Topiramate - Instructions For Use, Price, Reviews, Tablet Analogues

2024 Author: Rachel Wainwright | [email protected]. Last modified: 2023-12-15 07:39

Topiramate

Topiramate: instructions for use and reviews

1. 1. Release form and composition
2. 2. Pharmacological properties
3. 3. Indications for use
4. 4. Contraindications
5. 5. Method of application and dosage
6. 6. Side effects
7. 7. Overdose
8. 8. Special instructions
9. 9. Application during pregnancy and lactation
10. 10. Use in childhood
11. 11. In case of impaired renal function
12. 12. For violations of liver function
13. 13. Drug interactions
14. 14. Analogs
15. 15. Terms and conditions of storage
16. 16. Terms of dispensing from pharmacies
17. 17. Reviews
18. 18. Price in pharmacies

Latin name: Topiramate

ATX code: N03AX11

Active ingredient: topiramate (topiramate)

Producer: ALSI Pharma, CJSC (Russia), Hemofarm (Russia), Biocom (Russia), Valenta Pharmaceuticals (Russia), Makiz-Pharma (Russia), Aurobindo Pharma (India)

Description and photo update: 2018-21-11

Prices in pharmacies: from 167 rubles.

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Topiramate is a drug with antiepileptic action.

Release form and composition

Dosage form of Topiramate release - film-coated tablets: orange (in a cardboard box 1 can of 30, 60 or 100 tablets or 1-6 blisters of 7 or 10 tablets).

Composition of 1 tablet:

• active substance: topiramate - 25 or 100 mg;
• auxiliary components (25/100 mg): magnesium stearate - 0.4 / 1.6 mg; pregelatinized starch - 23/92 mg; microcrystalline cellulose - 31.4 / 125.6 mg; aerosil - 0.2 / 0.8 mg;
• shell (25/100 mg): Opadry II (macrogol - 0.65 / 2.58 mg; titanium dioxide - 0.23 / 0.93 mg; polyvinyl alcohol - 1.28 / 5.12 mg; talc - 0, 47 / 1.89 mg; aluminum varnish of dye of sunset yellow - 0.04 / 0.16 mg; aluminum varnish of quinoline yellow dye - 0.53 / 2.1 mg) - 3.2 / 12.8 mg.

Pharmacological properties

Pharmacodynamics

Topiramate belongs to the number of antiepileptic drugs (class of sulfate-substituted monosaccharides).

The main properties of the substance:

• blocking sodium channels and suppressing the appearance of repeated action potentials during prolonged depolarization of the neuron membrane;
• an increase in the activity of GABA (gamma-aminobutyric acid) in relation to some subtypes of GABA receptors (including GABA _A receptors);
• modulation of the activity of the GABA _A receptors themselves;
• inhibiting the activation of kainate / AMPK (a-amino-3-hydroxy-5-methylisoxazole-4-propionic acid) -receptors to glutamate.

Topiramate has no effect on the activity of N-methyl-D-aspartate (NMDA) against the NMDA receptor subtype.

The effects of the substance are dose-dependent at a plasma concentration of 1–200 µmol / L (the minimum activity is observed in the range of 1–10 µmol / L).

Topiramate also inhibits the activity of some isoenzymes of carbonic anhydrase (II – IV). This pharmacological effect is lower in severity than the effect of acetazolamide (a known carbonic anhydrase inhibitor), therefore, the indicated action of topiramate is not the main component of its antiepileptic activity.

Pharmacokinetics

Topiramate after oral administration from the gastrointestinal tract is absorbed well and quickly. Bioavailability is approximately 81%. C _max (maximum concentration of the substance) after oral administration at a dose of 400 mg is 0.001 5 mg / ml, the time to reach it is 120 minutes. Food intake does not have a clinically significant effect on the bioavailability of a substance. After repeated administration of topiramate 100 mg 2 times a day, the C _max value averages 0.006 76 mg / ml.

Pharmacokinetic processes of topiramate are linear, plasma clearance remains unchanged, AUC (area under the concentration-time curve) in the dose range of 100–400 mg increases in proportion to the dose.

