Expiration date: 04/2025

Structure and Composition:

The long-acting tablets. One tablet contains active substance:

Carbamazepine 200 or 400 mg

Excipients: Eudragit RS30D (ethyl acrylate, methyl methacrylate and trimetilammonioetilmetakrilata copolymer (1: 2: 0.1) - 11/22 mg Triacetin - 2.2 / 4.4 mg talc - 15.6 / 31.2 mg Eudragit L30D-55 (methacrylic acid and ethyl acrylate copolymer) - MCC mg 35/70 - 21.8 / 43.6 mg crospovidone - 12.4 / 24.8 mg colloidal silica - 1.33 / 2.66 mg of magnesium stearate - 0.67 / 1.34 mg

in blister PVC / PVDC / aluminum foil 10 pcs. a stack of cardboard 3, 4 or 5 blisters.

Description pharmaceutical form:

Sustained-release tablets 200 mg: white to white with a yellowish tint, flat round, with bevelled edges on the same side - the cruciform notch, on the other - engraved "S 200".

Sustained-release tablets 400 mg: white to white with a yellowish tint, flat round, with bevelled edges on the same side - the cruciform notch, on the other - engraved "400".

Characteristic:

Antiepileptics (derivative dibenzazepine).

Pharmacokinetics:

Absorption - slow, but complete (food intake does not significantly affect the rate and extent of absorption). After a single dose Finlepsin retard tablet Cmax is reached after 32 hours. Equilibrium plasma concentrations are reached within 1-2 weeks. Plasma protein binding in children - 55-59% in adults - 70-80%. The apparent volume of distribution - 0.8-1.9 l / kg. In the cerebrospinal fluid and saliva concentrations are proportional to the amount of unbound protein active substances (20-30%). It penetrates through the placental barrier. Concentration in breast milk is 25-60% of that in plasma. It is metabolized in the liver, principally by way of epoxy to form the main metabolites: active - carbamazepine-10,11-epoxide, and inactive conjugate with glucuronic acid. The basic isoenzyme providing Carbamazepine biotransformation carbamazepine-10,11-epoxide is cytochrome P450 (CYP 3A4). The result of these reactions, a metabolic and inactive metabolite 9-hydroxy-10-methyl-karbamoilakridan. T1 / 2 after receiving a single oral dose of 60-100 hours (average - 70 hours), when long-term treatment T1 / 2 decreases due to autoinduction liver enzyme systems. After a single dose of carbamazepine into 72% of the dose is excreted in urine and 28% - with the feces. About 2% of the dose is excreted in the urine as unchanged carbamazepine, about 1% - in the form of 10,11-epoxide metabolite.

No evidence of change in the pharmacokinetic parameters in elderly patients.

Description of the pharmacological actions:

It has analgesic effects in patients with neuralgia, also provides an antidiuretic effect.

Blocks voltage-gated sodium channels, resulting in stabilization of Membrane overexcited neurons, inhibition of occurrence of serial bits neurons and reduction of synaptic impulses. It prevents re-formation of the Na + -dependent action potentials in depolarized neurons. Reduces the release of excitatory amino acid neurotransmitter - glutamate increases CNS lowered seizure threshold and, thus, reduce the risk of epileptic seizure. K + increases the conductivity, voltage-sensitive Ca2 modulates + channels, which also may contribute to the anticonvulsive effects of the drug.

Clinical Pharmacology:

Effective with focal (partial) epileptic seizures (simple and complex), accompanied or not by secondary generalization, with generalized tonic-clonic epileptic seizures, as well as combinations of these types of seizures (usually not effective for small seizures - petit mal, absence seizures and myoclonic seizures ). In patients with epilepsy (especially in children and adolescents) noted a positive effect on symptoms of anxiety and depression, as well as reducing irritability and aggressiveness. Effects on cognitive function and psychomotor performance depends on the dose. Starting anticonvulsant effect varies from several hours to several days (sometimes up to 1 month due to autoinduction of metabolism). In essential and secondary trigeminal neuralgia in most cases prevents the appearance of pain attacks. Easing the pain of trigeminal neuralgia is celebrated through 8-72 hours. When alcohol withdrawal syndrome raises the seizure threshold (which in this state is usually reduced), and reduces the severity of the clinical manifestations of the syndrome (irritability, tremor, gait disorders). Antipsychotic (antimanic) action develops in 7-10 days, may be due to inhibition of metabolism of dopamine and norepinephrine.

