Pharmacodynamics and pharmacokinetics
Pharmacodynamics
A combined drug with membrane stabilizing, antiarrhythmic and antioxidant effects. Also has metabolic activity. The mechanism of action is associated with an increase in the level of adenosine triphosphoric acid inside the cell and activation of enzymes that are involved in redox reactions . Active components suppress lipid peroxidation and improve tissue condition under hypoxic . The use of Rhythmocor is accompanied by normalization of heart rhythm, in addition, it enhances the effects of antiarrhythmic drugs.
Pharmacokinetics
After oral administration, the maximum concentration of active components in the blood is determined after 1-1.5 hours. Within 48 hours, 95% of the drug is metabolized. Metabolites are excreted by the kidneys.
Rytmonorm®
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 interval from 2 to 3 hours after oral administration. Propafenone undergoes significant and saturable presystemic biotransformation using the CYP2D6 isoenzyme (first pass effect 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 a single dose study, chronic administration 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 at steady state ranges 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% 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 for the metabolism of propafenone. In more than 90% of patients, the drug is quickly and significantly metabolized, the half-life (T1/2) ranges from 2 to 10 hours (so-called “rapid metabolizers”). In such patients, propafenone is metabolized to form 2 active metabolites - 5-hydroxypropafenone via the CYP2D6 isoenzyme and N-depropylpropafenone (norpropafenone) via 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 quantities (so-called “poor metabolizers”). With this type of metabolism, T1/2 ranges from 10 to 32 hours. The clearance of propafenone ranges from 0.67 to 0.81 l/h/kg.
Since the equilibrium state of pharmacokinetic parameters or indicators is achieved 3-4 days after taking the drug in all patients, the dosage regimens of propafenone are the same for all patients, regardless of metabolic rate (“fast” or “slow” metabolizers).
With significant metabolism with a cycle of saturable hydroxylation using the CYP2D6 isoenzyme, the pharmacokinetics of propafenone are non-linear, and with slow metabolism - linear.
The pharmacokinetics of propafenone has significant individual variability, which is mainly due to the effect of “first pass” through the liver, as well as the nonlinearity of pharmacokinetics with significant metabolism. The variability of propafenone blood concentrations requires careful titration of the dose and monitoring of clinical and electrocardiographic signs of drug action.
Elderly patients
In elderly patients with normal renal function, the content of propafenone varied greatly and did not differ significantly from that in healthy young patients. The content of 5-hydroxypropafenone was approximately similar, but the content of propafenone glucuronides was twice as high.
Renal dysfunction
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.
Liver dysfunction
Bioavailability and T1/2 when taken orally are increased in patients with impaired liver function. It is necessary to adjust the dose of propafenone in case of liver dysfunction.
Indications for use
- arrhythmias due to a decrease in potassium and magnesium in the blood plasma;
- arrhythmias that occurred when taking cardiac glycosides;
- extrasystolic arrhythmia;
- cardiac ischemia;
- cardiopsychoneurosis;
- myocarditis and myocardiopathy ;
- liver diseases;
- chronic fatigue syndrome (as part of complex therapy).
RITHMONORM film-coated tablets 150 mg No. 50
When propafenone is used together with local anesthetics (for example, during implantation of a pacemaker, during surgery, in dentistry) or other drugs that reduce heart rate and/or reduce myocardial contractility (for example, beta-blockers, tricyclic antidepressants), side effects may increase. The simultaneous use of propafenone with drugs metabolized by the CYP2D6 isoenzyme (for example, venlafaxine) may cause an increase in the concentration of these drugs in the blood plasma. Increased plasma concentrations of propranolol, metoprolol, desipramine, cyclosporine, theophylline and digoxin may also be observed when taken concomitantly with propafenone. If necessary, if symptoms of overdose are detected, the doses of these drugs should be reduced. Drugs that inhibit the isoenzymes CYP2D6, CYP1A2, CYP3A4, for example, ketoconazole, cimetidine, quinidine, erythromycin and grapefruit juice, may cause an increase in the concentration of propafenone in the blood plasma. When using propafenone concomitantly with inhibitors of these isoenzymes, patients should be closely monitored and, if necessary, the dose of the drug should be adjusted. Combination therapy with amiodarone and propafenone can cause conduction and repolarization disturbances, as well as be accompanied by a proarrhythmogenic effect. In this case, the dose of both drugs may need to be adjusted. Although no changes in the pharmacokinetics of propafenone and lidocaine were observed when they were used together, an increased risk of lidocaine-related CNS side effects was reported. Because phenobarbital is an inducer of the CYP3A4 isoenzyme; the response to therapy should be monitored if propafenone is added to long-term therapy with phenobarbital. The simultaneous 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 simultaneously receiving indirect anticoagulants (phenprocoumon, warfarin), since propafenone can enhance the pharmacological effect of these drugs and cause an increase in prothrombin time. If necessary, if symptoms of overdose are detected, the doses of these drugs should be reduced. When propafenone is co-administered with selective serotonin reuptake inhibitors (such as fluoxetine or paroxetine), increased plasma concentrations of propafenone may occur. The combined use of propafenone and fluoxetine in “rapid 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 lower doses.
