Finlepsin^® retard (Tablets) Instructions for Use

Marketing Authorization Holder

Teva Pharmaceutical Industries, Ltd. (Israel)

Manufactured By

Teva Operations Poland, Sp. z o.o. (Poland)

Contact Information

TEVA (Israel)

ATC Code

N03AF01 (Carbamazepine)

Active Substance

Carbamazepine (Rec.INN registered by WHO)

Dosage Forms

	Finlepsin® retard	Prolonged-release tablets 200 mg: 30, 40, or 50 pcs.
		Prolonged-release tablets 400 mg: 30, 40, or 50 pcs.

Dosage Form, Packaging, and Composition

Prolonged-release tablets from white to yellowish, round, flat, in the shape of a clover leaf with beveled edges, with cross-shaped break lines on both sides and 4 notches on the side surface, with a smooth surface, intact edges, and a uniform appearance. The tablet can be divided into equal doses.

Excipients: Ammonio methacrylate copolymer (type B) dispersion (Eudragit^® RS30D), triacetin (glycerol triacetate), talc, methacrylic acid and ethyl acrylate copolymer (1:1) dispersion 30% (Eudragit^® L30D-55), crospovidone, colloidal silicon dioxide (anhydrous colloidal silicon dioxide), magnesium stearate, microcrystalline cellulose.

10 pcs. – blisters (3) – cardboard packs.
10 pcs. – blisters (4) – cardboard packs.
10 pcs. – blisters (5) – cardboard packs.

Prolonged-release tablets from white to yellowish, round, flat, in the shape of a clover leaf with beveled edges, with cross-shaped break lines on both sides and 4 notches on the side surface, with a smooth surface, intact edges, and a uniform appearance. The tablet can be divided into equal doses.

Excipients: Ammonio methacrylate copolymer (type B) dispersion (Eudragit^® RS30D), triacetin (glycerol triacetate), talc, methacrylic acid and ethyl acrylate copolymer (1:1) dispersion 30% (Eudragit^® L30D-55), crospovidone, colloidal silicon dioxide (anhydrous colloidal silicon dioxide), magnesium stearate, microcrystalline cellulose.

10 pcs. – blisters (3) – cardboard packs.
10 pcs. – blisters (4) – cardboard packs.
10 pcs. – blisters (5) – cardboard packs.

Clinical-Pharmacological Group

Anticonvulsant drug

Pharmacotherapeutic Group

Antiepileptic drug, carboxamide derivative

Pharmacological Action

Antiepileptic drug (dibenzazepine derivative). It also has antidepressant, antipsychotic, and antidiuretic effects, and has an analgesic effect in patients with neuralgia. The mechanism of action is associated with the blockade of voltage-gated sodium channels, which leads to stabilization of the membrane of overexcited neurons, inhibition of the occurrence of serial neuronal discharges, and reduction of synaptic impulse conduction. It prevents the re-formation of Na⁺-dependent action potentials in depolarized neurons. It reduces the release of glutamate (an amino acid with excitatory neurotransmitter properties), increases the lowered seizure threshold, and thus reduces the risk of an epileptic seizure. It increases potassium ion transport and modulates voltage-gated calcium channels, which may also contribute to the anticonvulsant action of the drug. It is effective in focal (partial) epileptic seizures (simple and complex), with or without secondary generalization, in generalized tonic-clonic epileptic seizures, as well as in a combination of the specified types of seizures (usually ineffective in petit mal, absences, and myoclonic seizures).

In patients with epilepsy (especially in children and adolescents), a positive effect on symptoms of anxiety and depression, as well as a reduction in irritability and aggressiveness, has been noted. The effect on cognitive function and psychomotor performance is dose-dependent.

The onset of the anticonvulsant effect varies from several hours to several days (sometimes up to 1 month due to autoinduction of metabolism).

In essential and secondary trigeminal neuralgia, in most cases, it prevents the occurrence of pain attacks. Pain relief in trigeminal neuralgia is noted within 8-72 hours.

