Topiramate Canon pills 25mg, 28pcs

Composition

1 film-coated tablet contains: Active ingredient:

topiramate 25 mg and 100 mg;

excipients:

calcium hydrogen phosphate dihydrate (65 mg,120 mg),

starch pregelatinization (starch) (70,5 mg 111 mg),

magnesium hydroxycarbonate heavy (magnesium carbonate heavy) (30 mg,50 mg),

magnesium stearate (1.5 mg,3 mg),

povidone (8 mg,16 mg);

the composition of the film shell Selamat AQ–02140 (6 mg,12 mg) [hypromellose (hydroxypropyl methylcellulose), macrogol (polyethylene glycol 400), macrogol (polyethylene glycol 6000), titanium dioxide, the colorant sunset yellow].

Pharmacological action

 The drug belongs to the class of sulfate-substituted monosaccharides.

Topiramate reduces the frequency of action potentials that are characteristic of a neuron in a state of persistent depolarization, which indicates the dependence of the blocking effect of the drug on sodium channels on the state of the neuron. This Active ingredient potentiates the activity of GABA against certain subtypes of GABA receptors (including GABAA receptors), modulates the activity of GABAA receptors themselves, and also prevents kainate from activating the sensitivity of kainate / AMPK receptors to glutamate and does not affect the activity of N-methyl-D-aspartate against NMDA receptors. These effects of topiramate are dose-dependent at plasma concentrations of topiramate ranging from 1 µm to 200 µm, with minimal activity ranging from 1 µm to 10 µm.

In addition, topiramate inhibits the activity of some carbonic anhydrase isoenzymes, but this effect in topiramate is weaker than in acetazolamide and, apparently, is not the main one in the antiepileptic activity of topiramate.

Pharmacokinetics

 After oral use, topiramate is absorbed quickly and effectively. Bioavailability – 81%. Food intake does not have a clinically significant effect on the bioavailability of topiramate. Binding to plasma proteins is 13-17%. After a single dose of up to 1.2 g, the average Vd is 0.55-0.8 l / kg.

The value of Vd depends on gender: in women, it is approximately 50% of the values observed in men, which is associated with a higher content of adipose tissue in the body of women. The pharmacokinetics of topiramate are linear. Plasma clearance remains constant, while AUC increases in proportion to the dose in the dose range from 100 to 400 mg. Css in plasma is reached after 4-8 days.

After repeated oral use at a dose of 100 mg 2 times/day, Cmax averages 6.76 mcg / ml. After oral use, about 20% of the dose is metabolized.

6 practically inactive metabolites were identified in human plasma, urine, and feces. It is mainly excreted by the kidneys in unchanged form (70%) and in the form of metabolites. Plasma clearance is 20-30 ml/min. After repeated use in doses of 50 mg and 100 mg 2 times/day, the average T1 / 2 of topiramate from plasma is 21 hours.

Indications

Epilepsy: as monotherapy for initial treatment in patients older than 2 years-partial or primary generalized tonic-clonic seizures; as part of complex therapy in patients older than 2 years-partial or generalized tonic-clonic seizures, as well as seizures on the background of Lennox-Gastaut syndrome.

Migraine: prevention of migraine attacks in adults.

Use during pregnancy and lactation

Adequate and strictly controlled clinical studies on the safety of topiramate use during pregnancy have not been conducted.

The use of topiramate during pregnancy can cause damage to the fetus. Data from the pregnancy registry show that intrauterine exposure to topiramate increases the risk of developing congenital malformations (for example, craniofacial defects such as cleft lip/cleft palate, hypospadias, and malformations of various body systems). These malformations were recorded both with topiramate monotherapy and with its use in combination therapy. Compared with the group of patients not taking antiepileptic drugs, data from the register of pregnant women with topiramate monotherapy indicate an increase in the frequency of children born with low body weight (less than 2500 g). No causal relationship has been established.

When treating women of childbearing age, the expected benefit of therapy to the mother and the potential risk to the fetus should be weighed, and alternative treatment options should be considered. If topiramate is used during pregnancy or if pregnancy occurs during treatment, the patient should be warned about the potential risk to the fetus.

A limited number of observations suggest that topiramate is excreted in breast milk. If it is necessary to use during lactation, the question of stopping breastfeeding should be decided.

Use in children

Do not use in children under 2 years of age.

Contraindications

Hypersensitivity to topiramate.

Use in patients with liver function disorders

Use with caution in patients with impaired liver function due to a possible decrease in the clearance of topiramate.

