Novocainamide (Tablets, Solution) Instructions for Use

ATC Code

C01BA02 (Procainamide)

Active Substance

Procainamide (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Antiarrhythmic drug. Class I A

Pharmacotherapeutic Group

Drugs for the treatment of heart diseases; antiarrhythmic agents, classes I and III; antiarrhythmic agents, class IA

Pharmacological Action

Class IA antiarrhythmic agent, possesses membrane-stabilizing activity. It inhibits the incoming fast sodium ion current and reduces the depolarization rate in phase 0. It suppresses conduction and slows repolarization. It reduces the excitability of the atrial and ventricular myocardium. It increases the duration of the effective refractory period of the action potential (to a greater extent in the affected myocardium). The slowing of conduction, which is observed regardless of the resting potential magnitude, is more pronounced in the atria and ventricles and less so in the AV node.

The indirect m-cholinoblocking effect is less pronounced compared to quinidine and disopyramide; therefore, paradoxical improvement of AV conduction is usually not observed. It affects phase 4 depolarization, reduces the automaticity of the intact and affected myocardium, and suppresses the function of the sinus node and ectopic pacemakers in some patients.

The active metabolite, N-acetylprocainamide, possesses pronounced activity of class III antiarrhythmic agents and prolongs the action potential duration. It has a weak negative inotropic effect (without significant effect on cardiac output), vagolytic and vasodilating properties, which causes tachycardia and a decrease in blood pressure and systemic vascular resistance.

Electrophysiological effects are manifested by widening of the QRS complex and prolongation of the PQ and QT intervals. The time to reach maximum effect after oral administration is 60-90 minutes, after IV administration – immediately, after IM administration – 15-60 minutes.

Pharmacokinetics

Absorption is rapid after oral and IM administration. Protein binding is 15-20%. It is metabolized in the liver to form the active metabolite N-acetylprocainamide. Usually, about 25% of the administered procainamide is converted to this metabolite; however, with rapid acetylation or impaired renal function, up to 40% of the dose is converted.

The T_1/2 of procainamide is 2.5-4.5 hours, and in case of impaired renal function – 11-20 hours; for N-acetylprocainamide – about 6 hours. It is excreted by the kidneys, 50-60% unchanged, the remainder as the metabolite. In case of impaired renal function or chronic heart failure, the metabolite rapidly accumulates in the blood to toxic concentrations, while the concentration of procainamide remains within acceptable limits.

Indications

Ventricular arrhythmias: extrasystole, paroxysmal ventricular tachycardia. Supraventricular arrhythmias. Paroxysm of atrial fibrillation or atrial flutter. Supraventricular tachycardia (including WPW syndrome).

ICD codes

Dosage Regimen

Solution

IV – 100-500 mg at a rate of 25-50 mg/min (under blood pressure and ECG control) until termination of the paroxysm (maximum dose – 1 g) or IV drip – 500-600 mg over 25-30 minutes. Maintenance dose with IV drip infusion – 2-6 mg/min; if necessary, start oral administration of the drug 3-4 hours after stopping the infusion.

In grade II heart failure, the dose is reduced by 1/3 or more.

IM administration: 5-10 ml (up to 20-30 ml/day).

For IV administration, the drug is diluted in 5% glucose solution or 0.9% sodium chloride solution. The rate of administration should not exceed 50 mg/min. Constant monitoring of heart rate, blood pressure, and ECG is necessary.

Maximum dose for adults with IM and IV (drip) administration: single – 1 g (10 ml of the drug), daily – 3 g (30 ml of the drug).

When switching to oral administration, the first dose is prescribed 3-4 hours after stopping the IV infusion.

Tablets

Individual. The initial oral dose ranges from 250 mg to 1 g, then, if necessary and considering tolerance, 250-500 mg every 3-6 hours.

For IM administration – 50 mg/kg/day in divided doses every 3-6 hours.

For IV bolus administration, a single dose is 100 mg; if necessary, repeated administrations until arrhythmia cessation are possible. For IV infusion, the dose is 500-600 mg.

Maximum doses for adults orally – 4 g/day; IV bolus with repeated administrations, the total dose is 1 g.

