Carbamazepine

When ATH:
N03AF01

Characteristic.

White or almost white crystalline powder. Practically insoluble in water, soluble in ethanol and acetone. Molecular weight 236,27.

Pharmacological action.
Anticonvulsant, antiepileptic, antipsychotic, timolepticheskoe, normotimicheskoe, analgesic.

Application.

Epilepsy (except little evil), mania, prevention of manic-depressive disorder, Alcoholic withdrawal, trigeminal and language-pharyngeal nerve, diabetic neuropathy.

Contraindications.

Hypersensitivity (incl. the tricyclic antidepressants), OF блокада, myelosuppression or acute porphyria history.

Pregnancy and breast-feeding.

Category actions result in FDA - D. (There is evidence of the risk of adverse effects of drugs on the human fetus, obtained in research or practice, However, the potential benefits, associated with drugs in pregnant, may justify its use, in spite of the possible risk, if the drug is needed in life-threatening situations or severe disease, when safer agents should not be used or are ineffective.)

Side effects.

Dizziness, excitation, hallucinations, depression, violent behavior, activation psychosis, headache, diplopia, accommodation disturbances, cataract, nistagmo, conjunctivitis, noise in ears, change in taste, speech disorders (dysarthria, gibberish), abnormal involuntary movements, peripheral neuritis, paresthesia, muscle weakness and symptoms of paresis, OF блокада, congestive heart failure, Hyper- or hypotension, thromboembolism, renal dysfunction, interstitial nephritis, nausea, vomiting, elevated liver enzymes, jaundice, hepatitis, osteomalacia, sexual dysfunction, moderate leukopenia, thrombocytopenia, violation of hematopoiesis, giponatriemiya, multiorgan delayed-type hypersensitivity, exfoliative dermatitis, lupus-like syndrome (skin rash, hives, hyperthermia, sore throat, joints, weakness), Stevens-Johnson syndrome, Layella, anaphylactic reactions.

Cooperation.

Incompatible with MAO inhibitors. Increases the hepatotoxicity of isoniazid. Reduces the effects of anticoagulants, anticonvulsants (hydantoin derivatives, or succinimides), ʙarʙituratov, clonazepam, prymydona, valproic acid. Fenotiazinы, pimozid, tioksantena enhance CNS depression; cimetidine, clarithromycin, diltiazem, verapamil, Erythromycin, propoxyphene impair metabolism (increased risk of toxicity). It decreases the activity of corticosteroids, estrogens and oral contraceptives estrogensoderjath, xinidina, cardiac glycosides (induction of metabolism). Against the background of carbonic anhydrase inhibitors increase the risk of osteopenia.

Overdose.

Symptoms: disorientation, drowsiness, excitation, hallucinations and coma, blurred vision, dysarthria, nistagmo, ataxia, dyskinesia, hyper / hyporeflexia, convulsions, myoclonus, gipotermiя; respiratory depression, pulmonary edema; tachycardia, hypo / hypertension, cardiac arrest, accompanied by loss of consciousness; vomiting, reduced motility of the colon; fluid retention, oliguria or anuria, changes in laboratory parameters: giponatriemiya, possible metabolic acidosis, giperglikemiâ, increased muscle creatinine phosphokinase fraction.

Treatment: induction of vomiting or gastric lavage, the appointment of activated charcoal and a saline laxative, diurez. To maintain patency of the Airways — tracheal intubation, artificial respiration and (or) use of oxygen. If hypotension or shock-plazmozameniteli, dopamine or dobutamine, with the emergence of convulsing-introduction of benzodiazepines (diazepam) or other. anticonvulsants (children may increase respiratory depression, in developing giponatriemii — fluid restriction, cautious in / infusion of isotonic sodium chloride solution. With the combination of severe poisoning with renal insufficiency shows kidney dialysis. The specific antidote is absent. It is anticipated the re-strengthening of the symptoms of overdose on the 2nd and 3rd day after its start, due to the slow absorption of the drug.

Dosing and Administration.

Inside, adults-100-1600 mg per day (depending on the indication and the severity of the disease), children — 10-20 mg/kg/day in a few receptions.

Precautions.

Before and during therapy is recommended regular blood tests (cellular elements) and urine, control of liver function tests. Be wary appointed with a history of heart disease, liver or kidney problems, when hematological disorders, increased intraocular pressure, latent psychosis, inadequate response to external stimuli, excitation, diseases, characterized by spasms of mixed character, in old age, drivers of vehicles and persons, exploiting mechanisms. Do not suddenly stop treatment. Women are recommended additional intake of folic acid (prior to pregnancy or during); in order to prevent excessive bleeding during the last weeks of pregnancy and the newborn can use vitamin K.

