough.5

Dr. Holmberg is a pharmacist with Phoenix Indian Medical Center, Phoenix, Ariz. The opinions expressed are those of the author and not necessarily of any government agency.

For a list of references, send a stamped, self-addressed envelope to: References Department, Attn. A. Stahl, Pharmacy Times, 241 Forsgate Drive, Jamesburg, NJ 08831; or send an e-mail request to: astahl@mwc.com.