Indications:

• primary generalized seizures (absences exception), partial epilepsy (simple or complex seizures), secondary generalized seizures
  
• tic douloureux
  
• idiopathic neuropathy, glossopharyngeal nerve
  
• painful diabetic polyneuropathy
  
• epileptiform seizures in multiple sclerosis, muscle spasms of the facial trigeminal neuralgia, tonic seizures, paroxysmal dysarthria and ataxia, paroxysmal paraesthesia and attacks of pain
  
• alcohol withdrawal syndrome (anxiety, convulsions, hyperexcitability, sleep disorders)
  
• psychotic disorders (affective and schizoaffective disorders, psychoses, dysfunction of the limbic system).
  

Contraindications:

• hypersensitivity (including the tricyclic antidepressants)
  
• violation of medullary hematopoiesis (anemia, leukopenia)
  
• AV block
  
• acute intermittent porphyria (including history)
  
• simultaneous treatment drugs lithium and MAO inhibitors
  
• Children up to age 6 years.
  

Carefully:

• severe heart failure
  
• lack of liver and kidney function
  
• Elderly patients
  
• active alcoholism (enhanced CNS depression, increased metabolism of carbamazepine)
  
• hyponatremia dilutions (ADH hypersecretion syndrome, hypopituitarism, hypothyroidism, adrenal insufficiency)
  
• prostatic hyperplasia
  
• increased intraocular pressure
  
• combination with sedative hypnotics.
  

Application of pregnancy and breastfeeding:

Women of childbearing age carbamazepine should, if possible, be used in a monotherapy (minimally effective dose) as frequency of congenital anomalies of newborns born to women who underwent a combined anti-epileptic medication, higher than in those who received each of these agents as monotherapy.

In the event of pregnancy (when deciding on the appointment of carbamazepine during pregnancy) should be carefully compare the expected benefits of therapy and its possible complications, especially in the first 3 months of pregnancy. There are few reports of cases of congenital diseases and malformations, including spina bifida (spina bifida).

Carbamazepine enhances folate deficiency is often observed during pregnancy, which can help to increase the frequency of birth defects in children (both before and during pregnancy is recommended folic acid supplementation). In order to prevent hemorrhagic complications in newborns of women in the last weeks of pregnancy and the newborn is recommended to prescribe vitamin K1.

Carbamazepine passes into breast milk. Compare the benefits and possible adverse effects of breastfeeding in the face of continued therapy.

Side effect:

On the part of the central and peripheral nervous system: often - dizziness, ataxia, drowsiness, weakness, headache, paresis of accommodation sometimes - abnormal involuntary movements (eg tremor, "fluttering" tremor -asterixis, muscular dystonia, tics), nystagmus is rare - orofacial dyskinesia oculomotor disturbances, speech disorders (eg dysarthria or slurred speech), horeoatetoidnye disorders, peripheral neuritis, paresthesia, muscle weakness and symptoms of paresis.

From the psychic sphere: rarely - hallucinations (visual or auditory), depression, loss of appetite, restlessness, aggressive behavior, agitation, disorientation, activation of psychosis.

From the side of hematopoiesis: often - leukopenia, thrombocytopenia, eosinophilia, rarely - leukocytosis, lymphadenopathy, folic acid deficiency, agranulocytosis, aplastic anemia, pure red cell aplasia, megaloblastic anemia, acute "intermittent" porphyria, reticulocytosis, hemolytic anemia, splenomegaly.

Allergic reactions: often - urticaria, sometimes - erythroderma, multiorgan delayed type hypersensitivity reactions with fever, skin rashes, vasculitis (including nodular erythema as a manifestation of cutaneous vasculitis), lymphadenopathy, symptoms resembling lymphoma, arthralgia, eosinophilia, hepatosplenomegaly and altered liver function. There may also be involved and other organs (lungs, kidneys, pancreas, myocardium, colon), aseptic meningitis, with myoclonus and peripheral eosinophilia, anaphylactoid reactions, angioedema, allergic pneumonitis or eosinophilic pneumonia. use of the drug should be discontinued If you have any of these reactions. Rarely - lupus-like syndrome, skin itching, erythema multiforme exudative (including Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell's syndrome), photosensitivity.

