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

Antiepileptics, dibenzazepine derivative provider normotimicheskoe, antimanic and analgesic action. Activates the central brake GABA-ergic system. Blocking voltage-dependent sodium channels of nerve cell membranes, which leads to stabilization of functional neurons that reduces the activity of the 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 quite 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-hydroxy-methyl-10-carbamoylacridan is also formed.Can induce own metabolism. The concentration of carbamazepine-10,11-epoxide is 30% of the concentration of 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 excreted as inactive 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 (except absences, myoclonic or flaccid seizures) - partial seizures with complex and simple symptoms, primary and secondary generalized forms of seizures with tonic-clonic convulsions, mixed forms of seizures (monotherapy or in combination with other antiepileptic drugs); idiopathic neuralgia of the trigeminal nerve; neuralgia of the trigeminal nerve with multiple sclerosis; idiopathic glossopharyngeal neuralgia; alcohol withdrawal syndrome; treatment of affective disorders; polydipsia and polyuria in diabetes insipidus; pain syndrome in diabetic polyneuropathy.

Prevention of phase-related affective disorders (manic-depressive psychosis, schizoaffective disorder, etc.).

Contraindications:

Hypersensitivity to carbamazepine and chemically similar drugs (tricyclic antidepressants) or to any other component of the drug, acute intermittent porphyria (including history), simultaneous administration of monoamine oxidase inhibitors (hereinafter MAO inhibitors) and for 2 weeks after their cancellation, violation of bone marrow hematopoiesis, atrioventricular blockade, pregnancy and lactation.

Carefully:

Hyponatremia of breeding, elderly age, alcohol intake, 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.

Dosing and Administration:

Inside, regardless of food intake with a small amount of liquid.

With epilepsy

If 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 of 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 of 1600 - 2000 mg.

For children the average daily dose is determined from the calculation of 10-20 mg / kg of body weight per day and is: for children aged 4 months to 1 year - 100-200 mg per day, from 1 to 5 years - 200-400 mg (for 1 -2 admission), from 6 to 10 years - 400-600 mg (for 2-3 doses), for 11-15 years - 600-1000 mg (for 2-3 doses).

With neuralgia of the trigeminal nerve and neurogenic pain syndrome

100-200 mg twice 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 to 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 to 3 times a day.

Diabetic neuropathy accompanied by pain

200 mg 2 to 4 times a day.

For the prevention of affective disorders

In the first week, the daily dose of 200 - 400 mg. Subsequently, the dose is increased by 200 mg per week, bringing it to 1 g / day. The daily dose is evenly divided into 3-4 doses.

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, general weakness, headache, paresis of accommodation, tremor, tics, nystagmus, orofacial dyskinesia, oculomotor disorders, dysarthria, choreoathetoid 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, multiform and erythema 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 from the lungs, characterized by fever, dyspnea, pneumonitis or pneumonia.

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

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

From the side of the liver: increased activity of gamma-glutamyltransferase (usually has no clinical significance), increased activity of alkaline phosphatase and "hepatic" transaminases, hepatitis (granulomatous, cholestatic, parenchymal (hepatocellular) or mixed); liver failure.

From the cardiovascular system: violations intracardiac 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 cramps.

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

Symptoms usually reflect violations of the central nervous system, cardiovascular system and respiratory system.

From the central nervous system and sense organs: oppression of CNS functions, disorientation, drowsiness, excitation, hallucinations, syncope, coma; visual disturbances ("fog" before the eyes), dysarthria, nystagmus, ataxia, dyskinesia; convulsions, psychomotor disorders, myoclonus, mydriasis.

From the side of the cardiovascular system: tachycardia, decreased blood pressure, sometimes increased blood pressure, intraventricular conduction disorders with expansion of the complex QRS, cardiac arrest.

On the part of the respiratory system: pulmonary edema.

From the digestive system: nausea and vomiting, delay the evacuation of food from the stomach.

From the urinary system: urine retention, oliguria or anuria, fluid retention, hyponatremia of dilution.

Laboratory indicators: leukocytosis or leukopenia, hyponatremia, metabolic acidosis, hyperglycemia and glucosuria, increased muscle CK fraction.

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 (hetraconazole, 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,a simultaneous decrease in serum felbamate concentration is possible.

The concentration of carbamazepine is reduced phenobarbital, phenytoin, primidon, metsuksimide, fensuksimid, theophylline, rifampicin, cisplatin, doxirubicin, possibly: clonazepam, valpromid, valproic acid, oxcarbazepine and herbal preparations containing St. John's wort (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 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, praziquantel, 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.

A sudden discontinuation of carbamazepine may provoke epileptic seizures.

Before the appointment of carbamazepine and during the treatment it is necessary to study the function of the liver. In case of strengthening of already existing violations of the liver function or when there is an active liver disease, the drug should be immediately canceled.

It should take into account the possibility of activation of latent psychoses, and in elderly patients - the possibility of developing disorientation or arousal.

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 pack or 40 tablets in a can of glass or 50 tablets in a can of polymeric material.

5 contour mesh packages or one can of glass or polymer material together with instructions for use in a pack of cardboard.

Storage conditions:

In a dry place, protected from light and out of reach of children, at a temperature not exceeding 25 ° C.

Shelf life:

2 years.

Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:P N001134 / 01

Date of registration:11.09.2008

The owner of the registration certificate:MARBIOFARM, OJSC MARBIOFARM, OJSC Russia

Manufacturer: & nbsp

MARBIOFARM, OJSC Russia

Information update date: & nbsp11.09.2008

Illustrated instructions

Instructions

Carbamazepine (Carbamazepine)