Diltiazem 24Hr Er (Cd) (diltiazem HCl)

Diltiazem hydrochloride is a nondihydropyridine calcium-channel blocking agent (calcium-channel blocker).

Diltiazem is a nondihydropyridine benzothiazepine-derivative calcium-channel blocker. The principal physiologic action of diltiazem is to inhibit the transmembrane influx of extracellular calcium ions across the membranes of myocardial cells and vascular smooth muscle cells. Diltiazem is a peripheral arterial vasodilator; the drug acts directly on vascular smooth muscle causing reduction in peripheral vascular resistance (afterload) and blood pressure.

Diltiazem exerts substantial inhibitory effects on the cardiac conduction system, acting principally at the atrioventricular (AV) node to slow conduction time and prolong AV nodal refractoriness.

Diltiazem hydrochloride is well absorbed from the GI tract following oral administration of the conventional tablets. Following single oral doses of the conventional tablets, detectable and peak plasma levels occur within 30-60 minutes and 2-4 hours, respectively, after administration. Following a single 120-mg dose of the extended-release capsules, detectable and peak plasma levels occur within 2-3 and 6-11 hours, respectively.

Following a single 360-mg dose of Cardizem(R) CD or Cartia XT(R) extended-release capsules, detectable plasma and peak plasma levels occur within 2 and 10-14 hours, respectively; absorption occurs throughout the dosing interval. Following a single 360-mg dose of Cardizem(R) LA and Matzim(R) LA extended-release tablets, detectable and peak plasma levels occur within 3-4 and 11-18 hours, respectively. The oral bioavailability of diltiazem from extended-release capsules at steady state is more than 93% when compared with that of the conventional tablets.

The absolute bioavailability of diltiazem from a single dose of Dilt-XR(R), compared with IV administration, is approximately 40%. Only about 40% of an oral dose of diltiazem reaches systemic circulation as unchanged drug since diltiazem undergoes extensive metabolism on first pass through the liver. Plasma diltiazem concentrations are higher following multiple oral doses of the drug than after single oral doses, indicating saturation of hepatic microsomal enzyme systems.

Food does not appear to affect the extent of absorption, but rate of absorption may be increased if some extended-release preparations are taken with a high-fat meal. About 70-80% of diltiazem is bound to plasma proteins; approximately 30% is bound to albumin while other constituents bind the remainder. Diltiazem has a large volume of distribution because of its lipophilicity and is rapidly and extensively distributed into body tissues.

Diltiazem is distributed into breast milk, apparently in concentrations approximately equal to maternal serum concentrations. Diltiazem is rapidly and almost completely metabolized in the liver via deacetylation, N-demethylation, and O-demethylation to several active and at least 5 inactive metabolites principally via the cytochrome P-450 (CYP) microsomal enzyme system and mainly by the isoenzyme 3A4 (CYP3A4); the drug and its metabolites also undergo glucuronide and/or sulfate conjugation. About 10-20% of diltiazem is metabolized to deacetyldiltiazem, which is 25-50% as potent as a coronary vasodilator when compared with diltiazem, the parent compound.

Following oral administration in healthy individuals, diltiazem has a plasma half-life of 2-11 hours; however, plasma half-life of unidentified metabolites may be increased to about 20 hours. The plasma elimination half-life following single or multiple drug administration of diltiazem conventional tablets is approximately 3-4.5 hours. The apparent elimination half-life after single or multiple dosing of Tiazac(R) extended-release capsules is 4-9.5 hours (mean 6.5 hours).

The apparent elimination half-life after single or multiple dosing of Cardizem(R) CD and Cartia XT(R) extended-release capsules is 5-8 hours. Each extended-release diltiazem hydrochloride capsule (Dilt-XR(R)) consists of multiple 60-mg tablets contained in a slowly disintegrating matrix that slowly releases the drug over approximately 24 hours throughout the GI tract. Controlled absorption of diltiazem begins within 1 hour, with maximum plasma concentrations within 4-6 hours of administration.

