Carbamazepine - instructions for use, dose, side effects, contraindications

Excipients: talc, silicon dioxide colloid (aerosil A-300), potato starch, povidone (polyvinylpyrrolidone low molecular weight), magnesium stearate, polysorbate (Tween 80).

Description:

Tablets are white or white with a yellowish tint of color, flat-cylindrical with a facet and a risk.

Pharmacotherapeutic group:Antiepileptic remedy

ATX: & nbsp

N.03.A.F.01 Carbamazepine

Pharmacodynamics:

Antiepileptic agent, a derivative of dibenzazepine, which has a normotimic, antimanic and analgesic effect. Activates the central brake GABA-ergic system. It blocks potential-dependent sodium channels of nerve cell membranes, which leads to functional stabilization of neurons, reduces the activity of excitatory neurotransmitter acids (glutamate, aspartate), interacts with central adenosine receptors (inhibition of adenylate cyclase activation).Increases the convulsive threshold, corrects epileptic changes in personality. When diabetes insipidus reduces diuresis and thirst (due to the antidiuretic effect).

Pharmacokinetics:

Absorption - slow, but fairly complete (eating does not affect the speed and degree of absorption). After a single intake, the maximum concentration (C_mOh) is achieved after 12 hours. Equilibrium concentrations of the drug in the plasma are achieved after 1-2 weeks. The concentrations of carbamazepine-10,11-epoxide (pharmacologically active metabolite) are about 30% of the concentration of carbamazepine. The connection with plasma proteins in children is 55-59%, in adults 70-80%. In the cerebrospinal fluid and saliva, concentrations are created in proportion to the amount of the active substance unbound with proteins (20-30%). Penetrates through the placental barrier. Concentration in breast milk is 25-60% of that in plasma.

Metabolised in the liver, mainly along the epoxide route with the formation of the main metabolites: active - carbamazepine-10,11-epoxide and inactive conjugate with glucuronic acid. A low-active metabolite of 9-hydroxymethyl-10-carbamoylacridan is also formed.Can induce own metabolism. The concentration of carbamazepine-10,11-epoxide is 30% of the concentration carbamazepine.

The half-life (T1 / 2) of single admission is 25-65 hours (an average of about 36 hours), after repeated admission - 12-24 hours. In patients receiving additionally other anticonvulsants T1 / 2 averagely 9-10 hours.

It is output in the form of NEAof the metabolites with urine (70%) and feces (30%). There is no evidence that the pharmacokinetics of carbamazepine change in elderly patients. Data on the pharmacokinetics of carbamazepine in patients with impaired renal or hepatic function are not yet sufficient.

Indications:

Epilepsy:

- complex or simple partial epileptic seizures (with or without loss of consciousness) with secondary generalization or without it;

- generalized tonic-clonic epileptic seizures; mixed forms of epileptic seizures.

In complex therapy of acute manic conditions, supportive therapy of bipolar affective disorders with the purpose of preventing exacerbations or alleviating clinical manifestations of exacerbation.

Complex therapy of alcohol withdrawal syndrome.

Idiopathic neuralgia of the trigeminal nerve and trigeminal neuralgia in multiple sclerosis (typical and atypical). Idiopathic neuralgia of the glossopharyngeal nerve.

Pain syndrome in diabetic neuropathy.

Polyuria and polydipsia of neurohormonal nature in diabetes insipidus of central genesis.

Contraindications:

Hypersensitivity to carbamazepine and chemically similar medicinal products (tricyclic antidepressants) or to any other component of the drug; acute intermittent porphyria (including in the anamnesis); simultaneous administration of monoamine oxidase inhibitors (hereinafter MAO inhibitors) and within 2 weeks after their cancellation; violation of bone marrow hematopoiesis; atrioventricular block; pregnancy and lactation.

This dosage form is not used in children under 3 years of age.

Carefully:

Hyponatremia of breeding, elderly age, reception, alcohol, oppression of bone marrow hematopoiesis against the background of taking medications (in the anamnesis); hyperplasia of the prostate, increased intraocular pressure, severe heart failure, hepatic insufficiency,chronic renal failure.

Pregnancy and lactation:The use of the drug is contraindicated in pregnancy and lactation.

Dosing and Administration:

Inside, regardless of the reception of food with a small amount of liquid.

With epilepsy: whenever possible, carbamazepine should be administered as a monotherapy. Treatment begins with a small daily dose, which is then slowly increased until an optimal effect is achieved. The addition of carbamazepine to already conducted antiepileptic therapy should be carried out gradually.

For adults, the initial dose is 100-200 mg 1-2 times a day. Then the dose is slowly increased to 400 mg 2-3 times a day. The maximum daily dose is 1600-2000 mg.

For children from 3 to 5 years of age - 200-400 mg (for 1-2 doses), from 6 to 10 years - 400-600 mg (for 2-3 doses), for 11-15 years - 600-1000 mg (for 2-3 reception).

