Propanorm® (Propanorm®)

Composition Pharmacodynamics Indications Carefully Contraindications Dosing and Administration Side effects Form release / dosage
Read on
Active substancePropafenonePropafenone
Similar drugsTo uncover
  • Propanorm®
    solution in / in 
    PRO.MED.CS Prague as.     Czech Republic
  • Propanorm®
    pills inwards 
    PRO.MED.CS Prague as.     Czech Republic
  • Propafenone
    solution in / in 
    Alkaloid, JSC     Macedonia
  • Propafenone
    pills inwards 
    R-PHARM, CJSC     Russia
  • Rhythmmonorm®
    pills inwards 
    Abbott Laboratories SA     Spain
    • Dosage form: & nbspsolution for intravenous administration
    Composition:

    1 ml of the preparation contains:

    active substance: propafenone hydrochloride 3.50 mg;

    excipients: dextrose (glucose) monohydrate 48.50 mg, water for injection up to 1.00 ml.

    Description:

    Transparent colorless liquid.

    Pharmacotherapeutic group:antiarrhythmic drug
    ATX: & nbsp

    C.01.B.C   Antiarrhythmic drugs Ic class

    C.01.B.C.03   Propafenone

    Pharmacodynamics:

    Propafenone is an antiarrhythmic drug that has membrane-stabilizing properties, sodium channel blocker properties (class IC), and poorly expressed β-adrenergic blocking activity (class II).

    Antiarrhythmic effect is based on local anesthetic and direct membrane-stabilizing action on cardiomyocytes, as well as on blockade of β-adrenoceptors and calcium channels.

    Propaphenone, blocking the fast sodium channels, causes a dose-dependent decrease in the rate of depolarization and inhibits the phase 0 of the action potential and its amplitude in Purkinje fibers and contractile fibers of the ventricles, inhibits automatism.Slows the pulse on the Purkinje fibers. Lengthens the time spent on the sinoatrial (SA) node and atria. With the use of prenaphenone, the PQ interval can be extended and the QRS complex expanded. as well as the extension of the intervals AH and HV. There is no significant change in the QT interval. Electrophysiological effects are more pronounced in ischemic than in normal myocardium. Propafenone reduces the rate of increase in the action potential, as a result of which the rate of conduction of the pulse decreases (negative dromotropic affect). The refractory period in the atrium, atrioventricular node on the ventricles lengthens. Propafenone also extends the refractory period in additional conductive pathways in patients with Wolff-Parkinson-White syndrome (WPW).

    Pharmacokinetics:

    With intravenous administration, the maximum concentration of propafenone in the blood plasma is reached within the first minute.

    Permeability through the blood-brain and planetary barrier is low.

    The volume of distribution is 3-4 l / kg. The connection with the proteins of the plasma of the kropi and internal organs (liver, lungs, etc.) is 85-97%.

    Propaphenone is subjected to a significant and saturate presystem biotransformation by means of an isoenzyme CYP2D6 (the effect of "primary passage" through the liver).

    There are 2 models of genetically determined metabolism of propafenone. More than 90% of patients propafenone rapidly and significantly metabolized, half-life (T1/2) is from 2.8 to 11 hours. 11 metabolites of propafenone are described, of which two are pharmacologically active: 5-hydroxypropaphenone is formed by isoenzyme CYP2D6, and N-dropropylpropaphenone (norpropaphenone) - with the help of isoenzymes CYP3A4 and CYP1A2. Less than 10% of patients propafenone is metabolized more slowly, since 5-hydroxynapafasmone is not formed or is formed in small amounts. In this winter of metabolism, the elimination half-life is about 17 hours.

    With extensive metabolism with a cycle of saturated hydroxylation with the help of isoenzyme CYP2D6 pharmacokinetics of propafenone is nonlinear, and for slow metabolism it is linear.

    Since the equilibrium state of the pharmacokinetic parameters is achieved 3-4 days after the administration of the drug in all patients, the recommended doses are the same for all patients, regardless of metabolic rate.

    Pharmacokinetics has a significant individual variability, which is mainly due to the effect of "primary transmission" through the liver, as well as its non-linearity in extensive metabolism.

    Propaphenone is excreted by the kidneys - 38% in the form of metabolites (less than 1% unchanged), through the intestine with bile - 53% (in the form of glucuronides and sulfates of metabolites and active substance). With hepatic failure, excretion decreases.

