Pharmacodynamics and pharmacokinetics
The main active component is procainamide . The active substance has a membrane-stabilizing effect.
The mechanism of action is based on inhibition of the fast, incoming flow of sodium ions, reducing the rate of depolarization in the zero phase. Novocainamide slows down repolarization , inhibits conductivity, reduces the excitability of the myocardium of the ventricles and atria. Under the influence of the drug, the time of the effective refractory period of the action potential increases (to a greater extent in the tissue of the affected myocardium).
Procainamide has vasodilating and vagolytic effects, which causes a drop in blood pressure and tachycardia .
Pharmacological properties
Procainamide (beta-diethylaminoethylamide para-aminobenzoic acid hydrochloride) is an antiarrhythmic agent.
novocainamide, like quinidine, contains a tertiary amide group in the molecule, which determines the mechanism of its membrane-suppressive action. prolongs the effective refractory period more than the action potential in the atria and ventricles. slows down conduction in the atria, atrioventricular node and ventricles, inhibits the excitability and, to a small extent, the contractility of the myocardium. has a vasodilating effect, causing arterial hypotension. blocks parasympathetic reactions (anticholinergic effect). After oral administration, it is absorbed in the stomach within 15–30 minutes, the maximum concentration in the blood plasma is achieved after 1 hour.
With intravenous administration and a plasma concentration of 2–4 mg/l, the drug begins to have some antiarrhythmic effect, 4–10 mg/l is effective, above 8 mg/l is toxic. At a therapeutic concentration of about 15%, Novocainamide-Darnitsa binds to macromolecular compounds in blood plasma. It is relatively little hydrolyzed by plasma esterases. In most tissues, except the brain, the concentration of Novocainamide-Darnitsa is higher than in blood plasma. With intravenous administration, after 1–1.5 hours, the maximum level of the drug in the blood is reduced by 50%. The drug concentration curve for this route of administration has 2 phases: fast (average constant - 6.4 minutes, half-life - 4.4 minutes), due to the rapid entry of the drug into the blood, and slow, independent of its concentration in the blood (average constant - 5.1 hours, half-life - 3.5 hours). It is biotransformed in the liver with the formation of N-acetylnovocainamide (with slow acetylation - only 7-12%, with fast acetylation - about 23%). N-acetylnovocainamide acts similarly to procainamide, causing an antiarrhythmic effect.
Excreted by the kidneys by glomerular filtration and tubular secretion; 50–60% - unchanged. About 15% of the dose taken appears in the urine in the form of N-acetylnovocainamide; 2–10% - in the form of PABA. The half-life of Novocainamide-Darnitsa is 3–4 hours, and its acetyl-regulated form is about 4 hours. Usually the drug does not accumulate in the body, but in patients with heart and kidney failure its excretion is slowed down and accumulation may occur with long-term use. In case of renal failure, the half-life is extended to 7–17 hours (for the acetylated drug - up to 40 hours). In severe liver failure, the metabolism of Novocainamide-Darnitsa is reduced by 1/3. With an alkaline urine reaction, excretion of the drug decreases. Novocainamide-Darnitsa and its acetylated metabolite are excreted during hemodialysis.
Contraindications
Novocainamide is not prescribed for leukopenia, arrhythmias due to an overdose of cardiac glycosides , 2-3 degree AV block, or intolerance to procainamide.
For SLE, pathology of the renal and hepatic systems, myasthenia gravis , myocardial infarction, arrhythmia due to an overdose of glycosides, decompensated form of CHF, arterial hypertension, total atherosclerosis, bronchial asthma, the elderly and for prolongation of the QT interval, Novocainamide is prescribed with caution.
Side effects
Nervous system: ataxia , psychotic reactions, convulsions, dizziness, hallucinations, myasthenia gravis, depression, headaches.
Possible inhibition of bone marrow hematopoiesis, taste disturbance, hemolytic anemia , leukopenia, ventricular paroxysmal tachycardia, drop in blood pressure, asystole, conduction disturbances (atrial, intraventricular).
Long-term use can cause lupus erythematosus .
Side effects may include the development of thrombocytopenia, microbial infections, and difficulty in wound healing.
Instructions for use of Novocainamide (Method and dosage)
The drug is administered intramuscularly, intravenously, or taken orally.
Instructions for use of Novocainamide in ampoules
Intravenously: 100-500 mg of procainamide is dissolved in sodium chloride 0.9%, administered slowly, at a rate of no more than 50 mg per minute, pressure control is required. In some cases, repeated infusions of the same dose every five minutes are required to achieve the effect. To prevent a recurrent attack of arrhythmia, an infusion is performed at a rate of 2-6 mg per minute.
After stopping an arrhythmic attack, the achieved effect can be maintained by intramuscular administration of procainamide in a dose of 0.5-1 grams, but it is preferable to administer intravenously.
