Topamax. 100 mg. 28 tablets
drink in patients with epilepsy;
adjunctive therapy in adults and children / or over 2 years with partial seizures or generalized tonic-clonic seizures;
Topamax. 100 mg. 28 tablets
WHAT TOPAMAX AND WHAT IT IS USED FOR?
Topamax Topiramate contains as the active substance.
Topamax is indicated;
• Monotherapy in patients with newly diagnosed epilepsy or conversion to Monotherapy-
drink in patients with epilepsy;
• adjunctive therapy in adults and children / or over 2 years with partial seizures or generalized tonic-clonic seizures;
• adjunctive therapy in adults and children with seizures associated with syndrome Lennox_Gastaut.
TOPAMAX has been indicated for the prevention of migraine in adults. Topamax for treatment of acute attacks of migraine is not yet studied.
2. BEFORE YOU TAKE TOPAMAX
Do not take Topamax
• if you are allergic (hypersensitive) to the active substance or to any of the other
ingredients of this medicine.
Take special care with Topamax
In patients with / or without a history of seizures or epilepsy, antiepileptic drugs, including Topamax should be withdrawn gradually to minimize the appearance of seizures or increase their frequency. In clinical trials, daily dosages were reduced to weekly intervals from 50 to 100 mg, in adults with epilepsy and at intervals of 25 to 50 mg, in adults taking Topamax in a dosage of up to 100 mg / day for the prevention of migraine. In clinical trials in children Topamax withdrawn gradually over a period of two to eight weeks.
Unchanged topiramate and its metabolites are eliminated primarily by the kidneys. Eliminated by this pathway is dependent on renal function and does not depend on age. In patients with moderate or severe renal insufficiency, it may take 10-15 days to reach steady-state plasma concentrations, compared in patients with normal renal function, this is 4-8 days.
As with all patients, the appointment of the regimen must be based on clinical
results, ie seizure control and prevention of side effects, keeping in mind that for a patient with renal impairment may be required over a longer period of time to attain steady state at each dose.
Proper hydration Lo during treatment with Topamax is very important. Hydration may reduce the risk of nephrolithiasis (see below). Proper hydration before and during activities associated with physical exertion or exposure to high temperatures can reduce the risk of side effects associated with heat (see, possible side effects).
Mood / Depression
Observed are more common manifestations of mood swings and depression during treatment topiramate.
Small number of people being treated with antiepileptics such as topiramate have had thoughts of hurt myself-tion or suicide. If you have these thoughts, immediately contact your doctor.
In some patients, and in particular susceptible to nephrolithiasis, the risk of kidney stone formation and the associated signs and symptoms such as renal colic, lumbar pain, or pain and the groin, can be larger.
Risk factors for nephrolithiasis include a history of prior stone formation, a family history of nephrolithiasis and hypercalciuria (svrahizhvarlyane of salts in the urine), none of these risk factors can not be sure predictor of kidney stones during treatment with toliramat.
Furthermore, the increased risk may be and patients treated with other medications associated with risk of nephrolithiasis.
Reduced hepatic function
In patients with a change in liver function are recommended prescription tapiramat caution, because it can reduce the purification of this medicament.
Acute myopia and secondary angle closure glaucoma
A syndrome, comprising acute myopia and secondary angle closure glaucoma is described in patients treated with Topamax. Early symptoms include a sharp reduction in visual acuity and / or ocular pain. Ocular findings include myopia, anterior chamber edema, ocular hyperemia (redness) and increased intraocular pressure. There may be, and may not have mydriasis (dilation of the pupils and iris). This syndrome may be associated with accumulation of fluid supratsiliarno resulting in displacement of the front lens and the iris, with secondary angle closure glaucoma. Symptoms usually occur one month after initiation of treatment with TOPAMAX. Unlike narrow-angle primary glaucoma, which is rare in people under 40 years of age, secondary angle closure glaucoma associated with topiramate has been reported in children than in adults. Treatment includes discontinuation of Topamax as quickly as possible and on the advice of the doctor, and adequate measures to reduce intraocular pressure. These measures generally lead to lower intraocular pressure.