Adverse Reactions

From the cardiovascular system arterial hypotension (up to the development of collapse), intraventricular block, ventricular tachycardia, tachyarrhythmia; with rapid IV administration – collapse, intraventricular block, asystole.

From the central nervous system hallucinations, depression, myasthenia, dizziness, headache, convulsions, psychotic reactions with productive symptoms, ataxia.

From the hematopoietic system with long-term use – suppression of bone marrow hematopoiesis (leukopenia, thrombocytopenia, neutropenia, agranulocytosis, hypoplastic anemia), hemolytic anemia with a positive Coombs test.

Allergic reactions skin rash, itching.

Other bitter taste in the mouth, with long-term use – drug-induced lupus erythematosus (in 30% of patients with therapy duration over 6 months); microbial infections, delayed healing processes, and gum bleeding due to the risk of leukopenia and thrombocytopenia are possible.

Contraindications

AV block of II and III degree (except in cases with a pacemaker), ventricular flutter or fibrillation, arrhythmias due to cardiac glycoside intoxication, leukopenia, hypersensitivity to procainamide.

Use in Pregnancy and Lactation

If it is necessary to use procainamide during pregnancy and lactation (breastfeeding), it should be considered that the active substance crosses the placental barrier and is excreted in breast milk. Therefore, the use of procainamide is possible only if the potential benefit to the mother outweighs the possible risk to the fetus or infant.

Use in Hepatic Impairment

Use with caution in hepatic insufficiency.

Use in Renal Impairment

Use with caution in renal insufficiency.

Geriatric Use

Use with caution in elderly patients.

Special Precautions

The arrhythmogenic effect of procainamide was noted in 5-9% of cases. Due to the possible suppression of myocardial contractility and decrease in blood pressure, it should be used with great caution in myocardial infarction. In severe atherosclerosis, Procainamide is not recommended.

Use with caution in bundle branch block, arrhythmias due to cardiac glycoside intoxication, myasthenia, hepatic and/or renal insufficiency, SLE (including history), bronchial asthma, chronic heart failure in the decompensation stage, ventricular tachycardia with coronary artery occlusion, surgical interventions (including in surgical dentistry), with prolonged QT interval, arterial hypotension, atherosclerosis, in myasthenia, in elderly patients.

Drug Interactions

With simultaneous use with antiarrhythmic agents, an additive cardiodepressant effect is possible; with antihypertensive agents – the antihypertensive effect is enhanced; with anticholinesterase agents – the effectiveness of anticholinesterase agents is reduced.

With simultaneous use with m-cholinoblockers, antihistamines, their cholinolytic effect is enhanced.

With simultaneous use, the effect of agents blocking neuromuscular transmission is enhanced; with simultaneous use of agents causing bone marrow hematopoiesis suppression, leukopenia and thrombocytopenia may be enhanced.

With simultaneous use with amiodarone, the QT interval increases due to an additive effect on its duration and the risk of developing torsades de pointes ventricular arrhythmia. The plasma concentration of procainamide and its metabolite N-acetylprocainamide increases, and side effects may be enhanced.

With simultaneous use with captopril, the risk of developing leukopenia may increase.

With simultaneous use with ofloxacin, an increase in the plasma concentration of procainamide is possible; with prenylamine – the negative inotropic effect and the risk of developing torsades de pointes ventricular arrhythmia are enhanced.

With simultaneous use with sotalol, quinidine, an additive increase in the QT interval is possible.

With simultaneous use with trimethoprim, the plasma concentration of procaine and its active metabolite N-acetylprocainamide increases, and there is a risk of developing toxic reactions.

With simultaneous use with cisapride, the duration of the QT interval significantly increases due to an additive effect, and there is a risk of developing ventricular arrhythmia (including torsades de pointes).

With simultaneous use with cimetidine, the plasma concentration of procainamide and the risk of increased side effects increase, especially in elderly patients and in cases of impaired renal function, which is due to a reduction in the renal excretion of procainamide by almost 1/3 or more under the influence of cimetidine.

Storage Conditions

Store at 2°C (36°F) to 30°C (86°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.