Carbamazepine

Carbamazepine is an anticonvulsant with psychotropic properties.

[1], [2], [3], [4], [5]

Indications Carbamazepine

Used for epilepsy:

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

It is also used in neuralgia affecting the 3-nerve in people with multiple sclerosis and idiopathic neuralgia of the neuralgia affecting the glossopharyngeal or the 3-nerve.

The drug is advised to use in combination with antipsychotics or lithium drugs for people with acute manic disorder. The drug can be administered in situations with neuropathy, which is diabetic in nature (with the presence of painful symptoms), alcohol withdrawal (severe convulsions, regular sleep disorders, marked hyper-excitability and anxiety), as well as with the central form of diabetes insipidus. , polyuria and polydipsia, having a neurohormonal origin.

Used for such violations:

• psychotic disorders (disorders with affective or schizoaffective character, psychosis, panic disorders and disorders in the work of the limbic structure);
• OCD;
• Kluvera-Bucy syndrome;
• senile dementia ;
• dysphoria, somatization, anxiety and depression;
• ear noise, chorea, phantom pain and multiple sclerosis;
• spinal marrow, 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;
• postherpetic neuralgia.

[6], [7], [8]

Release form

The release of the drug substance is made in tablet form - 10 pieces inside the cell packaging. In the box - 5 such packages.

Can also be produced in the amount of 50 tablets inside the container; 1 such container in a box.

[9], [10], [11],

Pharmacodynamics

The active drug element is dibenzazepine derivative. The drug has normtochemical, anti-manic, antidiuretic (in persons with non-sugar form of diabetes) and analgesic (in people with neuralgia) properties.

It acts by blocking the activity of potential-dependent Na channels, due to which there is a slowdown in the development of neural discharges and stabilization of neural walls. This weakens the conduction of impulses within synapses.

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

The drug helps reduce the amount of glutamate released and helps reduce the likelihood of an epilepsy attack. In the adolescent group (people with epilepsy), the use of the substance leads to the development of positive dynamics regarding the severity of anxiety and depression, and at the same time the feeling of irritability and aggression is weakened.

The effect on psychomotor data and cognitive activity depends on the size of the portion and has personal variations.

In people with neuralgia affecting the 3rd nerve (primary or secondary form), there is a decrease in the frequency of development of pain attacks.

In the case of paresthesias associated with injuries, postherpetic neuralgia and spinal marrow, the medication relieves neurogenic pain.

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

In diabetics, carbamazepine reduces diuresis and sensation of heat, and also quickly compensates for water balance.

Anti-maniacal (antipsychotic) influence develops after 7-10 days, due to the suppression of the metabolic processes of dopamine with norepinephrine.

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

[12], [13], [14], [15], [16],

Pharmacokinetics

Absorption.

Orally taken carbamazepine is absorbed almost fully, but rather slowly. With a single use of a simple tablet, plasma Cmax values are noted after 12 hours. With 1-time use of a pill with a volume of 0.4 g of carbamazepine, the average level Cmax of the unchanged active ingredient is approximately 4.5 μg / ml.

Food intake does not have a noticeable effect on the degree and rate of absorption of the drug component.

Distribution processes.

After complete absorption of carbamazepine, the values of the apparent distribution volume are in the range of 0.8-1.9 l / kg. The substance may cross the placenta barrier.

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

Exchange processes.

The exchange processes of carbamazepine are performed inside the liver (mainly by the epoxy method), forming the main metabolic components — a derivative of the type of 10,11-transdiol and its conjugate together with glucuronic acid. The main isoenzyme, which converts the active element of the drug to epoxy carbamazepine-10,11, which is a hemoprotein of the type P450 ZA4. Exchange processes also lead to the formation of a “small” metabolic substance - 9-hydroxy-methyl-10-carbamoyl acridane.

With 1-time oral use of drugs, approximately 30% of its main component is found inside the urine under the guise of finite elements of epoxy exchange. Other important ways of drug conversion form various derivatives of the monohydroxylate subtype, and with it the N-glucuronide of the active element, arising with the help of the UGT2B7 component.

Excretion.

