Procainamide dosages

Kll. Koch-Weser, J., and Klein, S. W., Procainamide dosage schedules, plasma concentrations, and clinical effects. J. Amer. Med. Ass. 215, 1464-1460 (1971). 

First-degree heart block Exercise caution if the patient exhibits or develops first-degree heart block while taking procainamide dosage reduction is advised. If the block persists despite dosage reduction, evaluate the continuation of procainamide on the basis of current benefit vs risk of increased heart block. Predigitalization for atrial flutter or fibrillation Cardiovert or digitalize patients with atrial flutter or fibrillation prior to procainamide administration to avoid enhancement... 

Procainamide is eliminated by hepatic metabolism to NAPA and by renal elimination. Its half-life is only 3-4 hours, which necessitates frequent dosing or use of a slow-release formulation (the usual practice). NAPA is eliminated by the kidneys. Thus, procainamide dosage must be reduced in patients with renal failure. The reduced volume of distribution and renal clearance associated with heart failure also require reduction in dosage. The half-life of NAPA is considerably longer than that of procainamide, and it therefore accumulates more slowly. Thus, it is important to measure plasma levels of both procainamide and NAPA, especially in patients with circulatory or renal impairment. 

To control ventricular arrhythmias, a total procainamide dosage of 2-5 g/d is usually required. In an occasional patient who accumulates high levels of NAPA, less frequent dosing may be possible. This is also possible in renal disease, where procainamide elimination is slowed. 

The interaction between procainamide and cimetidine is established. Concurrent use should be undertaken with care because the safety margin of procainamide is low. Reduce the procainamide dosage as necessary. This is particularly important in the elderly because they have a reduced ability to clear both drugs. Ranitidine and famotidine appear not to interact to a... 

All antiarrhythmic dra are used cautiously in patients with renal or hepatic disease. When renal or hepatic dysfunction is present, a dosage reduction may be necessary. All patients should be observed for renal and hepatic dysfunction. Quinidine and procainamide are used cautiously in patients with CHF. Disopyramide is used cautiously in patients with CHF, myasthenia gravis, or glaucoma, and in men with prostate enlargement. Bretylium is used cautiously in patients with digitalis toxicity because the initial release of norepinephrine with digitalis toxicity may exacerbate arrhythmias and symptoms of toxicity. Verapamil is used cautiously in patients with a history of serious ventricular arrhythmias or CHF. Electrolyte disturbances such as hypokalemia, hyperkalemia, or hypomagnesemia may alter the effects of the antiarrhythmic dru . Electrolytes are monitored frequently and imbalances corrected as soon as possible... 

Renai insufficiency Renal insufficiency may lead to accumulation of high plasma levels from conventional oral doses of procainamide, with effects similar to those of overdosage unless dosage is adjusted for the individual patient. 

Procainamide is an effective antiarrhythmic agent when given in sufficient doses at relatively short (3-4 hours) dosage intervals. Procainamide is useful in the treatment of premature atrial contractions, paroxysmal atrial tachycardia, and atrial fibrillation of recent onset. Procainamide is only moderately effective in converting atrial flutter or chronic atrial fibrillation to sinus rhythm, although it has... 

Acute cardiovascular reactions to procainamide administration include hypotension, A-V block, intraventricular block, ventricular tachyarrhythmias, and complete heart block. The drug dosage must be reduced or even stopped if severe depression of conduction (severe prolongation of the QRS interval) or repolarization (severe prolongation of the QT interval) occurs. 

If a rapid procainamide effect is needed, an intravenous loading dose of up to 12 mg/kg can be given at a rate of 0.3 mg/kg/min or less rapidly. This dose is followed by a maintenance dosage of 2-5 mg/min, with careful monitoring of plasma levels. The risk of gastrointestinal or cardiac toxicity rises at plasma concentrations greater than 8 mcg/mL or NAPA concentrations greater than 20 mcg/mL. 

Antiarrhythmic therapy carries with it a number of risks. In some cases, the risk of an adverse reaction is clearly related to high dosages or plasma concentrations. Examples include lidocaine-induced tremor or quinidine-induced cinchonism. In other cases, adverse reactions are unrelated to high plasma concentrations (eg, procainamide-induced agranulocytosis). For many serious adverse reactions to antiarrhythmic drugs, the combination of drug therapy and the underlying heart disease appears important. 

Pharmacokinetics Procainamide [pro kane A mide] is absorbed following oral administration. [Note The intravenous route is rarely used because hypotension occurs if the drug is too rapidly infused.] Procainamide has a relatively short half-life of 2-3 hours. A portion of the drug is acetylated in the liver to N-acetylprocainamide (NAPA), which has little effect on the maximum polarization of Purkinje fibers but prolongs the duration of the action potential. Thus, NAPA has properties of a Class III drug. NAPA is eliminated via the kidney, and dosages of procainamide may need to be adjusted in patients with renal failure. 

There have been a few previous reports of similar adverse effects with procainamide in therapeutic dosages, and in most cases the plasma concentrations of procainamide... 

Procainamide rarely causes nervous system effects. Acute confusion (10), cerebellar ataxia (11), tremor (12), and muscle weakness (13-16) have all been occasionally reported. In high dosages procainamide has anticholinergic effects (17). 

Nausea, vomiting, and diarrhea in response to procainamide are common with dosages of 4 g/day or more (32). Pseudo-obstruction has been attributed to the use of a modified-release formulation of procainamide, perhaps due to its anticholinergic effects (33). 

Amide-type local anesthetics (e.g., procainamide and lidocaine) also possess antiarrhythmic activity when given parenterally and at a subanesthetic dosage. Although this action can be attributed to their actions on sodium channels in cardiac tissues, current evidence suggests a distinctly different mechanism of action with respect to the modulation of channel receptors and the location of binding sites for these compounds (19,20). 

Please note that since peak time is independent of the dose administered, for a 500 mg tablet, the peak time will be identical (i.e. 0.971 h or 58.25 min). However, if an identical dose or even a different dose of procainamide is administered through a different extravascular route (e.g intramuscular), different dosage form (e.g. solution, capsule, controlled release tablet) or different formulation (e.g. tablet made by a different manufacturer or the same manufacturer with a different formulation), the peak time may be different. This is because the absorption rate constant may change with route of administration, dosage form and formulation. 

The absolute bioavailability (f) of procainamide from tablet dosage form in a normal subject by employing two different methods. 

When procainamide and amiodarone are used together the QT interval prolonging effects are increased, therefore the combination should generally be avoided. Serum procainamide levels are increased by about 60% and iV-acetylprocainamide levels by about 30% by amiodarone. If the combination is used, the dosage of procainamide will need to be reduced to avoid toxicity. 

Preliminary results of a study in 6 healthy subjects found that long-term treatment with propranolol [period and dosage not stated] increased the procainamide half-life from 1.71 to 2.66 hours and reduced the plasma clearance by 16%. However, a later study in 8 healthy subjects found that the pharmacokinetics of a single 500-mg dose of procainamide were only slightly altered by propranolol 80 mg three times daily or metoprolol 100 mg twice daily. The procainamide half-life of 1.9 hours increased to 2.2 hours with propranolol, and to 2.3 hours with metoprolol, but no sig-ni ficant changes in total clearance occurred. No changes in the AUC of the metabolite A-acetylprocainamide were seen. It seems unlikely that a clinically important adverse interaction normally occurs between these drugs. 

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