amiodarone hydrochloride

(redirected from Cordarone X)

amiodarone hydrochloride

Amyben (UK), Cordarone, Cordarone X (UK), Nexterone, Pacerone

Pharmacologic class: Benzofuran derivative

Therapeutic class: Antiarrhythmic (class III)

Pregnancy risk category D

FDA Box Warning

Oral products

• Because of substantial toxicity, drug is indicated only in patients with life-threatening arrhythmias.

• Drug may cause potentially fatal pulmonary toxicities, including hypersensitivity pneumonitis and interstitial/alveolar pneumonitis. Pulmonary toxicity is fatal about 10% of time.

• Hepatic injury is common but usually mild, manifesting only as abnormal liver enzyme levels. However, overt hepatic disease can occur and, in rare cases, is fatal.

• Drug may exacerbate arrhythmias by reducing tolerance for them or making them harder to reverse. Arrhythmias and significant heart block or sinus bradycardia occur in 2% to 5% of patients.

• Even in patients at high risk for arrhythmic death in whom toxicity is an acceptable risk, drug poses major management problems. Therefore, other agents should be tried first whenever possible.

• Difficulty of using drug effectively and safely poses significant risk. Patients with indicated arrhythmias must be hospitalized to receive loading dose; response generally takes at least 1 week, but usually 2 or more.

Action

Prolongs duration and refractory period of action potential. Slows electrical conduction, electrical impulse generation from sinoatrial node, and conduction through accessory pathways. Also dilates blood vessels.

Availability

Injection: 50 mg/ml in 3-ml ampules

Injection, premixed in dextrose: 1.5 mg/ml (150 mg/100 ml), 1.8 mg/ml (360 mg/200 ml) in single-use plastic containers

Tablets: 100 mg, 200 mg, 400 mg

Indications and dosages

Life-threatening ventricular arrhythmias

Adults: 150 mg in 100 ml of dextrose 5% in water (D5W) by rapid I.V. infusion over 10 minutes; then dilute 900 mg in 500 ml of D5W and administer 360 mg by slow I.V. infusion over next 6 hours; then 540-mg I.V. maintenance infusion over next 18 hours. Or 800 to 1,600 mg P.O. daily in one to two doses for 1 to 3 weeks; then 600 to 800 mg P.O. daily in one to two doses for 1 month; then 400-mg P.O. daily as maintenance dosage. All dosages are titrated to individual patient's clinical needs.

Frequently recurring ventricular fibrillation (VF), hemodynamically unstable ventricular tachycardia (VT)

Adults: Initially, 1,000 mg I.V. infusion over first 24 hours, by following infusion regimen: 150 mg/100 ml (1.5 mg/ml) rapid I.V. infusion over 10 minutes, followed by 360 mg (1 mg/minute) by slow I.V. infusion over 6 hours; then 540 mg (0.5 mg/minute) by slow I.V. infusion over remaining 18 hours as maintenance infusion. For breakthrough episodes of VF or hemodynamically unstable VT, repeat initial loading dose of 150 mg/100 ml I.V. infusion over 10 minutes as needed. After first 24 hours, continue maintenance infusion of 720 mg/24 hours (0.5 mg/minute) for up to 3 weeks. Increase maintenance infusion rate to achieve effective arrhythmia suppression as needed.

Off-label uses

• Atrioventricular (AV) nodal reentry tachycardia (with parenteral use)

• Conversion of atrial fibrillation to normal sinus rhythm

Contraindications

• Hypersensitivity to drug or its components, including iodine

• Cardiogenic shock

• Second- or third-degree AV block

• Marked sinus bradycardia

• Breastfeeding

• Neonates

Precautions

Use cautiously in:

• electrolyte imbalances, severe pulmonary or hepatic disease, thyroid disorders

• history of heart failure

• elderly patients

• pregnant patients

• children.

Administration

Know that I.V. amiodarone is a high-alert drug.

Give loading dose only in hospital setting with continuous ECG monitoring.

• Administer oral loading dose in two equal doses with meals. Give maintenance dose daily or in two divided doses to minimize GI upset.

• Don't give I.V. unless patient is on continuous ECG monitoring.

• Dilute I.V. drug (except premixed drug) with dextrose 5% in water and use an in-line filter. Drug isn't compatible with normal saline solution.

