Carbamazepine

2024 Author: Rachel Wainwright | [email protected]. Last modified: 2023-12-15 07:39

Carbamazepine: instructions for use and reviews

1. Release form and composition
2. Pharmacological properties
3. Indications for use
4. Contraindications
5. Method of application and dosage
6. Side effects
7. Overdose
8. Special instructions
9. Application during pregnancy and lactation
10. Use in childhood
11. Drug interactions
12. Analogs
13. Terms and conditions of storage
14. Terms of dispensing from pharmacies
15. Reviews
16. Price in pharmacies

Latin name: Carbamazepine

ATX code: N03AF01

Active ingredient: carbamazepine (carbamazepine)

Producer: OOO Rozpharm (Russia), ZAO ALSI Pharma (Russia), OAO Sintez (Russia)

Description and photo update: 2019-14-08

Prices in pharmacies: from 52 rubles.

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Carbamazepine is a drug with psychotropic, antiepileptic action.

Release form and composition

Carbamazepine is produced in the form of tablets (10, 15, 25 pieces in a blister strip, 1-5 packs in a cardboard box; 20, 30 pieces in a blister, 1, 2, 5, 10 packs in a cardboard box pack; 20, 30, 40, 50, 100 pcs. in a can, 1 can in a cardboard box).

The composition of 1 tablet includes:

Active ingredient: carbamazepine - 200 mg;
Auxiliary components: talc - 3.1 mg, povidone K30 - 14.4 mg, colloidal silicon dioxide (aerosil) - 0.96 mg, polysorbate 80 - 1.6 mg, potato starch - 96.64 mg, magnesium stearate - 3, 1 mg.

Pharmacological properties

Pharmacodynamics

Carbamazepine is a dibenzoazepine derivative that is characterized by antiepileptic, neurotropic and psychotropic effects.

At the moment, the mechanism of action of this substance has been studied only partially. It inhibits the synaptic transmission of excitatory impulses, prevents serial discharges of neurons and brings the membrane of overexcited neurons to a stable state. Presumably, the main mechanism of action of carbamazepine is to prevent the re-formation of sodium-dependent action potentials in depolarized neurons due to the blockade of “action” - dependent and voltage-dependent sodium channels.

When using the drug as monotherapy in patients with epilepsy (in particular, patients of childhood and adolescence), a psychotropic effect was observed, expressed in the elimination of symptoms of anxiety and depression, as well as a decrease in aggressiveness and irritability. There is no unambiguous information about the effect of carbamazepine on cognitive and psychomotor functions: in some studies, a double or negative effect was revealed, which was dose-dependent, while other studies confirmed the positive effect of the drug on memory and attention.

As a neurotropic agent, carbamazepine is effective in certain neurological diseases. For example, in secondary and idiopathic trigeminal neuralgia, it prevents the occurrence of paroxysmal pain attacks.

In patients with alcohol withdrawal syndrome, carbamazepine increases the seizure threshold, which in this condition is in most cases lowered, and reduces the severity of the clinical manifestations of the syndrome (these include gait disturbances, tremors, hyperexcitability).

In patients with diabetes insipidus, carbamazepine reduces urine output and eliminates the feeling of thirst.

As a psychotropic drug, the drug is prescribed for affective disorders, including the treatment of acute manic conditions, with the maintenance treatment of bipolar affective (manic-depressive) disorders (carbamazepine is used both as monotherapy and simultaneously with the use of lithium preparations, antidepressants or neuroleptics), with manic - depressive psychosis, accompanied by rapid cycles, with manic attacks, when carbamazepine is used in combination with antipsychotics, as well as with attacks of schizoaffective psychosis. The ability of the drug to suppress manic manifestations can be explained by inhibition of the exchange of norepinephrine and dopamine.

Pharmacokinetics

When taken orally, carbamazepine is almost completely absorbed in the gastrointestinal tract. Taking the drug in the form of tablets is accompanied by a relatively slow absorption. After a single dose of 1 tablet of carbamazepine, on average, its maximum concentration is determined after 12 hours. After a single dose of 400 mg of the drug, the approximate value of the maximum concentration of unchanged carbamazepine is approximately 4.5 μg / ml.

