Novokainamid-Darnitsa, the tab. on 0:25 g No. 20

General characteristics. Structure:

Active ingredient: procainamide;

1 tablet contains procaineamide of a hydrochloride (novokainamid) 250 mg;

excipients: коповидон, cellulose microcrystallic, starch prezhelatinizirovanny, silicon dioxide colloid anhydrous, calcium stearate.

Pharmacological properties:

Pharmacodynamics. Procaineamide – the antiarrhytmic drug Ia of a class, has membrane stabilizing effect. 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 AV node. Indirect M-holinoblokiruyushchy the effect in comparison with quinidine and Disopyramidum is expressed less therefore paradoxical improvement of AV conductivity usually is not noted. 4 depolarizations of membranes of cells 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   of N-atsetilprokainamid procaineamide has the expressed activity of antiarrhytmic means of the III class, extends duration of their action potential. Possesses a weak negative inotropic effect (without significant effect on cordial emission). Has vagolytic and vazodilatiruyushchy properties that causes tachycardia and a lowering of arterial pressure, the general peripheric vascular resistance. Electrophysiologic effects are shown by expansion of the QRS complex and lengthening of intervals of PQ and QT. Time of achievement of the maximum effect at intake makes 60-90 minutes.

Pharmacokinetics. Novokainamid is soaked up from a stomach in 15-30 min., its maximum concentration in a blood plasma after intake is observed in 1 hour. Effective therapeutic concentration in a blood plasma makes 4-10 mkg/ml. At therapeutic concentration – 15% of a novokainamid there is in the connected state with proteins of a blood plasma, and its other part – with fabrics (a liver, kidneys, a spleen, lungs, muscles). The preferential way of biotransformation of a novokainamid is N-acetylation. Its main metabolite is N-atsetilnovokainamid. He is more slowly brought from an organism, than новокаинамид therefore its average concentration is 1,5 times higher, than a novokainamida; the metabolite has antiarrhytmic effect, identical with it.

To 90% of a novokainamid it is removed with urine due to glomerular filtering and canalicular secretion. To 50% of a novokainamid 8-14% – in the form of its derivatives, 7,4-24% – in the form of other metabolites are removed in not changed look. In 6-8 hours with urine 50-60% of drug are removed. The elimination half-life of a novokainamid makes 3-4 hours, and its acetylized form – about 4 hours.

The pharmacokinetics of a novokainamid changes at patients with a renal failure, heart and a liver. The elimination half-life increases by 3 times at decrease in glomerular filtering to 10 ml/min., twice – at decrease in minute volume of heart and damage of a liver. At patients with heart failure and a myocardial infarction drug is badly soaked up from the digestive channel therefore it should be entered parenterally. At elderly people the dose of a novokainamid needs to be reduced.

Pharmaceutical characteristics.

Main physical and chemical properties: tablets of color, white or almost white with a creamy-gray shade, a round form, with a flat surface, a facet and risky.

Indications to use:

Frustration of a cordial rhythm: ventricular arrhythmias, paroxysms of a ciliary arrhythmia or atrial flutter, Bouveret's ventricular disease, ventricular premature ventricular contraction.

Route of administration and doses:

Drug is used inside.

The peroral dose and frequency of introduction have to be corrected individually for each specific patient on the basis of clinical assessment of severity of a basic disease of a myocardium, age of the patient, function of kidneys.

Adults.

So, for young adult patients with normal function of kidneys the initial general daily dose of procaineamide for oral administration usually makes to 50 mg/kg of body weight (14 tablets at the body weight of 70 kg) in the divided doses each 3 hours to support therapeutic level in blood. For patients, 50 years are especially more senior, or the smaller single dose or longer intervals between receptions is applied to patients with renal, liver or heart failure that provides maintenance of therapeutic level of drug in blood, and also reduces probability of emergence of dozozavisimy side reactions. To apply the general daily dose in the divided doses at an interval of 3, 4 or 6 hours and to adjust depending on reaction of the patient.

To provide a daily dose about 50 mg/kg of body weight, dosing of procaineamide is carried out according to the following scheme: *

Body weight of the patient, kg                     procaineamide Dose
 
                                                To 40-50 250 mg there are each 3 hours or
                                                         To 500 mg there are each 6 hours

                                                To 60-70 375 mg there are each 3 hours or
                                                         To 750 mg there are each 6 hours
 
                                                To 80-90 500 mg there are each 3 hours of Abo
                                                         To 1000 mg there are each 6 hours
 
>                                               To 100 625 mg there are each 3 hours of Abo
                                                         To 1250 mg there are each 6 hours

* Initial dosing is carried out only according to the schedule, adapts for each patient individually, depending on age, cardiorenal function, drug level in blood (if that is defined) and the clinical answer.

At ventricular premature ventricular contraction, tachycardia: the first dose of 250-500-1000 mg, the subsequent – to 250-500 mg is each 3-6 hours.

