Amiodarone Hydrochloride

Amiodarone Hydrochloride is used for: Ventricular arrhythmias, Ventricular fibrillation, Ventricular tachycardia, Atrial fibrillation, Hypertrophic cardiomyopathy, Supraventricular arrhythmias

Ventricular Arrhythmias PO Load: 800-1600 mg PO qDay for 1-3 weeks until response; once adequate arrhythmia control achieved, reduce dose to 600-800 mg/day for 1 mo; THEN reduce to maintenance dose Maintenance dose: 400 mg PO qDay IV 150 mg over first 10 min (15mg/min), followed by 360 mg over next 6 hr (1 mg/min), THEN 540 mg over remaining 18 hr (0.5 mg/min), for a total of 1000 mg over 24 hr before administering maintenance infusion Maintenance: 0.5 mg/min for a total 720 mg/24hr at a concentration of 1-6 mg/mL (360 mg/200mL), or 1.8 mg/mL Nexterone at rate of 278 mL/min Duration of therapy: May continue to administer 0.5 mg/min for 2-3 weeks regardless of patient's age, renal function or ventricular function Lower doses may be used for supraventricular arrhythmias. Daily doses may be divided. Close monitoring of the patient is recommended. Use the minimum effective dose. Elderly: Recommended to start dosing at the lower end of the dosing range because elderly may be predisposed to toxicity. Hepatic impairment: Dosage reduction may be necessary.

May be taken with or without food. Take consistently w/ or w/o meals. Take w/ meals if high dose or to reduce GI discomfort. Reconstitution: To make solution for 1st rapid loading infusion or supplemental infusion: Add 3 ml of amiodarone HCl concentrate (50 mg/ml) to 100 ml of dextrose 5% to give a final conc of 1.5 g/ml; for slow infusion: Add 18 ml of amiodarone HCl concentrate (50 mg/ml) to 500 ml of dextrose 5% to give a final conc of 1.8 mg/ml; for subsequent maintenance infusions, diluted solutions with conc ranging from 1-6 mg/ml may be used. Solutions with conc ?2 mg/ml should be administered via a central venous catheter.

Hypersensitivity to amiodarone or iodine. Severe sinus node dysfunction, 2nd and 3rd degree heart block (except in patients with a functioning artificial pacemaker), cardiogenic shock, pregnancy.

Close monitoring is recommended as amiodarone may worsen arrhythmia especially when used concurrently with other anti-arrhythmic drugs or drugs that prolong QT interval. May cause hypotension and bradycardia. May increase risk of liver toxicity. May cause visual disturbance/impairment; corneal refractive laser surgery is not recommended in patients on amiodarone treatment. May cause lung damage; monitor for pulmonary toxicity e.g. acute respiratory distress syndrome. Monitor liver functions regularly. May affect defibrillation or pacing thresholds of cardiac devices. Correct electrolyte imbalance before starting treatment. Caution when used in patients undergoing surgery. Avoid excessive sunlight exposure due to increased risk of photosensitivity. Hepatic impairment, thyroid disease, elderly. Lactation. Lactation: Excreted into breast milk; not recommended

Pregnancy Amiodarone can cause fetal harm when administered to a pregnant woman; fetal exposure may increase potential for adverse experiences including cardiac, thyroid, neurodevelopmental, neurological and growth effects in neonate; inform patient of potential hazard to fetus if amiodarone administered during pregnancy or if patient becomes pregnant while in therapy The incidence of ventricular tachycardia is increased and may be more symptomatic during pregnancy; ventricular arrhythmias most often occur in pregnant women with underlying cardiomyopathy, congenital heart disease, valvular heart disease, or mitral valve prolapse; most tachycardia episodes are initiated by ectopic beats and occurrence of arrhythmia episodes may therefore, increase during pregnancy due to increased propensity to ectopic activity; breakthrough arrhythmias may also occur during pregnancy, as therapeutic treatment levels may be difficult to maintain due to increased volume of distribution and increased drug metabolism inherent in pregnant state Amiodarone and its metabolite have been shown to cross the placenta; adverse fetal effects associated with maternal amiodarone use during pregnancy may include neonatal bradycardia, QT prolongation, and periodic ventricular extrasystoles, neonatal hypothyroidism (with or without goiter) detected antenatally or in the newborn and reported even after a few days of exposure, neonatal hyperthyroxinemia, neurodevelopmental abnormalities independent of thyroid function, including speech delay and difficulties with written language and arithmetic, delayed motor development, and ataxia, jerk nystagmus with synchronous head titubation, fetal growth restriction, and premature birth; monitor newborn for signs and symptoms of thyroid disorder and cardiac arrhythmias Labor and delivery Risk of arrhythmias may increase during labor and delivery; patients treated should be monitored continuously during labor and delivery Infertility Based on animal fertility studies, drug may reduce female and male fertility; not known if this effect is reversible Lactation Amiodarone and one of its major metabolites, DEA, are excreted in human milk, suggesting that breast-feeding could expose the nursing infant to a significant dose of the drug; risk of exposing infant to amiodarone and DEA must be weighed against potential benefit of arrhythmia suppression in the mother; advise mother to discontinue nursing There are cases of hypothyroidism and bradycardia in breastfed infants, although it is unclear if these effects are due to amiodarone exposure in breastmilk; breastfeeding is not recommended during treatment

Potentiation of antiarrhythmic drugs. Possible increased risk of adverse effects when used with anaesthetic agents. Monitor plasma levels of amiodarone when used with HIV protease inhibitors. Cimetidine may increase serum levels of amiodarone. Concurrent use may increase serum levels of ciclosporin. May increase risk of myopathy or rhabdomyolysis when used with HMG-CoA reductase inhibitors. Rifampin may reduce the serum levels of amiodarone. Potentially Fatal: Potentiates the effect of warfarin and other anticoagulants hence dose of warfarin generally needs to be reduced approx half. Raised plasma concentrations of digoxin, phenytoin and quinidine. Additive effect with beta-blockers and calcium-channel blockers (e.g. verapamil and diltiazem).

Side effects of Amiodarone Hydrochloride : >10% Increased liver AST or ALT levels (3-20%; as high as 40-50% in some studies), Hypotension (16%), Dizziness (3-40%), Headache (3-40%), Malaise (3-40%), Abnormal gait/ataxia (3-40%), Fatigue (3-40%), Impaired memory (3-40%), Involuntary movement (3-40%), Sleep disturbances (3-40%), Photosensitivity (10-75%), Hypothyroidism (1-22%), Constipation (10-33%), Anorexia (10-33%) 1-10% CHF (3%), Bradycardia (3-5%), AV block (5%), SA node dysfunction (1-3%), Hyperthyroidism (3-10%), Hepatitis and cirrhosis (<3%), Visual disturbances (2-9%), Optic neuritis (1%) Frequency Not Defined Corneal microdeposits, Demyelinating polyneuropathy Potentially Fatal: Pulmonary toxicity including pulmonary fibrosis and interstitial pneumonitis, hepatotoxicity, thyrotoxicity. Ventricular arrhythmias, pulmonary alveolitis, exacerbation of arrhythmias and rare serious liver injury. Generally in patients with high doses and having preexisting abnormalities of diffusion capacity.

Amiodarone is a class III antiarrhythmic agent which inhibits stimulation, prolongs action potential and refractory period in myocardial tissues. It also decreases AV conduction and sinus node function. Sinus rate is reduced by 15-20%, PR and QT intervals are increased. Amiodarone can cause marked sinus bradycardia or sinus arrest and heart block. In acute IV doses, amiodarone may exert a mild negative inotropic effect.