Contraindications
- increased sensitivity;
- hyperkalemia and hypermagnesemia ;
- atrioventricular block II-III degree;
- decompensated diabetes mellitus ;
- severe renal dysfunction;
- cardiogenic shock;
- arterial hypotension;
- Addisin's disease;
- age under 3 years (for capsules).
When taking it, keep in mind that 1 capsule contains 0.03 bread units.
Rhythmocor, instructions for use (Method and dosage)
Rhythmocor capsules (tablets) are taken orally without chewing or crushing. For maximum therapeutic effect, they should be taken 10-15 minutes before meals. The duration of treatment and dose are determined by the doctor.
Adults are recommended to take 1-2 capsules 3-4 times a day. In severe conditions, you can take 3 capsules 3 times a day. After achieving the effect, prescribe 1 capsule 3 times a day.
For chronic fatigue syndrome - 1 capsule 3 times a day. Duration of treatment is 3-5 months. Children from 3 to 6 years old are recommended to take 1 capsule 2 times a day, from 6 years old - 1 capsule 3 times a day.
Reviews about Rhythmocore
A decrease in the level of potassium in the blood causes the development of extrasystole and tachycardia . Therefore, maintaining potassium at normal levels is important for normal cardiac function. Hypokalemia increases the toxicity of cardiac glycosides and causes an imbalance in protein balance in the body.
A decrease in magnesium levels is observed in half of patients who take diuretics and, especially often, in the elderly. Hypomagnesemia also manifests itself as heart rhythm disturbances. Correction of disorders is carried out by prescribing potassium and magnesium drugs, among which are Panangin , Rhythmocor and Asparkam . They are usually well tolerated, especially since the dosage form in capsule form significantly reduces the incidence of adverse reactions from the gastrointestinal tract . Patients note effectiveness, reasonable price, and only in some cases the development of undesirable effects.
- “... An attack of arrhythmia begins suddenly and can last more than a week. After 2 days of taking Rhythmocor everything goes away.”
- “... There was a rhythm disturbance and pain like angina pectoris. I drank it for 10 days - everything returned to normal, including the cardiogram.”
- “... Helps with extrasystole.”
- “... Itching and rash appeared on the fifth day of use.”
- “... After it I felt heaviness in the liver and stomach.”
Ritmonorm tab p/pl/o 150 mg N50 (Abbott)
When propafenone is used together with local anesthetics (for example, during implantation of a pacemaker, during surgery, in dentistry) or other drugs that reduce heart rate and/or reduce myocardial contractility (for example, beta-blockers, tricyclic antidepressants), side effects may increase. The simultaneous use of propafenone with drugs metabolized by the CYP2D6 isoenzyme (for example, venlafaxine) may cause an increase in the concentration of these drugs in the blood plasma. Increased plasma concentrations of propranolol, metoprolol, desipramine, cyclosporine, theophylline and digoxin may also be observed when taken concomitantly with propafenone. If necessary, if symptoms of overdose are detected, the doses of these drugs should be reduced. Drugs that inhibit the isoenzymes CYP2D6, CYP1A2, CYP3A4, for example, ketoconazole, cimetidine, quinidine, erythromycin and grapefruit juice, may cause an increase in the concentration of propafenone in the blood plasma. When using propafenone concomitantly 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 disturbances, and may also be accompanied by a proarrhythmogenic effect. In this case, a dose adjustment of both drugs may be required. Although no changes in the pharmacokinetics of propafenone and lidocaine were observed when they were used together, an increased risk of lidocaine side effects from the central nervous system was reported. phenobarbital is an inducer of the CYP3A4 isoenzyme, the response to therapy should be monitored if propafenone is added to long-term therapy with phenobarbital. The simultaneous use of propafenone and rifampicin can 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 , while simultaneously receiving indirect anticoagulants (phenprocoumon, 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 drugs should be reduced. When using propafenone and selective serotonin reuptake inhibitors (such as fluoxetine or paroxetine) together, an increase in the concentration of propafenone in the blood plasma may occur. The combined use of propafenone and fluoxetine in “rapid 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 lower doses.
Rhythmocor price, where to buy
The drug is currently not available in pharmacies. You can buy analogues: Asparkam 56 tablets costing 76-106 rubles. and Panangin 50 tablets for 108-136 rubles.
- Online pharmacies in UkraineUkraine
Pharmacy24
- Rhythmocore 0.36 g N48 capsules TOV FC FarKos, Ukraine/ PrAT FF FarKos, Ukraine
57 UAH order - Rhythmokor 5 ml No. 10 solution for injection TOV"FC"FarKos", Ukraine/PrAT FF"FarKos",Ukraine
101 UAH order
