Carbamazepine

Active material: Carbamazepine
When ATH: N03AF01
CCF: Anticonvulsants
When CSF: 02.05.04
Manufacturer: ALSI Pharma Company Inc. (Russia)

Pharmaceutical form, composition and packaging

Pills white or white with a yellowish tint, ploskotsilindricheskoy form, a facet and Valium.

Excipients: potato starch, colloidal silicon dioxide (aэrosyl), magnesium stearate, talc, povidone, Tween-80.

10 PC. – packings Valium planimetric (1) – packs cardboard.
10 PC. – packings Valium planimetric (2) – packs cardboard.
10 PC. – packings Valium planimetric (3) – packs cardboard.
10 PC. – packings Valium planimetric (4) – packs cardboard.
10 PC. – packings Valium planimetric (5) – packs cardboard.

DESCRIPTION OF ACTIVE SUBSTANCES

Pharmacological action

Antiepileptics, tricyclic derivative iminostilbene. It is believed, that the anticonvulsive action associated with lowering the ability of neurons to maintain a high incidence of repetitive action potentials by inactivating sodium channel. Besides, apparently, It has a value of inhibition of neurotransmitter release by blocking presynaptic sodium channels and development of action potentials, which in turn reduces the synaptic transmission.

It has moderate antimanic, antipsihoticheskoe action, as well as the analgesic effect in neurogenic pain. The mechanisms of action, perhaps, GABA receptors are involved, that may be associated with calcium channel; also, apparently, It has a value of carbamazepine effect on neurotransmission modulators system.

Antidiuretic action of carbamazepine may be due to effects on hypothalamic osmoreceptors, which is mediated through the secretion of ADH, and also due to the direct effect on the renal tubules.

Pharmacokinetics

After oral carbamazepine almost completely absorbed from the gastrointestinal tract. Binding to plasma proteins is 75%. An inducer of hepatic enzymes and stimulates its own metabolism.

T_1/2 is 12-29 no. 70% excreted in the urine (active metabolites) and 30% – with feces.

Testimony

Epilepsy: big, Focal, hybrid (including large and focal) seizures. Neurogenic pain syndrome mainly genesis, incl. эssentsialynaya neuralgia nerve troynichnogo, trigeminal neuralgia in multiple sclerosis, эssentsialynaya glossofaringealynaya neuralgia. Prevention of seizures in alcohol withdrawal syndrome. Affective and schizoaffective psychosis (as a means of preventing). Diabetic neuropathy pain syndrome. Central diabetes insipidus, polyuria and polydipsia of neurohormonal nature.

Dosage regimen

Establish individually. When administered to adults and adolescents 15 years old and older starting dose is 100-400 mg. If necessary, and taking into account the clinical effect of the dosage is increased by no more than 200 mg/day with an interval 1 Sun. Reception frequency – 1-4 times / day. The maintenance dose is usually 600-1200 mg / day in divided doses. The duration of treatment depends on the indication, the effectiveness of treatment, the patient's response to therapy.

Children under the age of 6 years of use 10-20 mg / kg / day 2-3 divided doses; if necessary, taking into account the tolerance dose is increased by no more than 100 mg/day with an interval 1 Sun.; maintenance dose is usually 250-350 mg / day and does not exceed 400 mg / day. For children 6-12 years – by 100 mg 2 times / day for the first day, next dose 100 mg/day with an interval 1 Sun. until the optimum effect; maintenance dose is usually 400-800 mg / day.

The maximum dose: when administered to adults and adolescents 15 and older – 1.2 g / day, children – 1 g / day.

Side effect

From the central and peripheral nervous system: often – dizziness, ataxia, drowsiness; possible headache, diplopia, accommodation disturbances; rarely – involuntary movements, nistagmo; in some cases – oculomotor disturbances, dysarthria, peripheral neuritis, paresthesia, muscular weakness, symptoms of paresis, hallucinations, depression, feeling tired, violent behavior, ažitaciâ, disturbances of consciousness, activation of psychosis, dysgeusia, conjunctivitis, noise in ears, hyperacusis.

From the digestive system: nausea, GGT increase, increased activity of alkaline phosphatase, vomiting, dry mouth; rarely – increase in transaminases, jaundice, cholestatic hepatitis, diarrhea or constipation; in some cases – decreased appetite, stomach ache, glossitis, stomatitis.

Cardio-vascular system: rarely – conduction disturbances infarction; in some cases – bradycardia, Arrhythmia, AV-blockade with syncope, collapse, heart failure, manifestations of coronary insufficiency, thrombophlebitis, thromboembolism.

From the hematopoietic system: leukopenia, eozinofilija, thrombocytopenia; rarely – leukocytosis; in some cases – agranulocytosis, aplasticheskaya anemia, red cell aplasia, megaloblastnaya anemia, reticulocytosis, gemoliticheskaya anemia, granulomatous hepatitis.

Metabolism: giponatriemiya, fluid retention, swelling, weight gain, decrease in plasma osmolality; in some cases – acute intermittent porphyria, folic acid deficiency; disorders of calcium metabolism, high cholesterol and triglycerides.

