Topiramate - instructions for use, dose, side effects, contraindications

Has a complex, completely unexplained mechanism of action. According to some reports, it blocks potential-dependent sodium channels, and also activates the interaction of GABA with GABA receptors. It is possible that topiramate reduces the activity of receptors of excitatory amino acids (presumably, glutamate receptors of the kainate subtype). The drug is used as an additional therapy for partial and generalized tonic-clonic seizures in combination with other antiepileptic drugs.

Pharmacokinetics:

F - 80% (regardless of food intake). The connection with plasma proteins is 13-17%. Biotransformation by means of hydroxylation, hydrolysis and glucuronation with the formation of six inactive metabolites. Half-life is 21 hours. Elimination by the kidneys is 70%.

Indications:

Partial or generalized tonic-clonic seizures in adults and children (as monotherapy or in combination with other anticonvulsants); seizures associated with Lennox-Gastaut syndrome, in adults and children (as a means of complementary therapy).

ICD-10

VI.G40-G47.G40 Epilepsy

Contraindications:

Hypersensitivity, pregnancy, breast-feeding, children's age of 2 years.

Carefully:

Renal (hepatic) failure, nephrolithiasis (including in the anamnesis, including family history), hypercalciuria.

Pregnancy and lactation:

Adequate and well-controlled studies in humans have not been conducted. In postmarketing studies, an increase in the incidence of hypospadias in newborn males has been found in the intrauterine period and has been affected by topiramate and other anticonvulsants. Causal link is not established. Topiramate can be used during pregnancy only if the benefits exceed the risk to the fetus. There is no information on the penetration into human milk in humans; penetrates into breast milk in rats. The risk and benefit of using topiramate during breastfeeding should be assessed.

Recommendations FDA - category C.

Dosing and Administration:

Individual, depending on the indications, the patient's age, kidney function and the effectiveness of the therapy.

Side effects:

From the side CNS and peripheral nervous system: often (especially during the selection of a dose) - ataxia, impaired concentration, confusion, dizziness, fatigue, paresthesia, drowsiness, impaired thinking; rarely - excitation, amnesia, anorexia, aphasia, depression, emotional lability, speech disorders, diplopia, nystagmus, visual impairment, taste perversion.

From the side digestive system: nausea; in some cases - an increase in the indicators of functional liver tests (in patients who took topiramate in combination with other drugs or as a monotherapy), hepatitis, liver failure (with topiramate at the same time as massive drug therapy).

Other: nephrolithiasis, weight loss.

Overdose:

Increased severity of side effects.

Treatment is symptomatic; hemodialysis.

Interaction:Alcohol and other drugs that depress the central nervous system - Increased oppression of the central nervous system.

Valproic acida - a decrease in the concentration and efficacy of topiramate by 14%, an increased risk of hyperammonemia, accompanied by or without encephalopathy.

Inhibitors of carbonic anhydrase (acetazolamide) - increased risk of renal calculus formation.

Carbamazepine, phenytoin, phenobarbital - reduction of the concentration and efficacy of topiramate.

Lithium preparations - reduction of the concentration and efficacy of topiramate by 20%.

Phenytoin - reduction of the concentration and efficacy of topiramate by 48%.

Estrogen Contraceptives - there may be a decrease in efficiency.

Special instructions:

The drug is effective for the treatment of partial seizures in refractory epilepsy (in addition to traditional therapy), but studies were short-lived; there is no information on the effectiveness of long-term use of topiramate, use in monotherapy, as well as in other forms of epilepsy.

In case of undesirable side reactions, titration of the dose is recommended.

In patients with a predisposition to nephrolithiasis, it is necessary to increase the amount of fluid consumed.

It is necessary to periodically monitor the intraocular pressure (for diagnosis of intraocular hypertension), often increasing after 1 month. from the beginning of treatment and can lead to glaucoma and acute myopia.

In clinical studies, there was no correlation between the concentration of topiramate in the blood andclinical effectiveness; There is no need to monitor the plasma concentration of topiramate to optimize treatment.

Instructions

Topiramate (Topiramatum)