Expiration date: 06/2025
Composition
1 tablet film coating contains: 25 or 100 mg of topiramate.
Other ingredients: calcium hydrogen phosphate dihydrate (65 mg, 120 mg), pregelatinized starch (starch C * Pharm.) (70,5 mg, 111 mg), magnesium hydroxycarbonate heavy (heavy magnesium carbonate) (30 mg, 50 mg), magnesium stearate (1.5 mg, 3 mg), povidone (8 mg, 16 mg).
Composition of coating film: selekoat AQ-02140 (6 mg, 12 mg) [hypromellose (hydroxypropyl methylcellulose), Macrogol (polyethylene glycol 400), macrogol (polyethylene glycol 6000), titanium dioxide, sunset yellow dye].
Packaging
In packing 28 pcs.
pharmachologic effect
Topiramate - antiepileptic drug. It reduces the incidence of repetitive action potentials characteristic of a neuron in a state of persistent depolarization by blocking sodium channels. It increases the activity of ?-aminobutyric acid (GABA) in respect of certain subtypes of GABA receptors (including GABA [A] receptors), and modulates the activity of receptors themselves prevents activation sensitivity kainate subtype kainate / AMPA (?-amino-3- hydroxy-5-methylisoxazole-4-propionic acid) receptors to glutamate has no effect on the activity of N-methyl-D-aspartate (NMDA) against NMDA-receptor subtype. These effects are dose-dependent at concentrations of drug in plasma from 1 mol to 200 mol, with minimal activity in the range of 1 mol to 10 mol. Depresses the activity of certain isozymes of carbonic anhydrase, however, this effect is not a major antiepileptic activity of topiramate.
testimony
Epilepsy:
As monotherapy topiramate is used in adults and children over 3 years old with epilepsy (including in patients with newly diagnosed epilepsy).
In the combined therapy of topiramate is used in adults and children over 3 years old with partial or generalized tonic-clonic seizures and for the treatment of seizures in the background of Lennox-Gastaut syndrome.
Contraindications
Hypersensitivity, pregnancy, lactation. Topiramate in the dosage form (tablets) because of difficulties in swallowing are not recommended for use in children under 3 years.
Precautions: in renal and liver failure, nefrourolitiaze (including past and family history), hypercalciuria.
Pregnancy and breast-feeding
In absence of clinical data, it is not applicable for the treatment of pregnant women. Topiramate is excreted in breast milk in women. The drug is contraindicated in women during lactation. If you need the drug during lactation, breast-feeding should be discontinued.
Dosing and Administration
Inside, regardless of meals.
When used as monotherapy, it is necessary to take into account the possible impact of the abolition of concomitant anticonvulsant therapy on seizure frequency. In cases where there is no need to cancel sharply concomitant anticonvulsant therapy for safety reasons, it is advisable to reduce the dose of the concomitant drug by a third every 2 weeks. If you cancel the drugs that are inducers of "liver" enzymes, topiramate concentration in the blood will increase. In such situations, if clinically indicated dose of topiramate can be reduced.
Adult patients at the start of monotherapy should take 25 mg of topiramate 1 time a day at bedtime for 1 week. Then the dose is increased at intervals of 1-2 weeks at 25 or 50 mg (daily dose is divided into two steps). In such a regime of intolerance to the patient dose escalation is possible to increase the intervals between increasing the dose or increase the dose more slowly. In the selection of dose should be guided by clinical effect.
The recommended dose for topiramate monotherapy in adults is 100 mg per day and the maximum daily dose - 500 mg. Some patients with refractory forms of epilepsy tolerate topiramate monotherapy at doses up to 1 g / day.
Children older than 3 years in monotherapy in the first week of treatment - 0.5-1 mg / kg body weight per day, at bedtime. the dose was then increased at intervals of 1-2 weeks at 0.5-1 mg / kg per day (daily dose is divided into two steps). If a child can not tolerate such a dose escalation mode, it is possible to increase the dose more gradually or increase the interval between increasing the dose. In the selection of dose rate and its increase should be guided by clinical efficacy.