When carbamazepine is taken simultaneously with a meal, the degree and rate of absorption of the drug remain unchanged. The equilibrium concentration of the substance in the plasma is reached within 1–2 weeks. The time to reach it is individual and is determined by the degree of autoinduction of the liver enzyme systems by carbamazepine, the patient's condition before the start of treatment, the dose of the drug, the duration of therapy, as well as heteroinduction with other drugs that are used in combination with carbamazepine. There are significant interindividual differences in the values of equilibrium concentrations in the range of therapeutic doses: in most patients, these indicators vary from 4 to 12 μg / ml (17–50 μmol / L).

Carbamazepine binds to blood plasma proteins by about 70-80%. The content of the unchanged substance in saliva and cerebrospinal fluid is proportional to the concentration of the active component not bound to plasma proteins (20-30%). The content of carbamazepine in breast milk reaches 25-60% of its concentration in blood plasma.

Carbamazepine crosses the placental barrier. Since it is almost completely absorbed, the apparent volume of distribution is 0.8 - 1.9 l / kg.

Carbamazepine is metabolized in the liver. The most important way of biotransformation of a substance is epoxidation with the formation of metabolites, the main among which are the 10,11-transdiol derivative and the product of its conjugation with glucuronic acid. Carbamazepine-10,11-epoxide in the human body is converted into carbamazepine-10,11-transdiol with the participation of the microsomal enzyme epoxide hydrolase. The concentration of carbamazepine-10,11-epoxide, which is an active metabolite, is approximately 30% of the plasma concentration of carbamazepine. The main isoenzyme responsible for the conversion of carbamazepine to carbamazepine-10,11-epoxide is cytochrome P4503A4. As a result of metabolic processes, a small amount of another metabolite, 9-hydroxy-methyl-10-carbamoylacridane, is also formed.

Another important pathway for the metabolism of carbamazepine is the formation of various monohydroxylated derivatives, as well as N-glucuronides, using the UGT2B7 isoenzyme.

The half-life of the active substance in unchanged form after a single oral administration of the drug is on average 36 hours, and after repeated doses of the drug - approximately 16-24 hours, depending on the duration of therapy (this is due to the autoinduction of the monooxygenase system of the liver). It has been proven that in patients who combine carbamazepine with other drugs that induce liver enzymes (for example, phenobarbital, phenytoin), the half-life of the drug generally does not exceed 9-10 hours.

With oral administration of carbamazepine-10,11-epoxide, on average, its half-life is about 6 hours.

After a single oral administration of carbamazepine at a dose of 400 mg, 72% of the substance is excreted through the kidneys and 28% through the intestines. Approximately 2% of the dose taken is excreted in the urine, representing unchanged carbamazepine, and approximately 1% is in the form of a 10,11-epoxy metabolite exhibiting metabolic activity. After a single oral dose, 30% of carbamazepine is excreted through the kidneys as end products of the epoxidation process.

In children, a more rapid elimination of carbamazepine is noted, therefore, sometimes higher doses of the drug are required, which are calculated based on the child's body weight, compared with adult patients.

There is no information on the change in the pharmacokinetics of carbamazepine in elderly patients compared with younger patients.

The pharmacokinetics of carbamazepine in patients with renal and hepatic dysfunction have not been studied to date.

Indications for use

Epilepsy (except for flaccid or myoclonic seizures, absences) - secondary and primary generalized forms of seizures accompanied by tonic-clonic seizures, partial seizures with simple and complex symptoms, mixed forms of seizures (monotherapy or in combination with other drugs with an anticonvulsant effect);
Polyuria and polydipsia in diabetes insipidus, pain syndrome in diabetic polyneuropathy, trigeminal neuralgia in multiple sclerosis, idiopathic trigeminal neuralgia, alcohol withdrawal syndrome, idiopathic glossopharyngeal neuralgia, affective disorders;
Phase affective disorders, including schizoaffective disorders, manic-depressive psychosis, etc. (prevention).

Contraindications

Atrioventricular block;
Violation of bone marrow hematopoiesis;
Acute intermittent porphyria (including a history of indications);
Simultaneous reception with monoamine oxidase inhibitors and for 14 days after their cancellation;
Pregnancy and lactation;
Hypersensitivity to the components of the drug, as well as to drugs that are chemically similar to the active substance (tricyclic antidepressants).

