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Active ingredients
Carbamazepine
Release form
Pills
Composition
Carbamazepine - 200 mg. Adjuvants: MCC; carmellose sodium; magnesium stearate; silicon dioxide colloidal anhydrous (Aerosil 200)
Pharmacological effect
Antiepileptic agent, a derivative of tricyclic aminostilbene. It is believed that the anticonvulsant action is associated with a decrease in the ability of neurons to maintain a high frequency of development of repeated action potentials through the inactivation of sodium channels. In addition, it seems to be important to inhibit the release of neurotransmitters by blocking presynaptic sodium channels and developing action potentials, which in turn reduces synaptic transmission. It has a moderate anti-manic, antipsychotic effect, as well as an analgesic effect in neurogenic pain. The mechanisms of action may involve GABA receptors, which may be associated with calcium channels; The effect of carbamazepine on the neurotransmission modulator systems seems to be important. The antidiuretic effect of carbamazepine may be due to the hypothalamic effect on osmoreceptors, which is mediated through the secretion of ADH, and is also due to a direct effect on the renal tubules.
Pharmacokinetics
After oral administration, carbamazepine is almost completely absorbed from the gastrointestinal tract. Plasma protein binding is 75%. It is an inducer of liver enzymes and stimulates its own metabolism. T1 / 2 is 12-29 hours. 70% is excreted in the urine (as inactive metabolites) and 30% in feces.
Indications
Epilepsy: large, focal, mixed (including large and focal) epileptic seizures. The pain syndrome is predominantly neurogenic, including essential trigeminal neuralgia, trigeminal neuralgia in multiple sclerosis, essential glossopharyngeal neuralgia. Prevention of seizures with alcohol withdrawal syndrome. Affective and schizoaffective psychosis (as a means of prevention). Diabetic neuropathy with pain. Diabetes insipidus of central origin, polyuria and polydipsia of neurohormonal nature.
Contraindications
AV blockade preceding myelodepression, intermittent porphyria in history, simultaneous use of MAO inhibitors and lithium preparations, increased sensitivity to carbamazepine. If necessary, use during pregnancy (especially in the first trimester) and during lactation should carefully weigh the expected benefits of treatment for the mother and risk to the fetus or baby. In this case, carbamazepine is recommended to be used only as a monotherapy in the minimum effective doses. Non-hormonal contraceptives are recommended for women of childbearing age during treatment with carbamazepine. Use for hepatic impairment. Use with caution in severely impaired liver function. renal function. Use in childrenWith caution in children. Use in elderly patientsWith Robin used in elderly patients.
Use during pregnancy and lactation
If necessary, use during pregnancy (especially in the first trimester) and during lactation should carefully weigh the expected benefits of treatment for the mother and the risk to the fetus or child. In this case, carbamazepine is recommended to be used only as a monotherapy in the minimum effective doses. Non-hormonal contraceptives are recommended for women of childbearing age during treatment with carbamazepine.
Dosage and administration
Inside, during or after a meal, or in between meals. Tablets should be taken with a small amount of liquid. The drug can be used as a monotherapy, and as part of combination therapy. The syrup should be shaken before use. The purpose of the drug Tegretol in the form of a syrup (1 scored = 5 ml = 100 mg) is advisable for patients who have difficulty in swallowing the pills or require careful dose selection. When receiving the drug Tegretol in the form of a syrup, a higher maximum concentration is reached than when taking the same dose in a tablet form, it is therefore recommended to start treatment with small doses and gradually increase them to avoid adverse reactions.When transferring a patient from taking the drug Tegretol in the form of pills to receive a syrup, it is recommended to take the drug in the same daily dose, but in smaller doses and more often (for example, the syrup dosing regimen is 3 times a day, instead of 2 times a day for pills). taking the drug Tegretol in the form of conventional pills for taking the drug Tegretol CR prolonged-release pills Clinical experience shows that in some patients with the use of prolonged-release pills may increasing the dose of the drug. Considering drug interactions and the pharmacokinetics of antiepileptic drugs, elderly patients should be carefully selected. Epilepsy If possible, the drug should be prescribed as monotherapy. The drug is usually ineffective with small attacks (petit mal, absans) and myoclonic seizures. Treatment begins with the use of a small daily dose, which is subsequently slowly increased to achieve the optimal effect. To select the optimal dose of the drug, it is recommended to determine the concentration of the active substance in the blood plasma. When Tegretol is added to other antiepileptic drugs taken, the dose is increased gradually. If necessary, carry out the appropriate correction of doses of drugs taken. For adults, the initial dose of carbamazepine is 100-200 mg 1 or 2 times a day. Then the dose is slowly increased to achieve the optimal therapeutic effect; it is usually achieved at a dose of 400 mg 2-3 times a day. Some patients may need to increase the daily dose to 1600 or 2000 mg. In children aged 4 years and under, the recommended starting dose is 20-60 mg / day; further, the dose is increased by 20-60 mg every