Amiodarone Overview
Class: Class III antiarrhythmic (potassium channel blocker)
Formulations: IV, oral tablet
Mechanism of Action
Amiodarone primarily blocks potassium channels, prolonging phase 3 repolarization and the action potential duration.
It also exhibits Class I (Na⁺ channel blockade), Class II (noncompetitive β-blocking), and Class IV (Ca²⁺ channel blockade) effects — leading to:
- Decreased sinus node automaticity
- Slowed AV conduction
- Prolonged QT interval
Net effect: Broad-spectrum control of atrial and ventricular arrhythmias.
Clinical Uses in Oncology
Commonly indicated for:
- Atrial fibrillation/flutter (especially with structural heart disease or LV dysfunction)
- Ventricular tachycardia or fibrillation, often secondary to anthracycline-induced cardiotoxicity or post-chemotherapy cardiac dysfunction
- QT control in patients with oncology-related electrolyte disturbances (e.g., due to cisplatin, diarrhea, vomiting)
Key Toxicities and Monitoring
Amiodarone has multi-system toxicity, which is crucial for oncology pharmacists who manage polypharmacy and overlapping toxicities.
| System | Major Toxicity | Monitoring / Oncology Relevance |
|---|---|---|
| Pulmonary | Interstitial pneumonitis, fibrosis | Baseline & periodic chest X-ray, pulmonary function; may mimic bleomycin-induced lung injury |
| Thyroid | Hypo-/hyperthyroidism (contains iodine) | Baseline & q6 months TSH; interferes with thyroid function altered by neck radiation or iodine contrast |
| Hepatic | Elevated transaminases, hepatitis | Baseline & periodic LFTs; risk increases with hepatotoxic chemotherapy |
| Cardiac | Bradycardia, QT prolongation, torsades (rare) | ECG monitoring; caution with other QT-prolonging oncology drugs (e.g., TKIs, ondansetron) |
| Ocular | Corneal deposits, optic neuropathy | Ophthalmologic exam if visual symptoms |
| Dermatologic | Photosensitivity, blue-gray skin discoloration | Counsel on sun protection |
- Oral bioavailability: ~30–80%
- Half-life: extremely long (25–100 days) — requires loading dose
- Metabolism: hepatic (CYP3A4, CYP2C8); active metabolite (desethylamiodarone)
- Elimination: biliary (not renally cleared)
Drug Interactions
Highly relevant in oncology practice:
- ↑ Warfarin and digoxin levels → Reduce dose and monitor INR/digoxin levels
- ↑ Serum levels of cyclosporine, tacrolimus, and some statins
- Additive QT prolongation with TKIs (dasatinib, nilotinib, vandetanib), 5-HT₃ antagonists, and fluoroquinolones
- CYP3A4 inhibitors (e.g., azoles, macrolides) → ↑ amiodarone toxicity
Typical Dosing
IV: 150 mg IV bolus over 10 min → 1 mg/min x 6 hr → 0.5 mg/min x 18 hr
Oral (for rhythm control):
- Loading: 800–1600 mg/day divided for 1–3 weeks
- Maintenance: 100–400 mg/day
(Titrate based on rhythm response and tolerance.)
Clinical Pearls for Oncology Pharmacists
- Preferable in structural heart disease or EF <40%, unlike many other antiarrhythmics.
- Use cautiously or avoid if baseline pulmonary toxicity (e.g., bleomycin, radiation).
- Monitor drug-drug interactions closely—amiodarone affects CYP3A4, CYP2C9, and P-gp substrates common in oncology (TKIs, warfarin, DOACs).
- Long half-life means adverse effects and interactions can persist for weeks after discontinuation.