According to the instructions, Carbamazepine should be used with caution while taking alcohol, elderly patients, as well as patients with severe heart failure, dilution hyponatremia, increased intraocular pressure, inhibition of bone marrow hematopoiesis while taking medications (history), prostatic hyperplasia, liver failure, chronic renal failure.

Instructions for the use of Carbamazepine: method and dosage

Carbamazepine tablets are taken orally with a small amount of liquid. The drug can be taken with or without food.

In the treatment of epilepsy, when possible, the drug is prescribed as monotherapy. Taking the drug begins with a small daily dose, which is subsequently gradually increased to the optimum.

If antiepileptic therapy is already underway, Carbamazepine should be added gradually (depending on the indications, the doses of drugs used simultaneously can be adjusted).

The initial adult dose is 100-200 mg 1–2 times daily. If necessary, it is slowly increased until the optimal therapeutic effect is achieved (as a rule, up to 400 mg 2-3 times a day). The maximum daily dose is 1600-2000 mg.

Children are prescribed the following dosage regimen:

Up to 5 years: the initial daily dose is 20-60 mg, every other day the dose is gradually increased by 20-60 mg;
From 5 years old: the initial daily dose is 100 mg, every week the dose is gradually increased by 100 mg.

The maintenance dose for children is 10-20 mg / kg per day for 2-3 doses (to ensure accurate dosing in children under 5 years of age, liquid oral dosage forms of the drug should be used).

For other indications, carbamazepine tablets are prescribed:

Trigeminal neuralgia: on the first day - 200-400 mg per day; the dose is gradually increased until the pain syndrome stops, but not more than 200 mg per day (the average daily dose is 400-800 mg), then reduced to the minimum effective dose;
Pain syndrome of neurogenic genesis: on the first day - 100 mg 2 times a day; until the pain subsides, the dose is increased by no more than 200 mg per day (an increase of 100 mg every 12 hours is possible). Maintenance daily dose - 200-1200 mg (in divided doses);
Diabetic neuropathy, accompanied by pain: the average dose is 200 mg 2-4 times a day. For the prevention of relapses of schizoaffective and affective psychoses - 600 mg daily in 3-4 doses;
Diabetes insipidus: The average adult dose is 200 mg 2-3 times a day. For children, Carbamazepine is prescribed in accordance with the weight and age of the child;
Alcohol withdrawal syndrome: an average dose of 200 mg 3 times a day; in severe cases during the first few days, a single dose can be increased to 400 mg. At the beginning of therapy with severe withdrawal symptoms, it is recommended to use it simultaneously with drugs with sedative-hypnotic effects (clomethiazole, chlordiazepoxide);
Acute manic states and affective (bipolar) disorders: daily dose - 400-1600 mg (on average, the drug is taken at 400-600 mg in 2-3 doses). In the acute course of the disease, the dose is increased rapidly, with maintenance therapy of affective disorders - gradually (to improve tolerance).

Elderly patients and patients with hypersensitivity Carbamazepine is usually prescribed in an initial dose of 100 mg 2 times a day.

Side effects

During the use of Carbamazepine, the following side effects may develop:

