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Active ingredients
Topiramate
Release form
Capsules
Composition
Active ingredient: Topiramate (Topiramate) Concentration of active ingredient: 50 mg
Pharmacological effect
Antiepileptic drug belongs to the class of sulfamate-substituted monosaccharides. Topiramat blocks sodium channels and suppresses the occurrence of repeated action potentials against the background of long-term depolarization of the neuron membrane. Topiramate increases the activity of GABA (GABA) with respect to some subtypes of GABA receptors (including GABAA receptors), and also modulates the activity of the GABAA receptors themselves, inhibits the activation of kainate / AMPK sensitivity (alpha-amino-3-hydroxy -5-methylisoxazole-4-propionic acid) glutamate receptors, does not affect the activity of NMDA in relation to the NMDA receptor subtype. These effects of the drug are dose-dependent at plasma concentrations of topiramate from 1 μmol to 200 μmol, with a minimum activity ranging from 1 μmol to 10 μmol. In addition, topiramate inhibits the activity of some isoenzymes carbonic anhydrase. In terms of the severity of this pharmacological effect, topiramate is significantly inferior to acetazolamide, a known inhibitor of carbonic anhydrase, therefore this activity of topiramate is not the main component of its antiepileptic activity.
Pharmacokinetics
AbsorptionAfter receiving the drug inside topiramate is quickly and effectively absorbed from the gastrointestinal tract. Bioavailability is 81%. Food intake has no clinically significant effect on the bioavailability of the drug. Topramat pharmacokinetics is linear, plasma clearance remains constant, and AUC in the dose range from 100 mg to 400 mg increases proportionally to the dose. After repeated ingestion in a dose of 100 mg 2 times / day Cmax on average is 6.76 mcg / ml. Distribution Plasma protein binding is 13-17%. After a single dose of oral administration up to 1200 mg, the average Vd is 0.55-0.8 l / kg. Vd value depends on gender. In women, the values are about 50% of the values observed in men, which is associated with a higher content of adipose tissue in the body of women. Patients with normal kidney function may need 4 to 8 days to achieve an equilibrium. Metabolism After ingestion, about 20 are metabolized. % of dose. From plasma,Human urine and feces were isolated and identified 6 practically inactive metabolites. Excretion Topopymate (70%) and its metabolites are excreted mainly by the kidneys. After ingestion, the plasma clearance of the drug is 20-30 ml / min. After repeated administration of the drug in 50 mg and 100 mg 2 times / day, the average T1 / 2 averaged 21 hours. The pharmacokinetics in special clinical situations. The rate of topiramate excretion by the kidneys depends on the kidney function and does not depend on age. In patients with impaired renal function, moderate to severe (CC ≤ 70 ml / min) the renal and plasma clearance of topiramate is reduced, as a consequence, the Css of topiramate in the blood plasma may increase in comparison with patients with normal renal function. The time to Css topiramate in blood plasma in patients with moderate or severe renal impairment is from 10 to 15 days. Patients with moderate to severe renal insufficiency are recommended to use half of the recommended initial and maintenance dose. In elderly people who do not have kidney disease, plasma clearance of topiramate does not change. In patients receiving concomitant anti-epileptic drugs that induce enzymes involved in drug metabolism means, the metabolism of topiramate increased by 50%. Topiramat is effectively excreted by hemodialysis. Prolonged hemodialysis can lead to a decrease in the concentration of topiramate in the blood below the amount required to maintain anticonvulsant activity. In order to avoid a rapid drop in plasma topiramate concentration during hemodialysis, it may be necessary to prescribe an additional dose of Topamax. Dose adjustment should take into account: 1) the duration of hemodialysis, 2) the clearance of the used hemodialysis system, 3) the effective renal clearance of topiramate in a patient undergoing dialysis. The plasma clearance of topiramate is reduced by an average of 26% in patients with moderate liver failure or severe. Therefore, patients with hepatic impairment should use topiramate with caution. In children under the age of 12 years, the pharmacokinetic parameters of topiramate as well as in adults receiving the drug as adjuvant therapy are linear, while its clearance does not depend on the dose, and Css in plasma increases in proportion to the dose increase. It should be borne in mind that in children the clearance of topiramate is increased, and its T1 / 2 is shorter.Therefore, with the same dose per 1 kg of body weight, plasma topiramate concentrations in children may be lower than in adults. In children, as in adults, antiepileptic drugs that induce hepatic enzymes, cause a decrease in the concentration of topiramate in the blood plasma.