In alcohol withdrawal syndrome, it increases the seizure threshold (which is usually lowered in this condition) and reduces the severity of clinical manifestations of the syndrome (increased excitability, tremor, gait disturbances).

The antipsychotic (antimanic) effect develops after 7-10 days, which may be due to inhibition of dopamine and norepinephrine metabolism.

The prolonged-release dosage form ensures maintenance of a more stable blood concentration of carbamazepine when taken 1-2 times/day.

Pharmacokinetics

Absorption

Absorption is slow but complete (food intake does not significantly affect the rate and extent of absorption).

After a single dose of the tablet, C_max is reached after 32 hours. The mean C_max of the unchanged active substance after a single dose of 400 mg of carbamazepine is about 2.5 µg/ml.

Distribution

C_ss in plasma is reached after 1-2 weeks of constant use (the rate of achievement depends on individual metabolic characteristics: autoinduction of liver enzyme systems, heteroinduction by other concurrently used drugs, as well as on the patient’s condition, drug dose, and duration of treatment). Significant interindividual differences in C_ss values are observed within the therapeutic range: in most patients, these values range from 4 to 12 µg/ml (17-50 µmol/l). The concentration of Carbamazepine-10,11-epoxide (a pharmacologically active metabolite) is about 30% of the carbamazepine concentration.

Binding to plasma proteins in children is 55-59%, in adults 70-80%. Apparent V_d is 0.8-1.9 l/kg. Concentrations in cerebrospinal fluid and saliva are proportional to the amount of unbound active substance (20-30%).

It crosses the placental barrier and is excreted in breast milk (concentration is 25-60% of that in plasma).

Metabolism

It is metabolized in the liver, mainly via the epoxide pathway, with the formation of the main metabolites: active – Carbamazepine-10,11-epoxide and inactive conjugate with glucuronic acid. The main isoenzyme providing the biotransformation of carbamazepine into Carbamazepine-10,11-epoxide is CYP3A4. As a result of these metabolic reactions, the metabolite 9-hydroxymethyl-10-carbamoylacridan, which has weak pharmacological activity, is also formed. Carbamazepine can induce its own metabolism.

Excretion

T_1/2 after a single oral dose is 60-100 hours (on average about 70 hours); with prolonged use, T_1/2 decreases due to autoinduction of liver enzyme systems. After a single oral dose, 72% of the administered dose is excreted in the urine and 28% in the feces; with about 2% excreted in the urine as unchanged carbamazepine, about 1% as the 10,11-epoxide metabolite.

Pharmacokinetics in special clinical cases

There is no data indicating that the pharmacokinetics of carbamazepine changes in elderly patients.

Indications

• Epilepsy: primary generalized seizures (except for absences), partial forms of epilepsy (simple and complex seizures), secondary generalized seizures;
• Trigeminal neuralgia;
• Idiopathic glossopharyngeal neuralgia;
• Pain in peripheral nerve lesions in diabetes mellitus, pain in diabetic neuropathy;
• Epileptiform convulsions in multiple sclerosis, facial muscle spasms in trigeminal neuralgia, tonic convulsions, paroxysmal dysarthria and ataxia, paroxysmal paresthesias and pain attacks;
• Alcohol withdrawal syndrome (anxiety, convulsions, hyperexcitability, sleep disorders);
• Psychotic disorders (affective and schizoaffective disorders, psychoses, limbic system function disorders).

ICD codes

Dosage Regimen

The drug is taken orally during or after meals with a sufficient amount of liquid.

For ease of use, the tablet (as well as its half or quarter) can be pre-dissolved in water or juice, because the property of prolonged release of the active substance is preserved after the tablet is dissolved in liquid. The range of applied doses is 400-1200 mg/day. The daily dose is divided into 1-2 doses.

The maximum daily dose is 1600 mg.

Epilepsy

Whenever possible, Finlepsin^® retard should be prescribed as monotherapy. Treatment begins with a small daily dose, which is then slowly increased until the optimal effect is achieved.

The addition of Finlepsin^® retard to an ongoing antiepileptic therapy should be carried out gradually, while the doses of the drugs used are not changed or, if necessary, adjusted.