• Don't combine premixed drug with any other product in the same I.V. line or premixed container.

Don't use plastic containers in series connections because of risk of air embolism.

• Use central venous catheter when giving repeated doses. If possible, use dedicated catheter for drug.

Adverse reactions

CNS: dizziness, fatigue, headache, insomnia, paresthesia, peripheral neuropathy, poor coordination, involuntary movements, tremor, sleep disturbances

CV: hypotension, heart failure, worsening arrhythmia, AV block, sinoatrial node dysfunction, bradycardia, asystole, cardiac arrest, cardiogenic shock, electromechanical dissociation, ventricular tachycardia

EENT: corneal microdeposits, corneal or macular degeneration, visual disturbances, dry eyes, eye discomfort, optic neuritis or neuropathy, scotoma, lens opacities, photophobia, visual halos, papilledema

GI: nausea, vomiting, constipation, abdominal pain, abnormal salivation, anorexia

GU: decreased libido

Hematologic: coagulation abnormalities, thrombocytopenia

Hepatic: nonspecific hepatic disorders, hepatic dysfunction

Metabolic: hypothyroidism, hyperthyroidism

Respiratory: cough, adult respiratory distress syndrome, pulmonary inflammation or fibrosis, pulmonary edema

Skin: flushing, photosensitivity, toxic epidermal necrolysis

Other: abnormal taste and smell, edema, fever, Stevens-Johnson syndrome

Interactions

Drug-drug. Anticoagulants: increased prothrombin time (PT)

Azole antifungals, fluoroquinolones, loratadine, macrolide antibiotics, trazodone: increased risk of life-threatening arrhythmias

Beta-adrenergic blockers: increased risk of bradycardia and hypotension

Calcium channel blockers: increased risk of AV block (with verapamil, diltiazem) or hypotension (with any calcium channel blocker)

Cholestyramine: decreased amiodarone blood level

Cimetidine, ritonavir: increased amiodarone blood level

Class I antiarrhythmics (disopyramide, flecainide, lidocaine, mexiletine, procainamide, quinidine): increased blood levels of these drugs, leading to toxicity

Cyclosporine: elevated cyclosporine and creatinine blood levels

Dextromethorphan: impaired dextromethorphan metabolism (with amiodarone therapy of 2 weeks or longer)

Digoxin: increased digoxin blood level, leading to toxicity

Fentanyl: increased bradycardia, hypotension

Methotrexate: impaired methotrexate metabolism, possibly causing toxicity (with amiodarone use longer than 2 weeks)

Phenytoin: decreased amiodarone blood level or increased phenytoin blood level (with amiodarone use longer than 2 weeks)

Protease inhibitors (atazanavir, indinavir, nelfinavir): possible increased amiodarone concentration

Rifampin: decreased amiodarone concentration

Theophylline: increased theophylline blood level (with amiodarone use longer than 1 week)

Drug-diagnostic tests. Kidney function tests: abnormal results

Drug-food. Grapefruit juice: increased drug concentration

Drug-herb. St. John's wort: decreased drug blood level

Patient monitoring

Monitor patient closely. Drug may cause serious or life-threatening adverse reactions.

Watch for slow onset of life-threatening arrhythmias, especially after giving loading dose.

Monitor ECG continuously during loading dose and when dosage is changed.

• Check patient's blood pressure, pulse, and heart rhythm regularly.

• Assess for signs and symptoms of lung inflammation.

• Monitor baseline and subsequent chest X-rays, as well as pulmonary, liver, and thyroid function test results.

• Closely monitor patient who's receiving other drugs concurrently because amiodarone can interact with many drugs. Check digoxin blood level if patient is receiving digoxin; monitor PT or International Normalized Ratio if patient is receiving anticoagulants.

Patient teaching

Inform patient that drug may cause serious adverse reactions. Instruct him to report these immediately.

• Tell patient to take oral doses with meals. Advise him to divide daily dose into two doses if drug causes GI upset.

• Tell patient that adverse reactions are most common with high doses and may become more frequent after 6 months of therapy.

• Inform patient that he'll undergo regular blood testing, eye examinations, chest X-rays, and pulmonary function tests during therapy.

• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs and tests mentioned above.