Carbamazepine

Carbamazepine is an anticonvulsant with psychotropic properties.

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Indications Carbamazepine

Used for epilepsy:

• seizures of mixed type;
• seizures of a generalized nature, against the background of which tonic-clonic convulsions are observed;
• partial types of seizures.

It is also used for neuralgia affecting the trigeminal nerve in people with multiple sclerosis, and for idiopathic neuralgia affecting the glossopharyngeal or trigeminal nerve.

The drug is recommended to be used in combination with antipsychotics or lithium agents for people with acute manic disorder. The drug can be administered in situations with neuropathy of a diabetic nature (with the presence of pain symptoms), alcohol withdrawal (pronounced convulsions, regular sleep disorders, noticeable hyperexcitability and anxiety), affective disorders occurring in phases, and also in the central form of diabetes insipidus, polyuria and polydipsia of neurohormonal origin.

It is also used for the following disorders:

• psychotic disorders (disorders of an affective or schizoaffective nature, psychoses, panic disorders and disorders in the functioning of the limbic structure);
• OCD;
• Kluver-Bucy syndrome;
• senile dementia;
• dysphoria, somatization, anxiety and depression;
• tinnitus, chorea, phantom pain and multiple sclerosis;
• tabes dorsalis, an idiopathic form of neuritis in the acute stage;
• diabetic polyneuropathy;
• facial hemispasm;
• Willis disease;
• neuropathy or neuralgia of post-traumatic etiology;
• prevention of migraine development;
• neuralgia of a postherpetic nature.

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Release form

The medicinal substance is released in tablet form - 10 pieces inside a cellular package. There are 5 such packages in a box.

It can also be produced in the quantity of 50 tablets in a container; 1 such container in a box.

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Pharmacodynamics

The active ingredient of the drug is a derivative of dibenzazepine. The drug has normothymic, antimanic, antidiuretic (in people with diabetes insipidus) and analgesic (in people with neuralgia) properties.

It acts by blocking the activity of potential-dependent Na channels, which slows down the development of neuronal discharges and stabilizes neuronal walls. This weakens the conduction of impulses within synapses.

Carbamazepine prevents the re-formation of Na-dependent influence potentials within the structure of neurons of a depolarized nature.

The drug helps reduce the volume of released glutamate and helps reduce the likelihood of an epileptic seizure. In children and adolescents (people with epilepsy), the use of the substance leads to the development of positive dynamics regarding the degree of expression of anxiety and depression, and at the same time, the feeling of irritability and aggression is weakened.

The effects on psychomotor performance and cognitive function are portion size dependent and have individual variations.

People with neuralgia affecting the trigeminal nerve (either primary or secondary) experience a decrease in the frequency of pain attacks.

In cases of paresthesia associated with trauma, postherpetic neuralgia and tabes dorsalis, the drug relieves neurogenic pain.

In individuals with alcohol withdrawal, the drug reduces the severity of the main manifestations of the disorder (increased excitability, severe tremor affecting the limbs, and gait disturbances) and increases the seizure threshold.

In diabetics, Carbamazepine reduces diuresis and the feeling of heat, and also quickly compensates for water balance indicators.

The antimanic (antipsychotic) effect develops after 7-10 days, due to the suppression of metabolic processes between dopamine and norepinephrine.

The use of drugs in prolonged forms leads to the achievement of stable blood levels of its active ingredient.

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Pharmacokinetics

Absorption.

Orally administered carbamazepine is absorbed almost completely, but rather slowly. With a single use of a simple tablet, plasma Cmax values are noted after 12 hours. With a single use of a tablet of 0.4 g of carbamazepine, the average Cmax level of the unchanged active ingredient is approximately 4.5 mcg/ml.

Food intake has no significant effect on the extent and rate of absorption of the medicinal component.

Distribution processes.

After complete absorption of carbamazepine, the apparent distribution volume values are within the range of 0.8-1.9 l/kg. The substance can overcome the placental barrier.

Intraplasmic protein synthesis of the drug is 70-80%. The unchanged component in saliva and cerebrospinal fluid is proportional to the part of the active element not synthesized with protein (20-30%). The drug level in breast milk is 25-60% of its plasma values.

Exchange processes.

Metabolic processes of carbamazepine are carried out inside the liver (mainly by the epoxide method), forming the main metabolic components - a derivative of the 10,11-transdiol type and its conjugate together with glucuronic acid. The main isoenzyme, which ensures the transformation of the active element of the drug into epoxy carbamazepine-10,11, which is a hemoprotein of the P450 3A4 type. Metabolic processes also lead to the formation of a "small" metabolic substance - 9-hydroxy-methyl-10-carbamoyl acridan.

