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.
| Diltiazem Hydrochloride Extended-Release Capsule Placebo-Controlled Angina and Hypertension Trials Combined |
|---|
| Adverse Reactions | Diltiazem Hydrochloride Extended-Release Capsules
(n=607) | Placebo
(n=301) |
|---|
| Headache | 5.4% | 5.0% |
| Dizziness | 3.0% | 3.0% |
| Bradycardia | 3.3% | 1.3% |
| AV Block First Degree | 3.3% | 0.0% |
| Edema | 2.6% | 1.3% |
| ECG Abnormality | 1.6% | 2.3% |
| Asthenia | 1.8% | 1.7% |
In clinical trials of diltiazem hydrochloride extended-release capsules, diltiazem hydrochloride tablets, and diltiazem hydrochloride sustained-release capsules involving over 3200 patients, the most common events (i.e., greater than 1%) were edema (4.6%), headache (4.6%), dizziness (3.5%), asthenia (2.6%), first-degree AV block (2.4%), bradycardia (1.7%), flushing (1.4%), nausea (1.4%), and rash (1.2%).
In addition, the following events were reported infrequently (less than 1%) in angina or hypertension trials:
Cardiovascular: Angina, arrhythmia, AV block (second- or third-degree), bundle branch block, congestive heart failure, ECG abnormalities, hypotension, palpitations, syncope, tachycardia, ventricular extrasystoles
Nervous System: Abnormal dreams, amnesia, depression, gait abnormality, hallucinations, insomnia, nervousness, paresthesia, personality change, somnolence, tinnitus, tremor
Gastrointestinal: Anorexia, constipation, diarrhea, dry mouth, dysgeusia, dyspepsia, mild elevations of SGOT, SGPT, LDH, and alkaline phosphatase (see hepatic warnings), 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: 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, 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 therapy is yet to be established.
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