Diltiazem Hydrochloride

INDICATIONS AND USAGE Diltiazem hydrochloride extended-release capsules are indicated for the treatment of hypertension. It may be used alone or in combination with other antihypertensive medications. Diltiazem hydrochloride extended-release capsules are indicated for the management of chronic stable angina and angina due to coronary artery spasm.

DOSAGE AND ADMINISTRATION Patients controlled on diltiazem alone or in combination with other medications may be switched to diltiazem hydrochloride extended-release capsules, USP at the nearest equivalent total daily dose. Higher doses of diltiazem hydrochloride extended-release capsules, USP may be needed in some patients. Monitor patients closely. Subsequent titration to higher or lower doses may be necessary. There is limited general clinical experience with doses above 360 mg, but doses to 540 mg have been studied in clinical trials. The incidence of side effects increases as the dose increases with first-degree AV block, dizziness, and sinus bradycardia bearing the strongest relationship to dose. Hypertension : Adjust dosage to individual patient needs. When used as monotherapy, reasonable starting doses are 180 to 240 mg once daily, although some patients may respond to lower doses. Maximum antihypertensive effect is usually observed by 14 days of chronic therapy; therefore, schedule dosage adjustments accordingly. The usual dosage range studied in clinical trials was 240 to 360 mg once daily. Individual patients may respond to higher doses of up to 480 mg once daily. Angina : Dosages for the treatment of angina should be adjusted to each patient's needs, starting with a dose of 120 or 180 mg once daily. Individual patients may respond to higher doses of up to 480 mg once daily. When necessary, titration may be carried out over a 7- to 14-day period. Concomitant Use with Other Cardiovascular Agents Sublingual NTG : May be taken as required to abort acute anginal attacks during diltiazem hydrochloride therapy. P r ophylactic Nitrate Therapy : Diltiazem hydrochloride extended-release capsules, USP may be safely coadministered with short- and long-acting nitrates. Beta-blockers : (see WARNINGS and PRECAUTIONS ). Antihypertensives : Diltiazem hydrochloride extended-release capsules, USP have an additive antihypertensive effect when used with other antihypertensive agents. Therefore, the dosage of diltiazem hydrochloride extended-release capsules, USP or the concomitant antihypertensives may need to be adjusted when adding one to the other.

ADVERSE REACTIONS 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 have usually been excluded from these studies. The following table presents the most common adverse reactions reported in placebo-controlled angina and hypertension trials in patients receiving diltiazem hydrochloride extended-release capsules up to 360 mg with rates in placebo patients shown for comparison. In addition, the following events were reported infrequently (less than 1%) in angina or hypertension trials: Cardiovascular: Congestive heart failure, palpitations, syncope, ventricular extrasystoles. Nervous System: Abnormal dreams, amnesia, depression, gait abnormality, hallucinations, insomnia, nervousness, paresthesia, personality change, somnolence, tinnitus, tremor. G astrointestinal: Anorexia, constipation, diarrhea, dry mouth, dysgeusia, dyspepsia, mild elevations of SGOT, SGPT, LDH, and alkaline phosphatase (see WARNINGS, Acute Hepatic Injury ), thirst, vomiting, weight increase. Dermatological: Petechiae, photosensitivity, pruritus, urticaria. Other: Amblyopia, CPK increase, dyspnea, epistaxis, eye irritation, hyperglycemia, hyperuricemia, impotence, muscle cramps, nasal congestion, nocturia, osteoarticular pain, polyuria, sexual difficulties. 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), exfoliative dermatitis, 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. 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 number of well-documented cases of generalized rash, some characterized as leukocytoclastic vasculitis, have been reported. However, a definitive cause and effect relationship between these events and diltiazem hydrochloride therapy is yet to be established. To report SUSPECTED ADVERSE REACTIONS, contact Ingenus Pharmaceuticals, LLC Toll-Free at 1-877-748-1970 or FDA at 1-800-FDA-1088 or w w w.fda.gov/medwatch .