Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
In a total of 1836 patients in controlled and uncontrolled clinical trials, 14% of patients received intravenous amiodarone for at least one week, 5% received it for at least 2 weeks, 2% received it for at least 3 weeks, and 1% received it for more than 3 weeks, without an increased incidence of severe adverse reactions. The mean duration of therapy in these studies was 5.6 days; median exposure was 3.7 days.
The most important adverse reactions were hypotension, asystole/cardiac arrest/pulseless electrical activity (PEA), cardiogenic shock, congestive heart failure, bradycardia, liver function test abnormalities, VT, and AV block. Overall, treatment was discontinued for about 9% of the patients because of adverse reactions. The most common adverse reactions leading to discontinuation of intravenous amiodaronejherapy were hypotension (1.6%), asystole/cardiac arrest/PEA (1.2%), VT (1.1%), and cardiogenic shock (1%).
Table 4 lists the most common (incidence ≥ 2%) adverse reactions during intravenous amiodarone therapy considered at least possibly drug-related. These data were collected in clinical trials involving 1836 patients with life-threatening VT/VF. Data from all assigned treatment groups are pooled because none of the adverse reactions appeared to be dose-related.
Table 4: ADVERSE REACTIONS IN PATIENTS RECEIVING INTRAVENOUS AMIODARONE IN CONTROLLED AND OPEN-LABEL STUDIES ( ≥ 2% INCIDENCE)
|Study Event|| Controlled Studies
(n = 814)
| Open-Label Studies
(n = 1022)
(n = 1836)
|Body as a whole|
|Congestive heart failure||18||(2.2%)||21||(2.0%)||39||(2.1%)|
|Liver function tests abnormal||35||(4.2%)||29||(2.8%)||64||(3.4%)|
Other adverse reactions reported in less than 2% of patients receiving intravenous amiodaronejn controlled and uncontrolled studies included the following: abnormal kidney function, atrial fibrillation, diarrhea, increased ALT, increased AST, lung edema, nodal arrhythmia, prolonged QT interval, respiratory disorder, shock, sinus bradycardia, Stevens-Johnson syndrome, thrombocytopenia, VF, and vomiting.
The following adverse reactions have been identified during post-approval use of amiodarone. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Body as a Whole: anaphylactic/anaphylactoid reaction (including shock), fever
Cardiovascular: hypotension (sometimes fatal), sinus arrest
Dermatologic: toxic epidermal necrolysis (sometimes fatal), exfoliative dermatitis, erythema multiforme, Stevens-Johnson syndrome, skin cancer, pruritus, angioedema
Endocrine: syndrome of inappropriate antidiuretic hormone secretion (SIADH)
Hematologic: pancytopenia, neutropenia, hemolytic anemia, aplastic anemia, thrombocytopenia, agranulocytosis, granuloma
Hepatic: hepatitis, cholestatic hepatitis, cirrhosis
Injection Site Reactions: pain, erythema, edema, pigment changes, venous thombosis, phlebitis, thrombophlebitis, cellulitis, necrosis, and skin sloughing
Musculoskeletal: myopathy, muscle weakness, rhabdomyolysis
Nervous System: hallucination, confusional state, disorientation, and delirium, pseudotumor cerebri
Renal: renal impairment, renal insufficiency, acute renal failure,
Respiratory: bronchospasm, possibly fatal respiratory disorders (including distress, failure, arrest and ARDS), bronchiolitis obliterans organizing pneumonia (possibly fatal), dyspnea, cough, hemoptysis, wheezing, hypoxia, pulmonary infiltrates, and /or mass, pleuritis
Thyroid: thyroid nodules/thyroid cancer