AMIODARONE HYDROCHLORIDE

AMIODARONE HYDROCHLORIDe (a-mee'oh-da-rone) Cordarone, Amio-Aqueous, Pacerone Classifications: antiarrhythmic, class iii; Therapeutic: antiarrhythmic, class iii; antianginal Pregnancy Category: D

Availability

200 mg tablets; 50 mg/mL injection

Action

Class III antiarrhythmic; also has antianginal and antiadrenergic properties. Acts directly on all cardiac tissues by prolonging duration of action potential and refractory period without significantly affecting resting membrane potential.

Therapeutic Effect

By direct action on smooth muscle, decreases peripheral resistance and increases coronary blood flow. Blocks effects of sympathetic stimulation.

Uses

Prophylaxis and treatment of life-threatening ventricular arrhythmias and supraventricular arrhythmias, particularly with atrial fibrillation.

Unlabeled Uses

Treatment of nonexertional angina, conversion of atrial fibrillation to normal sinus rhythm, paroxysmal supraventricular tachycardia, ventricular rate control due to accessory pathway conduction in pre-excited atrial arrhythmia, after defibrillation and epinephrine in cardiac arrest, AV nodal reentry tachycardia.

Contraindications

Hypersensitivity to amiodarone, or benzyl alcohol; cardiogenic shock, severe sinus bradycardia, advanced AV block unless a pacemaker is available, severe sinus-node dysfunction or sick sinus syndrome, bradycardia, congenital or acquired QR prolongation syndromes, or history of torsade de pointes; severe liver disease, pregnancy (category D), lactation.

Cautious Use

Hepatic disease, cirrhosis; Hashimoto's thyroiditis, goiter, thyrotoxicosis, or history of other thyroid dysfunction; CHF, left ventricular dysfunction; hypersensitivity to iodine; older adults; Fabry disease, especially with visual disturbances; electrolyte imbalance, hypokalemia, hypomagnesemia, hypovolemia; preexisting lung disease, COPD; open heart surgery.

Route & Dosage

Arrhythmias Adult: PO Loading Dose 800–1600 mg/d in 1–2 doses for 1–3  wk PO Maintenance Dose 400–600 mg/d in 1–2 doses IV Loading Dose 150 mg over 10 min followed by 360 mg over next 6 h IV Maintenance Dose 540 mg over 18 h (0.5 mg/min), may continue at 0.5 mg/min Convert IV to PO Duration of infusion <1 wk use 800–1600 mg PO, 1–3 wk use 600–800 mg PO, >3 wk use 400 mg PO Child: IV 5 mg/kg then repeat to max of 300 mg total Hepatic Impairment Adjustment only suggested in severe hepatic impairment.

Administration

• Note: Correct hypokalemia and hypomagnesemia prior to initiation of therapy.

Oral

• Give consistently with respect to meals.
• Note: Only a physician experienced with the drug and treatment of life-threatening arrhythmias should give loading doses.
• Note: GI symptoms commonly occur during high-dose therapy, especially with loading doses. Symptoms usually respond to dose reduction or divided dose given with food, including milk.

Intravenous PREPARE: IV Infusion: First rapid loading dose infusion: Add 150 mg (3 mL) amiodarone to 100 mL D5W to yield 1.5 mg/mL.  Second infusion during first 24 h (slow loading dose and maintenance infusion): Add 900 mg (18 mL) amiodarone to 500 mL D5W to yield 1.8 mg/mL.  Maintenance infusions after the first 24 h: Prepare concentrations of 1–6 mg/mL amiodarone. Note: Use central line to give concentrations >2 mg/mL.   ADMINISTER: IV Infusion: Rapidly infuse initial 150 mg dose over the first 10 min at a rate of 15 mg/min. Over next 6 h, infuse 360 mg at a rate of 1 mg/min. Over the remaining 18 h, infuse 540 mg at a rate of 0.5 mg/min. After the first 24 h, infuse maintenance doses of 720 mg/24 h at a rate of 0.5 mg/min.   INCOMPATIBILITIES Solution/additive: Aminophylline, cefazolin, furosemide, quinidine. Y-site: Aminophylline, ampicillin/sulbactam, argatroban, bivalirudin, cefamandole, cefazolin, ceftazidime, digoxin, drotrecogin, heparin, imipenem/cilastatin, magnesium sulfate, piperacillin, piperacillin/tazobactam, potassium phosphate, sodium bicarbonate, sodium nitroprusside, sodium phosphate.

• Store at 15°–30° C (59°–86° F) protected from light, unless otherwise directed.