If a dose is missed, the missed dose should be taken as soon as it is noticed, but a double dose of the drug should not be taken.

Adults

The initial dose is 200-400 mg/day, then the dose is slowly increased until the optimal therapeutic effect is achieved. The maintenance dose is 800-1200 mg/day in 1-2 doses.

Children

The initial dose for children aged 6 to 15 years is 200 mg/day, then the dose is gradually increased by 100 mg/day until the optimal effect is achieved.

Maintenance doses for children aged 6-10 years are 400-600 mg/day (in 2 doses), for children aged 11-15 years are 600-1000 mg/day (in 2 doses).

The recommended dosing regimen is presented in the table.

The duration of use depends on the indication and the individual patient’s response to the drug.

The decision to transfer the patient to the use of Finlepsin^® retard, the duration of its use, or the withdrawal of treatment is made by the doctor individually. The dose of the drug can be reduced or completely discontinued no earlier than after 2-3 years of complete absence of seizures.

Treatment is discontinued by gradually reducing the dose over 1-2 years, under EEG control. In this case, in children, when reducing the daily dose, the increase in body weight with age should be taken into account.

Trigeminal neuralgia, idiopathic glossopharyngeal neuralgia

The initial dose is 200-400 mg/day in 2 doses. The initial dose is increased until the pain completely disappears, on average up to 400-800 mg/day. After this, in a certain proportion of patients, therapy can be continued at a lower maintenance dose of 400 mg/day.

Elderly patients and patients with individual sensitivity to the action of carbamazepine are prescribed Finlepsin^® retard at an initial dose of 200 mg once a day.

Pain in diabetic neuropathy

The drug is prescribed at 200 mg in the morning and 400 mg in the evening. In exceptional cases, Finlepsin^® retard can be prescribed at a dose of 600 mg twice a day.

Treatment of alcohol withdrawal in a hospital setting

The average daily dose is 600 mg (200 mg in the morning and 400 mg in the evening). In severe cases, in the first days the dose can be increased to 1200 mg/day, which is distributed over 2 doses.

If necessary, Finlepsin^® retard can be combined with other drugs used to treat alcohol withdrawal, except for sedatives and hypnotics.

During treatment, it is necessary to regularly monitor the carbamazepine content in blood plasma.

Due to the development of side reactions from the CNS and autonomic nervous system, patients should be carefully monitored in a hospital setting.

Epileptiform convulsions in multiple sclerosis

The average daily dose is 200-400 mg twice a day.

Treatment and prevention of psychoses

The initial dose and maintenance dose are usually the same: 200-400 mg/day. If necessary, the dose can be increased to 400 mg twice a day.

Adverse Reactions

When assessing the frequency of occurrence of various adverse reactions, the following criteria were used: very common (≥10%), common (≥1%, but <10%), uncommon (≥0.1%, but <1%), rare (≥0.01%, but <0.1%), very rare (<0.01%).

From the nervous system: common – dizziness, ataxia, drowsiness, general weakness, headache, accommodation paresis; uncommon – abnormal involuntary movements (e.g., tremor, asterixis, dystonia, tics), nystagmus; rare – hallucinations (visual or auditory), depression, decreased appetite, anxiety, aggressive behavior, psychomotor agitation, disorientation, psychosis activation, orofacial dyskinesia, oculomotor disturbances, speech disorders (e.g., dysarthria or slurred speech), choreoathetoid disorders, peripheral neuritis, paresthesia, muscle weakness, and paresis. The role of carbamazepine in the development of NMS, especially in combination with antipsychotics, remains unclear.

The development of side effects from the CNS may be a consequence of relative drug overdose or significant fluctuations in carbamazepine plasma concentration.

Allergic reactions: common – urticaria; uncommon – erythroderma, 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 parameters (the listed manifestations occur in various combinations). Other organs may also be involved (e.g., lungs, kidneys, pancreas, myocardium, colon), aseptic meningitis with myoclonus and peripheral eosinophilia, anaphylactoid reaction, angioneurotic edema, allergic pneumonitis or eosinophilic pneumonia. If the above allergic reactions occur, the use of the drug should be discontinued. Rare – lupus-like syndrome, skin itching, multiform exudative erythema (including Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell’s syndrome), photosensitivity.

