ADVERSE REACTIONS
Adverse reactions have been very common in virtually all series of patients treated with amiodarone HCl for ventricular arrhythmias with relatively large doses of drug (400 mg/day and above), occurring in about three-fourths of all patients and causing discontinuation in 7 to 18%. The most serious reactions are pulmonary toxicity, exacerbation of arrhythmia and rare serious liver injury (see " WARNINGS "), but other adverse effects constitute important problems. They are often reversible with dose reduction or cessation of amiodarone treatment. Most of the adverse effects appear to become more frequent with continued treatment beyond six months, although rates appear to remain relatively constant beyond one year. The time and dose relationships of adverse effects are under continued study.
Neurologic problems are extremely common, occurring in 20 to 40% of patients and including malaise and fatigue, tremor and involuntary movements, poor coordination and gait, and peripheral neuropathy; they are rarely a reason to stop therapy and may respond to dose reductions or discontinuation (see " PRECAUTIONS ").
Gastrointestinal complaints, most commonly nausea, vomiting, constipation and anorexia, occur in about 25% of patients but rarely require discontinuation of drug. These commonly occur during high-dose administration (i.e., loading dose) and usually respond to dose reduction or divided doses.
Ophthalmic abnormalities including optic neuropathy and/or optic neuritis, in some cases progressing to permanent blindness, papilledema, corneal degeneration, photosensitivity, eye discomfort, scotoma, lens opacities and macular degeneration have been reported (see " WARNINGS ").
Asymptomatic corneal microdeposits are present in virtually all adult patients who have been on drug for more than 6 months. Some patients develop eye symptoms of halos, photophobia and dry eyes. Vision is rarely affected and drug discontinuation is rarely needed.
Dermatological adverse reactions occur in about 15% of patients, with photosensitivity being most common (about 10%). Sunscreen and protection from sun exposure may be helpful, and drug discontinuation is not usually necessary. Prolonged exposure to amiodarone occasionally results in a blue-gray pigmentation. This is slowly and occasionally incompletely reversible on discontinuation of drug but is of cosmetic importance only.
Cardiovascular adverse reactions, other than exacerbation of the arrhythmias, include the uncommon occurrence of congestive heart failure (3%) and bradycardia. Bradycardia usually responds to dosage reduction but may require a pacemaker for control. CHF rarely requires drug discontinuation. Cardiac conduction abnormalities occur infrequently and are reversible on discontinuation of drug.
The following side-effect rates are based on a retrospective study of 241 patients treated for 2 to 1,515 days (mean 441.3 days). The following side effects were each reported in 10 to 33% of patients:
Gastrointestinal: Nausea and vomiting.
The following side effects were each reported in 4 to 9% of patients:
Dermatologic: Solar dermatitis/photosensitivity.
Neurologic: Malaise and fatigue, tremor/abnormal involuntary movements, lack of coordination, abnormal gait/ataxia, dizziness, paresthesias.
Gastrointestinal: Constipation, anorexia.
Ophthalmologic: Visual disturbances.
Hepatic: Abnormal liver-function tests.
Respiratory: Pulmonary inflammation or fibrosis.
The following side effects were each reported in 1 to 3% of patients:
Thyroid: Hypothyroidism, hyperthyroidism.
Neurologic: Decreased libido, insomnia, headache, sleep disturbances.
Cardiovascular: Congestive heart failure, cardiac arrhythmias, SA node dysfunction.
Gastrointestinal: Abdominal pain.
Hepatic: Nonspecific hepatic disorders.
Other: Flushing, abnormal taste and smell, edema, abnormal salivation, coagulation abnormalities. The following side effects were each reported in less than 1% of patients:
Blue skin discoloration, rash, spontaneous ecchymosis, alopecia, hypotension and cardiac conduction abnormalities.
In surveys of almost 5,000 patients treated in open U.S. studies and in published reports of treatment with amiodarone HCl, the adverse reactions most frequently requiring discontinuation of drug included pulmonary infiltrates or fibrosis, paroxysmal ventricular tachycardia, congestive heart failure and elevation of liver enzymes. Other symptoms causing discontinuations less often included visual disturbances, solar dermatitis, blue skin discoloration, hyperthyroidism and hypothyroidism.
POSTMARKETING REPORTS
In postmarketing surveillance, sinus arrest, hepatitis, cholestatic hepatitis, cirrhosis, epididymitis, impotence, vasculitis, pseudotumor cerebri, syndrome of inappropriate antidiuretic hormone secretion (SIADH), thrombocytopenia, angioedema, bronchiolitis obliterans organizing pneumonia (possibly fatal), bronchospasm, possibly fatal respiratory disorders (including distress, failure, arrest, and ARDS), fever, dyspnea, cough, hemoptysis, wheezing, hypoxia, pulmonary infiltrates, pleuritis, pancreatitis, toxic epidermal necrolysis, myopathy, rhabdomyolysis, hemolytic anemia, aplastic anemia, pancytopenia, neutropenia, erythema multiforme, Stevens-Johnson syndrome and exfoliative dermatitis also have been reported in patients receiving amiodarone.
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