FINLEPSIN RETARD

Active material: Carbamazepine
When ATH: N03AF01
CCF: Anticonvulsants
ICD-10 codes (testimony): F10.3, F23, F25, F31, G35, G40, G50.0, G52.1, G63.2, R20.2, R25.2, R27.0
When CSF: 02.05.04
Manufacturer: AWD.pharma GmbH & Co.KG (Germany)

Pharmaceutical form, composition and packaging

Sustained-release tablets from white to white with a yellowish tint, rounded, flat, with beveled edges, with cross fault lines on both sides and 4 notches on the side.

Excipients: ethyl acrylate copolymer, methyl methacrylate and trimetilammonioetilmetakrilata (1:2:0.1) (Eudragit^® RS30D), triacetine, talc, a copolymer of methacrylic acid and ethyl acrylate (Eudragit^® L30D-55), microcrystalline cellulose, krospovydon, colloidal silicon dioxide, magnesium stearate.

10 PC. – blisters (5) – packs cardboard.

Pharmacological action

The antiepileptic drug (derivative dibenzazepine). Also it has anti-depressant, antipsychotic and antidiuretic action, analgesic effect in patients with neuralgia. The mechanism of action related to the blockade of voltage-dependent sodium channels, which leads to stabilization of the membrane overexcited neurons, inhibition of the serial bits of neurons and reduction of synaptic impulses. Prevents re-formation of Na⁺-dependent action potentials in depolarized neurons. Lowers glutamate release (excitatory amino acid neurotransmitter properties), increases reduced seizure threshold and, thus, reduces the risk of epileptic seizure. Increases transport potassium ions, modulates the voltage-dependent calcium channels, which also may contribute to the anticonvulsive effects of the drug. Effective with the focal (partial) epileptic seizures (simple and complex), accompanied or not by secondary generalization, in generalized tonic-clonic epileptic seizures, as well as combinations of these types of attacks (usually not effective for small seizures, absences and myoclonic seizures).

In patients with epilepsy (especially in children and adolescents) It noted a positive effect on symptoms of anxiety and depression, as well as reducing irritability and aggression. The effect on cognitive function and psychomotor performance depends on the dose.

Starting anticonvulsant effect varies from several hours to several days (sometimes up 1 month due to auto-induction of metabolism).

In essential and secondary trigeminal neuralgia in most cases, prevents the appearance of pain attacks. Easing the pain of trigeminal neuralgia is marked by 8-72 no.

When alcohol withdrawal syndrome raises the seizure threshold (which in this state is usually reduced) and reduces the severity of the clinical manifestations of the syndrome (hypererethism, tremor, gait disturbance).

Antipsychotic (antimanic) action develops through 7-10 days, that may be due to inhibition of metabolism of dopamine and norepinephrine.

Prolonged dosage form maintains more stable concentrations of carbamazepine levels when receiving 1-2 times / day.

Pharmacokinetics

Absorption

When receiving the drug inside carbamazepine slowly, but almost completely absorbed from the gastrointestinal tract (food intake did not significantly affect the rate and extent of absorption).

After receiving a single dose 400 mg C_max achieved through 32 h, and averages about 2.5 ug / ml.

Distribution

C_ss plasma achieved through 1-2 weeks of continuous use (the rate of achievement depends on the individual metabolism: auto-induction of the liver enzyme systems, geteroinduktsiya other simultaneously used drugs, and the condition of the patient, dosage and duration of treatment). There are substantial interindividual differences in the value of C_ss TTR: in most patients, these values ​​range from 4 to 12 ug / ml (17-50 mmol / l). Concentrations carbamazepine-10,11-эpoksida (pharmacologically aktivnogo metabolite) account for about 30% the concentration of carbamazepine.

Plasma protein binding of children – 55-59%, adult – 70-80%. In Кажущийся_d – 0.8-1.9 l / kg. In the cerebrospinal fluid and saliva concentrations are proportional to the amount of unbound protein active substance (20-30%). It penetrates through the placental barrier and is excreted in breast milk (concentration is 25-60% from such blood plasma).

