Cordarone Side Effects

Generic Name: amiodarone

Please note - some side effects for Cordarone may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA at http://www.fda.gov/medwatch/ or 1-800-FDA-1088 (1-800-332-1088).

Side Effects of Cordarone - for the Consumer

Cordarone

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome when using Cordarone:

Abnormal skin sensations (loss of sensation; tingling; numbness; prickling); bitter taste in mouth; blue-green discoloring of skin (especially hands or feet); constipation; decreased sexual interest; dizziness; dry eyes; flushing of the face; general body discomfort; headache; involuntary muscle movements; loss of appetite; nausea; poor coordination; tiredness; trouble sleeping; vomiting.

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); chest pain; chills; coldness; cough; coughing up blood; dark urine; decreased urination; easy bruising or bleeding; enlarged thyroid gland; eye discomfort; fatigue; fever; irregular pulse; loss of coordination; menstrual changes; muscle pain, tenderness, or weakness (especially with fever or unusual tiredness); nervousness; persistent sore throat; severe dizziness; severe stomach pain; shortness of breath; skin reaction similar to serious sunburn; slow heartbeat; sluggishness; sweating; tingling or numbness of hands or feet; uncontrolled shaking or tremor; unexplained weight change; vision changes (seeing halos, blurred vision, loss of vision); wheezing; worsening of irregular heartbeat; yellowing of the skin or eyes.

Cordarone Side Effects - for the Professional

Cordarone

Adverse reactions have been very common in virtually all series of patients treated with Cordarone 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, but other adverse effects constitute important problems. They are often reversible with dose reduction or cessation of Cordarone 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.

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.

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 Cordarone 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 Cordarone, the adverse reactions most frequently requiring discontinuation of Cordarone 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, hypotension (sometimes fatal), sinus arrest, anaphylactic/anaphylactoid reaction (including shock), angioedema, urticaria, hepatitis, cholestatic hepatitis, cirrhosis, pancreatitis, renal impairment, renal insufficiency, acute renal failure, bronchospasm, possibly fatal respiratory disorders (including distress, failure, arrest, and ARDS), bronchiolitis obliterans organizing pneumonia (possibly fatal), fever, dyspnea, cough, hemoptysis, wheezing, hypoxia, pulmonary infiltrates and/or mass, pulmonary alveolar hemorrhage, pleuritis, pseudotumor cerebri, parkinsonian symptoms such as akinesia and bradykinesia (sometimes reversible with discontinuation of therapy), syndrome of inappropriate antidiuretic hormone secretion (SIADH), thyroid nodules/thyroid cancer, toxic epidermal necrolysis (sometimes fatal), erythema multiforme, Stevens-Johnson syndrome, exfoliative dermatitis, skin cancer, vasculitis, pruritus, hemolytic anemia, aplastic anemia, pancytopenia, neutropenia, thrombocytopenia, agranulocytosis, granuloma, myopathy, muscle weakness, rhabdomyolysis, hallucination, confusional state, disorientation, delirium, epididymitis, and impotence, also have been reported with amiodarone therapy.

Side Effects by Body System

Ocular

Amiodarone-induced ocular side effects are time- and dose-dependent. The most commonly affected ocular structure is the cornea with punctuate opacities occurring in 69% to 100% of patients. Lenticular changes may include anterior, subcapsular, small, yellow-white punctuate opacities.

The incidence of optic neuropathy, the most severe ocular side effect of amiodarone, ranges from 0.36% to 2%. Amiodarone-related optic neuropathy has been characterized as having an insidious onset, slow progression, bilateral vision loss, and protracted disc edema. In one report which was based on 50 cases, the median duration of treatment until onset of vision loss was 4 months. In one case, vision loss occurred after 24 months of treatment. It should be noted that because of similar clinical features, amiodarone-induced optic neuropathy can be confused with idiopathic nonarteritic anterior ischemic optic neuropathy.

Ocular side effects have been reported the most frequently and have included corneal microdeposits (up to 98%) which only rarely caused visual halos or blurred vision, corneal opacities, lenticular changes, loss of eyelashes or eyebrows, papilledema, photosensitivity, scotoma, macular degeneration, and optic neuropathy or optic neuritis.

