Topamax for obesity
Using and Administration
Inside, regardless of the meal
To achieve optimal control of epileptic seizures in children and adults are recommended to start treatment with low doses of the drug taking, followed by gradual titration to effective dose.
Capsules are intended for patients who have difficulties with swallowing tablets (eg children and does topamax cause weight loss elderly patients). In such cases, the capsule Topamax should be carefully opened, its contents mixed with a small amount (about 1 level spoon) any soft food. This mixture should be swallowed immediately without chewing. Do not store medicine mixed with food until the next reception. Topamax pills can be swallowed whole and.
Use in combination with other anticonvulsants in adult patients. Usually, total daily dose ranges from 200 to 400 mg taken in 2 divided doses. Some patients may need to increase to a maximum daily dose – 1600 mg. It is recommended to start treatment with low doses followed by gradual selection of effective dose. In the future, at weekly or 2-week intervals the dose can be increased to 25-50 mg and take it in 2 hours. If dosage topamax side effects must be guided by clinical effect. In some patients, the effect can be achieved while taking the drug 1 time a day. To achieve optimal therapeutic effect, drug Topamax is not necessary to control its concentration in plasma.
The recommendations for dosage applicable to all adult patients, including older people, if they have kidney disease (see “Cautions”).
The recommended total daily dose of the drug topamax side effects as a means of adjuvant therapy is 5 to 9 mg / kg and was adopted in 2 hours. Dosage should begin with 25 mg (or less, based on the initial dose – 1 to 3 mg / kg / day), taking them at night for 1 week. In the future, at weekly or 2-week intervals the dose can be increased by 1-3 mg / kg, and take it in 2 hours.
Topamax side effects the overall situation. If you cancel concomitant anticonvulsants in order to take into account the possible impact of this step on the frequency of seizures. In cases where there is no need to abruptly cancel the concomitant anticonvulsants for security reasons, it is recommended to reduce their dose gradually reducing the dose of concomitant antiepileptic drugs for 1 / 3 every 2 weeks.
With the abolition of drugs that are inducers of hepatic enzymes, the concentration of topamax side effects in the blood will increase. In such situations, if clinically indicated dose of the drug Topamax can be reduced.
Then increase the dose at intervals of 1-2 weeks at 25 or 50 mg (daily dose divided into does topamax cause weight loss). If the patient does not tolerate such treatment dose increase, then you can increase the intervals between the dose topamax side effects, or increase the dose more gradually. The initial dose of topamax side effects in adults is 100 mg / day, and the maximum daily dose should not exceed 500 mg. Some patients with refractory epilepsy tolerate topamax side effects at doses up to 1000 mg / day. Recommendations for dosage are all adults, including elderly patients not suffering from kidney disease.
Children older than 2 years in the first week of treatment should be given topamax side effects at a dose of 0,5-1 mg / kg of body weight before bedtime. Then increase the dose at intervals does topamax cause weight loss). If the child does not tolerate such a regime of increasing doses, it can raise the dose more slowly or increase the interval between dose topamax side effects. The value of dose and its rate of increase should be determined by clinical results.
The recommended dosage range for topamax side effects in children older than 2 years is 3.6 mg / kg / day. Children c newly diagnosed partial seizures can assign up to 500 mg / day.
The recommended total daily dose of topamax side effects for the prevention of migraine attacks is 100 mg in 2 divided doses. At the beginning of treatment the patient should take 25 mg of Topamax at bedtime for 1 week. Then increase the dose at intervals of 1 week at 25 mg / day. If the patient does not tolerate such treatment dose increase, then you can increase the intervals between the dose topamax side effects, or increase the dose more gradually.
In some patients the positive results achieved at a daily dose of topiramate at 50 mg. In clinical studies, patients received different daily doses of topiramate, but not more than 200 mg / day.
Cautions
Antiepileptic drugs, including drug Topamax, should be lifted gradually, to minimize the possibility of increasing the frequency of seizures. In clinical trials the dose was reduced by 50-100 mg at weekly intervals for the treatment of adults with epilepsy and 25-50 mg in adults receiving 100 mg / day the drug Topamax to prevent migraines. The children in clinical trials the drug Topamax gradually abolished within 2.8 weeks. If for medical reasons need quick removal of the drug Topamax, it is recommended to exercise appropriate control of the patient.
Speed excretion by the kidney depends on renal function and does not depend on age. In patients with moderate or severe renal impairment in order to achieve stable plasma concentrations may need from does topamax cause weight loss to 15 days, as opposed to 4-8 days in patients with normal renal function.
As with any illness, dose selection scheme should be guided by clinical effect (ie the degree of control the seizures, the absence of side effects does topamax cause weight loss) and take into account that patients with impaired renal function to establish a stable plasma concentration for each dose may need more long time.
When topamax weight loss therapy is very important to adequately increase the volume of fluid intake can reduce the risk of topamax weight loss, as well as side effects that may arise under the influence of physical activity or high temperatures.
In the treatment of t topamax weight loss observed an increased incidence of mood disorders and depression.
Suicide attempts. In conducting double-blind clinical studies using topamax weight loss in approved and investigational indications, suicide attempts occurred at a frequency of 0,003 while taking topamax weight loss (13 cases among 3999 topamax weight loss) with placebo – a rate of 0 (0 cases among 430 patients). It was noted that a completed suicide attempt in a clinical study on the application of the drug in bipolar disorder.