Indications
Epilepsy As a means of monotherapy: in adults and children older than 2 years with epilepsy (including patients with newly diagnosed epilepsy). In combination therapy: in adults and children older than 2 years with partial or generalized tonic- clonic seizures, as well as for the treatment of seizures on the background of Lennox-Gasto syndrome. Migraine. Prevention of migraine attacks in adults. The use of Topamax for the treatment of acute migraine attacks has not been studied.
Contraindications
Hypersensitivity to any of the components of this drug, children up to 2 years old. The use of topiramate for the prevention of migraine attacks is contraindicated during pregnancy, as well as in women with preserved childbearing potential, not using reliable methods of contraception.
Precautionary measures
Cancel Topamax (like other anti-epileptic drugs) should be gradually, to minimize the possibility of increasing the frequency of seizures.
Use during pregnancy and lactation
Special controlled studies in which Topamax was used to treat pregnant women have not been conducted. Pregnancy records show a possible connection between the use of Topamax during pregnancy and congenital malformations (for example, craniofacial defects such as cleft lip / cleft palate, hypospadias and abnormal development of various body systems). These malformations were recorded both in monotherapy with topiramate and in its use in the framework of polytherapy. Compared with the group of patients who do not take antiepileptic drugs, the records of pregnancies with monotherapy with Topamax indicate the likelihood of the birth of children with low body weight (less than 2500 g). The relationship of the observed phenomena with the intake of the drug has not been established. In addition, the records of pregnancies and the results of other studies suggest that the risk of teratogenic effects with the combined treatment with antiepileptic drugs may be higher than with monotherapy.Use of the drug Topamax during pregnancy is justified only when the potential benefits of therapy for the mother outweigh the possible risk to the fetus. When treating and consulting women with childbearing potential, the attending physician must weigh the balance of benefits and risks of treatment and consider alternative treatment options. If Topamax is used during pregnancy, or if the patient became pregnant while taking this drug, it should be warned about the potential risk to the fetus. A limited number of observations suggest that topiramate is excreted in breast milk from women. If necessary, the use of the drug Topamax during lactation should decide on the termination of breastfeeding.
Dosage and administration
Inside, regardless of the meal. In order to achieve optimal control of epileptic seizures in children and adult patients, it is recommended to start treatment with low doses of the drug followed by gradual titration to an effective dose. The capsules are intended for patients who have difficulty swallowing pills (eg, children and elderly patients). open, mix the contents of the capsules with a small amount (about 1 teaspoon) of any soft food. This mixture should be swallowed immediately, without chewing. Do not store the drug mixed with food until the next dose. Topamax capsules can be swallowed whole.
Side effects
Infections and invasions: very often - nasopharyngitis. On the part of the blood and lymphatic system: often - anemia; infrequently - leukopenia, lymphadenopathy, thrombocytopenia, eosinophilia; seldom - neutropenia *. For the immune system: often - hypersensitivity; frequency unknown - allergic edema *, conjunctival edema *. On the side of metabolism and nutrition: often - anorexia, loss of appetite; infrequently - metabolic acidosis, hypokalemia, increased appetite, polydipsia; rarely, hyperchloremic acidosis. Mental disorders: very often, depression; often - slow thinking, insomnia, disturbed speech, anxiety, confusion, disorientation, aggressive reactions, mood disorders, agitation, emotional lability, depressive mood, anger,violation of behavior; infrequently - suicidal thoughts, attempted suicide, hallucinations, psychotic disorders, auditory hallucinations, visual hallucinations, apathy, difficulty speaking, sleep disorders, affective lability, decreased libido, agitated state, crying, dysphemia, euphoric mood, paranoia, persever activity. , tearfulness, impaired reading skills, impaired sleep, flattening of emotions, abnormal thinking, loss of libido, lethargy, intrasomnic disorder, confusion, early morning awakenings, pa nical reactions, high spirits; rarely - mania, panic disorder, sense of hopelessness *, hypomania. On the side of the central nervous system: very often - paresthesia, drowsiness, dizziness; often - impaired concentration, impaired memory, amnesia, cognitive disorders, impaired thinking, psychomotor disturbances, convulsions, impaired coordination of movements, tremor, lethargy, hypesthesia, nystagmus, dysgeusia, impaired sense of balance, dysarthria, intentional tremor, sedation; infrequently - depressed consciousness, “grand mal” type tonic-clonic seizures, visual field disturbance, complex partial seizures, speech disorder, psychomotor hyperactivity, syncope, sensory disturbances, drooling, hypersomnia, aphasia, repetitive speech, hypokinesia, dyskinesia, postural dizziness , poor quality of sleep, burning sensation, loss of sensation, parosmia, cerebral syndrome, dysesthesia, hypogemia, stupor, clumsiness, aura, agevziya, dysgraphia, dysphasia, peripheral neuropathy, pre-fainting e, dystonia, goosebumps; seldom: apraxia, disturbance of the circadian rhythm of sleep, hyperesthesia, hyposmia, anosmia, essential tremor, akinesia, lack of reactions to stimuli. On the part of the organ of vision: often - blurred vision, diplopia, visual disturbances; infrequently - reduction of visual acuity, scotoma, myopia *, strange sensations in the eyes *, dry eyes, photophobia, blepharospasm, increased tearing, photopsia, mydriasis, presbyopia; rarely - unilateral blindness, transient blindness, glaucoma, disturbance of accommodation, disturbance of visual spatial perception, atrial scotoma, eyelid edema *, night blindness, amblyopia; frequency unknown: angle-closure glaucoma *,maculopathy *, impaired mobility of the eye *. On the side of the organ of hearing and balance: often - vertigo, ringing in the ears, pain in the ear; infrequently: deafness, unilateral deafness, neurosensory deafness, ear discomfort, hearing impairment. On the SSS side: infrequently - bradycardia, sinus bradycardia, feeling of heartbeat. On the vascular system: infrequently - hypotension, orthostatic hypotension, hot flashes, hot flushes. rarely - Raynaud's phenomenon. From the side of the respiratory system, organs of the chest and mediastinum: often - shortness of breath, nose bleeding, nasal congestion, rhinorrhea, cough *; infrequently - shortness of breath on exertion, hypersecretion in the paranasal sinuses, dysphonia. On the gastrointestinal tract: very often - nausea, diarrhea; often - vomiting, constipation, pain in the epigastric region, dyspepsia, abdominal pain, dry mouth, stomach discomfort, impaired sensitivity in the mouth, gastritis, abdominal discomfort; infrequently - pancreatitis, flatulence, gastroesophageal reflux, pain in the lower abdomen, decreased sensitivity in the oral cavity, bleeding gums, abdominal distention, discomfort in the epigastric region, sensitivity in the abdominal region, hypersalivation, oral pain, unpleasant smell, glosses, unpleasant body odor, gloom . For the hepatobiliary system: rarely - for hepatitis, liver failure. For the skin and subcutaneous tissues: often - alopecia, rash, itching; infrequently - anhidrosis, a violation of sensitivity in the face, urticaria, erythema, generalized itching, macular rash, a violation of skin pigmentation, allergic dermatitis, swelling of the face; infrequently - Stevens-Johnson syndrome *, polymorphic erythema *, change in skin odor, paraorbital edema *, localized urticaria; frequency is unknown - toxic epidermal necrolysis *. From the musculoskeletal system and connective tissue: often - arthralgia, muscle spasms, myalgia, muscle cramps, muscle weakness, musculoskeletal pain in the chest cell; infrequently: swelling of the joints *, stiffness of the muscles, pain in the side, fatigue in the muscles; seldom: discomfort in extremities *. From the side of kidneys and urinary tract: often - nephrolithiasis, pollakiuria, dysuria; infrequently - exacerbation of urolithiasis (kidney stones), stress urinary incontinence, hematuria, urinary incontinence, frequent urination,renal colic, pain in the kidney area; rarely - exacerbation of urolithiasis (stones in the urethra) renal tubular acidosis *. From the genital organs and the breast: infrequently - erectile dysfunction, sexual dysfunction. Common disorders and disorders caused by the method of use: very often - fatigue; often - increased body temperature, asthenia, irritability, gait disturbances, poor health, anxiety; infrequently - hyperthermia, thirst, flu-like syndrome *, sluggishness, cold extremities, intoxication, anxiety; rarely - swelling of the face, calcification. Changes in laboratory parameters: very often - weight loss; often - weight gain *; infrequently - crystalluria, an abnormal test result "tandem-gait", leukopenia, increased activity of liver enzymes in the blood serum, rarely - a decrease in the content of hydrocarbons in the blood.