Cardiovascular

Cardiovascular side effects have included hypotension (10% to 30%), bradycardia (1% to 10%), worsening heart failure (1% to 5%), asystole/cardiac arrest/electromechanical dissociation (3.5%), cardiogenic shock (3%), congestive heart failure (2.2%), ventricular tachycardia (1.8%), second- and third-degree AV nodal block (less than 2%), AV heart block (1%), and Torsades de pointes (0.7%). Rarely, cases of ventricular fibrillation have been reported. Hypotension, vasculitis, and sinus arrest have been reported in postmarketing experience. One- year sudden death has been reported. A case of endocarditis and pleuropericardial effusion has been reported.

Limited data have shown that the incidence of one-year sudden death was markedly and significantly increased in patients with advanced heart failure and a history of torsades de pointes taking amiodarone compared with such patients who were not taking amiodarone.

The results of a meta-analysis indicate that use of amiodarone for the prevention of postoperative atrial fibrillation increases the risk of developing bradycardia and hypotension. However, other meta- analyses have shown that the use of amiodarone in the same setting reduced the rate of postoperative atrial fibrillation and stroke.

Respiratory

Amiodarone-induced pulmonary toxicity (AIPT) occurs with an incidence of 1% to 17%, typically manifests as acute pneumonitis and chronic fibrosis, and can be life threatening. In general, AIPT develops in 0.1% to 0.5% of patients that take up to 200 mg daily and 5% to 15% of patients that take 500 mg or more daily. AIPT has proven fatal in approximately 5% to 10% of cases when patients were on dosages of more than 400 mg daily; however, in patients who develop acute respiratory failure due to AIPT and require ventilation, mortality is 50% to 100%. AIPT may occur early in therapy or after several years of treatment. Patients with preexisting pulmonary disease are at an increased risk of developing AIPT. The proposed mechanism of lung damage is the accumulation of phospholipids in the lungs. AIPT is reversible if diagnosed early. The more common form of AIPT is associated with doses of 400 mg daily or more, it has an insidious onset, typically manifests after 2 or more months of therapy and is characterized by a progressive nonproductive cough, dyspnea, weight loss, and possibly fever.

Respiratory side effects including chronic pulmonary fibrosis have been reported in 1% to 7% of patients. Bronchial asthma has also been reported. Rarely, acute respiratory failure and pneumonitis have been reported. Pulmonary infiltrates, alveolar hemorrhage, bronchospasm, wheezing, fever, dyspnea, cough, hemoptysis, hypoxia, pleuritis, possibly fatal respiratory distress, respiratory failure, respiratory arrest, acute respiratory distress syndrome, and bronchiolitis obliterans organizing pneumonia have been reported in postmarketing experience.

Endocrine

Endocrine side effects have included thyroid abnormalities (30%), hyper- and hypothyroidism (5% to 10%), and thyrotoxicosis. Rare cases of thyroiditis have been reported. Syndrome of inappropriate antidiuretic hormone secretion (SIADH), thyroid nodules, and thyroid cancer have been reported in postmarketing experience.

A 67-year-old male with SIADH developed hyponatremia. Although common comorbid conditions associated with SIADH were excluded as possible causes, his drug regimen and medical history were extensive. However, he had been taking spironolactone, amiodarone, and simvastatin for less than 3 months. The patient's serum sodium level began to rise within 3 days of discontinuation of amiodarone and returned to normal within 1 month.

Amiodarone-induced hypothyroidism occurs more frequently in iodine- sufficient regions than in iodine-deficient regions. It also occurs more frequently in female and elderly patients than in male or younger patients. Clinical manifestations of amiodarone- induced hypothyroidism may include fatigue, lethargy, bradycardia, dyspnea, cold intolerance, dry skin, weight gain, constipation, and reduced appetite.