From the hematopoietic system: common – leukopenia, thrombocytopenia, eosinophilia; rare – leukocytosis, lymphadenopathy, folic acid deficiency, agranulocytosis, aplastic anemia, true erythrocyte aplasia, megaloblastic anemia, acute “intermittent” porphyria, reticulocytosis, hemolytic anemia, splenomegaly.

From the digestive system: common – nausea, vomiting, dry mouth, increased GGT activity (due to induction of this enzyme in the liver), which usually has no clinical significance, increased ALP activity; uncommon – diarrhea or constipation, abdominal pain, increased liver transaminase activity; rare – glossitis, gingivitis, stomatitis, pancreatitis, hepatitis (cholestatic, parenchymal), jaundice, granulomatous hepatitis, liver failure.

From the cardiovascular system: rare – intracardiac conduction disorders; decrease or increase in blood pressure, bradycardia, arrhythmias, AV block with fainting, collapse, worsening or development of chronic heart failure, exacerbation of coronary artery disease (including appearance or increased frequency of angina attacks), thrombophlebitis, thromboembolic syndrome.

Endocrine system and metabolism side effects: frequent – edema, fluid retention, weight gain, hyponatremia (decreased plasma osmolality due to an effect similar to that of ADH, which in rare cases leads to dilutional hyponatremia accompanied by lethargy, vomiting, headache, disorientation, and neurological disorders); rare – increased prolactin concentration (may be accompanied by galactorrhea and gynecomastia); decreased L-thyroxine concentration and increased TSH concentration (usually not accompanied by clinical manifestations); disorders of calcium-phosphorus metabolism in bone tissue (decreased plasma Ca²⁺ and 25-OH-cholecalciferol concentrations): osteomalacia, hypercholesterolemia (including HDL-cholesterol), hypertriglyceridemia, and lymph node enlargement, hirsutism.

Genitourinary system side effects: rare – interstitial nephritis, renal failure, impaired renal function (e.g., albuminuria, hematuria, oliguria, increased urea concentration/azotemia), frequent urination, urinary retention, decreased potency.

Musculoskeletal system side effects: rare – arthralgia, myalgia, or cramps.

Sensory organ side effects: rare – taste disturbances, increased intraocular pressure, lens opacity, conjunctivitis; hearing disorders, incl. tinnitus, hyperacusis, hypoacusis, changes in pitch perception.

Dermatological reactions: skin pigmentation disorders, purpura, acne, sweating, alopecia.

Contraindications

• Impaired bone marrow hematopoiesis (anemia, leukopenia);
• AV block;
• Acute intermittent porphyria (including history);
• Concomitant use with lithium preparations and MAO inhibitors;
• Hypersensitivity to carbamazepine and other components of the drug;
• Hypersensitivity to tricyclic antidepressants.

The drug should be used with caution in decompensated chronic heart failure, in impaired liver and/or kidney function, in elderly patients, in patients with chronic alcoholism (CNS depression is enhanced, carbamazepine metabolism is enhanced), in dilutional hyponatremia (ADH hypersecretion syndrome, hypopituitarism, hypothyroidism, adrenal cortex insufficiency), in bone marrow hematopoiesis depression while taking drugs (in history), in prostate hyperplasia, increased intraocular pressure; with concomitant use of sedatives and hypnotics.

Use in Pregnancy and Lactation

For women of reproductive age Finlepsin^® retard is preferably prescribed as monotherapy, at the minimum effective dose, because the frequency of congenital anomalies in newborns from mothers receiving combined antiepileptic treatment is higher than with monotherapy.

If pregnancy occurs, the expected benefit of therapy and possible complications should be weighed, especially in the first trimester of pregnancy. It is known that children of mothers suffering from epilepsy are predisposed to intrauterine developmental disorders, including malformations. Finlepsin^® retard can increase the risk of these disorders. There are isolated reports of cases of congenital diseases and malformations, including spina bifida. Antiepileptic drugs enhance folic acid deficiency, often observed during pregnancy, which may contribute to an increased frequency of congenital defects in children, so folic acid intake is recommended before planned pregnancy and during pregnancy.