Overdose
Symptoms: convulsions, drowsiness, impaired speech and vision, diplopia, impaired thinking, impaired coordination, lethargy, stupor, arterial hypotension, abdominal pain, dizziness, agitation and depression. In most cases, the clinical consequences were not severe, but deaths were noted after an overdose using a mixture of several drugs, including topiramate. The development of severe metabolic acidosis is possible. There is a case of overdose, when the patient took a dose of topiramate from 96 to 110 g, which resulted in a coma lasting 20-24 hours. After 3-4 days, the symptoms of overdose were resolved. Treatment: if shortly before taking an excessive dose the patient took food, you must immediately flush the stomach or induce vomiting. In vitro studies have shown that activated carbon adsorbs topiramate. If necessary, symptomatic therapy should be carried out. An effective way to remove topiramate from the body is hemodialysis. Patients are recommended an adequate increase in fluid intake.
Interaction with other drugs
The effect of Topamax on the concentrations of other antiepileptic drugs (PEP). Simultaneous use of Topamax with other probes (phenytoin, carbamazepine, valproic acid, phenobarbital, primidone) does not affect the plasma Css values, except for certain patients who have added Topamax to phenytoin may cause an increase in plasma phenytoin concentration.This may be due to the inhibition of a specific polymorphic isoform of the cytochrome P450 enzyme system (CYP2Cmeph). Therefore, when symptoms of toxicity develop in patients receiving phenytoin, it is necessary to control the concentration of phenytoin in the blood plasma. In the pharmacokinetic study of patients with epilepsy, the addition of topiramate to lamotrigine did not affect the Css of the latter in plasma at doses of topiramate 100-400 mg / day. During and after the abolition of lamotrigine (the average dose of 327 mg / day), Css topiramate did not change. The effect of other AEDs on plasma plasma topiramate concentration Phenytoin and carbamazepine, while using Topamax, reduced the plasma concentration of topiramate. Adding or removing phenytoin or carbamazepine during treatment with Topamax may require a change in the dose of the latter. The dose is selected depending on the development of the required clinical effect. Addition or elimination of valproic acid does not cause clinically significant changes in the concentration of topiramate in the blood plasma and, therefore, does not require a change in the dose of Topamax. Add PEP Concentration of PEP Concentration of Topiramate Phenytoin no effect (increase in plasma concentration in isolated cases) decrease in plasma concentration by 48% Carbamazepine no effect decrease in plasma concentration by 40% Valproic acid no effect no effect Phenobarbital no effect not studied imidone no effect has not been studied. Interaction with other drugs. In studies conducted with simultaneous use of the drug Topamax in a single dose of AUC of digoxin was reduced by 12%. The clinical significance of this effect has not been established. When prescribing or canceling Topamax in patients receiving digoxin, it is necessary to monitor the concentration of digoxin in the serum. As part of clinical studies, the effects of the combined use of Topamax with drugs that depress the central nervous system, as well as with ethanol, have not been studied. The combined use of Topamax with drugs that have a depressant effect on the central nervous system and ethanol is not recommended. When Topamax and Hypericum perforatum preparations are taken together, Topiramate concentration in the plasma may decrease and, as a result, the effectiveness of the drug may also decrease .Clinical studies of the interaction of the drug Topamax and preparations based on Hypericum perforatum have not been conducted. With simultaneous use of an oral contraceptive containing norethisterone (1 mg) and ethinyl estradiol (35 μg), Topamax at doses of 50-800 mg / day did not significantly affect the effectiveness of norethisterone in doses of 50-200 mg / day - on the effectiveness of ethinyl estradiol. A significant dose-dependent decrease in the efficacy of ethinyl estradiol was observed at doses of the drug Topamax 200-800 mg / day. The clinical significance of the described changes is not clear. The risk of reducing the effectiveness of contraceptives and enhancing breakthrough bleeding should be considered in patients taking oral contraceptives in combination with Topamax. Patients taking estrogen-containing contraceptives should inform the doctor about any changes in the timing and nature of menstruation. The effectiveness of contraceptives can be reduced even in the absence of breakthrough bleeding. In healthy volunteers, lithium AUC decreased by 18% while taking topiramate at a dose of 200 mg / day. In patients with manic-depressive psychosis, the use of topiramate in doses up to 200 mg / day did not affect the pharmacokinetics of lithium, but at higher doses (up to 600 mg / day), lithium AUC was increased by 26%. With the simultaneous use of topiramate and lithium, the concentration of the latter in the