Diltiazem

What it is used for

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

How to take it

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 mg/day 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 diltiazem hydrochloride therapy.
• Prophylactic Nitrate Therapy. Diltiazem hydrochloride 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.

Side effects, and when to stop

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 tablets: 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 ScieGen Pharmaceuticals, Inc. at 1-855-724-3436 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Who should not take it

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

Other medicines and interactions

Due to the potential for additive effects, caution and careful titration are warranted in patients receiving diltiazem hydrochloride concomitantly with any agents known to affect cardiac contractility and/or conduction (see WARNINGS ).

Pharmacologic studies indicate that there may be additive effects in prolonging AV conduction when using beta-blockers or digitalis concomitantly with diltiazem hydrochloride (see WARNINGS ).

Diltiazem is both a substrate and an inhibitor of the Pg-p and cytochrome P450 3A4 enzyme system which may affect exposure to diltiazem and concomitant drugs metabolized by those pathways. Patients with renal and/or hepatic impairment may be particularly at risk of exposure changes.

General

Diltiazem hydrochloride is extensively metabolized by the liver and excreted by the kidneys and in bile. As with any drug given over prolonged periods, laboratory parameters of renal and hepatic function should be monitored at regular intervals. The drug should be used with caution in patients with impaired renal or hepatic function. In subacute and chronic dog and rat studies designed to produce toxicity, high doses of diltiazem were associated with hepatic damage. In special subacute hepatic studies, oral doses of 125 mg/kg and higher in rats were associated with histological changes in the liver, which were reversible when the drug was discontinued. In dogs, doses of 20 mg/kg were also associated with hepatic changes; however, these changes were reversible with continued dosing.

Dermatological events (see ADVERSE REACTIONS ) may be transient and may disappear despite continued use of diltiazem hydrochloride. However, skin eruptions progressing to erythema multiforme and/or exfoliative dermatitis have also been infrequently reported. Should a dermatologic reaction persist, the drug should be discontinued.