To prevent hemorrhagic complications in newborns, vitamin K is recommended for women in the last weeks of pregnancy, as well as for newborns.

Carbamazepine penetrates into breast milk, so the benefits and possible adverse consequences of breastfeeding during ongoing therapy should be weighed. If breastfeeding is continued while taking the drug, the child should be monitored due to the possibility of developing adverse reactions (e.g., marked drowsiness, allergic skin reactions).

Use in Hepatic Impairment

The drug should be used with caution in impaired liver function.

Use in Renal Impairment

The drug should be used with caution in impaired renal function.

Pediatric Use

The drug is prescribed to children over 6 years of age.

Geriatric Use

The drug should be used with caution in elderly patients.

Special Precautions

Carbamazepine should be used only under medical supervision.

Epilepsy monotherapy is started by prescribing the drug in low doses, gradually increasing them until the desired therapeutic effect is achieved.

When selecting the optimal dose, it is advisable to determine the plasma concentration of carbamazepine, especially during combination therapy. In some cases, the dose required for treatment may deviate significantly from the recommended initial and maintenance dose, for example, due to accelerated metabolism associated with induction of liver microsomal enzymes or as a result of drug interactions during combination therapy.

Finlepsin^® retard should not be combined with sedatives and hypnotics. If necessary, it can be combined with other substances used to treat alcohol withdrawal.

During treatment, it is necessary to regularly monitor the plasma concentration of carbamazepine. Due to the development of side effects from the central and autonomic nervous system, patients should be carefully monitored in a hospital setting.

When switching a patient to Carbamazepine, the dose of the previously prescribed antiepileptic drug should be gradually reduced until it is completely discontinued. Sudden discontinuation of carbamazepine may provoke epileptic seizures. If it is necessary to abruptly interrupt treatment, the patient should be switched to another antiepileptic drug under the cover of a drug indicated in such cases (e.g., diazepam administered intravenously or rectally, or phenytoin administered intravenously).

Several cases of vomiting, diarrhea and/or poor feeding, seizures and/or respiratory depression have been described in newborns whose mothers took Carbamazepine simultaneously with other anticonvulsant drugs (these reactions may represent manifestations of withdrawal syndrome in newborns).

Before prescribing carbamazepine and during treatment, liver function tests should be performed, especially in patients with a history of liver disease, as well as in elderly patients. If pre-existing liver function impairments worsen or active liver disease appears, the drug should be discontinued immediately.

Before starting treatment, it is necessary to conduct a blood count (including platelet and reticulocyte count), serum iron level, urinalysis, blood urea level, EEG, determination of serum electrolyte concentrations (and periodically during treatment, as hyponatremia may develop). Subsequently, these parameters should be monitored weekly during the first month of treatment, and then monthly.

In most cases, a transient or persistent decrease in the number of platelets and/or leukocytes is not a precursor to the onset of aplastic anemia or agranulocytosis. Nevertheless, before starting treatment, as well as periodically during treatment, clinical blood tests should be performed, including platelet count and possibly reticulocyte count, and serum iron levels should be determined. Non-progressive asymptomatic leukopenia does not require discontinuation, however, treatment should be stopped if progressive leukopenia or leukopenia accompanied by clinical symptoms of an infectious disease occurs.

Carbamazepine should be discontinued immediately if hypersensitivity reactions occur or symptoms presumably indicating the development of Stevens-Johnson syndrome or Lyell’s syndrome appear. Mild skin reactions (isolated macular or maculopapular exanthema) usually resolve within a few days or weeks even with continued treatment or after dose reduction (the patient should be under close medical supervision during this time).

The possibility of activation of latent psychoses should be taken into account, and in elderly patients, the possibility of developing disorientation or psychomotor agitation.