In some patients, especially with a predisposition to topamax weight loss may increase the risk of kidney stones and the appearance of related symptoms, such as renal colic. To reduce this risk, should be an adequate increase in the volume of fluid intake.
Topamax weight loss is a history (including family), topamax weight loss, concomitant therapy drugs, which contribute to the development of nephrolithiasis.
Patients with impaired hepatic function topiramate should be used with caution because of possible reduction in clearance of the drug.
In applying the drug Topamax described syndrome, including acute myopia associated with secondary angle-closure glaucoma. Symptoms include a sharp reduction in visual acuity and / or pain in the eye. At Ophthalmologic examination can be found myopia, flattening of the anterior chamber of the eye, hyperemia (redness) of the eyeball, increased intraocular pressure. Topamax weight loss may be observed. This syndrome may be accompanied by secretion of fluid, leading to a shift of the lens and the iris forward with the development of secondary angle-closure glaucoma. Symptoms usually appear 1 month after the beginning of the drug Topamax. In contrast to primary open-angle glaucoma, which is rarely observed in patients up to 40 years of age, secondary angle-closure glaucoma occurs when using topamax weight loss in adults and children. If you have a syndrome, including myopia associated with angle-closure glaucoma treatment includes discontinuation of the drug Topamax, as soon as the physician deems it feasible, and appropriate measures aimed at lowering intraocular pressure. Typically, these measures lead to normalization of intraocular pressure.
Elevated intraocular pressure of any etiology in the absence of adequate treatment may lead to serious complications, even blindness.
In the application of topamax weight loss may occur hyperchloraemic not associated with a deficit of anions, metabolic acidosis (eg, reduced concentration of bicarbonate in plasma below the normal level in the absence of respiratory alkalosis). This decrease in concentration of serum bicarbonate is a consequence of inhibitory effect of does topamax cause weight loss on renal topamax weight loss. In most cases, reducing the concentration of bicarbonate occurs at the beginning of the drug, although this effect may occur in any period of topiramate treatment. The level of concentration reduction is usually weak or moderate (mean of topamax weight loss when used in adult patients at a dose above 100 mg / day and about 6 mg / kg / day when used in pediatric patients). In rare cases, patients have reduced concentrations of bicarbonate below topamax weight loss. Some diseases or treatments that predispose to the development of acidosis (eg renal disease, severe respiratory diseases, status epilepticus, diarrhea, surgery, topamax weight loss diet, topamax weight loss medications) may be additional factors contributing to bicarbonate-lowering effect of topiramate.
In children, chronic metabolic acidosis can lead to slower growth. Effect of topiramate on growth and possible complications associated with the skeletal system have not been studied systematically in children and adults.
In connection with the foregoing, in the treatment of topiramate is recommended to conduct the necessary studies, including determination of the concentration of bicarbonate in serum. In the event of metabolic acidosis and its persistence, it is recommended to reduce the dose or stop taking does topamax cause weight loss.
If a patient loses weight in the treatment of drug Topamax for obesity, it is necessary to consider the desirability of increasing supply.
The drug Topamax affects the central nervous system and can cause drowsiness, dizziness and other symptoms. It can also cause blurred vision. These adverse effects can be dangerous for patients, for driving and moving mechanisms, particularly at a time until you set an individual patient’s reaction to the drug.
Buy topamax no prescription
Pharmacological action
Antiepileptic drugs, belongs to a class of sulfate-substituted monosaccharides.
Topiramate blocks sodium channels and inhibits the emergence of repetitive action potentials on a background of prolonged depolarization of the membrane of the neuron & buy topamax no prescription.
Topiramate enhances GABA activity against certain subtypes of GABA-receptors (including GABAA-receptor), and modulates the activity itself GABAA-receptor activation prevents kainate subtype of kainate sensitivity / AMPK (alpha-amino-3-hydroxy-5 – metilizoksazol-4-propionic acid) receptors for glutamate, does not affect the activity of N-methyl-D-aspartate (NMDA) on the NMDA-receptor topamax generic subtype. These effects are dose-related drug at a concentration of topiramate in plasma from 1 mmol to 200 mmol, with minimal activity in the range from 1 mmol to 10 mmol. In addition, topiramate inhibits some isoenzymes of carbonic anhydrase activity.
On expression of the pharmacologic effect of topiramate significantly inferior to acetazolamide – a known carbonic anhydrase inhibitor, so this activity of topiramate is not a major component of its antiepileptic activity.
Pharmacokinetics
Suction
After receiving the drug inside topiramate rapidly and efficiently absorbed buy topamax no prescription from the gastrointestinal tract. Bioavailability is 81%. Eating no clinically significant effect on bioavailability.
Following single dose oral pharmacokinetics of topiramate are linear in nature, plasma clearance remains constant, and the AUC in the range of doses from 100 mg to 400 mg increases in proportion to dose.
After repeated oral administration at a dose of 100 mg 2 Cmax average of 6.76 mg / ml.
Distribution
Plasma protein binding is 13-17%.
After a single oral dose to 1200 mg average Vd is 0.55-0.8 L / kg. The value of Vd depends on sex. In women, the values topamax generic are approximately 50% of the values observed in men, which is associated with a higher content of adipose tissue in women.