Cooperation

Active substance	Description of interaction
Aminofillin	FKV. How a CYP3A4 inducer increases (mutually) degradation rate and reduces the level of plasma.
Aцetazolamid	FMR. Increases (mutually) The risk of developing toxic effects.
Valproic Acid	By inhibiting CYP3A4, slows the biotransformation, incl. Active metabolita-10.11-epoxy (its plasma level rises), This also increases the risk of toxic effects on the liver. Against the background of carbamazepine increases clearance and decreases blood levels. Combined use may alter thyroid function.
Verapamil	FKV. FMR. Inhibits biotransformation, It increases the concentration in plasma and promotes toxic effects.
Haloperidol	FKV. May reduce the seizure threshold and relaxing anticonvulsant effect (with a joint appointment requires an increased dose). Against the background of carbamazepine enhanced CNS depression.
Halothane	Against the background of carbamazepine, inducing enzymes of biotransformation, possible increased production of metabolites of halothane, affects the liver.
Gestrinone	FKV. Against the background of carbamazepine increased the rate of destruction.
Dakarʙazin	FKV. FMR. Against the background of carbamazepine (inductor mikrosomalynыh fermentov) accelerating and reducing the effect of biotransformation; the combined appointment may require higher doses.
Danazol	FKV. By inhibiting CYP3A4, a few weeks after the start of administration, slows the biotransformation, increases plasma levels and increases the severity of effects, incl. by; the combined appointment may require dose reduction.
Desogestrel	FKV. FMR. Against the background of carbamazepine, inducing activity of hepatic CYP450, lowers plasma levels, may decrease the reliability of contraception. When combined with the appointment of an increased risk of breakthrough bleeding.
Desmopressin	Against the background of carbamazepine may increase the antidiuretic action; the combined appointment may require dose reduction.
Diltiazem	FKV. Inhibits CYP3A4, reduces the rate of destruction, increases plasma levels and contributes to the manifestation of toxicity.
Doxorubicin	FKV. Decreases (mutually) plasma concentration (induces CYP3A4), accelerates biotransformation.
Isoniazid	FKV. FMR. It increases concentration of plasma and contributes to the manifestation of the toxic effect. Against the background of carbamazepine, inducing microsomal enzymes, increases formation of active metabolites, causing disruption of the liver.
Quetiapine	FMR. May reduce the seizure threshold and relaxing anticonvulsant effect (with a joint appointment requires an increased dose). Against the background of carbamazepine enhanced CNS depression.
Clarithromycin	FKV. Slows biotransformation and increases the concentration in the blood; with a joint appointment in order to avoid toxic effects should be monitored plasma levels of carbamazepine.
Clonazepam	FKV. Against the background of carbamazepine, inducing activity of microsomal enzymes, uskoryaetsya biotransformation, decreases the blood concentration and duration T1/2; the combined appointment should be increased to reduce the dose or the interval between doses.
Levothyroxine sodium	FKV. Against the background of carbamazepine, inducing microsomal enzymes and enhances the biotransformation, reduced effect; while the appointment may need to increase the dose.
Maprotilin	Lowers seizure threshold and weakens the anticonvulsant effect; with a joint appointment may need to increase the dose.
Meʙendazol	FKV. FMR. On the background of carbamazepine reduced plasma concentration and therapeutic effect.
Mianserin	Against the background of accelerated carbamazepine biotransformation, reduced plasma concentration.
Moclobemide	FMR. As MAO inhibitor increases the likelihood of side effects; co-administration is contraindicated.
Nicotinamide	FKV. By inhibiting CYP3A4, slows degradation and increases the plasma levels of.
Olanzapine	FKV. FMR. Against the background of accelerated carbamazepine biotransformation, increases 1,5 clearance times, reduced plasma concentration.
Paracetamol	FKV. FMR. Against the background of carbamazepine, inducing liver enzymes, accelerated biotransformation and reduced therapeutic effect; at the same time enhances the formation of metabolites of paracetamol, violate the function of the liver.
Perfenazyn	FKV. FMR. Against the background of accelerated carbamazepine biotransformation.
Praziquantel	Against the background of carbamazepine, induktsiruyuschego microsomal cytochrome P450 enzymes, plasma concentration is reduced 10 time (the combined appointment of a higher dose).
Prymydon	FKV. FMR. As CYP3A4 inducer accelerates (mutually) biotransformation and reduces plasma levels; joint application may alter thyroid function.
Procarbazine	FMR. Inhibits MAO and provokes the development of side effects; co-administration is contraindicated.
Risperidone	FKV. FMR. Against the background of accelerated carbamazepine biotransformation, increased clearance and reduced plasma concentration.
Rifabutin	FKV. As activator lowers CYP3A4 (mutually) plasma concentration.
Rifampicin	FKV. As CYP3A4 inducer accelerates (mutually) biotransformation and lowers plasma levels.
Selegiline	FMR. MAO inhibitor significantly increases the risk and severity of adverse events; co-administration is contraindicated.
Theophylline	FKV. As CYP3A4 inducer increases the speed and reduces the degradation in plasma.
Toremifene	FKV. Against the background of accelerated carbamazepine biotransformation.
Tramadol	FKV. FMR. Against the background of accelerated biotransformation of carbamazepine and reduced effect.
Trifluoperazine	FKV. FMR. Against the background of accelerated carbamazepine biotransformation.
Phenytoin	FKV. FMR. Against the background of accelerated carbamazepine biotransformation. Co-administration may alter thyroid function.
Phenobarbital	FKV. FMR. As CYP3A4 inducer accelerates biotransformation and thus reduces the plasma levels of; combined use may alter thyroid function.
Fluvoxamine	FKV. Inhibits biotransformation and increases (in 3 times) plasma concentration.
Fluoxetine	FKV. As CYP3A4 inhibitor inhibits the biotransformation and increases in plasma.
Flufenazin	FKV. FMR. Against the background of accelerated carbamazepine biotransformation.
Folic acid	Against the background of carbamazepine may increase the need for folate.
Quinidine	Against the background of carbamazepine, inducing hepatic microsomal enzymes, reduced effect; with a joint appointment may need to increase the dose.
Chloroquine	FMR: antagonizm. Reduces anticonvulsant effect.
Chlorpromazine	FKV. FMR. Against the background of accelerated carbamazepine biotransformation.
Chlorprothixene	FKV. FMR. Against the background of accelerated carbamazepine biotransformation.
Cyclosporine	Against the backdrop of carbamazepine — accelerates the destruction is diminished effect; with a joint appointment may need to increase the dose.
Erythromycin	FKV. FMR. Inhibits biotransformation, It increases blood concentrations and promotes toxic effects.
Ethanol	Increases risk of side effects and their severity. Against the background of carbamazepine decreased tolerance to alcohol (to refrain from the use of alcohol-containing beverages during treatment).