Carbamazepine

General characteristics. Structure:

Active agent: carbamazepine of 200 mg.

Pharmacological properties:

Antiepileptic means derivative of tricyclic iminostilbene. Believe that anticonvulsant action is connected with decline in the ability of neurons to support the high frequency of development of repeated action potentials by means of an inactivation of natrium channels. Besides, apparently, braking of release of neurotransmitters by blocking of presynaptic natrium channels and development of action potentials matters that in turn reduces synoptic transfer.
Has moderate anti-maniacal, antipsychotic effect, and also analgetic action at neurogenic pains. In action mechanisms, perhaps, receptors of GABA which can be tied with calcium channels are involved; also, apparently, influence of carbamazepine on systems of modulators of neurotransfer matters.
Antidiuretic effect of carbamazepine can be connected with hypothalamic influence on osmoreceptors which is mediated through secretion of ADG, and also is caused by direct action on renal tubules.

Pharmacokinetics.
After intake carbamazepine is almost completely soaked up from a GIT. Linkng with proteins of a blood plasma makes 75%. Is the inductor of liver enzymes and stimulates own metabolism.
T1/2 makes 12-29 h 70% also 30% - with a stake are removed with urine (in the form of inactive metabolites).

Indications to use:

Epilepsy: big, focal, mixed (including big and focal) epileptic seizures. A pain syndrome of preferential neurogenic genesis, including an essential epileptiform neuralgia, an epileptiform neuralgia at multiple sclerosis, essential glossofaringealny neuralgia. Prevention of attacks at a syndrome of alcoholic abstinence. Affective and schizoaffective psychoses (as prophylactic). A diabetic neuropathy with a pain syndrome. Not diabetes mellitus of the central genesis, polyuria and polydipsia of the neurohormonal nature.

Route of administration and doses:

Establish individually. At intake for adults and teenagers of 15 years the initial dose is also more senior makes 100-400 mg. In need of and taking into account clinical effect the dose is increased no more than by 200 mg/days with an interval of 1 week. Reception frequency - 1-4 times/days. The maintenance dose usually makes 600-1200 mg/days in stages. Duration of treatment depends on indications, efficiency of treatment, reaction of the patient to therapy.

At children under 6 years apply 10-20 mg/kg/days in 2-3 divided doses; in need of and taking into account portability the dose is increased no more than by 100 mg/days with an interval of 1 week; the maintenance dose usually makes 250-350 mg/days and does not exceed 400 mg/days. To children at the age of 6-12 years - on 100 mg of 2 times/days in the first day, further a dose increase by 100 mg/days with an interval of 1 week before obtaining optimum effect; the maintenance dose usually makes 400-800 mg/days.

Maximum doses: at intake by the adult and to teenagers there are 15 years and are more senior - 1.2 g/days, to children - 1 g/days.

Features of use:

Carbamazepine is not applied at atypical or generalized small epileptic seizures, myoclonic or atonic epileptic seizures. It is not necessary to apply to removal of usual pains; as prophylactic during the long periods of remission of an epileptiform neuralgia.

With care apply at associated diseases of cardiovascular system, the expressed abnormal liver functions and/or kidneys, at a diabetes mellitus, increase in intraocular pressure, at instructions in the anamnesis on hematologic reactions to use of other drugs, a hyponatremia, an ischuria, hypersensitivity to tricyclic antidepressants, at instructions in the anamnesis on interruption of a course of treatment carbamazepine, and also to children and patients of advanced age.

Treatment should be carried out under control of the doctor. At prolonged treatment it is necessary to control a blood pattern, a functional condition of a liver and kidneys, concentration of electrolytes in a blood plasma, to conduct ophthalmologic examination. Periodic determination of level of carbamazepine in a blood plasma for control of efficiency and safety of treatment is recommended.

Not less than in 2 weeks prior to therapy by carbamazepine it is necessary to stop treatment by MAO inhibitors.

During treatment not to allow alcohol intake.

Influence on ability to driving of motor transport and to control of mechanisms

During treatment it is necessary to abstain from occupations potentially dangerous types of activity requiring special attention, speed of psychomotor reactions.

Side effects:

- From TsNS and a peripheral nervous system: often - dizziness, an ataxy, drowsiness; the headache, a diplopia, accommodation disturbances are possible; seldom - the involuntary movements, a nystagmus; in some cases - oculomotor disturbances, a dysarthtia, peripheral neuritis, paresthesias, muscular weakness, symptoms of paresis, hallucinations, a depression, feeling of fatigue, an agressive behavior, agitation, consciousness disturbances, activation of psychoses, disturbances of flavoring feelings, conjunctivitis, a sonitus, a hyperacusia.
- From the alimentary system: nausea, increase in GGT, increase in activity ShchF, vomiting, dryness in a mouth; seldom - increase in activity of transaminases, jaundice, cholestatic hepatitis, diarrhea or a lock; in some cases - a loss of appetite, abdominal pains, a glossitis, stomatitis.
- From cardiovascular system: seldom - disturbances of conductivity of a myocardium; in some cases - bradycardia, arrhythmias, AV blockade with a syncope, a collapse, heart failure, manifestations of coronary insufficiency, thrombophlebitises, a thrombembolia.
- From system of a hemopoiesis: leukopenia, eosinophilia, thrombocytopenia; seldom - a leukocytosis; in some cases - an agranulocytosis, aplastic anemia, an erythrocyte aplasia, megaloblastny anemia, a reticulocytosis, hemolitic anemia, granulematozny hepatitis.
- From a metabolism: hyponatremia, liquid delay, hypostases, increase in body weight, reduction of osmolality of plasma; in some cases - the acute alternating porphyria, deficit of folic acid; calcium exchange disturbances, increase in level of cholesterol and triglycerides.
- From endocrine system: gynecomastia or galactorrhoea; seldom - dysfunctions of a thyroid gland.
- From an urinary system: seldom - renal failures, intersticial nephrite and a renal failure.
- From respiratory system: in some cases - диспноэ, pneumonites or pneumonia.
- Allergic reactions: skin rash, itch; seldom - a lymphadenopathy, fever, a gepatosplenomegaliya, arthralgias.

