Accelerate the removal of carbamazepine from the body. Carbamazepine poisoning

Cases of overdose carbamazepine uncommon, death is rare. Supportive therapy and hemoperfusion using activated charcoal are effective. Overdoses of carbamazepine due to its slow absorption may delay the onset of coma in respiratory failure.

Carbamazepine antidotes no. Carbamazepine, like meprobamate, can cause neoplasms in the stomach. The most commonly reported toxic effects are neurological abnormalities (eg, ataxia, seizures, coma), cardiorespiratory disorders (eg, arrhythmias, conduction disturbances, respiratory depression), and ophthalmic complications such as nystagmus and ophthalmoplegia.

a) Structure and classification. Carbamazepine (Tegretol) is chemically and spatially similar to tricyclic antidepressants and, moreover, is spatially similar to phenytonin. In overdoses, many of the side effects of carbamazepine are similar to those of tricyclic antidepressants and phenytoin.

b) Toxicokinetics:
- Time to reach peak plasma levels: 6-24 hours
- Volume of distribution: 1-2 l/kg
- Plasma protein binding: 75-80%
- Half-life: 8-13 hours
- Displayed unchanged: 23%

in) Drug Interactions. Fluoxetine may inhibit the metabolism of carbamazepine and its epoxide metabolite. Erythromycin can inhibit the metabolism of carbamazepine in the liver, thereby causing carbamazepine intoxication. Dextropropoxyphene, isoniazid and calcium channel blockers cause an increase in the concentration of carbamazepine in serum.

Carbamazepine is able to induce a decrease in blood effective concentrations of drugs such as phenytoin, haloperidol, clonazepam and alprazolam, which are metabolized by the microsomal P450 oxidative system of the liver.

G) Pregnancy and lactation:

- Teratogenic effects. Described cases of developmental defects in children born to mothers taking only carbamazepine. Among these defects are spina bifida (in 1% of cases), congenital heart disease, diaphragmatic hernia, hypoplasia of the fingers and hydronephrosis. Cases of growth retardation, facial anomalies (eg, prominent forehead, downward slanting palpebral fissures, flat bridge of the nose, nostrils everted forward), and developmental delay have been observed.

The metabolite of carbamazepine, epoxide, may be mutagenic. Retrospective and prospective studies examining the effects of carbamazepine in utero have revealed the familiar pattern of small craniofacial defects, nail hypoplasia, and neurodevelopmental delay reported in the past with other anticonvulsant drugs. The data from this study needs to be confirmed. There were certain methodological difficulties in carrying out the work.
Newborns. If a mother during pregnancy or breastfeeding took carbamazepine, her child may develop cholestatic hepatitis.

e) Clinical picture of carbamazepine poisoning:

- Overdose: Effect on the nervous system. Based on a study of a number of cases of carbamazepine overdose, 4 clinical stages were identified:
I) coma, seizures (carbamazepine concentrations > 25 µg/ml);
II) aggressiveness, hallucinations, choreo-like movements (15-25 mcg/ml);
III) drowsiness, ataxia (11 - 15 mcg / ml);
iv) potentially catastrophic relapse (< 11 мкг/мл ).

Effect on the cardiovascular system. Carbamazepine exhibits class I antiarrhythmic properties. Kasarskis et al. There are 2 forms of cardiac dysfunction caused by the use of carbamazepine. One group of patients develops sinus tachycardia on the background of severe overdoses of carbamazepine. In the second group, mainly in elderly women, life-threatening bradyarrhythmias or delayed atrioventricular conduction develop, due to either therapeutic or moderately elevated serum concentrations of carbamazepine.
In an adult patient who swallowed 10 g of carbamazepine, T-wave flattening after 12 hours and T-wave inversion after 4 days were observed; the patient survived.

Influence on the respiratory system. In the first 24 hours, respiratory depression, irregular breathing, or apnea may occur. Possible pulmonary edema.

Deaths. Death can occur due to severe cardiovascular reactions, aspiration pneumonitis, severe hepatitis, or hypoplastic anemia. These complications also occur after chronic therapeutic use.

- Regular use. The use of carbamazepine can be accompanied by a number of side effects, including neutropenia, thrombocytopenia, skin rashes, water intoxication, impaired secretion of antidiuretic hormone, hyponatremia, ataxia, lupus, hepatitis, and hypoplastic anemia, which can be fatal. At therapeutic doses, carbamazepine may exacerbate Tourette's syndrome.

Effect on the kidneys. A case of acute tubular necrosis has been reported. Carbamazepine can in rare cases induce the formation of antinuclear antibodies and the development of a syndrome similar to systemic lupus erythematosus.

pseudolymphoma syndrome. The use of carbamazepine can induce the development of pseudolymphoma syndrome, similar to that observed after the use of phenytoin. The clinical features of the syndrome are lymphadenopathy, fever, rash and, in more rare cases, hepatosplenomegaly and eosinophilia. The syndrome is observed 4-30 days after the first medication. According to available data, cases of progression to malignant lymphoma were not observed.

e) Laboratory findings of carbamazepine poisoning:

- Analytical Methods. The Acculevel carbamazepine β monitoring test is a no-instrument in-office test with a sensitivity threshold of 2 µg/mL. Blood is obtained by finger prick (12 µl) and mixed with the reagent. To determine the content of carbamazepine in plasma, a plastic cassette with a strip of chromatographic paper is used.
Therapeutic plasma levels of carbamazepine range from 6 to 8 mg/l (25-34 µmol/l). At concentrations exceeding 10 mg/l (42 µmol/l), ataxia and nystagmus may occur.

