Amiodarone

Antiarrhythmic (Vaughan-Williams class III), Cardiovascular agent

Amiodarone

Cordarone, Pacerone, Nexterone (IV)

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Titration strategies

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Pharmacy

Starting dose

Oral load 800-1600 mg/d in divided doses for 1-3 weeks, then 600-800 mg/d for 1 month, then 200-400 mg/d maintenance; IV 150 mg over 10 min then 1 mg/min for 6 hours then 0.5 mg/min

Preparations

100, 200, 400 mg tablets; 50 mg/mL IV (with polysorbate 80 in older formulations causing hypotension); 1.5 mg/mL Nexterone IV (PVC-free, lower hypotension risk)

US FDA Max

Oral maintenance 400 mg/d typical; higher in refractory cases

Common uses

Classification(s)

Classes

Antiarrhythmic (Vaughan-Williams class III), Cardiovascular agent

Pharmacology

Routes

Oral, IV

Onset

IV: minutes; oral: weeks to load

Duration

Weeks after discontinuation (extremely long half-life)

Half-life

~58 days (parent); ~61 days (desethylamiodarone, active metabolite)

Bioavailability

~50% (oral; highly variable)

Pregnancy

Generally avoided; fetal goiter/hypothyroidism risk (iodine load). Used only for life-threatening arrhythmia.^{[citation needed]}

Legal status

Rx-only in US. Carries Boxed Warnings for pulmonary toxicity (interstitial pneumonitis, fibrosis), hepatotoxicity, and proarrhythmia

Purported mechanism

Amiodarone is a multi-class antiarrhythmic with primary class III (K+ channel blocker, prolongs action potential and refractoriness) action plus class I (Na+ channel blocker), class II (β-adrenergic antagonist), and class IV (Ca²⁺ channel blocker) effects.▲0▼ Heavily iodinated (37% iodine by weight); cumulative tissue burden underlies the constellation of organ toxicities: pulmonary fibrosis, thyroid (hyper- or hypothyroidism), hepatic, corneal microdeposits, blue-gray skin discoloration (slate-blue, especially sun-exposed), peripheral neuropathy, optic neuropathy. Routine monitoring: TSH, LFTs, CXR/PFTs, ECG (QT). Numerous drug interactions via CYP3A4, CYP2C9, and P-gp inhibition.