Ritmonorm tablets p / o 150mg, No. 50

• Paroxysmal supraventricular tachyarrhythmias, including AV nodal tachycardia, supraventricular tachycardia in patients with Wolff-Parkinson-White (WPW) syndrome and / or paroxysmal atrial fibrillation.

• Severe paroxysmal ventricular tachyarrhythmia, life threatening.

Inside.
Due to its bitter taste and local anesthetic effect, RitmonormЃ should be swallowed whole without chewing and drinking some liquid.
The dose of RitmonormЃ should be selected individually, depending on the patient's response and the effect obtained.
It is recommended to start therapy in a hospital, having previously canceled all antiarrhythmic drugs (under the control of blood pressure (BP), ECG, determination of the width of the QRS complex).
In patients with significantly widened QRS complexes and AV block, it is recommended to reduce the dose.
Adults :
With a patient's body weight of 70 kg or more, the initial dose is 150 mg 3 times a day (in a hospital under the control of ECG and blood pressure). The dose can be increased at intervals of at least 3-4 days, up to 300 mg (2 tablets) 2 times a day, and, if necessary, up to a maximum dose of 300 mg 3 times a day.
If the patient weighs less than 70 kg, treatment should be started with lower doses of the drug. Do not start increasing the dose if the duration of the drug is less than 3-4 days.
Elderly patients

There were no differences in the efficacy and safety of using RitmonormЃ in elderly patients and younger patients. However, individual hypersensitivity reactions to propafenone or any other component of the drug cannot be ruled out, therefore drug therapy should be carried out under the close supervision of a physician. They also do the same during maintenance therapy. Do not start increasing the dose if the duration of the drug is less than 5-8 days.
Impaired renal and / or liver
function In patients with impaired renal and / or liver function due to possible accumulation of the drug, dose titration is necessary under close clinical control and ECG control.

Each tablet contains:
Active ingredient: 150 mg propafenone hydrochloride.
Excipients : 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.

• Known hypersensitivity to propafenone or any other component of the drug.

• Brugada syndrome (see section 'Special instructions').

• Myocardial infarction in the past 3 months.

• Significant organic changes in the myocardium, such as:

  • refractory chronic heart failure with left ventricular ejection fraction less than 35%;

  • cardiogenic shock, with the exception of arrhythmic shock;

  • severe bradycardia;

  • sick sinus syndrome, atrial conduction disturbances, AV block, bundle branch block or distal block (in patients without a pacemaker);

  • severe arterial hypotension.

• Severe violations of water and electrolyte balance (for example, violations of potassium metabolism).

• Severe forms of chronic obstructive pulmonary disease (COPD).

• Concomitant use of ritonavir.

• Myasthenia gravis.

• Age up to 18 years (efficacy and safety have not been established).

Carefully

impaired liver and / or kidney function, paroxysmal atrial fibrillation (see section 'Special instructions'), use in patients with a pacemaker, advanced age, organic changes in the myocardium (see section 'Method of administration and doses'), pregnancy and breastfeeding , obstructive respiratory diseases, incl. bronchial asthma.

Trade name of the drug:

RitmonormЃ

International non-proprietary name:

Propafenone

Dosage form:

Film-coated tablets.

Composition:

Each tablet contains:
Active ingredient: 150 mg propafenone hydrochloride.
Excipients : 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.

Description:

Round biconvex film-coated tablets, white or almost white, engraved with '150' on one side.

Pharmacotherapeutic group:

Antiarrhythmic agent

Pharmacological properties

Pharmacodynamics
Propafenone has membrane stabilizing properties, properties of a sodium channel blocker (class 1C) and a weakly expressed beta-adrenergic blocking activity (class II).
It slows down the growth of the action potential, as a result of which the speed of the impulse is reduced (negative dromotropic effect). The refractory period in the atrium, atrioventricular (AV) node and ventricles is lengthened. Propafenone also lengthens the refractory period in accessory pathways in patients with Wolff-Parkinson-White (WPW) syndrome.