With 1-fold oral use of the drug, the half-life of the unchanged active component reaches 36 hours on average, and when reapplied it is approximately 16-24 hours (due to autoinduction of the hepatic monooxygenase system), taking into account the duration of therapy.

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

[17], [18], [19], [20], [21],

Dosing and administration

The medication is taken orally, washed down with ordinary water.

In the case of epilepsy, the drug is recommended as a monotherapy. The course itself begins with small portions, followed by their gradual increase - this allows you to get the optimal effect. Adult initial portion is 0.1-0.2 g, 1-2 times per day.

For neuralgia affecting the 3rd nerve, on the first day of treatment 0.2-0.4 g of the substance is taken. Further, the dosage is gradually increased to 0.4-0.8 g per day. Cancellation of the application should also be carried out gradually.

In the case of a neurogenic etiology of pain syndrome, you must first take 0.1 g of drug 2 times a day, increasing the dosage at 12-hour intervals until the pain subsides. The size of the maintenance portion is 0.2-1.2 g per day (use for several uses).

The size of the average portion with alcohol withdrawal is 0.2 g 3 times a day. In the case of a serious violation, you need to increase the daily dosage to 0.4 g 3 times per day.

During the first days of treatment, you should additionally use colmetiazole, chlordiazepoxide and other sedative-hypnotic drugs.

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

Persons with diabetic neuropathy, accompanied by pain, should take 0.2 g of the drug 2-4 times per day.

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

The size of the daily portion with BAR and manic states is 0.4-1.6 g.

[26], [27], [28]

Use Carbamazepine during pregnancy

In animal tests, oral administration of drugs led to the appearance of defects.

In infants of women suffering from epilepsy, there is a tendency to the appearance of disorders in fetal development, including congenital anomalies. There are reports that carbamazepine (typical of most anticonvulsants) increases the incidence of these disorders, but there is no convincing data from controlled trials of monotherapy with drug intake.

At the same time, there is information about the occurrence of disorders associated with the use of the drug in fetal growth and congenital anomalies - among them the vertebral fissure, all sorts of defects affecting the maxillofacial area, cardiovascular anomalies or hypospadias with maturation defects affecting various structures of the body.

It is necessary to take into account such warnings:

• use of medication for the treatment of epilepsy during pregnancy must be extremely cautious;
• at the stage of pregnancy or during conception, which occurred during the use of the drug, or during its planning, 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 during the 1st trimester);
• women of child-bearing age require, if possible, the use of medication in the form of monotherapy;
• minimum effective portions are required and plasma values of carbamazepine are monitored;
• the patient should be notified that the risk of an innate abnormality in the infant increases. In addition, it is necessary to provide her with the ability to perform antenatal screening;
• It is impossible to stop effective antiepileptic treatment during pregnancy, because due to exacerbation of the disease there may be a threat to the health of the woman and fetus.

It was determined that during pregnancy there may be a deficiency of folic acid, which sometimes increases under the influence of anticonvulsants. Because of this, before pregnancy and during its course, it is necessary to additionally prescribe the patient receiving folic acid.

There is information about cases of seizures or suppression of the respiratory process in newborns; There is also evidence of diarrhea, vomiting, or poor appetite in newborns, which may be associated with the use of carbamazepine and other anticonvulsants.

Carbamazepine is able to stand out with breast milk (25-60% of the plasma indicator). Before you start using the drug, you need to carefully evaluate all the risks and benefits of simultaneous breastfeeding. It is allowed to continue it during therapy only on condition that the infant constantly monitors the possible appearance of negative symptoms (for example, too much drowsiness or signs of allergy to the epidermis).

Contraindications

Main contraindications:

• AV blockade;
• acute stage of porphyria moving type;
• circulatory disorders within the bone marrow (anemia or leukopenia);
• the presence of hypersensitivity in relation to the active component of drugs or tricyclics.

Carefully and with the assessment of all probable risks, they are used for some disorders:

• active form of alcoholism;
• CHF decompensated type;
• adrenal insufficiency;
• hypothyroidism;
• Skien syndrome;
• syndrome of increased secretion of the ADH element;
• dilutional hyponatremia;
• suppression of blood-forming processes within the bone marrow;
• increased IOP;
• prostatic hyperplasia;
• kidney related diseases.