Metabolism

It is metabolized in the liver, mainly by way of epoxy, to form the major metabolites: active – carbamazepine-10,11-эpoksida and neaktivnogo konayugata with glyukuronovoy kislotoy. The basic isoenzyme, providing biotransformation carbamazepine, carbamazepine-10,11-epoxide, isoenzyme 3A4 is a cytochrome P450. As a result of metabolic reactions also formed inactive metabolite 9-hydroxy-10-methyl-karbamoilakridan. Carbamazepine can induce its own metabolism.

Deduction

T_1/2 after a single oral administration of 60-100 no (an average of about 70 no), during long-term treatment of T_1/2 decreases due to auto-induction of the liver enzyme systems. After a single oral 72% the dose is excreted in the urine and 28% with feces; with about 2% excreted in the urine as unchanged carbamazepine, about 1% - as 10,11- эpoksidnogo metabolite.

Pharmacokinetics in special clinical situations

No data, testifying, that the pharmacokinetics of carbamazepine changes in elderly patients.

Testimony

- Epilepsy: primary generalized seizures (except for absences), partial form of epilepsy (simple and complex seizures), secondary generalized seizures;

- Neuralgia nerve troynichnogo;

- Idiopaticheskaya nerve neuropathy yazыkoglotochnogo;

- Painful diabetic polyneuropathy;

- Épileptiformnye sudorogi at rasseânnom sclerosis, spasms of the facial muscles of trigeminal neuralgia, tonic convulsions, ataxia and dysarthria paroksizmalynaya, paresthesia and paroxysmal pain attacks;

- Alcohol withdrawal syndrome (alarm, convulsions, hyperexcitability, sleep disorders);

- Psychotic disorders (affective and schizoaffective disorders, psychoses, dysfunction of the limbic system).

Dosage regimen

The tablets are taken orally during or after meal, drinking plenty of fluids. If necessary, tablets (as well as its half or quarter) It can be dissolved in water or juice (while maintaining the ability for sustained release of the active substance).

The average range of doses 400-1200 mg / day, the multiplicity of reception – 1-2 times / day. The maximum daily dose – 1600 mg.

At epilepsy where, where possible, drug finlepsin^® retard should be administered as monotherapy. The treatment begins with the application of a small daily dose, which thereafter slowly increased until the optimum effect.

Joining drug finlepsin^® retard to the already ongoing antiepileptic therapy should be gradual, while the dose of the drugs do not change or, if necessary, corrected.

Omitting receive another dose of the drug should take the missed dose immediately, as soon as it is noticed, This is not to take a double dose.

To Adult starting dose is 200-400 mg / day, then the dose is slowly increased until the optimal therapeutic effect. The maintenance dose is 800-1200 mg / day (in 1-2 admission).

The initial dose for children aged 6 to 15 years – 200 mg / day, then gradually increase the dose to 100 mg / day until the optimum effect. Supporting dose children 6-10 years – 400-600 mg / day (in 2 admission), to children 11-15 years – 600-1000 mg / day (in 2 admission).

The recommended dosing regimen.

Duration of treatment depends on the indication and the patient's individual response to the drug.

The decision to transfer the patient to use the drug finlepsin^® retard, the duration of its use or cancellation of the treatment adopted by the doctor individually. The dose can be reduced or completely canceled earlier, than after 2-3 years of total absence seizures. Abolition of the drug was gradually, reducing the dose for 1-2 years, under the control of the EEG. Thus in children at lower daily dose should take into account body weight increase with age.

At trigeminal neuralgia, idiopathic glossopharyngeal neuralgia starting dose is 200-400 mg / day 2 admission. The initial dose is increased up to the complete disappearance of pain, to an average 400-800 mg / day. After that a certain proportion of patients may continue treatment at a lower maintenance dose 400 mg / day.