In some cases, treatment with antiepileptic drugs has been accompanied by the occurrence of suicide attempts/suicidal intentions. This has also been confirmed by a meta-analysis of randomized clinical trials using antiepileptic drugs. Since the mechanism of suicide attempts when using antiepileptic drugs is unknown, their occurrence cannot be ruled out when treating patients with Finlepsin^® retard. Patients (and caregivers) should be warned to monitor for the appearance of suicidal thoughts/suicidal behavior and to seek immediate medical attention if symptoms occur.

Male fertility disorders and/or spermatogenesis disorders are possible, but the relationship of these disorders with carbamazepine intake has not yet been established.

Intermenstrual bleeding may occur with concomitant use of oral contraceptives. Carbamazepine may adversely affect the reliability of oral contraceptive drugs, so women of reproductive age should use alternative methods of contraception during treatment.

Patients should be informed about the early signs of toxicity, as well as symptoms related to the skin and liver. The patient should be informed of the need to consult a doctor immediately if adverse reactions such as fever, sore throat, rash, ulceration of the oral mucosa, unexplained bruising, petechial or purpuric hemorrhages occur.

Before starting treatment, an ophthalmological examination is recommended, including fundus examination and intraocular pressure measurement. When prescribing the drug to patients with increased intraocular pressure, its constant monitoring is necessary.

The drug is prescribed in lower doses to patients with severe cardiovascular diseases, liver and kidney damage, as well as to elderly persons.

Although the relationship between the dose of carbamazepine, its concentration and clinical efficacy or tolerability is very insignificant, regular determination of plasma carbamazepine concentration is also useful in case of a sharp increase in the frequency of seizures; to check the patient’s regularity of taking the drug; during pregnancy; when treating children or adolescents; if impaired drug absorption is suspected; if toxic reactions are suspected in case the patient is taking several medications.

During treatment with Finlepsin^® retard, it is recommended to refrain from drinking alcohol.

Overdose

Symptoms usually reflect disorders of the CNS, cardiovascular and respiratory systems.

CNS and sensory organs: CNS function depression, disorientation, drowsiness, agitation, hallucinations, coma, blurred vision, slurred speech, dysarthria, nystagmus, ataxia, dyskinesia, hyperreflexia (initially), hyporeflexia (later), seizures, psychomotor disorders, myoclonus, hypothermia, mydriasis.

Cardiovascular system: tachycardia, decreased BP, sometimes increased BP, intraventricular conduction disturbances with QRS complex widening, fainting, cardiac arrest.

Respiratory system: respiratory depression, pulmonary edema.

Digestive system: nausea, vomiting, delayed gastric emptying, decreased colon motility.

Urinary system: urinary retention, oliguria or anuria; fluid retention.

Laboratory parameters: leukocytosis or leukopenia, hyponatremia, possible metabolic acidosis, possible hyperglycemia and glucosuria, increased muscle fraction of CPK.

Treatment: specific antidote is absent. Symptomatic supportive treatment in the ICU is necessary, monitoring of heart function, body temperature, corneal reflexes, kidney and bladder function, correction of electrolyte disorders. Determination of plasma carbamazepine concentration is necessary to confirm poisoning with this agent and assess the degree of overdose, gastric lavage, administration of activated charcoal. Late evacuation of gastric contents may lead to delayed absorption on days 2 and 3 and reappearance of intoxication symptoms during recovery). Forced diuresis, hemodialysis and peritoneal dialysis are ineffective; however, dialysis is indicated in case of combination of severe poisoning and renal failure. Children may require hemotransfusion.

Drug Interactions

With concomitant use with CYP3A4 isoenzyme inhibitors, an increase in plasma carbamazepine concentration and development of adverse reactions is possible.

Concomitant use with CYP3A4 isoenzyme inducers may lead to accelerated metabolism and decreased plasma carbamazepine concentration and reduced therapeutic effect. Conversely, their discontinuation may reduce the rate of carbamazepine biotransformation and lead to an increase in its concentration.

With concomitant use, plasma carbamazepine concentration is increased by 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, protease inhibitors used in HIV therapy (e.g., ritonavir) (when using such combinations, dose regimen adjustment or monitoring of plasma carbamazepine concentration is required).

