Amiodarone: Uses, Indications, Dosages, Precautions, Contraindications, Side Effects & Interactions

Amiodarone

(a-mi-oh-da-rone)
Classification 
Pharmacotherapeutic: Cardiac agent
Clinical: Antiarrhythmic

Apo-Amiodarone

Nexterone

Pacerone

CATEGORY AND SCHEDULE

Pregnancy Risk Category: D

Do not confuse:

amiodarone/inamrinone, Cordarone/Inocor

General Information

Amiodarone is used to treat a variety of abnormal heart rhythms (arrhythmias). It works by slowing the nerve impulses in the heart muscle. Amiodarone is given to prevent recurrence of atrial and ventricular fibrillation and to treat ventricular and supraventricular tachycardias and Wolff-Parkinson-White syndrome. Often the last option when other treatments have failed, especially for long-term use, has serious side effects including liver damage, thyroid problems, and eye and lung damage. Treatment should only be started under the supervision of a specialist or in the hospital

Amiodarone can cause severe reactions, including: severe and life-threatening pulmonary toxicity (alveolitis, pulmonary fibrosis, pneumonia, acute respiratory distress syndrome) which may present with progressive dyspnea and cough with crackles, reduced breathing sounds, pleurisy, HF, or hepatotoxicity. It can worsen existing arrhythmias or cause new arrhythmias

Action

Prolongs action potential duration and  the effective refractory period, the non-competitive alpha and beta adrenergic inhibition; increases PR and QT intervals, decreases sinus rate, decreases peripheral vascular resistance

Therapeutic Effect

Suppresses arrhythmias

Availability (Rx)

Tablets (Cordarone): 200 mg

Tablets (Pacerone): 100 mg, 200 mg, 400 mg

Injection (Cordarone): 50 mg/mL

Uses

Hemodynamically unstable ventricular tachycardia, supraventricular tachycardia, ventricular fibrillation not controlled by 1st-line agents

Unlabeled uses: Atrial fibrillation treatment/prophylaxis, atrial flutter, cardiac arrest, cardiac surgery, CPR, heart failure, PSVT, Wolff-Parkinson-White (WPW) syndrome

Precautions

Pregnancy D, breastfeeding, neonates, severe sinus node dysfunction, hypersensitivity to this product/iodine/benzyl alcohol, cardiogenic shock, goiter, Hashimoto’s thyroiditis, electrolyte imbalances, CHF, severe respiratory disease, children, torsades de pointes

Black Box Warning: Cardiac arrhythmias, pneumonitis, pulmonary fibrosis, severe hepatic disease

Make sure to tell your doctor if:

• You have long-term liver problems

• You have heart problems

• You have eye disease

• You have a lung disorder such as asthma or bronchitis

• You have a thyroid disorder

• You are sensitive to iodine

• You are taking other medicines

Indications and Dosages

‣ To Treat life-threatening recurrent ventricular fibrillation or hemodynamically unstable ventricular tachycardia

PO

• Adults, Elderly: Initially, load with (unless patient has been on IV treatment) 800-1600 mg/day in 2-4 divided doses for 1-3 wks. After arrhythmia is controlled or side effects occur, reduce to 600-800 mg/ day for about 4 wks. Maintenance:

200-600 mg/day with a usual maintenance dose of 400 mg/day

IV

Adults: Initially, 150 mg over 10 min (15 mg/min), then 360 mg over 6 h; then 540 mg over 18 h. May continue at 0.5 mg/min. After first 24 hrs, infuse 720 mg/24 hrs (0.5 mg/min) with a concentration of 1–6 mg/mL

‣ Dosage in Renal Impairment

• No dose adjustment

‣ Dosage in Hepatic Impairment

• Use caution

Pharmacokinetics

Slowly, variably absorbed from GI tract; oral bioavailability is 35%-65%. Protein binding: 96%. Extensively metabolized by CYP3A4 and CYP2C8 to active metabolite. Excreted via bile; not removed by hemodialysis. Half-life: 26-107 days; metabolite, 61 days

Implementation

Start with patient hospitalized and monitored

PO route

• Give reduced dosage slowly with ECG monitoring only

• Loading dose with food to decrease nausea

IV, direct route

• Peripheral: max 2 mg/ml for longer than 1 hr; preferred through central venous line with in-line filter; concentration .2 mg/ml should be given by central line

