Rytmonorm, pills 150mg, 50pcs

Composition

Each tablet contains:

• Active ingredient:
• propafenone hydrochloride 150 mg.
• Auxiliary substances:
• microcrystalline cellulose -25.40 mg;
• croscarmellose sodium -10.00 mg;
• corn starch-20.00 mg;
• hypromellose-2910 8.00 mg;
• magnesium stearate-0.50 mg;
• water-6.10 mg.
• Film coating:
• macrogol 400 -0.52 mg; macrogol 6000-4.176 mg; hypromellose-2910 – 6.264 mg, titanium dioxide (E 171) – 1.04 mg

Pharmacological action

Propafenone has membrane-stabilizing properties, sodium channel blocker properties (Class 1C), and weak beta-adrenoblocking activity (Class II).

It slows down the increase in the action potential, as a result of which the pulse conduction rate decreases (negative dromotropic effect). The refractory period in the atrium, atrioventricular (AV) node and ventricles is prolonged. Propafenone also prolongs the refractory period in accessory pathways in patients with Wolf-Parkinson-White syndrome (WPW).

Pharmacokinetics

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

Suction

The maximum concentration (Cmax) of the drug in the blood plasma is created in the range from 2 to 3 hours after oral use. Propafenone undergoes significant and saturated presystemic biotransformation with the help of the CYP2D6 isoenzyme (the effect of “primary passage” through the liver), and therefore 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 the single-dose study, long-term dietary use of propafenone 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 depends on the concentration and decreases from 97.3% with a dose of 0.25 ng / ml to 91.3% with a dose of 100 ng / ml.

Metabolism and elimination

There are two genetically determined pathways of propafenone metabolism. In more than 90% of patients, the drug is rapidly and significantly metabolized, the half – life (Ts) is from 2 to 10 hours (so-called “fast metabolizers”), In such patients, propafenone is metabolized to form 2 active metabolites-5-hydroxypropafenone using the CYP2D6 isoenzyme and N-depropropropafenone (norpropafenone) using the CYP3A4 and CYP1A2 isoenzymes. In less than 10% of patients, propafenone is metabolized more slowly, since 5-hydroxypropafenone is not formed or is formed in small amounts (so-called “slow metabolizers”). With this type of metabolism, Ts is from 10 to 32 hours. Propafenone clearance ranges from 0.67 to 0.81 l / h / kg. Since the equilibrium state of pharmacokinetic parameters or indicators is reached 3-4 days after taking the drug in all patients, the dosage regimens of propafenone are the same for all patients, regardless of the metabolic rate (“fast” or “slow” metabolizers).

The pharmacokinetics of propafenone are non-linear in the case of significant metabolism with a cycle of saturated hydroxylation using the CYP2D6 isoenzyme, and linear in the case of slow metabolism.

The pharmacokinetics of propafenone have significant individual variability, which is mainly due to the effect of “primary passage” through the liver, as well as non-linearity of pharmacokinetics with significant metabolism. The variability in the concentration of propafenone in the blood requires careful titration of the dose and monitoring of clinical and electrocardiographic signs of the drug’s action.

Elderly patients

In elderly patients with normal renal function, the propafenone content was highly variable and did not significantly differ from that in healthy young patients. The content of 5-hydroxypropaphenone was approximately similar, but the content of propafenone glucuronides was twice as high.

Impaired renal function

In patients with impaired renal function, the content of propafenone and 5-hydroxypropafenone was similar compared to healthy volunteers, but accumulation of glucuronide metabolites was observed. If renal function is impaired, propafenone should be used with caution.

Impaired liver function

Oral bioavailability and half-life are increased in patients with impaired liver function. It is necessary to adjust the dose of propafenone in case of impaired liver function.

Indications

Supraventricular and ventricular extrasystoles; supraventricular tachycardia, ventricular tachycardia.

Contraindications

• severe forms of chronic heart
• failure electrolyte imbalance
• myasthenia
• gravis bronchial asthma
• hypersensitivity to Rytmonorm.

Side effects

Possible proarrhythmogenic effects, increased heart failure, orthostatic hypotension, dyspeptic disorders, headache, visual and taste disorders, fatigue.