Intravenous drip: 500 mg per half hour. The maintenance dose is about 5 mg per minute.
Intramuscular: the average dose is 50 mg per kg per day over several injections.
Instructions for Novocainamide tablets
Used one hour before meals or 2 hours after meals with water. Do not chew the tablet.
At the beginning, 1 tablet is used as a test. A therapeutic dose of one to three tablets is then used. One tablet every 6 hours is prescribed as a maintenance dose.
Ventricular arrhythmia: every six hours, 50 mg/kg/day.
Novocainamide 100 mg/ml 5 ml 10 pcs. solution for intravenous and intramuscular administration
pharmachologic effect
Class Ia antiarrhythmic drug, has a membrane-stabilizing effect.
Inhibits the incoming fast Na+ current, reduces the rate of depolarization in phase 0. Inhibits conductivity, slows down repolarization. Reduces the excitability of the myocardium of the atria and ventricles. Increases the duration of the effective refractory period of the action potential (to a greater extent in the affected myocardium). The conduction slowdown, which is observed regardless of the value of the resting potential, is more pronounced in the atria and ventricles, less in the AV node.
The indirect m-anticholinergic effect, compared to quinidine and disopyramide, is less pronounced, so a paradoxical improvement in AV conduction is usually not observed.
Affects phase 4 of depolarization, reduces the automaticity of intact and damaged myocardium, inhibits the function of the sinus node and ectopic pacemakers in some patients.
The active metabolite, N-acetyl procainamide (N-APA), has pronounced activity as a class III antiarrhythmic drug and prolongs the duration of the action potential.
It has a weak negative inotropic effect (without a significant effect on IOC). It has vagolytic and vasodilating properties, which causes tachycardia and a decrease in blood pressure and peripheral vascular resistance.
Electrophysiological effects are manifested in widening of the QRS complex and prolongation of the PQ and QT intervals. The time to achieve the maximum effect when taken orally is 60-90 minutes, when administered intravenously - immediately, when administered intramuscularly - 15-60 minutes.
Composition and release form Novocainamide 100 mg/ml 5 ml 10 pcs. solution for intravenous and intramuscular administration
1 ml of solution contains the active ingredient: procainamide 100 mg.
The package contains 10 ampoules of 5 ml.
Directions for use and doses
For adults. For intravenous administration, 100 mg is diluted in 0.9% NaCl solution or 5% dextrose solution to a concentration of 2-5 mg/ml and administered slowly under blood pressure control at a rate of no more than 50 mg/min. If necessary, repeat the administration at the same dose every 5 minutes until the effect is achieved or up to a total dose of 1 g. To prevent re-development of arrhythmia, infusion can be performed at a rate of 2-6 mg/min.
After stopping the arrhythmia, to maintain the effect, intramuscular administration is possible - 0.5-1 g (up to 2-3 g / day), but oral or intravenous administration is preferable.
Inside. For atrial rhythm disturbances that do not require emergency treatment, the loading dose is 1.25 g, then 0.75 g every 1-2 hours if necessary and taking into account tolerance, 0.5-1 g every 2-3 hours. Maintenance dose - 0.5-1 g, in depending on effectiveness and tolerability, every 4-6 hours.
For ventricular arrhythmias that do not require emergency treatment, the loading dose is 50 mg/kg/day in 8 divided doses (every 3 hours), the dose is adjusted if necessary.
Pharmacokinetics
When taken orally and intramuscularly, absorption is rapid. Protein binding is 15-20%. Metabolized in the liver to form the active metabolite N-acetylprocainamide. Typically, about 25% of the administered procainamide is converted to this metabolite; however, with rapid acetylation or impaired renal function, 40% of the dose is converted.
T1/2 of procainamide is 2.5-4.5 hours, and in case of impaired renal function - 11-20 hours; N-acetylprocainamide - about 6 hours. Excreted by the kidneys, 50-60% unchanged, the rest as a metabolite. In case of impaired renal function or chronic heart failure, the metabolite quickly accumulates in the blood to toxic concentrations, while the concentration of procainamide remains within acceptable limits.
Indications for use Novocainamide 100 mg/ml 5 ml 10 pcs. solution for intravenous and intramuscular administration
Supraventricular arrhythmias: atrial fibrillation and/or flutter (including paroxysmal), tachycardia (including WPW syndrome), atrial extrasystole, ventricular arrhythmias (tachycardia, ventricular extrasystole).
Contraindications
Hypersensitivity, AV block II-III stage. (except in cases of use of an electrical pacemaker), ventricular flutter or fibrillation, arrhythmias due to intoxication with cardiac glycosides, leukopenia. With caution. Myocardial infarction, bundle branch block, arrhythmias due to intoxication with cardiac glycosides, myasthenia gravis, liver and/or renal failure, SLE (including history), bronchial asthma, decompensated CHF, ventricular tachycardia due to coronary artery occlusion, surgical interventions (including dental surgery), prolongation of the QT interval, arterial hypotension, severe atherosclerosis, myasthenia gravis, old age.