At paroxysms of a ciliary arrhythmia or an atrial flutter it is recommended to apply a "load" dose of drug – 1250 mg. If this dose is inefficient, then in an hour in addition accept drug in a dose of 750 mg and further every 2 hour in a dose of 500-1000 mg before stopping of a paroxysm.

 

Features of use:

Use during pregnancy or feeding by a breast.

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

During pregnancy drug is appointed according to vital indications.

Procaineamide is excreted in breast milk therefore during treatment it is necessary to stop feeding by a breast.

Children. As safety and efficiency of use of drug to children were not studied, drug use is not recommended to children.

In an initiation of treatment procaineamide it is necessary to watch carefully the patient regarding emergence of reactions of hypersensitivity, especially in the presence in the anamnesis of hypersensitivity to Procainum or other local anesthetics, and also regarding development of muscular weakness in patients with predisposition to a myasthenia.

When changing fibrillation of auricles with a normal sinoatrial rate by means of any means, including at procaineamide use, there is a threat of a thromboembolism that it must be kept in mind.

Stable therapeutic concentration of procaineamide in a blood plasma at the recommended dosing decides approximately in a day after the beginning of administration of drug on the peaks of concentration in 90-120 minutes after reception of each dose. After achievement and at maintenance of therapeutic concentration in a blood plasma it is recommended to carry out periodically monitoring of the vital functions and the electrocardiogram.

If during treatment the QRS expansion more than for 25% or signs lengthening of an interval of QT is observed, it is necessary to suspect overdose, and reduction of a dosage makes sense if there are 50% increase in the QRS complex or interval of QT.

Increase in serumal creatinine or urea, decrease in clearance of creatinine or renal failure in the anamnesis, and also use to patients, is especially more senior than 50 years, give the grounds to assume that the dose smaller, than usually and longer periods between administrations of drug can provide sufficient clinical performance. At a chronic renal failure the interval between reception of doses makes 4 hours (clearance of creatinine more than 50 ml/min.), 6-12 hours (clearance of creatinine of 10-50 ml/min.), 12-24 hours (clearance of creatinine less than 10 ml/min.).

Definition of concentration in a procaineamide blood plasma is possible, but attentive observation of clinical performance is the most important criterion for evaluation of effect of drug.

In the long term the periodic developed blood tests are useful to identification of possible characteristic hematologic effects of procaineamide on neutrophils, thrombocytes or erythrocytes (a leukopenia, a neutropenia, thrombocytopenia, an agranulocytosis, hemolitic anemia with positive test of Koombs). Increase in a caption of antinuclear antibodies of serum can precede clinical symptoms of a lupoid syndrome. If the syndrome, similar to a lupus erythematosus, develops at patients with recurrent life-threatening arrhythmia which is not regulated by other drugs, along with purpose of procaineamide therapy preferential corticosteroids is applicable.

The procaineamide-induced lupoid syndrome seldom includes dangerous pathological changes of kidneys therefore at its emergence therapy by procaineamide shall not be stopped, however, if symptoms of a serositis develop and there are signs of further development of effects of a lupoid syndrome, the risk from procaineamide use continuation in that case prevails over its efficiency in treatment of disturbances of a cordial rhythm that demands drug withdrawal.

At patients with bystry acetylation development of a lupoid syndrome even after long therapy by procaineamide is less probable.

Due to the possible oppression of sokratitelny ability of a myocardium and a lowering of arterial pressure it is necessary to use carefully drug at a myocardial infarction. At the expressed atherosclerosis drug is not recommended to be used. At chronic heart failure the daily dose is reduced on 1/3 and more.

When performing therapy it is necessary to carry out monitoring of arterial pressure, control of the electrocardiogram, indicators of peripheral blood (the developed blood test), especially leukocytes (each 2 weeks within the first 3 months of therapy, further – with longer intervals), definition of creatinine of blood serum or an urea nitrogen. During prolonged treatment or at emergence of symptoms, similar to a system lupus erythematosus, it is necessary to define a caption of antinuclear antibodies periodically.

Ability to influence speed of response at control of motor transport or work with other mechanisms.

At use of drug it is necessary to refrain from driving and performance of other potentially dangerous types of activity requiring special attention and speed of psychomotor reactions.

Side effects:

From a nervous system: weakness, a depression, a myasthenia, dizziness, a headache, spasms, drowsiness, psychotic reactions with productive symptomatology, an ataxy.

From the alimentary system: anorexia, an abdominal pain, bitterness in a mouth, nausea, vomiting, diarrhea.

From bodies of a hemopoiesis and system of a hemostasis: at prolonged use – a leukopenia, a neutropenia, thrombocytopenia, an agranulocytosis, hemolitic anemia with positive test of Koombs.

From sense bodys: taste disturbance.

From cardiovascular system: lowering of arterial pressure, ventricular Bouveret's disease, AV blockade, asystolia.