Side effects

Nervous system disorders:  paresthesia, drowsiness, dizziness, attention disorders, memory disorders, amnesia, psychomotor disorders, convulsions, poor coordination, tremor, lethargy, hypesthesia, nystagmus, dysgeusia, balance disorders, articulation disorders, intentional tremors (dynamic), sedation, depression of consciousness, convulsions like large convulsive seizures, visual field defect, complex partial seizures, speech disorder, psychomotor disability hyperactivity, syncope, sensory disturbances, drooling, aphasia, repetitive speech, hypokinesia, dyskinesia, postural vertigo, poor sleep quality, burning sensation, loss of sensation, parosmia, cerebellar syndrome, dysesthesia, hypogeusia, stupor, clumsiness, aura, ageusia, dysgraphy, dysphasia, peripheral neuropathy, pre-syncope, dystonia, apraxia, circadian rhythm disorder sleep rhythm disorders, hyperesthesia, hyposmia, anosmia, essential tremor, akinesia, lack of response to stimuli, learning difficulties.

Mental disorders:  depression, slow thinking, cognitive disorders, insomnia, severe speech disorders, anxiety, confusion, disorientation, aggression, mood lability, anxious arousal, emotional lability, depressive mood, anger, inappropriate behavior, suicidal ideation or attempts, auditory and visual hallucinations, psychotic disorder, apathy, lack of spontaneous speech, sleep disorders, affective lability, decreased libido, anxiety, tearfulness, dysphemia, euphoria, paranoid states, perseveration of thinking, panic attack, tearfulness, impaired reading skills, flattening of emotions, falling asleep disorder, abnormal thinking, loss of libido, lethargy, intrasomnic disorder, pathologically increased distractibility, early morning awakenings, panic reaction, mania, panic disorder, feelings of despair, hypomanic state.

From the side of the visual organ:  blurred vision, diplopia, visual impairment, decreased visual acuity, scotoma, myopia, abnormal eye sensations, dry eyes, photophobia, blepharospasm, increased lacrimation, photopsia, mydriasis, presbyopia, unilateral blindness, transient blindness, glaucoma, accommodation disorders, visual depth perception disorders, atrial scotoma, eyelid edema, night blindness, amblyopia, angle-closure glaucoma, maculopathy, oculomotor disorders.

From the hematopoietic system:  anemia, leukopenia, thrombocytopenia, lymphadenopathy, eosinophilia, neutropenia.

From the immune system:  hypersensitivity, allergic edema, conjunctival edema.

From the side of metabolism:  anorexia, decreased appetite, metabolic acidosis, hypokalemia, increased appetite, polydipsia, hyperchloremic acidosis.

From the side of the organ of hearing and balance:  vertigo, tinnitus, ear pain, deafness, unilateral deafness, sensorineural deafness, tinnitus discomfort, hearing impairment.

From the cardiovascular system:  bradycardia, sinus bradycardia, rapid heartbeat, orthostatic hypotension, hot flashes, hyperemia, Raynaud’s phenomenon.

Respiratory system disorders:  nasopharyngitis, dyspnoea, nosebleeds, nasal congestion, rhinorrhea, cough, shortness of breath during exercise, hypersecretion in the paranasal sinuses, dysphonia.

From the digestive system:  nausea, diarrhea, vomiting, constipation, upper abdominal pain, dyspepsia, abdominal pain, dry mouth, stomach discomfort, oral paresthesia, gastritis, abdominal discomfort, pancreatitis, flatulence, gastroesophageal reflux disease, lower abdominal pain, oral hypesthesia, bleeding gums, bloating, epigastric discomfort, soreness all over the body abdominal pain, salivary gland hypersecretion, oral pain, bad breath, glossodynia, hepatitis, liver failure.

Skin and subcutaneous tissue disorders:  alopecia, pruritus, rash, anhidrosis, facial hypesthesia, urticaria, erythema, generalized pruritus, macular rash, skin discoloration, allergic dermatitis, facial edema, Stevens-Johnson syndrome, erythema multiforme, skin odor, periorbital edema, localized urticaria, toxic epidermal necrolysis.

Musculoskeletal disorders:  arthralgia, muscle spasms, myalgia, muscle cramps, muscle weakness, muscle pain in the chest, joint swelling, muscle stiffness, side pain, muscle fatigue, discomfort in the extremities.

From the urinary system: nephrolithiasis, pollakiuria, dysuria, urinary stones, urinary incontinence under stress, hematuria, urgent painful urge to urinate, renal colic, pain in the kidney area, ureteral stones, renal tubular acidosis.

From the side of the reproductive system: erectile dysfunction, sexual dysfunction.

General reactions: fatigue, pyrexia, asthenia, irritability, gait disturbance, unusual sensations, malaise, hyperthermia, thirst, flu-like state, inertia, cold extremities, feeling intoxicated, anxiety, facial edema, calcification.

From the side of laboratory parameters: weight loss, weight gain, crystalluria, abnormal tandem gait test, leukopenia, increased activity of liver enzymes, hypokalemia, decrease in the content of bicarbonates in the blood.