Application Novocainamide 100 mg/ml 5 ml 10 pcs. solution for intravenous and intramuscular administration during pregnancy and lactation
When used in children, higher doses may be required to maintain therapeutic concentrations; Older people are more likely to develop hypotension.
When prescribed during pregnancy, there is a potential risk of developing arterial hypotension in the mother, which can lead to uteroplacental insufficiency.
special instructions
During the treatment period, care must be taken when driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.
Overdose
Symptoms: confusion, oliguria, fainting, drowsiness, severe dizziness (especially in elderly patients), rapid or irregular heartbeat, nausea, vomiting, diarrhea, loss of appetite, decreased amplitude of the QRS complex and T wave, decreased blood pressure, collapse, AV blockade, ventricular paroxysmal tachycardia, asystole.
Treatment: if taken recently - gastric lavage, use of drugs that acidify urine; hemodialysis; when blood pressure decreases, norepinephrine or phenylephrine is administered.
Side effects Novocainamide 100 mg/ml 5 ml 10 pcs. solution for intravenous and intramuscular administration
From the nervous system: hallucinations, depression, myasthenia gravis, dizziness, headache, convulsions, psychotic reactions with productive symptoms, ataxia.
From the digestive system: bitterness in the mouth.
From the hematopoietic organs and hemostasis system: with long-term use - inhibition of bone marrow hematopoiesis (leukopenia, thrombocytopenia, neutropenia, agranulocytosis, hypoplastic anemia), hemolytic anemia with a positive Coombs test.
From the senses: taste disturbances.
From the cardiovascular system: decreased blood pressure, ventricular paroxysmal tachycardia. With rapid intravenous administration, collapse, disruption of atrial or intraventricular conduction, and asystole are possible.
Allergic reactions: skin rash.
Other: with long-term use - drug-induced lupus erythematosus (in 30% of patients with a duration of therapy of more than 6 months).
Drug interactions
Enhances the effect of antiarrhythmic, hypotensive, anticholinergic and cytostatic drugs, muscle relaxants, side effects of bretylium tosylate. When used simultaneously with antihistamines, atropine-like effects may increase; with pimozide - prolongation of the QT interval. Reduces the activity of anti-myasthenic drugs.
Cimetidine reduces the renal clearance of procainamide and prolongs T1/2.
When combined with class III antiarrhythmic drugs, the risk of developing an arrhythmogenic effect increases.
Drugs that inhibit bone marrow hematopoiesis increase the risk of myelosuppression.
Overdose
Characterized by severe dizziness, oliguria , drowsiness, fainting, confusion, vomiting, rapid heartbeat, asystole, paroxysmal tachycardia, loss of appetite, diarrhea, AV block, collapse, drop in blood pressure.
Administration of phenylephrine and norepinephrine is required when blood pressure drops.
Hemodialysis, gastric lavage, and prescription of drugs that acidify urine are effective.
Interaction
Novocainamide enhances the effect of muscle relaxants, anticholinergics, cytostatics, and antihypertensive drugs.
Atropine-like effects are enhanced when taken simultaneously with antihistamines.
Prolongation of the QT interval has been reported when procainamide is taken with pimozode.
Novocainamide enhances the side effects of bretylium tosylate and suppresses the effect of antimyasthenic drugs.
The risk of developing myelosuppression increases with the use of drugs that inhibit bone marrow function.
The likelihood of an arrhythmogenic effect increases when prescribed simultaneously with class 3 antiarrhythmic drugs.
The half-life of Novocainamide increases and renal clearance decreases when taking cimetidine.
special instructions
Novocainamide is taken on an “empty stomach”, the desired time of administration is two hours after meals or an hour before bedtime. Take the tablets with water and milk.
The solution must be diluted before intravenous administration.
Procainamide therapy involves monitoring blood pressure, ECG, leukocyte levels, and peripheral blood status.
After long-term therapy, 80% of patients experience an increase in the titer of antinuclear antibodies.
Long-term use of the long-acting drug Novocainamide after cardiac surgery leads to the development of leukopenia.
Elderly people may develop hypotension .
Children need to be prescribed higher doses compared to therapeutic dosages.
Administration to pregnant women leads to an increased risk of developing arterial hypotension in mothers, which causes uteroplacental insufficiency.
Novocainamide affects concentration and transport control.
Novocainamide-Darnitsa solution for injection, 5 ml in ampoule, 100 mg/ml, 10 pcs.
When administering the drug, monitoring of pulse, blood pressure, ECG and other vital functions of the body should be carried out.
