Talopsa^® (Tablets) Instructions for Use

Marketing Authorization Holder

Rinpharm LLC (Russia)

Manufactured By

Pharmproekt, JSC (Russia)

ATC Code

N03AX03 (Sultiame)

Active Substance

Sultiame (Rec.INN registered by WHO)

Dosage Forms

	Talopsa®	Film-coated tablets, 50 mg: 50 or 200 pcs.
		Film-coated tablets, 200 mg: 50 or 200 pcs.

Dosage Form, Packaging, and Composition

Film-coated tablets white, round, biconvex, with a score on one side; the core on the cross-section is white or almost white.

Excipients: lactose monohydrate, corn starch, hypromellose (hydroxypropylcellulose), colloidal silicon dioxide, magnesium stearate.

Film coating composition Opadry white (YS-1-7040) [hypromellose (hydroxypropylmethylcellulose), macrogol, titanium dioxide, talc].

50 pcs. – polyethylene jars (1) – cardboard packs.
200 pcs. – polyethylene jars (1) – cardboard packs.

Film-coated tablets white, round, biconvex, with a score on one side; the core on the cross-section is white or almost white.

Excipients: lactose monohydrate, corn starch, hypromellose (hydroxypropylcellulose), colloidal silicon dioxide, magnesium stearate.

Film coating composition Opadry white (YS-1-7040) [hypromellose (hydroxypropylmethylcellulose), macrogol, titanium dioxide, talc].

50 pcs. – polyethylene jars (1) – cardboard packs.
200 pcs. – polyethylene jars (1) – cardboard packs.

Clinical-Pharmacological Group

Antiepileptic drug

Pharmacotherapeutic Group

Antiepileptic agents; other antiepileptic agents

Pharmacological Action

Anticonvulsant of the second generation. The structure of sultiame differs from other anticonvulsants. It is a derivative of a cyclic sulfonamide without antimicrobial activity. The mechanism of action has not been fully elucidated.

It is believed that Sultiame inhibits carbonic anhydrase (isoenzyme II), which is responsible for regulating the pH composition of the blood. It depresses the motor centers of the cerebral cortex and increases the seizure threshold. It easily penetrates the histohematic barriers, crosses the placental barrier and into breast milk.

It reduces the frequency of focal seizures with and without secondary generalization, suppresses epileptiform activity characteristic of absences. It is also effective in myoclonic seizures.

Pharmacokinetics

After oral administration, it is rapidly and almost completely absorbed from the gastrointestinal tract, mainly in the upper parts of the small intestine. The time to reach C_max is from 2 to 8 hours. T_1/2 is from 2 to 9 hours. The therapeutic concentration is 60-100 µg/ml. It binds to plasma proteins by approximately 60%. Bioavailability has not been fully studied. The theoretical bioavailability is at least 90%.

It is excreted mainly in the urine – 80-90%, 10-20% is excreted in the bile. Within 24 hours, 32% of the administered substance was excreted by the kidneys unchanged.

Indications

Adults and children from 3 years of age: treatment of focal epileptic seizures with or without secondary generalization; treatment of age-dependent forms of childhood epilepsy (when other drugs are ineffective); correction of behavioral disorders in epilepsy; correction of hyperkinetic behavior; treatment of forms of epilepsy with myoclonic seizures.

ICD codes

Dosage Regimen

For oral administration.

The dosage regimen is set individually depending on the clinical picture of the disease, the effectiveness and tolerability of sultiame.

Adults – initial dose 100 mg 2 times/day or 50 mg 3 times/day, then the recommended dose is 200 mg 3 times/day.

Children – initial dose is 3-5 mg/kg/day in equally divided doses, then the optimal dose is 10-15 mg/kg/day, divided equally into several doses.

Adverse Reactions

Blood and lymphatic system disorders uncommon – leukopenia.

Metabolism and nutrition disorders very common – anorexia; common – weight loss.

Psychiatric disorders uncommon – hallucinations, anxiety, lack of motivation, mental changes, depression, behavioral abnormalities, suicidal thoughts and behavior.

Nervous system disorders common – ataxia, paresthesia in the limbs and face (dose-dependent), dizziness; uncommon – headache, muscle weakness, increased seizure activity, drooling, insomnia; frequency unknown – polyneuritis.

Eye disorders common – double vision.

Cardiac disorders common – angina pectoris, tachycardia.

Respiratory, thoracic and mediastinal disorders very common – rapid breathing, shortness of breath; common – hiccups.

Gastrointestinal disorders very common – stomach complaints (in about 10% of patients), uncommon – abdominal pain, nausea.

Hepatobiliary disorders frequency unknown – hepatotoxic reactions, increased activity of liver enzymes.

Skin and subcutaneous tissue disorders uncommon – Stevens-Johnson syndrome; frequency unknown – rash, Lyell’s syndrome.

Musculoskeletal and connective tissue disorders uncommon – joint pain.