In patients with normal renal function to achieve equilibrium may require 4 to 8 days.
Metabolism
After oral administration, is metabolized about 20% of the dose.
The plasma, urine and human feces were isolated and identified 6 virtually inactive metabolites.
Withdrawal
Topiramate (70%) and its metabolites are eliminated primarily by the kidneys.
After oral administration, plasma clearance of the drug is 20-30 ml / min.
After repeated administration of the drug for 50 and 100 mg, 2 average T1 / 2 was 21 h.
Pharmacokinetics in special clinical cases buy topamax no prescription
Topiramate kidney excretion rate topamax generic depends on renal function and does not depend on age.
Patients with impaired renal function (CC ≤ 60 mL / min) renal and plasma clearance of topiramate is reduced.
Time to reach equilibrium in patients c moderate to severe impaired renal function from 10 to 15 days.
Elderly patients not suffering from kidney disease, plasma clearance of topiramate is unchanged.
In patients with moderate and severe hepatic impairment the plasma clearance is reduced.
Patients receiving concomitant therapy antiepileptic drugs buy topamax no prescription that induce enzymes involved in the metabolism of drugs, the metabolism of topiramate increased by 50%.
Topiramate effectively displayed by hemodialysis.
Children under the age of 12 years, pharmacokinetic parameters of topiramate as well as in adults receiving the drug as an adjunctive therapy, are linear, while its clearance is not dependent on the dose and Css in plasma increases proportionally with increasing dose. Note that the clearance of topiramate in children increased, and its T1 / 2 shorter. Therefore, when the same dose per 1 kg body weight concentrations of topiramate in plasma in children may be lower than in adults. Children, like adults, antiepileptic drugs that induce hepatic enzymes that cause reduction Css topiramate in plasma.
Indications
Monotherapy:
*
epilepsy (including patients with newly diagnosed epilepsy) in adults and children older than 2 years.
In the complex therapy:
*
partial or generalized tonic-clonic seizures in adults and children older than 2 years;
*
seizures associated with Lennox-Gastaut syndrome, in adults and children older than 2 years.
Capsules 50 mg are also used to prevent migraine attacks (adults).
The use Topamax for treatment of acute migraine attacks is not known.
Dosage regimen
The drug is taken by mouth, regardless of the meal.
To achieve optimal control of epileptic seizures in adults and children is recommended to start treatment with the drug in low doses with subsequent titration to effective dose.
Tablets Topamax is not recommended to divide into parts.
Capsules are intended for patients who have difficulties with swallowing tablets (eg, children and elderly patients).
The capsules should be carefully opened, their contents mixed with a small amount (about 1 teaspoon) of any soft food. This mixture should be swallowed immediately buy topamax no prescription without chewing. Do not store medication mixed with food until the next reception. Topamax capsules may be swallowed whole.
When using Topamax as part of combination therapy with other anticonvulsants in adults, including elderly topamax generic patients with normal renal function, the minimum effective dose is 200 mg / day. Average daily dose is 200-400 mg, number of intakes – 2 times / day.
Selection of doses beginning with 25-50 mg 1 time per day. at night, taking medication for 1 week. The following is to increase the dose by 25-50 mg at intervals of 1 or 2 weeks before the selection of effective dose, number of intakes – 2 If necessary, may increase to a maximum daily dose – 1600 mg. The criterion for selection of dose is the clinical effect. In some patients the effect is achieved when receiving the drug 1 time / day. To achieve optimal effect of treatment
Topamax is not necessarily control its concentration in plasma.
When using Topamax as part of combination therapy with other anticonvulsants in children older than 2 years, the recommended total daily dose is from 5 to 9 mg / kg and was adopted in 2 hours. Selection of the starting dose of 25 mg / day. (or less, the rate of 1-3 mg / kg body weight / day.), take medication at night for 1 week. In the future, with weekly or biweekly intervals dose can be increased by 1-3 mg / kg, and take the drug in 2 hours. The selection of doses should be guided by clinical effect. The daily dose of 30 mg / kg of body weight, usually well tolerated.
If you cancel a concomitant anticonvulsants topiramate monotherapy in order to take into account the possible impact of this step on the frequency of seizures. In cases where there is no need to topamax generic abruptly cancel the concomitant anticonvulsants for security reasons, it is recommended to reduce their dose gradually reducing the dose of concomitant antiepileptic drugs by one third every 2 weeks.
With the abolition of drugs that are inducers of hepatic enzymes, the concentration of topiramate in the blood will increase. In such situations, if clinically indicated dose of Topamax can be reduced.
In conducting monotherapy for adults, including elderly patients with normal renal function, at the beginning of treatment prescribed Topamax 25 mg 1 time per day. bedtime for 1 week. Then increase the dose at intervals of 1-2 weeks at 25-50 mg / day. 2 admission. If intolerance of such a treatment regimen increase the dose to a smaller size or with buy topamax no prescription large intervals. The dose is selected depending on the clinical effect. The initial dose is 100 mg, the maximum daily dose – 500 mg. In some cases, the form of refractory epilepsy patients tolerate Topamax monotherapy in doses up to 1000 mg / day.