After achieving and maintaining therapeutic concentrations of procainamide in the blood plasma, it is also recommended to periodically monitor vital functions and ECG, and with long-term use of the drug, periodic detailed blood tests should be performed to identify possible characteristic hematological effects of procainamide on neutrophils, platelets or red blood cells.
If first degree blockade or arterial hypotension occurs, the dose should be reduced or the drug should be discontinued; if necessary, vasopressors should be prescribed with caution.
In case of excessive widening of the QRS complex or prolongation of the PR interval, the drug should be discontinued.
During use of the drug, the patient should be carefully monitored for the development of hypersensitivity reactions, especially if there is a history of allergic reactions to procaine or other local anesthetics, as well as muscle weakness in patients with a tendency to myasthenia gravis.
The drug should be used with caution in patients with acute coronary heart disease, cardiomyopathy and myocardial infarction due to the possibility of inhibition of myocardial contractility.
The drug is not recommended for use in cases of severe atherosclerosis.
It should be borne in mind that when changing atrial fibrillation to normal sinus rhythm by any means, including the use of procainamide, there is a risk of thromboembolism.
If during treatment there is an expansion of the QRS complex by more than 25% or signs of prolongation of the QT interval, an overdose may develop. If the QRS complex or QT interval widens by more than 50%, dose adjustment should be made.
Procainamide-induced lupus syndrome rarely involves dangerous pathological changes in the kidneys. If it occurs, the drug does not have to be stopped, but if symptoms of serositis develop and there are signs of further development of the consequences of lupus syndrome, treatment with novocainamide should be stopped.
Patients with rapid acetylation are less likely to develop lupus syndrome even after long-term procainamide therapy.
An increase in serum antinuclear antibody titer may precede clinical symptoms of lupus syndrome. If a lupus erythematosus-like syndrome develops in patients with recurrent life-threatening arrhythmias that are not controlled by other drugs, treatment with predominantly corticosteroids may be used concomitantly with procainamide.
Hypokinesia of the gastrointestinal tract may develop (especially in patients with diabetes), which is due to the anticholinergic properties of procainamide.
Hypersensitivity reactions may also include hepatitis, intrahepatic cholestasis, increased activity of liver enzymes, and fever.
Should not be used in patients with digoxin toxicity.
Cross-reactions with novocaine are possible.
Accumulation of procainamide may occur in patients with cardiac, hepatic or renal impairment.
Novocainamide price, where to buy
20 tablets are sold for approximately 100 rubles.
10 ampoules of solution cost 150-200 rubles.
- Online pharmacies in RussiaRussia
- Online pharmacies in UkraineUkraine
ZdravCity
- Novocainamide tablets 250 mg 20 pcs. JSC Organika
118 rub. order - Novocainamide solution for intravenous and intramuscular administration. 100mg/ml amp. 5ml 10 pcs. JSC Organika
RUB 176 order
Pharmacy Dialogue
- Novocainamide (tab. 250 mg No. 20)Organika (Novokuznetsk Autonomous Okrug)
108 RUR order
- Novocainamide (tab. 250 mg No. 20 (10x2)) Organics (Novokuznetsk Autonomous Okrug)
115 rub. order
show more
Pharmacy24
- Novocainamide-Darnitsa 10% 100 mg/ml No. 10 solution PrAT" Pharmaceutical company "Darnitsa", Ukraine
100 UAH. order
Application
For paroxysmal ventricular tachycardia, 0.2–0.5 g is administered intravenously over 10 minutes under the control of an ECG and blood pressure. if the pressure decreases by more than 15 mm Hg. Art. sympathomimetics are administered or the administration of procainamide-Darnitsa is stopped. after the attack stops, 0.25-0.5 g is prescribed orally every 4-6 hours. For paroxysm of atrial fibrillation or atrial flutter - 0.5-1 g intramuscularly 4 times a day until the attack stops, but not more than 72 hours after restoration of the rhythm, continue to administer 0.5 g 4 times a day for 2 days or prescribe orally 0.25–0.5 g 4 times a day under the control of an ECG and blood pressure. with this type of arrhythmia, you can first administer orally in a loading dose of 1.25 g, if there is no effect - after 1 hour - 0.75 g, and then every 2 hours 0.5-1 g, but not more than 4 g per day ( highest dose).
Orally for ventricular extrasystole, adults are prescribed an initial dose of 0.25–0.5–1 g, then 0.25–0.5 g every 4–6 hours. If necessary, the daily dose can be increased to 3, sometimes to 4 d. The duration of treatment depends on the effectiveness and tolerability of the drug.
For paroxysms of atrial fibrillation or atrial flutter, the recommended loading dose for oral administration is 1.25 g. If this dose is ineffective, then after 1 hour an additional 0.75 g is prescribed and then every 2 hours - 0.5–1 g until relief paroxysm; the maximum daily dose is 3–4 g.