With overdoses, peak serum concentrations ranged from 18 to 70 µg/mL (78-285 µmol/L). Serum concentrations of carbamazepine equal to or greater than 40 μg / ml (170 μmol / l) increase the risk of serious complications such as coma, seizures, respiratory failure and cardiac conduction disorders. The risk of serious illness after overdose of carbamazepine in children aged 1 to 12 years occurs at lower serum concentrations of the drug than in adults.

- Ancillary research. With systematic overdoses of carbamazepine, which are possible in patients with epilepsy, there may be an increase in the number of paroxysmal anomalies. In the acute phase of intoxication after an overdose of carbamazepine, the electroencephalogram (EEG) may be dominated by occipital delta activity.

An overdose of Carbamazepine leads to serious consequences, intoxication can be fatal. Therefore, it is forbidden to take the medicine on its own. It is necessary to conduct a diagnosis and follow all the recommendations of the doctor.

ICD code 10 T36-T50.

Characteristics of the drug

A common antiepileptic drug in pharmacies is also found under the names Finlepsin (finlepsin), Carbamazepine Akri or Retard. Designed to eliminate convulsive seizures. A positive effect is achieved by acting on hormones. By inhibiting them, the medicine reduces the number of manifestations of pathology, removes aggressive mood, anxiety, irritability. With neuralgia, it helps to eliminate the characteristic pain sensations.

The substance is absorbed by the mucous membranes of the gastrointestinal tract by almost 85%, the maximum dosage in the blood is detected 8–16 hours after ingestion. Decomposed in the liver, excreted in the urine.

Indications

Carbamazepine is prescribed for the following health problems:

1. Partial seizures.
2. Excessive urine output in diabetes insipidus.
3. Neuralgia of the glossopharyngeal or trigeminal nerve, as well as of an unexplained nature.
4. Withdrawal syndrome in case of treatment of alcoholism.
5. Acute manic state.
6. Worsening of pain severity in patients with diabetes mellitus.

The use of the drug is accompanied by such effects:

• Eliminates cramps.
• Positive effect on the central nervous system.
• Improves sleep, memory, improves mood.
• Removes hallucinations, delirium.
• Facilitates the excretion of urine and the emptying of the bladder.

The absorption of the drug does not depend on food intake.

Contraindications

It is forbidden to take in the presence of:

• hypersensitivity to ingredients;
• anemia;
• leukopenia;
• AV blockade;
• acute porphyria;
• alcoholism;
• liver failure;
• oppression of blood circulation in the tissues of the brain;
• prostate hyperplasia;
• increased intraocular pressure.

Use with caution in elderly patients. Prohibited joint reception with MAO inhibitors.

It is unacceptable to take alcohol during the course. In addition, the drug reduces attention, so it is undesirable to drive a vehicle.

Causes of poisoning

An overdose of Finlepsin or Carbamazepine occurs as a result of exceeding the permissible norm - a person seeks to quickly get rid of convulsions or pain, therefore he takes a significant number of tablets. In addition, the following factors contribute to intoxication:

• non-compliance with doctor's recommendations;
• independent appointment;
• accidental use by a child;
• suicide attempt.

At the slightest sign of malaise, they call for emergency care - the therapy is of a professional nature, otherwise the death of the victim is likely.

Clinical picture of overdose

Carbamazepine poisoning negatively affects, first of all, the nervous system, the state of the heart muscle. Main symptoms:

• cephalgia;
• dizziness;
• drowsiness;
• fatigue;
• problems with coordination of movements;
• fuzzy image, diagonal bifurcation of the object;
• fast, rhythmic and involuntary contractions of muscle tissue;
• nervous tics;
• partial paralysis;
• fluctuation of the eyeballs;
• smacking, sticking out the tongue, licking the lips;
• taste disorder;
• decrease or increase in blood pressure;
• slowing of the heartbeat.

A significant overdose negatively affects the psyche, causing hallucinations, a delusional state. Often accompanied by anorexia. Lack of therapy provokes collapse, thromboembolism.

Acute damage leads to the development of such symptoms:

• nausea and vomiting;
• dryness of the oral mucosa or excessive salivation;
• strong thirst;
• diarrhea or diarrhoea.

If you are allergic to the ingredients, dermatitis, systemic lupus, urticaria, erythema nodosum, vasculitis are likely. Often, against the background of an overdose, pancreatitis, liver failure or granulomatous hepatitis, pneumonia is manifested. Hair falls out, sweat increases.

Poisoning with Finlepsin or Carbamazepine disrupts metabolism, resulting in fluid retention and edema. Bones become extremely brittle and break easily. In men, there is a decrease in potency, a violation of spermatogenesis.

Sometimes intoxication provokes inflammation of the lining of the brain.

Lethal dose

The instructions clearly spell out the norms of the drug, increase only with the approval of the doctor, gradually, often combining Carbamazepine with sedative or hypnotic drugs. In some cases, it is allowed to use up to 1600 mg per day in 2-3 doses. Failure to comply with such rules provokes severe poisoning, more likely to lead to death.

First aid

If you suspect an overdose, call the ambulance. Before the arrival of doctors, they try to alleviate the condition of the victim:

1. To remove residual carbamazepine, gastric lavage.
2. Sorbents are used, for example, activated charcoal, which binds the drug particles and removes them with feces.
3. You can perform a colon cleanse with an enema or give the person a laxative.

Calling an ambulance team is necessary, since first aid measures reduce symptoms and further intoxication develops imperceptibly, manifesting itself 2–3 days after an overdose.

Antidote

There is no drug that can neutralize the action of Carbamazepine.