Interaction

When propafenone is co-administered with local anesthetics (for example, during pacemaker implantation, during surgery, in dentistry) or other medications that reduce heart rate and / or reduce myocardial contractility (for example, beta-blockers, tricyclic antidepressants), side effects may increase.

Concomitant use of propafenone with drugs metabolized by the CYP2D6 isoenzyme (for example, venlafaxine) may cause an increase in the concentration of these drugs in blood plasma. Increased plasma concentrations of propranolol, metoprolol, desipramine, cyclosporine, theophylline, and digoxin may also occur when propafenone is co-administered. If necessary, if symptoms of overdose are detected, the doses of these medications should be reduced.

Drugs that inhibit the isoenzymes CYP2D6, CYP1A2, and CYP3A4, such as ketoconazole, cimetidine, quinidine, erythromycin, and grapefruit juice, may cause an increase in the concentration of propafenone in blood plasma. When propafenone is co-administered with inhibitors of these isoenzymes, patients should be closely monitored, and if necessary, the dose of the drug should be adjusted.

Combined therapy with amiodarone and propafenone can cause conduction and repolarization disorders, as well as be accompanied by a proarrhythmogenic effect. In this case, it may be necessary to adjust the dose of both drugs.

Although no changes in the pharmacokinetics of propafenone and lidocaine were observed when they were used together, an increased risk of developing side effects of lidocaine from the central nervous

system was reported. Since phenobarbital is an inducer of the CYP3A4 isoenzyme, the response to therapy should be monitored if propafenone is added to long-term phenobarbital therapy.

Concomitant use of propafenone and rifampicin may reduce the concentration of propafenone in the blood plasma and, as a result, reduce its antiarrhythmic activity.

It is necessary to monitor the state of the blood coagulation system in patients who are simultaneously receiving indirect anticoagulants (fenprocumone, warfarin), since propafenone can enhance the pharmacological effect of these drugs and cause an extension of prothrombin time. If necessary, if symptoms of overdose are detected, the doses of these medications should be reduced.

When propafenone is co-administered with selective serotonin reuptake inhibitors (such as fluoxetine or paroxetine), the concentration of propafenone in the blood plasma may increase. The combined use of propafenone and fluoxetine in” fast metabolizers ” increases the 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 by using propafenone in smaller doses.

How to take, course of use and dosage

Rytmonorm is used inside, after eating, without chewing, with a small amount of liquid. The dosage and treatment regimen are selected individually. During the period of dose selection and maintenance therapy, the daily dose is 450-600 mg; the maximum daily dose is 900 mg in 3 divided doses.

Overdose

Symptoms

From the side of the myocardium:  the consequences of an overdose of propafenone for the myocardium are manifested by such disorders as prolongation of the PQ interval, expansion of the QRS complex, suppression of automatism of the sinus node, AV block, ventricular tachycardia, ventricular fibrillation, ventricular flutter. Reduced contractility (negative inotropic effect) can lead to a marked decrease in blood pressure, which in severe cases can cause collapse.

Extracardial symptoms:  headache, dizziness, blurred vision, paresthesia, tremor, nausea, constipation and dryness of the oral mucosa can often occur. Seizures resulting from overdose have been reported in very rare cases. A fatal case was also reported. In cases of severe poisoning, clonic-tonic convulsions, paresthesia, drowsiness, coma and respiratory arrest are possible.

Treatment

Attempts to remove Rytmonorm from the body by hemoperfusion are ineffective.

Since propafenone has a large Vd and a high degree of binding to plasma proteins (>95%), hemodialysis is ineffective.

In addition to carrying out general emergency measures, it is necessary to monitor vital signs in the intensive care unit and adjust them if necessary.

Defibrillation, as well as infusions of dopamine and isoproterenol are effective measures to control heart rate and blood pressure. Convulsions are stopped by intravenous use of diazepam.

General supportive measures may be required, such as connecting to a ventilator and indirect heart massage.

Form of production

Tablets

Storage conditions

Store in a dry place, protected from light, at a temperature not exceeding 25 °C.

Shelf life

5 years

Active ingredient

Propafenone

Conditions of release from pharmacies

By prescription

Dosage form

Tablets