lamotrigine primobolan depot dosage is a blocker of voltage-dependent sodium channels inhibits pathological release of glutamic acid (an amino acid that plays a key role in the development of epileptic seizures), and inhibits the depolarization caused by glutamate. AbsorptionLamotrigine is rapidly and completely absorbed from the gut, almost presistemnomu subjected to first pass metabolism. Maximum plasma concentration is reached after about 2.5 hours after ingestion of the drug. Time to maximum concentration increases slightly after ingestion, but the degree of absorption is unchanged. When receiving a single dose of 450 mg is linear pharmacokinetics. There is considerable inter-individual fluctuations in the maximum concentration in an equilibrium state, but with occasional variations primobolan depot dosage in each individual patient. Distribution Lamotrigine binds to plasma proteins about 55%. It is unlikely that the drug release from the connection to the protein may lead to toxic effects. The volume of distribution is 0,92-1,22 l / kg. Metabolism The metabolism of lamotrigine participates enzyme UDP-glucuronyl. Lamotrigine a small extent increases its own metabolism in a dose dependent manner. There is no evidence that lamotrigine affects the pharmacokinetics of other antiepileptic drugs (AEDs), and that between lamotrigine and other drugs metabolized by the cytochrome P-450, possible interactions. Elimination In adults lamotrigine clearance in a state of equilibrium concentrations averaged 39 ± 14 ml / min. Lamotrigine is metabolized to glucuronide, which are excreted in the urine and less than 10% of the drug is excreted in the urine in unchanged form, about 2% – with the feces. The clearance half-life, and do not depend on the dose. The half-life in adults averages from 24 hours to 35 hours. In patients with Gilbert’s syndrome observed decrease in clearance of the drug by 32%, which, however, does not go primobolan depot dosage beyond the normal range for the general population. On the half-life of lamotrigine is greatly affected by drugs taken together (see. “Interaction with other medicinal products”). Children Children lamotrigine clearance in the calculation of the body mass is higher than in adults (highest in children under 5 years). Periode of lamotrigine is generally shorter than in adults. Its average value is approximately equal to 7 hours, while the appointment of drugs that stimulate glucuronidation, such as carbamazepine and phenytoin and is increased to an average of 45-50 hours, with a joint appointment with valproate (see. “Assigning mode and dose”, “Interaction with other medicines “). elderly patients no clinically significant differences in the clearance of lamotrigine in elderly patients compared to younger patients are not detected.patients with impaired renal function, a dose reduction may be required only when a significant decrease in kidney function. patients with hepatic impairment Initial, and increasing maintenance dose should be reduced by approximately 50% in patients with moderate hepatic impairment (step B by Child-Pugh) and 75% – in patients with severe (step C in Child-Pugh) hepatic insufficiency. Increasing the dose and the maintenance dose should be primobolan depot dosage adjusted depending on clinical response.
- as adjunctive or monotherapy epilepsy (partial and generalized seizures, including tonic-clonic seizures and seizures in the syndrome of Lennox -Gasto) in adults and children older than 12 years;
- as adjunctive therapy epilepsy (partial and generalized seizures, including tonic-clonic seizures and seizures in the syndrome of Lennox -Gasto) in children from 3 to 12 years. After reaching epilepsy control against the background kombininirovannoy therapy, concomitant AEDs may be canceled and continued receiving lamotrigine as monotherapy;
- Monotherapy of typical absence seizures.
Bipolar disorder For prevention of mood disorders (depression, mania, hypomania, mixed episodes) in adults with bipolar disorder.
CONTRAINDICATIONS Hypersensitivity to any component of the drug, children under 3 years of age. With caution: renal insufficiency.
Pregnancy and lactation Pregnancy As with other drugs, lamotrigine should be administered during pregnancy only if the expected therapeutic benefit to the mother outweighs the potential risk to the fetus.Physiological changes that develop during pregnancy may affect lamotrigine levels and / or therapeutic effect. There are reports of decrease in the concentration of lamotrigine during pregnancy. LactationAccording to preliminary data, lamotrigine passes into breast milk in concentrations corresponding to about 40% – 60% of the concentration in maternal plasma. It is necessary to correlate the potential benefits of breast milk feeding and the potential risk of adverse effects in a child.