Diagnostics

If a drug is prescribed, it is necessary to periodically check the blood, controlling the concentration of the active substance and the main biochemical parameters. In case of overdose, examination is performed during therapy, a fresh sample is studied every 4-5 hours, and ECG monitoring is indicated.

Treatment Methods

A person in serious condition is transported to the intensive care unit. The following procedures are recommended:

1. With shock and a sharp decrease in blood pressure, Dopamine is administered.
2. Seizures are relieved with benzodiazepines.
3. For cardiovascular disorders, sodium bicarbonate is used.
4. Eliminate respiratory failure with tracheal intubation.
5. For kidney problems, dialysis is used.
6. In case of an overdose, the child is given a blood transfusion.
7. Hemodialysis and forced diuresis with this type of poisoning do not give a positive effect. But hemosorption with activated carbon helps.

If a state of shock has developed, a coma has been diagnosed, pacing is used.

Possible consequences

An overdose is often accompanied by irreversible complications that affect the central nervous system, vision, the cardiovascular system, and the kidneys. Therefore, it is necessary to follow all the recommendations of the doctor and, if symptoms appear, immediately contact qualified help.

Prevention

To prevent poisoning, do not neglect a number of rules:

1. Before taking, carefully study the instructions.
2. Do not leave Carbamazepine in places accessible to the child.
3. Do not take expired medicine.
4. Follow the prescribed dosage.
5. Do not exceed the duration of the treatment course.
6. Do not prescribe the remedy yourself.
7. During therapy, intraocular pressure is monitored, as well as the biochemistry of urine and blood.

Even with permission to increase the number of tablets, do it gradually, eliminating the risks of intoxication. Remember, illiterate use can lead to death.

Trade names

Actinerval, Gen-Karpaz, Zagretol, Zeptol, Karbadak, Karbalepsin retard, Karbapin, Karbasan, Karbatol, Karzepin, Mazepin, Stazepin, Tegretol, Timonil, Finzepin, Finlepsin, Epial.
Group affiliation

Anticonvulsant

Description of the active substance (INN)

Carbamazepine
Dosage form

syrup, tablets, prolonged-release tablets, film-coated tablets
pharmachologic effect

An antiepileptic drug (a derivative of dibenzazepine), which also has a normothymic, antimanic, antidiuretic (in patients with diabetes insipidus) and analgesic (in patients with neuralgia) action. The mechanism of action is associated with the blockade of voltage-dependent Na + channels, which leads to stabilization of the neuron membrane, inhibition of the occurrence of serial discharges of neurons and a decrease in synaptic conduction of impulses. Prevents the re-formation of Na+-dependent action potentials in depolarized neurons. Reduces the release of the excitatory neurotransmitter amino acid glutamate, increases the reduced seizure threshold, and so on. reduces the risk of developing an epileptic seizure. Increases conductivity for K +, modulates voltage-dependent Ca2 + channels, which can also determine the anticonvulsant effect of the drug. Corrects epileptic personality changes and ultimately improves the sociability of patients, contributes to their social rehabilitation. It can be prescribed as the main therapeutic drug and in combination with other anticonvulsant drugs. Effective in focal (partial) epileptic seizures (simple and complex), accompanied or not accompanied by secondary generalization, with generalized tonic-clonic epileptic seizures, as well as a combination of these types (usually ineffective in small seizures - petit mal, absences and myoclonic seizures) . Patients with epilepsy (especially children and adolescents) showed a positive effect on the symptoms of anxiety and depression, as well as a decrease in irritability and aggressiveness. The effect on cognitive function and psychomotor performance is dose dependent and highly variable. The onset of the anticonvulsant effect varies from several hours to several days (sometimes up to 1 month due to autoinduction of metabolism). With essential and secondary trigeminal neuralgia, in most cases it prevents the occurrence of pain attacks. Effective for the relief of neurogenic pain in spinal cord dryness, post-traumatic paresthesias and post-herpetic neuralgia. Relief of pain in trigeminal neuralgia is noted after 8-72 hours. With alcohol withdrawal syndrome, it increases the threshold for convulsive readiness (which is usually reduced in this condition) and reduces the severity of the clinical manifestations of the syndrome (irritability, tremor, gait disturbances). In patients with diabetes insipidus leads to rapid compensation of water balance, reduces diuresis and thirst. Antipsychotic (anti-manic) action develops after 7-10 days, may be due to inhibition of the metabolism of dopamine and norepinephrine. The prolonged dosage form ensures the maintenance of a more stable concentration of carbamazepine in the blood without "peaks" and "dips", which allows to reduce the frequency and severity of possible complications of therapy, to increase the effectiveness of therapy even when using relatively low doses. Dr. An important advantage of the prolonged form is the possibility of taking 1-2 times a day.
Indications

Epilepsy (excluding 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 anticonvulsant drugs). Idiopathic trigeminal neuralgia, trigeminal neuralgia in multiple sclerosis (typical and atypical), idiopathic glossopharyngeal neuralgia. Acute manic states (monotherapy and in combination with Li + and other antipsychotic drugs). Phase-flowing affective disorders (including bipolar) prevention of exacerbations, weakening of clinical manifestations during exacerbation. Alcohol withdrawal syndrome (anxiety, convulsions, hyperexcitability, sleep disturbances). Diabetic neuropathy with pain syndrome. Diabetes insipidus of central origin. Polyuria and polydipsia of a neurohormonal nature. It is also possible to use (the indications are based on clinical experience, controlled studies have not been conducted): - for psychotic disorders (for affective and schizoaffective disorders, psychoses, panic disorders, treatment-resistant schizophrenia, dysfunction of the limbic system), - for aggressive behavior of patients with organic brain damage, depression, chorea; - with anxiety, dysphoria, somatization, tinnitus, senile dementia, Kluver-Bucy syndrome (bilateral destruction of the amygdala complex), obsessive-compulsive disorders, withdrawal of benzodiazepine, cocaine; - with pain syndrome of neurogenic origin: with dorsal tabes, multiple sclerosis, acute idiopathic neuritis (Guillain-Barré syndrome), diabetic polyneuropathy, phantom pains, "tired legs" syndrome (Ekbom's syndrome), hemifacial spasm, post-traumatic neuropathy and neuralgia, postherpetic neuralgia ; - for the prevention of migraine.
Contraindications

