Absorption – high, bioavailability – 80%. Food intake has no clinically significant effect on bioavailability.The time to reach maximum concentration in plasma -2 hours after ingestion of 400 mg. The nolvadex side effects maximum blood concentration after repeated oral administration of 100 mg 2 times a day – 6.76 pg / ml. Relationship to plasma proteins – 13-17%.
The volume of distribution (1.2 g after administration) – 0,55-0,8 l / kg, depends on sex (female – 50% of the values observed in men). The equilibrium concentration is reached after 4-8 days, with renal failure – 10-15 days. It penetrates into breast milk. It is metabolized in the liver by hydroxylation, hydrolysis and glyukuronirovaniya 6 to form a pharmacologically inactive metabolites. Pharmacokinetics after single oral buy testosterone cypionate uk administration is linear, plasma clearance remains constant – 20-30 ml / min; value of the area under the curve “concentration – time» in the dose range of 100-400 mg increases proportionally with dose. The e after multiple-dose 100 and 50 mg 2 times a day -21 hours. In severe hepatic and renal (creatinine clearance less than 60 mL / min) and the plasma deficiency reduces renal clearance. Excreted by the kidneys in unchanged form (70%) and in the form of metabolites. Removed from the plasma by dialysis.
Indications for use as monotherapy – newly diagnosed epilepsy. As a subsidiary of the drug in adults and children older than 3 years – partial or generalized tonic-clonic seizures; seizures on the background of Lennox-Gastaut syndrome.
Contraindications: Hypersensitivity, pregnancy, lactation, children’s age (up to 3 years).
Precautions Renal or hepatic impairment, nolvadex side effects nefrourolitiaz (in history, including a family), hypercalciuria.
Dosing and Administration Inside, regardless of meals. Tablets should not be divided. When used as monotherapy, it is necessary to take into account the possible impact of the abolition of concomitant anticonvulsant therapy on seizure frequency. In cases where sharp cancel undesirable concomitant anticonvulsant therapy, reduce the dose of drug gradually reducing the dose to 1/3 every 2 weeks. If you cancel the drugs that are inducers of microsomal “liver” enzymes, topiramate plasma concentrations are increased. In such situations, if clinically indicated dose can be reduced. Adults masteron in the early monotherapy – 25 mg 1 time a day at bedtime for 1 week. Then increase the dose at intervals of 1 – 2 weeks at 25-50 mg / day (daily dose divided into 2 admission). At intolerance of such regimen, the dose is increased by a smaller amount, or over large intervals. The dose is adjusted depending on the effect. The recommended dose – 100 mg / day, maximum daily dose – 500 mg. In nolvadex side effects some cases, monotherapy for refractory epilepsy treatment topiramate dose of 1 g / day. Children over 3 years as monotherapy in the first week of treatment – 0.5-1 mg / kg / day (daily dose divided into 2 admission). The size of the dose and its rate of increase determined by the clinical efficacy and tolerability of therapy. The recommended dose range of topiramate monotherapy in children over 3 years – 3-6 mg / kg / day. When newly diagnosed partial seizures – up to 500 mg / day. When administered in combination with other antiepileptic drugs in adults the initial dose – 50 mg 1 time a day at night for 1 week. Further dose increase of 25-50 mg weekly until the effective dose. The average daily dose -200-400 mg, the multiplicity of reception – 2 times a day. If necessary, can be increased to a maximum daily dose – 1600 mg. The criterion for selection of the dose is the clinical effect, in some patients it may be achieved by taking the drug one time per day.
In carrying out the combination anticonvulsant therapy in children older than 3 years, the recommended total daily dose – 5-9 mg / kg in 2 divided doses. Selection of doses begin with 25 mg / day at night for 1 week. Further the dose can be increased to 1.3 mg / kg per 1-2 weeks and to take 2 doses. The daily dose of 30 mg / kg is generally well tolerated. In the days of hemodialysis, topiramate should be administered in addition to a dose equal to half the daily dose in 2 divided doses (before and after the procedure). Cancel the drug should be gradual to minimize the possibility of increasing the frequency seizures (100 mg / week).
Side effects of ataxia, decreased ability to concentrate, confusion, dizziness, fatigue, paresthesia, drowsiness, abnormal thinking; seldom – agitation, amnesia, decreased appetite, aphasia, depression, emotional lability, impaired speech, nystagmus, visual disturbances (including diplopia), perversion of taste sensations, nausea, nefrourolitiaz, weight loss. occurrence of the syndrome is possible nolvadex side effects (usually through 1 month after initiation of therapy), characterized by myopia accompanied by increased ocular hypertension. It also noted a sharp decrease in visual acuity and / or pain in the eye. Ophthalmic manifestations include: myopia, reducing the depth of the anterior chamber of the eye, bloodshot eyes and mucosa increased intraocular pressure. In some cases – mydriasis. A possible mechanism methenolone of this syndrome is the increase supratsiliarnogo effusion, leading to forward displacement of the lens and the iris, and as a result the development of secondary angle-closure glaucoma. Treatment includes discontinuation and measures aimed at reducing the intraocular pressure. Perhaps the development of allergic reactions.
Overdosing Symptoms: increased side effects. Treatment: gastric lavage, symptomatic therapy. The use of activated charcoal is ineffective because in in vitro experiments have shown that it does not adsorb topiramate. An effective way to removing topiramate from the body – hemodialysis.
Interaction with other drugs reduces the effectiveness of oral estrogensoderjath contraceptives. Reduces the AUC of digoxin by 12%. It is not recommended concomitant use of ethanol and other drugs which depress the central nervous system. When concomitantly with carbamazepine nolvadex side effects of carbamazepine remains constant or varies slightly (by less than 10 .%), whileof topiramate reduced by 40% When coadministered phenytoin remains unchanged or is increased by 25%, whereas the primobolan enanthate of topiramate reduced by 48%; may require correction dosing regime of the latter. While the use of valproic acid valproic acid is reduced by 11%, topiramate – nA 14%. Carbonic anhydrase inhibitors (acetazolamide) increase the risk of kidney stones.
Cautions In patients with a predisposition to nefrourolitiaz increases the risk of kidney stones, to prevent which to adequately increase the volume of fluid intake. Effects on ability to drive and use other mechanisms.In the period of treatment must be careful when driving and occupation of other potentially hazardous activities that require high concentration and speed of psychomotor reactions.