Elderly patients and patients with individual sensitivity to the drug carbamazepine finlepsin^® retard administered at an initial dose 200 mg / day 1 time / day.

At pain in diabetic neuropathy the drug is prescribed for 200 mg in the morning and 400 mg in the evening. In exceptional cases, the drug finlepsin^® retard may be administered at a dose of 600 mg 2 times / day.

At treatment of alcohol withdrawal in hospital the average daily dose is 600 mg (200 mg in the morning and 400 mg in the evening). In severe cases in the early days the dose can be increased to 1200 mg / day 2 admission.

If necessary, medication finlepsin^® retard can be combined with other drugs, used to treat alcohol withdrawal, in addition to sedatives and opiates. During treatment should regularly monitor the content of carbamazepine in plasma. In connection with the development of side effects of the central nervous system and the autonomic nervous system of patients establish close observation in hospital.

At épileptiformnyh sudorogah at rasseânnom sclerosis the average daily dose is 200-400 mg 2 times / day.

To treatment and prevention of psychoses starting dose and maintenance dose is 200-400 mg / day. If necessary, the dose can be increased to 400 mg 2 times / day.

Side effect

In estimating the frequency of occurrence of various side reactions, the following criteria: Often (≥10%), often (≥1%, but <10%), sometimes (≥0.1%, but <1%), rarely (≥0.01%, but <0.1%), rarely (<0.01%).

From the central and peripheral nervous system: often – dizziness, ataxia, drowsiness, generalized weakness, headache, Parez akkomodacii; sometimes – abnormal involuntary movements (eg, tremor, “flittering” tremor, dystonia, tics), nistagmo; rarely – hallucinations (visual or auditory), depression, decreased appetite, anxiety, violent behavior, psychomotor agitation, disorientation, activation psychosis, orofatsialynaya dyskinesia, oculomotor disturbances, speech disorders (eg, dysarthria or slurred speech), horeoatetoidnye disorders, peripheral neuritis, paresthesia, muscle weakness, and paresis. Role in the development of carbamazepine CSN, especially in conjunction with neuroleptics, It remains unclear.

The development of side effects from the central nervous system may be a consequence of relative overdosing or significant fluctuations in the concentration of carbamazepine in plasma.

Allergic reactions: often – hives; sometimes – erythroderma, multiorgan delayed-type hypersensitivity reaction with fever, skin rash, vasculitis (incl. uzlovataya эritema, as a manifestation of cutaneous vasculitis), limfadenopatieй, features, resembling lymphoma, arthralgia, leukopenia, eosinophilia, hepatosplenomegaly and altered liver function (these symptoms occur in different combinations). There may also be involved, and other organs (eg, lungs, kidneys, pancreas, myocardial, colon), aseptic meningitis with myoclonus and peripheral eosinophilia, anaphylactoid reactions, angioedema, hypersensitivity pneumonitis or eosinophilic pneumonia. In the event the above allergic reactions using the product should be discontinued. Rarely – lupus-like syndrome, itchy skin, erythema multiforme exudative (incl. Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell's syndrome), photosensitivity.

From the hematopoietic system: often – leukopenia, thrombocytopenia, eozinofilija; rarely – leukocytosis, lymphadenopathy, folic acid deficiency, agranulocytosis, aplasticheskaya anemia, istinnaya эritrotsitarnaya aplasia, megaloblastnaya anemia, acute “intermittent” porphyria, reticulocytosis, gemoliticheskaya anemia, splenomegaly.

From the digestive system: often – nausea, vomiting, dry mouth, increased activity of GGT (due to the induction of this enzyme in the liver), which usually has no clinical significance, increased activity of alkaline phosphatase; sometimes – diarrhea or constipation, abdominal pain, increase in liver transaminases; rarely – glossitis, gingivitis, stomatitis, pancreatitis, hepatitis (cholestatic, parenhimatoznыy), jaundice, granulomatous hepatitis, hepatic failure.