When monotherapy for children older than 2 years in the first week of treatment prescribed topiramate at a dose of 0.5-1 mg / kg body weight before bedtime. Then increase the dose at intervals of 1-2 weeks to 0.5-1 mg / kg / day., The daily dose divided into 2 hours. If intolerance of such a regime can increase the dose to a smaller size or with large intervals. The value of dose and its rate of increase determined by the clinical effectiveness of therapy. The recommended dosage range for topiramate monotherapy in children older than 2 years is 3-6 mg / kg / day. In newly diagnosed partial seizures dose can be up to 500 mg / day.
For the prevention of migraine attacks daily dose of topiramate was 100 mg in 2 divided doses. At the beginning of topamax generic treatment prescribed by 25 mg at bedtime for 1 week. Then increase the dose of 25 mg at intervals of 1 week. If intolerance of such a treatment regimen increase the dose to a smaller size or with large intervals.
The dose is selected depending on the clinical effect. In some cases, a positive result is achieved at a daily dose of topiramate 50 mg. In clinical studies, patients received different doses, but not more than 200 mg / day.
Side effects
Side effects are shown with the distribution of frequencies and organ systems. The frequency of side effects were classified as follows: very common (≥ 1 / 10), common (≥ 1 / 100, <1 / 10), uncommon (≥ 1 / 1000 and <1 / 100), rare (≥ 1 / 10 000 and <1 / 1000) and very rarely (<1 / 10 000).
From the side of the central nervous system and peripheral nervous system: very often – drowsiness, dizziness, paresthesia, children – apathy, a violation of attention, often – loss of coordination, nystagmus, lethargy, impaired memory, violation of concentration, tremor, amnesia, poor gait, hypesthesia, perversion of taste, thought disorder, topamax generic, speech disorder, dysarthria, cognitive disorders, lethargy, mental impairment, psychomotor disorders, sedative effect; infrequently – the loss of taste sensitivity, akinesia, loss of smell, aphasia, burning sensation, cerebellar syndrome, a violation of the circadian rhythm of sleep, clumsiness, postural dizziness, increased salivation, numbness, dysgraphia, dyskinesia, dysphasia, crawl, hyperesthesia, gipogevziya, hypokinesia, buy topamax no prescription hyposphresia, peripheral neuropathy, parosmiya, presyncope, repetitive speech, paraphia, stupor, fainting, lack of response to stimuli in children – psychomotor hyperactivity.
Mental disorders: frequent – slow thinking, expressed by speech disturbances, confusion, depression, insomnia, aggressive reaction, agitation, irritability, dizorientatsiya, emotional lability, erektilnayaya dysfunction in children – changing behavior, learning disabilities, infrequent – anorgasmia, sexual dysfunction, apathy , the cries, the violation of sexual arousal, disfemiya, increased distractibility, early awakening in the morning, elated and euphoric mood, auditory and visual hallucinations, gipomaniakalnyoe state, a decrease topamax generic in libido, mania, a state of panic, paranoid state, perseveration of thought, a violation of Reading, restlessness, sleep disturbances, suicidal ideation or attempts, crying, very rarely – a sense of despair.
Also, there were nervousness, headache, psychomotor retardation, ataxia, additionally in children – personality disorder, hyperkinesia, rare – psychotic symptoms in children – hallucinations.
From the digestive system: very often – a reduction or increase of appetite, anorexia, frequent – nausea, diarrhea; rare – abdominal pain, constipation, stomach discomfort, dyspepsia, dry mouth, a violation of the sensitivity in the mouth, gastritis, gastroesophageal reflux, bleeding gums, heavy feeling in the stomach; infrequently – bad breath, discomfort in the epigastrium, flatulence, glossodiniya, pain in the mouth, hypersecretion buy topamax no prescription of the salivary glands, thirst, the children – vomiting rarely – increased activity of hepatic transaminases, hepatitis, liver failure .
From the Musculoskeletal System: Frequent – myalgia, muscle cramps, muscle cramps, muscle pain topamax generic in the chest, arthralgia; infrequently – the pain in his side, fatigue, weakness, muscle stiffness, very rarely – a swelling of the joints, discomfort in the limbs.
Since the cardiovascular system: Infrequent – bradycardia, palpitations, flushing, orthostatic hypotension, vibration disease.
On the part of the organ of vision: it is often – diplopia, blurred vision, dry eyes, infrequent – disturbance of accommodation, amblyopia, blepharospasm, transient blindness, unilateral blindness, increased lacrimation, mydriasis, night blindness, Photopsia, presbyopia, scintillating scotoma, scotoma, reduced visual acuity ; very rarely – unpleasant sensations in the eyes, angle-closure glaucoma, the violation of eye movements, swelling of eyelids, myopia.
The part of the organ of hearing: often – earaches, ringing in the ears, children – vertigo; infrequently – deafness, sensorineural deafness, unilateral deafness, discomfort in the ears, hearing loss.
On the part of the respiratory system: often – difficulty breathing, nose bleeding, infrequent – hoarseness, shortness of breath on exertion, nasal obstruction, hypersecretion in the paranasal sinuses in children – running nose, very rarely – nasopharyngitis.