Dosing and Administration Inside. If the calculated dose of lamotrigine (for example, when assigning children or patients with impaired liver function) can not be divided into a whole number of tablets, the patient this dose should be administered, which corresponds to the nearest value of the whole tablet at a lower dosage . It should not exceed the initial dose and increasing doses recommended mode because of the risk of eruption.
Monotherapy in adults and children over 12 years.
The initial dose of lamotrigine 25 mg once a day for 2 weeks, followed by increasing doses up to 50 mg once a day for 2 weeks. Then the dose should be increased by 50-100 mg every 1-2 weeks until the optimum therapeutic effect. Usually, a maintenance dose of 100-200 mg per day in one or two steps. Some patients require up to 500 mg / day. . Additional therapy in adults and children over 12 years
in patients receiving valproate in combination with other AEDs or without an initial dose of lamotrigine is 25 mg every other day for 2 weeks later – on 25 mg once daily for 2 weeks. Then, the dose should be increased by up to 25-50 mg / day every 1-2 weeks until the optimal therapeutic effect is achieved. Usually, a maintenance dose of 100-200 mg / day in one or two steps. In patients receiving concomitant therapy with AEDs or other drugs that stimulate glucuronidation lamotrigine, in combination with other AEDs or without (except valproate), the initial dose of lamotrigine is 50 mg once a day for 2 weeks later – 100 mg / day in two divided doses for 2 weeks. Then, the maximum dosage is increased by 100 mg every 1-2 weeks until the optimum therapeutic effect. Usually a maintenance dose of 200 400 mg per day in two divided doses. Some patients may require up to 700 mg / day. Patients who take oxcarbazepine primobolan depot dosage in combination with any other inducers or inhibitors of glucuronidation of lamotrigine or without an initial dose of lamotrigine is 25 mg once a day for 2 weeks later – 50 mg / day at once for 2 weeks. Then, the dose is increased by up to 50100 mg every 1-2 weeks until the optimal therapeutic effect. Usually, a maintenance dose of 100-200 mg per day in one or two steps. Because of the risk of rash should not exceed the initial dose and increase the dose recommended by treatment. Monotherapy in children from 3 to 12 and lepi The initial dose of lamotrigine in patients with typical absence seizures was 0.3 mg / kg / day in one or in two doses for 2 weeks, followed by increasing doses up to 0.6 mg / kg / day in one or two stages over two weeks. Then increase the maximum dose of 0.6 mg / kg every 1-2 weeks until the optimum therapeutic effect. Usually, the maintenance dose is between 1 and 15 mg / kg / day in one or two steps, although some patients require higher doses. Adjunctive therapy in children aged 3 to 12 years. The children taking valproate in combination with other AEDs or without an initial dose of lamotrigine is 0.15 mg / kg once a day for 2 weeks later – 0.3 mg / kg per day at once in 2 weeks. Then, the dose can be increased to 0.3 mg / kg every 1-2 weeks until the optimum therapeutic effect. Usual maintenance dose is 1 – 5 mg / kg per day in one or two steps. The maximum daily dose – 200 mg. Patients receiving concomitant therapy as a probe, or other drugs that stimulate lamotrigine glucuronidation (in combination with other AEDs or without (except valproate)), the initial dose of lamotrigine is 0.6 mg / kg receiving 2 daily for 2 weeks later – 1.2 mg / kg / day. in two doses for 2 weeks. Then, the dose is increased by up to 1.2 mg / kg / day. every 1-2 weeks until the optimum therapeutic effect. The usual maintenance dose is 5-15 mg / kg per day in two stages with a maximum dose of 400 mg / day. Patients receiving oxcarbazepine without any other inducers or inhibitors of lamotrigine glucuronidation, the initial dose of lamotrigine is 0.3 mg / kg / d. one or two stages over two weeks later – 0.6 mg / kg / day in one or two stages over two weeks. Then, the dose is increased by up to 0.6 mg / kg every 1-2 weeks until the optimum therapeutic effect is attained. Usually, the maintenance dose is 1-10 mg / kg / day. in one or two steps. The maximum dose is 200 mg / day. To make sure that the therapeutic dose is maintained, it is necessary to control the weight of the child and to adjust the dose of the drug when it changes. The exact dosage for initial therapy of lamotrigine tablets of 5 mg is not possible if the child weighs less than 17 kg. It is likely that children aged 3 to 6 years old will require the greatest maintenance doses. The general recommendations for dosage of lamotrigine in the treatment of epilepsy If you cancel the related PEP , transfer to lamotrigine monotherapy or appointment in patients receiving lamotrigine other drugs or AEDs should be taken into account that this may have an effect on the pharmacokinetics of lamotrigine.
