Carbamazepine, tablets 200 mg 50 pcs

The antiepileptic agent (dibenzazepine derivative) which also has normotensive, antimanic, antidiuretic (in patients with non-sugar diabetes) and analgesic (in patients with neuralgia) effects.

The mechanism of action is associated with blockade of potential-dependent Na+-channels, which leads to stabilization of the neuronal membrane, inhibition of the occurrence of serial discharges of neurons and reduction of synaptic conduction of impulses. Prevents the reformation of Na+-dependent action potentials in depolarized neurons. Reduces the release of the excitatory neurotransmitter amino acid glutamate, increases the reduced seizure threshold and thus reduces the risk of an epileptic seizure. Increases conductance for K+, modulates potential-dependent Ca2+ channels, which may also determine the anticonvulsant effect of the drug. Corrects epileptic personality changes and, eventually, increases patients’ communicability and contributes to their social rehabilitation. It can be prescribed as the main therapeutic drug and in combination with other anticonvulsants. It is effective in focal (partial) epileptic seizures (simple and complex), accompanied or not accompanied by secondary generalization, in generalized tonic-clonic epileptic seizures, as well as in combinations of these types (usually ineffective in small seizures – petit mal, absences and myoclonic seizures).

In patients with epilepsy (especially in children and adolescents) a positive effect on symptoms of anxiety and depression, as well as reduction of irritability and aggressiveness was noted. The effect on cognitive function and psychomotor performance is dose-dependent and highly variable.

The onset of 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 it prevents the occurrence of painful attacks in most cases. It is effective for relief of neurogenic pain in spinal tenderness, post-traumatic paresthesias and post-herpetic neuralgia. Relief of pain in trigeminal neuralgia is noted in 8-72 hours. In alcohol withdrawal syndrome it increases the threshold of seizure readiness (which is usually lowered in this condition) and reduces the severity of clinical manifestations of the syndrome (increased excitability, tremor, gait disturbances).

In patients with non-sugar diabetes it leads to rapid compensation of the water balance, reduces diuresis and the feeling of thirst.

The antipsychotic (antimanic) effect develops in 7-10 days, may be due to inhibition of dopamine and noradrenaline metabolism.

Indications

Epilepsy (excluding absences, myoclonic or flaccid seizures) – partial seizures with complex and simple symptomatology, primary and secondary generalized forms of seizures with tonic-clonic convulsions, mixed seizure forms (monotherapy or in combination with other anticonvulsant drugs); idiopathic trigeminal neuralgia, trigeminal neuralgia in multiple sclerosis, idiopathic lingual pharyngeal neuralgia, alcohol withdrawal syndrome, treatment of affective disorders, polydipsia and polyuria in non-sugar diabetes, pain syndrome in diabetic polyneuropathy.

Prevention of phasic affective disorders (manic-depressive psychosis, schizoaffective disorders, etc.).

Active ingredient

Composition

One tablet contains:

The active ingredient is carbamazepine 200 mg;

Excipients: colloidal silicon dioxide (aerosil) 960 µg, potato starch 96.64 mg, povidone K30 14.4 mg, polysorbate 80 1.6 mg, talcum powder 3.2 mg, magnesium stearate 3.2 mg.

Interaction

Carbamazepine enhances the activity of microsomal liver enzymes and may reduce the effectiveness of drugs that are metabolized in the liver. Concomitant administration of carbamazepine with CYP3A4 inhibitors may increase its plasma concentrations. Concomitant use with CYP3A4 inducers may lead to acceleration of carbamazepine metabolism and decrease its concentration in blood plasma, conversely, their withdrawal may decrease the biotransformation rate of carbamazepine and lead to increase of its concentration.