    Indications:

    Cessation of paroxysms:

    - atrial fibrillation;

    - atrial flutter;

    - supraventricular tachycardias (including, with the syndrome WPW);

    - ventricular tachycardia (with preserved contractile function of the left ventricle).
    Contraindications:

    - Hypersensitivity to propafenone and auxiliary components of the drug;

    - Brugada syndrome;

    - syndrome of weakness of the sinus node, impaired excitation between the atria and ventricles, as well as intraventricular conduction (sinoatrial, atrioventricular II and III degree and intraventricular blockade) provided there is no pacemaker;

    - lengthening of the interval QT and simultaneous reception of drugs that extend the interval QT (incl.phenothiazines, cisapride, bepridil, tricyclic antidepressants and macrolides for oral administration);

    acute coronary syndrome;

    - severe bradycardia and severe arterial hypotension;

    - expressed disturbances of water-electrolyte balance (for example, disturbances of potassium metabolism) - should be eliminated before the administration of the drug:

    - Severe chronic obstructive pulmonary disease (COPD);

    - significant organic changes in the myocardium, such as severe refractory chronic heart failure with a left ventricular ejection fraction of less than 35%;

    - Cardiogenic shock, with the exception of arrhythmic shock:

    - myasthenia gravis gravis;

    - simultaneous application of ritonavir;

    - age to 18 years (efficacy and safety not established).

    Carefully:

    Bronchial asthma, COPD, hypo- and hyperkalemia, arterial hypotension, use in patients with pacemaker, elderly age, organic myocardial damage, hepatic and / or renal insufficiency.

    Pregnancy and lactation:

    Adequate and well-controlled studies in pregnant women have not been conducted. During pregnancy, Propanorm® should be used only in those cases,when the expected benefit for the mother exceeds the potential risk to the fetus.

    Propaphenone penetrates the placental barrier. The concentration of propafenone in the umbilical cord is 30% of its concentration r mother's blood.

    Propaphenone is secreted into breast milk, so if it is necessary to use the drug during lactation, breastfeeding should be discontinued.

    Dosing and Administration:

    The drug is used only parenterally: intravenously struino or in the form of infusions. The maximum daily dose is 560 mg.

    Each patient receiving the preparation of Propanorm® intravenously should perform an ECG study and assess the clinical condition before and during therapy for the early detection of side effects, evaluate the effectiveness of the drug and the need to continue therapy.

    The dosage regimen is set individually and adjusted by the doctor.

    Intravenous injections: The dose of the drug at the rate of 1.5-2.0 mg / kg is administered slowly, within 10 minutes. In the absence of a therapeutic effect, this dose can be reintroduced after 90-120 minutes.

    Short-term intravenous infusion: the drug is administered in a dose of 0.5-2.0 mg / kg at a rate of 0.5-1.0 mg / min for 1-3 hours. If necessary, repeat the infusion after 1-2 hours.

    Continuous intravenous infusions: the maximum daily dose is 560 mg (equivalent to 160 ml of the preparation Propanorm®, solution for intravenous administration). Continuous infusions are administered intravenously drip 3-5 minutes after intravenous administration. In severe arrhythmia, short-term or prolonged infusions of propafenone in a 5% glucose solution are used.

    To prepare the infusion solution, it is necessary to use only a solution of 5% glucose (when mixed with 0.9% solution of sodium chloride, a precipitate is possible!).

    If an expansion of the complex is recorded during the infusion QRS by 25% or more, a significant change in heart rate (heart rate) or lengthening interval QT more than 20%, the drug should be discontinued immediately!

    In patients with impaired hepatic function and / or kidneys Cumulation of the active substance in the body can occur even with the usual therapeutic doses. In these patients, titration doses of propafenone can be used, but with careful monitoring of the ECG and the concentrations of propafenone in the blood plasma.

    Side effects:

    Frequency of occurrence of side effects (number of cases / number of observations): very often (> 1/10); often (> 1/100 to <1/10); infrequently (> 1/1000 to <1/100): rarely (> 1/10000 to <1/1000); very rarely (<1/10 000), the frequency is unknown (can not be estimated based on available data).