With neuralgia of the trigeminal or glossopharyngeal nerves: 100-200 mg 2 times a day, then gradually increase the dose by no more than 200 mg per day until the pain ceases (on average, up to 600-800 mg), then reduced to the minimum effective dose. The effect usually occurs 1-3 days after the start of treatment. Assign the drug for a long time; with the premature cancellation of the drug pain can resume.In the treatment of elderly patients, the initial dose is 100 mg 2 times a day.

Alcohol abstinence syndrome: the average dose is 200 mg 3 times a day. In severe cases, in the first days the dose can be increased to 400 mg 3 times a day. At the beginning of treatment for severe phenomena, withdrawal is prescribed in combination with detoxification therapy and sedative-hypnotic drugs.

Non-diabetes mellitus: the average dose for adults is 200 mg 2-3 times a day. Diabetic neuropathy, accompanied by pain: 200 mg 2-4 times a day

Acute manic conditions and maintenance therapy of affective disorders: daily dose varies from 400 to 1600 mg. The average daily dose is 400-600 mg (in 2-3 doses). In acute manic state, the dose should be increased rather quickly. With maintenance therapy for bipolar disorders, in order to ensure optimal tolerability, each next dose increase should be small, the daily dose increases gradually.

The transition to carbamazepine treatment should be gradual, with a decrease in the dose of the previous drug. Stop treatment should be gradual. The duration of treatment is determined by the doctor.

Side effects:

From the central nervous system: Dizziness, ataxia, drowsiness, weakness, headache, paresis of accommodation, tremors, tics, eye, orofacial dyskinesia, oculomotor disturbances, dysarthria, horeoatetoidnye disorders, peripheral neuritis, paresthesia, muscle weakness, and paresis.

From the psychic sphere: 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 nodosum. Possible multiorgan delayed-type hypersensitivity with fever, skin rashes, vasculitis, lymphadenopathy, symptoms resembling lymphoma, arthralgia, leukopenia, eosinophilia, hepatosplenomegaly and altered liver function (indicated manifestations occur in different combinations). Other organs may also be involved (eg, lungs, kidneys, pancreas, myocardium, large intestine).Very rarely - aseptic meningitis with myoclonus, anaphylactic reaction, angioedema, hypersensitivity reactions on the part of the lungs characterized by fever, dyspnoea, pneumonitis or pneumonia.

On the part of the organs of hematopoiesis: leukopenia, thrombocytopenia, eosinophilia, leukocytosis, lymphadenopathy; agranulocytosis, aplastic anemia, pure red cell aplasia, megaloblastic anemia, acute intermittent porphyria, reticulocytosis, hemolytic anemia.

From the gastrointestinal tract: nausea, vomiting, dry mouth, diarrhea or constipation, abdominal pain, glossitis, stomatitis, pancreatitis.

From the side of the liver: Increased activity of gamma-glutamyl transferase (usually has no clinical significance), elevated alkaline phosphatase, and "liver" enzymes, hepatitis (granulomatous, cholestatic, parenchymal (hepatocellular) or mixed type), hepatic failure.

From the side of the cardiovascular system: intracardiac disorders conduction, decrease or increase in blood pressure; bradycardia, arrhythmias, atrioventricular blockade with syncope, collapse,aggravation or development of congestive heart failure, exacerbation of coronary heart disease (including the appearance or increase in angina attacks), thrombophlebitis, thromboembolic syndrome.

From the endocrine system and metabolism: edema, weight gain, hyponatremia, increased prolactin levels (may be accompanied by galactorrhea and gynecomastia); a decrease in the level of L-thyroxine (free T4, T3) and an increase in the thyroid-stimulating hormone (TSH) level (usually not accompanied by clinical manifestations), calcium-phosphorus metabolism in bone tissue (Ca concentration decrease²⁺ and 25-OH-cholecalciferol in blood plasma), osteomalacia; hypercholesterolemia and hypertriglyceridemia.

From the genitourinary system: interstitial nephritis, renal failure, renal dysfunction (albuminuria, hematuria, oliguria, urea / azotemia increase), frequent urination, urinary retention, sexual function disorders / impotence.

From the side of the musculoskeletal system: arthralgia, myalgia or convulsions.

From the sense organs: disorders of taste sensations, clouding of the lens, conjunctivitis; hyper- or hypoacusia,changes in perception of pitch.

Other: disorders of skin pigmentation, purpura, acne, sweating, alopecia.

Overdose:

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

Treatment: there is no specific antidote. Gastric lavage, the appointment of activated charcoal (late evacuation of gastric contents can lead to delayed absorption on day 2-3 and the re-emergence of symptoms of intoxication), symptomatic therapy. Intense diuresis, hemodialysis and peritoneal dialysis are ineffective (dialysis is indicated by a combination of severe poisoning and kidney failure). Children may have a need for exchange blood transfusion. It is recommended to carry out hemosorption on carbon sorbents.

Interaction:

Carbamazepine enhances the activity of microsomal liver enzymes and can reduce the effectiveness of drugs metabolized in the liver. Simultaneous administration of carbamazepine with inhibitors CYP3A4 can lead to an increase in its concentration in the blood plasma.Joint application with inductors CYP3A4 can lead to an acceleration of the metabolism of carbamazepine and a decrease in its concentration in the blood plasma, on the contrary, their removal can reduce the rate of biotransformation of carbamazepine and lead to an increase in its concentration.

