Propafenone, 150 mg 50 pcs

Pharmacotherapeutic group

antiarrhythmic drug

Pharmacodynamics:

Propafenone is an antiarrhythmic drug with membrane-stabilizing properties as a sodium channel blocker (class IC) and mild beta-adrenoblocking activity (class II).

The local anesthetic effect approximately corresponds to the activity of procaine. It reduces the maximum speed of depolarization of phase 0 action potential and its amplitude in Purkinje fibers and ventricular contractile fibers suppresses automatism. Slows conduction along Purkinje fibers. Lengthens conduction time in the sinoatrial (SA) node and atria. Does not affect or slightly increases the corrected recovery time of sinus node function during programmed electrical stimulation.

Lengthens the effective refractory period of the atrioventricular node inhibits conduction through additional pathways in the retrograde and antegrade directions increases the ventricular stimulation threshold.

The electrophysiological effects are more pronounced in ischemic than in normal myocardium. It has a negative inotropic effect, which is usually manifested when left ventricular ejection fraction decreases below 40%. Action begins 1 hour after oral administration and lasts for 8-12 hours.

Pharmacokinetics:

Absorption

The absorption of more than 95% of the drug. Systemic bioavailability is 5-50%. Intake with food increases the bioavailability in patients with intensive metabolism.

Propafenone exhibits dose-dependent bioavailability which increases nonlinearly with increasing dose: it increases from 5% to 12% with increasing a single dose from 150 mg to 300 mg, and with 450 mg – up to 40-50%. The time of reaching maximum plasma concentration (TSmax) after oral administration is 1-35 hours, and its value varies from 500 to 1500 mcg/l. The equilibrium plasma concentration (Css) is reached 3-4 days after the start of therapy.

Distribution

Propafenone has low permeability through the blood-brain barrier and the placental barrier. The concentration of propafenone in the umbilical cord is 30% of its concentration in maternal blood. The volume of distribution is 3-4 l/kg.

The binding to plasma proteins and internal organs (liver, lungs, etc.) is 85-97%. Propafenone undergoes significant and saturable presystemic biotransformation by CYP2D6 isoenzyme (effect of “primary passage” through the liver) that leads to absolute bioavailability of dose-dependent and dosage form of the drug.

Metabolism

There are 2 models of the genetically determined metabolism of propafenone. In more than 90% of patients, propafenone is rapidly and significantly metabolized with a half-life (T1/2) of 28 to 11 hours.

Eleven metabolites of propafenone have been described, of which two are pharmacologically active: 5-hydroxypropafenone is formed by the CYP2D6 isoenzyme and N-depropylpropafenone (norpropafenone) by the CYP3A4 and CYP1A2 isoenzymes. In less than 10% of patients propafenone is metabolized more slowly because 5-hydroxypropafenone is not formed or is formed in small amounts. With this type of metabolism, the elimination half-life is about 17 h. In significant metabolism with saturable hydroxylation cycle by CYP2D6 isoenzyme the pharmacokinetics of propafenone is nonlinear and in slow metabolism it is linear. Since the equilibrium state of pharmacokinetic parameters is reached 3-4 days after oral administration in all patients, the drug dosing regimen is the same for all patients regardless of metabolic rate. Pharmacokinetics has a significant individual variability that is mainly due to the effect of “primary passage” through the liver as well as its non-linearity in extensive metabolism. The variability in propafenone blood concentrations requires cautious dose titration and patient monitoring with ECG monitoring.

Extracted by the kidneys – 38% as metabolites (less than 1% unchanged) through the intestine with the bile – 53% (as glucuronides and sulfate metabolites and unchanged propafenone. In hepatic insufficiency, excretion is reduced.

Indications

Prevention and treatment of ventricular arrhythmias;

Prevention and treatment of paroxysmal supraventricular tachyarrhythmias (including atrial fibrillation/tremor; Paroxysmal supraventricular tachyarrhythmias of the reentry type with involvement of the atrioventricular node or additional conduction pathways when other therapy is ineffective or contraindicated).

Active ingredient

Composition

1 film-coated tablet contains:

The core:

the active ingredient: propafenone hydrochloride 150,000 mg;

the excipients: lactose monohydrate 10,120 mg, sodium lauryl sulfate 2,300 mg, sodium carboxymethyl starch 18,400 mg, magnesium stearate 0,690 mg, povidone 11,500 mg, talc 0,460 mg, microcrystalline cellulose 36,530 mg.

The shell:

Please white opadray Y-1-7000 5.000 mg (hypromellose 5cP 3.125 mg, titanium dioxide E171 1.5625 mg, macrogol-400 0.3125 mg).

How to take, the dosage

Ingestion. Tablets should be swallowed whole after a meal with a small amount of water.

The dosing regimen is determined individually and adjusted by the physician. It is recommended that therapy should be started in a hospital after all antiarrhythmic drugs have been discontinued (with BP monitoring and QRS latitude evaluation by ECG).