Cardio vascular system: rarely – intracardiac conduction disorders; reduction or increase in blood pressure, bradycardia, Arrhythmia, AV block with syncope, collapse, worsening or development of chronic heart failure, aggravation of coronary artery disease (incl. the appearance or increased frequency of angina attacks), tromboflebit, thromboembolism.

Endocrine and metabolic: often – swelling, fluid retention, weight gain, giponatriemiya (decrease in plasma osmolarity due to the effect, similar to the action of ADH, in rare cases, lead to hyponatremia dilutions, accompanied by lethargy, vomiting, headache, disorientation and neurological disorders); rarely – increased concentration of prolactin (It may be accompanied by galactorrhea and gynecomastia); reducing the concentration of L-thyroxine and the increase in the concentration of TSH (not usually accompanied by clinical signs); the calcium-phosphorus metabolism in bone (decrease in the concentration of Ca²⁺ and 25-OH-kolekaltsiferola plasma): osteomalacia, hypercholesterolemia (including cholesterol-HDL), hypertriglyceridemia and lymphadenopathy, girsutizm.

With the genitourinary system: rarely – interstitial nephritis, renal failure, impairment of renal function (eg, albuminuria, hematuria, oligurija, increasing concentrations of urea / azotemia), frequent urination, urinary retention, reduced potency.

On the part of the musculoskeletal system: rarely – arthralgia, myalgia or cramps.

From the senses: rarely - a violation of taste sensations, increased intraocular pressure, cataract, conjunctivitis; hearing loss, incl. noise in ears, hyperacusis, gipoakuziя, changes in the perception of pitch.

Dermatological reactions: violation of skin pigmentation, purpura, acne, Sweating, alopecia.

Contraindications

- Violations of bone marrow hematopoiesis (anemia, leukopenia);

- AV блокада;

- Acute intermittent porphyria (incl. history);

- Simultaneous use with lithium and MAO inhibitors;

- Hypersensitivity to carbamazepine and other components of the drug, and tricyclic antidepressants.

FROM caution the drug should be used in decompensated chronic heart failure, in violation of the liver and / or kidney, in elderly patients, in patients with active alcoholism (enhanced CNS depression, intensifies metabolism of carbamazepine), when hyponatremia breeding (ADG syndrome gipersekrecii, gipopituitarizm, gipotireoz, adrenocortical insufficiency), the oppression of bone marrow hematopoiesis in patients receiving drugs (history), when prostatic hyperplasia, increased intraocular pressure; while the use of sedative and hypnotic drugs.

Pregnancy and lactation

In women of reproductive age drug finlepsin^® retard should, possibly, administered as monotherapy (Using the minimum effective dose), tk. the frequency of congenital anomalies of newborn, mothers who received the combined treatment of antiepileptic, higher, than those, who received each of these funds in the form of monotherapy.

In the event of pregnancy (or in deciding on the appointment of carbamazepine during pregnancy) must carefully compare the expected benefits of therapy and possible complications of it, especially in the I trimester of pregnancy. Known, children, whose mothers suffered from epilepsy, prone to violations of pre-natal development, including malformations. The drug finlepsin^® retard can increase the risk of these disorders. There are few reports of cases of congenital diseases and malformations, including spina bifida (spina bifida).

Carbamazepine increases folate deficiency, often observed during pregnancy, that may increase the incidence of congenital defects in children, so offensive planned pregnancy and during pregnancy is recommended supplementation with folic acid. In order to prevent bleeding complications in newborns, women in the last weeks of pregnancy, as well as the newborn is recommended to prescribe vitamin K.

Carbamazepine is excreted in breast milk. If necessary, the appointment during lactation should be weighed against the benefits and possible adverse effects of breastfeeding in the face of continued therapy. Mothers, taking carbamazepine, can breastfeed provided, that the child will be placed under surveillance to identify possible adverse reactions (eg, severe drowsiness, allergic skin reactions).