Interaction with other medicines:

At simultaneous use of inhibitors of an isoenzyme of CYP3A4 increase in concentration of carbamazepine in a blood plasma is possible.

At simultaneous use of inductors of an isoenzyme of CYP3A4 of system carbamazepine metabolism acceleration, decrease in its concentration in a blood plasma, reduction of therapeutic effect is possible.

At simultaneous use carbamazepine stimulates metabolism of anticoagulants, folic acid.

At simultaneous use with valproic acid reduction of concentration of carbamazepine and considerable reduction of concentration of valproic acid in a blood plasma is possible. At the same time concentration of a metabolite of carbamazepine - carbamazepine-epoxide (possibly owing to inhibition of its transformation into a carbamazepine-10,11-trance-diol) which also has anticonvulsant activity therefore effects of this interaction can be leveled increases, but there are side reactions more often - a sight illegibility, dizziness, vomiting, weakness, a nystagmus. At simultaneous use of valproic acid and carbamazepine development of hepatotoxic effect is possible (apparently, owing to formation of a minor metabolite of valproic acid which possesses a hepatotoxic action).

At simultaneous use вальпромид reduces metabolism in a liver of carbamazepine and its metabolite of carbamazepine-epoxide owing to enzyme inhibition hydrolase epoxide. The specified metabolite has anticonvulsant activity, but at substantial increase of concentration in a blood plasma can have toxic effect.

At simultaneous use with verapamil, diltiazem, an isoniazid, dextropropoxyphene, viloksaziny, fluoxetine, fluvoksaminy, Cimetidinum, acetazoleamide, danazoly, desipramine, niacinamide (at adults, only in high doses), erythromycin, troleandomitsiny, dzhozamitsiny, klaritromitsiny; with azoles (including with itrakonazoly, ketokonazoly, flukonazoly), terfenadiny, loratadiny increase in concentration of carbamazepine in a blood plasma with risk of development of side effects (dizziness, drowsiness, an ataxy, a diplopia) is possible.

At simultaneous use with a hexamidine anticonvulsant effect of carbamazepine is weakened; with a hydrochlorothiazide, furosemide - reduction of content of sodium in blood is possible; with hormonal contraceptives - weakening of action of contraceptives and development of acyclic bleedings is possible.

At simultaneous use with hormones of a thyroid gland increase in elimination of hormones of a thyroid gland is possible; with clonazepam - increase in clearance of clonazepam and reduction of clearance of carbamazepine is possible; with lithium drugs - perhaps mutual strengthening of neurotoxic action.

At simultaneous use with Primidonum reduction of concentration of carbamazepine in a blood plasma is possible. There are messages that Primidonum can increase concentration in plasma pharmacological of an active metabolite - carbamazepine-10,11-epoxide.

At simultaneous use with ritonaviry strengthening of side effect of carbamazepine is possible; with sertraline - reduction of concentration of sertraline is possible; with theophylline, rifampicin, Cisplatinum, doxorubicine - reduction of concentration of carbamazepine in a blood plasma is possible; with tetracycline - easing of effects of carbamazepine is possible.

At simultaneous use with felbamaty reduction of concentration of carbamazepine in a blood plasma is possible, but increase in concentration of an active metabolite of carbamazepine-epoxide, at the same time is possible decrease in concentration in plasma of a felbamat.

At simultaneous use with Phenytoinum, phenobarbital concentration of carbamazepine in a blood plasma decreases. Perhaps mutual weakening of anticonvulsant action, and in rare instances - its strengthening.

Contraindications:

AV blockade, the previous miyelodepressiya, the alternating porphyria in the anamnesis, a concomitant use of MAO inhibitors and drugs of lithium, hypersensitivity to carbamazepine.

Use at pregnancy and feeding by a breast
In case of need uses at pregnancy (especially in the I trimester) and in the period of a lactation it is necessary to weigh carefully expected advantage of treatment for mother and risk for a fruit or the child. At the same time carbamazepine is recommended to be applied only in the form of monotherapy in minimal effective doses.
Women of childbearing age during treatment by carbamazepine are recommended to use non-hormonal contraceptives.

Use at abnormal liver functions
With care apply at the expressed abnormal liver functions.

Use at renal failures
With care apply at the expressed renal failures.

Use for elderly patients
With care apply at patients of advanced age.

Use for children
With care apply at children.

Overdose:

There are no data.

Storage conditions:

List B.
In the dry place protected from light at a temperature not above 25 °C. To store in the place, unavailable to children.

 

Issue conditions:

According to the recipe

Packaging:

Tablets of 200 mg: 20, 30 or 50 pieces.