In patients with a significantly dilated QRS complex and AV block of II and III degree it is recommended to reduce the dose.

In patients with a body weight of 70 kg or more, the initial dose is 150 mg 3 times per day (in hospital under control of BP ECG). The dose may be increased gradually at 3 to 4 day intervals to 300 mg 2 times a day and, if necessary, to a maximum dose of 300 mg 3 times a day.

In elderly patients with a body weight of less than 70 kg, the drug is started at a lower dose, gradually increasing the dose. The same tactics should be followed for maintenance therapy. Do not start increasing the dose of the drug if the duration of use is less than 5-8 days.

In patients with hepatic impairment (cumulation is possible) Propafenone is used in doses of 20-30% of the usual dose in patients with renal impairment (creatinine clearance less than 10%) the initial dose is 50% of the usual dose.

Interaction

Pharmacodynamic interaction

In intravenous administration of lidocaine concomitantly with propafenone – increased risk of central nervous system damage.

Concomitant use with beta-adrenoblockers may increase antiarrhythmic effect with local anesthetics and drugs that suppress cardiac activity – increase the effect of propafenone. Concomitant use of propafenone with misolastin ritonavir tricyclic antidepressants or neuroleptics increases the risk of arrhythmias.

The use of propafenone in combination with phenobarbital and/or rifampicin may reduce the antiarrhythmic effectiveness of propafenone hydrochloride.

Amiodarone increases the risk of pirouette tachycardia. Doses of both drugs may need to be adjusted depending on the therapeutic response. Drugs depressing the sinoatrial and atrioventricular nodes and having a negative inotropic effect increase the risk of side effects. Drugs that suppress medullary hematopoiesis increase the risk of myelosuppression.

Pharmacokinetic interaction

Enhances plasma concentrations of propranolol metoprolol digoxin (increases the risk of glycoside intoxication) indirect anticoagulants cyclosporine theophylline desipramine. Increases the effect of warfarin (blocks metabolism).

Cimetidine quinidine ketoconazole tropisetron dolasetron misolastin erythromycin and grapefruit juice slowing metabolism increase plasma propafenone concentration by 20% so patients should be carefully monitored and the dose of propafenone rifampicin should be adjusted accordingly.

The use of propafenone hydrochloride in combination with venflaxin may lead to increased concentration of venflaxin. Concomitant use of propafenone hydrochloride and fluoxetine in “fast” metabolizers increases Cmax S-propafenone by 39% and AUC by 50% and Cmax R-propafenone by 71% and AUC by 50%. Therefore, lower doses of propafenone may be sufficient to achieve the desired therapeutic response.

Elevated plasma levels of propafenone may occur with concomitant use with paroxetine so the propafenone dose should be reduced.

The concomitant use of propafenone hydrochloride and ritonavir at a dose of 800-1200mg/day is contraindicated due to the potential for increased plasma concentrations.

Special Instructions

EKG monitoring is required during the course of treatment, especially at the beginning of therapy. It is recommended to start treatment under hospital conditions since there is an increased risk of arrhythmogenic effects associated with the use of Propafenone.

Propafenone should be used under control of blood electrolyte balance (especially potassium) and ECG. If ECG changes, such as QRS prolongation or Q-T interval prolongation greater than 25% or PR interval greater than 50% or Q-T interval greater than 500 msec or increased frequency and severity of cardiac arrhythmias are noted, the decision should be made whether to continue treatment.

In elderly patients or patients with significant impairment of left ventricular function (left ventricular ejection fraction <35%) or with organic myocardial changes, treatment should be started gradually with extreme caution and doses should be increased gradually. The same applies to maintenance therapy. Any dose increases that may be necessary should be made after 5 to 8 days of treatment.

In elderly patients or patients with organic myocardial changes, the drug dose should be titrated with great caution. When treating paroxysmal atrial fibrillation, there may be a transition from atrial fibrillation to atrial flutter with 2:1 or 1:1 conduction to the ventricles with a very high ventricular contraction rate (i.e. >180 beats per minute).

The drug treatment can affect the sensitivity and frequency threshold of artificial pacemakers. Therefore, pacemakers should be checked and, if necessary, reprogrammed because the drug may affect the sensitivity and frequency threshold of the artificial pacemaker. Liver transaminase activity should be determined periodically.

In the treatment of ventricular rhythm disturbances, Propafenone is more effective than Class IA and IB antiarrhythmic agents.

In patients with impaired liver function, the bioavailability of Propafenone increases by 70% in these patients, and it is recommended to reduce the dose and monitor laboratory parameters regularly.

The indication and dose should be particularly carefully determined for patients with an artificial pacemaker.

Patients receiving long-term treatment with anticoagulants and hypoglycemic agents should be closely monitored both clinically and laboratory.

If during therapy sinoatrial block or grade III atrioventricular block or recurrent extrasystoles occur, treatment should be stopped.