Svrahkiselinnata metabolic acidosis, without a loss of the anion, i.e. the reduction of serum bicarbonate levels below normal reference without respiratory alkalosis is associated with topiramate. This drop in serum bicarbonate is due to the inhibitory esrekt topiramate on renal carbonic anhydrase. Typically, the decrease in the bicarbonate occurs at the beginning, but can occur at any time during treatment. The reduction of the bicarbonate is usually mild to moderate (mean decrease of 4 mmol / l, at a dose equal to or greater than 100 mg topiramate per day for adults and about 6 mg / kg / day for children. Rarely occurs in some patients, a decrease in values below 10 mmol / L. The clinical or therapeutic conditions which predispose to the occurrence of acidosis, e.g., renal disease, severe respiratory disease, status epilepticus, diarrhea, surgery, ketogenic diet, or certain drugs, may have an additive effect on the reduction of bicarbonate induced by topiramate Chronic metabolic acidosis in children can slow growth, the effect of topiramate on growth and the effect on the bone has not been studied systematically in children or adults. depending on underlying conditions during topiramate treatment, it is recommended that do research in plasma bicarbonate. If the show metabolic acidosis and continues, to be taken to reduce the dose or discontinuing topiramate (using dose tapering).
Should be considered include supplements or increase food intake by patients who lose weight during treatment with this medication.
Taking Topamax with other medications
Effects of topamax on other antiepileptic drugs
Adding Topamax to other antiepileptic drugs (phenytoin, carbamazepine, valproic acid, phenobarbital or primidone) does not affect the plasma concentrations at steady state, with the exception of individual cases where the addition of TOPAMAX phenytoin may result in increased plasma concentrations phenytoin. This is probably due to inhibition of a specific isoform of the polymorphic enzyme (SYR2S19). Therefore, in any patient undergoing treatment with phenytoin, wherein the signs and symptoms of toxicity, must be carried out monitoring of plasma levels of phenytoin. Pharmacokinetic interaction studies in patients with epilepsy suggests that the addition of topiramate to lamotrigine had no effect on its plasma concentrations of topiramate dose of 100 to 400 mg / day. Furthermore, there is no change in the plasma concentrations of topiramate during and after discontinuation of lamotrigine (average dose 327 mg / day).
Effects of other antiepileptic drugs on topamax
Phenytoin and karbamazelin lowering plasma concentrations of toliramat. Addition or withdrawal of phenytoin or carbamazepine, in conducting therapy with TOPAMAX, may require adjustment of dosage him. These changes must be made after evaluation of clinical effect. Adding or interruption of treatment with valproic acid does not cause clinically significant changes in plasma concentrations of topiramate, which is why, in this case, it is not necessary to make a change in the dosage of Topamax
Other interactions Digoxin
In single-dose study, the area under the curve (AUC) of plasma concentration of serum digoxin decreased by 12% due to concomitant administration of TOPAMAX. The clinical relevance of this observation has not been determined. When you add or discontinue topamax in patients treated with digoxin should pay special attention to the routine monitoring of serum levels of digoxin.
Depressants of the central nervous system
Coadministration of topamax and alcohol or other drugs depressing the central nervous system has not been evaluated in clinical trials. It is not recommended to use simultaneously Topamax with alcohol or other drugs that depress the central nervous system,
In a study on the pharmacokinetic interactions in healthy volunteers assigned concurrent combination contraceptive product containing 1 mg norethindrone +35 mcg ethinylestradiol and topamax, taken in the absence of other medications at doses of 50 to 200 mg / day was not associated with statistically significant changes in mean exposure (AUC) of any component of oral contraceptives. In another study, ethinyl estradiol is reduced by a statistically significant at doses of Topamax 200.400 and 800 mg / day (18%, 21% and 30% respectively), when administered as adjunctive therapy in patients taking valproic acid. In both studies, Topamax (50 mg / day to 800 mg / day did not significantly affect} effect of norethindrone. Although there is a dose-dependent reduction of ethinyl-effects at doses between 200-800 mg / day, no significant dose-dependent change in etiniestradiop-exposure at doses between 50 and 200 mg / day. clinical significance of the changes observed is not known. could avoid the possibility of a reduction in contraceptive effectiveness and increase breakthrough bleeding in patients taking combination oral contraceptive products with Topamax . Patients taking estrogen containing contraceptives should be asked to report any changes in their menstruation, contraceptive efficacy may be reduced even in the absence of breakthrough bleeding.
In healthy volunteers saw a reduction of 18% of ADR in systemic exposure of lithium during concomitant topiramate 200 mg / day. In patients with bipolar disease, the pharmacokinetics of the lithium is not affected during the treatment with topiramate to 200 mg / day. Moreover, it is observed an increase of 26% of the systemic exposure to A11S of lithium after topiramate therapy at doses up to 600 mg / day. Serum lithium levels should be monitored when prescribing with topiramate.