For topiramate, the connection with blood plasma proteins is 13–17% (the range of plasma concentration in the blood is 0.000 5–0.25 mg / ml). Average V _d after a single dose of less than 1200 mg - 0.55-0.8 l / kg.

In women, the V _d value is approximately 50% of the values observed in men, which is associated with a higher content of adipose tissue in the body of women.

C _ss ^max (maximum steady-state concentration of a substance in the blood) in the absence of renal dysfunction is reached after 4–8 days. Topiramate passes into breast milk and through the placental barrier.

Approximately 20% of the oral dose is metabolized. Metabolism occurs by hydroxylation, hydrolysis and glucuronidation. However, against the background of concomitant therapy with AEDs (antiepileptic drugs), which are inducers of microsomal enzymes, there is an increase in the metabolism of topiramate up to 50%. 6 practically inactive metabolites have been identified. The metabolic rate of topiramate when combined with inducers of cytochrome P ₄₅₀ isoenzymes is up to 50%.

The main route of elimination of unchanged topiramate (approximately 70%) and its metabolites is through the kidneys. Plasma clearance of the substance after oral administration is 20-30 ml / min. On average, T _1/2 (half-life) after repeated administration of 50 and 100 mg 2 times a day is 21 hours. It is removed from plasma by hemodialysis.

With an average degree of renal failure (creatinine clearance - 30–69 ml / min) plasma and renal clearance of topiramate decreases by 42%, and with severe pathology (creatinine clearance - less than 30 ml / min) - by 54% or more.

In moderate to severe liver failure, plasma clearance of topiramate is reduced by 20-30%.

In children, the clearance of topiramate increases, and T _1/2 decreases; therefore, the plasma concentration of the substance in the blood when using the same dose per 1 kg of body weight is lower in children than in adults.

Indications for use

• partial (with / without secondary generalization) or primary generalized tonic-clonic seizures in children from 6 years of age and adults (monotherapy);
• partial (with / without secondary generalization) or generalized tonic-clonic seizures, as well as seizures due to Lennox-Gastaut syndrome, in children from 3 years of age and adults (simultaneously with other drugs);
• migraine attacks in adults (prevention; indicated after careful evaluation of all available alternatives; Topiramate is not intended for the treatment of acute migraine attacks).

Contraindications

Absolute:

• childbearing age in women who do not use effective methods of contraception;
• age up to 3, 6 or 18 years (when administered simultaneously with AED in the treatment of epilepsy, when used as monotherapy for epilepsy, or when used to prevent migraine, respectively);
• pregnancy and lactation period;
• individual intolerance to the components of the drug.

Relative (Topiramate is prescribed under medical supervision):

• hypercalciuria;
• liver failure;
• renal failure;
• nephrourolithiasis, including a burdened personal or family history.

Instructions for the use of Topiramate: method and dosage

Topiramate is intended for oral administration. Do not divide the tablets. You can take the drug regardless of food intake.

For optimal control of seizures, it is recommended to start treatment with low doses. During the use of the drug as monotherapy, the effect of the withdrawal of concomitant AEDs on the frequency of seizures should be taken into account. In cases where there is no need to abruptly cancel such funds, it is recommended to reduce their doses gradually (every 14 days by 1/3). With the abolition of drugs that are inducers of liver microsomal enzymes, the plasma concentration of topiramate in the blood will increase.

The recommended scheme for the use of Topiramate during monotherapy:

• adults: 1 time per day (at night), 25 mg for 7 days. Then, with an interval of 1–2 weeks, the dose is increased by 25–50 mg per day (the frequency of administration is 2 times a day). The recommended starting target daily dose is 100-200 mg. Maximum - 500 mg per day;
• children from 6 years old: once a day (at night) at 0.5-1 mg / kg for 7 days. Then, with an interval of 1–2 weeks, the dose is increased by 0.5–1 mg / kg per day (the frequency of administration is 2 times a day). The recommended daily dose is 100 mg (for children 6-16 years old - 2 mg / kg per day).

With poor intolerance, the dose may be increased more slowly. The optimal dose is considered to be highly effective and well tolerated.