other day. In children over the age of 4 years, treatment can be started with the use of 100 mg / day; the dose is increased gradually, by 100 mg per week. In children younger than 3 years old, it is preferable to use the drug in the form of a syrup due to the difficulty of applying solid dosage forms in this age group. Maintenance doses: for children, it is set at the rate of 10–20 mg / kg / day (in several doses). For children aged 4–5 years, the daily dose is 200–400 mg; 6–10 years old - 400–600 mg; 11–15 years - 600–1000 mg. The trigeminal nerve neuralgia. The initial dose is 200–400 mg / day. It is slowly increased to the disappearance of pain (usually - up to a dose of 200 mg 3-4 times a day).Then the dose is gradually reduced to the minimum maintenance. The recommended initial dose for elderly patients is 100 mg 2 times a day. Alcohol withdrawal syndrome. The average dose is 200 mg 3 times a day. In severe cases, during the first few days, the dose may be increased (for example, 400 mg 3 times a day). In severe manifestations of alcohol withdrawal, treatment begins with the use of the drug in combination with drugs that have sedative and hypnotic effects (for example, clomethiazole, chlordiazepoxide). After the resolution of the acute phase, treatment with the drug can be continued as monotherapy. Polyuria and polydipsia of neurohormonal nature with central diabetes insipidus diabetes. The average dose for adults is 200 mg 2-3 times a day. In children, the dose of the drug should be reduced in accordance with the age and body weight of the child. Pain syndrome in diabetic neuropathy The average dose is 200 mg 2–4 times a day. Acute manic states and supportive treatment of affective (bipolar) disorders. The daily dose is 400–1600 mg. . The average daily dose is 400–600 mg (in 2–3 doses). In the acute manic state, the dose should be increased rather quickly. With the maintenance therapy of bipolar disorders in order to ensure optimal tolerability, each subsequent dose increase should be small, the daily dose should be increased gradually.
Side effects
From the side of the central nervous system and peripheral nervous system: often - dizziness, ataxia, drowsiness; headache, diplopia, accommodation disturbances are possible; rarely - involuntary movements, nystagmus; in some cases, oculomotor disorders, dysarthria, peripheral neuritis, paresthesias, muscle weakness, symptoms of paresis, hallucinations, depression, fatigue, aggressive behavior, agitation, impairment of consciousness, activation of psychosis, taste disturbances, conjunctivitis, tinnitus, hyperacussion. On the part of the digestive system: nausea, increased GGT, increased activity of alkaline phosphatase, vomiting, dry mouth; rarely, increased transaminase activity, jaundice, cholestatic hepatitis, diarrhea or constipation; in some cases - loss of appetite, abdominal pain, glossitis,stomatitis. From the side of the cardiovascular system: rarely - myocardial conduction disturbances; in some cases - bradycardia, arrhythmias, AV-blockade with syncope, collapse, heart failure, manifestations of coronary insufficiency, thrombophlebitis, thromboembolism. From the side of the hemopoietic system: leukopenia, eosinophilia, thrombocytopenia; rarely - leukocytosis; in some cases - agranulocytosis, aplastic anemia, erythrocyte aplasia, megaloblastic anemia, reticulocytosis, hemolytic anemia, granulomatous hepatitis. On the metabolic side: hyponatremia, fluid retention, edema, weight gain, reduction of plasma osmolality; in some cases - acute intermittent porphyria, folic acid deficiency; disorders of calcium metabolism, increased cholesterol and triglycerides. For the endocrine system: gynecomastia or galactorrhea; rarely, dysfunction of the thyroid gland. From the urinary system: rarely, kidney dysfunction, interstitial nephritis and renal failure. From the respiratory system: in some cases, dyspnea, pneumonitis or pneumonia. Allergic reactions: skin rash, itching; rarely - lymphadenopathy, fever, hepatosplenomegaly, arthralgia.
Overdose
Symptoms: Central nervous system; CNS function depression; disorientation, drowsiness, agitation, hallucinations, coma; blurred vision, slurred speech, dysarthria, nystagmus, ataxia, dyskinesia, hyperreflexia (first), hyporeflexia (later); convulsions, psychomotor disorders, myoclonus, hypothermia, mydriasis. Respiratory system. Purge of respiration, pulmonary edema. Cardiovascular system. Tachycardia, arterial hypotension; sometimes - hypertension, disturbances of conductivity with expansion of the QRS complex; cardiac arrest, syncope. gastrointestinal tract, delayed passage of food from the stomach, decreased colon motility. Urinary system, urinary retention, oliguria or anuria; fluid retention; dilution hyponatremia due to the effect of carbamazepine, similar to the effect of antidiuretic hormone. Changes from laboratory parameters Hyponatremia, possible metabolic acidosis, possible hyperglycemia, increased muscle fraction of creatinine phosphokinase. Treatment. First, the treatment should be based on the clinical condition of the patient; hospitalization is indicated.Concentration of carbamazepine in plasma is carried out to confirm poisoning with this agent and to assess the degree of overdose. The contents of the stomach are evacuated, the stomach is washed, and activated charcoal is used. Late evacuation of gastric contents can lead to delayed absorption and the reappearance of symptoms of intoxication during the recovery period. Symptomatic supportive therapy is used in the intensive care unit, monitoring of heart function, careful correction of electrolyte disorders. There is no specific antidote.