blood plasma should be monitored. Studies of drug interactions conducted with a single and repeated administration of topiramate to healthy volunteers and patients with manic-depressive psychosis gave the same results. With the simultaneous use of topiratam in daily doses of 250 mg or 400 mg of AUC of risperidone, taken in doses of 1-6 mg / day, reduced by 16% and 33%, respectively. At the same time, the pharmacokinetics of 9-hydroxyrisperidone did not change, and the total pharmacokinetics of the active substances (risperidone and 9-hydroxyrisperidone) changed insignificantly. Changes in the level of systemic exposure to risperidone / 9-hydroxyrisperidone and topiramate were not clinically significant, and this interaction is unlikely to have clinical significance. Drug interaction was studied in healthy volunteers with separate and co-administration of hydrochlorothiazide (25 mg) and topiramate (96 mg).The research results showed that while taking topiramate and hydrochlorothiazide, there is an increase in Cmax of topiramate by 27% and its AUC by 29%. The clinical significance of these studies has not been identified. When administering hydrochlorothiazide to patients taking topiramate, dose adjustment of topiramate may be required. No significant changes in the pharmacokinetic parameters of hydrochlorothiazide were observed with concomitant therapy with topiramate. Drug interactions were studied in healthy volunteers who received metformin or a combination of metformin and topiramate. Research results showed that while taking topiramate and metformin, Cmax and AUC of metformin increased by 18% and 25%, respectively, while clearance of metformin while being administered simultaneously with topiramate decreased by 20%. Topiramate had no effect on Tmax of metformin in the blood plasma. The clearance of a topiramat at joint appointment with metformin decreases. The degree of clearance changes have not been studied. The clinical significance of the effects of metformin on the pharmacokinetics of topiramate is not clear. In the case of the addition or withdrawal of Topamax in patients receiving metformin, the state of patients with diabetes should be monitored. Drug interactions have been studied in healthy volunteers with separate and co-administration of pioglitazone and topiramate. It was revealed a decrease in the AUC of pioglitazone by 15%, without changing the Cmax of the drug. These changes were not statistically significant. Also for the active hydroxymetabolite pioglitazone, a decrease in Cmax and AUC was detected by 13% and 16%, respectively, and for active ketometabolite, a decrease in both Cmax and AUC by 60% was detected. The clinical significance of this data has not been elucidated. When patients are jointly prescribed Topamax and pioglitazone, the patient’s condition should be carefully monitored to assess the course of diabetes. A drug interaction study was conducted to study the pharmacokinetics of glibenclamide (5 mg / day) in an equilibrium state, used alone or simultaneously with topiramate (150 mg / day ) in patients with type 2 diabetes. When using topiramate, the AUC of glibenclamide was reduced by 25%. The level of systemic exposure to active metabolites, 4-trans-hydroxy-glibenclamide and 3-cis-hydroxy-glibenclamide, was also reduced (by 13% and 15%, respectively). Glibenclamide did not affect the pharmacokinetics of topiramate in equilibrium.A statistically insignificant decrease in the AUC of pioglitazone by 15% was found with no change in its Cmax. When topiramate is prescribed to patients receiving glibenclamide (or prescribing glibenclamide to patients receiving topiramate), the patient’s condition should be carefully monitored to assess the course of diabetes. With the simultaneous use of Topamax with other drugs predisposing to the development of nephrolithiasis, the risk of kidney stones may increase. During the period of treatment with Topamax, the use of such drugs should be avoided, since they can cause physiological changes that contribute to the development of nephrolithiasis. The combined use of topiramate and valproic acid in patients who tolerate each drug well separately is accompanied by hyperammonemia with or without encephalopathy. In most cases, the symptoms and signs disappear after discontinuation of one of the drugs. This adverse event is not caused by pharmacokinetic interaction. The relationship between hyperammonemia and the use of topiramate alone or in combination with other drugs has not been established. When co-taking topiramate and valproic acid, hypothermia may occur (unintended decrease in body temperature below 35 ° C) in combination with hyperammonemia or independently. This phenomenon can occur both after the start of joint administration of valproic acid and topiramate, as well as with an increase in the daily dose of topiramate. Clinical studies have been conducted to assess the potential options for drug interaction between topiramate and other drugs. The results of this interaction are summarized in the table. Additive drug The concentration of the added drug * Topiramate concentration * Amitriptyline increase in Cmax and