The recommended scheme for the use of Topiramate as part of a combination treatment (with other AEDs):

• adults: 1 time per day (at night), 25-50 mg for 7 days. Then, with an interval of 1 week, the dose is increased by 25-50 mg per day. The minimum effective daily dose is 200 mg, the average is from 200 to 400 mg. Frequency rate of admission - 2 times a day. The efficacy / safety of doses greater than 1600 mg per day has not been studied. In some cases, the clinical effect and tolerability are achieved when the drug is taken once a day;
• children from 3 years old: 1 time a day (at night) at 25 mg (1-3 mg / kg) for 7 days. In the future, the dose is increased by 1–3 mg / kg for 1–2 weeks. Frequency rate of admission - 2 times a day. The average daily dose is 5-9 mg / kg for 2 doses. The drug is usually well tolerated at doses up to 30 mg / kg.

The main criterion for selecting a dosage regimen is tolerance and clinical efficacy.

The recommended daily dose for the prevention of migraine in adults is 100 mg in 2 divided doses. The drug is taken at bedtime. Therapy begins with a dose of 25 mg or less for 7 days. Then, with an interval of 1 week, the daily dose is increased by 25 mg. In some cases, a positive result is achieved when taking Topiramate in a daily dose of 50 mg. An additional effect does not develop when the dose is increased above 100 mg per day.

With moderate to severe renal failure, the initial dose should be halved. The dose should be increased by a smaller amount or at longer time intervals. It should be borne in mind that after each increase in the dose of topiramate, more time is required to reach an equilibrium concentration (10-15 days).

On the days of hemodialysis, Topiramate is prescribed in a daily dose increased by 50%. The additional dose is divided into 2 parts, one is taken before the start of hemodialysis, the second after its completion. The additional dose is selected depending on the clinical effect, it may differ depending on the equipment used and the characteristics of dialysis.

Due to the reduced clearance of topiramate in liver failure, therapy should be carried out under medical supervision.

Topiramate should be canceled gradually to minimize the likelihood of an increase in the frequency of seizures. The dose is reduced with an interval of 7 days: with epilepsy - by 50-100 mg, with migraine - by 25-50 mg.

It is necessary to cancel the drug in children within 2-8 weeks. If it is necessary to abruptly cancel Topiramate, medical supervision should be established for the patient's condition.

Side effects

The most common adverse reactions during Topiramate therapy are: decreased appetite, diarrhea, nausea, anorexia, impaired coordination of movements / attention, slowing mental activity, depression, slurred speech, insomnia, dizziness, paresthesias, nystagmus, drowsiness, diplopia, tremor, dysarthria, lethargy, hypesthesia, impaired taste, memory loss, visual impairment, irritability, weight loss, increased fatigue.

Disorders that are more common in children than in adults: hypokalemia, hyperchloremic acidosis, gait disturbance, increased / decreased appetite, behavioral disturbances, aggression, apathy, sleep disturbance, attention disturbance, suicidal thoughts, drowsiness, sinus bradycardia, increased lacrimation, disturbance circadian rhythm of sleep, poor quality of sleep, general unsatisfactory condition.

The following adverse reactions occur exclusively in children: hyperthermia, fever, eosinophilia, psychomotor agitation, vomiting, vertigo, learning disabilities.

Possible side effects (> 10% - very often;> 1% and 0.1% and 0.01% and <0.1% - rarely; <0.01% - very rare; in the absence of an opportunity to establish the frequency of side effects - with an unspecified frequency):

