Index of drugs

Monotherapy of partial epileptic seizures with or without secondary generalization and primary generalized clonic-tonic seizures in adults, adolescents and children over 6 years of age. Complementary therapy in children (2 years of age and above), adolescents and adults with partial epileptic seizures with or without secondary generalization or with primary generalized tonic-clonic epilepsy and for the treatment of epileptic seizures associated with Lennox-Gastaut syndrome. Topiramate is indicated for the prevention of migraine in adults after careful consideration of other alternative treatments. Topiramate is not recommended for the treatment of acute headache.

1 tabl powl. contains 25 mg, 50 mg or 100 mg topiramate. The drug contains lactose.

Antiepileptic medicine. It is also effective in the prevention of migraines. The three pharmacological properties of topiramate may contribute to anti-epileptic activity. Topiramate reduces the frequency of action potentials in neurons undergoing prolonged depolarization, indicating blocking the voltage-dependent sodium channels. Increases GABA activity through GABA receptors_AND. It has an antagonistic effect on the stimulation of glutamate receptors belonging to the kainate / AMPA receptor subtype without any visible effect on the NMDA subtype receptors. In addition, topiramate inhibits some carbonic anhydrase isoenzymes (however, this effect is not considered to be the main antiepileptic component of topiramate activity). The drug quickly, regardless of the presence of food is absorbed from the digestive tract (bioavailability is about 81%), reaching C_max about 2-3 hours after serving. In 13-17% it is associated with plasma proteins. It 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 by the kidneys. T_0,5 in the elimination phase is about 21 h. In patients with normal renal function, the blood levels reach steady state after 4-8 days of treatment. Plasma and renal clearance of topiramate is reduced in patients with impaired renal function. Plasma clearance is reduced in patients with moderate and severe hepatic impairment. In children, clearance is higher in topiramate, and T_0,5 in the elimination phase, shorter than in adult patients.

Hypersensitivity to the active substance or to any of the excipients. Prevention of migraines in pregnant women and women of childbearing potential who do not use effective methods of contraception.

Use with caution in patients with impaired renal or hepatic function (reduced clearance of topiramate). Some patients may experience weight loss during topiramate treatment; Monitoring for weight loss is recommended in patients taking topiramate. If weight loss occurs, an increase in the amount of food intake or a supplementary diet may be considered. When using topiramate, it is important to properly hydrate the patient because the risk of kidney stones is reduced. Treatment with topiramate may reduce the secretion of sweat, especially in children and adolescents. Activities such as physical exercise or exposure to high ambient temperatures when using topiramate may increase the risk of side effects related to overheating. In some patients, especially those with a predisposition to nephrolithiasis, there may be an increased risk of kidney stones and related signs and symptoms, such as renal colic, pain in the lumbar region or in the side. Risk factors for nephrolithiasis are: previous occurrence of stones, family history of urolithiasis and excessive excretion of Calcium in the urine. However, none of these factors clearly predict the occurrence of nephrolithiasis during treatment with topiramate. In addition, this risk may be increased in patients who are taking other products that promote kidney stones.A syndrome consisting of sudden myopia and secondary angle-closure glaucoma has been reported in patients taking topiramate. In the case of secondary glaucoma with a closed angle of infiltration, the drug should be discontinued and treatment should be implemented to reduce the intraocular pressure. It should be determined whether patients with history of eye disorders can be treated with topiramate. The treatment with topiramate is associated with the occurrence of hyperchloraemic metabolic acidosis with a normal anionic gap. Disease conditions or treatments that predispose to acidosis (such as kidney disease, severe respiratory disorder, status epilepticus, diarrhea, operations, ketogenic diet or certain medications) may potentiate the effect of topiramate to reduce bicarbonate levels. Chronic metabolic acidosis increases the risk of kidney stones and potentially may lead to osteopenia. Chronic metabolic acidosis in children can slow down the rate of growth. The effect of topiramate on skeletal growth and development has not been systematically studied in the pediatric population or in adults. Depending on the coexisting predisposing conditions, proper assessment including the determination of serum bicarbonate is recommended during topiramate treatment. In case of symptoms of metabolic acidosis (such as eg Kussmar's breathing, dyspnea, anorexia, nausea, vomiting, excessive fatigue, tachycardia or arrhythmia) it is recommended to measure the level of bicarbonate in the serum. If metabolic acidosis occurs and persist, a dose reduction or discontinuation of topiramate therapy should be considered (preceded by gradual dose reduction). Topiramate should be used with caution in patients with, or undergoing treatment for, a risk for metabolic acidosis. Patients should be monitored for symptoms of depression, suicidal ideation and attempts, and directed to appropriate treatment if necessary. Due to lack of data, it is not recommended for children under 2 years of age. The drug contains lactose lactose - should not be used in patients with rare hereditary disorders, such as galactose intolerance, Lapp lactase deficiency or malabsorption of glucose-galactose.

