DILTIAZEM HYDROCHLORIDE

Diltiazem hydrochloride, USP is a calcium ion cellular influx inhibitor (slow channel blocker or calcium antagonist). Chemically, diltiazem hydrochloride, USP is 1,5-Benzothiazepin-4(5 H )-one, 3-(acetyloxy)-5-[2-(dimethylamino)ethyl]-2, 3-dihydro-2-(4- methoxyphenyl)-, monohydrochloride,(+)- cis -. The chemical structure is: Diltiazem hydrochloride, USP is a white to off-white crystalline powder with a bitter taste. It is freely soluble in chloroform, in formic acid, in methanol and in water, sparingly soluble in dehydrated ethanol, insoluble in ether. It has a molecular weight of 450.98. Each diltiazem hydrochloride tablet, USP contains 30 mg, 60 mg, 90 mg, or 120 mg of diltiazem hydrochloride, USP. Also contains: colloidal silicon dioxide, D&C Yellow No. 10 Aluminum Lake, FD&C Blue No. 1 Aluminum Lake (30 mg and 90 mg), FD&C Yellow No. 6 Aluminum Lake (60 mg and 120 mg), hypromellose, lactose monohydrate, magnesium stearate, microcrystalline cellulose, polyethylene glycol 400, talc and titanium dioxide. For oral administration. FDA approved dissolution test specifications differ from USP. diltiazem-str.jpg

Diltiazem hydrochloride tablets are indicated for the management of chronic stable angina and angina due to coronary artery spasm.

Exertional Angina Pectoris Due to Atherosclerotic Coronary Artery Disease or Angina Pectoris at Rest Due to Coronary Artery Spasm: Dosage must be adjusted to each patient’s needs. Starting with 30 mg four times daily, before meals and at bedtime, dosage should be increased gradually (given in divided doses three or four times daily) at 1- to 2-day intervals until optimum response is obtained. Although individual patients may respond to any dosage level, the average optimum dosage range appears to be 180 to 360 mg/day. There are no available data concerning dosage requirements in patients with impaired renal or hepatic function. If the drug must be used in such patients, titration should be carried out with particular caution. Concomitant Use with Other Cardiovascular Agents • Sublingual NTG may be taken as required to abort acute anginal attacks during CARDIZEM (diltiazem hydrochloride) therapy. • Prophylactic Nitrate Therapy. Diltiazem hydrochloride tablets may be safely coadministered with short- and long- acting nitrates, but there have been no controlled studies to evaluate the antianginal effectiveness of this combination. • Beta-blockers. (see WARNINGS and PRECAUTIONS. ) 30 mg – Diltiazem hydrochloride tablets may be swallowed whole, crushed, or chewed. Do not split diltiazem hydrochloride tablets. 60 mg, 90 mg, and 120 mg – Diltiazem hydrochloride tablets may be swallowed whole, crushed, or chewed.

Diltiazem hydrochloride tablets are contraindicated in: • Patients with sick sinus syndrome except in the presence of a functioning ventricular pacemaker • Patients with second- or third-degree AV block except in the presence of a functioning ventricular pacemaker • Patients with hypotension (less than 90 mm Hg systolic) • Patients who have demonstrated hypersensitivity to the drug • Patients with acute myocardial infarction and pulmonary congestion documented by x-ray on admission

Serious adverse reactions have been rare in studies carried out to date, but it should be recognized that patients with impaired ventricular function and cardiac conduction abnormalities usually have been excluded. In domestic placebo-controlled angina trials, the incidence of adverse reactions reported during diltiazem hydrochloride therapy was not greater than that reported during placebo therapy. The following represent occurrences observed in clinical studies of angina patients. In many cases, the relationship to diltiazem hydrochloride has not been established. The most common occurrences from these studies, as well as their frequency of presentation, are edema (2.4%), headache (2.1%), nausea (1.9%), dizziness (1.5%), rash (1.3%), and asthenia (1.2%). In addition, the following events were reported infrequently (less than 1%): Cardiovascular: Angina, arrhythmia, AV block (first-degree), AV block (second- or third-degree – see WARNINGS, Cardiac Conduction ), bradycardia, bundle branch block, congestive heart failure, ECG abnormality, flushing, hypotension, palpitations, syncope, tachycardia, ventricular extrasystoles Nervous System: Abnormal dreams, amnesia, depression, gait abnormality, hallucinations, insomnia, nervousness, paresthesia, personality change, somnolence, tremor Gastrointestinal: Anorexia, constipation, diarrhea, dysgeusia, dyspepsia, mild elevations of alkaline phosphatase, SGOT, SGPT, and LDH (see WARNINGS, Acute Hepatic Injury ), thirst, vomiting, weight increase. Dermatological: Petechiae, photosensitivity, pruritus, urticaria Other: Amblyopia, CPK elevation, dry mouth, dyspnea, epistaxis, eye irritation, hyperglycemia, hyperuricemia, impotence, muscle cramps, nasal congestion, nocturia, osteoarticular pain, polyuria, sexual difficulties, tinnitus The following postmarketing events have been reported infrequently in patients receiving diltiazem hydrochloride: acute generalized exanthematous pustulosis, allergic reactions, alopecia, angioedema (including facial or periorbital edema), asystole, erythema multiforme (including Stevens-Johnson syndrome, toxic epidermal necrolysis), extrapyramidal symptoms, gingival hyperplasia, hemolytic anemia, increased bleeding time, leukopenia, photosensitivity (including lichenoid keratosis and hyperpigmentation at sun- exposed skin areas), purpura, retinopathy, myopathy, and thrombocytopenia. There have been observed cases of a generalized rash, some characterized as leukocytoclastic vasculitis. In addition, events such as myocardial infarction have been observed, which are not readily distinguishable from the natural history of the disease in these patients. A definitive cause and effect relationship between these events and diltiazem hydrochloride therapy cannot yet be established. Exfoliative dermatitis (proven by rechallenge) has also been reported. To report SUSPECTED ADVERSE REACTIONS, contact Alembic Pharmaceuticals Limited at 1-866-210-9797 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.