Interaction with other drugs
With simultaneous use of CYP3A4 isoenzyme inhibitors, plasma concentrations of carbamazepine can be increased. With simultaneous use of the CYP3A4 system isoenzyme inducers, carbamazepine metabolism can be accelerated, its plasma concentrations can be reduced, and therapeutic effects can be reduced. use of valproic acid may reduce the concentration of carbamazepine and significantly reduce valproic acid concentration in plasma. This increases the concentration of the metabolite carbamazepine - carbamazepine-epoxide (probably due to inhibition of its conversion to carbamazepine-10,11-trans-diol), which also has anticonvulsant activity, therefore the effects of this interaction can be leveled, but more often side reactions occur - blurred vision, dizziness, vomiting, weakness, nystagmus. With simultaneous use of valproic acid and carbamazepine, a hepatotoxic effect may develop (presumably due to the formation of a secondary metabolite of valproic acid, which has a hepatotoxic effect). With simultaneous use of valpromid, metabolism in the liver of carbamazepine and its metabolite carbamazepine-epoxy decreases inhibition of the epoxide inhibition enzyme. The specified metabolite has anticonvulsant activity, but with a significant increase in plasma concentration may have a toxic effect. When used simultaneously with verapamil, diltiazem, isoniazid,dextropropoxyfen, viloxazine, fluoxetine, fluvoxamine, cimetidine, acetazolamide, danazol, desipramine, nicotinamide (in adults, only in high doses), erythromycin, troleandomycin, josamycin, clarithromycin; with azoles (including with itraconazole, ketoconazole, fluconazole), terfenadine, loratadine, plasma concentrations of carbamazepine may be elevated with the risk of side effects (dizziness, drowsiness, ataxia, diplopia). When used simultaneously with hexamidine, the anti-convulsant effect of carbamases decreases. ; with hydrochlorothiazide, furosemide - possible reduction of sodium in the blood; with hormonal contraceptives - possible weakening of the action of contraceptives and the development of acyclic bleeding. With simultaneous use of thyroid gland hormones may increase the elimination of thyroid hormones; with clonazepam - possible increase in clearance of clonazepam and a decrease in clearance of carbamazepine; with lithium preparations - mutual enhancement of neurotoxic action is possible. With simultaneous use with primidone, a decrease in plasma plasma concentration of carbamazepine is possible. There are reports that primidone may increase the plasma concentration of a pharmacologically active metabolite, carbamazepine-10,11-epoxide. If used simultaneously with ritonavir, the side effects of carbamazepine may be enhanced; with sertraline - a decrease in sertraline concentration is possible; with theophylline, rifampicin, cisplatin, doxorubicin - it is possible to decrease the concentration of carbamazepine in the blood plasma; with tetracycline - the effects of carbamazepine may be reduced. When used simultaneously with felbamate, plasma concentrations of carbamazepine may decrease, but the concentration of the active metabolite carbamazepine-epoxide may increase, while the concentration of carbamazepine in plasma may decrease. blood plasma. Perhaps the mutual weakening of the anticonvulsant action, and in rare cases - its strengthening.
special instructions
Carbamazepine is not used for atypical or generalized minor epileptic seizures, myoclonic or atonic epileptic seizures.It should not be used to relieve ordinary pain; as a prophylactic during prolonged periods of remission of the trigeminal neuralgia. It is used with caution in case of concomitant diseases of the cardiovascular system, marked disorders of the liver and / or kidneys, diabetes mellitus, increased intraocular pressure, with a history of hematological reactions to the use other drugs, hyponatremia, urinary retention, increased sensitivity to tricyclic antidepressants, with indications of a history of interruption of treatment arbamazepinom, as well as children and elderly patients vozrasta.Lechenie should be under the supervision of a physician. With long-term treatment, it is necessary to monitor the blood picture, the functional state of the liver and kidneys, the concentration of electrolytes in the blood plasma, and an ophthalmologic examination. Periodic determination of the level of carbamazepine in the blood plasma is recommended to monitor the efficacy and safety of treatment. Not less than 2 weeks before starting therapy with carbamazepine, it is necessary to discontinue treatment with MAO inhibitors. Avoid alcohol consumption during the treatment period. Influence on the ability to drive motor vehicles and control mechanisms should refrain from engaging in potentially hazardous activities that require increased attention, speed of psychomotor reactions.