From the digestive system: often - nausea, vomiting, dry mouth, sometimes - diarrhea or constipation, abdominal pain, rarely - glossitis, gingivitis, stomatitis, pancreatitis.

On the part of the hepatobiliary system: often - increasing the activity of gamma-glutamyl transferase (due to induction of this enzyme in the liver), which usually has no clinical significance, increased alkaline phosphatase activity is sometimes - increase in liver transaminases, rarely - hepatitis cholestatic, parenchymal (hepatocellular) type, jaundice, granulomatous hepatitis, hepatic failure.

Since the cardiovascular system: rarely - a violation of intracardiac conduction decrease or increase in blood pressure, bradycardia, arrhythmias, AV block with fainting, collapse, worsening or development of congestive heart failure, aggravation of coronary heart disease (including the appearance or increased frequency of angina attacks ), thrombophlebitis, thromboembolic syndrome.

On the part of the endocrine system and metabolism: often - edema, fluid retention, weight gain, hyponatremia (decrease in plasma osmolarity due to an effect similar to the action of antidiuretic hormone, which in rare cases leads to hyponatremia breeding, accompanied by lethargy, vomiting, headache, disorientation and neurological disorders), rarely - increased prolactin levels (may be accompanied by galactorrhea and gynecomastia) reduction in L-thyroxine and increased TSH (usually not accompanied by clinical symptoms) disorders of calcium-phosphorus metabolism in bone tissue (reduction of the concentration of Ca2 + and 25-OH -holekaltsiferola plasma) osteomalacia, hypercholesterolemia, hypertriglyceridemia, and swollen lymph nodes, hirsutism.

From the urogenital system: rarely - interstitial nephritis, renal failure, renal impairment (eg albuminuria, haematuria, oliguria, increased levels of urea / azotemia), urinary frequency, urinary retention, reduced potency.

From the musculoskeletal system: rarely - arthralgia, myalgia or cramps.

From the sensory organs: rarely - a violation of taste sensations, cataract, conjunctivitis hearing disorders, including tinnitus, hyperacusis, Gipoakuzija, changes in the perception of pitch.

Other: disorders of skin pigmentation, purpura, acne, sweating, alopecia.

Drug Interactions:

Simultaneous administration of carbamazepine with CYP 3A4 inhibitors may increase its concentration in blood plasma and cause adverse reactions. Combined use of CYP 3A4 inducers may accelerate metabolism of carbamazepine, carbamazepine reduce the concentration in plasma and decrease the therapeutic effect, on the contrary, their removal may reduce the rate of biotransformation of carbamazepine and lead to an increase in its concentration.

Increasing the concentration of carbamazepine in plasma: verapamil, diltiazem, felodipine, dextropropoxyphene, viloksazin, fluoxetine, fluvoxamine, cimetidine, acetazolamide, danazol, desipramine, nicotinamide (in adults, only in high doses), macrolides (erythromycin, josamycin, clarithromycin, troleandomycin) azoles ( itraconazole, ketoconazole, fluconazole), terfenadine, loratadine, isoniazid, propoxyphene, grapefruit juice, protease inhibitors of virus used in the treatment of HIV infection (eg ritonavir) - requires correction dosing regimen or monitoring of carbamazepine plasma concentration.

Felbamate reduces the concentration of carbamazepine in the plasma and increases the concentration of carbamazepine-10,11-epoxide, possibly with simultaneous reduction in serum concentration of felbamate.

The concentration of carbamazepine reduce phenobarbital, phenytoin, primidone, metsuksimid, fensuksimid, theophylline, rifampicin, cisplatin, doxorubicin, possibly clonazepam, valpromid, valproic acid, oxcarbazepine, and herbal preparations containing St. John's wort (Hypericum perforatum). It is possible to displace valproic acid and primidone carbamazepine in connection with plasma proteins and increase in the concentration of the pharmacologically active metabolite (carbamazepine-10,11-epoxide). If concomitant use of valproic acid with finlepsin in exceptional cases can occur coma, and confusion. Isotretinoin modifies the bioavailability and / or clearance of carbamazepine and carbamazepine-10,11-epoxide (carbamazepine be monitored plasma concentration).