Hypersensitivity to carbamazepine or chemically similar drugs (for example, tricyclic antidepressants) or to any other component of the drug; disorders of bone marrow hematopoiesis (anemia, leukopenia), acute "intermittent" porphyria (including history), AV blockade, concomitant use of MAO inhibitors. With caution. Decompensated CHF, dilution hyponatremia (ADH hypersecretion syndrome, hypopituitarism, hypothyroidism, adrenal insufficiency), old age, active alcoholism (increased CNS depression, increased metabolism of carbamazepine), suppression of bone marrow hematopoiesis while taking drugs (in history); liver failure, chronic renal failure; prostatic hyperplasia, increased intraocular pressure.
Side effects

When assessing the frequency of occurrence of various adverse reactions, the following gradations were used: very often - 10% and more often; often - 1-10%; sometimes - 0.1-1%; rarely - 0.01-0.1%; very rarely - less than 0.01%. Dose-dependent adverse reactions usually resolve within a few days, both spontaneously and after a temporary reduction in the dose of the drug. The development of adverse reactions from the central nervous system may be the result of a relative overdose of the drug or significant fluctuations in plasma concentrations of the active substance. In such cases, it is recommended to monitor the concentration of drugs in plasma. From the side of the central nervous system: very often - dizziness, ataxia, drowsiness, asthenia; often - headache, paresis of accommodation; sometimes - abnormal involuntary movements (for example, tremor, "fluttering" tremor - asterixis, dystonia, tics); nystagmus; rarely - orofacial dyskinesia, oculomotor disorders, speech disorders (eg dysarthria), choreoathetoid disorders, peripheral neuritis, paresthesia, myasthenia gravis and symptoms of paresis. The role of carbamazepine as a drug that causes or contributes to the development of neuroleptic malignant syndrome, especially when it is administered in conjunction with antipsychotics, remains unclear. From the mental sphere: rarely - hallucinations (visual or auditory), depression, loss of appetite, anxiety, aggressive behavior, agitation, disorientation; very rarely - activation of psychosis. Allergic reactions: often - urticaria; sometimes - erythroderma; rarely - lupus-like syndrome, skin itching; very rarely - erythema multiforme exudative (including Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell's syndrome), photosensitivity. Rarely - delayed-type multiorgan hypersensitivity reactions with fever, skin rashes, vasculitis (including erythema nodosum as a manifestation of cutaneous vasculitis), lymphadenopathy, signs resembling lymphoma, arthralgia, leukopenia, eosinophilia, hepatosplenomegaly and altered liver function tests (these manifestations occur in various combinations). Other organs (eg, lungs, kidneys, pancreas, myocardium, colon) may also be involved. Very rarely - aseptic meningitis with myoclonus and peripheral eosinophilia, anaphylactoid reaction, angioedema, allergic pneumonitis or eosinophilic pneumonia. If the above allergic reactions occur, the use of the drug should be discontinued. On the part of the hematopoietic organs: very often - leukopenia; often - thrombocytopenia, eosinophilia; rarely - leukocytosis, lymphadenopathy, folic acid deficiency; very rarely - agranulocytosis, aplastic anemia, true erythrocyte aplasia, megaloblastic anemia, acute "intermittent" porphyria, reticulocytosis, hemolytic anemia. From the digestive system: very often - nausea, vomiting; often - dry mouth; sometimes - diarrhea or constipation, abdominal pain; very rarely - glossitis, stomatitis, pancreatitis. On the part of the liver: very often - an increase in GGT activity (due to the induction of this enzyme in the liver), which usually does not matter; often - increased activity of alkaline phosphatase; sometimes - increased activity of "liver" transaminases; rarely - hepatitis of cholestatic, parenchymal (hepatocellular) or mixed type, jaundice; very rarely - granulomatous hepatitis, liver failure. From the side of the CCC: rarely - intracardiac conduction disturbances; decrease or increase in blood pressure; very rarely - bradycardia, arrhythmias, AV blockade with syncope, collapse, aggravation or development of CHF, exacerbation of coronary artery disease (including the appearance or increase in angina attacks), thrombophlebitis, thromboembolic syndrome. On the part of the endocrine system and metabolism: often - edema, fluid retention, weight gain, hyponatremia (decrease in plasma osmolarity due to an effect similar to the action of ADH, which in rare cases leads to dilution hyponatremia, accompanied by lethargy, vomiting, headache, disorientation and neurological disorders) very rarely - hyperprolactinemia (may be accompanied by galactorrhea and gynecomastia); a decrease in the concentration of L-thyroxine (free T4, T4, T3) and an increase in the concentration of TSH (usually not accompanied by clinical manifestations); violations of calcium-phosphorus metabolism in bone tissue (decrease in the concentration of Ca2 + and 25-OH-colcalciferol in plasma): osteomalacia; hypercholesterolemia (including HDL cholesterol) and hypertriglyceridemia. From the genitourinary system: very rarely - interstitial nephritis, renal failure, impaired renal function (for example, albuminuria, hematuria, oliguria, increased urea / azotemia), frequent urination, urinary retention, decreased potency. From the musculoskeletal system: very rarely - arthralgia, myalgia or convulsions. From the senses: very rarely - taste disturbances, clouding of the lens, conjunctivitis; hearing impairment, incl. tinnitus, hyperacusis, hypoacusis, changes in pitch perception. Other: skin pigmentation disorders, purpura, acne, increased sweating, alopecia. Rare cases of hirsutism have been reported, but the causal relationship of this complication to carbamazepine administration remains unclear. Overdose. Symptoms: usually reflect disorders of the central nervous system, cardiovascular system and respiratory system. From the side of the central nervous system and sensory organs - depression of the functions of the central nervous system, disorientation, drowsiness, agitation, hallucinations, fainting, coma; visual disturbances ("fog" before the eyes), dysarthria, nystagmus, ataxia, dyskinesia, hyperreflexia (initially), hyporeflexia (later); convulsions, psychomotor disorders, myoclonus, hypothermia, mydriasis). From the side of the CCC: tachycardia, decreased blood pressure, sometimes increased blood pressure, intraventricular conduction disturbances with an expansion of the QRS complex; heart failure. On the part of the respiratory system: respiratory depression, pulmonary edema. From the digestive system: nausea and vomiting, delayed evacuation of food from the stomach, decreased motility of the colon. From the urinary system: urinary retention, oliguria or anuria; fluid retention; breeding hyponatremia. Laboratory indicators: leukocytosis or leukopenia, hyponatremia, metabolic acidosis, hyperglycemia and glucosuria, increased muscle fraction of CPK. Treatment: There is no specific antidote. Treatment is based on the clinical condition of the patient; hospitalization, determination of the concentration of carbamazepine in plasma (to confirm poisoning with this drug and assess the degree of overdose), gastric lavage, administration of activated charcoal (late evacuation of gastric contents can lead to delayed absorption by 2 and 3 days and the reappearance of symptoms of intoxication during the recovery period) . Forced diuresis, hemodialysis and peritoneal dialysis are ineffective (dialysis is indicated for a combination of severe poisoning and renal failure). Young children may need an exchange transfusion. Symptomatic supportive treatment in the intensive care unit, monitoring of heart function, body temperature, corneal reflexes, kidney and bladder function, correction of electrolyte disorders. With a decrease in blood pressure: position with a lowered head end, plasma substitutes, with inefficiency - intravenous dopamine or dobutamine; in case of heart rhythm disturbances - treatment is selected individually; with convulsions - the introduction of benzodiazepines (for example, diazepam), with caution (due to a possible increase in respiratory depression), the introduction of others. anticonvulsants (such as phenobarbital). With the development of dilution hyponatremia (water intoxication) - restriction of the introduction of fluids and slow intravenous infusion of 0.9% NaCl solution (may help prevent the development of cerebral edema). Carrying out hemosorption on coal sorbents is recommended.
Dosage and administration