With a single oral use of the drug, approximately 30% of its main component is found in the urine as end elements of epoxide exchange. Other important ways of transforming the drug form various derivatives of the monohydroxylate subtype, and along with this, N-glucuronide of the active element, which occurs with the help of the UGT2B7 component.

Excretion.

With a single oral administration of the drug, the half-life of the unchanged active component reaches an average of 36 hours, and with repeated use it is approximately 16-24 hours (due to autoinduction of the hepatic monooxygenase system), taking into account the duration of the therapy.

In people using Carbamazepine together with other drugs that induce the same liver enzyme structure (for example, phenobarbital or phenytoin), its half-life is on average close to 9-10 hours.

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Dosing and administration

The medicine is taken orally with plain water.

In case of epilepsy, the medication is recommended to be used as monotherapy. The course itself begins with small portions, with their subsequent gradual increase - this allows you to get the optimal effect. The adult initial portion is 0.1-0.2 g, 1-2 times a day.

For neuralgia affecting the trigeminal nerve, 0.2-0.4 g of the substance is taken on the first day of treatment. Then the dosage is gradually increased to 0.4-0.8 g per day. The use should also be discontinued gradually.

In case of pain syndrome of neurogenic etiology, it is necessary to take 0.1 g of the drug 2 times a day at first, increasing the dosage at 12-hour intervals until the pain subsides. The size of the maintenance dose is 0.2-1.2 g per day (to be used in several doses).

The average serving size for alcohol withdrawal is 0.2 g 3 times a day. In case of severe disorder, the daily dosage should be increased to 0.4 g 3 times a day.

During the first days of treatment, colmethiazole, chlordiazepoxide and other sedative-hypnotics should be used additionally.

In case of diabetes insipidus, 0.2 g of the substance is consumed 2-3 times per day.

People with diabetic neuropathy accompanied by pain syndrome should take 0.2 g of the drug 2-4 times a day.

To prevent the development of psychoses of an affective or schizoaffective nature, 0.6 g of the substance is taken 3-4 times per day.

The daily portion size for bipolar disorder and manic states is 0.4-1.6 g.

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Use Carbamazepine during pregnancy

In animal tests, oral administration of the drug resulted in defects.

Infants of women with epilepsy are prone to developing intrauterine developmental disorders, including congenital anomalies. There are reports that carbamazepine (typical of most anticonvulsants) increases the incidence of such disorders, but there is no convincing data from controlled trials of monotherapy with the drug.

At the same time, there is information about the occurrence of drug-related disorders in intrauterine growth and congenital anomalies - among them the spinal cleft, all kinds of defects affecting the maxillofacial area, cardiovascular anomalies or hypospadias with malformations in maturation, affecting various structures of the body.

The following caveats should also be taken into account:

• medication for the treatment of epilepsy should be used with extreme caution during pregnancy;
• during pregnancy or during conception that occurred during the use of the drug, or when planning it, in case of the need to use the drug Carbamazepine, it is necessary to carefully evaluate all the risks and benefits of its use (especially in the 1st trimester);
• Women of childbearing age should, if possible, use the drug in monotherapy form;
• it is necessary to use the minimum effective doses and monitor plasma carbamazepine values;
• The patient should be informed that the risk of congenital anomalies in the infant is increased and should be provided with the opportunity to undergo antenatal screening;
• It is impossible to stop effective antiepileptic treatment during pregnancy, because an exacerbation of the disease may pose a threat to the health of the woman herself and the fetus.

It has been determined that folic acid deficiency may occur during pregnancy, which is sometimes increased by anticonvulsants. Because of this, it is necessary to additionally prescribe folic acid to the patient before and during pregnancy.

There are reports of cases of seizures or respiratory depression in neonates; there are also reports of diarrhea, vomiting, or poor feeding in neonates, which may be associated with the use of carbamazepine and other anticonvulsants.

Carbamazepine can be excreted in breast milk (25-60% of the plasma level). Before starting to use the drug, it is necessary to carefully evaluate all the risks and benefits of simultaneous breastfeeding. It is allowed to continue during therapy only on condition that the baby is constantly monitored for possible negative symptoms (for example, excessive drowsiness or signs of allergy on the epidermis).

Contraindications

Main contraindications:

• AV block;
• acute stage of porphyria of the mobile type;
• circulatory disorders within the bone marrow (anemia or leukopenia);
• the presence of hypersensitivity to the active component of the drug or tricyclics.

Use with caution and with an assessment of all possible risks in some disorders:

• active form of alcoholism;
• CHF decompensated type;
• adrenal cortex insufficiency;
• hypothyroidism;
• Sheehan syndrome;
• syndrome of increased secretion of the element ADH;
• dilutional hyponatremia;
• suppression of hematopoietic processes within the bone marrow;
• increased IOP levels;
• prostate hyperplasia;
• kidney related diseases.