Carbamazepine may lower the plasma concentration (reduce or even reverse the effects) and require correction doses of the following drugs: klobazama, clonazepam, digoxin, ethosuximide, primidone, valproic acid, alprazolam, corticosteroids (prednisone, dexamethasone), cyclosporin, tetracyclines (doxycycline) haloperidol, methadone, oral drugs containing estrogen and / or progesterone (requires selection of alternative contraceptive methods), theophylline, oral anticoagulants (warfarin, fenprokumona, dicumarol), lamotrigine, topiramate, tricyclic antidepressants (imipramine, amitriptyline, nortriptyline, clomipramine), clozapine , felbamate, tiagabine, oxcarbazepine, protease inhibitors used in the treatment of HIV infection (indinavir, ritonavir, saquinavir), calcium channel blockers (group of dihydropyridine such as felodipine), itraconazole, levothyroxine, midazolam, olanzapine, praziquantel, risperidone, tramadol, ziprasidone .

It is possible to increase or decrease phenytoin plasma carbamazepine on the background and raising mefenitoina (in rare cases). In an application finlepsin and drugs lithium may increase neurotoxic effect of both active substances. Tetracyclines may reduce the therapeutic effect finlepsin. Carbamazepine or combined with paracetamol increases the risk of toxic effects on the liver and reduces the therapeutic efficacy (acceleration of metabolism of paracetamol).

Co-administration of carbamazepine with phenothiazines, pimozide, thioxanthenes (Chlorprothixenum) molindone, haloperidol, maprotiline, clozapine and tricyclic antidepressants leads to increased inhibitory action on the central nervous system and weaken the anticonvulsant effect of carbamazepine.

MAO inhibitors increase the risk of giperpireticheskih crises, hypertensive crises, convulsions, death (before the appointment of carbamazepine MAO inhibitors should be discontinued at least 2 weeks, or if the clinical situation allows, even for a longer period).

Co-administration with a diuretic (hydrochlorothiazide, furosemide) may lead to hyponatremia, accompanied by clinical symptoms.

It reduces the effects of non-depolarizing muscle relaxants (pancuronium). In the case of such a combination may be necessary to increase the dose of muscle relaxants, and the need to carry out careful monitoring of patients as fast as possible termination of the action of muscle relaxants.

Reduces portability of ethanol.

It accelerates the metabolism of indirect anticoagulants, hormonal contraceptive drugs, folic acid, praziquantel, may enhance the elimination of thyroid hormones.

It accelerates the metabolism of anesthetic agents (enflurane, halothane, halothane) with an increased risk of hepatotoxic effects enhances the formation of nephrotoxic metabolites methoxyflurane.

It enhances the hepatotoxic effects of isoniazid.

Dosage and administration:

Inside, during or after meals, drinking plenty of fluids. For convenience tablet (and its half or quarter) can be dissolved in water or juice, as sustained release property of the active ingredient after dissolution of the tablet in the fluid is maintained. The range of the doses of 400-1200 mg / day, which is distributed on 1-2 times daily.

The maximum daily dose should not exceed 1600 mg.

Epilepsy

In cases where this is possible, Finlepsin retard should be prescribed as monotherapy. Treatment starts with application of a small daily dose, which subsequently slowly increased until the optimum effect. Joining finlepsin retard to the already ongoing antiepileptic therapy should be gradual, with the dose of the drugs do not change or, if necessary, correcting. If the patient has forgotten to take timely the next dose, the missed dose should be taken as soon as the omission was noticed, while you can not take a double dose of the drug.

Adults

Starting dose - 200-400 mg / day, then gradually increase the dose until the optimum effect. Maintenance dose - 800-1200 mg / day, which is distributed on 1-2 receptions a day.

Children

The starting dose for children 6 to 15 years - 200 mg / day and then gradually increase the dose to 100 mg / day to achieve the optimal effect.

Supporting dose for children 6-10 years - 400-600 mg / day (in 2 divided doses) for children 11-15 years - 600-1000 mg / day (2 admission).