    From the cardiovascular system: very often - conduction disorders, palpitations; often bradycardia, worsening of the course of heart failure (in patients with reduced contractile function of the left ventricle). SA blockade, AV blockade, violations of intraventricular conduction, ventricular tachyarrhythmias, supraventricular tachyarrhythmias, when taken in high doses - a marked decrease in blood pressure, including postural and orthostatic hypotension; rarely - proarhythmias, which manifest themselves in the form of increased pulse (tachycardia) or ventricular fibrillation; frequency unknown - worsening of the course of chronic heart failure.

    From the digestive system: often - dyspeptic disorders, taste disorders, dryness of the oral mucosa: infrequently - liver disease, cholestasis, jaundice, hepatitis; frequency unknown - the urge to vomit.

    Co the central nervous system: very often dizziness; often - a syncope; infrequently - anxiety, confusion, headache, ataxia, paresthesia; rarely - diplopia, blurred vision; frequency is unknown - convulsions, extrapyramidal symptoms.

    From the musculoskeletal system and connective tissue: rarely a syndrome resembling systemic lupus erythematosus.

    From the genitals and mammary glands: rarely - impotence; frequency unknown - decrease in the number of spermatozoa (return to normal after discontinuation of the use of propafenone).

    Allergic reactions: infrequently - redness of the skin, rashes, itching, hives.

    Laboratory research: infrequently - increased activity of liver enzymes (alanine aminotransferase, asparagine aminotransferase, alkaline phosphatase), thrombocytopenia; rarely - leukopenia, agranulocytosis; frequency is unknown - granulocytopenia.

    Other: weakness, bronchospasm, arthralgia.

    Overdose:

    Intoxication may occur with a single-dose dose of 2 times the daily dose. Symptoms of intoxication appear after 1 hour, a maximum - in a few hours.

    Symptoms: marked reduction in blood pressure, confusion, bradycardia, disturbances intraatrial and intraventricular conduction, extrapyramidal disorder, ventricular tachyarrhythmias, asystole; extracardiac symptoms: headache, dizziness, blurred vision, paraesthesia, tremor, nausea, in exceptional cases - seizures; reported a lethal outcome. In case of severe poisoning, clonic-tonic convulsions, drowsiness, coma and respiratory arrest are possible.

    Treatment: defibrillation, administration of dobutamine, diazepam (with convulsions); if necessary - artificial ventilation and indirect heart massage. Because the propafenone has a large volume distribution and a high degree of binding to plasma proteins (95%), the hemodialysis and hemoperfusion for elimination of the drug is not effective.

    Interaction:

    Increased side effects propafenone may occur while the application of local anesthetics (e.g., after implantation of the pacemaker, during surgery, during extirpation teeth) or with other drugs which slows heart rate and / or myocardial contractility (e.g., β-blockers, tricyclic antidepressants ).

    Propafenone increases the concentrations of propranolol, metoprolol, cyclosporine, desipramine, theophylline in the blood plasma.

    The simultaneous use of propafenone with digoxin leads to an increase in the concentration of digoxin at plasma, in which case the dose of the latter should be reduced by 25%.

    Strengthens the effect of indirect anticoagulants (fenprokumone, warfarin) at the expense of blocking their metabolism - control prothrombin time is necessary.

    Simultaneous administration of propafenone with drugs metabolized by isoenzyme CYP2D6 (for example, venlafaxine), may cause an increase in the concentration of these drugs in the blood plasma.

    The level of propafenone in the blood plasma can increase drugs that inhibit isoenzymes CYP2D6, CYP1A2, CYP3A4. For example, ketoconazole, cimetidine, quinidine, erythromycin and grapefruit juice increase its concentration in blood plasma by 20%. The joint use of ritonavir with propafenone is contraindicated because of the risk of increasing the concentration of drugs in the blood plasma.

    Simultaneous therapy with amiodarone and propafenone can cause disturbance of conduction and repolarization and is accompanied by arrhythmogenic effect.In this case, you may need to adjust the dose of both drugs.

    The combination of propafenone and rifampicin can reduce the concentration of propafenone in the blood plasma and, as a consequence, reduce its antiarrhythmic activity.

    With simultaneous use of propafenone and selective serotonin reuptake inhibitors, such as fluoxetine and paroxetine the maximum concentration of propafenone in blood plasma can increase. The simultaneous use of propafenone and fluoxetine in patients with "fast metabolism" increases the maximum concentration (Cmax) and AUC (area under the concentration-time curve) S-propacenone by 39% and 50%, and R-propacenone - by 71% and 50% respectively. With the simultaneous use of propafenone with paroxetine, the concentration of propafenone in the blood plasma increases. Thus, the necessary therapeutic affect can be achieved by using propafenone in smaller doses.

