Topiramate

1 film-coated tablet contains:
active substance:

topirate 25 mg and 100 mg;

excipients:

calcium hydrophosphate dihydrate (65 mg, 120 mg),

pregelatinized starch (starch) (70.5 mg, 111 mg),

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

magnesium stearate (1.5 mg, 3 mg),

povidone (8 mg, 16 mg);

composition of the film shell - Selecoate AQ-02140 (6 mg, 12 mg) [hypromellose (hydroxypropyl methyl cellulose), macrogol (polyethylene glycol 400), macrogol (polyethylene glycol 6000), titanium dioxide, dye sun sunset yellow].

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 action of the drug on sodium channels on the condition of the neuron.

This active substance potentiates GABA activity for some subtypes of GABA receptors (including GABAA receptors), modulates the activity of GABAA receptors themselves, as well as prevents cainate/AMPC receptor sensitivity to glutamate and does not affect the activity of N-methyl-D-aspartate against NMDA receptors. These effects of topiramate are dose-dependent at a plasma concentration of topiramate 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 carboangidrase, but this effect in topiramate is weaker than in acetazolamide and does not seem to be the main one in the antiepileptic activity of topiramate.

Pharmacokinetics

After ingestion, the topyrate is absorbed quickly and efficiently. Bioavailability - 81%. Eating does not have a clinically significant effect on the bioavailability of the topyracate. Plasma protein binding 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 about 50% of the values observed in men, which is associated with a higher adipose tissue content in women's body. The pharmacokinetics of topiramate is linear. Plasma clearance remains constant, with the AUC increasing proportional to the dose in the dose range from 100 to 400 mg. Css in plasma is achieved in 4-8 days.

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

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

Epilepsy: as a means of monotherapy for initial treatment in patients over 2 years of age - partial or primary generalized tonic-clonal seizures; as part of complex therapy in patients over 2 years of age - partial or generalized tonic-clonal seizures, as well as seizures against the background of Lennox-Gasto syndrome.

Migraine: prevention of migraine attacks in adults.

There have been no adequate and strictly controlled clinical studies on the safety of topyracate during pregnancy.

The use of topyramate during pregnancy can cause damage to the fetus. Data from the Maternity Register show that intrauterine exposure to the fetus increases the risk of congenital malformations (e.g. craniofacial defects such as "hale lip"/"wolf mouth", hypospadia and abnormalities in the development of various body systems).

These malformations were recorded both in monotherapy with topiramate and in its use in combination therapy. Compared to a group of patients who do not take antiepileptic drugs, data from the register of pregnant women with monotherapy with topiracyrate indicate an increase in the frequency of birth of low-weight children (less than 2500 g). Cause and effect has not been established.

In the treatment of women of childbearing age, the expected benefits of therapy for 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 the pregnancy occurred during treatment, the patient should be warned of the potential risk to the fetus.

A limited number of observations suggests that topiramate is secreted with breast milk. If necessary, use during lactation, the issue of stopping breastfeeding should be resolved.

Application in children

Do not use in children under 2 years of age.

Hypersensitivity to topiracate.

Use for liver disorders

Use with caution in patients with liver disorders due to a possible decrease in topyracate clearance.

On the part of the nervous system: paresthesia, drowsiness, dizziness, attention impaired, memory disorders, amnesia, psychomotor disorders, seizures, improper coordination, tremors, lethargy, hypesthesia, nystagmus, dysgeusia, articulation disorder, intentional trembling (dynamic), sedative effect, consciousness oppression, seizures such as large seizures, visual field defect, complex partial seizures, speech disorder, speech disorder, psychomotor hyperactivity, fainting, sensory, sensory, salivation, and phase, repeated speech, hypokidia, dyskinesia, dyskinesia, postural dizziness, hyponesia, hyponesia, quality of sensational quality of sleep, hypomorrhosis, hypoxia, neuropathy, neuro

Mental disorders: depression, slow thinking, cognitive disorders, insomnia, pronounced speech disorders, anxiety, confusion, disorientation, aggression, mood lability, anxiety, emotional lability, depressive mood, anger, inadequate behavior, suicidal ideas or attempts, auditory and visual hallucinations, psychotic disorder, apathy, lack of spontaneous speech

From the part of the visual organ: blurred vision, diplopia, visual impairment, reduced visual acuity, scotoma, myopia, pathological sensations in the eyes, dry eyes, photophobia, blepharospasm, increased tearing, photopsy, mydriasis, presbyopia,

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

From the immune system: hypersensitivity, allergic edema, conjunctiva swelling.

Metabolic side: anorexia, decreased appetite, metabolic acidosis, hypokalemia, increased appetite, polydipsia, hyperchloremic acidosis.

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

From the cardiovascular system: bradycardia, sinus bradycardia, rapid heartbeat, orthostatic hypotension, blood surges, hyperemia, Raynaud phenomenon.

From the respiratory system: nasopharyngitis, dyspnea, nasal bleeding, nasal congestion, rhinorrhoea, cough, shortness of breath during physical activity, 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, gum bleeding, bloating, discomfort in the epigastric area, pain throughout the abdomen, hypersecretion of the salivary glands, oral pain, bad breath, glossodynia, hepatitis, liver failure.

