Amiodarone-induced hyperthyroidism usually poses a greater hazard to the patient than hypothyroidism because of the possibility of thyrotoxicosis and arrhythmia breakthrough or aggravation, all of which may result in death. The incidence of thyroid tumors in rats was greater than the incidence of controls even at the lowest dose level tested, i.e., 5 mg/kg/day (much less, on a body surface area basis, than the maximum recommended human maintenance dose of 600 mg/day).Mutagenicity studies conducted with amiodarone HCL (Ames, micronucleus, and lysogenic induction tests) were negative.No fertility studies were conducted with intravenous administration of amiodarone. arrhythmias, some patients will require antiarrhythmic treatment for Each milliliter of the amiodarone formulation contains 50 mg of amiodarone hydrochloride, 20.2 mg of benzyl alcohol, 100 mg of polysorbate 80, and water for injection.Amiodarone Hydrochloride Injection contains polysorbate 80, which is known to leach di-(2-ethylhexyl)phthalate (DEHP) from polyvinylchloride (PVC) [(see Dosage and Administration (2)].Amiodarone is generally considered a class III antiarrhythmic drug, but it possesses electrophysiologic characteristics of all four Vaughan Williams classes. treatment of symptomatic heart failure (HF) as well as in patients with atrial Monitor the initial rate of infusion closely and do not exceed the recommended rate [see Dosage and Administration (2)].In some cases, hypotension may be refractory and result in a fatal outcome [see Adverse Reactions (6.2)].In 90 (4.9%) of 1836 patients in clinical trials, drug-related bradycardia that was not dose-related occurred while they were receiving intravenous amiodarone for life-threatening VT/VF. populations with multiple cardiovascular problems that are candidates for and With inhibition, serum concentrations of medication generally increase. interaction. The development of maximal ventricular class III effects after oral amiodarone administration in humans correlates more closely with DEA accumulation over time than with amiodarone accumulation. In a pediatric trial of 61 patients, aged 30 days to 15 years, hypotension (36%), bradycardia (20%), and AV block (15%) were common dose-related adverse reactions and were severe or life-threatening in some cases. Amiodarone Hydrochloride Injection is a sterile clear, pale-yellow micellar solution visually free from particulates. amiodarone, azithromycin, clarithromycin ... * cited as example of combined P-gp inducer and strong CYP3A4 inducer in US PI ... AVOID USE (1) based on human in vivo data, in Cytochrome P450 Enzymes and Transports Table, from Hansten PD and Horn JR. For example, digoxin in the form of a solution may be less Effects of an inadvertent overdose of intravenous amiodarone include hypotension, cardiogenic shock, bradycardia, AV block, and hepatotoxicity. The recommended starting dose of amiodarone is about 1000 mg over the first 24 hours of therapy, delivered by the following infusion regimen:After the first 24 hours, continue the maintenance infusion rate of 0.5 mg/min (720 mg per 24 hours) utilizing a concentration of 1 to 6 mg/mL (Use a central venous catheter for amiodarone concentrations greater than 2 mg/mL). These data were collected in clinical trials involving 1836 patients with life-threatening VT/VF. Reported examples include the following:Amiodarone inhibits p-glycoprotein and certain CYP450 enzymes, including CYP1A2, CYP2C9, CYP2D6, and CYP3A. In view of the long and variable half-life of amiodarone, potential for drug interactions exists not only with concomitant medication but also with drugs administered after discontinuation of amiodarone.Since amiodarone is a substrate for CYP3A and CYP2C8, drugs/substances that inhibit these isoenzymes may decrease the metabolism and increase serum concentration of amiodarone. there is a clinically relevant drug interaction between the two, wherein The action of antithyroid drugs may be especially delayed in amiodarone-induced thyrotoxicosis because of substantial quantities of preformed thyroid hormones stored in the gland. Symptoms include a striking onset of gasping respiration, hypotension, bradycardia, and cardiovascular collapse.Clinical studies of amiodarone did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Mortality was not affected in these studies.Amiodarone Hydrochoride Injection, 50 mg/mL, is supplied as follows:NDC 0143-9875-10 3 mL Single Dose Vials (Cartons of 10 vials)Store at 20º-25ºC (68º-77ºF) [See USP Controlled Room Temperature].Use carton to protect contents from light until time of use.Amiodarone has the potential to cause serious side effects that limit its use to life-threatening and hemodynamically unstable cardiac arrhythmias. Therefore, surgical and anesthetic management require careful planning.Amiodarone can cause fetal harm when administered to a pregnant woman.