Renal and urinary disorders frequency unknown – acute renal failure.

General disorders and administration site conditions one case of sultiame use has been reported, which led to progressive limb weakness, hypersalivation, slurred speech, increasing drowsiness up to coma. Symptoms decreased within a few hours after discontinuation of Sultiame. Sultiame is a carbonic anhydrase inhibitor, therefore, when using sultiame, adverse effects due to carbonic anhydrase inhibition, such as kidney stone formation, metabolic acidosis, hemodilution, changes in serum electrolyte levels, cannot be excluded. Disorders of calcium and vitamin D metabolism have sometimes been reported in connection with long-term anticonvulsant therapy.

Contraindications

Hypersensitivity to sultiame, other sulfonamides; hyperthyroidism; arterial hypertension; acute porphyria; children under 3 years of age (for oral administration in tablet form).

With caution

Renal impairment, renal failure, hepatic failure, history of mental illness, women of childbearing age.

Use in Pregnancy and Lactation

Contraindicated for use during pregnancy and breastfeeding.

Use in Hepatic Impairment

Use with caution in hepatic failure.

Use in Renal Impairment

Use with caution in renal impairment, renal failure.

Pediatric Use

Contraindicated for use in children under 3 years of age in the oral tablet dosage form.

Geriatric Use

There are no data on the use of sultiame in elderly patients.

Special Precautions

Patients, their caregivers, and family members should be instructed to immediately consult with the attending physician if fever, sore throat, allergic skin reactions with swollen lymph nodes, and/or flu-like symptoms occur during treatment with sultiame.

Progressive thrombocytopenia or leukopenia, accompanied by clinical symptoms such as fever or sore throat, require discontinuation of treatment. In cases of severe allergic reactions, the use of sultiame must be stopped immediately.

Treatment should also be discontinued if there is a prolonged increase in plasma creatinine concentration. Complete blood count, blood biochemistry, liver enzyme levels, and urinalysis should be performed regularly.

Antiepileptic drugs, including Sultiame, increase the risk of suicidal thoughts or behavior in patients taking these drugs for any indication.

Patients receiving any antiepileptic drug for any indication should be monitored for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior.

Epilepsy and many other conditions for which antiepileptic drugs, including Sultiame, are prescribed are themselves associated with morbidity and mortality, as well as an increased risk of suicidal thoughts and behavior. If suicidal thoughts and behavior occur during treatment, the relationship of these symptoms in a particular patient should be assessed, as it may be related to the underlying disease.

Patients, their caregivers, and family members should be informed that Sultiame increases the risk of suicidal thoughts and behavior and should be informed of the need to be vigilant for the emergence or worsening of signs and symptoms of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts, behavior, or thoughts of self-harm. Concerning behavior should be reported immediately to the attending physician.

It is recommended to monitor blood count, liver parameters, and renal function before starting therapy with sultiame, then at weekly intervals for the first month of treatment, then at monthly intervals. After six months of treatment, monitoring 2-4 times a year is possible.

Effect on ability to drive vehicles and operate machinery

The speed of psychomotor reactions may decrease after taking sultiame. Therefore, during the treatment period, patients must avoid driving vehicles and other activities requiring high concentration and speed of psychomotor reactions. Children are not recommended to ride bicycles, scooters, especially near the road, and to play games requiring high concentration on a busy street.

Drug Interactions

Ethanol is contraindicated during treatment. Since Sultiame is a sulfonamide derivative, it may theoretically have the same effect as disulfiram. Manifestations include a systemic reaction caused by vasodilation, with throbbing headache, respiratory depression, nausea, vomiting, tachycardia, arterial hypotension, amblyopia, confusion, shock reactions, arrhythmias, loss of consciousness, and convulsions. The severity and duration of these symptoms can vary greatly.

Concomitant use of sultiame and primidone may lead to serious side effects, especially in children, including dizziness, unsteady gait, drowsiness, and psychotic reactions.

It has been shown that the addition of sultiame to existing phenytoin therapy is accompanied by an increase in plasma phenytoin concentration. It is suggested that this may be due either to inhibition of phenytoin hydroxylation by sultiame or to displacement of phenytoin from the deposition site by sultiame. The dose of phenytoin may be reduced when sultiame is added. This combination requires particularly strict and frequent monitoring of plasma phenytoin concentration, especially in case of renal impairment.

Sultiame may cause an increase in serum phenobarbital concentration.

There are indications that the serum concentration of sultiame may decrease with simultaneous administration of carbamazepine.

In combination with lamotrigine, an increase in plasma lamotrigine concentration was also observed in individual cases. Therefore, lamotrigine levels should be monitored more frequently, especially at the beginning of treatment.

Concomitant use of sultiame and other carbonic anhydrase inhibitors (e.g., topiramate, acetazolamide) may increase the risk of adverse effects due to carbonic anhydrase inhibition.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

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.