Topiramate was teratogenic in mice, rats and rabbits. In rats, topiramate passes through the placental barrier. The risk of congenital malformations in children of mothers using topiramate increases almost 3-fold. In addition, there was an increase in the birth rate of infants with low birth weight (<2500 g) after treatment with topiramate relative to the reference group. Topiramate should be prescribed for use during pregnancy after giving the patient complete information on the known risk of uncontrolled seizures and the potential risk to the fetus resulting from the use of the drug. Topiramate is contraindicated in pregnancy and in women of childbearing potential who do not use effective methods of contraception. Limited observations in patients indicate that topiramate is largely excreted in breast milk. A decision should be made whether to give up breastfeeding or to discontinue or discontinue topiramate therapy, taking into account the benefits of taking the medicine to the mother. It is recommended that women of childbearing age use adequate contraception.

Very common: weight loss, paresthesia, drowsiness, dizziness, nausea, diarrhea, inflammation of the nose and throat, fatigue, depression. Common: weight gain, anemia, attention disorders, memory disorders, amnesia, cognitive disorders, mental retardation, psychomotor disorders, convulsions, impaired motor coordination, tremor, lethargy, hypoaesthesia, nystagmus, dysgeusia, balance disorders, speech impairment, tremor intentional, sedation, visual disturbances (including blurred vision, double vision), peripheral dizziness, tinnitus, earache, shortness of breath, nosebleeds, nasal congestion, watery runny nose, vomiting, constipation, epigastric pain, indigestion, abdominal pain, dry mouth, discomfort in the stomach, paresthesia in the mouth area, gastritis, abdominal discomfort, kidney stones, pollakiur, dysuria, alopecia, rash, pruritus, arthralgia, muscle spasms, muscle pain, muscle tremors, muscular weakness, musculoskeletal pain in the cage thorax, anorexia, decreased appetite, fever, asthenia, irritability, gait disturbance, malaise, apathy, hypersensitivity reactions, slowing down of thought processes, insomnia, speech expression disorders, anxiety, confusion, disorientation, aggression, mood changes, excitement, mood instability , depressive mood, anger, abnormal behavior.Uncommon: presence of crystals in the urine, abnormal footing test (tandem), decreased white blood cell count, bradycardia, sinus bradycardia, palpitations, leukopenia, thrombocytopenia, enlarged lymph nodes, eosinophilia, decreased level of consciousness, grand mal convulsions , visual field disorders, partial seizure syndrome, speech disorders, psychomotor hyperactivity, fainting, sensory disorder, excessive saliva production, excessive drowsiness, aphasia, repetition of words, hypokinesis, dyskinesia, postural dizziness, poor sleep quality, burning sensation, loss of sensation, angina, cerebellar syndrome, dysesthesia, impaired taste, stupor, clumsiness, migraine aura, lack of taste, dysgraphia, dysphasia, peripheral neuropathy, pre-urgent conditions, dystonia, tingling, reduced visual acuity, scotoma, myopia, abnormal sensations in the eye, dry eye , photophobia, blepharospasm, increased tearing, flashes, mydriasis, presbyopia, deafness, one-sided deafness, neurosensory deafness, discomfort in the ear, hearing loss, exercise dyspnoea, excessive secretion from the paranasal sinuses, dysphonia, pancreatitis, bloating, gastroesophageal reflux disease, pain in the lower abdomen, hypoaesthesia of the mouth area, bleeding gums, abdominal distension, epigastric discomfort, abdominal tenderness, excessive salivation, mouth pain, unpleasant smell from the mouth, tongue pain, stones in the urinary tract, urinary incontinence, hematuria, sudden feeling of urge to the bladder, renal colic, kidney pain, lack of sweat, hypoaesthesia, urticaria, erythema, pruritus, macular rash, skin discoloration, allergic dermatitis, facial edema, swollen joints, musculoskeletal stiffness, pain in side, muscle fatigue, metabolic acidosis, hypokalemia, increased y appetite, polydipsia, hypotension, orthostatic hypotension, facial flushing, hot flushes, hyperthermia, excessive thirst, flu-like symptoms, lethargy, peripheral coolness, feeling of intoxication, feeling of anxiety, learning disabilities, erectile dysfunction, sexual dysfunction, suicidal thoughts , suicide attempts, hallucinations, psychotic disorders, auditory hallucinations, visual hallucinations, apathy, lack of spontaneous speech, disturbed sleep, lability of affect, lower libido, restlessness, crying, stuttering in speech, euphoric mood, paranoia, perseveration, panic disorder, crying, difficulty in reading, insomnia, flat affect, abnormal thinking, abused libido, indifference, middle insomnia, distraction, early waking in the morning, anxiety attacks, elevated mood. Rare: decrease in blood bicarbonate levels, neutropenia, apraxia, circadian rhythm disorder, hyperesthesia, weakening of smell, lack of smell, spontaneous tremor, akinesia, lack of response to stimuli, one-sided blindness, transient blindness, glaucoma, accommodation disorders, change in the perception of depth of the image, glaring scars, swollen eyelids, twilight blindness, amblyopia, ureteric stones, renal tubular acidosis, Stevens-Johnson syndrome, erythema multiforme, abnormal skin smell, eye edema, local urticaria, discomfort in the extremities, hyperchloraic acidosis, Raynaud's syndrome, face edema, calcineosis, mania, anorgasmia, anxiety disorders, sexual arousal disorder, a sense of hopelessness / despair, orgasmic disorders, hypomania, and reduced orgasmic experience. Not known: Near-angle glaucoma, macular degeneration, eye disorder, toxic epidermal necrolysis, allergic edema, and conjunctival edema. Side effects reported more frequently in children (≥2-fold) than in adults include: decreased appetite, increased appetite, hyperchloraemic acidosis, hypokalemia, behavioral disorders, aggression attacks, apathy, sleep problems, suicidal thoughts, concentration disorders, lethargy, impaired circadian rhythm, low-quality sleep, increased tearing, sinus bradycardia, malaise and gait disturbances. Side effects that were reported only in children during double-blind and placebo-controlled studies include eosinophilia, psychomotor hyperactivity, dizziness, vomiting, hyperthermia, fever and learning problems.