Pharmacokinetics
Propafenone is a racemic mixture consisting of R-propafenone and S-propafenone.
Absorption The
maximum concentration (Cmax) of the drug in the blood plasma is created in the interval from 2 to 3 hours after ingestion. Propafenone undergoes significant and saturable presystemic biotransformation using the isoenzyme CYP2D6 (the effect of 'primary passage' through the liver), therefore, the absolute bioavailability of the drug depends on the dose and dosage form. Although food intake caused an increase in bioavailability and Cmax in blood plasma in a single dose study, long-term use of propafenone with food in healthy volunteers did not lead to a significant change in bioavailability.
Distribution
Propafenone is rapidly distributed in the body. The volume of distribution at equilibrium is from 1.9 to 3.0 l / kg. The degree of binding of propafenone to blood plasma proteins depends on the concentration and decreases from 97.3% at a dose of 0.25 ng / ml to 91.3% at a dose of 100 ng / ml.
Metabolism and excretion
There are two genetically determined pathways for the metabolism of propafenone. In more than 90% of patients, the drug is rapidly and significantly metabolized, the half-life (Tm) is from 2 to 10 hours (the so-called 'fast metabolizers'). In such patients, propafenone is metabolized to form 2 active metabolites - 5-hydroxypropafenone using the isoenzyme CYP2D6 and N-depropafenone (norpropafenone) using isoenzymes CYP3A4 and CYP1A2. 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 'slow metabolizers'). With this type of metabolism, Tsh is from 10 to 32 hours. The clearance of propafenone is 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 for propafenone are the same for all patients, regardless of the metabolic rate ('fast' or 'slow' metabolizers).
With significant metabolism with a cycle of saturated hydroxylation using the isoenzyme CYP2D6, the pharmacokinetics of propafenone is nonlinear, and with slow metabolism, it is linear.
The pharmacokinetics of propafenone has significant individual variability, which is mainly due to the effect of 'primary passage' through the liver, as well as the nonlinearity of pharmacokinetics with significant metabolism. The variability of the concentration of propafenone in the blood requires careful dose titration 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 5-hydroxypropafenone content was roughly similar, but the propafenone glucuronide content 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, however, cumulation of glucuronide metabolites was observed. In case of impaired renal function, propafenone should be used with caution.
Liver dysfunction
Bioavailability and T? when taken orally, they increase in patients with impaired liver function. Dose adjustment of propafenone is necessary for liver dysfunction.

Indications for use

• Paroxysmal supraventricular tachyarrhythmias, including AV nodal tachycardia, supraventricular tachycardia in patients with Wolff-Parkinson-White (WPW) syndrome and / or paroxysmal atrial fibrillation.

• Severe paroxysmal ventricular tachyarrhythmia, life threatening.

Contraindications

• Known hypersensitivity to propafenone or any other component of the drug.

• Brugada syndrome (see section 'Special instructions').

• Myocardial infarction in the past 3 months.

• Significant organic changes in the myocardium, such as:

  • refractory chronic heart failure with left ventricular ejection fraction less than 35%;

  • cardiogenic shock, with the exception of arrhythmic shock;

  • severe bradycardia;

  • sick sinus syndrome, atrial conduction disturbances, AV block, bundle branch block or distal block (in patients without a pacemaker);

  • severe arterial hypotension.

• Severe violations of water and electrolyte balance (for example, violations of potassium metabolism).

• Severe forms of chronic obstructive pulmonary disease (COPD).

• Concomitant use of ritonavir.

• Myasthenia gravis.

• Age up to 18 years (efficacy and safety have not been established).

Carefully

impaired liver and / or kidney function, paroxysmal atrial fibrillation (see section 'Special instructions'), use in patients with a pacemaker, advanced age, organic changes in the myocardium (see section 'Method of administration and doses'), pregnancy and breastfeeding , obstructive respiratory diseases, incl. bronchial asthma.

Application during pregnancy and during breastfeeding

Pregnancy
Appropriate and well-controlled studies in pregnant women have not been conducted. The drug can be used during pregnancy only if the expected benefit to the mother outweighs the potential risk to the fetus. Propafenone crosses the placental barrier. The concentration of propafenone in the umbilical cord is approximately 30% of the concentration in the mother's blood.
Breastfeeding period
Studies of the excretion of propafenone in breast milk have not been conducted. However, there is limited evidence that propafenone can be excreted in breast milk. RitmonormЃ should be used with caution during breastfeeding.

Method of administration and dosage

Inside.
Due to its bitter taste and local anesthetic effect, RitmonormЃ should be swallowed whole without chewing and drinking some liquid.
The dose of RitmonormЃ should be selected individually, depending on the patient's response and the effect obtained.
It is recommended to start therapy in a hospital, having previously canceled all antiarrhythmic drugs (under the control of blood pressure (BP), ECG, determination of the width of the QRS complex).
In patients with significantly widened QRS complexes and AV block, it is recommended to reduce the dose.
Adults :
With a patient's body weight of 70 kg or more, the initial dose is 150 mg 3 times a day (in a hospital under the control of ECG and blood pressure). The dose can be increased at intervals of at least 3-4 days, up to 300 mg (2 tablets) 2 times a day, and, if necessary, up to a maximum dose of 300 mg 3 times a day.
If the patient weighs less than 70 kg, treatment should be started with lower doses of the drug. Do not start increasing the dose if the duration of the drug is less than 3-4 days.
Elderly patients

There were no differences in the efficacy and safety of using RitmonormЃ in elderly patients and younger patients. However, individual hypersensitivity reactions to propafenone or any other component of the drug cannot be ruled out, therefore drug therapy should be carried out under the close supervision of a physician. They also do the same during maintenance therapy. Do not start increasing the dose if the duration of the drug is less than 5-8 days.
Impaired renal and / or liver
function In patients with impaired renal and / or liver function due to possible accumulation of the drug, dose titration is necessary under close clinical control and ECG control.

