Ritmonorm, 150 mg 50 pcs.

Propafenone has membrane stabilizing properties, properties of a sodium channel blocker (class 1C) and weakly expressed beta-adrenoblocking activity (class II).

It slows down the rise of action potential, due to which the pulse conduction velocity decreases (negative dromotropic effect). The refractory period in the atrium, atrioventricular (AV) node and ventricles is prolonged. Propafenone also lengthens the refractory period in additional conduction pathways in patients with Wolff-Parkinson-White syndrome (WPW).

Pharmacokinetics

Propafenone is a racemic mixture consisting of R-propafenone and S-propafenone.

Introduction

The maximum plasma concentration (Cmax) of the drug is generated between 2 and 3 hours after oral administration. Propafenone undergoes significant and saturable presystemic biotransformation via CYP2D6 isoenzyme (effect of “primary passage” through the liver), in connection with this the absolute bioavailability of the drug depends on the dose and dosage form. Although food intake caused an increase in bioavailability and plasma Cmax in a single-dose study, long-term use of propafenone with food in healthy volunteers did not result in a significant change in bioavailability.

Distribution

Propafenone is rapidly distributed in the body. The volume of distribution in the equilibrium state is from 1.9 to 3.0 L/kg. The degree of binding of propafenone to plasma proteins is concentration-dependent and decreases from 97.3% when a dose of 0.25 ng/ml is administered to 91.3% when a dose of 100 ng/ml is administered.

Metabolism and excretion

There are two genetically determined pathways of propafenone metabolism. In more than 90% of patients, the drug is rapidly and significantly metabolized, with a half-life (Tsh) of 2 to 10 hours (so-called “fast metabolizers”), In these patients propafenone is metabolized to form 2 active metabolites – 5-hydroxypropafenone via CYP2D6 isoenzyme and N -depropylpropafenone (norpropafenone) via 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 (so-called “slow metabolizers”). In this type of metabolism, Tsh ranges from 10 to 32 hours. The clearance of propafenone is 0.67 to 0.81 L/h/kg. Since the equilibrium state of pharmacokinetic parameters or parameters is reached 3-4 days after drug administration in all patients, the dosing regimens of propafenone are the same for all patients regardless of metabolic rate (“fast” or “slow” metabolizers).

In significant metabolism with a saturable hydroxylation cycle via the CYP2D6 isoenzyme, the pharmacokinetics of propafenone is nonlinear; in slow metabolism, it is linear.

The pharmacokinetics of propafenone have considerable individual variability, which is mainly due to the effect of “primary passage” through the liver, as well as nonlinearity of pharmacokinetics with significant metabolism. The variability of propafenone blood concentrations requires cautious dose titration and monitoring of clinical and electrocardiographic signs of the drug.

Elderly Patients

In elderly patients with normal renal function, propafenone levels varied widely and were not significantly different from those in healthy young patients. The 5-hydroxypropafenone content was approximately similar, but the propafenone glucuronide content was twice as high.

Renal dysfunction

In patients with impaired renal function, propafenone and 5-hydroxypropafenone levels were similar compared with healthy volunteers, but there was cumulation of glucuronide metabolites. Propafenone should be used with caution if renal function is impaired.

Hepatic impairment

Bioavailability and T½ with oral administration are increased in patients with hepatic impairment. Dose adjustment of propafenone in patients with hepatic impairment is necessary.

Indications

Interventricular and ventricular extrasystoles; supraventricular tachycardia, ventricular tachycardia.

Active ingredient

Composition

Each tablet contains:

How to take, the dosage

Rhythmonorm is used orally, after eating, without chewing, with a small amount of liquid. Doses and scheme of treatment are chosen individually. During dose selection and for maintenance therapy, the daily dose is 450-600 mg; the maximum daily dose is 900 mg in 3 doses.

Interaction

The concomitant use of propafenone with local anesthetics (e.g., during pacemaker implantation, surgical interventions, dentistry) or other drugs that reduce heart rate and/or myocardial contractility (e.g., beta-adrenoblockers, tricyclic antidepressants) may cause increased side effects.

The concomitant use of propafenone with drugs metabolized with CYP2D6 isoenzyme (e.g., venlafaxine) may increase plasma concentrations of these drugs. Increased plasma concentrations of propranolol, metoprolol, desipramine, cyclosporine, theophylline and digoxine may also be observed when concomitantly taken with propafenone. If necessary, in case of overdose symptoms, the doses of these drugs should be reduced.

Drugs that inhibit the CYP2D6, CYP1A2, CYP3A4 isoenzymes, such as ketoconazole, cimetidine, quinidine, erythromycin and grapefruit juice, may cause increased plasma propafenone concentrations. When concomitant use of propafenone with inhibitors of these isoenzymes, patients should be closely monitored, if necessary, the dose of the drug should be adjusted.

Combined therapy with amiodarone and propafenone may cause impaired conduction and repolarization, and be accompanied by a proarrhythmogenic effect. In this case, dosage adjustment of both drugs may be required.

While no changes in the pharmacokinetics of propafenone and lidocaine have been observed with their combined use, an increased risk of CNS side effects of lidocaine has been reported.

To the extent that phenobarbital is an inducer of CYP3A4 isoenzyme, the response to therapy should be monitored if propafenone is added to long-term therapy with phenobarbital.

The concomitant use of propafenone and rifampicin may decrease the plasma concentration of propafenone and, consequently, its antiarrhythmic activity.

The state of the clotting system in patients concomitantly receiving indirect anticoagulants (phenprocoumon, warfarin) should be monitored, since propafenone may enhance the pharmacological effect of these drugs and cause prolongation of prothrombin time. If necessary, in case of overdose symptoms, the doses of these drugs should be reduced.

When propafenone and selective serotonin reuptake inhibitors (such as fluoxetine or paroxetine) are used together, plasma concentrations of propafenone may increase. Co-administration of propafenone and fluoxetine in “fast metabolizers” increases Cmax and AUC of propafenone S by 39% and 50% and propafenone R by 71% and 50%, respectively. Thus, the desired therapeutic effect can be achieved with propafenone at lower doses.

Contraindications

Side effects

Proarrhythmogenic effects, increased heart failure, orthostatic hypotension, dyspeptic disorders, headache, visual and taste disorders, fatigue are possible.

Overdose

Symptoms

Myocardial effects: the effects of propafenone overdose on the myocardium are manifested by such disorders as prolongation of the PQ interval, dilated QRS complex, suppression of sinus node automatism, AV-blockade, ventricular tachycardia, ventricular fibrillation, ventricular flutter. Decrease of contractility (negative inotropic effect) may lead to marked BP decrease, which in severe cases may cause collapse.

Extracardiac symptoms: headache, dizziness, blurred vision, paresthesia, tremor, nausea, constipation and dry oral mucosa may often be observed. In very rare cases, seizures have been reported as a result of overdose. A case of lethal outcome has also been reported. In cases of severe poisoning, clonic-tonic seizures, paresthesia, somnolence, coma and respiratory arrest are possible.

Treatment

Trying to eliminate Ritmonorm from the body by hemoperfusion is ineffective.

Because propafenone has a high Vd and high plasma protein binding (>95%), hemodialysis is not effective.

In addition to performing general emergency measures, vital signs should be monitored in the ICU and corrected as necessary.

For control of heart rate and BP, defibrillation and infusions of dopamine and isoproterenol are effective measures. Seizures are stopped by intravenous diazepam.

General supportive measures such as ventilator assistance and indirect cardiac massage may be necessary.