Dermatological reactions: often – a rash, alopecia, pruritus, reduction in sensitivity person; infrequently – no sweats, allergic dermatitis, skin redness, pigmentation disorders of the skin, rashes, swelling of the face, an unpleasant smell of skin, rash, very rarely – a polymorphic erythema, pemphigus, periorbital edema, Stevens-Johnson syndrome, toxic epidermal necrolysis (especially when using in conjunction with topamax generic other drugs that cause adverse reactions from the skin and mucous membranes).
The part of the urinary system: often – nephrolithiasis, dysuria, thamuria; infrequently – urolithiasis, hematuria, urinary incontinence, frequent urge to urinate, renal colic, pain in the kidney, very rarely – pochechnokanaltsevy acidosis.
The part of the hemopoietic system: often – anemia; infrequently – leukopenia, lymphadenopathy, thrombocytopenia, topamax generic in children – eosinophilia; very rarely – neutropenia.
Laboratory findings: Infrequent – reduce the content of bicarbonate in the blood, crystalluria, hypokalemia, metabolic acidosis, hyperchloraemic acidosis.
General disorders: very common – fatigue, irritability, weight loss, often – asthenia, anxiety in children – fever infrequently – face edema, allergic reactions, cold extremities, very buy topamax no prescription rarely – generalized edema, influenza-like illness, allergic edema, conjunctival edema, weight gain.
Other: rarely – oligogidroz (mostly children).
Contraindications
*
Children under 2 years;
*
Hypersensitivity to the ingredients.
Precautions should be used in renal or hepatic insufficiency, nefrourolitiaze (including past or family history), and hypercalciuria.
Pregnancy and lactation
Studies that Topamax would be used for the treatment of pregnant women, were not conducted. Nevertheless, use topamax generic during pregnancy is only possible in cases where the anticipated benefits to the mother outweighs the potential risk to the fetus.
A limited number of observations suggest that topiramate is excreted in breast milk. If necessary, use Topamax in lactation period should settle the question of termination of breastfeeding.
Application for violations of liver function
Precautions should be applied to liver failure.
In patients with moderate and severe hepatic topamax generic impairment the plasma clearance is reduced.
Use in Renal Impairment
In the appointment of the drug to patients with moderately or severely impaired renal function expressed should be aware that in order to achieve the equilibrium state of this category of patients may need 10-15 days, as opposed to 4-8 days in patients with normal renal buy topamax no prescription function. Since topiramate is removed from plasma during hemodialysis, in the days of the meeting should be prescribed an additional dose equal to half the daily dose in 2 hours (before and after the procedure).
Precautions should be used in renal failure, nefrourolitiaze (including past or family history), and hypercalciuria.
Cautions
Cancel Topamax should be gradual, to minimize the possibility of increasing the frequency of seizures. When conducting clinical trials of the drug dose was reduced by 50-100 mg 1 time per week – for the treatment of adults with epilepsy and 25-50 mg – in adults receiving topamax generic in doses of 100 mg for the prevention of migraine.
The children in clinical trials Topamax gradually abolished within 2-8 weeks. If for medical reasons need quick removal of Topamax, it is recommended to exercise appropriate control of the patient. In some patients, removal of the drug has been accelerated and passed without any complications.
Topamax
Topamax is for the treatment of epilepsy. It is suitable for adults and children older than 2 years. Used for newly diagnosed epilepsy, partial or generalized tonic-clonic seizures, Lennox-Gastaut syndrome.
The composition and the form of:
Topamax capsules or coated tablets, and 28 or 60 pieces. in the package.
Topamax 1 capsule contains: topiramate 15, 25 or 50 mg.
Topamax 1 tablet contains: topiramate 25 or 100 mg.
Active-active substance: Topiramate
Properties / Action:
Topamax – antiepileptic. It belongs to a class of sulfate-substituted monosaccharides.
Antiepileptic activity of topamax side effects is caused by a number of its properties. Topamax (topiramate) blocks sodium channels and reduces the frequency of action potentials characteristic of the neuron in a state of persistent depolarization. Topiramate potentiates the activity of GABA (gamma-aminobutyric acid, GABA) in respect of certain subtypes of GABA-receptors (including GABAA-receptor), and modulates the activity itself GABAA-receptor activation prevents kainate sensitivity of kainate / AMPK-receptors for glutamate does not affect the activity of N-methyl-D-aspartate for NMDA-receptors. These effects are dose-related with Topamax topiramate concentrations in plasma from 1 mmol to 200 mmol, with minimal activity in the range from 1 mmol to 10 mmol.
In addition, Topamax (topiramate) inhibits the activity of some isozymes of carbonic anhydrase, but this effect in topiramate weaker than that of acetazolamide, and, apparently, is not central to the antiepileptic activity of topiramate.
