Novokainamid

General characteristics. Structure:

Active ingredient: 100 mg of a novokainamid (hydrochloride procaineamide) in 1 ml of solution. 

Excipients: sodium disulphite (sodium metabisulphite), water for injections.

Pharmacological properties:

Pharmacodynamics. Antiarrhytmic drug IA of a class. Brakes the entering bystry current of ions of sodium, reduces depolarization speed in a phase 0. Conductivity oppresses, slows down repolarization. Reduces excitability of a myocardium of auricles and ventricles. Increases duration of the effective refractory period of action potential (in the affected myocardium - more). Conductivity delay which is observed irrespective of rest potential size is more expressed in auricles and ventricles, it is less in an atrioventricular (AV) node.

The indirect m-holinoblokiruyushchy effect, in comparison with quinidine and Disopyramidum, is expressed less therefore paradoxical improvement of AV of conductivity usually is not noted.

4 depolarizations influence a phase, reduces automatism of the intact and affected myocardium, oppresses function of a sinus node and ectopic pacemakers at some patients.

The active metabolite - N-atsetilprokainamid (N-APA) has the expressed antiarrhytmic activity, extends action potential duration. Possesses a weak negative inotropic effect (without significant effect on the minute volume of blood (MVB)). Renders m-holinoblokiruyushchee and vazodilatiruyushchy action that causes tachycardia and a lowering of arterial pressure (ABP), the general peripheric vascular resistance (GPVR).

Electrophysiologic effects are shown in broadening of the QRS complex and lengthening of intervals of PQ and QT. Time of achievement of the maximum effect at intravenous maintaining - immediately, at intramuscular - 15-60 min.

Pharmacokinetics. Gets through a blood-brain barrier, cosecretes with breast milk. It is metabolized in a liver with formation of an active metabolite - N-acetyl-prokainamida, has effect of "the first passing" through a liver. About 25% of the entered procaineamide turn into the specified metabolite, however at bystry acetylation or the chronic renal failure (CRF) 40% of a dose are exposed to transformation. At HPN or chronic heart failure the metabolite quickly collects in blood to toxic concentration, at the same time concentration of procaineamide remains in acceptance limits.

Elimination half-life - 2,5-4,5 h; at HPN - 11-20 h; N-atsetilprokainamida about 6 h. About 25% of the administered drug are removed by kidneys (50-60% in not changed look), and through intestines with bile.

Indications to use:

- ventricular disturbances of a rhythm: ventricular tachycardia, ventricular premature ventricular contraction.

- atrial disturbances of a rhythm: atrial tachycardia, fibrillation and atrial flutter.

Route of administration and doses:

Intravenously: 100-500 mg with a speed of 25-50 mg/min. (under control of the ABP and an ECG) before stopping of a paroxysm (the maximum dose - 1 g) or intravenously kapelno: 500-600 mg in 25-30 min. The maintenance dose at intravenous drop administration - 2-6 mg/min., if necessary in 3-4 h after the termination of infusion to begin administration of drug inside.

At heart failure of the II degree the dose is reduced (on 1/3 and more). Intramusculary enter 5-10 ml (to 20-30 ml a day). At intravenous administration drug is dissolved in 5% solution of a dextrose (glucose) or 0,9% chloride sodium solution.

Rate of administering should not exceed 50 mg/min. At the same time constant control of the heart rate (HR), the ABP and an ECG is necessary.

The highest dose for adults at intramuscular and intravenous (drop) administration: one-time - 1 g (10 ml of drug), daily - 3 g (30 ml of drug). Upon transition to administration of drug inside the first dose is appointed in 3-4 h after the termination of intravenous infusion.

Features of use:

Pregnancy and lactation. To apply only in that case when the advantage for mother surpasses potential risk for the fruit/child.

At appointment during pregnancy there is a potential risk of development of arterial hypotension in mother that can result in fetoplacental insufficiency.

In need of use in the period of a lactation, breastfeeding needs to be stopped.

Before intravenous administration it is necessary to part, enter with a speed no more than 50 mg/min.; it is necessary to apply only in the conditions of a hospital.

When performing therapy it is necessary to carry out constant control of the ABP, an ECG, formula of peripheral blood (at the end of therapy).

At patients of advanced age development of arterial hypotension is more probable.

Side effects:

From the central nervous system: the general weakness, hallucinations, a depression, a myasthenia, dizziness, a headache, sleeplessness, spasms, psychotic reactions with productive symptomatology, an ataxy.

From the alimentary system: bitterness in a mouth, diarrhea, nausea, vomiting.

From cardiovascular system: decrease in the ABP, ventricular Bouveret's disease.

At bystry in introduction development of a collapse, disturbance of atrial or intra ventricular conduction, an asystolia is possible.

Allergic reactions: skin rash.

Interaction with other medicines:

Strengthens effect of the depolarizing muscle relaxants (succinylcholine salt), hypotensive, antiarrhytmic means, side effects of a bretylium of tosylate.

At simultaneous use with antihistamines m-holinoblokiruyushchiye effects can amplify; with Pimozidum - lengthening of an interval of QT.

Reduces activity of anti-myasthenic means.

Cimetidinum, ranitidine reduce renal clearance of procaineamide and extend an elimination half-life.

At a combination therapy with antiarrhytmic means of the III class the risk of development of aritmogenny effect increases.

The medicines oppressing a marrowy hemopoiesis increase risk of a miyelosupressiya.

Contraindications:

Hypersensitivity to drug; the ventricular arrhythmia caused by intoxication cardiac glycosides, sinuatrial and atrioventricular blockade of the II-III degree (in the absence of the implanted electrocardiostimulator), arterial hypotension, cardiogenic shock; ventricular tachycardias like "pirouette", the extended QT interval, a leukopenia, age up to 18 years (efficiency and safety are not established).

With care: in connection with possible decrease in contractility of a myocardium and decrease in the ABP it is necessary to appoint carefully drug at a myocardial infarction. Perhaps aritmogenny action.

Blockade of legs of a ventriculonector, atrioventricular block of the I degree, chronic heart failure in a decompensation stage, gravis myasthenia, bronchial asthma, a liver and/or renal failure, ventricular tachycardia at occlusion of a coronary artery, a system lupus erythematosus (including in the anamnesis), surgical interventions (including surgical stomatology), the expressed atherosclerosis, advanced age.

Overdose:

Symptoms: drug has the small therapeutic width therefore there can easily be heavy intoxication (especially at simultaneous use of other antiarrhytmic means): bradycardia, sinuatrial and atrioventricular blocks, asystolia, lengthening of an interval of QT, paroxysms of polymorphic ventricular tachycardia, decrease in contractility of a myocardium, permanent decrease in the ABP, fluid lungs, spasms, coma, apnoea.

Treatment: symptomatic. For treatment of ventricular tachycardia not to use antiarrhytmic means of IA or 1C of classes. Natrii hydrocarbonas is capable to eliminate expansion of the QRS complex or arterial hypotension.

Storage conditions:

To store in the place protected from light, at a temperature not above 25 °C. To store in the place, unavailable to children. A period of validity - 5 years. Not to use after the expiry date specified on packaging.

Issue conditions:

According to the recipe

Packaging:

Solution for intravenous and intramuscular administration, 100 mg/ml. Packaging: on 5 ml in ampoules of neutral glass. On 5 ampoules in a blister strip packaging from a film polyvinyl chloride. 1 or 2 blister strip packagings with the scarificator ampoule ceramic or a knife for opening of ampoules and the application instruction in a pack from a cardboard. When using ampoules with a ring of a break or a point of a break the knife or the scarificator do not put.