The recommended dose range with topiramate monotherapy in children over the age of 3 years is 3-6 mg / kg per day. The maximum daily dose for children with newly diagnosed partial seizures do not exceed 500 mg per day.
Side effects
General disorders: often - fatigue, irritability, weight loss, often - fatigue, anxiety in children fever, rarely - swelling of the face, metabolic acidosis, polydipsia, cold extremities, very rare - generalized edema, flu-like symptoms.
On the part of the central nervous system: very often - ataxia (incoordination of movements), decreased ability to concentrate, dizziness, paresthesia, often - drowsiness, abnormal thinking, rarely - nystagmus, emotional lability, tremor, amnesia, perversion of taste sensations, speech disorder (aphasia, dysarthria).
From the digestive system: very often - loss of appetite, often - nausea, diarrhea, constipation, dyspepsia, dry mouth, gastritis, gastroesophageal reflux disease, rarely - bloating, bad breath, excessive salivation, thirst.
From the musculoskeletal system: often - arthralgia, muscle cramps, muscle cramps, myalgia, including the chest, rarely - muscle stiffness very rare: joint swelling, discomfort in the limbs.
Violations of the cardiovascular system: rarely - bradycardia, tachycardia, orthostatic hypotension,
From the senses: common - blurred vision (diplopia), increased lacrimation, mydriasis, night blindness, reduced visual acuity, rarely - conjunctival edema, after 1 month of therapy may develop ocular hypertension, as a consequence - myopia, angle-closure glaucoma .
On the part of the organ of hearing: often - pain in the ears, tinnitus, vertigo in children, rarely - discomfort in the ears, hearing loss, deafness, including sensorineural deafness and unilateral deafness.
With the respiratory system: often - shortness of breath, nosebleeds, rarely - nasal congestion, hypersecretion in the paranasal sinuses, rhinorrhea have children.
For the skin: often - alopecia, pruritus.
Allergic reactions: seldom - allergic dermatitis, urticaria.
Violations of the urinary system: rarely - stone formation in the kidney (nephrolithiasis), urination disorders.
Laboratory parameters: infrequently - in the blood - increased number of leukocytes, platelets (leukopenia, thrombocytopenia), in children in the blood - increased number of eosinophils (eosinophilia), reducing the concentration of hydrogen, the concentration of potassium in the blood, detection of crystals in the urine (crystalluria) seldom : reduction in the number of neutrophils (neutropenia) .pripadkami not exceed 500 mg per day.
Drug interactions
Effect of topiramate on the concentrations of other antiepileptic drugs (AEDs): concomitant use of topiramate with other AEDs (phenytoin, carbamazepine, valproic acid, phenobarbital, primidone) has no effect on the values ??of their equilibrium concentrations in the plasma, except for certain patients in whom the addition of topiramate to phenytoin may increase phenytoin plasma concentrations. Every patient who receives phenytoin and which develop clinical signs or symptoms of toxicity, it is necessary to monitor the concentration of phenytoin in plasma. In a study of the pharmacokinetics in patients with epilepsy the addition of topiramate to lamotrigine had no effect on the equilibrium concentration of the last at doses of 100-400 mg topiramate per day. In the course of therapy and after the abolition of lamotrigine (mean dose of 327 mg per day), the equilibrium concentration of topiramate did not change.
Exposure to other antiepileptic drugs in the concentration of topiramate: Phenytoin and carbamazepine reduce plasma concentrations of topiramate. The addition or withdrawal of phenytoin or carbamazepine during treatment with topiramate may require changes in the dose of the latter. The dose should be selected, focusing on achieving the desired clinical effect. The addition or cancellation of valproic acid do not cause clinically significant changes in plasma concentrations of topiramate and, therefore, does not require changing the dose of topiramate.
Digoxin: the study while receiving topiramate using a single dose of digoxin Digoxin AUC in plasma was reduced by 12%. In the application or cancellation of topiramate to patients receiving digoxin, special attention should be given to the routine monitoring of digoxin serum concentrations.