On the part of the endocrine system: gynecomastia or galactorrhea; rarely – thyroid dysfunction.

From the urinary system: rarely – renal dysfunction, interstitial nephritis and renal insufficiency.

The respiratory system: in some cases – dyspnoea, pneumonitis or pneumonia.

Allergic reactions: skin rash, itch; rarely – lymphadenopathy, fever, hepatosplenomegaly, artralgii.

Contraindications

AV блокада, previous mielodeprescia, intermittent porphyria history, simultaneous MAO inhibitors and drugs lithium, hypersensitivity to carbamazepine.

Pregnancy and lactation

If necessary, use in pregnancy (especially in the I trimester) and during lactation should carefully weigh the potential benefits of treatment for the mother and the risk to the fetus or child. Thus carbamazepine are only recommended as monotherapy in the minimum effective doses.

Women of childbearing age during treatment with carbamazepine is recommended to use non-hormonal contraception.

Cautions

Carbamazepine is not used in atypical or small generalized seizures, myoclonic or atonic seizures. should not be used to relieve common pains; as a prophylactic agent during prolonged periods of remission trigeminal neuralgia.

To use caution in concomitant diseases of the cardiovascular system, function expressed by human liver and / or kidney, for patients with diabetes, increased intraocular pressure, When specifying a history of hematologic response to application of other preparations, giponatriemii, urinary retention, hypersensitivity to tricyclic antidepressants, When specifying a history of interrupted treatment with carbamazepine, as well as children and elderly patients.

Treatment should be under the supervision of a physician. Prolonged treatment is necessary to control blood picture, the functional state of the liver and kidneys, the concentration of electrolytes in the blood plasma, conduct eye examination. Recommended periodic determination of plasma levels of carbamazepine to monitor the efficacy and safety of treatment.

Not less than 2 weeks prior to the initiation of therapy with carbamazepine should be discontinued treatment MAO inhibitors.

During treatment, avoid alcohol.

Effects on ability to drive vehicles and management mechanisms

During treatment should refrain from activities potentially hazardous activities, require attention, psychomotor speed reactions.

Drug Interactions

With simultaneous use of isozyme inhibitors of CYP3A4 may increase the concentration of carbamazepine in plasma.

With simultaneous use of isozyme CYP3A4 inducers system may accelerate metabolism of carbamazepine, reducing its concentration in blood plasma, reduction of the therapeutic effect.

With simultaneous use of carbamazepine stimulates the metabolism of anticoagulants, folic acid.

While the use of valproic acid may decrease the concentration of carbamazepine and significant decrease in the concentration of valproic acid in blood plasma. This increases the concentration of a metabolite of carbamazepine – carbamazepine-epoxide (probably by inhibiting its conversion into carbamazepine-10,11-trans-diol), which also possesses anticonvulsant activity, therefore, the effects of interaction can be offset, but side reactions often occur – blurred vision, dizziness, vomiting, weakness, nistagmo. With simultaneous application of valproic acid, carbamazepine may develop hepatotoxicity (apparently, due to formation of a secondary metabolite of valproic acid, which has hepatotoxic).

With simultaneous application valpromid reduces hepatic metabolism of carbamazepine and its metabolite carbamazepine-epoxide due to inhibition of the enzyme epoxide hydrolase. Said metabolite possesses anticonvulsant activity, but with a significant increase in plasma concentrations may be toxic.

While the use of verapamil, diltiazemom, izoniazidom, dekstropropoksifenom, viloksazinom, fluoxetine, fluvoksaminom; possible - with cimetidine, acetazolamide, danazolom, desipramine, nicotinamide (adult, Only high doses); Erythromycin, troleandomycin, dzhozamytsynom, clarithromycin; with azolami (incl. with itrakonazolom, ketoconazole, fluconazole), terfenadine, loratadine may increase carbamazepine plasma concentrations with the risk of side effects (dizziness, drowsiness, ataxia, diplopia).

While the use of attenuated geksamidinom anticonvulsant effect of carbamazepine; hydrochlorothiazide, furosemidom – may decrease blood sodium; with hormonal contraceptives – may weaken the effect of contraceptives and the development of acyclic bleeding.

While the use of thyroid hormones may increase the elimination of thyroid hormones; with clonazepam – may increase the clearance of clonazepam and carbamazepine decrease in clearance; with lithium – possible mutual enhancement of neurotoxicity.

While the use of primidone may decrease carbamazepine plasma levels. There are reports, primidone that may increase the plasma concentration of the pharmacologically active metabolite – karʙamazepina-10,11-epoksida.

While the use of ritonavir possibly increased side effects of carbamazepine; with sertralinom – may decrease the concentration of sertraline; theophylline, rifampicin, cisplatin, doxorubicin – may decrease the concentration of carbamazepine in plasma; with tetratsiklinom – possible weakening effects of carbamazepine.

In an application with carbamazepine felbamate may decrease plasma concentrations of, but the increase in the concentration of the active metabolite carbamazepine-epoxide, with the possible decrease in plasma concentration of felbamate.

In an application with phenytoin, phenobarbital carbamazepine reduced plasma concentration. Perhaps the relative weakening of anticonvulsant action, and in rare cases – its strengthening.