Cautions

The drug should only be subject to regular medical control.

Begins with monotherapy of epilepsy prescribing low doses, gradually raising them to achieve the desired therapeutic effect.

In some cases, treatment with antiepileptic drugs was accompanied by the emergence of siutsidalnyh attempts and intentions. This was also confirmed in meta-analyzes of randomized clinical trials involving antiepileptics. Since the mechanism of occurrence siutsidalnyh attempts using antiepileptic drugs is not known, their occurrence can not be excluded and the treatment of drug finlepsin^® retard. Patients (and staff) to warn of the need to know when thinking siutsidalnyh, behavior, and in the event of symptoms seek immediate medical attention.

It is advisable to determine the concentration of carbamazepine in plasma in order to select the optimal dose, especially in combination therapy. In some cases, necessary for the treatment dosage may deviate significantly from the recommended starting and maintenance dose, eg, due to rapid metabolism due to the induction of microsomal liver enzymes or by the interaction of drugs in combination therapy.

The drug finlepsin^® retard should not be combined with sedative hypnotics. If necessary, it can be combined with other substances, used to treat alcohol withdrawal.

When transferring a patient on carbamazepine should gradually reduce the dose previously assigned antiepileptic until its complete abolition. Sudden discontinuation of carbamazepine can cause epileptic seizures. If you want to dramatically interrupt treatment, the patient should be transferred to other antiepileptic drugs under the cover shown in such cases the drug (eg, diazepam in / or rectally, or phenytoin in /).

Described several cases of vomiting, diarrhea and / or reduced power, convulsions and / or respiratory depression in the newborn, whose mothers took carbamazepine in conjunction with other anticonvulsant (perhaps, these reactions are manifestations of neonatal withdrawal syndrome).

It will be appreciated, Carbamazepine may adversely affect the reliability of oral contraceptive drugs, so women of childbearing age during treatment should use alternative methods of contraception (likely intermenstrual bleeding in women, while the use of oral contraceptives).

Before the appointment of carbamazepine and during treatment requires monitoring of liver function tests, especially in patients, a history which has information about diseases of the liver, as well as in the elderly. In the case of strengthening the already existing liver dysfunction or active liver disease appears, the drug should be lifted immediately. Before treatment is necessary to undertake a study of the blood picture (including platelet counts, retikulotsitov), iron levels in the serum, urinalysis, urea level in blood, EEG, determining the concentration of electrolytes in serum; blood (and periodically during treatment, tk. may develop hyponatremia). Subsequently, these indicators should be monitored during the first month of treatment on a weekly basis, and then – monthly.

In most cases, a transient or a persistent decline in the number of platelets and / or white blood cells are not harbingers of the beginning of aplastic anemia or agranulocytosis. Nonetheless, before treatment, and periodically during the treatment process should be carried out clinical blood, including counting the number of platelets, and, perhaps, retikulotsitov, and to determine the level of iron in the serum. Nonprogressive asymptomatic leukopenia does not require cancellation, However, treatment should be discontinued when a progressive leukopenia or leucopenia, accompanied by clinical symptoms of an infectious disease.

Carbamazepine should be immediately canceled the appearance of hypersensitivity reactions or symptoms, presumably indicating the development of Stevens-Johnson syndrome or Lyell's syndrome. Mild skin reactions expressed (isolated makuleznaya or maculo-papular rash) usually disappear within a few days or weeks, even with continued treatment or after reduction of the dose (at this time the patient must be under the supervision of a physician).

In applying the drug should take into account the possibility of activation of a latent psychosis occurring, and elderly patients - the possibility of disorientation or agitation.

There are male fertility disorders and / or disorders of spermatogenesis (the relationship of these disorders with carbamazepine is not installed).

The patient should be informed of the early signs of possible toxic reactions on the part of the hematopoietic system, liver and dermatological reactions and the need to consult a doctor immediately in case of occurrence of adverse reactions, fever, sore throat, rash, ulceration of the oral mucosa, wanton appearance of hematomas, hemorrhages in the form of petechiae or purpura.