The recommended dosing regimen:

	Starting dose	Maintenance dose
Adults	200-300 mg in the evening	200-600 mg in the morning 400-600 mg in the evening
Children aged 6 to 10 years	200 mg in the evening	200 mg in the morning 200-400 mg in the evening
Children from 11 to 15 years	200 mg in the evening	200-400 mg in the morning 400-600 mg in the evening

Duration of treatment depends on the indication and the patient's individual response to treatment. The decision to transfer the patient to Finlepsin retard the duration of its use, and the abolition of the treatment is taken by the doctor individually. The possibility of reducing the dose or discontinuation of treatment is considered after a 2-3-year period, the total absence of seizures.

Treatment was discontinued, gradually reducing the dose over 1-2 years, under the control of the EEG. In children, while reducing the daily dose should be taken into account body weight increase with age.

Trigeminal neuralgia, idiopathic neuralgia glossofaringealnaya

The initial dose is 200-400 mg / day, which was partitioned into 2 admission. The initial dose is increased up to the complete disappearance of pain, on average: up to 400-800 mg / day. After that a certain part of the treatment of patients can continue to lower maintenance dose of 400 mg.

Elderly patients and patients sensitive to karabamazepinu, Finlepsin retard administered in an initial dose of 200 mg 1 time per day.

Pain in diabetic neuropathy

The average daily dose - 200 mg in the morning and 400 mg in the evening. In exceptional cases Finlepsin retard can be administered in a dose of 600 mg 2 times a day.

Treatment of alcohol withdrawal in a hospital

The average daily dose - 600 mg (200 mg in the morning and 400 mg in the evening).

In severe cases in the early days of the dose can be increased to 1200 mg / day, which is partitioned into 2 admission.

If necessary Finlepsin retard can be combined with other agents used to treat alcohol withdrawal, in addition to sedative-hypnotic drugs.

During treatment should regularly monitor the content of carbamazepine in plasma.

In connection with the possible development of side effects of the central and autonomic nervous system of patients is set close observation in the hospital.

Epileptiform seizures in multiple sclerosis

The average daily dose - 200-400 mg 2 times a day.

Treatment and prevention of psychoses

The initial and maintenance dozs usually the same - 200-400 mg / day. If necessary, the dose may be increased to 400 mg 2 times a day.

Overdose:

Symptoms occur in overdose symptoms and complaints usually reflect a violation of the CNS, cardiovascular and respiratory systems.

Central nervous system and sensory organs - the oppression of the CNS, disorientation, drowsiness, agitation, hallucinations, coma "blurred" vision, slurred speech, dysarthria, nystagmus, ataxia, dyskinesia, hyperreflexia (first), hyporeflexia (later), convulsions, psychomotor disturbances, myoclonus , hypothermia, mydriasis.

Cardiovascular system: tachycardia, decreased blood pressure, increased blood pressure sometimes, violations of intraventricular conduction with the expansion of the QRS complex fainting, cardiac arrest.

Respiratory system: respiratory depression, pulmonary edema.

Digestive system: nausea and vomiting, delayed evacuation of food from the stomach, decreased motility of the colon.

Urinary system: urinary retention, oliguria or anuria, fluid retention, hyponatremia.

Laboratory and instrumental indicators: leukocytosis or leukopenia, hyponatremia, metabolic acidosis, hyperglycemia and glucosuria, increased muscle creatine phosphokinase fraction.

Treatment: there is no specific antidote. Treatment is based on the clinical condition of the patient's hospitalization, the determination of carbamazepine concentration in plasma, the evacuation of gastric contents, gastric lavage, the appointment of activated carbon. Ineffective forced diuresis, hemodialysis and peritoneal dialysis. Children may need blood transfusions. Symptomatic supportive treatment in the intensive care unit, monitoring of cardiac function, body temperature, corneal reflexes, kidney and bladder, correction of electrolyte disorders.

Precautionary measures:

Monotherapy of epilepsy begin with low doses destination individually raising them to achieve the desired therapeutic effect.

It is advisable to determine the concentration in plasma in order to select the optimal dose, in particular in combination therapy. In some cases, the dose needed for treatment can significantly deviate from the recommended initial and maintenance doses, for example due to rapid metabolism due to the induction of hepatic microsomal enzymes, or due to interactions of drugs in combination therapy. Carbamazepine should not be combined with a sedative-hypnotic.