Pharmacokinetics:
After receiving oral topiramate Topamax quickly and efficiently absorbed from the gastrointestinal tract. Bioavailability is about 80%. Eating no clinically significant effect on the bioavailability of Topamax. In healthy volunteers the average maximum plasma concentration (Cmax) after multi-dose oral Topamax 100 mg 2 times a day was 6.76 mg / ml. Plasma protein binding is 13-17%. After a single oral dose to 1200 mg of the average volume of distribution (Vd) of 0.55-0.8 l / kg. The value of Vd depends on sex. In women, the values are approximately 50% of the values observed in men, which is associated with a higher content of adipose tissue in women. After receiving a single oral Topamax topiramate pharmacokinetics is linear, the plasma clearance remained constant at 20-30 ml / min, and AUC in the range of doses from 100 mg to 400 mg increases proportionally with dose. In patients with normal renal function to achieve equilibrium may require 4 to 8 days. About 20% of topiramate biotransformed with the formation of 6 metabolites, 2 of which are essentially retain the structure of topiramate, and either do not possess anticonvulsant activity, or show it to a minimum extent. Topiramate and its metabolites are primarily in the urine (70%). After multi-dose Topamax for 50 and 100 mg 2 times a day the average T1 / 2 was 21 hours. Patients receiving concomitant therapy antiepileptic drugs that induce the enzymes responsible for the metabolism of drugs, the metabolism of topiramate increased to 50%.
Patients with impaired renal function (creatinine clearance below 60 ml / minute), renal and plasma clearance of topiramate is reduced. Time needed to reach equilibrium in patient’s c moderate to severe impaired renal function from 10 to 15 days. Topiramate effectively removed from plasma by hemodialysis. In patients with moderately and severely impaired hepatic function expressed plasma clearance topimirate reduced. In children, clearance of topiramate is elevated, and T1 / 2 – faster. At the same dose, per 1 kg of body weight, plasma concentrations of topiramate in children may be lower than in adults. Elderly patients` plasma clearance of topiramate is unchanged.
Indications:
Topamax is used in adults and children older than 2 years:
Partial or generalized tonic-clonic seizures (in combination with other anticonvulsants);
Of newly diagnosed epilepsy (monotherapy);
Seizures associated with Lennox-Gastaut syndrome (Additional therapy).
Topamax dosage and administration:
Topamax appointed interior, regardless of the meal. Tablets should not chew. Capsules are intended for patients who have difficulties with swallowing tablets (eg, children or elderly patients). In such cases, the capsule should be carefully opened, mix the contents with a small amount (1 teaspoon) of any soft food. This mixture should be swallowed immediately without chewing. Do not store medicine mixed with food until the next reception. Capsules can be swallowed whole and. To achieve optimal control of epileptic seizures in children and adults are recommended to start treatment with low doses of the drug taking, followed by gradual titration to effective dose. In determining the rate of increasing doses of Topamax and its value, the determining criterion is the clinical effect – the degree of control the seizures, the absence of side effects. To achieve optimal effect of treatment does not necessarily control topimirate concentration in blood plasma.
Combination therapy:
When using Topamax as part of combination therapy with other anticonvulsants in adult patients the minimum effective dose is 200 mg per day. Average daily dose of Topamax is 200-400 mg, number of intakes – 2 times a day. It is recommended to start treatment with doses of 25-50 mg 1 time a day at night for 1 week. This is followed by increasing the dose of 25-50 mg at intervals of 1 or 2 weeks before the selection of effective dose, number of intakes – 2 times a day. If necessary, may increase to a maximum daily dose – 1600 mg. In some patients the effect is achieved while taking Topamax 1 times per day. When using Topamax as part of combination therapy with other anticonvulsants in children older than 2 years, the recommended total daily dose is from 5 to 9 mg / kg and was adopted in 2 hours. Selection of the starting dose is 25 mg / day (or less, the rate of 1-3 mg / kg body weight per day), taken at night, for 1 week. In the future, with weekly or biweekly intervals Topamax dose can be increased by 1-3 mg / kg and take in 2 hours. The daily dose of 30 mg / kg of body weight is usually well tolerated.
Recommendations for dosage Topamax in combination therapy are all adults, including elderly patients not suffering from kidney disease.
Monotherapy:
When using Topamax as a means of monotherapy should take into account the possible impact of the abolition of concomitant anticonvulsant therapy (PST) to control the frequency of seizures. In cases where undesirable sharply cancel accompanying PST, gradually reduce the dose of drugs, reducing the dose by 1 / 3 every 2 weeks. With the abolition of drugs that are inducers of hepatic microsomal enzymes, the concentration of topiramate in plasma will increase. In such situations, if clinically indicated dose of Topamax can be reduced.
At the beginning of Topamax monotherapy adults should take 25 mg 1 time a day at bedtime for 1 week. Then increase the dose of Topamax at intervals of 1-2 weeks at 25-50 mg / day (daily dose divided into 2 admissions). In such a regime of intolerance to therapy, increase the dose of lesser value, or over large intervals. The recommended dose is 100 mg per day, maximum daily dose – 500 mg. In some cases, a single agent to treat refractory epilepsy dose of Topamax may be 1000 mg per day.
In the first week of treatment of children older than 2 years of monotherapy with Topamax is prescribed in doses of 0.5-1 mg / kg body weight per day (daily dose divided into 2 admissions). The value of dose and its rate of increase is determined by the clinical efficacy and tolerability of therapy. On average, increase the dose at intervals of 1-2 weeks to 0.5-1 mg / kg per day. The recommended dose range for monotherapy Topamax in children older than 2 years is 3-6 mg / kg per day. In newly diagnosed partial seizures dose can be up to 500 mg per day, number of intakes – 2 times a day. Recommendations for dosage Topamax in monotherapy apply to all adults, including elderly patients not suffering from kidney disease.