Others: at prolonged use – a medicamentous lupus erythematosus (at 30% of patients lasting therapy more than 6 months), arthritis, exudative pleurisy, a pericardis, fever, a fever, muscle pain.

From skin: Quincke's disease, small tortoiseshell, itch, reddening, skin rash, makulopapulezny rash.

Interaction with other medicines:

Antiarrhytmic drugs: parallel use with procaineamide can result in cumulative or antagonistic cardial effects and/or increase in toxic effects. Reduction of a dosage can be required.

Parallel use with antiarrhytmic means of a class I (for example, quinidine or Disopyramidum) can become the reason of delay of conductivity or a depression of sokratitelny function of a myocardium and arterial hypotension, especially at patients with a cordial decompensation. Such combination can be appointed to patients with serious arrhythmia which does not give in to monotherapy, and has to be applied only on condition of careful observation.

Combined use with Amiodaronum can lead to increase in concentration of procaineamide and N-atsetilprokainamida in a blood plasma, to increase in toxicity. The dose of procaineamide has to be in that case reduced. Besides, summation of electrophysiologic effects can arise at a concomitant use with drugs which extend QT interval.

It is undesirable to use drug with cardiac glycosides because of a possibility of sharp oppression of atrioventricular conductivity.

Beta-blockers: procaineamide can strengthen cardiodepressive action          of beta-blockers, such as propranolol.

Anticholinergics: procaineamide strengthens anticholinergic effects. At such combination it is necessary to observe extra care.

Antikholinesterazny means: procaineamide is an antagonist of effect of antikholinesterazny means at a myasthenia of gravis and recurrent paralysis.
Anti-hypertensive drugs: procaineamide can strengthen hypotensive effect of thiazide diuretics and other anti-hypertensive means. There can be necessary correction of a dose.

Cimetidinum: the antagonist of H2 - histamine receptors Cimetidinum can reduce renal clearance of procaineamide and N-atsetilprokainamida that leads to increase in concentration of the last in a blood plasma and prolongation of their effects. It is necessary to be careful at use of these drugs at the same time, especially at the elderly people having the lowered possibility of a conclusion of all these three means. In that case change of a dosage can be required.

Blockers of neuromuscular conductivity: procaineamide exponentiates effects of muscle relaxants, such as сукцинилхолин. Procaineamide can strengthen or prolong myorelaxation activity of bacitracin, a kolistimetat, dihydrostreptomycin, gentamycin, gramicidin, Kanamycinum, Neomycinum, polymyxin B, streptomycin and Viomycinum that can lead to respiratory depression.

Antibiotics: procaineamide can interact with Kanamycinum, Neomycinum and streptomycin, causing an apnoea and muscular weakness that is connected with strengthening of myorelaxation effects.

Trimethoprimum: the renal clearance of procaineamide and N-atsetilprokainamida decreases that leads to increase in the pharmakodinamichesky answer.

Procaineamide is not applied along with streptocides and lidocaine (owing to possible summation of side neurologic effects).

Strengthens effects of cytostatic means, side effect of a bretylium of tosylate.

Contraindications:

Hypersensitivity to any of drug components. Atrioventricular blockade of II and III degrees, blockade of branches of a ventriculonector, heart failure of the II-III stage; the arrhythmias connected with glikozidny intoxication; arrhythmias like "pirouette"; arterial hypotension; heavy renal and liver failure, parkinsonism, lupus erythematosus, bronchial asthma, myasthenia.

Overdose:

Symptoms: oppression of the central nervous system, confusion of consciousness, tremor, respiratory depression, severe dizziness, collapse, nausea, vomiting, lowering of arterial pressure, progressive expansion of the QRS complex, lengthening of intervals of QT and PR, decrease in teeth of R and T, AV blockade, ventricular premature ventricular contraction, ventricular Bouveret's disease, fibrillation of ventricles, asystolia.

Treatment. There is no special antidote. The call of vomiting and a gastric lavage can reduce absorption of procaineamide at overdose. Carry out careful observation, monitoring of the vital functions of an organism.

Actions at overdose include a symptomatic treatment, ECG control, monitoring of arterial pressure. Intravenous administration 1/6 molar sodium lactates reduces cardiotoxic effects of overdose by procaineamide.

Procaineamide removal speed kidneys is directly proportional to a glomerular filtration rate, and also increases at reduction рН urine therefore apply the means acidifying urine. At heavy arterial hypotension apply a dopamine, a phenylephine hydrochloride or noradrenaline, infusional therapy. Symptomatic therapy at ventricular tachycardia; hemodialysis. Peritoneal dialysis is inefficient. At AV blockade of II and III degrees electrocardiostimulation use is reasonable.

Storage conditions:

Term godnosti.1,5 years. To store in the place, unavailable to children, in original packaging at a temperature not above 25 °C.

Issue conditions:

According to the recipe

Packaging:

On 10 tablets in a blister strip packaging; on the 2nd blister strip packagings in a pack.