Inside, regardless of the meal, along with a small amount of liquid. Retard tablets (whole tablet or half) should be swallowed whole, without chewing, with a small amount of liquid, 2 times a day. In some patients, when using retard tablets, it may be necessary to increase the dose of the drug. Epilepsy. Where possible, carbamazepine should be given as monotherapy. Treatment begins with the use of a small daily dose, which is then slowly increased until the optimal effect is achieved. The addition of carbamazepine to the already ongoing antiepileptic therapy should be carried out gradually, while the doses of the drugs used do not change or, if necessary, correct. For adults, the initial dose is 100-200 mg 1-2 times a day. Then the dose is slowly increased until the optimal therapeutic effect is achieved (usually 400 mg 2-3 times a day, maximum 1.6-2 g / day). Children from 4 years old - at an initial dose of 20-60 mg / day, gradually increasing by 20-60 mg every other day. In children over 4 years old - at an initial dose of 100 mg / day, the dose is increased gradually, every week by 100 mg. Maintenance doses: 10-20 mg / kg per day (in divided doses): for 4-5 years - 200-400 mg (in 1-2 doses), 6-10 years - 400-600 mg (in 2-3 doses) ), for 11-15 years - 600-1000 mg (in 2-3 doses). With trigeminal neuralgia, 200-400 mg / day is prescribed on the first day, gradually increased by no more than 200 mg / day until the pain stops (on average 400-800 mg / day), and then reduced to the minimum effective dose. With pain syndrome of neurogenic origin, the initial dose is 100 mg 2 times a day on the first day, then the dose is increased by no more than 200 mg / day, if necessary, increasing it by 100 mg every 12 hours until the pain is relieved. Maintenance dose - 200-1200 mg / day in divided doses. In the treatment of elderly patients and patients with hypersensitivity, the initial dose 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 can be increased to 400 mg 3 times a day. At the beginning of treatment for severe withdrawal symptoms, it is recommended to prescribe in combination with sedative-hypnotic drugs (clomethiazole, chlordiazepoxide). Diabetes insipidus: the average dose for adults is 200 mg 2-3 times a day. In children, the dose should be reduced according to the age and body weight of the child. Diabetic neuropathy accompanied by pain: the average dose is 200 mg 2-4 times a day. In the prevention of relapse of affective and schizoaffective psychoses - 600 mg / day in 3-4 doses. In acute manic states and affective (bipolar) disorders, daily doses are 400-1600 mg. The average daily dose is 400-600 mg (in 2-3 doses). In an acute manic state, the dose is increased quickly, with maintenance therapy for affective disorders - gradually (to improve tolerance).
special instructions