In appointing Topamax patients with moderately or severely impaired renal function expressed should be aware that in order to achieve the equilibrium state of this category of patients may need 10-15 days, as opposed to 4-8 days in patients with normal renal function. Since topiramate is removed from plasma during hemodialysis, in the days of the meeting should be prescribed an additional dose of Topamax, equal to half the daily dose in 2 hours (before and after the procedure).
Topamax therapy withdrawal:
Cancel Topamax should be gradual, to minimize the possibility of increasing the frequency of seizures. It is recommended each week to reduce the dosage to 100 mg.
Topamax overdose:
Symptoms: increased side effects, seizures, drowsiness, disturbances of speech and vision, diplopia, disturbances of thinking, disturbances of coordination, lethargy, stupor, hypotension, abdominal pain, dizziness, agitation and depression. In most cases the clinical consequences were not severe, but there were fatalities after an overdose with the use of a combination of several drugs, including Topamax. Overdose Topamax can cause severe metabolic acidosis. The patient, who received topiramate at a dose of 96 to 110 g, was hospitalized in a coma, which lasted 20-24 hours. After 3-4 days the patient fully recovered. Treatment: gastric lavage, if necessary, carry symptomatic therapy is recommended adequate increase in the volume of fluid intake. Application of activated carbon is not shown (not adsorb topiramate). Effective way of removing topiramate from the body is hemodialysis.
Contraindications:
Idiosyncrasy (including a history of hypersensitivity) components Topamax;
Children age 2 years (safety and efficacy not established).
Topamax is used with caution:
Renal or hepatic impairment;
Nefrourolitiaz (including past or family history);
Hypercalciuria.
Topamax application during pregnancy and breastfeeding:
There are no adequate and strictly controlled clinical trials the safety of Topamax during pregnancy was conducted. Nevertheless, the use of Topamax during pregnancy is possible in the case when the anticipated benefits to the mother outweigh the potential risk to the fetus. Derivation topiramate in breast milk has not been studied in controlled trials. A limited number of observations suggest that topiramate is excreted in breast milk. If necessary, use Topamax in lactation period should settle the question of termination of breastfeeding.
Side effects:
From the side of the central nervous system and price of topamax of peripheral nervous system: ataxia, violation of concentration, fatigue, drowsiness, thought disorder, confusion, dizziness, paresthesias (often, especially during the selection of the dose), nervousness, psychomotor retardation, headaches, speech disorders and visual impairment ; children – personality disorder, hyperkinesia (possible); stimulation, emotional lability, cognitive disorders, amnesia, aphasia, depression, diplopia, nystagmus, irregular gait, apathy, psychotic symptoms, aggressive reaction (rare), suicidal ideation or attempts, have children – hallucinations (very rare). From the digestive system: diarrheal effects, nausea, abdominal pain, anorexia, diarrhea, dry mouth; in children – increased salivation (possible), taste perversion, increased hepatic transaminases (rare), hepatitis, hepatic failure (very rare). Ophthalmic: approximately 1 month after starting treatment Topamax may cause a syndrome characterized by myopia accompanied by increased intraocular pressure. It also noted a sharp decrease in visual acuity and / or pain in the eye. Manifestations include: myopia, reducing the depth of the anterior chamber of the eye, congestion of the mucous membrane of the eye and increased intraocular pressure, mydriasis (in some cases). A possible mechanism of this syndrome is an increase supratsiliarnogo effusion, which leads to a shift forward of the lens and iris, and as a result of the development of secondary angle-closure glaucoma.
Allergic and Dermatological reactions: erythema multiforme, pemphigus, Stevens-Johnson syndrome and toxic epidermal necrolysis in patients treated with Topamax in conjunction with other drugs that cause adverse reactions from the skin and mucous membrane (very rare).
Other: nephrolithiasis, weight loss, leukopenia, oligogidroz (in children), metabolic acidosis (rare).
The safety profile of Topamax is set based on the analysis of data on the application of the drug in 1800 patients and healthy volunteers. Due to the fact that Topamax mainly used in combined therapy, to establish the exact cause of adverse effects is very difficult.
Cautions and precautions:
Cancel Topamax should be gradual, to minimize the possibility of increasing the frequency of seizures. When conducting clinical trials of topamax no prescription dose was reduced by 100 mg 1 time per week.
Patients undergoing hemodialysis, in the days of the meeting must be given an additional dose of Topamax (about 1 / 2 daily dose) before and after the procedure. Speed topimirata excretion by the kidney depends on renal function and does not depend on age. In patients with moderate or severe renal impairment in order to achieve sustainable topimirata concentrations in plasma may be needed from 10 to 15 days, as opposed to 4-8 days in patients with normal renal function hypertension due to topamax. As with any disease, Topamax dose selection scheme should focus on clinical effect and take into account that patients with impaired renal function to establish a stable plasma concentration for each dose may need more time.
When using Topamax may increase the risk of kidney stones and the appearance of related symptoms (renal colic, pain in the side and in the kidneys), particularly in patients with a predisposition to nephrolithiasis (the formation of stones in the past, a family history of nephrolithiasis, hypercalciuria) and considering the use of other drugs that promote the development of nephrolithiasis. To reduce the risk of nephrolithiasis, as well as side effects that may arise under the influence of physical activity or high temperatures should increase fluid intake. If while taking Topamax patient decreases body weight, you should adjust the power regime (high-calorie diet). Patients with impaired hepatic function Topamax should be used with caution because of possible reduction in clearance topimirata.