Interaction

When used concomitantly with topiramate, phenytoin and carbamazepine reduce its concentration in blood plasma. This is due to the induction under the influence of phenytoin and carbamazepine of enzymes involved in the metabolism of topiramate. In some cases, when using topiramate, an increase in the concentration of phenytoin in blood plasma was observed.

With simultaneous use of a single dose of topiramate and digoxin, a decrease in the AUC of digoxin may occur.

When an oral contraceptive containing norethindrone and ethinyl estradiol was used simultaneously, topiramate did not significantly affect the clearance of norethindrone, but the plasma clearance of ethinyl estradiol increased significantly. Thus, when taking topiramate with oral contraceptives at the same time, their effectiveness may be reduced.

In patients taking metformin, pioglitazone, glibenclamide, with simultaneous use or withdrawal of topiramate, fluctuations in plasma glucose levels may occur. With these combinations, plasma glucose levels should be monitored.

Concomitant use of topiramate with drugs predisposing to the development of nephrolithiasis may increase the risk of kidney stones.

How to take, course of use and dosage

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

Overdose

Symptoms: seizures, drowsiness, speech and vision disorders, diplopia, thinking disorders, coordination disorders, dizziness, lethargy, stupor, hypotension, abdominal pain, dizziness, agitation and depression, metabolic acidosis. In most cases, the clinical consequences were not severe, but deaths were reported after overdose using a mixture of several drugs, including topiramate. There is a known case of overdose of topiramate in a dose of up to 110 g, which led to coma within 20-24 hours, and then after 3-4 days — full recovery.

Treatment: there is no specific antidote to the drug, and if necessary, symptomatic therapy is performed. It is necessary to immediately induce vomiting and flush the stomach, increase water intake. In vitro studies have shown that activated carbon adsorbs topiramate. Hemodialysis is the most effective way to remove topiramate from the body. Patients are advised to increase their fluid intake appropriately.

Special instructions

The use of topiramate for the treatment of acute migraine attacks has not been studied.

It should be used with caution in patients with renal and hepatic insufficiency, nephrourolithiasis (including personal and family history), hypercalciuria.

Patients with impaired renal function and patients on hemodialysis need to adjust the dosage regimen of topiramate.

Topiramate should be discontinued gradually to minimize the possibility of an increase in the frequency of seizures. In clinical studies in adults treated with epilepsy, doses were reduced by 50-100 mg at 1-week intervals. and by 25-50 mg in adults receiving topiramate at a dose of 100 mg / day for the prevention of migraines. In children in clinical trials, topiramate was gradually discontinued for 2-8 weeks. If a rapid withdrawal of topiramate is medically necessary, it is recommended to monitor the patient’s condition.

To reduce the risk of developing nephrolithiasis during treatment, you should increase the amount of fluid consumed.

With the use of topiramate, sweating and hyperthermia may decrease, especially in young children, in conditions of elevated ambient temperature. Adequate replacement of fluid loss before and during activities such as exercise or exposure to high temperatures can reduce the risk of overheating-related complications.

During the treatment period, it is necessary to monitor the condition of patients in order to detect signs of suicidal idealization and prescribe appropriate treatment. Patients (and, if necessary, caregivers) should be advised to seek immediate medical attention if signs of suicidal ideation or suicidal behavior appear.

If visual disturbances occur, including a syndrome involving myopia associated with angle-closure glaucoma, topiramate should be discontinued as soon as the attending physician considers it possible. If necessary, measures should be taken to reduce intraocular pressure.

To avoid the occurrence of metabolic acidosis, during treatment with topiramate, it is recommended to conduct the necessary studies, including determining the concentration of bicarbonates in serum. If metabolic acidosis occurs and persists, it is recommended to reduce the dose or stop taking topiramate. In children, chronic metabolic acidosis can lead to growth retardation. The effect of topiramate on growth and possible bone-related complications has not been systematically studied in children and adults.

If the body weight decreases during treatment, the diet should be adjusted.

Concomitant use of other drugs that have a depressing effect on the central nervous system is not recommended.

During the treatment period, the patient should avoid drinking alcohol.

Influence on the ability to drive motor vehicles and manage mechanisms

It should be used with caution in patients engaged in potentially dangerous activities that require increased attention and speed of psychomotor reactions, since topiramate can cause drowsiness, dizziness, and visual disturbances.

Form of production

Tablets covered with a film-coated orange color, round, biconvex. The cross-section is white or almost white in color.

Storage conditions

Store in a dry place, protected from light, at a temperature not exceeding 25 °C

Shelf life

2 years

Active ingredient

Topiramate

Conditions of release from pharmacies

By prescription

Dosage form

Tablets

Purpose

For adults as prescribed by a doctor, for children as prescribed by a doctor

Indications

Migraine, Epilepsy