Epilepsy monotherapy begins with the appointment of small doses, individually increasing them until the desired therapeutic effect is achieved. It is advisable to determine the concentration in plasma in order to select the optimal dose, especially in combination therapy. When transferring a patient to carbamazepine, the dose of the previously prescribed antiepileptic drug should be gradually reduced until it is completely canceled. Sudden discontinuation of carbamazepine may provoke epileptic seizures. If it is necessary to abruptly interrupt treatment, the patient should be transferred to another antiepileptic drug under the cover of the drug indicated in such cases (for example, diazepam administered intravenously or rectally, or phenytoin administered intravenously). Several cases of vomiting, diarrhea and / or malnutrition, convulsions and / or respiratory depression have been described in newborns whose mothers took carbamazepine simultaneously with other anticonvulsant drugs (possibly these reactions are manifestations of the "withdrawal" syndrome in newborns). Before prescribing carbamazepine and during treatment, it is necessary to study liver function, especially in patients with a history of liver disease, as well as in elderly patients. In the event of an increase in already existing liver dysfunction or the appearance of active liver disease, the drug should be immediately discontinued. Before starting treatment, it is also necessary to conduct a study of the blood picture (including counting platelets, reticulocytes), the concentration of Fe in the blood serum, a general urine test, the concentration of urea in the blood, EEG, the determination of the concentration of electrolytes in the blood serum (and periodically during treatment, because possible development of hyponatremia). Subsequently, these indicators should be monitored during the first month of treatment weekly, and then monthly. Carbamazepine should be immediately discontinued if allergic reactions or symptoms appear, presumably indicative of the development of Stevens-Johnson syndrome or Lyell's syndrome. Mild skin reactions (isolated macular or maculopapular exanthema) usually disappear within a few days or weeks, even with continued treatment or after a dose reduction (the patient should be under close medical supervision at this time). Carbamazepine has a weak anticholinergic activity; when prescribed to patients with elevated intraocular pressure, it is necessary to constantly monitor it. The possibility of activation of latently occurring psychoses should be taken into account, and in elderly patients, the possibility of developing disorientation or arousal. To date, isolated reports of impaired male fertility and / or impaired spermatogenesis have been registered (the relationship of these disorders with taking carbamazepine has not yet been established). There are reports of bleeding in women between periods in cases where oral contraceptives were used simultaneously. Carbamazepine may adversely affect the reliability of oral contraceptive drugs, so women of reproductive age during the treatment period should use alternative methods of contraception. Carbamazepine should only be used under medical supervision. Patients should be informed about early signs of toxicity associated with possible hematological disorders, as well as skin and liver symptoms. The patient is informed of the need to immediately consult a doctor in the event of such adverse reactions as fever, sore throat, rash, ulceration of the oral mucosa, unreasonable bruising, hemorrhages in the form of petechiae or purpura. In most cases, a transient or persistent decrease in the number of platelets and / or leukocytes is not a harbinger of the onset of aplastic anemia or agranulocytosis. However, before starting treatment, and periodically during treatment, clinical blood tests should be performed, including counting the number of platelets and, possibly, reticulocytes, as well as determining the concentration of Fe in the blood serum. Non-progressive asymptomatic leukopenia does not require discontinuation, however, treatment should be discontinued if progressive leukopenia or leukopenia occurs, accompanied by clinical symptoms of an infectious disease. An ophthalmological examination, including a slit-lamp examination of the fundus and measurement of intraocular pressure, if necessary, is recommended before starting treatment. In the case of prescribing the drug to patients with increased intraocular pressure, constant monitoring of this indicator is required. It is recommended to stop drinking ethanol. The drug in prolonged form can be taken once, at night. The need to increase the dose when switching to retard tablets is extremely rare. Although the relationship between the dose of carbamazepine, its concentration and clinical efficacy or tolerability is very small, nevertheless, regular determination of the concentration of carbamazepine may be useful in the following situations: with a sharp increase in the frequency of seizures; in order to check whether the patient is taking the drug properly; during pregnancy; in the treatment of children or adolescents; if you suspect a violation of the absorption of the drug; if the development of toxic reactions is suspected if the patient takes several drugs. In women of reproductive age, carbamazepine should, if possible, be used as monotherapy (using the lowest effective dose) - the frequency of congenital anomalies in newborns born to women who received combined antiepileptic treatment is higher than in those who received each of these drugs as monotherapy. When pregnancy occurs (when deciding whether to prescribe carbamazepine during pregnancy), it is necessary to carefully compare the expected benefits of therapy and its possible complications, especially in the first 3 months of pregnancy. It is known that children born to mothers with epilepsy are predisposed to intrauterine development disorders, including malformations. Carbamazepine, like all other antiepileptic drugs, can increase the risk of these disorders. There are isolated reports of cases of congenital diseases and malformations, including non-fusion of the vertebral arches (spina bifida). Patients should be provided with information about the possibility of an increased risk of malformations and the opportunity to undergo antenatal diagnosis. Antiepileptic drugs exacerbate folic acid deficiency, often observed during pregnancy, which may contribute to an increase in the frequency of birth defects in children (folic acid supplementation is recommended before and during pregnancy). In order to prevent increased bleeding in newborns, women in the last weeks of pregnancy, as well as newborns, are recommended to prescribe vitamin K1. Carbamazepine passes into breast milk, the benefits and possible undesirable consequences of breastfeeding in the context of ongoing therapy should be compared. Mothers taking carbamazepine may breastfeed their children, provided that the child is monitored for possible adverse reactions (eg severe drowsiness, allergic skin reactions). During the period of treatment, care must be taken when driving vehicles and engaging in other potentially hazardous activities that require an increased concentration of attention and speed of psychomotor reactions.
Interaction