Amiodarone-induced thyrotoxicosis (AIT) occurs more frequently in iodine-deficient regions and it primarily occurs in men (male to female ratio 3:1). AIT may develop in patients with or without preexisting thyroid dysfunction and at anytime during therapy including following discontinuation of treatment. In patients with AIT, laboratory results will reveal marked increases in the serum levels of thyroxine (T4) and possibly triiodothyronine (T3). When AIT occurs in patients with preexisting thyroid dysfunction (e.g., goiter, Grave's disease) it is referred to as AIT type I. When AIT occurs in patients without preexisting thyroid dysfunction it is referred to as AIT type II. AIT type II may be related to destructive inflammatory thyroiditis, caused by the cytotoxic effects of amiodarone and its metabolites on thyroid cells, which results in glandular damage and subsequent leakage of preformed thyroid hormones. Clinical manifestations of AIT may include palpitations, supraventricular tachycardia, weight loss, sweating, muscle weakness, tremor, insomnia, and mood swings. In type I AIT, serum levels of interleukin-6 are normal or slightly elevated, 24-hour uptake of radioactive iodine by the thyroid gland is normal to high, and there is an increase in vascularity. In type II AIT, serum levels of interleukin-6 are markedly increased, 24-hour uptake of radioactive iodine by the thyroid gland is low to none, and vascularity is normal. It should be noted that a patient may also have a mixture of type I and II AIT where the different features of the two types may coexist.

Gastrointestinal

Gastrointestinal side effects including anorexia have been reported in 2% to 20% of patients. Nausea, vomiting, constipation, and altered taste have been reported.

Hypersensitivity

Hypersensitivity side effects including photosensitivity have been reported in 70% of patients. Toxic epidermal necrolysis and exfoliative dermatitis have been reported rarely. Anaphylactic/anaphylactoid reaction (including shock), angioedema, Stevens-Johnson syndrome, and erythema multiforme have been reported in postmarketing experience. A case of drug-induced lupus erythematosus has been reported.

A hypersensitivity (possible cross-reactivity) reaction (i.e., lip swelling and tingling) to oral amiodarone has been described in a patient with a previous history of hypersensitivity to an iodinated radiocontrast agent.

Immunologic

Immunologic side effects have been reported rarely. These have included polyserositis and cutaneous leukocytoclastic vasculitis.

Hepatic

In one case report, a patient developed hepatic cirrhosis associated with microvesicular steatosis after 22.5 months of low-dose (200 mg daily) oral amiodarone therapy.

According to the results of a retrospective study (n=720), the prevalence of significant liver dysfunction in patients taking oral amiodarone with or without elevated baseline alanine aminotransferase (ALT) is similar. The authors suggest that amiodarone may be safety administered to patients with elevated baseline ALT, but recommend close monitoring of liver function.

Hepatic side effects including symptomatic elevations in liver function tests have been reported in 50% of patients. Rarely, fatal cases of cirrhosis have been reported. A single case of hepatitis with pancreatitis has been reported. Jaundice has been reported. Hepatitis, cholestatic hepatitis, pancreatitis, and cirrhosis have been reported in postmarketing experience.

Dermatologic

Dermatologic side effects have included photosensitivity (24% to 57%) and blue/gray skin discoloration (1% to 7%). Rarely, cases of toxic epidermal necrolysis, exfoliative dermatitis, reversible alopecia, bullous dermatosis, linear IgA disease, cutaneous vasculitis, and pustular psoriasis have been reported. Exfoliative dermatitis, toxic epidermal necrolysis, skin cancer, and pruritus have been reported in postmarketing experience. Additional postmarketing reports have included urticaria.

A retrospective study of 44 patients found by univariate analysis that patients who experienced dermatologic side effects were younger than patients who did not (mean age 48 years vs. 60 years, respectively). Patients younger than 60 years were more likely to develop photosensitivity or blue-gray skin discoloration than those 60 years or older.

Nervous system

In one study of 102 patients treated for a mean duration of nine months, 45 (44%) developed some sort of neurotoxic reaction that required discontinuation of therapy. The most frequent findings were tremor in 44, peripheral neuropathy in 10, and ataxia in 7 patients.

Nervous system side effects have been reported the most frequently. These have included tremor (9% to 59%), ataxia (2% to 37%), and peripheral neuropathy (1% to 10%). Dyskinesia, disorientation, confusion, paresthesias, headache, sleep disturbances, impaired memory, ataxia, diplopia, proximal muscle weakness, acute narcotizing myopathy, acute intracranial hypertension, and pseudotumor cerebri have been reported. Pseudotumor cerebri, confusional state, disorientation, and parkinsonian symptoms such as akinesia and bradykinesia (sometimes reversible upon discontinuation of therapy) have been reported in postmarketing experience.