The plasma concentrations of carbamazepine are increased: Verapamil, diltiazem, felodipine, dextropropoxyphene, viloxazine, fluoxetine, fluvoxamine, cimetidine, acetazolamide, danazol, desipramine, nicotinamide (in adults, in high doses only); macrolides (erythromycin, jozamycin, clarithromycin, troleandomycin); azoles (itraconazole, ketoconazole, fluconazole), terfenadine, loratadine, isoniazid, propoxyphene, grapefruit juice, viral protease inhibitors used in HIV therapy. Felbamate decreases plasma concentrations of carbamazepine and increases concentrations of carbamazepine-10,11-epoxide, with a possible simultaneous decrease in serum concentrations of felbamate. Phenobarbital, phenytoin, primidone, metsuximide, fensuximide, theophylline, rifampicin, cisplastine, doxyrubicin, possibly: clonazepam, valpromide, valproic acid, oxcarbazepine and herbal preparations containing St John’s wort (Hypericum perforatum) reduce carbamazepine concentration. There are reports of possible displacement of carbamazepine from plasma protein binding by valproic acid and primidone and increased concentrations of the pharmacologically active metabolite (carbamazepine-10,11-epoxide). Isotretinoin changes the bioavailability and/or clearance of carbamazepine and carbamazepine-10,11-epoxide (monitoring of plasma concentrations of carbamazepine is required). Carbamazepine may reduce plasma concentrations (reduce or even completely negate the effects) and require dose adjustments of the following drugs: Clobazam, clonazepam, etoximide, primidone, valproic acid, alprazolam, glucocorticosteroids (prednisolone, dexamethasone), cyclosporine, doxycycline, haloperidol, methadone, oral drugs estrogens and/or progesterone (alternative methods of contraception should be selected), theophylline, oral anticoagulants (warfarin, phenprocoumon, dicumarol), lamotrigine, topiramate, tricyclic antidepressants (imipramine, amitriptyline, nortriptyline, clomipramine), clozapine, felbamate, tiagabine, oxcarbazepine, protease inhibitors used in HIV therapy (indinavir, ritonavir, saquinovir), calcium channel blockers (dihydropyridone group, such as felodipine), itraconazole, levothyroxine, midazolam, olazapine, praziquantel, risperidone, tramadol, cyprazidone. There are reports that during carbamazepine administration plasma levels of phenytoin may both increase and decrease, and levels of mefenitoin may increase (in rare cases). Carbamazepine combined with paracetamol increases the risk of its toxic effects on the liver and reduces therapeutic efficacy (acceleration of metabolism of paracetamol). Concomitant administration of carbamazepine with phenothiazine, pimozide, tioxan-thens, molindone, haloperidol, maprotiline, clozapine and tricyclic antidepressants leads to increased CNS depression and weakened anticonvulsant effect of carbamazepine. Concomitant administration with diuretics (hydrochlorothiazide, furosemide) may lead to hyponatremia accompanied by clinical manifestations. Reduces the effects of nondepolarizing myorelaxants (pancuronium). Reduces tolerance to ethanol. Accelerates metabolism of indirect anticoagulants, hormonal contraceptives, folic acid; praziquantel, may increase elimination of thyroid hormones. Accelerates metabolism of agents for general anesthesia (enflurane, halothane, fluorothane) with increased risk of hepatotoxic effects; increases formation of nephrotoxic metabolites of methoxyflurane. Increases hepatotoxic effects of isoniazid.

Directions for use

Ingestion, regardless of meals, along with small amounts of liquid.

Epilepsy. Whenever possible, carbamazepine should be prescribed as monotherapy. Treatment begins with a small daily dose, which is slowly increased until optimal effect is achieved.

The addition of carbamazepine to existing antiepileptic therapy should be done gradually, and the doses of the drugs used should not be changed or adjusted if necessary.

For adults, the initial dose is 100-200 mg once or twice daily. Then the dose is slowly increased until the optimal therapeutic effect is achieved (usually 400 mg 2-3 times a day, maximum 1.6-2 g/day).

In children from 3 years of age, an initial dose of 20-60 mg/day, gradually increasing by 20-60 mg every other day.

In children over 3 years of age, an initial dose of 100 mg/day, increasing the dose gradually by 100 mg each week. Maintenance doses: 10-20 mg/kg per day. (in several doses): for 4-5 years – 200-400 mg (in 1-2 doses), 6-10 years – 400-600 mg (in 2-3 doses), for 11-15 years – 600-1000 mg (in 2-3 doses).

In trigeminal neuralgia, 200-400 mg/day is prescribed on the first day, gradually increasing by no more than 200 mg/day until pain ceases (400-800 mg/day on average), and then decreasing to the minimum effective dose.

In pain syndrome of neurogenic genesis, the initial dose is 100 mg twice a day for the first day, then the dose is increased by no more than 200 mg/day, increasing it by 100 mg every 12 hours, if necessary, until the pain subsides. The maintenance dose is 200-1200 mg/day in several doses.

When treating elderly and hypersensitive patients, the starting dose is 100 mg twice daily.

Alcohol withdrawal syndrome: the average dose is 200 mg 3 times a day; in severe cases during the first few days the dose may be increased to 400 mg 3 times a day. At the beginning of treatment in severe withdrawal symptoms it is recommended to prescribe in combination with sedative-hypnotic drugs (clomethiazole, chlordiazepoxide).

Nonspecific diabetes: the average dose for adults is 200 mg 2-3 times a day. In children the dose should be reduced according to the age and body weight of the child.

Diabetic neuropathy accompanied by pain: the average dose is 200 mg 2-4 times a day. In the prevention of relapses of affective and schizoaffective psychoses, 600 mg/day in 3-4 doses.

In acute manic states and affective (bipolar) disorders the daily dose is 400-1600 mg. The average daily dose is 400-600 mg (in 2-3 doses). In acute manic states the dose is increased rapidly, in maintenance therapy of affective disorders – gradually (to improve tolerability).

Special Instructions

Before starting treatment, it is necessary to perform a general blood count (including platelet count, reticulocyte count), a general urinalysis, determine iron levels, serum electrolyte and urea concentrations. Subsequently, these parameters should be monitored during the first month of treatment weekly and then monthly. If administered to patients with elevated intraocular pressure, its periodic monitoring is necessary. Non-progressive asymptomatic leukopenia does not require withdrawal; however, treatment should be discontinued if progressive leukopenia or leukopenia accompanied by clinical symptoms of infectious disease occurs.