[22], [23], [24]

Side effects Carbamazepine

The severity of the negative effect depends on the portion size. Among the side effects:

• NA lesions: asthenia, accommodative paresis, ataxia, severe dizziness, or severe headaches. Occasionally, abnormal movements appear that carry an involuntary form (pronounced tremor, strong tics or the occurrence of dystonia), nystagmus, choreoathetoid disturbances, paresthesias and speech disorders, and with it the peripheral form of neuritis, myasthenia, eye movements, signs of paresis and dysplasia, as an organism.
• mental impairment: disorientation, anxiety or noticeable excitement, activation of existing psychosis, depression, aggressive behavior, loss of appetite and pronounced hallucinations (having an auditory or visual form);
• signs of allergy: erythroderma, photoallergy, pruritus, PET, urticaria or SSD;
• disorders of hematopoietic processes: leukocytosis, anemia, which has a hemolytic or aplastic form, lymphadenopathy, and in addition reticulocytosis and thrombocytopenia;
• problems with digestive function: stomatitis, pancreatitis or glossitis, disorders of the chair and pain in the epigastric zone, as well as jaundice, liver failure, hepatitis granulomatous nature and an increase in the level of hepatic enzymes;
• disorders of the work of the cardiovascular system: aggravation of the course of CHF, AV blockade, accompanied by fainting, exacerbation of IHD, instability of blood pressure values, bradycardia, thrombophlebitis, arrhythmia, intracardiac conduction disorder and thromboembolic syndrome;
• problems with endocrine function and metabolism: hyponatremia, edema, hyperprolactinemia, decrease in L-thyroxine, hypercholesterolemia, fluid retention inside the body, weight gain and osteomalacia;
• lesions of the urogenital system: disorders of renal function, impairment of potency, increased urination, hematuria or albuminuria, as well as tubulo-interstitial nephritis and oliguria;
• ODA disorders: arthralgia, convulsions, or myalgia;
• disorders of the sensory organs: hyper- or hypoacusia, conjunctivitis, ear noise, impaired perception of audible sound height, auditory or gustatory disorders, and clouding of the eye lens;
• others: acne, hirsutism, hyperhidrosis, epidermal pigmentation disorder, alopecia and purpura.

[25]

Overdose

In case of poisoning, there are dysfunctions of the NA, cardiovascular system and respiratory system.

NA and the senses: a feeling of strong excitement, disorientation or drowsiness, dysarthria, nystagmus, convulsions, syncope, myoclonus, and besides hyporeflexia, mydriasis, hallucinations, visual disturbance and hypothermia.

CCC: conduction disorder inside the ventricles, cardiac arrest, instability of blood pressure values and tachycardia.

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

The drug does not have an antidote. Symptomatic interventions are carried out.

[29], [30], [31], [32], [33], [34], [35], [36],

Interactions with other drugs

The exchange processes of carbamazepine occur with the participation of hemoprotein CYP3A4. The 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 speed of metabolic processes and reduce blood parameters of the drug, which weakens the severity of its drug effects.

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

Cisplatin, metsuksimid and phenobarbital with theophylline, and besides rifampicin, primidone with Fensuxidom, valpromid with phenytoin, doxorubicin with valproic acid and clonazepam are also able to increase the blood level of carbamazepine.

[37], [38], [39], [40], [41]

Storage conditions

Carbamazepine is required to be stored in a dark, dry place for small children. Temperatures - no higher than 25 ° C.

[42],

Shelf life

Carbamazepine can be used within a 36-month period from the time the therapeutic agent is manufactured.

[43]

Application for children

For children (taking into account the accelerated elimination of the substance), it may be necessary to assign higher portions of Carbamazepine (the calculation is carried out in proportions of mg / kg) than an adult.

Prescribe medication can children older than 5 years of age.

[44], [45], [46], [47],

Analogs

Analogues of the medication are substances Finlepsin, Septol and Tegretol with Carbalex, as well as Mezacar and Carbapin with Timonil.

[48], [49], [50], [51], [52]