• Cardiac arrest: give 300 mg bol diluted to a total volume of 20 ml D5W; may repeat 150 mg after 3-5 min

Intermittent IV INF route

• Rapid loading: add 3 ml (150 mg), 100 ml D5W (1.5 mg/ml), give over 10 min

• Slow loading: add 18 ml (900 mg), 500 ml D5W (1.8 mg/ml), give over next 6 hr

Continuous IV infusion route

• After 24 hr, dilute 50 ml to 1-6 mg/ml, give 1-6 mg/ml at 1 mg/ml for the first 6 hr, then 0.5 mg/min

Contraindications

Bradycardia-induced syncope (except in the presence of a pacemaker), cardiogenic shock, second- and third-degree AV block, severe hepatic disease, severe sinus-node dysfunction; hypersensitivity to amiodarone or its components, including iodine

Cautions: May prolong QT interval. Thyroid disease, electrolyte imbalance, hepatic disease, hypotension, left ventricular dysfunction, pulmonary disease. Pts taking warfarin, surgical pts

Interactions

Individual drugs

• Sofosbuvir: increased severe bradycardia

• Thioridazine: concentration and produce additive prolongation of QT interval

• Carvedilol, labetalol, metoprolol, warfarin: May increase effect of beta
blockers, closely monitor International Normalized Ratio 

• ARIPiprazole, colchicine, digoxin, phenytoin: increased concentration, increased toxicity

• Simvastatin: Increased risk of myopathy/rhabdomyolysis; limit simvastatin dose to 20 mg/day

• Lovastatin: Increased risk of myopathy/rhabdomyolysis; limit lovastatin dose to 40 mg/day

• Cyclosporine: Increased cyclosporine concentrations

Drug classifications

• Antiarrhythmics: May increase cardiac effects

• Azoles, fluoroquinolones, macrolides: increased QT prolongation. Risk of cardiac arrhythmias, including torsades de pointes, may be increased 

• b-Adrenergic blockers, calcium channel blockers: increased bradycardia

• Class I antidysrhythmics: increased levels HMG-CoA reductase inhibitors: increased myopathy

• Protease inhibitors: increased amiodarone concentrations, possible serious dysrhythmias, reduce dose

Drug/laboratory tests

• May increase serum ALT, AST, alkaline phosphatase, ANA titer. May cause changes in EKG, thyroid function test results

• Therapeutic serum level: 0.5–2.5 mcg/mL; toxic serum level not established

Drugs/food

• Grapefruit products may alter effect

Herbal

• St. John’s wort may decrease effect

• Ephedra may worsen arrhythmia. Herbals with hypotensive properties may increase levels/effects of amiodarone

Side effects

• CNS: Abnormal gait, ataxia, confusion, delirium, demyelinating polyneuropathy,

disorientation, dizziness, fatigue, fever, hallucinations, headache, insomnia, involuntary motor activity, lack of coordination, malaise, paresthesia, parkinsonian symptoms, peripheral neuropathy, pseudotumor cerebri, sleep disturbances, tremor

• CV: Arrhythmias (including bradycardia, electromechanical dissociation, torsades de pointes, and ventricular tachycardia or fibrillation), cardiac arrest, cardiogenic shock, edema, heart failure, hypotension, vasculitis

• EENT: Abnormal salivation, abnormal taste and smell, blurred vision, corneal microdeposits, dry eyes, halo vision, lens opacities, macular degeneration, optic neuritis, optic neuropathy, papilledema, permanent blindness, photophobia, scotoma

• ENDO: Hyperthyroidism, hypothyroidism, syndrome of inappropriate ADH secretion, thyroid cancer

• GI: Abdominal pain, anorexia, cirrhosis, constipation, diarrhea, elevated liver function test results, hepatitis, nausea, pancreatitis, vomiting

• GU: Acute renal failure, decreased libido, epididymitis, impotence

• HEME: Agranulocytosis, aplastic or hemolytic anemia, coagulation abnormalities, neutropenia, pancytopenia, spontaneous bruising, thrombocytopenia

• MS: Muscle weakness, myopathy, rhabdomyolysis

• RESP: Acute respiratory distress syndrome; bronchospasm; eosinophilic pneumonia; infiltrates that lead to dyspnea, cough, hemoptysis, hypoxia, pulmonary fibrosis, pulmonary alveolar hemorrhage, pulmonary interstitial pneumonitis, crackles, and wheezing; pleural effusion; pleuritis; pneumonia; respiratory arrest or failure