Cytochrome CYP3A4 is the main enzyme involved in the metabolism of carbamazepine. Co-administration of carbamazepine with CYP3A4 inhibitors may lead to an increase in its plasma concentration and cause adverse reactions. The combined use of CYP3A4 inducers can lead to an acceleration of the metabolism of carbamazepine, a decrease in the plasma concentration of carbamazepine and a decrease in the therapeutic effect, on the contrary, their cancellation can reduce the rate of metabolism 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 the treatment of HIV infection (eg ritonavir) - correction of the dosing regimen or monitoring of plasma concentrations of carbamazepine is required. Felbamate reduces the plasma concentration of carbamazepine and increases the concentration of carbamazepine-10,11-epoxide, while a simultaneous decrease in the serum concentration of felbamate is possible. The concentration of carbamazepine is reduced by phenobarbital, phenytoin, primidone, metsuximide, fensuximide, theophylline, rifampicin, cisplatin, doxorubicin, possibly: clonazepam, valpromide, valproic acid, oxcarbazepine and herbal drugs containing St. John's wort (Hypericum perforatum). There are reports of the possibility of displacement of carbamazepine by valproic acid and primidone from its association with plasma proteins and an increase in the concentration of the pharmacologically active metabolite (carbamazepine-10,11-epoxide). Isotretinoin alters the bioavailability and / or clearance of carbamazepine and carbamazepine-10,11-epoxide (control of the concentration of carbamazepine in plasma is necessary). Carbamazepine may reduce plasma concentrations (reduce or even completely eliminate effects) and require dose adjustment of the following drugs: clobazam, clonazepam, ethosuximide, primidone, valproic acid, alprazolam, corticosteroids (prednisolone, dexamethasone), cyclosporine, doxycycline, haloperidol, methadone, oral drugs containing estrogens and / or progesterone (selection of alternative methods of contraception is necessary), theophylline, oral anticoagulants (warfarin, phenprocoumon, 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), BMKK (a group of dihydropyridones, such as felodipine), itraconazole, levothyroxine, midazolam, olazapine, praziquantel, risperidone, tramadol, ciprasidone. There are reports that while taking carbamazepine, the plasma level of phenytoin can both increase and decrease, and the level of mephenytoin can increase (in rare cases). Carbamazepine, when used together with paracetamol, increases the risk of its toxic effects on the liver and reduces therapeutic efficacy (acceleration of the metabolism of paracetamol). The simultaneous administration of carbamazepine with phenothiazine, pimozide, thioxanthenes, molindone, haloperidol, maprotiline, clozapine and tricyclic antidepressants leads to an increase in the inhibitory effect on the central nervous system and a weakening of the anticonvulsant effect of carbamazepine. MAO inhibitors increase the risk of developing hyperpyretic crises, hypertensive crises, seizures, death (before prescribing carbamazepine, MAO inhibitors should be canceled at least 2 weeks in advance or, if the clinical situation allows, even longer). Simultaneous administration with diuretics (hydrochlorothiazide, furosemide) can lead to hyponatremia, accompanied by clinical manifestations. Weakens the effects of non-depolarizing muscle relaxants (pancuronium). In the case of the use of such a combination, it may be necessary to increase the dose of muscle relaxants, while careful monitoring of patients is necessary, since their effect may be stopped more quickly). Reduces ethanol tolerance. Accelerates the metabolism of indirect anticoagulants, hormonal contraceptive drugs, folic acid; praziquantel may increase the elimination of thyroid hormones. Accelerates the metabolism of drugs for general anesthesia (enflurane, halothane, halothane) with an increased risk of hepatotoxic effects; enhances the formation of nephrotoxic metabolites of methoxyflurane. Enhances the hepatotoxic effect of isoniazid. Myelotoxic drugs increase the manifestations of hematotoxicity of the drug.

Gross formula

C 15 H 12 N 2 O

Pharmacological group of the substance Carbamazepine

Nosological classification (ICD-10)

CAS code

298-46-4

Characteristics of the substance Carbamazepine

White or almost white crystalline powder. Practically insoluble in water, soluble in ethanol and acetone. Molecular weight 236.27.

Pharmacology

pharmachologic effect- analgesic, antipsychotic, antiepileptic, anticonvulsant, normothymic, thymoleptic.

It blocks the sodium channels of the membranes of hyperactive nerve cells, reduces the effect of excitatory neurotransmitter amino acids (glutamate, aspartate), enhances inhibitory (GABAergic) processes and interaction with central adenosine receptors. Anti-manic properties are due to the inhibition of the metabolism of dopamine and norepinephrine. Anticonvulsant effect is manifested in partial and generalized seizures (grand mal). Effective (especially in children and adolescents) for the relief of symptoms of anxiety and depression, as well as reducing irritability and aggressiveness (epilepsy). Prevents attacks of trigeminal neuralgia, reduces the severity of clinical manifestations of alcohol withdrawal (including agitation, tremor, gait disturbances) and reduces convulsive activity. In diabetes insipidus, it reduces diuresis and thirst.