There may be cases of secondary angle-closure glaucoma in children and adults. Treatment includes possible discontinuation of and measures aimed at lowering intraocular pressure. Elevated intraocular pressure of any etiology in the absence of adequate treatment may lead to serious complications, even blindness. In the treatment Topamax observed an increased incidence of mood disorders and depression. In conducting double-blind clinical trials with topiramate use, suicide attempts occurred at a frequency of 0.3% while taking topiramate and 0% for placebo. In applying Topamax may occur hyperchloraemic not associated with a deficit of anions, metabolic acidosis (eg, reducing the concentration of bicarbonate in plasma below the normal level in the absence of respiratory alkalosis). This decrease in concentration of serum bicarbonate is a consequence of inhibitory effect of topiramate on renal. In most cases, reducing the concentration of bicarbonate occurs at the beginning of the reception Topamax, although this effect may occur in any period of treatment to topamax warningsbuy topamax usa. The level of concentration reduction is usually weak or moderate. Some diseases or treatments that predispose to the development of acidosis (renal disease, severe respiratory diseases, status epilepticus, diarrhea, surgery, ketogenic diet, and certain medications) may be additional factors contributing to bicarbonate-lowering effect of topiramate. In children, chronic metabolic acidosis can lead to slower growth. Effect of topiramate on growth and possible complications associated with the skeletal system have not been studied systematically in children and adults. Therefore, the treatment Topamax is recommended to determine the concentration of bicarbonate in serum. In the event of metabolic acidosis and its persistence, it is recommended to reduce the dose or stop taking Topamax. Topamax approved for use in children older than 2 years, does topamax cause weight loss?
Effects on ability to drive vehicles and management mechanisms:
Should not assign Topamax patients involved in potentially hazardous activities that require increased attention and quickness of psychomotor reactions, because Topamax can cause drowsiness and dizziness.
Drug Interactions:
With simultaneous use of Topamax with carbamazepine, valproic acid, phenobarbital, primidone topimirat no effect on the values of their equilibrium concentrations in plasma. For some patients the simultaneous application led to increased concentrations of phenytoin, which is connected, apparently, with inhibition of isoenzyme CYP 2Cmeph. Patients receiving phenytoin and who developed clinical signs or symptoms of toxicity, it is necessary to monitor the concentration of phenytoin in plasma.
Phenytoin and carbamazepine while applicated with Topamax, reduce the concentration of topiramate in plasma. Addition or removal of phenytoin or carbamazepine on the background of treatment Topamax may require changes in dose of the latter. With simultaneous use of Topamax with valproic acid does not require a change in dose of topamax weight loss, because the concentration of topiramate in plasma did not actually change. In the study on simultaneous application of a single dose Topamax AUC of digoxin decreased by 12%. In the appointment or termination of Topamax patients taking digoxin, special attention should be paid to monitoring the concentration of digoxin in serum. In an application with Topamax oral contraceptive containing norethindrone and ethinyl estradiol, topimirat had no significant effect on the clearance of norethindrone, but the plasma clearance estrogen component increases significantly. Thus, while receiving Topamax with oral contraceptives (non-ovlon, rigevidon, marvelon, silest, lindinet, etc.), their effectiveness may be reduced. Risk reducing the effectiveness of contraceptives and increased breakthrough bleeding should be considered in patients taking oral contraceptives in combination with Topamax. Patients receiving estrogen contraceptives should report any changes in the timing and nature of menstruation. At the same time metformin and generic topamax average Cmax and AUC of metformin increased (by 18% and 25%), while the average clearance is reduced by 20%. In this case the plasma clearance of topiramate is reduced. It showed a reduction in AUC pioglitazone (15%), Cmax and AUC of active gidroksimetabolita (13% and 16%) and Cmax and AUC of active ketometabolita (60%) pioglitazone. The clinical significance of this interaction is unclear.
The clinical significance of this interaction is unclear. In the appointment or termination of Topamax patients taking metformin or pioglitazone, you need to pay special attention to regular monitoring of the state of carbohydrate metabolism. The results showed that while receiving topiramate and hydrochlorothiazide is an increase in Cmax and AUC topiramate (27% and 29%). The clinical significance of this interaction is unclear. Appointment of hydrochlorothiazide in patients taking Topamax, may require a dosage adjustment Topamax. Pharmacokinetic parameters of hydrochlorothiazide have not been significant change with concomitant therapy Topamax. Patients taking Topamax should abstain from alcohol. During treatment Topamax does not recommend the use of other drugs that have an inhibitory effect on the CNS. With simultaneous use of Topamax with drugs predisposing to nephrolithiasis, may increase the risk of stone formation in kidneys. With amitriptyline: an increase in Cmax and AUC by 20% for nortriptyline (metabolite amitriptillina).
Haloperidol: an increase in AUC of 31% for the metabolite of haloperidol.
With propranolol: an increase in Cmax by 17% for 4-OH propranolol (a metabolite of propranolol) increased Cmax by 16% for topiramate.
Storage:
List B. Store in a dry place at temperatures not above 25 ° C.
Expiration: tablets – 3 years; capsules – 2 years.
Condition of supply of topamax for obesity is prescription.