Before treatment, it is recommended to eye examination, Fundus examination including slit-lamp and if necessary the measurement of intraocular pressure. In appointing the drug to patients with increased intraocular pressure, it needs constant monitoring.

Patients with severe diseases of the cardiovascular system, liver and kidney, as well as the elderly drug prescribed at lower doses.

Although the relationship between the dose of carbamazepine, its concentration and clinical efficacy or tolerability is very low, Nevertheless regular determination of the concentration of carbamazepine in the plasma is also useful when a sharp increase in the frequency of attacks; to verify the regularity of the drug the patient; Pregnancy; in the treatment of children and adolescents; for suspected violations of absorption of the drug; in cases of suspected development of toxic reactions in the event of, if the patient receives more drugs.

Against the background of the drug is recommended to give up alcohol.

Overdose

The resulting overdose symptoms and complaints usually reflect violations of the central nervous system, cardiovascular and respiratory system.

On the part of the central nervous system and sensory organs: oppression of the CNS, disorientation, drowsiness, excitation, hallucinations, coma; blurred vision, gibberish, dysarthria, nistagmo, ataxia, dyskinesia, hyperreflexia, turning into hyporeflexia, convulsions, psychomotor disturbances, myoclonus, gipotermiя, midriaz.

Cardio-vascular system: tachycardia, decrease in blood pressure, sometimes increase blood pressure, intraventricular conduction disturbances with extension of the QRS complex, swoon, cardiac arrest.

The respiratory system: respiratory depression, pulmonary edema.

From the digestive system: nausea, vomiting, delay evacuation food from the stomach, reduced motility of the colon.

From the urinary system: urinary retention, oliguria or anuria; fluid retention.

From the laboratory parameters: leukocytosis or leukopenia, giponatriemiya, possible metabolic acidosis, possible hyperglycemia and glycosuria, increase muscle fraction CK.

Treatment: there is no specific antidote. Treatment is prescribed depending on the clinical condition of the patient; hospitalization, determining the concentration of carbamazepine in plasma (to confirm the status and assess the extent of overdose), gastric lavage, appointment of activated carbon (tardive gastric emptying can result in delayed absorption at 2 and 3 day and re-emergence of symptoms of intoxication during the recovery period). Ineffective forced diuresis, e pyeritonyealinyi dialysis and hemodialysis (dialysis is indicated for severe combined overdose and renal failure). Children may need blood transfusion. If necessary spend symptomatic therapy in the ICU, monitoring indicators of the cardiovascular system and the kidneys and bladder, fever, control of corneal reflexes, correction of electrolyte disorders.

Drug Interactions

In an application with inhibitors of CYP3A4 may increase the concentration of carbamazepine in plasma and the development of adverse reactions.

The combined use of inducers of CYP3A4 may accelerate the metabolism and decrease the concentration of carbamazepine in plasma and reducing the therapeutic effect. Opposite, Cancellations can reduce the rate of biotransformation of carbamazepine and lead to an increase in its concentration.

When combined concentration of carbamazepine in plasma increase verapamil, diltiazem, felodipine, dextropropoxyphene, viloksazin, fluoxetine, fluvoxamine, cimetidine, aцetazolamid, danazol, desipramine, nicotinamide (adult, Only high doses); makrolidы (Erythromycin, dzhozamitsin, clarithromycin, troleandomiцin); azole (itraconazole, ketoconazole, fluconazole), terfenadine, loratadine, Isoniazid, propoksyfen, grapefruit juice, protease inhibitors, used in the treatment of HIV infection (eg, ritonavir) (the application of such combinations requires correction dosing regimen or monitoring the concentration of carbamazepine in plasma).

Felbamate reduces the concentration of carbamazepine in the plasma and increases the concentration of carbamazepine-10,11-epoxide, thus possible to simultaneously decrease the serum concentration felbamata.

