Mezakar

Mezacar is an anticonvulsant medication.

Indications Mezakara

It is used in such conditions:

• epilepsy ;
• bouts of seizures of a partial nature, having a simple or complex variety (with or without a concomitant loss of consciousness; with the development of generalization symptoms with or without a secondary character);
• seizures of mixed character;
• convulsions of tonic-clonic nature (generalized form);
• manic behavior of an acute nature;
• alcohol withdrawal;
• BAR (as a supporting agent) - to reduce the severity of clinical symptoms during exacerbations, and also to prevent them;
• neuralgia affecting the 3nich nerve (idiopathic), and neuralgia in the region of the 3-nerve, developing on the background of sclerosis, which has a diffuse character;
• neuralgia affecting the nerve located in the glossopharyngeal zone (idiopathic form).

Release form

The release of the pharmaceutical agent is produced in tablets - 10 pieces inside the cell plate. In a pack - 5 such records.

Pharmacodynamics

Possesses anti-mania and normo-chemical (stabilizes mood) activity.

The active element activates the slowing GABAergic brain system. At the same time, it blocks the activity of potential-dependent Na channels (inside the membranes of nerve cells), due to which their work is stabilized. In addition, it weakens the effect of neurotransmitter acids (glutamate with aspartate) and interacts with adenosine endings inside the brain.

Increases the convulsive threshold, and also corrects personal changes associated with epilepsy.

Pharmacokinetics

Absorption.

Orally taken carbamazepine is absorbed almost fully, although not at a very high speed. With 1 drug use, plasma Cmax values are recorded after 12 hours. There are no clinically significant differences in the level of absorption of drugs when using its different oral forms. At 1-fold oral administration of a tablet with a volume of 0.4 g of carbamazepine, the average Cmax of the unchanged active ingredient is approximately 4.5 μg / ml.

The consumption of food does not have a significant impact on the degree and rate of absorption of carbamazepine.

Equilibrium plasma parameters of drugs are observed after 7-14 days, taking into account the personal characteristics of metabolic processes (carbamazepine autoinduction of enzyme hepatic systems or heteroinduction with other medicines used in combination), and in addition to this patient's condition, duration of therapy and dosage size.

There are significant interpersonal differences in the equilibrium indices in the drug spectrum: in many patients they vary from 4 to 12 μg / ml (range 17-50 μmol / l). The level of carbamazepine 10,11-epoxide (drug active metabolic product) reaches almost 30% compared with the values of carbamazepine.

Distribution processes.

After complete absorption of the therapeutic component, the apparent distribution volume is in the range of 0.8-1.9 l / kg.

The substance may cross the placenta. Its synthesis with intraplasma blood protein is 70-80%. The level of the unchanged element inside the saliva with CSF is proportional to the part of the active component that is not synthesized with proteins (20-30%).

Indicators of carbamazepine inside breast milk are equal to 25-60% of the values inside the blood plasma.

Exchange processes.

The metabolism of carbamazepine is produced inside the liver, mainly through the epoxy pathway. In this case, the main metabolic products are formed - 10,11-transdiol derivative, and in addition, its conjugate together with glucuronic acid.

The main isoenzyme that converts the active drug element to the carbamazepine 10,11-epoxide is the hemoprotein of the subtype P450 ZA4. With such exchange reactions, a “small” element of metabolism is formed - 9-hydroxy-methyl-10-carbamoyl acridane.

With 1-time oral use, approximately 30% of the active ingredient is recorded inside the urine (final epoxy metabolic products). Other important pathways for the conversion of carbamazepine cause the formation of a variety of monohydroxylate derivatives, and with it the carbamazepine N-glucuronide, which is formed with the help of the UGT2B7 component.

Excretion.

After 1-fold oral administration of drugs, the half-life of an unchanged element is on average 36 hours, and when it is re-taken the average is 16-24 hours (after autoinduction of the monooxygenase hepatic system), taking into account the duration of the therapeutic cycle.

For individuals who also use other drugs that induce a similar enzyme hepatic system (for example, phenobarbital or phenytoin), the average half-life of a substance is 9-10 hours.

The plasma half-life of the metabolic product 10,11-epoxide is approximately 6 hours (with 1-fold use of epoxide).