Overdose

Symptoms
From 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. Decreased contractility (negative inotropic effect) can lead to a pronounced decrease in blood pressure, which in severe cases can cause collapse.
Extracardiac symptoms: Headache, dizziness, blurred vision, paresthesia, tremors, nausea, constipation and dryness of the oral mucosa may often occur. In very rare cases, seizures as a result of overdose have been reported. A fatal case has also been reported. In cases of severe poisoning, clonic-tonic convulsions, paresthesia, drowsiness, coma and respiratory arrest are possible.
Treatment:
Attempts to remove RitmonormЃ from the body through hemoperfusion are ineffective.
Since propafenone has a large volume of distribution and a high degree of binding to blood 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 and dopamine and isoproterenol infusions are effective measures to control heart rate and blood pressure. Convulsions are controlled by intravenous diazepam.
General supportive measures such as connection to a respirator and chest compressions may be required.

Interaction with other medicinal products

With the joint use of propafenone with local anesthetics (for example, during the 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 isoenzyme CYP2D6 (for example, venlafaxine) may cause an increase in the concentration of these drugs in the blood plasma. An increase in the concentration of propranolol, metoprolol, desipramine, cyclosporine, theophylline and digoxin in blood plasma can also be observed when taken simultaneously with propafenone. If necessary, if symptoms of an 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, can cause an increase in the concentration of propafenone in the blood plasma. With the simultaneous 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 can cause conduction disturbances and repolarization, as well as be accompanied by a proarrhythmogenic effect. In this case, a dose adjustment of both drugs may be required. Although there were no changes in the pharmacokinetics of propafenone and lidocaine 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.
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 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 an overdose are detected, the doses of these drugs should be reduced.
With the combined use of propafenone and selective serotonin reuptake inhibitors (such as fluoxetine or paroxetine), an increase in the concentration of propafenone in the blood plasma may occur. The combined use of propafenone and fluoxetine in 'rapid metabolizers' increases Cmax (maximum plasma concentration) and the area under the concentration-time pharmacokinetic curve (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 the use of propafenone in lower doses.

special instructions

Treatment should be started in a hospital setting, since the risk of arrhythmogenic effects associated with the use of RitmonormЃ is increased. It is recommended that prior antiarrhythmic therapy be discontinued prior to initiation of treatment within 2-5 half-lives of these drugs.
Each patient who receives RitmonormЃ should undergo an electrocardiographic and clinical examination before starting therapy and during its duration for early detection of side effects, assessment of the effectiveness of the drug and the need to continue therapy.
Taking propafenone can reveal asymptomatic Brugada syndrome and cause brugada-like ECG changes. Therefore, after starting therapy with RitmonormЃ, an electrocardiographic examination should be performed to exclude the presence of Brugada syndrome and brugada-like changes on the ECG.
Pacemakers must be checked and, if necessary, reprogrammed, since RitmonormЃ can affect the sensitivity threshold and frequency threshold of artificial pacemakers.
There is a risk of conversion of paroxysmal atrial fibrillation to atrial flutter with AV block 2: 1 or 1: 1.
As with the use of other class 1C antiarrhythmic drugs, patients with significant organic changes in the myocardium may experience serious side effects while taking RitmonormЃ (see section 'Contraindications'),

Influence on the ability to drive vehicles and work with mechanisms

Blurred vision, dizziness, increased fatigue and postural arterial hypotension can impair the patient's reaction rate and the ability to drive transport and work with mechanisms, therefore, during the period of using RitmonormЃ, one should refrain from driving and engaging in potentially hazardous activities that require increased concentration and speed psychomotor reactions.

Release form

Film-coated tablets, 150 mg.
10 tablets in a PVC / A1 foil blister. 2, 5 or 10 blisters with instructions for use in a cardboard box.

Storage conditions

Store at temperatures between 15 and 25 ? C. Keep out of the reach of children.

Shelf life

3 years. Do not use after the expiration date printed on the package.

Vacation conditions

Dispensed by prescription.