Felbamate decreases plasma carbamazepine concentration and increases Carbamazepine-10,11-epoxide concentration, while a simultaneous decrease in serum felbamate concentration is possible.

With concomitant use, carbamazepine concentration is decreased by phenobarbital, phenytoin, primidone, methsuximide, phensuximide, theophylline, rifampicin, cisplatin, doxorubicin. A similar effect is possibly caused by clonazepam, valpromide, valproic acid, oxcarbazepine and herbal preparations containing St. John’s wort (Hypericum perforatum).

With concomitant use, valproic acid and primidone may displace Carbamazepine from plasma protein binding and increase concentrations of the pharmacologically active metabolite (carbamazepine-10,11-epoxide). When Finlepsin is used in combination with valproic acid, coma and confusion may occur in exceptional cases.

With concomitant use, isotretinoin alters the bioavailability and/or clearance of carbamazepine and carbamazepine-10,11-epoxide (monitoring of plasma carbamazepine concentration is necessary).

With concomitant use, Carbamazepine may decrease plasma concentration and, consequently, reduce or even completely negate the effects and require dose adjustment of the following drugs: clobazam, clonazepam, digoxin, ethosuximide, primidone, valproic acid, alprazolam, corticosteroids (prednisolone, dexamethasone), cyclosporine, tetracyclines (doxycycline), haloperidol, methadone, oral drugs containing estrogen and/or progesterone (selection of alternative contraceptive methods is necessary), theophylline, oral anticoagulants (warfarin, phenprocoumon, dicumarol), lamotrigine, topiramate, tricyclic antidepressants (imipramine, amitriptyline, nortriptyline, clomipramine), clozapine, felbamate, tiagabine, oxcarbazepine, protease inhibitors used in HIV therapy (indinavir, ritonavir, saquinavir), calcium channel blockers (dihydropyridine group, e.g., felodipine), itraconazole, levothyroxine, midazolam, olanzapine, praziquantel, risperidone, tramadol, ziprasidone.

There is a possibility of increase or decrease in plasma phenytoin against the background of carbamazepine and an increase in mephenytoin levels.

With concomitant use of carbamazepine and lithium preparations, the neurotoxic effects of both active substances may be enhanced.

Tetracyclines may weaken the therapeutic effect of carbamazepine.

Carbamazepine, when used concomitantly with paracetamol, increases the risk of its toxic effect on the liver and reduces therapeutic efficacy (accelerated metabolism of paracetamol).

Concomitant administration of carbamazepine with phenothiazine, pimozide, thioxanthenes, molindone, haloperidol, maprotiline, clozapine and tricyclic antidepressants leads to an enhancement of the CNS depressant effect and a weakening of the anticonvulsant effect of carbamazepine.

MAO inhibitors increase the risk of hyperthermic crises, hypertensive crises, seizures, fatal outcome (before prescribing carbamazepine, MAO inhibitors should be discontinued at least 2 weeks before or, if the clinical situation allows, even longer).

Concomitant administration with diuretics (hydrochlorothiazide, furosemide) may lead to hyponatremia accompanied by clinical manifestations.

Carbamazepine, when used concomitantly, weakens the effects of non-depolarizing muscle relaxants (pancuronium). In case of using such a combination, it may be necessary to increase the dose of muscle relaxants, and careful monitoring of patients should be carried out, since a faster cessation of their action is possible.

Carbamazepine reduces ethanol tolerance.

Myelotoxic drugs enhance the manifestations of hematotoxicity of carbamazepine.

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

May enhance the elimination of thyroid hormones.

Accelerates the metabolism of anesthetic agents (enflurane, halothane, fluorothane) with an increased risk of hepatotoxic effects.

Enhances the formation of nephrotoxic metabolites of methoxyflurane.

Enhances the hepatotoxic effect of isoniazid.

Storage Conditions

The drug should be stored out of the reach of children at a temperature not exceeding 30°C (86°F).

Shelf Life

The shelf life is 3 years. Do not use after the expiration date.

Dispensing Status

The drug is dispensed by prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.