Information about possible effect of the drug for medical use on the ability to drive vehicles, mechanisms. During the treatment period, caution must be exercised while driving vehicles and engaging in other potentially dangerous activities requiring increased concentration and quick psychomotor reactions.

Contraindications

Hypersensitivity to carbamazepine and chemically similar drugs (tricyclic antidepressants) or to any other component of the drug, acute intermittent porphyria (including history of history), concomitant use of monoamine oxidase inhibitors (hereinafter referred to as MAO inhibitors) and within 2 weeks after their withdrawal, disorders of medullary hematopoiesis, atrioventricular blockade, pregnancy and lactation.

With caution . Dilution hyponatremia, advanced age, alcohol intake, inhibition of medication-induced bone marrow hematopoiesis (history); prostatic hyperplasia, increased intraocular pressure, marked heart failure, liver failure, chronic renal failure.

Side effects

Central nervous system disorders: dizziness, ataxia, somnolence, general weakness, headache, accommodation paresis, tremor, tics, nystagmus, orofacial dyskinesia, oculomotor disorders, dysarthria, choreoathetoid disorders, peripheral neuritis, paresthesias, muscle weakness and paresis.

Psychiatric disorders: hallucinations, depression, loss of appetite, anxiety, aggressive behavior, agitation, disorientation, activation of psychosis. Allergic reactions: urticaria, exfoliative dermatitis, erythroderma, lupus-like syndrome, Stevens-Johnson syndrome, toxic epidermal necrolysis, photosensitivity, erythema multiforme and nodular erythema. Multiorgan delayed-type hypersensitivity reactions with fever, skin rash, vasculitis, lymphadenopathy, lymphoma-like signs, arthralgia, leukopenia, eosinophilia, hepatosplenomegaly and altered liver function indices are possible (these manifestations occur in various combinations). Other organs (e.g., lungs, kidneys, pancreas, myocardium, colon) may also be involved. Very rarely – aseptic meningitis with myoclonus, anaphylactic reaction, angioedema, hypersensitivity reactions on the lungs, characterized by fever, dyspnea, pneumonitis or pneumonia.

Hematopoietic organs: leukopenia, thrombocytopenia, eosinophilia, leukocytosis, lymphoadenopathy; agranulocytosis, aplastic anemia, true erythrocytic aplasia, megaloblastic anemia, acute intermittent porphyria, reticulocytosis, hemolytic anemia.

Digestive system disorders (hereinafter gastrointestinal system): nausea, vomiting, dry mouth, diarrhea or constipation, abdominal pain, glossitis, stomatitis, pancreatitis.

Hepatic disorders: increased gamma-glutamyltransferase activity (usually of no clinical significance), increased alkaline phosphatase activity and “hepatic” transaminases, hepatitis (granulomatous, cholestatic, parenchymatous (hepatocellular) or mixed type); liver failure.

Cardiovascular system disorders: intracardiac conduction disorders; decreased or increased blood pressure; bradycardia, arrhythmias, atrioventricular block with fainting, collapse, aggravation or development of congestive heart failure, exacerbation of coronary heart disease (including the appearance or increased frequency of coronary heart disease).including appearance or increase in frequency of angina attacks), thrombophlebitis, thromboembolic syndrome.

Endocrine system and metabolic disorders: edema, weight gain, hyponatremia, increased levels of prolactin (may be accompanied by galactorrhea and gynecomastia); decreased levels of L-thyroxine (free T4, TZ) and increased levels of thyroid hormone (TSH) (usually not accompanied with clinical manifestations), disorders of calcium-phosphorus metabolism in bone tissue (decrease of plasma concentration of Ca2+ and 25-OH-cholecalciferol); osteomalacia; hypercholesterolemia and hypertriglyceridemia.

Urogenital system disorders: interstitial nephritis, renal failure, renal dysfunction (albuminuria, hematuria, oliguria, increased urea/azotemia), frequent urination, urinary retention, disorders of sexual function/impotence.

Musculoskeletal disorders: arthralgia, myalgia or cramps.

Sensory organs: disorders of taste sensation, blurred lens, conjunctivitis; hyper- or hypoacusis, changes in pitch perception.

Others: skin pigmentation disorders, purpura, acne, sweating, alopecia.

Overdose

Symptoms: respiratory depression, hyperreflexia changing to hyporeflexia, hypothermia, suppression of gastrointestinal motility, increased severity of side effects.

Treatment: there is no specific antidote. Gastric lavage, prescription of activated charcoal (late evacuation of gastric contents may lead to delayed absorption for 2-3 days and reappearance of intoxication symptoms), symptomatic therapy. Forced diuresis, hemodialysis and peritoneal dialysis are ineffective (dialysis is indicated when severe poisoning and renal failure are combined). Blood exchange transfusion may be necessary in children. Hemosorption with carbon sorbents is recommended.

Similarities