Topamax capsules 25mg №60

Capsules

Composition

1 caps contains topiramate 25 mg

60 pcs.

Mechanism of action

Topamax - an antiepileptic drug. Belongs to the class of sulfate-substituted monosaccharides.
Antiepileptic activity of the drug due to a number of its properties. Topiramate reduces the frequency of action potentials characteristic of a neuron in a state of persistent depolarization, which indicates the dependence of the blocking action of the drug on sodium channels on the state of the neuron. Topiramate potentiates the activity of GABA for certain subtypes of GABA receptors (including GABA_Areceptors), and also modulates the activity of GABA itself_A-receptors, prevents the activation of kainate sensitivity of the kainate / AMPK receptors to glutamate, does not affect the activity of N-methyl-D-aspartate towards NMDA receptors. These effects of the drug are dose-dependent when plasma topiramate concentration is from 1 μM to 200 μM, with a minimum activity ranging from 1 μM to 10 μM.
In addition, topiramate inhibits the activity of some isoenzymes of carbonic anhydrase, however, this effect is weaker in topiramate than in acetazolamide and, apparently, is not central to the antiepileptic activity of topiramate.

Indications and usage

- partial or generalized tonic-clonic seizures in adults and children over 2 years of age (as monotherapy or in combination with other anticonvulsants);
- seizures associated with Lennox-Gastaut syndrome in adults and children older than 2 years (as a means of additional therapy).

Contraindications

- pregnancy;
- lactation period (breastfeeding);
- children under 2 years old;
- hypersensitivity to the drug.

Pregnancy and Breastfeeding

Adequate and strictly controlled clinical studies of the safety of using Topamax in pregnancy have not been conducted. However, the use of the drug during pregnancy is possible only in the case when the intended benefit to the mother outweighs the potential risk to the fetus.
Excretion of topiramate with breast milk has not been studied in controlled studies. A limited number of observations suggests that topiramate is excreted in breast milk. If necessary, the use of Topamax during lactation should decide on the termination of breastfeeding.

Dosage and administration

Inside regardless of the meal.

To achieve optimal control of epileptic seizures in children and adult patients, it is recommended to begin treatment with the administration of low doses of the drug, followed by gradual titration to an effective dose.

Capsules are intended for patients who have difficulty swallowing pills (for example, children and elderly patients). In such cases, the capsule of the drug Topamax should be carefully opened, mix its contents with a small amount (about 1 tsp) of any soft food. This mixture should be swallowed immediately, without chewing. Do not store medicine mixed with food until the next dose. Capsules drug Topamax can be swallowed whole.

Use in combination with other anticonvulsants in adult patients. The minimum effective dose is 200 mg per day. Typically, the total daily dose ranges from 200 to 400 mg and is taken in 2 divided doses. Some patients may need to increase the daily dose to the maximum - 1600 mg. It is recommended to start treatment with a low dose, followed by gradual selection of an effective dose. Selection of the dose begins with 25-50 mg, taking them overnight for 1 week. In the future, with weekly or 2-week intervals, the dose can be increased by 25-50 mg and taken in 2 divided doses. The selection of the dose should be guided by the clinical effect. In some patients, the effect can be achieved when taking the drug 1 time per day. To achieve the optimal effect of treatment with Topamax, it is not necessary to control its plasma concentration.

These dosage recommendations apply to all adult patients, including the elderly, in the absence of kidney disease (see"Special instructions").

Combined anticonvulsant therapy in children older than 2 years. The recommended total daily dose of Topamax as an additional therapy is from 5 to 9 mg / kg and is taken in 2 divided doses. The selection of the dose should be started with 25 mg (or less, based on the initial dose - from 1 to 3 mg / kg per day), taking them overnight for 1 week. In the future, with weekly or 2-week intervals, the dose can be increased by 1-3 mg / kg and taken in 2 divided doses. The selection of the dose should be guided by the clinical effect. Daily dosages up to 30 mg / kg are usually well tolerated.

