Topiramate (Toreal) 25 mg – [28 tablets]

Topiramate refers to sulfate-substituted monosaccharides. It blocks sodium channels and suppresses the occurrence of repetitive action potentials against the background of prolonged depolarization of the neuron membrane. Increases γ – aminobutyric acid (GABA) activity against certain subtypes of GABA receptors. Prevents activation of kainatom kainat/AMPK (alpha-amino-Z-hydroxy-5-methylisoxazole-4-propionic acid) – glutamate receptors, without affecting N-methyl-D-aspartate (NMDA) activity with respect to NMDA – receptors. These effects are dose-dependent. In addition, topiramate inhibits the activity of some carboanhydrase isoenzymes. This effect is much weaker than that of the carboanhydrase inhibitor acetazolamide and is not a major component of the antiepileptic activity of topiramate.

– monotherapy of epilepsy in adults and children over 2 years of age (including patients with newly diagnosed epilepsy);

– as part of complex therapy in adults and children over 2 years of age with partial or generalized tonic-clonic seizures, as well as seizures against the background of Lennox-Gastaud syndrome;

– prophylaxis of migraine attacks in adults. Use of Toreal® for treatment of acute migraine attacks has not been studied.

– Hypersensitivity to any component of the drug;

– childhood under 2 years old;

– pregnancy and in women with preserved fertile potential, who do not use safe methods of contraception and during breast-feeding;

– lactase deficiency, lactose intolerance, glucose-galactose malabsorption.

Caution

Caution should be used with caution in hepatic or renal insufficiency, nephrourolithiasis (including past or family history), hypercalciuria. It should be taken into account that the risk of depression and suicidal syndrome increases when taking the drug. The dose should be reduced or the drug Toreal® should be withdrawn gradually to minimize the possibility of increasing the frequency of seizures.  According to clinical trials, doses were reduced by 50-100 mg at weekly intervals for adults receiving epilepsy therapy and by 25-50 mg in adults receiving 100 mg of topiramate daily for migraine prophylaxis. In children in clinical trials, topiramate was gradually withdrawn over 2-8 weeks. If a rapid withdrawal of Toreal® is medically necessary, appropriate monitoring of the patient is recommended.

 

• Orally, swallow the tablet whole, without chewing, regardless of meals.  For optimal seizure control, it is recommended to start treatment with a low dose followed by gradual titration to an effective dose.
• Toreal® tablets should not be divided into portions.
• Partial or generalized tonic-tonic seizures, as well as seizures on the background of Lennox-Gastaud syndrome
• Use in combination with other anticonvulsants in adult patients
• Minimum effective dose is 200 mg/day. Usually the total daily dose is 200-400 mg (in 2 doses). Some patients may need to increase the daily dose to a maximum of 1600 mg. Treatment starts with 25-50 mg daily at night for 1 week. Then the dose is increased by 25-50 mg daily for 1-2 weeks, with 2 times a day. The dose and frequency of administration are adjusted depending on the clinical effect. In some patients, the effect can be achieved by taking the drug once a day. It is not necessary to monitor the plasma concentration of Toreal® to achieve the optimal effect of the treatment. These recommendations apply to all adult patients, including the elderly, in the absence of renal disease.
• Combined anticonvulsant therapy in children over 2 years of age
• Recommended total daily dose of Toreal® preparation as additional therapy is from 5 to 9 mg/kg of body weight and should be taken in 2 intakes. Treatment is started with a dose of 25 mg (or less, based on the initial dose of 1 to 3 mg/kg/day) at night for 1 week. The dose is then increased by 1-3 mg/kg/day for 1 to 2 weeks, with a frequency of 2 doses per day, until optimal clinical effect is achieved.
• Daily doses up to 30 mg/kg are usually well tolerated.
• Epilepsy (including newly diagnosed)
• Monotherapy: general considerations
• When withdrawing concomitant anticonvulsant medications for the purpose of topiramate monotherapy, the possible effect of this step on seizure frequency must be considered. Where it is not necessary to abruptly withdraw a concomitant anticonvulsant for safety reasons, it is recommended to reduce their doses gradually, reducing the dose of the concomitant antiepileptic drug by one-third every 2 weeks.
• When drugs that are inducers of hepatic enzymes are withdrawn, blood concentrations of topiramate will increase. In such situations, if clinically indicated, the dose of Toreal® can be reduced.
• Monotherapy: adults
• Treatment starts with 25 mg at night for 1 week. Then the dose is increased by 25-50 mg per day for 1-2 weeks, with 2 times a day. If this dosing regimen is intolerable, the dose is increased by a smaller amount or at longer intervals. The dose and frequency of administration are adjusted according to the clinical effect. The recommended starting dose of topiramate for monotherapy in adults with newly diagnosed epilepsy is 100 mg/day, with a maximum recommended dose of 500 mg/day. These doses are recommended for all adults, including older adults with normal renal function.
• Monotherapy: children
• In children over 2 years of age, treatment begins with a dose of 0.5-1 mg/kg body weight at night for 1 week. Then the dose is increased by 0.5-1 mg/kg/day for 1-2 weeks, the frequency of administration is 2 times a day. If this dosing regimen is intolerant, the dose is increased by a smaller amount or at longer intervals. The dose and frequency of administration are adjusted depending on the clinical effect. The recommended dose range is 3-6 mg/kg body weight. Children with newly diagnosed partial seizures may be prescribed up to 500 mg per day.
• Migraine
• The recommended total daily dose of topiramate for the prevention of migraine attacks is 100 mg and is taken in 2 doses. At the beginning of treatment a patient should take 25 mg of Toreal® before sleep for 1 week. Then the dose is increased with an interval of 1 week by 25 mg per day. If a patient cannot tolerate this dose escalation regimen, the intervals between dose escalations may be increased or the dose may be raised more gently. Dose selection should be guided by clinical effect. In some patients, positive results are achieved at a daily dose of 50 mg of topiramate. In clinical trials, patients received different daily doses of topiramate, but not more than 200 mg per day.
• Special patient groups
• Renal impairment.
• Patients with moderate to severe renal impairment may need a reduced dose. Half the recommended starting dose and maintenance dose are recommended.
• Hemodialysis
• Since topiramate is removed from plasma during hemodialysis, an additional dose of Toreal® should be given on the days of hemodialysis, equal to about half of the daily dose. The additional dose should be divided into two doses taken at the beginning and after the completion of hemodialysis.