After 1-fold use of carbamazepine in a portion of 0.4 g, 72% of the component is excreted in the urine, and 28% in the feces. About 2% of the dosage leaves the body through the urine in an unchanged state and about 1% in the form of the therapeutically active metabolic element 10,11-epoxide.

Dosing and administration

The drug is used orally, without reference to food intake. Selected daily portion should be divided into 2-3 uses. The size of the dosage is determined based on the diagnosis.

Sizes of standard adult servings: 0.1-0.2 g 1-2 times per day; it is necessary to increase the dosage slowly until the desired result is obtained. Thus, the patient can take 0.8–2 g of the substance per day.

Sizes of standard children's dosages: 0.1 g per day; a gradual increase in servings is performed weekly (by 0.1 g). The usual portion is 10-20 mg / kg per day (in several uses).

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Use Mezakara during pregnancy

It is impossible to appoint Mezakar if the woman is pregnant or nursing.

Contraindications

The main contraindications:

• severe intolerance associated with medication elements;
• history of allergy to tricyclics;
• AV blockade;
• suppression of bone marrow activity;
• hepatic type of porphyria (it can be a mixed, acute intermittent or late epidermal subtype), as well as its history;
• use of drugs MAOI.

Side effects Mezakara

Among the side effects:

• changes in test readings: lymphadenopathy, reticulocytosis, leuko-, pancyto- or thrombocytopenia, agranulocytosis with leukocytosis and eosinophilia, and in addition, aplastic, hemolytic or megaloblastic form of anemia, porphyria, erythrocytic aplasia, and deficiencies;
• immune disorders: delayed intolerance, epidermal rash, lymphadenopathy or vasculitis, and in addition hepatosplenomegaly, aseptic type of meningitis, which is complemented by the development of myoclonus or peripheral eosinophilia, and bile duct disappearance syndrome. Anaphylaxis, angioedema, or hypogammaglobulinemia may also occur;
• endocrine disorders: weight gain, hyponatremia, puffiness, reduction of plasma osmolarity, hyperhidria (vomiting, confusion, lethargy and headaches) and an increase in prolactin values (gynecomastia, galactorrhea and bone metabolism);
• metabolic disorders: folate deficiency and loss of appetite;
• mental problems: feelings of excitement, anxiety, confusion or aggressiveness, hallucinations, activation of the state of psychosis and depression;
• neurological signs: ataxia, dizziness, drowsiness, cephalalgia and diplopia, as well as visual impairment and movements that are involuntary (dystonia, tremor (sometimes fluttering) and tic). In addition, the orofacial variety of dyskinesia, polyneuropathy, dysarthria and nystagmus, choreoathetosis, eye movement disorders, slurred speech, taste disorder, paresthesia, muscle weakness, aseptic meningitis and paresis;
• visual impairment: glaucoma, conjunctivitis, accommodative disorder and opacification of the eye lens;
• hearing problems: ear ringing, hearing loss and an increase or decrease in hearing sensitivity;
• cardiovascular problems: conduction disorders within the heart, congestive heart failure, elevated or decreased values of blood pressure, syncope and thromboembolism, and in addition bradycardia, exacerbation of the course of coronary artery disease, thrombophlebitis, arrhythmia and circulatory collapse;
• respiratory disorders: pneumonitis, dyspnea, or pneumonia;
• digestive disorders: obstructive or diarrhea, nausea, glossitis, dry oral mucosa, abdominal pain and stomatitis. In addition, pancreatitis, hepatitis, liver failure, an increase in GGT, transaminase and alkaline phosphatase, jaundice, biliary tract syndrome, and granulomatous hepatitis;
• epidermal lesions: erythroderma, SLE, pruritus, allergic dermatitis, SSD, urticaria, photosensitization and epidermal necrolysis. In addition, polyformal or nodular erythema, acne and purpura, hirsutism, severe alopecia, hyperhidrosis and skin pigmentation disorder;
• ODA disorders: arthralgia, muscle weakness and muscle spasms;
• urogenital problems: tubulointerstitial nephritis, urinary retention, impotence, insufficiency of kidney function, disorders of spermatogenesis, renal dysfunctions (albuminuria with hematuria, azotemia or oliguria), and increased urination;
• systemic disorders: feeling of weakness.