Monotherapy, general provisions. When canceling concomitant anticonvulsant drugs for the purpose of monotherapy with topiramate, it is necessary to consider the possible influence of this step on the frequency of seizures. In cases where there is no need to abruptly cancel concomitant anticonvulsants for safety reasons, it is recommended to reduce their doses gradually, reducing the dose of the concomitant anti-epileptic drug by 1/3 every 2 weeks.

With the abolition of drugs that are inducers of liver enzymes, the concentration of topiramate in the blood will increase. In such situations, in the presence of clinical indications, the dose of Topamax can be reduced.

Monotherapy in adults. At the beginning - 25 mg of the drug Topamax at bedtime for 1 week. Then the dose is increased with an interval of 1–2 weeks by 25 or 50 mg (the daily dose is divided into 2 doses).If the patient does not tolerate such a mode of increasing the dose, it is possible to increase the intervals between dose increases, or to increase the dose more smoothly. The selection of the dose should be guided by the clinical effect.

The initial dose for monotherapy with topiramate in adults is 100 mg / day, and the maximum daily dose should not exceed 500 mg. Some patients with refractory forms of epilepsy tolerate monotherapy with topiramate in doses up to 1000 mg / day. Dosing recommendations apply to all adults, including elderly patients who are not suffering from kidney disease.

Monotherapy in children. Children over the age of 2 years in the first week of treatment should be given topiramate at a dose of 0.5-1 mg / kg body weight before bedtime. Then the dose is increased with an interval of 1–2 weeks by 0.5–1 mg / kg / day (the daily dose is divided into 2 doses). If the child does not tolerate such a mode of increasing the dose, it is possible to increase the dose more smoothly or increase the intervals between dose increases. The magnitude of the dose and the rate of its increase should be determined by the clinical result.

The recommended dose range for monotherapy with topiramate in children over the age of 2 years is 3–6 mg / kg / day. Children with newly diagnosed partial seizures can be prescribed up to 500 mg / day.

Migraine. The recommended total daily dose of topiramate for the prevention of migraine attacks is 100 mg in 2 divided doses. At the beginning of treatment, the patient should take 25 mg of Topamax at bedtime for 1 week.Then the dose is increased with an interval of 1 week at 25 mg / day. If the patient does not tolerate such a mode of increasing the dose, you can increase the intervals between dose increases, or increase the dose more smoothly. The selection of the dose should be guided by the clinical effect.

In some patients, a positive result is achieved with a daily dose of topiramate of 50 mg. In clinical studies, patients received various daily doses of topiramate, but not more than 200 mg / day.