Absorbed in the gastrointestinal tract, albeit slowly, but almost completely; food does not affect the rate and extent of absorption. C max with a single dose of a conventional tablet is achieved after 12 hours. With a single or repeated administration of retard tablets, C max (25% less than after a conventional tablet) is noted within 24 hours. The retard form reduces daily fluctuations in plasma levels (determined after 1 -2 weeks) without changing the minimum value of the equilibrium concentration. Bioavailability when taking retard tablets is 15% lower than after using other dosage forms. Binding to blood proteins is 70-80%. In the cerebrospinal fluid and saliva, concentrations are created in proportion to the proportion of the active substance that is not bound to proteins (20-30%). Penetrates into breast milk (25-60% of plasma levels) and through the placental barrier. The apparent volume of distribution is 0.8-1.9 l / kg. It is biotransformed in the liver (mainly along the epoxide pathway) with the formation of several metabolites - the 10,11-trans-diol derivative and its conjugates with glucuronic acid, monohydroxylated derivatives, and N-glucuronides. T 1 / 2 - 25-65 hours, with prolonged use - 8-29 hours (due to the induction of metabolic enzymes); in patients taking inducers of the monooxygenase system (phenytoin, phenobarbital), T 1 / 2 is 8-10 hours. After a single oral dose of 400 mg, 72% of the dose taken is excreted by the kidneys and 28% through the intestines. In urine, 2% of unchanged carbamazepine, 1% of active (10,11-epoxy derivative) and about 30% of other metabolites are determined. In children, excretion is accelerated (higher doses may be required in terms of body weight). The onset of anticonvulsant action varies from several hours to several days (sometimes up to 1 month). Antineuralgic effect develops after 8-72 hours, anti-manic - after 7-10 days.

The use of the substance Carbamazepine

epilepsy (excluding petite mal), manic states, prevention of manic-depressive disorders, alcohol withdrawal, trigeminal and glossopharyngeal neuralgia, diabetic neuropathy.

Contraindications

Hypersensitivity (including to tricyclic antidepressants), AV blockade, myelosuppression or acute porphyria in history.

Use during pregnancy and lactation

Side effects of carbamazepine

Dizziness, agitation, hallucinations, depression, aggressive behavior, activation of psychosis, headache, diplopia, disturbances of accommodation, clouding of the lens, nystagmus, conjunctivitis, tinnitus, change in taste sensations, speech disorders (dysarthria, slurred speech), abnormal involuntary movements, peripheral neuritis, paresthesias, muscle weakness and symptoms of paresis, AV block, congestive heart failure, hyper- or hypotension, thromboembolism, renal dysfunction, interstitial nephritis, nausea, vomiting, elevated liver enzymes, jaundice, hepatitis, osteomalacia, sexual dysfunction , moderate leukopenia, thrombocytopenia, hematopoietic disorders, hyponatremia, delayed-type multiorgan hypersensitivity reactions, exfoliative dermatitis, lupus-like syndrome (skin rash, urticaria, hyperthermia, sore throat, joints, weakness), Stevens-Johnson syndrome, Lyell, anaphylactic reactions.

Interaction

Incompatible with MAO inhibitors. Increases the hepatotoxicity of isoniazid. Reduces the effects of anticoagulants, anticonvulsants (hydantoin derivatives or succinimides), barbiturates, clonazepam, primidone, valproic acid. Phenothiazines, pimozide, thioxanthenes increase CNS depression; cimetidine, clarithromycin, diltiazem, verapamil, erythromycin, propoxyphene reduce metabolism (the risk of toxic effects increases). Reduces the activity of corticosteroids, estrogens and estrogen-containing oral contraceptives, quinidine, cardiac glycosides (metabolism induction). Against the background of carbonic anhydrase inhibitors, the risk of osteogenesis disorders increases.

Overdose

Symptoms: disorientation, drowsiness, agitation, hallucinations and coma, blurred vision, dysarthria, nystagmus, ataxia, dyskinesia, hyper/hyporeflexia, convulsions, myoclonus, hypothermia; respiratory depression, pulmonary edema; tachycardia, hypo- / hypertension, cardiac arrest, accompanied by loss of consciousness; vomiting, decreased motility of the colon; fluid retention, oliguria or anuria, changes in laboratory parameters: hyponatremia, metabolic acidosis, hyperglycemia, increased muscle fraction of creatinine phosphokinase.

Treatment: induction of vomiting or gastric lavage, the appointment of activated charcoal and saline laxative, forced diuresis. To maintain airway patency - tracheal intubation, artificial respiration and (or) the use of oxygen. With hypotension or shock - plasma substitutes, dopamine or dobutamine, with the appearance of seizures - the introduction of benzodiazepines (diazepam) or other anticonvulsants (in children, respiratory depression may increase, with the development of hyponatremia - fluid restriction, careful intravenous infusion of isotonic sodium chloride solution. When severe poisoning is combined with renal insufficiency, renal dialysis is indicated.There is no specific antidote.It should be expected to re-increase the symptoms of an overdose on the 2nd and 3rd day after its onset, which is associated with slow absorption of the drug.

Routes of administration

inside.

Precautions Substance Carbamazepine

Before starting and during therapy, regular blood tests (cell elements) and urine, monitoring of liver function indicators are recommended. It is prescribed with caution in the presence of a history of diseases of the heart, liver or kidneys, with hematological disorders, increased intraocular pressure, latent psychosis, inadequate response to external stimuli, agitation, diseases characterized by convulsions of a mixed nature, in old age, drivers of vehicles and persons operating mechanisms. You should not suddenly stop treatment. Women are advised to supplement with folic acid (before or during pregnancy); in order to prevent increased bleeding in the last weeks of pregnancy and in newborns, vitamin K may be used.

Interactions with other active substances

Trade names

Name	The value of the Wyshkovsky Index ®
	0.2141