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.

amiodarone hydrochloride

an oral antiarrhythmic drug.
indications It is prescribed for the treatment of life-threatening recurrent ventricular fibrillation and recurrent, hemodynamically unstable ventricular tachycardia refractory to other drugs; it is not considered induction therapy because of toxicities.
contraindications This drug should not be given when patients have severe sinus-node dysfunction or second- or third-degree atrioventricular block or when episodes of bradycardia have resulted in syncope, except when used with a pacemaker. It also should not be used during pregnancy or in combination with certain other drugs such as ritonavir or certain quinolone antibiotics (e.g., sparfloxacin, moxifloxacin, gatifloxacin).
adverse effects Among the most serious adverse effects are pulmonary toxicity, liver dysfunction, nausea, vomiting, constipation, anorexia, malaise, fatigue, tremor, involuntary movements, visual disorders, bradycardia, cyanosis, and congestive heart failure.