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Side effects Carbamazepine

The severity of the negative impact depends on the portion size. Side effects include:

• lesions of the nervous system: asthenia, accommodative paresis, ataxia, severe dizziness or severe headaches. Rarely, abnormal movements of an involuntary nature (pronounced tremor, severe tics or the development of dystonia), nystagmus, choreoathetoid disorders, paresthesia and speech disorders appear, as well as peripheral neuritis, myasthenia, oculomotor disorders, signs of paresis and dyskinesia of an orofacial nature;
• mental disorders: disorientation, feeling of anxiety or noticeable agitation, activation of existing psychosis, depressive state, aggressive behavior, loss of appetite and pronounced hallucinations (auditory or visual);
• signs of allergy: erythroderma, photoallergy, itching, TEN, urticaria or SJS;
• disorders of hematopoietic processes: leukocytosis, anemia, which has a hemolytic or aplastic form, lymphadenopathy, and also reticulocytosis and thrombocytopenia;
• problems with digestive function: stomatitis, pancreatitis or glossitis, bowel disorders and pain in the epigastric region, as well as jaundice, liver failure, granulomatous hepatitis and increased levels of liver enzymes;
• disorders of the cardiovascular system: worsening of CHF, AV block accompanied by fainting, exacerbation of coronary heart disease, instability of blood pressure values, bradycardia, thrombophlebitis, arrhythmia, intracardiac conduction disorder and thromboembolic syndrome;
• problems with endocrine function and metabolism: hyponatremia, edema, hyperprolactinemia, decreased L-thyroxine levels, hypercholesterolemia, fluid retention in the body, weight gain and osteomalacia;
• lesions of the urogenital system: renal dysfunction, decreased potency, increased frequency of urination, hematuria or albuminuria, as well as tubulointerstitial nephritis and oliguria;
• disorders of the musculoskeletal system: arthralgia, cramps or myalgia;
• disorders of the sensory organs: hyper- or hypoacusis, conjunctivitis, tinnitus, impaired perception of audible pitch, hearing or taste disorders, and clouding of the lens of the eye;
• Others: acne, hirsutism, hyperhidrosis, epidermal pigmentation disorder, alopecia and purpura.

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Overdose

In case of poisoning, dysfunctions of the nervous system, cardiovascular system and respiratory system occur.

NS and sensory organs: feeling of intense excitement, disorientation or drowsiness, dysarthria, nystagmus, seizures, syncope, myoclonus, as well as hyporeflexia, mydriasis, hallucinations, visual disturbances and hypothermia.

CVS: conduction disturbances within the ventricles, cardiac arrest, instability of blood pressure values and tachycardia.

In addition, there is respiratory depression, weakening of colon motility, fluid retention or removal of food from the stomach; pulmonary edema, anuria, hyperglycemia, vomiting, hyponatremia, oliguria, nausea and metabolic acidosis develop.

The drug has no antidote. Symptomatic measures are taken.

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Interactions with other drugs

Metabolic processes of Carbamazepine occur with the participation of the hemoprotein CYP3A4. Combination with substances that slow down the activity of this hemoprotein leads to an increase in its values and the severity of negative symptoms. Substances that induce hemoprotein increase the rate of metabolic processes and reduce blood indicators of the drug, which weakens the severity of its medicinal effect.

Blood values of the drug increase when combined with such drugs: cimetidine and terfenadine with nicotinamide, felodipine with verapamil, fluvoxamine with danazol, and also fluoxetine with diltiazem and viloxazine. This list also includes desipramine, ritonavir with acetazolamide, isoniazid with propoxyphene and loratadine, and also azoles (such as itraconazole with fluconazole and ketoconazole) and macrolides (erythromycin with clarithromycin and troleandomycin with josamycin).

Cisplatin, methsuximide and phenobarbital with theophylline, as well as rifampicin, primidone with phensuximide, valpromide with phenytoin, doxorubicin with valproic acid and clonazepam can also increase blood levels of Carbamazepine.

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Storage conditions

Carbamazepine should be stored in a dark, dry place, out of the reach of small children. Temperature indicators should not exceed 25°C.

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Shelf life

Carbamazepine can be used within a 36-month period from the date of manufacture of the therapeutic agent.

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Application for children

For children (taking into account the accelerated elimination of the substance), it may be necessary to prescribe higher doses of Carbamazepine (calculated in mg/kg proportions) than for an adult.

The medication can be prescribed to children over 5 years of age.

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Analogues

The analogs of the drug are the substances Finlepsin, Zeptol and Tegretol with Carbalex, as well as Mezakar and Carbapine with Timonil.

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