FDA label 3d1ebaad-0fb7-641a-e054-00144ff8d46c

WARNINGS Cardiac Conduction Congestive Heart Failure Although diltiazem has a negative inotropic effect in isolated animal tissue preparations, hemodynamic studies in humans with normal ventricular function have not shown a reduction in cardiac index nor consistent negative effects on contractility (dp/dt). An acute study of oral diltiazem in patients with impaired ventricular function (ejection fraction of 24%6%) showed improvement in indices of ventricular function without significant decrease in contractile function (dp/dt). Worsening of congestive heart failure has been reported in patients with preexisting impairment of ventricular function. Experience with the use of diltiazem in combination with beta-blockers in patients with impaired ventricular function is limited. Caution should be exercised when using this combination. Hypotension Decreases in blood pressure associated with diltiazem therapy may occasionally result in symptomatic hypotension. Acute Hepatic Injury Mild elevations of serum transaminases with and without concomitant elevation in alkaline phosphatase and bilirubin have been observed in clinical studies. Such elevations were usually transient and frequently resolved even with continued diltiazem treatment. In rare instances, significant elevations in alkaline phosphatase, LDH, SGOT, SGPT, and other phenomena consistent with acute hepatic injury have been noted. These reactions tended to occur early after therapy initiation (1 to 6 weeks) and have been reversible upon discontinuation of drug therapy. The relationship to diltiazem is uncertain in some cases, but probable in some others (see PRECAUTIONS ).

ADVERSE REACTIONS Serious adverse reactions to diltiazem hydrochloride have been rare in studies with other formulations, as well as with diltiazem hydrochloride extended-release capsules (once-a-day dosage). It should be recognized, however, that patients with impaired ventricular function and cardiac conduction abnormalities have usually been excluded from these studies. Hypertension The most common adverse events (frequency1%) in placebo-controlled, clinical hypertension studies with diltiazem hydrochloride extended-release capsules (once-a-day dosage) using daily doses up to 540 mg are listed in the table below with placebo-treated patients included for comparison. MOST COMMON ADVERSE EVENTS IN DOUBLE-BLIND, PLACEBO-CONTROLLED HYPERTENSION TRIALS Adverse Events (COSTART Term)Diltiazem Hydrochloride Extended-release Capsules (Once-a-Day Dosage) * n = 303 # pts (%)Placebo n = 87 # pts (%) * Adverse events occurring in 1% or more of patients receiving diltiazem hydrochloride extended-release capsules (once-a-day dosage).rhinitis29 (9.6)7 (8.0)headache27 (8.9)12 (13.8)pharyngitis17 (5.6)4 (4.6)constipation11 (3.6)2 (2.3)cough increase9 (3.0)2 (2.3)flu syndrome7 (2.3)1 (1.1)edema, peripheral7 (2.3)0 (0.0)myalgia7 (2.3)0 (0.0)diarrhea6 (2.0)0 (0.0)vomiting6 (2.0)0 (0.0)sinusitis6 (2.0)1 (1.1)asthenia5 (1.7)0 (0.0)pain, back5 (1.7)2 (2.3)nausea5 (1.7)1 (1.1)dyspepsia4 (1.3)0 (0.0)vasodilatation4 (1.3)0 (0.0)injury, accident4 (1.3)0 (0.0)pain, abdominal3 (1.0)0 (0.0)arthrosis3 (1.0)0 (0.0)insomnia3 (1.0)0 (0.0)dyspnea3 (1.0)0 (0.0)rash3 (1.0)1 (1.1)tinnitus3 (1.0)0 (0.0) Angina The most common adverse events (frequency1%) in a placebo-controlled, short-term (2 week) clinical angina study with diltiazem hydrochloride extended-release capsules (once-a-day dosage) are listed in the table below with placebo-treated patients included for comparison. In this trial, following a placebo phase, patients were randomly assigned to once daily doses of either 120 mg, 240 mg or 480 mg of diltiazem hydrochloride extended-release capsules (once-a-day dosage). MOST COMMON ADVERSE EVENTS IN A DOUBLE-BLIND, PLACEBO-CONTROLLED SHORT-TERM, ANGINA TRIAL Adverse Events (COSTART Term)Diltiazem Hydrochloride Extended-release Capsules (Once-a-Day Dosage) * n = 139 # pts (%)Placebo n = 50 # pts (%) * Adverse events occurring in 1% or more of patients receiving diltiazem hydrochloride extended-release capsules (once-a-day dosage).asthenia5 (3.6)2 (4.0)headache4 (2.9)3 (6.0)pain, back4 (2.9)1 (2.0)rhinitis4 (2.9)1 (2.0)constipation3 (2.2)1 (2.0)nausea3 (2.2)0 (0.0)edema, peripheral3 (2.2)1 (2.0)dizziness3 (2.2)0 (0.0)cough, increased3 (2.2)0 (0.0)bradycardia2 (1.4)0 (0.0)fibrillation, atrial2 (1.4)0 (0.0)arthralgia2 (1.4)0 (0.0)dream, abnormal2 (1.4)0 (0.0)dyspnea2 (1.4)0 (0.0)pharyngitis2 (1.4)1 (2.0) Infrequent Adverse Events The following additional events (COSTART Terms), listed by body system, were reported infrequently (less than 1%) in all subjects, hypertensive (n = 425) or angina (n = 318) patients who received diltiazem hydrochloride extended-release capsules (once-a-day dosage), or with other formulations of diltiazem. Hypertension Cardiovascular: First-degree AV block, arrhythmia, postural hypotension, tachycardia, pallor, palpitations, phlebitis, ECG abnormality, ST elevation. Nervous System: Vertigo, hypertonia, paresthesia, dizziness, somnolence. Digestive System: Dry mouth, anorexia, tooth disorder, eructation. Skin and Appendages: Sweating, urticaria, skin hypertrophy (nevus). Respiratory System: Epistaxis, bronchitis, respiratory disorder. Urogenital System: Cystitis, kidney calculus, impotence, dysmenorrhea, vaginitis, prostate disease. Metabolic and Nutritional Disorders: Gout, edema. Musculoskeletal System: Arthralgia, bursitis, bone pain. Hemic and Lymphatic System: Lymphadenopathy. Body as a Whole: Pain, unevaluable reaction, neck pain, neck rigidity, fever, chest pain, malaise. Special Senses: Amblyopia (blurred vision), ear pain. Angina Cardiovascular: Palpitations, AV block, sinus bradycardia, bigeminal extrasystole, angina pectoris, hypertension, hypotension, myocardial infarct, myocardial ischemia, syncope, vasodilatation, ventricular extrasystole. Nervous System: Abnormal thinking, neuropathy, paresthesia. Digestive System: Diarrhea, dyspepsia, vomiting, colitis, flatulence, GI hemorrhage, stomach ulcers. Skin and Appendages: Contact dermatitis, pruritus, sweating. Respiratory System: Respiratory distress. Urogenital System: Kidney failure, pyelonephritis, urinary tract infection. Metabolic and Nutritional Disorders: Weight increase. Musculoskeletal System: Myalgia. Body as a Whole: Chest pain, accidental injury, infection. Special Senses: Eye hemorrhage, ophthalmitis, otitis media, taste perversion, tinnitus. There have been post-marketing reports of Stevens-Johnson Syndrome and toxic epidermal necrolysis associated with the use of diltiazem.