Amiodarone dosing

B. An exception to this rule of thumb is amiodarone, which is so extensively distributed to tissues that even massive single overdoses produce little or no toxicity (toxicity usually occurs only after accumulation during chronic amiodarone dosing). 

A woman with congenital heart disease and atrial and ventricular arrhythmias managed by an implanted cardioverter defibrillator, epicardial pacing and amiodarone 400 mg daily, experienced deterioration in the control of her condition. She developed palpitations and experienced a shock from the defibrillator. Her amiodarone serum levels were 40% lower than 2 months previously, and her A-desethylamiodarone levels were undetectable. It was noted that 5 weeks earlier rifampicin 600 mg daily had been started to treat an infection of the pacing system. The amiodarone dose was doubled, but the palpitations continued. Amiodarone and A-desethy-lamiodarone levels increased after rifampicin was discontinued. Rifampicin is a potent enzyme inducer and it may have increased the metabolism and clearance of amiodarone. This case suggests that combined use of amiodarone and rifampicin should be well monitored. 

Six patients with symptomatic cardiac arrhythmias took part in a two-phase study. Initially, lidocaine 1 mg/kg was given intravenously over 2 minutes. In phase I, loading doses of amiodarone 500 mg daily for 6 days were given, followed by the same lidocaine dose. After 19 to 21 days, when the total cumulative amiodarone dose was 13 g, the same lidocaine dose was given again (phase II). The lidocaine AUC increased by about 20% and the systemic clearance decreased by about 20%. The elimination half-life and distribution volume at steady-state were unchanged. The pharmacokinetic parameters of lidocaine in phase II were the same as those in phase I, indicating that the interaction occurs early in... 

Ventricular fibrillation should be terminated by electrical defibrillation. Alternatively, lidocaine can be injected intravenously. In cases with lower frequency, ventricular tachyarrhythmia class I diugs such as aj marine, flecainide or propafenone are more effective as a result of the use-dependence of lidocaine. For prophylaxis treatment, amiodarone or sotalol may be helpful or the implantation of a cardioverter-defibrillator system. Acute amiodarone (i.v. in higher doses) can also terminate ventricular tachyarrhythmias. This action, however, seems to be mediated by its INa-blocking side effects and not (or less) by its class III like effects. 

Maintenance doses widely vary among patients (e.g., from 1 to 20 mg/day for warfarin), and are influenced by diet (variable vitamin K intake) and medications that affect coumarin metabolism (decreased drug clearance e.g., cotrimoxazole, amiodarone, erythromycin increased clearance e.g., barbiturates, carbamaze-pine, rifampin). Thus, regular monitoring is needed... 

Lidocaine can be considered an alternative to amiodarone in patients with VF/ PVT, The initial dose is 1-1,5 mg/kg IV. Additional doses of 0.5-0.75 mg/kgcan be administered at 5-to 10-minute intervals to a maximum dose of 3 mg/kg if VF/PVT persists. 

Maintenance dose 0.125-0.25 mg PO/IV qd low potassium or magnesium levels potentiate toxicity reduce dose in renal failure toxicity indicated by nausea, headache, visual disturbances (yellow-green halos), ventricular arrhythmias. Quinidine, verapamil, and amiodarone elevate digoxin level. 

Amiodarone (Figure 8.2) is an efficacious drug that causes a number of side-effects. The presence of iodine in the molecule is unusual and hypo- and hyperthyroidism have been reported in patients. Although the loss of iodine is relatively slow the relatively large daily dose size and long half-life of the drug and its de-ethylated metabolite suggest that the presence of iodine in the molecule is responsible for its toxicity [3]. 

For the treatment of hemodynamically stable ventricular tachycardia in children, procainamide (loading dose of 15 mg/kg IV infused over 30 to 60 minutes) may be considered as an alternative agent to amiodarone. 

Administration with amiodarone When flecainide is given in the presence of amiodarone, reduce the usual flecainide dose by 50% and monitor the patient closely for adverse effects. Plasma level monitoring is strongly recommended to guide dosage with such combination therapy. 

Parenteral Amiodarone shows considerable interindividual variation in response. Thus, although a starting dose adequate to suppress life-threatening arrhythmias is needed, close monitoring with adjustment of dose as needed is essential. The... 

Amiodarone IV Dose Recommendations During the First 24 Hours ... 

The first 24-hour dose may be individualized for each patient however, in controlled clinical trials, mean daily doses greater than 2100 mg were associated with an increased risk of hypotension. The initial infusion rate should not exceed 30 mg/min. Based on the experience from clinical studies, a 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. There has been limited experience in patients receiving amiodarone IV for more than 3 weeks. 

Amiodarone adsorbs to polyvinyl chloride (PVC) tubing, and the clinical trial dose administration schedule was designed to account for this adsorption. Clinical trials were conducted using PVC tubing therefore its use is recommended. The concentrations and rates of infusion provided in Administration and Dosage reflect doses identified in these studies. It is important that the recommended infusion regimen be followed closely. 

The following table provides suggested doses of oral amiodarone to be initiated after varying durations of IV administration. These recommendations are made on the basis of a comparable total body amount of amiodarone delivered by the IV and oral... 

Duration of amiodarone IV infusions- Initial daily dose of oral amiodarone... 

Absorption - Following oral administration, amiodarone is slowly and variably absorbed bioavailability is approximately 50%. Maximum plasma concentrations are attained 3 to 7 hours after a single dose. Plasma concentrations with chronic dosing at 100 to 600 mg/day are approximately dose-proportional, with a mean 0.5 mg/L increase for each 100 mg/day. 

Ophthalmologic effects Optic neuropathy or neuritis may occur at any time following initiation of therapy, in some cases, visual impairment has progressed to permanent blindness. Corneal microdeposits appear in virtually all adults treated with amiodarone. They give rise to symptoms such as visual halos or blurred vision in as many as 10% of patients. Corneal microdeposits are reversible upon reduction of dose or drug discontinuation. Asymptomatic microdeposits are not a reason to reduce dose or stop treatment. Some patients develop photophobia and dry eyes. Vision is rarely affected and drug discontinuation is rarely needed. 

Hyperthyroidism - Hyperthyroidism usually poses a greater hazard to the patient than hypothyroidism because of the possibility of arrhythmia breakthrough or aggravation. If any new signs of arrhythmia appear, consider the possibility of hyperthyroidism. Aggressive medical treatment is indicated, including, dose reduction or withdrawal of amiodarone. 

Concomitant amiodarone or verapamil (immediate-release only) - In patients taking amiodarone or verapamil concomitantly with lovastatin, the dose should not exceed 40 mg/day. 

Amiodarone (Cordarone, Pacerone) [Ventricular Antiarrhythmic/Adrenergic Blocker] Uses RecumMit VF or hemo-dynamically unstable VT, supraventricular arrhythmias, AF Action Class III antiarrhythmic (Table VI-7) Dose Adul. Ventricular arrhythmias IV 15 mg/min... 

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