Central nervous system: ataxia, dizziness, general weakness, drowsiness, oculomotor disorders, headache, nystagmus, paresis of accommodation, tics, tremor, orofacial dyskinesia, choreoathetoid disorders, peripheral neuritis, dysarthria, paresthesia, paresis, muscle weakness;
Cardiovascular system: decrease or increase in blood pressure, intracardiac conduction disorders, collapse, bradycardia, arrhythmias, atrioventricular block with fainting, development or worsening of congestive heart failure, exacerbation of coronary heart disease (including increased frequency or occurrence of angina pectoris attacks), thromboembolism syndrome;
Digestive system: dry mouth, vomiting, nausea, constipation or diarrhea, abdominal pain, stomatitis, glossitis, pancreatitis;
Genitourinary system: renal failure, interstitial nephritis, impaired renal function (hematuria, albuminuria, oliguria, azotemia / increased urea), urinary retention, urinary frequency, impotence / sexual dysfunction;
Endocrine system and metabolism: hyponatremia, weight gain, edema, increased prolactin levels (possibly simultaneously with the development of galactorrhea and gynecomastia); a decrease in the level of L-thyroxine (free T4, T3) and an increase in the level of thyroid-stimulating hormone (as a rule, clinical manifestations are not accompanied), osteomalacia, disorders of calcium-phosphorus metabolism in bone tissue (a decrease in the concentration of 25-OH-cholecalciferol and ionized form of calcium in plasma blood), hypertriglyceridemia, hypercholesterolemia;
Musculoskeletal system: arthralgia, convulsions, myalgia;
Liver: increased activity of gamma-glutamyltransferase (as a rule, has no clinical significance), increased activity of alkaline phosphatase and "hepatic" transaminases, hepatitis (granulomatous, mixed, cholestatic or parenchymal (hepatocellular) type), liver failure;
Hematopoietic organs: thrombocytopenia, leukopenia, leukocytosis, eosinophilia, lymphadenopathy, aplastic anemia, acute intermittent porphyria, agranulocytosis, megaloblastic anemia, true erythrocytic aplasia, hemolytic anemia, reticulocytosis;
Sense organs: changes in the perception of pitch, lens opacity, disturbances in taste, conjunctivitis, hypo- or hyperacusis;
Mental sphere: anxiety, hallucinations, loss of appetite, depression, aggressive behavior, disorientation, agitation, activation of psychosis;
Allergic reactions: lupus-like syndrome, exfoliative dermatitis, urticaria, Stevens-Johnson syndrome, erythroderma, toxic epidermal necrolysis, photosensitivity, erythema nodosum and multiforme. Possible multiorgan delayed-type hypersensitivity reactions with vasculitis, fever, lymphadenopathy, skin rashes, eosinophilia, lymphoma-like symptoms, leukopenia, arthralgias, altered liver function and hepatosplenomegaly (these manifestations can occur in various combinations). Involvement of other organs is possible, for example, kidneys, lungs, myocardium, pancreas, colon. Very rarely - aseptic meningitis with myoclonus, angioedema, anaphylactic reaction, pulmonary hypersensitivity reactions, characterized by shortness of breath, fever,pneumonitis or pneumonia;
Others: purpura, skin pigmentation disorders, sweating, acne, alopecia.

Overdose

In case of an overdose of Carbamazepine, the following symptoms are mainly observed:

on the part of the cardiovascular system: high or low blood pressure, tachycardia, conduction disorders accompanied by an expansion of the QRS complex, cardiac arrest and fainting triggered by cardiac arrest;
from the side of the central nervous system: mydriasis, convulsions, depression of central nervous system functions, hypothermia, disorientation in space, hallucinations, agitation, drowsiness, impaired consciousness, coma, myoclonus, dysarthria, slurred speech, ataxia, blurred vision, nystagmus, hyperreflexia (at the initial stage) and hyporeflexia (hereinafter), psychomotor conditions, dyskinesia, seizures;
from the gastrointestinal tract: reduced rate of evacuation of food from the stomach, vomiting, impaired motility of the colon;
from the respiratory system: oppression of the respiratory center, pulmonary edema;
from the urinary system: water intoxication (dilution hyponatremia) associated with the effect of carbamazepine, similar to the action of antidiuretic hormone, fluid retention, urinary retention, anuria or oliguria;
changes in laboratory parameters: the development of hyperglycemia or metabolic acidosis, increased activity of the muscle fraction of creatine phosphokinase is possible.

The specific antidote to carbamazepine is unknown. The course of treatment for an overdose should be based on the clinical condition of the patient, and it is recommended that he be admitted to a hospital.

The plasma concentration of carbamazepine should be determined to confirm drug poisoning and to assess the severity of the overdose.

It is necessary to wash the stomach and evacuate its contents, as well as take activated charcoal. Late evacuation of gastric contents often promotes delayed absorption, which can lead to re-development of symptoms of intoxication during the recovery period. Also, good results are obtained by symptomatic supportive treatment, which is carried out in the intensive care unit and is accompanied by monitoring of cardiac function and careful correction of violations of water and electrolyte balance.

With diagnosed arterial hypotension, intravenous administration of dobutamine or dopamine is indicated. With the development of arrhythmia, treatment is selected individually. In the case of seizures, benzodiazepines such as diazepam or other anticonvulsants such as paraldehyde or phenobarbital are recommended (the latter is used with caution due to the increased risk of respiratory depression).

