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 general, start at the low end of the dosing range in the elderly to reflect the greater frequency of decreased hepatic, renal, or cardiac function, and concomitant disease or other drug therapy.There have been cases, some fatal, of amiodarone overdose. In addition to blocking sodium channels, amiodarone blocks myocardial potassium channels, which contributes to slowing of conduction and prolongation of refractoriness. In clinical trials, after 48 hours of continued infusions (125,500 or 1000 mg/day) plus supplemental (150 mg) infusions (for recurrent arrhythmias), amiodarone mean serum concentrations between 0.7 to 1.4 mg/L were observed (n=260).N-desethylamiodarone (DEA) is the major active metabolite of amiodarone in humans. However, oral amiodarone caused a statistically significantly, dose-related increase in the incidence of thyroid tumors (follicular adenoma and carcinoma) in rats. Although no dosage adjustment for patients with renal, hepatic, or cardiac abnormalities has been defined during chronic treatment with oral amiodarone, close clinical monitoring is prudent for elderly patients and those with severe left ventricular dysfunction.There is no established relationship between drug concentration and therapeutic response for short-term intravenous use. Renal impairment does not influence the pharmacokinetics of amiodarone. 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. molecular weight of 337.46 and the following structural formula: Danazol capsules for oral administration contain 50 mg, 100 mg or 200 mg danazol. The maintenance infusion of up to 0.5 mg/min can be cautiously continued for 2 to 3 weeks regardless of the patient's age, renal function, or Left-ventricular function. 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. In some instances hyperthyroidism was also present [see Adverse Reactions (6.2)].Hyperthyroidism occurs in about 2% of patients receiving amiodarone, but the incidence may be higher among patients with prior inadequate dietary iodine intake. The highly variable systemic availability of oral amiodarone may be attributed to large interindividual variability in CYP3A activity.From in vitro studies, the protein binding of amiodarone is >96%. Amiodarone Hydrochloride Injection also can be used to treat patients with VT/VF for whom oral amiodarone is indicated, but who are unable to take oral medication. The drug prevents the recurrence of life-threatening ventricular arrhythmias and produces a modest reduction of sudden deaths in high-risk patients. Monitor patients for QTc prolongation during infusion with amiodarone. During transfer to oral amiodarone, reduce the dose levels of previously administered agents by 30 to 50% several days after the addition of oral amiodarone. Do not use evacuated glass containers for admixing, as incompatibility with a buffer in the container may cause precipitation.Amiodarone adsorbs to polyvinyl chloride (PVC) tubing, but all of the clinical experience has been with PVC tubing and the concentrations and rates of infusion provided in DOSAGE AND ADMINISTRATION reflect dosing in these studies.Amiodarone has been found to leach out plasticizers, including DEHP [di-(2-ethylhexyl)phthalate] from intravenous tubing (including PVC tubing). Treat hypotension and cardiogenic shock by slowing the infusion rate or with standard therapy: vasopressor drugs, positive inotropic agents, and volume expansion. Manage hypothyroidism by reducing the amiodarone dose and considering the need for thyroid hormone supplement. See package insert for oral amiodarone.Amiodarone inhibits peripheral conversion of thyroxine (T4) to triiodothyronine (T3) and may cause increased T4 levels, decreased T3 levels, and increased levels of inactive reverse T3 (rT3) in clinically euthyroid patients.