DILTIAZEM HCI

WARNINGS Cardiac Conduction. Diltiazem prolongs AV nodal conduction and refractoriness that may rarely result in second- or third-degree AV block in sinus rhythm. Concomitant use of diltiazem with agents known to affect cardiac conduction may result in additive effects (see PRECAUTIONS-DRUG INTERACTIONS . If high-degree AV block occurs in sinus rhythm, intravenous diltiazem should be discontinued and appropriate supportive measures instituted (see OVERDOSAGE ). Congestive Heart Failure. Although diltiazem has a negative inotropic effect in isolated animal tissue preparations, hemodynamic studies in humans with normal ventricular function and in patients with a compromised myocardium, such as severe CHF, acute MI, and hypertrophic cardiomyopathy, have not shown a reduction in cardiac index nor consistent negative effects on contractility (dp/dt). Administration of oral diltiazem in patients with acute myocardial infarction and pulmonary congestion documented by x-ray on admission is contraindicated. Experience with the use of diltiazem hydrochloride injection in patients with impaired ventricular function is limited. Caution should be exercised when using the drug in such patients. Hypotension. Decreases in blood pressure associated with diltiazem hydrochloride injection therapy may occasionally result in symptomatic hypotension (3.2%). The use of intravenous diltiazem for control of ventricular response in patients with supraventricular arrhythmias should be undertaken with caution when the patient is compromised hemodynamically. In addition, caution should be used in patients taking other drugs that decrease peripheral resistance, intravascular volume, myocardial contractility or conduction. Acute Hepatic Injury. In rare instances, significant elevations in enzymes such as alkaline phosphatase, LDH, SGOT, SGPT, and other phenomena consistent with acute hepatic injury have been noted following oral diltiazem. Therefore, the potential for acute hepatic injury exists following administration of intravenous diltiazem. Ventricular Premature Beats (VPBs). VPBs may be present on conversion of PSVT to sinus rhythm with diltiazem hydrochloride injection. These VPBs are transient, are typically considered to be benign, and appear to have no clinical significance. Similar ventricular complexes have been noted during cardioversion, other pharmacologic therapy, and during spontaneous conversion of PSVT to sinus rhythm.

ADVERSE REACTIONS The following adverse reaction rates are based on the use of diltiazem hydrochloride injection in over 400 domestic clinical trial patients with atrial fibrillation/flutter or PSVT under double-blind or open-label conditions. Worldwide experience in over 1,300 patients was similar. Adverse events reported in controlled and uncontrolled clinical trials were generally mild and transient. Hypotension was the most commonly reported adverse event during clinical trials. Asymptomatic hypotension occurred in 4.3% of patients. Symptomatic hypotension occurred in 3.2% of patients. When treatment for hypotension was required, it generally consisted of administration of saline or placing the patient in the Trendelenburg position. Other events reported in at least 1% of the diltiazem-treated patients were injection site reactions (e.g., itching, burning) - 3.9%, vasodilation (flushing) - 1.7%, and arrhythmia (junctional rhythm or isorhythmic dissociation) - 1%. In addition, the following events were reported infrequently (less than 1%): Cardiovascular: Asystole, atrial flutter, AV block first degree, AV block second degree, bradycardia, chest pain, congestive heart failure, sinus pause, sinus node dysfunction, syncope, ventricular arrhythmia, ventricular fibrillation, ventricular tachycardia Dermatologic: Pruritus, sweating Gastrointestinal: Constipation, elevated SGOT or alkaline phosphatase, nausea, vomiting Nervous System: Dizziness, paresthesia Other: Amblyopia, asthenia, dry mouth, dyspnea, edema, headache, hyperuricemia Although not observed in clinical trials with diltiazem hydrochloride injection, the following events associated with oral diltiazem may occur: Cardiovascular: AV block (third degree), bundle branch block, ECG abnormality, palpitations, syncope, tachycardia, ventricular extrasystoles Dermatologic: Alopecia, erythema multiforme (including Stevens-Johnson syndrome, toxic epidermal necrolysis), exfoliative dermatitis, leukocytoclastic vasculitis, petechiae, photosensitivity, purpura, rash, urticaria Gastrointestinal: Anorexia, diarrhea, dysgeusia, dyspepsia, mild elevations of SGPT and LDH, thirst, weight increase Nervous System: Abnormal dreams, amnesia, depression, extrapyramidal symptoms, gait abnormality, hallucinations, insomnia, nervousness, personality change, somnolence, tremor Other: Acute generalized exanthematous pustulosis, allergic reactions, angioedema (including facial or periorbital edema), CPK elevation, epistaxis, eye irritation, gingival hyperplasia, hemolytic anemia, hyperglycemia, impotence, increased bleeding time, leukopenia, muscle cramps, myopathy, nasal congestion, nocturia, osteoarticular pain, photosensitivity (including lichenoid keratosis and hyperpigmentation at sun-exposed skin areas), polyuria, retinopathy, sexual difficulties, thrombocytopenia, tinnitus. Events such as myocardial infarction have been observed which are not readily distinguishable from the natural history of the disease for the patient.