When combined concentration of carbamazepine reduce phenobarbital, phenytoin, prymydon, metsuksimid, fensuksimid, theophylline, rifampicin, cisplatin, doxorubicin. A similar effect is possible clonazepam, valpromyd, valproic acid, oxcarbazepine, and herbal preparations, containing St. John's wort (Hypericum perforatum).

In a joint application valproic acid and carbamazepine, primidone may displace from binding to plasma proteins and increase the concentration of the pharmacologically active metabolite (karʙamazepina-10,11-epoksida). The combined application of the drug finlepsin^® retard with valproic acid in exceptional cases can occur coma, and confusion.

When used together isotretinoin modifies the bioavailability and / or clearance of carbamazepine and carbamazepine-10,11-epoxide (requires monitoring plasma concentrations of carbamazepine).

With simultaneous use of carbamazepine may reduce the plasma concentration and, Consequently, reduce or even reverse the effects and require dose adjustment following drugs: clobazam, clonazepam, digoksina, ethosuximide, prymydona, valproic acid, alprazolam, GCS (prednisolone, deksametazona), cyclosporine, tetracyclines (doxycycline), haloperidol, metadona, oral medications, containing estrogen and / or progesterone (requires selection of alternative methods of contraception), teofillina, oral anticoagulants (varfarina, fenprokumona, dikumarola), lamotrignine, topiramate, tricyclic antidepressants (imipramine, amitriptyline, nortriptyline, clomipramine), clozapine, felbamate, tiagaʙina, oxcarbazepine, protease inhibitors, used in the treatment of HIV infection (indinavir, Ritonavir, saquinavir), calcium channel blockers (dihydropyridine group, eg, felodipine), itraconazole, levothyroxine, midazolama, olanzapine, praziquantel, risperidone, tramadol, ziprasidona.

It is possible to increase or decrease phenytoin in blood plasma carbamazepine background and raising mefenitoina (rarely).

With simultaneous use of drugs lithium and carbamazepine may be synergistic neurotoxic effects.

Tetracyclines may reduce the therapeutic effect of carbamazepine.

Carbamazepine or combined with paracetamol increases the risk of toxic effects on the liver and reduces the therapeutic efficacy (acceleration of metabolism of paracetamol).

Co-administration of carbamazepine phenothiazine, pimozidom, tyoksantenamy (chlorprothixene), molindonom, haloperidol, Maprotiline, clozapine and tricyclic antidepressants leads to increased inhibitory action on the central nervous system and the weakening effect of the anticonvulsant carbamazepine.

MAO inhibitors increase the risk of hyperthermia crises, hypertensive crises, seizures, death (before prescribing carbamazepine MAO inhibitors should be abolished, least, for 2 weeks or, If the clinical situation allows, even for a longer period).

Co-administration with diuretics (gidroxlorotiazid, furosemid) can lead to hyponatremia, accompanied by clinical signs.

Carbamazepine in the combined use reduces the effects of nondepolarizing muscle relaxants (pancuronium). In the case of such a combination may need higher doses of muscle relaxant, thus it is necessary to carry out careful monitoring of patients, as fast as possible termination of their actions.

Reduces ethanol tolerance.

Myelotoxic drugs increase the expression gematotoksichnosti carbamazepine.

It accelerates the metabolism of indirect anticoagulants, hormonal contraceptive drugs, folic acid; praziquantel.

May enhance elimination of thyroid hormones.

It accelerates the metabolism of narcosis (enflurane, halothane, ftorotana) with increased risk of hepatotoxic effects.

Enhances the formation of nephrotoxic metabolites metoksiflurana.

It enhances the hepatotoxic effects of isoniazid.

Conditions of supply of pharmacies

The drug is released under the prescription.

Conditions and terms

List B. The drug should be stored out of reach of children at or above 30 ° C. Shelf life – 3 year.