• immune system: often - hypersensitivity; with an unknown frequency - conjunctival edema, angioedema;
• hematopoietic and lymphatic system: often - anemia; infrequently - lymphadenopathy, leukopenia, eosinophilia, thrombocytopenia; rarely, neutropenia;
• psyche: very often - depression; often - agitation, slurred speech, depressed mood, mental retardation, insomnia, mood changes, anxiety, confusion, disorientation, aggressiveness, behavior disturbance, mood swings, anger; infrequently - reading disorder, suicidal thoughts / attempts, hallucinations (including visual / auditory), paranoia, apathy, psychotic disorders, lack of spontaneous speech, nervousness, dysfemia, crying, euphoria, emotional lability, panic reaction, sleep disturbance, decreased libido, emotional coldness, perseveration, panic attacks, tearfulness, sleep disturbance, high spirits, impaired thinking, distraction, lack of libido, apathy, early morning awakening; rarely - a feeling of despair, mania, hypomania, panic disorder;
• metabolism and nutrition; often - decreased appetite, anorexia; infrequently - hypokalemia, metabolic acidosis, polydipsia, increased appetite; rarely - hyperchloremic acidosis;
• organ of vision and hearing: often - blurred vision, diplopia, tinnitus, vertigo, ear pain, visual impairment; infrequently - hearing loss, unilateral hearing loss, deafness, discomfort in the ear, sensorineural hearing loss, pathological sensations in the eye, decreased visual acuity, myopia, scotoma, dry eyes, photophobia, mydriasis, blepharospasm, photopsia, lacrimation, presbyopia; rarely - glaucoma, atrial fibrillation, one-sided blindness, impaired binocular vision, night blindness, eyelid edema, transient blindness, amblyopia, impaired accommodation; with an unknown frequency - maculopathy, angle-closure glaucoma, eye movement disorder;
• nervous system: very often - drowsiness, paresthesia, vertigo; often - impaired attention / memory, amnesia, sedation, impaired cognitive / mental functions, intentional tremor, impaired psychomotor skills, lethargy, tremor, seizures, dysgeusia, impaired coordination of movements, hypesthesia, nystagmus, imbalance, dysarthria; infrequently - large seizures, speech impairment, depression of consciousness, narrowing of visual fields, complex partial seizures, psychomotor agitation, fainting, salivation, loss / impairment of sensitivity, hypersomnia, aphasia, poor sleep quality, repetition of words, dyskinesia, hypokinesia, postural dizziness, burning sensation, parosmia, cerebellar syndrome, aura, ageusia, dysgraphia, dysphasia, dysesthesia, peripheral neuropathy, hypogeusia, stupor, clumsiness, tingling, light-headedness, dystonia;rarely - disturbance of the circadian rhythm of sleep, akinesia, apraxia, hyperesthesia, anosmia, hyposmia, lack of response to stimuli, loss of smell;
• respiratory system: often - nosebleeds, shortness of breath, rhinorrhea, nasal congestion; infrequently - hypersecretion of the paranasal sinuses, shortness of breath during exertion, dysphonia;
• heart and blood vessels: infrequently - bradycardia (including sinus), vasomotor disturbances, decreased blood pressure, orthostatic hypotension, hot flashes, palpitations; rarely - Raynaud's syndrome;
• liver and biliary tract: rarely - liver failure, hepatitis;
• digestive system: very often - diarrhea, nausea; often - constipation, vomiting, epigastric / abdominal pain, dyspepsia, xerostomia, abdominal discomfort, gastritis, paresthesia of the oral mucosa; infrequently - bad breath, flatulence, lower abdominal pain, pancreatitis, gastroesophageal reflux, bloating, hypoesthesia of the oral mucosa, bleeding from the gums, cheek pain, peritoneal irritation, epigastric discomfort, glossodynia, hypersalivation;
• musculoskeletal system: often - muscle spasm, chest muscle pain, arthralgia, muscle contracture, myalgia, muscle weakness; infrequently - stiffness, joint swelling, muscle fatigue, musculoskeletal pain in the side; rarely - discomfort in the limbs;
• skin and subcutaneous tissue: often - rash, alopecia, itching; infrequently - allergic reactions, dermatitis, anhidrosis, facial hypoesthesia, erythema, urticaria, macular rash, generalized itching, discoloration of the skin, facial edema; rarely - focal urticaria, unpleasant skin odor, Stevens-Johnson syndrome, periorbital edema, erythema multiforme; with an unknown frequency - toxic epidermal necrolysis;
• genitals and mammary gland: infrequently - violation of sexual function / erection;
• kidneys and urinary tract: often - pollakiuria, nephrolithiasis, dysuria; infrequently - urinary incontinence, pain in the kidney, urinary calculus, hematuria, renal colic, urge to urinate; rarely - renal tubular acidosis, calculus in the urethra;
• social circumstances: infrequently - learning disabilities;
• laboratory and instrumental indicators: very often - weight loss; often - an increase in body weight; infrequently - increased activity of liver microsomal enzymes, pathological leukopenia, crystalluria; rarely - a decrease in serum bicarbonate;
• infections and infestations: very often - rhinopharyngitis;
• general disorders: very often - fatigue; often - asthenia, fever, imbalance, irritability, malaise, discomfort; infrequently - thirst, hyperthermia, feeling of nervousness, flu-like syndrome, cold extremities, asthenia, feeling of intoxication; rarely - calcification.