    It is not recommended simultaneous reception of propafenone with drugs that extend the interval QT (including phenothiazines, cisapride, bepridil, tricyclic antidepressants and macrolides for oral administration).

    Drugs that suppress bone marrow hematopoies increase the risk of myelosuppression.

    Special instructions:

    The chemical and physical stability of the preparation Propanorm® after dilution in a 5% glucose solution is maintained at 25 ° C for 72 hours. However, from the microbiological point of view, the prepared solution should be used immediately. In this case, it is recommended to use the preparation no later than 24 hours under the temperature conditions of its storage - 2-8 ° C, and only if the solution was diluted under controlled aseptic conditions.

    Given the likely proaritmogenic effect of the drug, treatment with Propanorm® is recommended only for the intended purpose and under the supervision of a doctor.

    During the course of treatment, especially at the beginning of therapy - it is necessary to carry out ECG monitoring, control of water-electrolyte balance (especially the content of potassium) and periodically determine the activity of microsomal liver enzymes, especially transaminases.

    Pacemakers should be checked and, if necessary, reprogrammed,since the drug can affect the sensitivity threshold and the frequency threshold of the artificial pacemaker.

    When treatment paroxysmal atrial fibrillation may arise the transition from atrial fibrillation to atrial flutter, with 2: 1 or 1: 1 ventricles with a very high ventricular contraction rate (ie> 180 beats / min).

    Propanorm® can worsen the condition of the Nazi with myasthenia gravis gravis.

    For patients undergoing long-term treatment with anticoagulants and hypoglycemic drugs, it is necessary to conduct careful clinical as well as laboratory monitoring.

    In elderly patients, treatment should be started gradually, the dose of the drug should be titrated with special caution and increased gradually. The same applies to maintenance therapy. Any increase in dose that may be required should be made only after 5-8 days of therapy.

    Indications and dose of the drug should be carefully determined for patients with an artificial pacemaker.

    In patients with impaired hepatic and / or renal function, caspulation of propafenone in the body can occur even with conventional therapeutic doses.For such patients, it is recommended to reduce the dose and regularly conduct ECG monitoring and regular monitoring of laboratory parameters.

    The use of Propanorma® can reveal the asymptomatic course of the Brugada syndrome and cause brugal-like changes on the ECG. Therefore, after the beginning of therapy with the drug, an electrocardiologic examination should be performed to exclude the Brugada syndrome and brugad-like changes on the ECG.

    If during the therapy SA blockade or AV blockade II-III degree or frequently recurring extrasystole, treatment with Propanorm® should be stopped!

    It should be taken into account that in the treatment of ventricular arrhythmias, the preparation Propanorm® is more effective than antiarrhythmic drugs IA and IIn the classes.

    Effect on the ability to drive transp. cf. and fur:

    Visual impairment, dizziness, fatigue and postural hypotension may affect the ability to drive vehicles and mechanisms, so during the treatment period it is necessary to refrain from these activities.

    Form release / dosage:

    Solution for intravenous administration, 3.5 mg / ml.

    Packaging:

    10 ml per ampoule of neutral glass Ihydrolytic class with a fault point, the corresponding ISO 9187 and Ph.Eur. The presence of one or more colored rings is allowed on the head of the ampoule.

    5 ampoules per contour pack of PVC film.

    2 contour squares, together with instructions for use, are placed in a cardboard box.

    Storage conditions:

    In a dry, protected from the candle place, at a temperature of 15-25 ° C.

    Keep out of the reach of children.

    Shelf life:

    4 years.

    Do not use after the expiration date.

    Terms of leave from pharmacies:On prescription
    Registration number:LP-002948
    Date of registration:08.04.2015
    The owner of the registration certificate:PRO.MED.CS Prague as.PRO.MED.CS Prague as. Czech Republic
    Manufacturer: & nbsp
    Representation: & nbspPRO.MED.CS Prague as. PRO.MED.CS Prague as. Czech Republic
    Information update date: & nbsp04.09.2015
    Illustrated instructions
      Instructions
      Up