• SKIN: Alopecia, bluish gray pigmentation, eczema, erythema multiforme, exfoliative dermatitis, flushing, photosensitivity, pruritus, rash, skin cancer, Stevens-Johnson syndrome, toxic epidermal necrolysis, urticaria

• Other: Anaphylactic shock, angioedema

 

Nursing considerations

Baseline assessment

• Obtain baseline serum ALT, AST, alkaline phosphatase, EKG; pulmonary

function tests, CXR in pts with pulmonary disease

• Assess B/P, apical pulse immediately before drug is administered (if pulse is 60/min or less or systolic B/P is less than 90 mm Hg, withhold medication, contact physician)

Intervention/evaluation

• Monitor for symptoms of pulmonary toxicity (progressively worsening dyspnea,

cough). Dosage should be discontinued or reduced if toxicity occurs

• Assess pulse for quality, rhythm, bradycardia

Monitor EKG for cardiac changes (e.g., widening of QRS, prolongation of PR and QT intervals)

• Notify physician of any significant interval changes

• Assess for nausea, fatigue, paresthesia, tremor

• Monitor for signs of hypothyroidism (periorbital edema, lethargy, pudgy hands/feet, cool/pale skin, vertigo, night cramps) and hyperthyroidism (hot/dry skin, bulging eyes [exophthalmos], frequent urination, eyelid edema, weight loss, difficulty breathing)

• Monitor serum ALT, AST, alkaline phosphatase for evidence of hepatic toxicity. 

• Assess skin, cornea for bluish discoloration in pts who have been on drug therapy longer than 2 mos

• Monitor thyroid function test results. If elevated hepatic enzymes occur, dosage reduction or discontinuation is necessary

• Monitor for therapeutic serum level (0.5–2.5 mcg/mL). Toxic serum level not established

Equipment must be available for anaphylaxis

• Monitor electrolytes: potassium, sodium, chloride

• Monitor chest x-ray, thyroid function tests

• Monitor liver function studies: AST, ALT, bilirubin, alkaline phosphatase

• Monitor ECG continuously to determine product effectiveness; measure PR, QRS, QT intervals; check for PVCs, other dysrhythmias; monitor B/P continuously

for hypo/hypertension; check for rebound hypertension after 1-2 hr

• Monitor for dehydration or hypovolemia, monitor PT, INR if using warfarin

• Assess for CNS symptoms: confusion, psychosis, numbness, depression, involuntary movements; if these occur, product should be discontinued

• Assess for hypothyroidism: lethargy, dizziness, constipation, enlarged thyroid gland, edema of extremities, cool, pale skin

• Monitor hyperthyroidism: restlessness, tachycardia, eyelid puffiness, weight loss, frequent urination, menstrual irregularities, dyspnea, warm, moist skin

• Assess for pulmonary toxicity including ARDS, pulmonary fibrosis: dyspnea, fatigue, cough, fever, chest pain; product should be discontinued if these occur, increased at higher doses, toxicity is common

• Monitor cardiac rate, respiration: rate, rhythm, character, chest pain, ventricular tachycardia, supraventricular tachycardia or fibrillation

• Assess sight and vision before treatment and throughout therapy; microdeposits on the cornea may cause blurred vision, halos, and photophobia, to prevent corneal deposits use methylcellulose

Evaluation

Positive therapeutic result

• Decreased ventricular tachycardia

• Decreased supraventricular tachycardia or fibrillation

Patient/family teaching

• Instruct patient to report side effects immediately to prescriber; more common at high dose NO

• Instruct patient to bluish skin discoloration gradually disappears when drug is discontinued

• Instruct patient to report shortness of breath, cough

• Instruct patient to outpatients should monitor pulse before taking medication

• Advice patient to do not abruptly discontinue medication

• Tell patient to protect against photosensitivity reaction on skin exposed to sunlight

• Tell patient to report any vision changes, signs/symptoms of cardiac arrhythmias

• Instruct patient to complete follow-up appointment with health care provider including pulmonary function studies, chest x-ray, ophthalmic examinations

• Tell patient to compliance with therapy regimen is essential to control arrhythmias

• Advice patient to restrict salt, alcohol intake

• Advice patient to avoid grapefruit products

Treatment of Overdose:

Administer O2, artificial ventilation, ECG, DOPamine for circulatory depression, diazepam or thiopental for seizures, isoproterenol