Special notes

Cancel Topamax should gradually to minimize the possibility of increasing the frequency of seizures. When conducting clinical trials, the dose of the drug was reduced by 100 mg once a week.
The use of Topamax may increase the risk of kidney stones and associated symptoms (renal colic, pain in the side and in the kidney area), especially in patients with a predisposition to nephrolithiasis (stone formation in the past, nephrolithiasis in the family history, hypercalciuria), as well as against the background of the use of other drugs that contribute to the development of nephrolithiasis. To reduce the risk of nephrolithiasis, increase the amount of fluid consumed.
When using topiramate, hyperchloremic, not associated with anion deficiency, metabolic acidosis can occur (for example, a decrease in plasma bicarbonate concentration below the normal level in the absence of respiratory alkalosis).Such a decrease in serum bicarbonate concentration is a consequence of the inhibitory effect of topiramate on renal carbonic anhydrase. In most cases, a decrease in the concentration of bicarbonates occurs at the beginning of the drug intake, although this effect may appear in any period of treatment with topiramate. The level of reduction is usually weak or moderate (the average value is 4 mmol / l when used in adult patients at a dose of more than 100 mg / day and about 6 mg / kg body weight / day when used in pediatric practice). In rare cases, patients had a decrease in concentration below the level of 10 mmol / l. Some diseases or treatments that predispose to the development of acidosis (for example, kidney disease, severe respiratory diseases, status epilepticus, diarrhea, surgical interventions, ketogenic diet, taking certain medications) can be additional factors that increase the bicarbonate-reducing effect of topiramate.
In children, chronic metabolic acidosis can lead to stunted growth. The effect of topiramate on growth and possible complications associated with the skeletal system have not been systematically studied in children and adults.
In connection with the foregoing, in the treatment with topiramate it is recommended to conduct the necessary studies, including the determination of the concentration of bicarbonate in serum. If metabolic acidosis occurs and persists, it is recommended to reduce the dose or stop taking topiramate.
In the event of a syndrome involving myopia associated with angle-closure glaucoma, treatment includes discontinuation of Topamax (as soon as the doctor deems it possible) and appropriate measures aimed at reducing intraocular pressure. Usually these measures lead to the normalization of intraocular pressure.
If, against the background of taking the drug Topamax, the patient's body weight decreases, then the diet should be adjusted.
In patients with impaired liver function, topiramate should be used with caution because of a possible decrease in the clearance of this drug.
Patients taking Topamax should refrain from drinking alcohol.
During Topamax therapy, they do not recommend the use of other drugs that have a depressant effect on the central nervous system.
Use in pediatrics
The drug is approved for use in children over 2 years.
Influence on ability to drive motor transport and control mechanisms
Precautions should be prescribed the drug to patients engaged in potentially hazardous activities that require increased attention and speed of psychomotor reactions, because the drug may cause drowsiness, dizziness.

With simultaneous use with Carbamazepine , valproic acid, phenobarbital, primidone Topamax does not affect the values ​​of their equilibrium concentrations in plasma.The simultaneous use of Topamax led in some cases to an increase in the concentration of phenytoin, which is apparently due to inhibition of the isoenzyme (CYP 2C_meph).
Phenytoin and carbamazepine, while used with Topamax, reduce the concentration of topiramate in the plasma. Adding or removing phenytoin or carbamazepine during treatment with Topamax may require a dose change of the latter.
With the simultaneous use of valproic acid does not affect the concentration of topiramate in the plasma.
In studies conducted with the simultaneous use of a single dose of Topamax AUC Digoxin decreased by 12%.
When an oral contraceptive containing norethindrone and ethinyl estradiol was used simultaneously with Topamax, Topamax did not significantly affect the clearance of norethindrone, but the plasma clearance of the estrogen component increased significantly. Thus, while taking Topamax with oral contraceptives, their effectiveness can be reduced.
The drug interaction of hydrochlorothiazide and topiramate was evaluated in healthy volunteers with separate and co-administration of hydrochlorothiazide (at a dose of 25 mg) and topiramate (at a dose of 96 mg). Studies have shown that when you take topiramate and hydrochlorothiazide at the same time, there is an increase in C_max Topiramate by 27% and AUC Topiramate by 29%. The clinical significance of these studies has not been identified.The administration of hydrochlorothiazide to patients taking topiramate may require a dose adjustment of the latter. The pharmacokinetic parameters of hydrochlorothiazide did not undergo significant changes with concomitant therapy with topiramate.
The drug interaction of pioglitazone and topiramate was evaluated in healthy volunteers with separate and co-administration of drugs. A 15% decrease in the AUC of pioglitazone was found, C_max did not change. These changes were not statistically significant. A decrease in C was also found for the active hydroxymetabolite pioglitazone._max and AUC by 13% and 16%, respectively, and a decrease in C was detected for active ketometabolite_max, and AUC by 60%. The clinical significance of this data has not been elucidated. When co-prescribing patients Topamax and pioglitazone, special attention should be paid to the careful study of the diabetic status of these patients.

Symptoms: may increase the manifestations of the described side effects.
Treatment: gastric lavage; if necessary, conduct symptomatic therapy. The use of Activated carbon is not shown, since In vitro experiments have shown that activated carbon does not adsorb topiramate. An effective way to remove topiramate from the body is hemodialysis.

The drug should be stored in a dry place at temperatures not above 25 ° C.

3 years.