With due to the probable proarrhythmogenic effect on the patient’s prognosis, it is recommended that the drug should only be used as directed and supervised by a physician.

The drug contains lactose monohydrate. It must be taken into account in patients with lactase deficiency with lactose intolerance glucose-galactose malabsorption.

Particular effects of the drug when withdrawing

While there is no withdrawal syndrome with BMKK (slow calcium channel blocker), a gradual decrease in doses is recommended before discontinuing treatment.

Patient’s physician (paramedic) should take the missed dose as soon as the omission is discovered. If it is already time for the next dose, the missed dose should be skipped and the missed dose should be taken as directed. It is not acceptable to take a double dose to make up for the missed dose.

During treatment, it is necessary to refrain from operating vehicles and engaging in potentially hazardous activities that require increased concentration and rapid psychomotor reactions.

Contraindications

If you have any of the following conditions, be sure to consult your physician before taking this medication.

– Hypersensitivity to propafenone and components of the drug;

– Severe forms of chronic heart failure (decompensation stage) uncontrolled chronic heart failure;

– cardiogenic shock (except for arterial hypotension due to tachycardia and antiarrhythmic shock);

– Severe bradycardia and arterial hypotension;

– sinoatrial conduction disturbance sinoatrial block;

– Gis bundle branch block or distal block (in patients without a pacemaker);

– significant electrolyte and water balance disorders (e.g., potassium metabolism disorders)

– myasthenia gravis;

– severe forms of chronic obstructive pulmonary disease (COPD) bronchospasm (history);

– intraventricular bifascicular block and atrioventricular block of degree II-III (without pacemaker);

– sinus node weakness syndrome;

– tachycardia-bradycardia syndrome;

– significant organic myocardial changes such as refractory chronic heart failure with left ventricular ejection fraction less than 35% and cardiogenic shock other than arrhythmic shock;

– concomitant use of ritonavir at a dose of 800-1200 mg/day;

Patients with lactase deficiency lactose intolerance glucose-galactose malabsorption;

– Age

Side effects

Blood organs: leukopenia granulocytopenia thrombocytopenia agranulocytosis increased bleeding time manifestation of antinuclear antibodies; Immune system: allergic hypersensitivity reactions (manifested by cholestasis pathological changes in the blood).

Metabolism disorders: decreased appetite.

Nervous system disorders: headache dizziness fainting impairment of movement coordination anxiety anxiety confusion; nightmares sleep disorders extrapyramidal symptoms vertigo paresthesia convulsions.

Visual disorders: blurred vision (hazy) diplopia.

Cardiovascular system disorders: marked bradycardia atrioventricular dissociation ventricular tachyarrhythmias angina pectoris worsening the course of heart failure (in patients with reduced left ventricular function) conduction disorders (sinoatrial block atrioventricular block intraventricular block) proaritmogenic effect (tachycardia ventricular fibrillation) supraventricular tachyarrhythmias when taken in high doses – Significant decrease in BP including postural and orthostatic hypotension (especially in elderly patients) chest pain.

Gastrointestinal disorders: nausea vomiting constipation dry mouth bitterness abdominal pain diarrhea flatulence belching change in taste; liver disorders including hepatocellular disorders cholestatic jaundice cholestasis hepatitis.

Skin disorders: lupus-like syndrome skin redness skin rash pruritus exanthema urticaria hemorrhagic skin rash.

Urogenital system: oligospermia decreased potency.

Other: weakness increased sweating bronchospasm.

Laboratory findings: increased activity of “liver” transaminases.

If any of the side effects listed in the instructions worsen, or if you notice any other side effects not listed in the instructions, tell your doctor.

Overdose

Intoxication may occur when a single dose of twice the daily dose is taken; symptoms of intoxication appear after 1 hour to a maximum of several hours.

The symptoms of overdose: persistent decrease in blood pressure nausea dry mouth vomiting mydriasis somnolence extrapyramidal disorders confusion bradycardia prolonged Q-T interval disorders intraatrial and intraventricular conduction ventricular tachyarrhythmias paroxysms of polymorphic ventricular tachycardia sinoatrial and atrioventricular blocks asystole coma seizures delirium pulmonary edema.

Treatment: gastric lavage defibrillation administration of dobutamine diazepam; if necessary – artificial lung ventilation and indirect heart massage. Because propafenone has a large volume of distribution and high degree of binding to plasma proteins (more than 95%), hemodialysis and hemoperfusion are not effective.

Pregnancy use

Propafenone use during pregnancy, especially in the first trimester, is possible only when the expected benefit to the mother exceeds the potential risk to the fetus. Propafenone penetrates the placental barrier. The concentration of propafenone in the umbilical cord is 30% of its concentration in maternal blood.

Propafenone is excreted in breast milk. If it is necessary to use propafenone during lactation, breastfeeding should be stopped.