Amiodarone - Cordarone Flashcards
Antiarrhythmic class
Predominantly Class III
Mechanism of action
- ↑ myocardial cell action potential duration and refractory period
- Alpha- and b-adrenergic inhibition
Indications
Second-line therapy for:
- Recurrent VF
- Recurrent hemodynamically unstable VT AF
Guidelines recommend oral amiodarone as a possible 2nd-line therapy for rate control or rhythm control but warn about potential toxicities and drug interactions with long-term use
Oral Dosing Strengths
200 mg
Dosing
• Uniform, optimal dose not determined; titration suggested
— Lowest effective dose important to minimize AEs (monitor closely for extended period when adjusting dose)
• PI provides dosage for VA only:
— LD: 800–1600 mg for 1 to 3 weeks, then 600–800 mg for 1 month, then 400 mg maintenance dose
• AF guidelines recommendation for oral amiodarone: — For rate control: 100-200 mg QD (after an IV loading dose)
— For rhythm control: 400–600 mg daily in divided doses for 2-4 wk; maintenance typically 100-200 mg QD
No adjustment based on renal insufficiency or hepatic insufficiency
Treatment setting
• Loading Dose in hospital facility with continuous ECG and electrophysiologic techniques available
Monitoring requirements at initiation
• In-hospital cardiac monitoring during LD
Pharmacokinetics
• ~Dose proportional
Bioavailability/ absorption
- ~ 50% • Maximum plasma levels at 3–7 hours
- Food increases absorption
- In absence of LD, steady state between 130 and 535 days
Half-life
58 Days
Protein binding
~96%
Metabolism
• Primarily hepatic and biliary: CYP3A4, CYP2C8
Major active metabolite
• Desethylamiodarone (DEA)
— Accumulates in tissues
— Plasma terminal elimination half-life ~36 days
— Class III effects correlate with DEA levels more than with amiodarone levels
Route of elimination
• Hepatic metabolism and biliary excretion
Overdosage
- Fatal cases of amiodarone overdosage have occurred
- Monitor cardiac rhythm and BP
- Bradycardia (treat with b-adrenergic agent or pacemaker)
- Hypotension (treat with inotropic and/ or vasopressor agents)
Contraindications
- Cardiogenic shock
- Severe sinus-node dysfunction causing sinus bradycardia
- 2nd- and 3rd-degree AV block
- Bradycardia causing syncope (except with pacemaker)
- Hypersensitivity to drug, iodine, or any components
- Surgery with most corneal laser surgery devices
Boxed Warning
- Use only in life-threatening arrhythmias because of toxicity
- Fatal toxicities
— Pulmonary toxicity
— Liver injury
— Exacerbation of arrhythmia
- Life threatening in population at risk for sudden death • LD in hospital
- Switching to other AADs may be problematic due to prolonged amiodarone accumulation
Warnings(except boxed warning—see above)
Warnings
• May cause pulmonary toxicity
— Hypersensitivity pneumonitis
— Interstitial/alveolar pneumonitis
- May cause worsened arrhythmia, TdP, bradycardia, or sinus arrest
- Use with implantable cardiac devices may affect pacing
- May cause thyrotoxicosis; some reports of death
- May cause liver injury
- May cause loss of vision
- May cause fetal harm; neonatal hypothyroidism or hyperthyroidism
Precautions
• Amiodarone may cause Optic neuropathy or neuritis •Corneal microdeposits Peripheral neuropathy •Photosensitivity Thyroid abnormalities (may persist for months after discontinuation)
- Hypothyroidism
- Hyperthyroidism
- In surgery, amiodarone may cause General anesthesia sensitivity Hypotension post bypass Postoperative ARDS
- Contraindicated with most corneal refractive laser surgery devices
- Advise patient to read medication guide
- Monitor liver enzymes
Drug interactions
• CYP3A4 inhibitors may ↑ serum amiodarone:
— Protease inhibitors (indinavir)
— Histamine antagonists (loratadine, cimetidine)
— Antidepressants (trazodone)
— Grapefruit juice
• Drugs that are substrates of CYP1A2, CYP2C9, CYP2D6, CYP3A4, or P-gP may be affected by amiodarone:
— Immunosuppressives (cyclosporine)
— HMG-CoA reductase inhibitors
— Digoxin
— Other antiarrhythmics (quinidine, procainamide, phenytoin)
— b-blockers (propranolol)
— CCBs (verapamil, diltiazem)
— Anticoagulants (warfarin, clopidogrel)
• CYP3A4 inducers may ↓ amiodarone serum levels:
— Rifampin
— Herbal preparations (St John’s wort)
• Other interactions:
— Fentanyl
— Lidocaine
— Dextromethorphan
— Cholestyramine
— Disopyramide
— Fluoroquinolones, macrolide antibiotics, azoles
— General anesthetic agents
— Drugs that induce hypokalemia or hypomagnesemia
• Drug–laboratory tests: — Alters thyroid-function test results
Adverse Reactions
- Most serious AEs: pulmonary toxicity, exacerbation of arrhythmia, rare serious liver injury
- Common events: neurologic (20%– 40%), GI (25%), corneal microdeposits (virtually all after 6 months’ therapy), dermatologic (15%)
- Safety evaluated in 241 patients given amiodarone — AEs in 10% to 33%
■■ Nausea and vomiting
— AEs in 4% to 9%
■■ Solar dermatitis/photosensitivity
■■ Malaise and fatigue, tremor/ involuntary movements, lack of coordination, abnormal gait/ ataxia, dizziness, paresthesias
■■ Constipation, anorexia
■■ Visual disturbances
■■ Abnormal liver function tests
■■ Pulmonary inflammation or fibrosis — AEs in 1% to 3%
■■ Hypothyroidism, hyperthyroidism
■■ Decreased libido, insomnia, headache, sleep disturbances
■■ CHF, cardiac arrhythmias, SA node dysfunction
■■ Abdominal pain
■■ Hepatic disorders