AUC of nortriptyline (amitriptyline metabolite) by 20% has not been studied Dihydroergotamine (inside and sc) ** ** Haloperidol increase in AUC metabolite by 31 % was not studied. Propranolol Cmax 4-OH propranolol increased by 17% (topiramate 50 mg), Cmax increased by 9% and 16%, the AUC increased by 9% and 17% (propranolol 40 mg and 80 mg every 12 hours, respectively) Sumatriptan (inside and s / c) * * not investigated. Pisothiphene ** ** Diltiazem decreased diltiazem AUC by 25% and desacetyldiltiazem by 18% and** for N-demethyldiltiazem an increase in AUC by 20% Venlafaxine ** ** Flunarizine an increase in AUC by 16% (50 mg every 12 hours) 1 *** expressed in% of Cmax and AUC values in monotherapy ** no change in Cmax and AUC (≤ 15% of baseline data) 1 With repeated use of flunarizin (monotherapy), an increase in AUC by 14% was observed, which may be due to the accumulation of the drug in the process of achieving an equilibrium state
special instructions
To reduce the dose by 25-50 mg, Topamax is used in the form of capsules in a dosage of 15 mg or 25 mg. In clinical studies, the dose of the drug was reduced by 50-100 mg 1 time per week - for adults with epilepsy therapy and 25-50 mg - in adults receiving Topamax at a dose of 100 mg / day for the prevention of migraine. In children in clinical studies, Topamax was gradually canceled over a period of 2–8 weeks. If, for medical reasons, rapid withdrawal of Topamax is necessary, it is recommended to carry out appropriate monitoring of the patient's condition. As with any disease, the dosage regimen should be set in accordance with the clinical effect (ie, the degree of control of seizures, no side effects) and take that in patients with impaired renal function, it may be necessary to take a longer time for each dose to establish a stable plasma concentration. With topiramate therapy, it may be possible oligohydrosis (reduced sweating) and anhidrosis. Reduced sweating and hyperthermia (increased body temperature) can occur in children exposed to high ambient temperatures. In therapy with topiramate, it is very important to adequately increase the volume of fluid consumed, thereby reducing the risk of developing nephrolithiasis, as well as the side effects that can occur under physical exertion or elevated temperatures. , including Topamax, increases the risk of suicidal thoughts and suicidal behavior in patients taking these reparata according to any of the indications. In double-blind clinical studies, the incidence of phenomena associated with suicide (suicidal thoughts, suicide attempts, suicide) was 0.5% in patients treated with topiramate (46 people out of 8652), which is about 3 times higher compared with patients receiving placebo (0.2%; 8 people out of 4045).One case of suicide was recorded in a double-blind study of bipolar disorder in a patient receiving topiramate. Thus, it is necessary to monitor the condition of patients in order to identify signs of suicidal thoughts and prescribe appropriate treatment. Patients (and, if necessary, caregivers) should be advised to immediately seek medical attention if they show signs of suicidal thoughts or suicidal behavior. Some patients, especially those with a predisposition to nephrolithiasis, may have an increased risk of kidney stones and these symptoms, such as renal colic. To reduce this risk, an adequate increase in fluid intake is needed. Risk factors for nephrolithiasis are a history of nephrolithiasis (including family), hypercalciuria, concomitant therapy with other drugs that contribute to the development of nephrolithiasis. Care should be taken when prescribing Topamax to patients with renal insufficiency (CC <70 ml / min). This is due to the fact that in these patients the clearance of the drug is lowered. In patients with impaired liver function, Topamax should be used with caution because of a possible decrease in clearance of topiramat. Symptoms include acute reduction in visual acuity and / or pain in the eye. Ophthalmologic examination may show myopia, flattening of the anterior chamber of the eye, hyperemia (redness) of the eyeball, increased intraocular pressure. Mydriasis may occur. This syndrome may be accompanied by the secretion of fluid, leading to the displacement of the lens and the iris forward with the development of secondary angle-closure glaucoma. Symptoms usually appear 1 month after starting Topamax. Unlike primary open-angle glaucoma, which is rarely seen in patients under 40 years of age, secondary angle-closure glaucoma is observed with the use of topiramate in both adults and children. In the event of a syndrome involving myopia associated with angle-closure glaucoma, treatment includes discontinuing Topamax as soon as the attending physician considers it possible, and appropriate measures aimed at lowering intraocular pressure.Typically, these measures lead to the normalization of intraocular pressure. Increased intraocular pressure of any etiology in the absence of adequate treatment can lead to serious complications, including loss of vision. When using topiramate, hyperchloremic, not associated with anion deficiency, metabolic acidosis (for example,