Drug interaction studies performed with single or multiple dose in healthy volunteers and bipolar patients have yielded similar results. Risleridon when used concomitantly with topiramate at escalating doses on 100 200 n 400 mg / day. nastygva reduction in the systemic exposure of risperidone (16% and 33% of the AUC at steady state topiramate at dosages of 250 and 400 mg / day, respectively), when given in doses ranging between 1 and 6 mg / day. In all of the active antipsychotic fraction (risperidone and 9-hydroxyrisperidone) were observed minimal changes in pharmacokinetics that do not become apparent in the isolated 9-hydroxyrisperidone. There were no clinically significant changes in systemic exposure to the total active fraction of risperidone and topiramate. Therefore, this interaction is probably not clinically significant.
A drug interaction study in healthy volunteers evaluated the steady state pharmacokinetics of NST2 (25 mg / day) and topiramate (96 mg for 12/12 hours) taken separately or simultaneously. The survey results showed that Cmax of combed-mate has increased by 25% and AUC increased by 29% after the addition of topiramate to NST2. The clinical significance of this change is unknown. Adding NSTZ to treatment with topiramate may require adjustment of the dose of topiramate. Steady-state pharmacokinetics of NSTZ not changed significantly since the adoption of topiramate Laboratory results showed a decrease in serum potassium after topiramate or adopting NSTZ. This decrease is more pronounced when the adoption of topiramate and NSTZ simultaneously.
Study conducted in healthy volunteers for drug-drug interaction evaluated the steady state pharmacokinetics of metformin and topiramate in plasma when teyopsh was given alone and when teyoggsh and topiramate were given simultaneously. The study results showed that the average C max and average AUC 0-12h. increased by 18% and 25%, while the average CL / F decreased 20% when metformin was co-administered with topiramate. Toriramat not affect Tmah metformin. The clinical significance of the effect of topiramate tip metformin pharmacokinetics is unclear. Oral plasma clearance of topiramate was decreased when administered with metformin. The degree of change in the clearance is unclear. The clinical significance of the effect of metformin on the pharmacokinetics of topiramate is not clear. When topiramate is added or discontinued in patients treated with metformin, more attention should be given to the routine monitoring for adequate control of their diabetes.
Drug interaction study conducted in healthy volunteers evaluated the equilibrium concentration of topiramate and pioglitazone when administered alone and in combination. There is a 15% reduction in the AUC of pioglitazone unchanged with no statistical monitoring max.Tova znachimostpri active A hydroxy and 60% decrease in Cmax and AUC for the active keto-metabolite. The clinical significance of these findings is unknown. Upon addition of topiramate to treatment with pioglitazone or if pioglitazone is added to topiramate therapy, careful routine prospedyavane patients for adequate control of their diabetes.
A study of drug interaction in patients with diabetes type II, assess pharmaco-kinetics at steady state of glyburide (5mg/dnevno) and topiramate (150mg/dnevno) taken separately or simultaneously. Was noted a 25% reduction of AUC 24 of glyburide when given topiramate. Systemic exposure to the active metabolite 4-trans-hydroxy-glyburide (M1) and 3-cis-hydroxy-glyburide decreased by 13% and 15%, respectively, steady-state pharmacokinetics of topiramate were unaffected by concomitant administration of glyburide. When topiramate is given concomitantly with glyburide or vice versa, should pay special attention to routine monitoring for adequate control of diabetes.
Medications that predispose to nephrolithiasis
When used in conjunction with other medications that may predispose to nephrolithiasis, Topamax can increase the risk of nephrolithiasis. During treatment with Topamax to avoid these drugs, as they can establish a physiological medium, which could increase the risk of formation of kidney stones.
Co-administration of topiramate and valproic acid was coupled with svrahamoniemiya with / or without encephalopathy in patients who tolerated these drugs when they are administered separately. In most cases, the signs and symptoms disappear after cessation of treatment. This undesirable effect is not due to a pharmacokinetic interaction. No association was found between svrahamoniemiyata and topiramate therapy or concomitant treatment with other anti-epileptic drug.
Results from clinical studies indicate that topiramate was associated with a mean decrease of 4 mmol / l of serum bicarbonate (see Special considerations Topamax).
Pregnancy and lactation
Consult your doctor or pharmacist before taking any medication.
All women of childbearing age (who may become pregnant) should get specialist advice before starting treatment, because of the increased risk of congenital malformations. Treatment with protivoepiliptichni medications must be assessed again when the woman is planning to become pregnant. 06iknoveno risk of congenital malformations is 2-3 times greater in children pregnant women, treated with anti-epileptic drugs during pregnancy. The most common malformations affecting the lips and oral cavity, the cardiovascular system and the neural tube.
Treatment with other anti-epileptic drugs (polytherapy) is associated with a higher risk of congenital malformations than treatment with a single medicament (Monotherapy). Whenever possible, polytherapy regimens should be simplified.