Orally.In both adults and children, treatment should be started at a low dose and then gradually increased until the effective dose is reached. If the patient does not tolerate the dose titration scheme described below, it can be increased by smaller amounts or at longer intervals.Epilepsy. monotherapy. 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 reduce the dose of the antiepileptic drug by 1/3 every two weeks. After discontinuation of hepatic enzyme-inducing drugs, topiramate concentrations will increase and it may be necessary to reduce the dose of topiramate, depending on the clinical response of the patient.Adults: 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 divided doses. The recommended initial target dose in monotherapy is 100-200 mg per day in 2 divided doses, and the maximum recommended daily dose - 500 mg in 2 divided doses. Some patients with refractory epilepsy require a dose of up to 1,000 mg per day.Children aged> 6 years and young people: initially 0.5-1 mg / kg, in the evening, for one week. Then increase the dose at 1- to 2-week intervals by 0.5-1 mg / kg. daily and administered in 2 divided doses. The recommended initial target dose as monotherapy in children is 100 mg / day (ie approximately 2 mg / kg / day).Complementary therapy for patients with partial epileptic seizures with or without secondary generalization or with primary generalized tonic-clonic epilepsy and for the treatment of epileptic seizures associated with Lennox-Gastaut syndrome. Adults: 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 divided doses. In some patients, clinical efficacy can be achieved with the medicine once a day. The lowest effective dose is 200 mg per day. The usual daily dose is 200-400 mg in 2 divided doses.Children aged 2 and above and young people: initially 25 mg (or less, in the range of 1-3 mg / kg), in the evening, for one week. Then the dose should be increased by 1-3 mg / kg at 1- to 2-week intervals. daily and administered in 2 divided doses. The recommended total dose of topiramate in children is 5-9 mg / kg. daily in 2 divided doses. Doses up to 30 mg / kg were tested. daily and these doses were well tolerated.Migraine. Adults: initially 25 mg, in the evening, for one week. Then increase the dose at 25-week intervals by 25 mg daily. The recommended total daily dose of topiramate for prophylaxis of migraine is 100 mg / day in 2 divided doses. Some patients may benefit from a total daily dose of 50 mg. Some patients require a daily dose of 200 mg (in this case, special attention should be paid to the increased risk of side effects). Topiramate is not recommended for the prophylaxis of migraine in children and adolescents.Special groups of patients. In patients with renal insufficiency, the time to steady-state after each dose adjustment may be longer. 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 divided doses, at the beginning and after hemodialysis. The supplementary dose may vary depending on the type of dialysis and the equipment used. No dose adjustment is required in the elderly. It is not necessary to control the concentration of the drug in the blood. If topiramate is used in combination with phenytoin, the dose of phenytoin may need to be adjusted. The inclusion or discontinuation of phenytoin and carbamazepine may require dose adjustment of topiramate.
Topiramate should be discontinued gradually: in adult patients with epilepsy, reduce the dose by 50-100 mg daily at 1-week intervals and by 25-50 mg daily at 1-week intervals in the prevention of migraine; in children, the drug should be discontinued for 2-8 weeks. The preparation can be taken regardless of meals, with the right amount of liquid. The tablets should not be divided.