- Bipolar disorder in adults
Should follow transition dosage regimen, which includes increasing during 6 weeks dose of lamotrigine to maintenance stabilizing doses then, if indicated, it is possible to cancel other psychotropic and / or probe.
Target stabilizing dose varies depending on the clinical effect. A) Additional therapy in patients taking inhibitors glucuronidation lamotrigine (e.g., valproate). The initial dose of lamotrigine in patients taking drugs inhibiting glucuronidation (such as valproate) of 25 mg every other day for two weeks, followed by 25 mg once a day within 2 weeks. The dose should be increased to 50 mg (1-2 doses) for 5 weeks.Typically, the target dose of 100 mg / day (1-2 doses). The maximum daily dose – 200 mg. B) Additional therapy in patients concurrently taking drugs that stimulate the glucuronidation of lamotrigine and not taking inhibitors of glucuronidation of lamotrigine (eg valproate). This mode should be used with phenytoin, carbamazepine, phenobarbital, primidone or other inducers glucuronidation of lamotrigine. The initial dose of lamotrigine is 50 mg once a day for 2 weeks followed by 100 mg per day in two divided doses for 2 weeks. At the 5th week of the dose should be increased to 200 mg per day in two doses. At the 6-th week, the dose may be increased to 300 mg a day, but usually, the target dose is 400 mg per day (two doses) and assigned starting at 7 weeks of treatment. C) Monotherapy lamotrigine or adjunctive therapy in patients taking drugs primobolan depot dosage lithium, bupropion, olanzapine, oxcarbazepine, or other drugs which do not have a significant inducing or inhibitory effect on glucuronidation of lamotrigine. The initial dose of lamotrigine is 25 mg once a day for 2 weeks followed by 50 mg per day (one or 2 doses) for 2 weeks. The dose should be increased to 100 mg a day for 5 weeks. Typically, the target dose is 200 mg per day (1 or 2 divided doses). After reaching the target supports the stabilizing dose of other psychotropic medications may be removed. If necessary, the dose may be increased to 400 mg / day. A) Therapy of lamotrigine after the abolition of additional therapy inhibitors of glucuronidation of lamotrigine (eg valproate): immediately after the abolition of valproate, stabilizing the initial dose lamotrigine doubles and maintained at this level. b) after cancellation of lamotrigine therapy adjunctive therapy inducers of lamotrigine glucuronidation depending on original maintenance dose. this mode should be used when using phenytoin, carbamazepine, phenobarbital, primidone or other inducers of lamotrigine glucuronidation. Lamotrigine dose is gradually reduced over 3 weeks after discontinuation of inductors glucuronidation. C) Therapy of lamotrigine after the abolition of concomitant psychotropic or AED, no significant pharmacokinetic interaction with lamotrigine (eg lithium drugs, bupropion, olanzapine, oxcarbazepine). During the cancellation related to lamotrigine medications target dose of lamotrigine reached in the process of enhancing the regime should be maintained. There is no clinical experience in the correction of single daily doses of lamotrigine after the addition of other drugs. However, the following guidelines (Table 1) can be given based on the studies of drug interactions.