Description of the active substance:
This information is a reference and it is not enough that the drug has been prescribed by a doctor ..
PHARMACHOLOGIC EFFECT
Antiepileptic agent, derivative of tricyclic iminostilbene. It is believed that anticonvulsant action is associated with a decrease in the ability of neurons to maintain a high frequency of development of repeated action potentials through inactivation of sodium channels. In addition, it seems that inhibition of the release of neurotransmitters by blocking the presynaptic sodium channels and the development of action potentials, which in turn reduces the synaptic transmission, is important.
Has a moderate antimanic, antipsychotic effect, as well as analgesic effect with neurogenic pain. The mechanisms of action may involve GABA receptors, which may be associated with calcium channels; Also, apparently, the effect of carbamazepine on the systems of neurotransmitter modulators is important.
The antidiuretic effect of carbamazepine may be associated with a hypothalamic effect on the osmoreceptors, which is mediated through the secretion of ADH, and is also due to direct action on the renal tubules.
PHARMACOKINETICS
After ingestion, carbamazepine is almost completely absorbed from the digestive tract. Binding to plasma proteins is 75%. It is an inducer of hepatic enzymes and stimulates its own metabolism.
T 1/2 is 12-29 hours. 70% is excreted in the urine (in the form of inactive metabolites) and 30% - with feces.
INDICATIONS
Epilepsy: large, focal, mixed (including large and focal) epileptic seizures. Pain syndrome predominantly of a neurogenic genesis, incl. Essential neuralgia of the trigeminal nerve, trigeminal neuralgia with multiple sclerosis, essential glossopharyngeal neuralgia. Prevention of seizures in alcohol withdrawal syndrome. Affective and schizoaffective psychosis (as a means of prevention). Diabetic neuropathy with pain syndrome. Non-diabetes mellitus of central genesis, polyuria and polydipsia of neurohormonal nature.
DOSING MODE
Install individually. When ingested for adults and adolescents 15 years and older, the initial dose is 100-400 mg. If necessary, and taking into account the clinical effect, the dose is increased by no more than 200 mg / day at intervals of 1 week. The frequency of admission is 1-4 times / day. The maintenance dose is usually 600-1200 mg / day in several doses. The duration of treatment depends on the indications, the effectiveness of treatment, the patient's response to therapy.
Children under the age of 6 years are administered 10-20 mg / kg / day in 2-3 divided doses; if necessary and taking into account the tolerability dose is increased by no more than 100 mg / day with an interval of 1 week; the maintenance dose is usually 250-350 mg / day and does not exceed 400 mg / day. Children aged 6-12 years - 100 mg 2 times / day on the first day, then the dose is increased by 100 mg / day at intervals of 1 week. until the optimum effect is obtained; the maintenance dose is usually 400-800 mg / day.
Maximum doses: when administered to adults and adolescents 15 years and older - 1.2 g / day, children - 1 g / day.
SIDE EFFECT
From the side of the central nervous system and peripheral nervous system: often - dizziness, ataxia, drowsiness; possible headache, diplopia, accommodation disorders; rarely - involuntary movements, nystagmus; in some cases - oculomotor disorders, dysarthria, peripheral neuritis, paresthesia, muscle weakness, paresis symptoms, hallucinations, depression, fatigue, aggressive behavior, agitation, mental disorders, activation of psychoses, taste sensations, conjunctivitis, tinnitus, hyperacusia.
On the part of the digestive system: nausea, increased GGT, increased activity of alkaline phosphatase, vomiting, dry mouth; rarely - increased activity of transaminases, jaundice, cholestatic hepatitis, diarrhea, or constipation; in some cases - a decrease in appetite, abdominal pain, glossitis, stomatitis.
From the cardiovascular system: rarely - violations of the conductivity of the myocardium; in some cases - bradycardia, arrhythmias, AV-blockade with syncope, collapse, heart failure, manifestations of coronary insufficiency, thrombophlebitis, thromboembolism.
On the part of the hematopoiesis system: leukopenia, eosinophilia, thrombocytopenia; rarely - leukocytosis; in some cases - agranulocytosis, aplastic anemia, erythrocytic aplasia, megaloblastic anemia, reticulocytosis, hemolytic anemia, granulomatous hepatitis.
On the part of metabolism: hyponatremia, fluid retention, swelling, weight gain, decreased plasma osmolality; in some cases - acute intermittent porphyria, deficiency of folic acid; impaired calcium metabolism, increased cholesterol and triglycerides.
On the part of the endocrine system: gynecomastia or galactorrhea; rarely - thyroid dysfunction.
From the urinary system: rarely - violations of kidney function, interstitial nephritis and renal failure.
From the respiratory system: in some cases - dyspnea, pneumonitis or pneumonia.
Allergic reactions: skin rash, itching; rarely - lymphadenopathy, fever, hepatosplenomegaly, arthralgia.
CONTRAINDICATIONS
AV-blockade, previous mielodepression, intermittent porphyria in the anamnesis, simultaneous administration of MAO inhibitors and lithium preparations, increased sensitivity to carbamazepine.
PREGNANCY AND LACTATION
If necessary, use during pregnancy (especially in the first trimester) and during lactation should carefully weigh the expected benefit of treatment for the mother and the risk to the fetus or child. In this case, carbamazepine is recommended only in the form of monotherapy in the lowest effective doses.