Overdose

The main symptoms and signs of overdose: arterial hypotension, metabolic acidosis, speech / vision disorders, drowsiness, convulsions, diplopia, dizziness, stupor, lethargy, thinking / coordination disorders, abdominal pain, depression, agitation. The clinical consequences of an overdose are usually not severe, but deaths have been recorded after using a mixture of several drugs, including Topiramate.

There is no specific antidote. If necessary, symptomatic treatment is indicated. Immediately, you should rinse the stomach, induce vomiting, increase water intake. It is possible to take activated carbon. The most effective way to remove topiramate from the body is hemodialysis.

special instructions

During therapy, it is very important to adequately increase the volume of fluid intake. This will reduce the likelihood of nephrolithiasis, as well as adverse reactions that can develop under the influence of high temperatures or physical exertion.

During the period of taking Topiramate, there is an increase in the incidence of mood disorders (including increased aggressiveness), depression and psychotic reactions. There is evidence of cases associated with increased suicidal activity. When using Topiramate, patients should be screened for suicidal behavior / thoughts. If suicidal activity is detected, appropriate treatment should be considered.

Patients with any personality disorders need special control, especially at the beginning of taking Topiramate.

If you have a predisposition to nephrolithiasis, the likelihood of kidney stones increases. The prevention of this process is facilitated by an adequate increase in the volume of fluid intake. The main risk factors for the development of nephrolithiasis: hypercalciuria, a burdened history of nephrolithiasis (including familial), concomitant drug therapy that contribute to the appearance of nephrolithiasis.

There is evidence of cases of development of a syndrome including acute myopia with concomitant secondary angle-closure glaucoma. Symptoms include acute decrease in visual acuity / eye pain. When conducting an ophthalmological examination, myopia, flattening of the depth of the anterior chamber, increased intraocular pressure and hyperemia, and possibly mydriasis, are revealed. In most cases, symptoms develop after a month of initial therapy. Secondary angle-closure glaucoma associated with the use of Topiramate can occur in both adults and children. At the discretion of the doctor, it is possible to cancel therapy with Topiramate and take measures aimed at reducing intraocular pressure. In the absence of adequate treatment, increased intraocular pressure can lead to the development of serious complications, including loss of vision.

Reception of Topiramate can cause the development of hyperchloremic, not associated with anion deficiency, metabolic acidosis. A decrease in the concentration of blood serum hydrocarbons in this case is associated with the inhibitory effect of topiramate on renal carbonic anhydrase. Usually, a violation occurs at the beginning of taking the drug, although the likelihood of its development in any period of therapy is possible.

During treatment, research is required, including the determination of the serum concentration of hydrocarbons in the blood. With the development of metabolic acidosis and its persistence, it is recommended to reduce the dose or cancel Topiramate.

If there is a decrease in body weight against the background of therapy, the question of the advisability of enhanced nutrition should be considered.

During therapy with Topiramate, oligohydrosis or anhidrosis may occur. Hyperthermia and decreased sweating can occur in children who are exposed to high ambient temperatures. Because of this, it is important to consume adequate amounts of fluids to reduce the likelihood of side effects, including nephrolithiasis.

During treatment, some patients developed hypokalemia, defined as a decrease in serum potassium concentration to <3.5 mmol / L.

Influence on the ability to drive vehicles and complex mechanisms

Due to the presence of a potential threat associated with the likelihood of drowsiness, visual impairment, dizziness, patients are advised to refrain from driving vehicles and complex mechanisms.

Application during pregnancy and lactation

Contraindication to taking Topiramate is pregnancy and the period of breastfeeding, as well as childbearing age in women who do not use effective methods of contraception.

