Cartia XT - Clinical Pharmacology

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Diltiazem Hydrochloride Extended-release Capsules USP (once-a-day dosage) reduces the renal and peripheral effects of angiotensin II. Hypertensive animal models respond to diltiazem with reductions in blood pressure and increased urinary output and natriuresis without a change in urinary sodium/ potassium ratio. In a double-blind, parallel dose-response study of doses from 60 mg to 480 mg once daily, diltiazem hydrochloride extended-release capsule (once-a-day dosage) increased time to termination of exercise in a linear manner over the entire dose range studied.

The improvement in time to termination of exercise utilizing a Bruce exercise protocol, measured at trough, for placebo, 60 mg, 120 mg, 240 mg, 360 mg, and 480 mg was 29, 40, 56, 51, 69 and 68 seconds, respectively. As doses of diltiazem hydrochloride extended-release capsule (once-a-day dosage) were increased, overall angina frequency was decreased. Diltiazem hydrochloride extended-release capsule (once-a-day dosage), 180 mg once daily, or placebo was administered in a double-blind study to patients receiving concomitant treatment with long-acting nitrates and/ or beta-blockers.

A significant increase in time to termination of exercise and a significant decrease in overall angina frequency was observed. In this trial the overall frequency of adverse events in the diltiazem hydrochloride extended-release capsule (once-a-day dosage) treatment group was the same as the placebo group.

Intravenous diltiazem in doses of 20 mg prolongs AH conduction time and AV node functional and effective refractory peri-ods by approximately 20%. In a study involving single oral doses of 300 mg of diltiazem hydrochloride in six normal vol-unteers, the average maximum PR prolongation was 14% with no instances of greater than first-degree AV block. Diltiazem-associated prolongation of the AH interval is not more pronounced in patients with first-degree heart block.

In patients with sick sinus syndrome, diltiazem significantly prolongs sinus cycle length (up to 50% in some cases). Chronic oral administration of diltiazem hydrochloride to patients in doses of up to 540 mg/ day has resulted in small increases in PR interval, and on occasion produces abnormal prolongation. (See WARNINGS).