Increase the concentration of carbamazepine in plasma: verapamil, diltiazem, felodipine, dextropropoxyphene, viloxazine, fluoxetine, fluvoxamine, cimetidine, acetazolamide, danazol, desipramine, nicotinamide (in adults, only in high doses); macrolides (erythromycin, josamycin, clarithromycin, troleandomycin); azoles (itraconazole, ketoconazole, fluconazole), terfenadine, loratadine, isoniazid, propoxyphene, grapefruit juice, viral protease inhibitors used in HIV therapy. Felbamate reduces the concentration of carbamazepine in plasma and increases the concentration of carbamazepine-10,11-epoxide, while a simultaneous decrease in serum felbamate concentration is possible.

The concentration of carbamazepine is reduced phenobarbital, phenytoin, primidon, metsuksimide, fensuksimid, theophylline, rifampicin, cisplatin, doxorubicin, perhaps: clonazepam, valpromid, valproic acid, oxcarbazepine and herbal preparations containing St. John's wort perfumed (Hypericum perforatum). There are reports of the possibility of displacing valproic acid and primidone carbamazepine from plasma protein binding and increasing the concentration of pharmacologically active metabolite (carbamazepine-10,11-epoxide). Isotretinoin changes the bioavailability and / or clearance of carbamazepine and carbamazepine-10,11-epoxide (carbamazepine concentration in the plasma is monitored).

Carbamazepine can reduce the concentration in the plasma (reduce or even completely neutralize the effects) and require correction of the doses of the following drugs: clobazam, clonazepam, ethosuximide, primidon, valproic acid, alprazolam, glucocorticosteroids (prednisolone, dexamethasone), cyclosporine, doxycycline, haloperidol, methadone, oral preparations containing estrogens and / or progesterone (the choice of alternative methods of contraception), theophylline, oral anticoagulants (warfarin, fenprocumone, dicumarol), lamotrigine, topiramate, tricyclic antidepressants (imipramine, amitriptyline, nortriptyline, clomipramine), clozapine, felbamate,tiagabine, oxcarbazepine, protease inhibitors used in the treatment of HIV infection (indinavir, ritonavir, saquinovir), calcium channel blockers (a group of dihydropyridones, for example, felodipine), itraconazole, levothyroxine, midazolam, olazapine, praziquantel, risperidone, tramadol, and ziprasidone.

It has been reported that in patients receiving carbamazepine phenytoin plasma levels may either rise or fall, and mephenytoin level - increase (in rare cases).

Carbamazepine when combined with paracetamol increases the risk of its toxic effect on the liver and reduces therapeutic effectiveness (acceleration of the metabolism of paracetamol).

The simultaneous appointment of carbamazepine with phenothiazines, pimozide, thioxanthenes, molindone, haloperidol, maprotiline, clozapine and tricyclic antidepressants leads to increased inhibitory action on the central nervous system and weaken the anticonvulsant effect of carbamazepine.

Simultaneous administration with diuretics (hydrochlorothiazide, furosemide) can lead to hyponatremia, accompanied by clinical manifestations.

Reduces the effects of nondepolarizing muscle relaxants (pancuronium).

Reduces the tolerance of ethanol.

Accelerates the metabolism of indirect anticoagulants, hormonal contraceptives, folic acid; prazikvantela, can enhance the elimination of thyroid hormones.

Accelerates the metabolism of agents for general anesthesia (enflurane, halothane, fluorotan) with an increased risk of hepatotoxic effects; enhances the formation of nephrotoxic metabolites of methoxyflurane.

Enhances the hepatotoxic effect of isoniazid.

Special instructions:

Before starting treatment, it is necessary to perform a general blood test (including platelet count, reticulocyte count), a general urine test, determine the level of iron, the concentration of electrolytes and urea in the blood serum. Subsequently, these indicators should be monitored during the first month of treatment on a weekly basis, and then on a monthly basis. When appointing patients with increased 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 occurs, accompanied by clinical symptoms of an infectious disease.

It is recommended to stop drinking alcohol.

Effect on the ability to drive transp. cf. and fur:During the treatment period, it is necessary to refrain from engaging in potentially dangerous activities that require a high concentration of attention and speed of psychomotor reactions.

Form release / dosage:

Tablets 200 mg.

Packaging:For 10 tablets in a planar cell package.

1, 2 or 5 contour mesh packages together with instructions for use in a pack of cardboard.

Storage conditions:

In a dry, the dark place at a temperature of no higher than 25 ° C. Keep out of the reach of children.

Shelf life:

2 years.

Do not use after the expiration date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:P N002370 / 01

Date of registration:29.08.2008 / 06.02.2017

Expiration Date:Unlimited

The owner of the registration certificate:ROSFARM, LLC ROSFARM, LLC Russia

Manufacturer: & nbsp

ROSFARM, LLC Russia

Information update date: & nbsp07.12.2017

Illustrated instructions

Instructions

Carbamazepine (Carbamazepine)