Index of drugs

Monotherapy and supportive treatment for partial seizures and / or secondary generalized tonic-clonic seizures in adults and adolescents from 12 years. A second-line treatment for the prevention of migraines in adults.

1 tabl powl. contains 25 mg, 50 mg, 100 mg or 200 mg topiramate.

Antiepileptic medicine. It is also effective in the prevention of migraines. The three pharmacological properties of topiramate may contribute to anticonvulsant activity. Topiramate reduces the frequency of action potentials in neurons undergoing prolonged depolarization, probably by blocking voltage-dependent sodium channels. It increases the effect of GABA on certain types of GABA-ergic receptors. It exhibits weak antagonistic activity in the field of stimulation of the glutamate recipe, which belongs to the kainate / AMPA subtype, with no visible effect on the NMDA subtype receptor. In addition, topiramate inhibits some carbonic anhydrase isoenzymes (however, this effect is not considered to be the main antiepileptic component of topiramate activity). Following oral administration, topiramate is rapidly and independently absorbed from the gastrointestinal tract (bioavailability of about 50%), reaching a peak in the blood after about 2 hours. The pharmacokinetics of topiramate are linear. The degree of binding to plasma proteins is 13-17%. Topiramate is approximately 20% metabolised in the liver. Co-administration of anti-epileptic drugs that induce hepatic enzymes may increase the metabolism of topiramate to 50%. Topiramate and its metabolites are mainly excreted in the urine. After repeated topiramate administration at doses of 50-100 mg 2 times daily, mean T_0,5 was about 21 h. Steady state in patients with normal renal function is established after 4-8 days of treatment, and in severe renal failure after 10-15 days. The clearance of topiramate is reduced in patients with moderate to severe renal insufficiency and moderate to severe hepatic impairment.

Hypersensitivity to topiramate or other ingredients. The use of topiramate in the prevention of migraine is contraindicated in pregnancy and in women of childbearing potential not using effective methods of contraception.

Caution in patients with moderate or severe renal or hepatic impairment, in patients prone to kidney stones (history of stones, hypercalciuria) and patients taking drugs predisposeing to kidney stones or using a ketogenic diet (due to the formation of physiological conditions conducive to the formation of kidney stones ). Hydration during topiramate treatment may reduce the risk of kidney stones. Topiramate may reduce perspiration, which should be taken into account during increased physical activity and being in high temperature, due to the increased risk of overheating related side effects. During treatment with topiramate, it is recommended to determine the concentration of bicarbonates in the blood, especially in patients with an increased tendency to metabolic acidosis (patients with kidney disease, severe respiratory disorder, status epilepticus, diarrhea, after surgery, during a ketogenic diet and taking drugs that inhibit carbonic anhydrase). If metabolic acidosis develops and persists, dose reduction or discontinuation of topiramate should be considered. Patients treated with topiramate should be regularly weighed and monitored for weight loss, if clinically significant weight loss occurs during treatment, additional feeding or discontinuation of the medicine should be considered. Due to the possibility of mood disorders, depression and suicidal thoughts, patients taking topiramate should be under constant medical supervision. There is limited information on the use of the product in children under 12 years of age. Due to the sucrose content, patients with fructose intolerance, sucrase-isomaltase deficiency and glucose-galactose malabsorption should not use the preparation.

In animal studies, topiramate penetrated the placental barrier and was teratogenic. In the treatment of epilepsy, the preparation can be used during pregnancy only if the expected benefit to the mother outweighs the potential risk to the fetus. Interruption of seizure prophylaxis in pregnant women may be associated with a significant risk for both the mother and the fetus, which is probably greater than the risk of developing malformations. The use of topiramate in the prophylaxis of migraine is contraindicated in pregnancy. Topiramate is excreted in breast milk - use breast milk only after careful consideration of the benefits and risks of using it. Women of childbearing age treated with topiramate should use effective contraception.

Very common: weight loss, memory problems, anorexia, confusion, psychomotor slowing, depression, concentration disorders, anxiety; ataxia, paresthesia, speech disorders, aphasia; eye disorders (including double vision); pain and dizziness, fatigue, drowsiness, nervousness, nausea. Common: anemia, nosebleeds, purpura, leukopenia, thrombocytopenia; metabolic acidosis; apathy, weakness, euphoria, emotional instability, agitation, cognitive impairment, decreased libido, aggression, psychosis or psychotic symptoms; tremor, abnormal coordination, walking disorder, nystagmus, dysgeusia; constipation, abdominal pain; alopecia; urinary incontinence, kidney stones; menstrual disorders, impotence. Uncommon: hallucinations, personality disorders, suicidal thoughts, suicide attempts; hypokinesia, stupor; dyspnoea; diarrhea, vomiting, dryness of the oral mucosa; inflammation of the hair follicles, pruritus. Rare: neutropenia; acute myopia, glaucoma with a closed angle of perception, eye pain; increase in liver enzymes. Apart from the above the effects of post-marketing marketing have rarely been reported to reduce sweating with fever and facial flushing; very rarely transient loss of vision; isolated cases of hepatitis and hepatic failure, convulsions after discontinuation of topiramate and erythema multiforme, pemphigus, Stevens-Johnson syndrome, toxic epidermal necrolysis.

Orally. It is recommended to gradually increase the dose to a therapeutic level in order to avoid dose-related side effects. It is not necessary to assess the concentrations of topiramate in the blood to optimize the treatment with the preparation.Epilepsy (adults and adolescents from 12 years).monotherapy: initially 25 mg, in the evening, for one week. Then increase the dose at 1- to 2-week intervals by 25-50 mg daily and administer in 2 doses. In the event that the patient does not tolerate the above dose escalation scheme, it can be increased by smaller amounts or at longer intervals. The recommended initial target dose as monotherapy is 100 mg per day, and the maximum recommended daily dose - 400 mg. When discontinuing concomitant antiepileptic drugs, in order to obtain topiramate monotherapy, attention should be paid to the potential impact on seizure control. It is recommended to gradually discontinue other medications by reducing the dose of these drugs by 1/3 every other week. After the addition of drugs inducing hepatic enzymes, the concentration of topiramate will increase and it may be necessary to reduce the dose of topiramate, depending on the clinical response of the patient.Supportive treatment: initially 25-50 mg, in the evening, for one week. Then increase the dose at 1- to 2-week intervals by 25-50 mg daily and administer in 2 doses. The lowest effective dose is 200 mg per day. The usual daily dose is 200-400 mg in 2 doses. Some patients require a maximum daily dose of 800 mg.Prophylaxis of migraine (adults): initially 25 mg, in the evening, for one week. Then increase the dose by 25 mg a day every week. In the event that the patient does not tolerate the above dose escalation regimen, it can be increased at longer intervals. The recommended total daily dose of topiramate for prophylaxis of migraine is 100 mg / day in 2 doses.
Patients with moderate and severe renal impairment: it is recommended to start treatment with half of the usual daily dose and to increase the dose by a smaller amount and at a slower rate. In these patients, it may take longer (10-15 days) to achieve a steady-state concentration after each dose change.For patients on hemodialysis, an additional dose of topiramate should be given at approximately half the daily dose on the day of hemodialysis. The additional dose should be given in 2 doses at the beginning and after hemodialysis. The supplementary dose may vary depending on the type of dialysis and the equipment used.
The preparation can be taken regardless of meals, with the right amount of liquid. The tablets should not be divided.