Novocainamide-Ferein^® (Solution) Instructions for Use

Marketing Authorization Holder

Bryntsalov-A, JSC (Russia)

ATC Code

C01BA02 (Procainamide)

Active Substance

Procainamide (Rec.INN registered by WHO)

Dosage Form

Novocainamide-Ferein®

Solution for injection 10%: amp. 5 ml 5 or 10 pcs.

Dosage Form, Packaging, and Composition

Solution for injection in the form of a transparent, colorless or slightly yellowish liquid.

Excipients: sodium disulfite (sodium metabisulfite) – 5 mg, water for injection – up to 1 ml.

5 ml – ampoules of colorless glass (5) – contour cell packaging (1) – cardboard packs.
5 ml – ampoules of colorless glass (5) – contour cell packaging (2) – cardboard packs.
5 ml – ampoules of colorless glass (5) – cardboard packs.
5 ml – ampoules of colorless glass (10) – cardboard packs.

Clinical-Pharmacological Group

Antiarrhythmic drug. Class I A

Pharmacotherapeutic Group

Antiarrhythmic agent

Pharmacological Action

Antiarrhythmic agent of class IA, possesses membrane-stabilizing activity. It inhibits the incoming fast sodium ion current and reduces the depolarization rate in phase 0. It depresses 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, so paradoxical improvement of AV conduction is usually not observed. It affects phase 4 of depolarization, reduces the automaticity of the intact and affected myocardium, and depresses 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 manifest as widening of the QRS complex and prolongation of the PQ and QT intervals. The time to reach maximum effect when taken orally is 60-90 minutes, with IV administration – immediately, with IM administration – 15-60 minutes.

Pharmacokinetics

Absorption is rapid after oral and intramuscular 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

Individual. When taken orally, the initial dose ranges from 250 mg to 1 g, then, if necessary and taking into account tolerance, 250-500 mg every 3-6 hours.

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

With intravenous bolus administration, a single dose is 100 mg; if necessary, repeated administration is possible until the arrhythmia stops. With intravenous infusion, the dose is 500-600 mg.

Maximum doses for adults when taken orally – 4 g/day; with intravenous bolus administration with repeated injections, 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 intravenous 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 – inhibition of bone marrow hematopoiesis (leukopenia, thrombocytopenia, neutropenia, agranulocytosis, hypoplastic anemia), hemolytic anemia with a positive Coombs test.

Allergic reactions skin rash, itching.

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

Contraindications

AV block of II and III degree (except for 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 taken into account 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 depression of myocardial contractility and decrease in blood pressure, it should be used with great caution in myocardial infarction. It is not recommended to use Procainamide in severe atherosclerosis.

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

With simultaneous use, the effect of agents blocking neuromuscular transmission is enhanced; with simultaneous use of agents causing inhibition of bone marrow hematopoiesis, 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, the plasma concentration of procainamide may increase; 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 procainamide 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 25°C (77°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.