Hematologic

Hematologic side effects have been reported rarely. Cases of bone marrow suppression resulting in normocytic, normochromic anemia or thrombocytopenia have been reported. Granuloma formation and neutropenia have been reported. Agranulocytosis, hemolytic anemia, aplastic anemia, pancytopenia, neutropenia, thrombocytopenia, and granuloma have been reported in postmarketing experience.

A 45-year-old male with Wolff-Parkinson-White syndrome developed diffuse petechiae and ecchymoses associated with thrombocytopenia two weeks after beginning amiodarone. The patient's lymphocytes showed a high stimulation index using amiodarone, but not with other antiarrhythmic agents, such as quinidine. The platelet count returned to normal after amiodarone was stopped and prednisone was given. Rechallenge two months later resulted in recurrent thrombocytopenia.

A 63-year-old male with atrial fibrillation developed bone marrow granulomas after 17 months of treatment with amiodarone. The patient's course was suggestive of amiodarone-induced granulomas, although a definitive cause was not determined.

A 71-year-old male with a history of chronic lymphatic leukemia underwent amiodarone therapy after developing atrial fibrillation. Four weeks after amiodarone therapy was initiated, the patient developed neutropenia which later resolved seven days after discontinuation.

Renal

In a series of 30 consecutive patients started on amiodarone and followed for 12 months, 28 (93%) developed a mean increase in the serum creatinine of 11%. Two patients were excluded from analysis. One had previous exposure to amiodarone, which was consider a confounding variable, and one had severe congestive heart failure, which was considered the probable cause of decreased renal function in that case. No patient had renal insufficiency that warranted discontinuation of therapy. Amiodarone may alter creatinine renal tubular secretion or creatinine release by muscle. It is not known whether amiodarone affects the vascular tone of the afferent or efferent arterioles of the renal glomeruli.

Renal side effects including renal insufficiency, acute renal failure, and renal impairment have been reported in postmarketing experience.

Psychiatric

A 66-year-old male with refractory ventricular tachycardia developed psychotic delusions 17 days after beginning amiodarone therapy. The delirium persisted after the addition of benzodiazepines and when all drugs except amiodarone were discontinued. Delusions resolved one week after amiodarone was stopped. The patient subsequently did well after substitution with flecainide.

Psychiatric side effects including altered mental status, hallucinations, and delirium have been reported in postmarketing experience.

Genitourinary

A significant correlation between the development of epididymitis and prolonged therapy with high dose amiodarone has been noted in the urological literature. In one series of 56 men who were treated with amiodarone, an atypical epididymitis syndrome developed in 6, of whom 5 had bilateral scrotal swelling. The mean daily dose was 700 mg and the mean duration of amiodarone therapy at the time of presentation ranged from 7 to 15 months.

Genitourinary side effects have been reported rarely. These have included noninfectious epididymitis, testicular dysfunction, and male impotence. Epididymitis and impotence have been reported in postmarketing experience.

Metabolic

Metabolic side effects have included increased total serum cholesterol and triglycerides, decreased glucose tolerance, and increased or decreased thyroid hormone secretion.

Local

Local side effects have included thrombophlebitis.

Oncologic

Oncologic side effects have included basal cell carcinoma.

Musculoskeletal

Musculoskeletal side effects including myopathy, muscle weakness, and rhabdomyolysis have been reported in postmarketing experience.

General

Generally, checking amiodarone blood levels has limited clinical usefulness since there is wide interpatient variability in the blood amiodarone level and toxicity profile. Side effects occurred more frequently with prolonged administration (greater than 6 months) and appeared to be related to the total cumulative dose. Although as many as 80% of patients have had some side effects, discontinuation of therapy because of serious or disturbing toxicity has occurred in only 10% to 15% of patients.

Disclaimer: Every effort has been made to ensure that the information provided is accurate, up-to-date, and complete, but no guarantee is made to that effect. In addition, the drug information contained herein may be time sensitive and should not be utilized as a reference resource beyond the date hereof. This information does not endorse drugs, diagnose patients, or recommend therapy. This drug information is a reference resource designed as supplement to, and not a substitute for, the expertise, skill , knowledge, and judgement of healthcare practitioners in patient care. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug of drug combination is safe, effective, or appropriate for any given patient. Drugs.com does not assume any responsibility for any aspect of healthcare administered with the aid of information provided. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse, or pharmacist.