Pediatric use

Therapy is contraindicated:

• up to 3 years: use simultaneously with AED in the treatment of epilepsy;
• up to 6 years: use as monotherapy for epilepsy;
• under 18 years of age: use for the prevention of migraine.

With impaired renal function

According to the instructions, Topiramate for renal failure should be used under medical supervision.

For violations of liver function

Topiramate for liver failure should be used under medical supervision.

Drug interactions

Possible interactions with other AEDs:

• phenobarbital, phenytoin, valproic acid, carbamazepine, primidone: topiramate usually does not affect the values of their stable plasma concentrations; in exceptional cases, when topiramate is added to phenytoin, an increase in the plasma concentration of the latter may be observed. When clinical signs or symptoms of toxicity appear, the plasma concentration of phenytoin should be monitored. The concentration of topiramate in the blood plasma decreases when combined with phenytoin, carbamazepine and, to a lesser extent, with lamotrigine;
• valproic acid: hyperammonemia develops with / without encephalopathy. Signs of impairment usually disappear after one of the drugs is discontinued. Hypothermia (an unintentional drop in body temperature below 35 ° C) may also occur. The disorder may appear in isolation or in combination with hyperammonemia.

Other possible interactions:

• drugs that depress the central nervous system, alcohol: the combination is not recommended;
• digoxin: its AUC decreases; when prescribing / canceling topiramate, it is necessary to control the serum concentration of digoxin;
• oral contraceptives: there is a possibility of a decrease in their effectiveness; in cases of development of any changes in the nature and timing of menstruation, medical advice is required;
• St. John's wort: a decrease in the plasma concentration of topiramate in the blood is possible, which may cause a decrease in its effectiveness;
• risperidone: its AUC decreases; has no clinical significance;
• lithium: its AUC varies (depending on the dose of topiramate and the presence of concomitant diseases); if necessary, combined use requires monitoring the plasma concentration of lithium in the blood;
• metformin: its C _max and AUC increase, clearance - decreases. When adding / canceling topiramate in patients receiving metformin, it is necessary to monitor the course of diabetes mellitus;
• hydrochlorothiazide: dose adjustment of Topiramate may be required;
• glibenclamide (when used in patients with type 2 diabetes mellitus at a dose of 5 mg per day): its AUC decreases. When conducting combined therapy, it is necessary to take into account the possible pharmacokinetic interaction and monitor the condition of patients to assess the course of diabetes mellitus;
• pioglitazone: its AUC decreases without changing C _max. If necessary, combined use must be carefully monitored for diabetes;
• drugs that predispose to the development of nephrolithiasis: the combination is recommended to be avoided.

Analogs

The analogues of Topiramat are: Topiromax, Epimax, Topsaver, Topamax, Ropimat, Maksitopyr, Torepimat, Epitop, Topalepsin, Toreal.

Terms and conditions of storage

Store in a place protected from light at temperatures up to 25 ° C. Keep out of the reach of children.

The shelf life is 2 years.

Terms of dispensing from pharmacies

Dispensed by prescription.

Reviews about Topiramate

According to reviews, Topiramate is an effective drug. In the case of the selection of an adequate dose, it is usually possible to achieve complete remission and prevent the development of sudden attacks. Among the shortcomings, they point to its high cost.

The price of Topiramate in pharmacies

The approximate price for Topiramate is 139-189 rubles (30 tablets of 25 mg), 366-459 rubles (30 tablets of 100 mg).

Topiramate: prices in online pharmacies

Drug name Price Pharmacy

Topiramate 25 mg film-coated tablets 30 pcs. 167 r Buy

Topiramate Canon 25 mg film-coated tablets 28 pcs. 175 RUB Buy

Topiramate tablets p.p. 25mg 28 pcs. 208 RUB Buy

Topiramate 100 mg film-coated tablets 30 pcs. 399 RUB Buy

Topiramate 100 mg film-coated tablets 30 pcs. 432 RUB Buy

Topiramate Canon 100 mg film-coated tablets 28 pcs. 469 r Buy

Anna Kozlova Medical journalist About the author

Education: Rostov State Medical University, specialty "General Medicine".

Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!