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 capsule (once-aday dosing)
product up to 360 mg with rates in placebo patients shown for comparison.
Diltiazem Hydrochloride Extended-release Capsule
(once-a-day) Placebo-controlled Angina and Hypertension Trials Combined
||Diltiazem Extended-release Capsule (once-a-day)
|AV Block First Degree
In clinical trials of diltiazem hydrochloride
extended-release capsules (Once A Day Dosage), diltiazem hydrochloride tablets
and diltiazem hydrochloride extended-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
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 WARNINGS, Acute Hepatic Injury),
thirst, vomiting, weight increase.
Dermatological: Petechiae, photosensitivity,
Other: Amblyopia, CPK increase, dyspnea,
epistaxis, eye irritation, hyperglycemia, hyperuricemia, impotence, muscle
cramps, nasal congestion, nocturia, osteoarticular pain, polyuria, sexual
The following postmarketing events have been reported
infrequently in patients receiving diltiazem: 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 therapy is yet to be established.
To report SUSPECTED ADVERSE REACTIONS, contact Actavis
at 1-800-272-5525 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.