If the patient develops water intoxication (hyponatremia), fluid administration should be limited and a 0.9% sodium chloride solution should be carefully administered intravenously, which in many cases prevents the development of brain damage. Good results are obtained by carrying out hemosorption on coal sorbents. Peritoneal dialysis, hemodialysis and forced diuresis are considered insufficiently effective in removing carbamazepine from the body. On the second and third days after the appearance of signs of an overdose, her symptoms may increase, which is explained by the slow absorption of the drug.

special instructions

Before starting the use of Carbamazepine, it is necessary to conduct an examination: a general analysis of urine and blood (including counting reticulocytes, platelets), determining the level of iron, the concentration of urea and electrolytes in the blood serum. In the future, these indicators need to be monitored weekly during the first month of treatment, and then - once a month.

When prescribing carbamazepine to patients with increased intraocular pressure, it must be periodically monitored.

Therapy should be discontinued with the development of progressive leukopenia or leukopenia, which is accompanied by clinical symptoms of an infectious disease (non-progressive asymptomatic leukopenia does not require withdrawal of Carbamazepine).

During therapy, care must be taken when driving vehicles and performing other potentially hazardous types of work that require an increased concentration of attention and rapid psychomotor reactions.

Application during pregnancy and lactation

It has been proven that children born to mothers diagnosed with epilepsy have a higher risk of intrauterine growth disorders, including the occurrence of developmental defects. There is evidence that carbamazepine may increase this predisposition, although there is no definitive confirmation of this fact, which would have been obtained in controlled clinical trials with the appointment of the drug as monotherapy, at the moment.

There are reports of cases of congenital diseases, malformations, including spina bifida (non-closure of the arches of the vertebrae), and other anomalies of a congenital nature, such as hypospadias, defects in the development of the cardiovascular system and other organ systems, as well as craniofacial structures.

Care should be taken to prescribe carbamazepine to pregnant women with epilepsy. If a woman taking the drug becomes pregnant, or plans to become pregnant, and if it is necessary to use carbamazepine during pregnancy, it is recommended to carefully weigh the expected benefits of treatment for the mother and the risk of potential complications, especially in the first trimester of pregnancy.

With sufficient clinical efficacy, patients of reproductive age should be prescribed carbamazepine exclusively as monotherapy, since the incidence of congenital malformations of the fetus during the course of combined antiepileptic therapy is higher than with monotherapy.

It is necessary to prescribe the drug in the minimum effective dose. You should also regularly monitor the content of the active component in the blood plasma.

Patients should be made aware of the increased risk of malformations. It is also desirable for them to undergo antenatal diagnostics.

During pregnancy, interruption of effective antiepileptic therapy is contraindicated, since the progression of the disease can have a negative impact on the mother and the fetus.

There is evidence that carbamazepine increases the folic acid deficiency that develops during pregnancy. This may increase the incidence of birth defects in babies born to women taking this drug. Therefore, it is advisable to take additional doses of folic acid before and during pregnancy.

As a prophylactic measure to prevent increased bleeding in newborns, women in the last weeks of pregnancy, as well as newborns, should be given vitamin K ₁.

Several cases of respiratory depression and / or epileptic seizures have been described in newborns whose mothers have combined carbamazepine with other anticonvulsants. There are also occasional cases of diarrhea, vomiting and / or decreased appetite in newborns whose mothers took carbamazepine. It is assumed that these reactions are manifestations of withdrawal syndrome in newborns.

Carbamazepine is determined in breast milk, its level in it is 25-60% of the substance level in blood plasma. Therefore, it is recommended to compare the benefits and possible undesirable effects of breastfeeding in the context of long-term drug treatment. While taking carbamazepine, mothers can breastfeed their babies, but only if they are constantly monitored for side effects (for example, allergic reactions on the skin and severe drowsiness).

Pediatric use

It is possible to use Carbamazepine in children over 4 years of age in strict accordance with the dosage regimen.