If necessary Finlepsin retard can be combined with other agents used to treat alcohol withdrawal. During the treatment it is necessary to periodically monitor the contents of carbamazepine in plasma. In connection with the development of side effects of the central and autonomic nervous system of patients is set close observation in the hospital. When transferring a patient on carbamazepine should gradually reduce the dose previously designated antiepileptic until its complete abolition. Sudden discontinuation of carbamazepine may trigger epileptic seizures. If necessary abruptly interrupt treatment, the patient should be transferred to another antiepileptic drug undercover shown in such cases the drug (e.g. diazepam administered in / or rectally, or phenytoin administered in / in).

It described several cases of vomiting, diarrhea and / or low power, seizures and / or respiratory depression in newborns whose mothers took carbamazepine concomitantly with other anticonvulsants (probably these reactions are manifestations of neonatal withdrawal syndrome).

Before the appointment of carbamazepine in the treatment process to be a study of liver function, especially in patients with a history of which there is evidence of liver disease and in elderly patients. In the case of strengthening the already existing liver dysfunction or when active liver disease drug should be discontinued immediately. Also, before the start of treatment necessary to study blood picture (including platelet count, reticulocyte count), the iron level in serum, urine (total analysis) urea level in the blood, EEG, determining the concentration of electrolytes in serum (and periodically during the treatment, T .K. develop hyponatremia) is possible. Subsequently, these indicators should be monitored during the first month of treatment - a weekly, and later - on a monthly basis.

In most cases, a transient or a persistent decline in the number of platelets and / or leukocytes is not a harbinger of the beginning of aplastic anemia or agranulocytosis. However, before treatment and periodically during the treatment process should be carried out clinical blood tests, including counting the number of platelets and possibly reticulocytes and determine the level of iron in the blood serum. Non-progressive asymptomatic leukopenia does not require the abolition, but the treatment should be discontinued when a progressive leukopenia or leucopenia, accompanied by clinical symptoms of the infectious disease.

Carbamazepine should be immediately canceled the appearance of hypersensitivity reactions or symptoms, presumably indicating the development of Stevens-Johnson syndrome or Lyell's syndrome. Weakly expressed skin reactions (isolated macular or maculopapular rash) usually disappear within a few days or weeks, even with continued treatment or after the dose of the drug (the patient at this time should be under close medical supervision).

Carbamazepine has a weak anticholinergic activity, when administered to patients with elevated intraocular pressure it needs constant monitoring.

It is necessary to take into account the possibility of activation of a latent psychosis occurring, and in elderly patients - the possibility of disorientation or agitation.

Possible violations of fertility in men and / or disorders of spermatogenesis (the relationship of these disorders with carbamazepine is not installed). Also, the likelihood of bleeding in women in the period between periods when both used oral contraceptives. Carbamazepine may adversely affect the reliability of oral contraceptive pills, so women of childbearing age during treatment should use alternative methods of contraception.

Carbamazepine should be used only under medical supervision. It is necessary to bring to the attention of patients about the early signs of toxicity inherent probable hematological disorders, as well as the symptoms of the skin and liver. The patient was informed of the need to consult a doctor immediately in case of adverse reactions such as fever, sore throat, rash, ulceration of the mucous membrane of the mouth, wanton bruising, hemorrhages in the form of petechiae or purpura.

Before the treatment it is recommended to conduct an eye examination, including the study of the fundus and measuring a slit lamp, if necessary, the intraocular pressure. In the case of the appointment of the drug to patients with increased intraocular pressure, continuous monitoring of this parameter.

In the period of treatment should refrain from activities potentially hazardous activities that require high concentration and psychomotor speed reactions.

It is recommended to give up alcohol.

Patients with severe cardiovascular disease, liver disease and kidney failure, as well as the elderly prescribe a lower dose of the drug.

Although the relationship between the carbamazepine dose, its concentration and clinical efficacy or tolerability is very small, however, the regular definition of carbamazepine levels may be useful in the following situations: when a sharp increase in the frequency of attacks in order to check whether the patient is taking medication properly during pregnancy in the treatment of children and adolescents with suspected malabsorption of the drug in cases of suspected development of toxic reactions if the patient is taking multiple drugs.