The apparent steady-state half-life of diltiazem following once daily administration of Dilt-XR(R) is 5-10 hours; this prolongation is attributed to continued absorption of diltiazem rather than to alterations in its elimination. The apparent elimination half-life after single or multiple dosing of Cardizem(R) LA and Matzim(R) LA extended-release tablets is 6-9 hours. Plasma half-life of diltiazem may be increased in geriatric patients.

Liver cirrhosis has been shown to increase diltiazem's apparent AUC and to prolong its half-life. Some evidence suggests that the pharmacokinetic profile of the oral drug does not differ significantly in patients with severely impaired renal function compared with those patients having normal renal function. Diltiazem does not appear to be eliminated by hemodialysis or peritoneal dialysis.

Limited data suggest that plasmapheresis or charcoal hemoperfusion may hasten diltiazem elimination following overdosage. Approximately 2-4% of a dose of the drug is excreted in urine unchanged. The remainder of the drug is eliminated in urine and via bile, mainly as metabolites.

Following administration of 1 or 2 direct IV injections of diltiazem hydrochloride, reductions in heart rate usually occur within 3 minutes; maximal heart rate reduction generally occurs within 2-7 minutes and persists for 1-3 hours. Following direct IV injection of diltiazem hydrochloride over a 2-minute period, hemodynamic effects (e.g., decrease in blood pressure) generally occur by the end of the 2-minute period and reach a maximum within 2-11 minutes. Blood pressure reductions following direct IV injection of diltiazem, if they occur, generally are short-lived but may last 1-3 hours.

In patients with paroxysmal supraventricular tachycardia (PSVT) conversion to normal sinus rhythm usually occurs within 3 minutes of the first or second direct IV injections of diltiazem hydrochloride. After initiation of a continuous IV infusion of diltiazem, effects on the AV node generally occur within minutes and may persist for 0.5-10 hours (mean duration 7 hours) postinfusion. Following a single IV injection of diltiazem in healthy adults, pharmacokinetics are dose proportional over a dosage range of 10.5-21 mg with a half-life of approximately 3.4 hours and a systemic clearance of approximately 65 L/hour.

In patients with atrial fibrillation or atrial flutter receiving 10 or 15 mg/hour of diltiazem via continuous IV infusion, the half-life increases to 6.8 or 6.9 hours and the systemic clearance decreases to 42 or 31 L/hour, respectively. Following single diltiazem doses administered via direct IV injection, plasma concentrations of the principal metabolites, deacetyldiltiazem and N-monodesmethyldiltiazem, are initially low or undetectable; however, detectable plasma concentrations of active metabolites are observed following 24 hour constant rate intravenous infusion. Other unidentified metabolites were noted in the plasma after short-term IV administration in healthy adults and appeared in higher concentrations than unchanged diltiazem; these metabolites were more slowly eliminated than the parent drug.

Constant rate diltiazem IV infusions at 3, 5, 7, and 11 mg/h are predicted to produce steady-state plasma diltiazem concentrations equivalent to 120-, 180-, 240-,and 360-mg total daily oral doses of diltiazem tablets or diltiazem hydrochloride extended-release capsules based on the results of pharmacokinetic studies in healthy volunteers administered different oral diltiazem hydrochloride formulations.

USES: This medication is used to treat high blood pressure. Lowering high blood pressure helps prevent strokes, heart attacks, and kidney problems. It is also used to prevent chest pain (angina).

It may help to increase your ability to exercise and decrease how often you may get angina attacks. Diltiazem belongs to a class of drugs known as calcium channel blockers. It works by relaxing blood vessels so blood can flow more easily.

It may also lower your heart rate.

Generic name: diltiazem HCl
Pronunciation: (dill-TIE-uh-zem)

The following indications are listed for Diltiazem 24Hr Er (Cd):

• Hypertension
• Prevention Of Anginal Pain Associated With Coronary Artery Disease

Also known as: Elevated Blood Pressure, Essential Hypertension, Hyperpiesia, Hyperpiesis, Hypertensive Disorder, Prevention Of Anginal Pain Associated With Cad, Systemic Arterial Hypertension.

No ICD codes are available for this drug.