Overdose

Signs of poisoning are: drowsiness, agitation or disorientation, deterioration of consciousness, visual misting, nystagmus, ataxia and hallucinations. In addition, slurred speech, coma, hypo- or hyperreflexia, dysarthria, convulsions and dyskinesia, as well as mydriasis, psychomotor disturbances, hypothermia, myoclonus and pulmonary edema. Along with this, it is possible to suppress respiration, cardiac arrest, impaired cardiac conduction function, tachycardia, fainting, a decrease or increase in blood pressure, hyperhidria, and rhabdomyolysis. There may be a metabolic type of acidosis, delayed eating inside the stomach, anuria or oliguria, fluid or urine retention, increased CPK values (muscle fraction), hyperglycemia, or hyponatremia.

Persons with such disorders need to be hospitalized, gastric lavage should be performed, sorbents should be prescribed and supportive measures should be carried out. It is also necessary to determine the blood values of carbamazepine, monitor the heart and correct electrolyte abnormalities.

Interactions with other drugs

Medications that have the ability to increase the carbamazepine values inside the blood plasma.

Because with an increase in the above indicators, negative symptoms may develop (for example, drowsiness, and besides diplopia, severe dizziness or ataxia), the portion size of the Mezacar should be changed or its plasma values should be monitored when combined with similar substances. Among these medications are:

• anti-inflammatory and analgesic drugs: ibuprofen or dextropropoxyphene;
• androgens: substance danazol;
• antibiotics: macrolides (for example, yosamycin with erythromycin, ciprofloxacin and troleandomycin with clarithromycin);
• antidepressants: fluoxetine, viloxazine, desipramine with trazodone, nefazodone with fluvoxamine and paroxetine;
• anticonvulsants: vigabatrina and stiripentol;
• antimycotics: azoles (for example, ketoconazole with itraconazole and voriconazole with fluconazole). Alternative anticonvulsants may be prescribed to individuals who use itraconazole or voriconazole;
• antihistamine substances: terfenadine or loratadine;
• antipsychotics: loxapine with olanzapine and quetiapine;
• TB drugs: isoniazid;
• agents that slow down the activity of carbonic anhydrase: acetazolamide component;
• antiviral drugs: substances that slow down HIV protease (for example, ritonavir);
• medications for the treatment of cardiovascular disease: verapamil with diltiazem;
• agents used in diseases of the gastrointestinal tract: omeprazole or cimetidine;
• muscle relaxants: dantrolene with oxybutinin;
• anti-agent drugs: ticlopidine;
• other means: this includes grapefruit juice, and besides this nicotinamide (for adults and only in large portions).

Substances with the ability to increase intraplasma values of the active carbamazepine metabolic product - 10,11-epoxide.

Among these drugs are prohabid, loxapine, valpromid with quetiapine, and with this, valproic acid with primidone and valnoctamide. The dosage portion of the drug with a single use with these substances should be adjusted (or you need to monitor its plasma values).

Medications that reduce intraplasma carbamazepine values.

Changing the dosage of the drug may be needed when combined with the following substances:

• anticonvulsants: metsuksimid, fensuksimid and felbamate with phenobarbital and oxcarbazepine, as well as phenytoin (to prevent phenytoin poisoning and submedicamentotic values of carbamazepine, it is necessary to change the plasma level of the first to 13 mcg / ml before using the carbamazepine, to use the current figure, I will not have 4, I already be 5), I will not have 4. (information about it is contradictory);
• anticancer drugs: doxorubicin or cisplatin;
• anti-tuberculosis drugs: rifampicin;
• Anti-asthma substances or bronchodilators: aminophylline or theophylline;
• dermatological agents: isotretinoin.

Interaction with other drugs.

Mefloquine can lead to the development of antagonistic effects regarding the anticonvulsant action of Mezacar, so the dosage of the latter must be changed accordingly.

Isotrenoin is known to alter the bioavailability indicators or the clearance of carbamazepine with its metabolic product, which is why during therapy it is necessary to monitor the plasma values of carbamazepine.

The effect of the drug on the plasma values of the substances combined with it.

