Amiron

Amiodarone hydrochloride.

Each uncoated tablet contains: Amiodarone Hydrochloride BP 200 mg.

Pharmacotherapeutic group: Amiodarone hydrochloride is an antiarrhythmic.
Pharmacology: Pharmacokinetics: Amiodarone is absorbed variably and erratically from the gastrointestinal tract. It is extensively distributed to body tissues and accumulates notably in muscle and fat; it has been reported to be about 96% bound to plasma proteins. The terminal elimination half-life is about 50 days with a range of about 20 to 100 days due to its extensive tissue distribution.
A major metabolite has antiarrhythmic properties. There is very little urinary excretion of Amiodarone or its metabolites, the major route of excretion being in faeces via the bile; some enterohepatic recycling may occur. Amiodarone and desethylamiodarone are reported to cross the placenta and to be distributed into the breast milk. After intravenous injection, the maximum effect is achieved within 1 to 30 minutes and persists for 1 to 3 hours.

Prevention of tachyarrhythmias associated with Wolff-Parkinson-White syndrome and other types of tachyarrhythmias of paroxysmal nature, including supraventricular, nodal and ventricular tachycardia, atrial flutter and atrial fibrillation and ventricular fibrillation, when other medicines cannot be used.

The minimum effective dose should be used at all times. Dosage should be adjusted according to individual patient's response and well being. The following dosage regimen is generally effective.
Initial stabilization: initiate treatment with 200 mg three times daily for one week. Reduce this dosage to 200 mg twice daily.
Maintenance: following the initial stabilization period, the dosage should be reduced to 200 mg daily, or less, if appropriate. The scored 100 mg tablet should be used to titrate the minimum dosage. The maintenance dose should be regularly reviewed, especially when this exceeds 200 mg daily.
Or as prescribed by the physician.
Pediatric population: No controlled paediatric studies have been undertaken.
In published studies, the safety of Amiodarone was evaluated in 1118 pediatric patients with various arrhythmias.
The following doses were used in pediatric clinical trials.
Oral: Loading dose: 10 to 20 mg/kg/day for 7 to 10 days (or 500 mg/m²/day if expressed per square meter).
Maintenance dose: The minimum effective dosage should be used; according to individual response, it may range between 5 to 10 mg/kg/day (or 250 mg/m²/day if expressed per square meter).
Intravenous: Loading dose: 5 mg/kg body weight over 20 minutes to 2 hours.
Maintenance dose: 10 to 15 mg/kg/day from a few hours to several days.
If needed, oral therapy may be initiated concomitantly at the usual loading dose.

Overdosage may lead to severe bradycardia and to conduction disturbances with the appearance of an idioventricular rhythm, particularly in elderly patients or during digitalis therapy. In these circumstances, Amiodarone therapy should be withdrawn. Gastric lavage may be employed to reduce absorption, in addition to general supportive measures. Patients should be monitored and if bradycardia ensues, beta adrenostimulants or glucagon may be given. Spontaneously resolving attacks of ventricular tachycardia may also occur. Due to the pharmacokinetics of Amiodarone, adequate and prolonged surveillance of the patient, particularly cardiac status, is recommended.

Amiodarone is contraindicated in patients with sinus bradycardia and sinoatrial heart block. Amiodarone should be used only in conjunction with a pacemaker when treating patients with severe conduction disturbances (e.g. high grade AV block, bifascicular or trifascicular block). Amiodarone is contraindicated in patients with evidence or history of thyroid dysfunction. Since Amiodarone contains iodine, it should be avoided in patients with severe respiratory failure. Amiodarone may induce erratic results from thyroid function tests. Too high of a dosage may lead to severe bradycardia and to conduction disturbances with the appearance of idioventricular rhythm, particularly in elderly patients or during digitalis therapy. In these circumstances therapy should be withdraw. If necessary, beta adrenal stimulants or glucagon may be given. Amiodarone is not contraindicated in patients with latent or manifest heart failure, but caution should be exercised as existing heart failure may be worsened by Amiodarone. Amiodarone is contraindicated during pregnancy and lactation.

Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this drug. Amiodarone is intended for use only in patients with indicated life-threatening arrhythmias because its use is accompanied by substantial toxicity.

Pregnancy: There are insufficient data on the use of Amiodarone during pregnancy in humans to judge any possible toxicity.
However, in view of its effect on the fetal thyroid gland, Amiodarone is contraindicated during pregnancy, except in exceptional circumstances.
If, because of the long half-life of Amiodarone, discontinuation of the drug is considered prior to planned conception, the real risk of reoccurrence of life-threatening arrhythmias should be weighed against the possible hazard for the fetus.
Lactation: Amiodarone is excreted into the breast milk in significant quantities and breastfeeding is contraindicated.

Ophthalmological: Bradycardia that was generally moderate has been reported. Impaired visual acuity due to optic neuritis has been observed.
Cardiac: Bradycardia that was generally moderate and dose-dependent has been reported. In some cases (sinus node disease, elderly patients), marked bradycardia or sinus arrest has occurred. Rare instances of conduction disturbances (sinoatrial block, various degrees of AV block) have been reported.
Dermatological: Photosensitization may be induced in certain individuals; a bluish discoloration of the skin has been reported.
Thyroid: Both hyper- and hypothyroidism; mass loss, asthenia, restlessness, increase in heart rate or the recurrence of cardiac dysrhythmia, angina or congestive heart failure, should alert the clinician. In cases of severe hyperthyroidism, course of antithyroid medication have been used and large doses are required initially. These may not always be effective and concomitant high dose corticosteroids may be required for several weeks. Thyroid hypofunction usually resolves within 3 months of discontinuation of Amiodarone therapy and it may be treated cautiously with L-thyroxine.
Pulmonary: Severe pulmonary toxicity has been reported, including fibrosis and interstitial pneumonitis. Diffuse pulmonary alveolitis may also occur, sometimes presenting as unexplained or disproportionate dyspnea.
Hepatic: Liver function, particularly transaminase, should be monitored before treatment and periodically thereafter. Occasional cases of acute liver disorders with elevated serum transaminase and/or jaundice may occur. These normally resolve once treatment has been withdrawn.
Neurological: Peripheral neuropathy and/or myopathy. These conditions may be serious and may be reversible on withdrawal of Amiodarone. Nightmares, vertigo, headaches and sleeplessness may occur. Tremor and ataxia have also been reported, usually with complete regression following reduction of dose or withdrawal of treatment. Benign raised intracranial pressure has been reported.
ECG: Amiodarone will induce ECG changes; QT interval lengthening corresponding to prolonged repolarization, U waves and deformed T waves may occur because of the fixing of Amiodarone in the cardiac tissue. These are not signs of toxicity and dosing may continue.
Other: Nausea, vomiting, metallic taste (which usually occur with loading dose and which regress on dose reduction), fatigue and epididymo-orchitis have been reported.
Isolated cases suggesting hypersensitivity have been reported. Symptoms include vasculitis, renal involvement with moderate elevation of creatinine levels or thrombocytopenia have been observed.

Amiodarone is an inhibitor of CYP3A4 and p-glycoprotein. Therefore, Amiodarone has the potential for interactions with drugs or substances that may be substrates, inhibitors, or inducers of CYP3A4 and substrates of p-glycoprotein.

Store at temperatures not exceeding 30°C.

Cardiac Drugs

C01BD01 - amiodarone ; Belongs to class III antiarrhythmics.

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