Women of childbearing age during the treatment with carbamazepine are recommended to use non-hormonal contraceptives.
APPLICATION FOR FUNCTIONS OF THE LIVER
With caution apply for severe impairment of kidney function.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
With caution apply for severe violations of liver function.
APPLICATION FOR CHILDREN
Use with caution in children.
APPLICATION IN ELDERLY PATIENTS
Use with caution in elderly patients.
SPECIAL INSTRUCTIONS
Carbamazepine is not used in atypical or generalized small epileptic seizures, myoclonic or atonic epileptic seizures. Do not use to relieve normal pain; as a preventive agent during long periods of remission of trigeminal neuralgia.
They are used with caution in case of concomitant diseases of the cardiovascular system, expressed violations of the liver and / or kidney function, diabetes mellitus, increased intraocular pressure, with a history of hematological reactions to other drugs, hyponatremia, urinary retention, hypersensitivity to tricyclic antidepressants , with a history of interrupting the course of treatment with carbamazepine, as well as children and elderly patients.
Treatment should be carried out under the supervision of a doctor. With long-term treatment, it is necessary to monitor the blood picture, the functional state of the liver and kidneys, the concentration of electrolytes in the blood plasma, and conduct an ophthalmological examination. It is recommended to periodically determine the level of carbamazepine in the blood plasma to monitor the effectiveness and safety of treatment.
At least 2 weeks before the initiation of carbamazepine therapy, treatment with MAO inhibitors should be discontinued.
During the treatment period, do not drink alcohol.
Impact on the ability to drive vehicles and manage mechanisms
During treatment, one should refrain from engaging in potentially dangerous activities that require increased attention, speed of psychomotor reactions.
DRUG INTERACTION
With the simultaneous use of inhibitors of the isoenzyme CYP3A4, an increase in the concentration of carbamazepine in the blood plasma is possible.
With the simultaneous use of inducers of the CYP3A4 isoenzyme system, it is possible to accelerate the metabolism of carbamazepine, reduce its concentration in the blood plasma, reduce the therapeutic effect.
With the simultaneous use of carbamazepine stimulates the metabolism of anticoagulants, folic acid.
With simultaneous application with valproic acid, a decrease in the concentration of carbamazepine and a significant decrease in the concentration of valproic acid in the blood plasma are possible. This increases the concentration of the carbamazepine-epoxide metabolite (probably due to the inhibition of its conversion to carbamazepine-10,11-trans-diol), which also has anticonvulsant activity, so the effects of this interaction can be leveled, but more often there are side reactions - blurred vision, dizziness, vomiting, weakness, nystagmus. With the simultaneous use of valproic acid and carbamazepine, the development of a hepatotoxic effect is possible (apparently due to the formation of a secondary metabolite of valproic acid, which has a hepatotoxic effect).
With the simultaneous use of valpromide reduces the metabolism in the liver of carbamazepine and its metabolite carbamazepine-epoxide due to inhibition of the enzyme epoxide hydrolase. This metabolite has anticonvulsant activity, but with a significant increase in the concentration in the blood plasma can have toxic effects.
With simultaneous use with verapamil, diltiazem, isoniazid, dextropropoxyphene, viloxazine, fluoxetine, fluvoxamine, cimetidine, acetazolamide, danazolum, desipramine, nicotinamide (in adults, only in high doses), erythromycin, troleandomycin, josamycin, clarithromycin; with azoles (including with itraconazole, ketoconazole, fluconazole), terfenadine, loratadine, an increase in the concentration of carbamazepine in the blood plasma is possible with a risk of side effects (dizziness, drowsiness, ataxia, diplopia).
When used simultaneously with hexamidine, the anticonvulsant effect of carbamazepine is weakened; with hydrochlorothiazide, furosemide - it is possible to reduce the sodium content in the blood; with hormonal contraceptives - it is possible to weaken the effect of contraceptives and to develop acyclic bleeding.
With simultaneous use with thyroid hormones, an increase in the elimination of thyroid hormones is possible; with clonazepam - it is possible to increase the clearance of clonazepam and decrease the clearance of carbamazepine; with lithium preparations - the mutual enhancement of neurotoxic action is possible.
With simultaneous application with primidone, a decrease in the concentration of carbamazepine in the blood plasma is possible. There are reports that primidone may increase the concentration in the plasma of the pharmacologically active metabolite - carbamazepine-10,11-epoxide.
With simultaneous application with ritonavir, the side effect of carbamazepine may be increased; with sertraline - may decrease sertraline concentration; with theophylline, rifampicin, cisplatinum, doxorubicin - a decrease in the concentration of carbamazepine in the blood plasma; with tetracycline - possibly weakening the effects of carbamazepine.
When used simultaneously with felbamate, a decrease in the concentration of carbamazepine in the blood plasma is possible, but an increase in the concentration of the active metabolite of carbamazepine-epoxide, while a decrease in the felbamate plasma concentration is possible.
With simultaneous use with phenytoin, phenobarbital, the concentration of carbamazepine in the blood plasma decreases. Possible mutual weakening of anticonvulsant action, and in rare cases - its amplification.