Carbamazepine is able to reduce the plasma performance of individual drugs, as well as to weaken or level their therapeutic activity. Considering the clinical data, a dosage change of the following medications may be required:

• anti-inflammatory or analgesic substances: methadone with buprenorphine and paracetamol (long-term administration of carbamazepine together with paracetamol (or acetaminophen) can provoke hepatotoxicity), and with that tramadol with phenazone (antipyrine);
• antibiotics: among these are rifabutin or doxycycline;
• anticoagulants taken orally: for example, fenprocumone, acenocoumarol with warfarin, and dicoumarol;
• antidepressants: this includes nefazodone with bupropion, trazodone with sertraline, citalopram, and tricyclics (for example, amitriptyline with imipramine, clomipramine, and nortriptyline);
• antiemetic medicine: aperitant;
• anticonvulsants: clonazepam, tiagabine, clobazam with felbamate, valproic acid, ethosuccimide with primidone, and also lamotrigine, zonisamide, oxcarbazepine and topiramate. There is information about the increase in plasma values of phenytoin under the influence of carbamazepine, and about their decrease, as well as (single) about the increase in plasma parameters of mephenytoin;
• antimycotics: voriconazole with itraconazole and ketoconazole. People who use itraconazole or voriconazole should use alternative anticonvulsants;
• anthelmintic substances: albendazole or praziquantel;
• anticancer drugs: cyclophosphamide with imatinib, as well as temsirolimus and lapatinib;
• neuroleptics: haloperidol with aripiprazole, clozapine with risperidone, and in addition bromperidol with ziprasidone and olanzapine, as well as quetiapine and paliperidone;
• antiviral drugs: drugs that slow down HIV protease activity (for example, saquinavir with indinavir and ritonavir);
• anxiolytics: midazolam with alprazolam;
• antiasthmatic substances and bronchodilators: theophylline;
• contraceptives: hormonal contraception (it is necessary to consider the option with the selection of alternative contraceptives);
• substances for treating cardiovascular diseases: Ca channel blockers (a category of dihydropyridine), among which are digoxin with lovastatin, felodipine, simvastatin, cerivastatin with quinidine, and in addition, ivabradine with propranolol and atorvastatin;
• corticosteroids: dexamethasone or prednisone;
• substances used for impotence: tadalafil;
• immunosuppressant drugs: tacrolimus with cyclosporine and sirolimus with everolimus;
• thyroid drugs: levothyroxine;
• other substances: drugs that contain progesterone or estrogen (alternative contraception must be selected), sertraline with buprenofinom, mianserin and gestrinone, as well as tormifene with tibolone.

Combinations of drugs that require separate study.

Combination of the drug with levetiracetam may cause potentiation of the toxicity of Mezacar.

The combination of drugs with isoniazid can trigger the potentiation of hepatotoxicity of the latter.

Introduction together with lithium drugs or metoclopramide, and in addition with neuroleptics (thioridazine or haloperidol) can cause potentiation of negative neurological signs (with the latter combination, even in the case of therapeutic plasma indicators).

The use of the drug together with a separate diuretic (furosemide or hydrochlorothiazide) can cause the appearance of a symptomatic hyponatremia.

Carbamazepine can act as an antagonist of non-depolarizing muscle relaxants (for example, pancuronium). In this case, you can expect the need to increase the portions of these funds, and patients should be carefully monitored to prevent neuromuscular blockade.

Like other psychotropic drugs, carbamazepine is able to reduce the tolerance of alcoholic beverages, which is why patients need to stop using them during therapy.

Prohibited combinations.

Because the structure of carbamazepine is close to tricyclics, the drug cannot be combined with MAOI. It is necessary to stop the introduction of the latter at least 14 days before the start of using Mezacar

The effect of the drug on serological testing data.

Carbamazepine is able to give a false positive reaction in the UPPER analysis used during the determination of perphenazine values.

Carbamazepine together with 10,11-epoxide can give false positive indications in immunological studies using polarized fluorescence, which are carried out to establish indicators of tricyclics.

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Storage conditions

Mezacar is required to be kept at temperature marks in the range of 15-25 ° C.

Shelf life

Mezacar can be used for a 24-month period from the time the drug is manufactured.

Application for children

In children, a more pronounced elimination of carbamazepine is registered, which is why they may require increased amounts of medication (in terms of kilograms of weight). Prescribing pills allowed for children over 5 years of age.

Analogs

Analogues of the drug are Finlepsin, Septol with Tegretol, Carbelex with Carbapine, and in addition Carbamazepine and Timonil.