Drug interactions

With the simultaneous use of Carbamazepine with certain drugs, undesirable effects may occur:

Inhibitors of CYP3A4: increased concentration of carbamazepine in blood plasma;
Dextropropoxyphene, verapamil, felodipine, diltiazem, viloxazine, fluoxetine, fluvoxamine, desipramine, cimetidine, danazol, acetazolamide, nicotinamide (only in high doses in adults); macrolides (josamycin, erythromycin, clarithromycin, troleandomycin); azoles (ketoconazole, itraconazole, fluconazole), loratadine, terfenadine, isoniazid, grapefruit juice, propoxyphene, viral protease inhibitors used in HIV therapy: increasing the concentration of carbamazepine in the blood plasma;
Felbamate, fensuximide, phenobarbital, primidone, phenytoin, metsuximide, theophylline, cisplatin, rifampicin, doxorubicin, possibly: valpromide, clonazepam, valproic acid, oxcarbazepine, and herbal preparations with the content of St. John's wort;
Valproic acid and primidone: displacement of carbamazepine from the bond with plasma proteins and an increase in the concentration of a pharmacologically active metabolite (carbamazepine-10,11-epoxide);
Isotretinoin: changes in the bioavailability and / or clearance of carbamazepine and carbamazepine-10,11-epoxide (monitoring of plasma concentration is required);
Clobazam, clonazepam, primidone, ethosuximide, alprazolam, valproic acid, glucocorticosteroids (prednisolone, dexamethasone), haloperidol, cyclosporin, doxycycline, methadone, oral drugs containing progesterone and / or estrogens, alternative methods fenprocoumon, warfarin, dicumarol), topiramate, lamotrigine, tricyclic antidepressants (imipramine, nortriptyline, amitriptyline, clomipramine), felbamate, clozapine, tiagabine, protease inhibitors, which are used in the treatment of HIV infection (ritonavir, cvacvine, itytarakvepine), calcium channel blockers (a group of dihydropyridones, for example, felodipine), midazolam, levothyroxine, praziquantel, olazapine, risperidone, tramadol, ziprasidone:a decrease in their concentration in plasma (a decrease or even complete leveling of their effects, a correction of the doses used may be required);
Phenytoin: an increase or decrease in its level in blood plasma;
Mefenytoin: an increase (in rare cases) of its level in blood plasma;
Paracetamol: an increase in the risk of its toxic effects on the liver and a decrease in therapeutic efficacy (accelerating the metabolism of paracetamol);
Phenothiazine, pimozide, thioxanthenes, molindone, haloperidol, maprotiline, clozapine and tricyclic antidepressants: increasing the inhibitory effect on the central nervous system and weakening the anticonvulsant effect of carbamazepine;
Diuretics (furosemide, hydrochlorothiazide): development of hyponatremia accompanied by clinical manifestations;
Non-depolarizing muscle relaxants (pancuronium): reducing their effects;
Ethanol: decreased tolerance;
Indirect anticoagulants, hormonal contraceptives, folic acid: accelerate metabolism;
Means for general anesthesia (enflurane, halothane, fluorothane): acceleration of metabolism with an increase in the risk of developing hepatotoxic effects;
Methoxyflurane: increased formation of nephrotoxic metabolites;
Isoniazid: increased hepatotoxic effect.

Analogs

Carbamazepine analogs are: Finlepsin, Finlepsin retard, Tegretol, Tegretol CR, Zeptol, Karbaleks, Karbapin, Mezakar, Timonil.

Terms and conditions of storage

Store in a dark, dry place out of reach of children at temperatures up to 25 ° C.

Shelf life is 2 years.

Terms of dispensing from pharmacies

Dispensed by prescription.

Reviews about Carbamazepine

On the forums, there are only a few reviews about Carbamazepine, used as a remedy. Basically there are discussions about the possible narcotic effect of the drug.

Patients who took Carbamazepine in the treatment of various mental disorders and depressive conditions, argue that, compared with modern analogues, it is less effective and has a large number of adverse reactions. In the treatment of trigeminal neuralgia, the use of the drug practically does not give a result. Patients often suffer from insomnia during treatment.

The price of carbamazepine in pharmacies

The approximate price for Carbamazepine is 55-62 rubles (the package contains 40 tablets).

Carbamazepine: prices in online pharmacies

Drug name

Price

Pharmacy

Carbamazepine 200 mg tablets 40 pcs.

52 RUB

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