Adverse Effects (≥1%)

CNS: Peripheral neuropathy (muscle weakness, wasting numbness, tingling), fatigue, abnormal gait, dyskinesias, dizziness, paresthesia, headache. CV: Bradycardia, hypotension (IV), sinus arrest, cardiogenic shock, CHF, arrhythmias; AV block. Special Senses: Corneal microdeposits, blurred vision, optic neuritis, optic neuropathy, permanent blindness, corneal degeneration, macular degeneration, photosensitivity. GI: Anorexia, nausea, vomiting, constipation, hepatotoxicity. Metabolic: Hyperthyroidism or hypothyroidism; may cause neonatal hypo- or hyperthyroidism if taken during pregnancy. Respiratory: (Pulmonary toxicity) Alveolitis, pneumonitis (fever, dry cough, dyspnea), interstitial pulmonary fibrosis, fatal gasping syndrome with IV in children. Skin: Slate-blue pigmentation, photosensitivity, rash. Other: With chronic use, angioedema.

Interactions

Drug: Significantly increases digoxin levels; enhances pharmacologic effects and toxicities of disopyramide, procainamide, quinidine, flecainide, lidocaine, lovastatin, simvastatin; anticoagulant effects of oral anticoagulants enhanced; verapamil, diltiazem, beta-adrenergic blocking agents may potentiate sinus bradycardia, sinus arrest, or AV block; may increase phenytoin levels 2- to 3-fold; cholestyramine may decrease amiodarone levels; fentanyl may cause bradycardia, hypotension, or decreased output; may increase cyclosporine levels and toxicity; cimetidine may increase amiodarone levels; ritonavir may increase risk of amiodarone toxicity, including cardiotoxicity. Herbal: Echinacea possible increase in hepatotoxicity.

Pharmacokinetics

Absorption: 22–86% absorbed. Onset: 2–3 d to 1–3 wk. Peak: 3–7 h. Distribution: Concentrates in adipose tissue, lungs, kidneys, spleen; crosses placenta. Metabolism: Extensively in liver; undergoes some enterohepatic cycling; via CYP2C8 and 3A4. Elimination: Excreted chiefly in bile and feces; also in breast milk. Half-Life: Biphasic, initial 2.5–10 d, terminal 40–55 d.

Nursing Implications

Assessment & Drug Effects

• Monitor BP carefully during infusion and slow the infusion if significant hypotension occurs; bradycardia should be treated by slowing the infusion or discontinuing if necessary. Monitor heart rate and rhythm and BP until drug response has stabilized; report promptly symptomatic bradycardia. Sustained monitoring is essential because drug has an unusually long half-life.
• Monitor for S&S of: Adverse effects, particularly conduction disturbances and exacerbation of arrhythmias, in patients receiving concomitant antiarrhythmic therapy (reduce dosage of previous agent by 30–50% several days after amiodarone therapy is started); drug-induced hypothyroidism or hyperthyroidism (see Appendix F), especially during early treatment period; pulmonary toxicity (progressive dyspnea, fatigue, cough, pleuritic pain, fever) throughout therapy.
• Lab tests: Baseline and periodic assessments should be made of liver, lung, thyroid, neurologic, and GI function. Drug may cause thyroid function test abnormalities in the absence of thyroid function impairment.
• Monitor for elevations of AST and ALT. If elevations persist or if they are 2–3 times above normal baseline readings, reduce dosage or withdraw drug promptly to prevent hepatotoxicity and liver damage.
• Auscultate chest periodically or when patient complains of respiratory symptoms. Check for diminished breath sounds, rales, pleuritic friction rub; observe breathing pattern. Drug-induced pulmonary function problems must be distinguished from CHF or pneumonia. Keep physician informed.
• Anticipate possible CNS symptoms within a week after amiodarone therapy begins. Proximal muscle weakness, a common side effect, intensified by tremors presents a great hazard to the ambulating patient. Assess severity of symptoms. Supervision of ambulation may be indicated.

Patient & Family Education

• Check pulse daily once stabilized, or as prescribed. Report a pulse <60.
• Take oral drug consistently with respect to meals.
• Become familiar with potential adverse reactions and report those that are bothersome to the physician.
• Use dark glasses to ease photophobia; some patients may not be able to go outdoors in the daytime even with such protection.
• Follow recommendation for regular ophthalmic exams, including funduscopy and slit-lamp exam.
• Wear protective clothing and a barrier-type sunscreen that physically blocks penetration of skin by ultraviolet light (e.g., titanium oxide or zinc formulations) to prevent a photosensitivity reaction (erythema, pruritus); avoid exposure to sun and sunlamps.

---

Common adverse effects in italic, life-threatening effects underlined; generic names in bold; classifications in SMALL CAPS; Canadian drug name; Prototype drug