From the skin and subcutaneous tissues: alopecia, itching, rash, anhydrosis, facial hypoesthesia, hives, erythema, generalized itching, macular rash, skin color change, allergic dermatitis, facial swelling, Stevens-Johnson syndrome, multiform erythema

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

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

From the reproductive system: erectile dysfunction, sexual dysfunction.

General reactions: fatigue, pyrexia, asthenia, irritability, gait disorders, unusual sensations, malaise, hyperthermia, thirst, flu-like condition, inertia, cold limbs, feeling intoxication, anxiety, facial swelling, calcinosis.

On the part of laboratory indicators: weight loss, increase in body weight, crystalluria, abnormal test of tandem walk, leukopenia, increased activity of liver enzymes, hypokalemia, reduction of hydrocarbonate content in the blood.

When used simultaneously with topyracate, phenytoin and carbamazepine reduce its concentration in blood plasma. This is due to the induction of enzymes under the influence of phenytoin and carbamazepine, with the participation of which topiracate metabolism is carried out. In some cases, when using topyramate, there was an increase in the concentration of phenytoin in blood plasma.

Simultaneous use of a single dose of topyracate and digoxin may reduce AUC digoxin.

With simultaneous use of an oral contraceptive containing norethindron and ethinylestradiol, the topyramate did not have a significant effect on the clearance of norethindron, but the plasma clearance of ethinylestradiol increased significantly. Thus, when taking topiramate with oral contraceptives at the same time, their effectiveness may be reduced.

Patients taking metformin, pyoglitasone, glibenclamide may fluctuate plasma glucose levels when used or canceled simultaneously. With these combinations, plasma glucose levels should be monitored.

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

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

Symptoms: seizures, drowsiness, speech and vision disorders, diplopia, mental disorders, coordination disorders, dizziness, lethargy, stupor, arterial hypotension, abdominal pain, dizziness, arousal and depression, metabolic acidosis. In most cases, the clinical consequences were not severe, but there were deaths after an overdose using a mixture of severaldrances, including topyramate. There is a case of overdose of topiracate at a dose of up to 110 g, which led to a coma within 20-24 hours, and then after 3-4 days - a complete recovery.

Treatment: there is no specific antidote of the drug, symptomatic therapy is carried out if necessary. It is necessary to immediately induce vomiting and rinse the stomach, increase water consumption. In vitro studies, activated carbon adsorbs topirates. Hemodialysis is the most effective way to remove topiramate from the body. Patients are recommended to adequately increase the volume of fluid consumed.

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

Care should be used for renal and liver failure, nephrourolithiase (including personal and family history), hypercalciuria.

Patients with kidney dysfunction and patients on hemodialysis require correction of the topyramate dosing regimen.

The cancellation of the topiracyrate should be gradually in order to minimize the possibility of increasing the frequency of seizures. In clinical trials in adults, doses were reduced by 50-100 mg at intervals of 1 week and by 25-50 mg in adults receiving topiramate at a dose of 100 mg/day for the prevention of migraine. In children in clinical trials, topiracate was gradually abolished within 2-8 weeks. If rapid cancellation of topiracate is necessary for medical reasons, it is recommended to monitor the patient's condition.

To reduce the risk of nephrolithiasis during treatment, the volume of fluid consumed should be increased.

Against the background of the use of topyramate, sweating and hyperthermia may decrease, especially in young children, in conditions of elevated ambient temperature. Sufficient replenishment of fluid loss before and during activities such as exercise or exposure to high temperatures can reduce the risk of complications caused by overheating.

During treatment, it is necessary to monitor the condition of patients in order to identify signs of suicidal idealization and prescribe appropriate treatment. Patients (and, if necessary, caregivers) should be encouraged to seek medical attention immediately in case of signs of suicidal idealization or suicidal behavior.

In case of visual impairments, including syndrome involving myopia associated with closed-angle glaucoma, the topirate should be canceled as soon as the attending physician deems it possible. If necessary, measures should be taken to reduce intraocular pressure.

In order to avoid metabolic acidosis, it is recommended to conduct the necessary studies during the treatment with trampiramate, including determining the concentration of hydrocarbonates in the serum. In case of metabolic acidosis and its persistence, it is recommended to reduce the dose or stop taking topiracate. In children, chronic metabolic acidosis can slow down growth. The effect of topiracate on growth and possible complications associated with the bone system were not studied systematically in children and adults.

If body weight decreases against the background of treatment, the diet should be adjusted.

Simultaneous use of other drugs that have an oppressive effect on the CNS is not recommended.

During treatment, the patient should avoid drinking alcohol.

Impact on the ability to drive vehicles and drive mechanisms

Caution should be used in patients engaged in potentially dangerous activities that require increased attention and speed of psychomotor reactions, as topyracate can cause drowsiness, dizziness, visual impairment.

Tablets covered with orange film shell, round, biconvex. On the cross section of white or almost white color.