Do not take topiramate with alcohol or other drugs that cause central nervous system depression.
Oral Contraceptives: Significant dose-dependent decrease in efficiency was observed at doses of ethinyl estradiol topiramate 200-800 mg per day. The risk of reducing the effectiveness of contraceptives and increased breakthrough bleeding should be considered in patients taking oral contraceptives in combination with topiramate. Patients receiving estrogensoderzhaschie contraceptives, you must report any changes in the timing and nature of menstruation. Contraceptive effectiveness can be further reduced in the absence of breakthrough bleeding.
Lithium Drugs: If concomitant use of topiramate and lithium preparations should monitor the concentration of lithium in blood plasma.
Risperidone: In an application of topiramate at dosages of 250 or 400 mg per day of risperidone AUC received at doses 6.1 mg per day, respectively reduced by 16% and 33%. The overall pharmacokinetics of the active agents (risperidone and 9-hydroxyrisperidone) changed insignificantly.
Hydrochlorothiazide: In simultaneous reception of topiramate and hydrochlorothiazide is an increase in the maximum concentration of topiramate by 27% and AUC by 29% of topiramate. The use of hydrochlorothiazide in patients treated with topiramate may require dose adjustment of topiramate. Pharmacokinetic parameters of hydrochlorothiazide has not been subjected to significant change with concomitant topiramate therapy.
Metformin: In simultaneous reception of topiramate and metformin is an increase in the maximum concentration and AUC of metformin by 18% and 25% respectively, whereas metformin clearance while the use of topiramate was reduced by 20%. Topiramate does not affect the time to maximum concentration of metformin in plasma. The clearance of topiramate when used together with metformin reduced. The extent of the revealed changes of clearance has not been studied. The clinical significance of the impact of metformin on the pharmacokinetics of topiramate is unclear. In the case of addition or cancellation of topiramate in patients receiving metformin should focus on careful study of the state of patients suffering from diabetes.
Pioglitazone: In clinical trials revealed a decrease in AUC of pioglitazone by 15%, without changing the maximum concentration of the drug. These changes were not statistically significant. In a joint application by patients topiramate and pioglitazone should focus on careful study of the state of patients suffering from diabetes.
Glibenclamide: a study was conducted to study drug interactions pharmacokinetics of glibenclamide (5 mg per day) in an equilibrium state, used alone or together with topiramate (150 mg daily) in patients with type 2 diabetes. In the application of topiramate glibenclamide AUC was decreased by 25%. There was also reduced the level of systemic exposure to the active metabolite. Glibenclamide did not affect the pharmacokinetics of topiramate in an equilibrium state. In the application of topiramate in patients receiving glyburide (glibenclamide or application in patients receiving topiramate), the patient should be carefully monitored to assess the condition of diabetes mellitus.
Other drugs: the simultaneous use of topiramate with drugs predisposing to nephrolithiasis, may increase the risk of kidney stones.
Valproic acid: the combined use of topiramate and valproic acid in patients undergoing well each drug separately, accompanied by hyperammonemia with or without encephalopathy her. In most cases, the signs and symptoms disappear after withdrawal of one of the drugs. This adverse event is not due to pharmacokinetic interactions. Communication between the application and hyperammonemia topiramate alone or in combination with other drugs is not established.
Amitriptyline: amitriptyline, while the application is an increase topiramate to maximum concentration AUC metabolite nortriptyline and 20%,
Haloperidol: while the use of haloperidol to haloperidol AUC topiramate increase occurs at 31%
Diltiazem: the simultaneous use of diltiazem is a reduction with topiramate diltiazem AUC by 25% increase in AUC is 20% of topiramate.
Overdose
Symptoms: increased dose-related side effects.
Treatment: acute overdose should immediately wash out the stomach. If necessary spend symptomatic therapy. An effective way of removing topiramate from the body is hemodialysis.
Storage conditions
In a dry, dark place at a temperature no higher than 25 ° C.
Shelf life
2 years.
