primobolan depot dosage

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.

Indications Epilepsy

  • 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.

  • Epilepsy

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.

buy primobolan depot

Stabilizes voltazhzavisimye sodium tubule cell membranes and blocks the release of neurotransmitters, especially glutamate. As activating amino acid glutamate plays a key role in the occurrence of epileptic seizures.
Rapidly and completely absorbed in the intestine without being substantially primary metabolism in the liver. After 2.5 hours after ingestion reached maximum plasma concentration. Eating slows down the process of absorption, but does not affect its effectiveness. The pharmacokinetics of single dose not exceeding buy primobolan depot, is linear. The concentration in the saturation stage is pronounced individual character. The bioavailability of . Contact proteins is, it is unlikely that the displacement of lamotrigine due to proteins may cause toxic effects. The volume of distribution buy primobolan depot body weight.

Metabolism in the liver due glucuronyl transferase uridine-diphosphate. Among all the metabolites predominate N-glucuronides. The moderate, dose-dependent manner, Lamotrigine induces its own metabolism.

Excretion: average clearance in the saturation stage in healthy adults is 39 ± 14 ml / min. Displayed along with the urine in the form of glucuronide conjugate, less than 10% – unchanged buy primobolan depot. About 2% of active compound and degradation products are displayed, along with stool. The clearance half-life and do not depend on the dosage. t 1/2 = healthy volunteers 24-35 hours.

Provided with breast milk. Concentration in breast milk is 40-60% of the plasma concentration. In some cases, the drug concentration in the serum of infants whose mothers took the drug during lactation reaches therapeutic levels.

Children’s age: Clearance, recalculated per kg of body weight in children is higher than in adults, is highest under 5 years of age. The half-life is usually shorter than that of adults, while admission enziminduktora is 7 hours, and when taking sodium valproate – 45-60 hours.

Advanced age Ground clearance of lamotrigine young and elderly patients with epilepsy minimally different from each other.

Indications Epilepsy Adults and children over 12 years: as monotherapy or in combination with other antiepileptic drugs for the treatment of partial and generalized seizures, including tonic-clonic seizures and seizures with Lennox-Gastaut syndrome.

Children over 2 years: In combination with other antiepileptic drugs for the treatment of partial and generalized seizures, including tonic-clonic seizures and seizures with Lennox-Gastaut syndrome.

Bipolar disorder
patients older than 18 years: prevention and treatment mainly episodes of depression.

Contraindications
: Hypersensitivity to any component of the drug
– Children under 2 years
– Pregnancy
– Lactation

Precautions
Renal failure (due to the possible cumulation glucuronide metabolite). It should be used with caution in children lamotrigine as the drug of choice as monotherapy in the treatment of epilepsy.

Pregnancy and lactation:
Pregnancy: Due to the inhibitory effects of lamotrigine on dihydrofolate reductase, likely to develop malformations of the fetus in the case of the treatment of pregnant women, however, available data are insufficient to determine the degree of safety of lamotrigine for pregnant women. Receiving Lamotrigine is contraindicated during pregnancy except in cases where the expected benefit to pregnant exceeds the degree of potential risk to the fetus.

Lactation: The number of observations in the period of lactation is limited. Concentration in breast milk lamotrigine is 40-60% of the plasma concentration. A few observations show that the drug concentration in the serum of infants whose mothers took the drug during lactation reaches therapeutic levels. You should carefully weigh the benefits of breast-feeding while taking the drug and the risk of side effects in infants.

Dosage and administration Monotherapy Epilepsy Adults and children over 12 years: initial dose for 2 weeks 25 mg once daily; in the next 2 weeks – 50 mg once a day. Subsequently, every 1-2 weeks the daily dose can be increased to 50-100 mg until until the optimum effect is reached. Usually maintenance daily dose, distributed on one or two steps, is 100-200 mg. In rare cases, the desired effect is provided by doses of 500 mg / day.

 

Combination therapy Epilepsy
Adults and children over 12 years: patients taking sodium valproate in combination with other antiepileptic buy primobolan depot drugs or without them, the initial dose of lamotrigine in two weeks is 25 mg every other day; for the next two weeks of daily take one 25 mg once a day. Subsequently, every 1-2 weeks the dose may be increased to 25-50 mg until until it reaches an optimal effect. Regular maintenance daily dose is 100-200 mg in 1-2 reception.

Patients receiving antiepileptic drug being enziminduktorom (phenytoin, carbamazepine, phenobarbital, primidone)) in combination with other antiepileptic drugs, or without them, but not receiving sodium valproate, the initial daily dose of lamotrigine for two weeks is 50 mg once a day ; for the next two weeks at 100 mg per day, 2 Hour. Subsequently, every 1-2 weeks the dose can be increased by no more than 100 mg to obtain an optimal effect. Regular maintenance daily dose is 200-400 mg in 1-2 reception. In rare cases, a 700 mg / day.

In the case of treatment of antiepileptic drugs, a pharmacokinetic interaction with lamotrigine is not known, the dose of lamotrigine should be increased for smaller doses of the scheme described for taking sodium valproate.

Interaction with other medicines
Sodium valproate competitively blocks liver enzymes and inhibits the metabolism of lamotrigine, increasing almost twice its average t 1/2, extending it to 70 hours.

Antiepileptics Inductors of hepatic enzymes (phenytoin, carbamazepine, phenobarbital, primidone), paracetamol stimulate the metabolism of lamotrigine and shorten its TA 2 times, ie, to 14 hours (phenytoin, carbamazepine). Patients taking carbamazepine, lamotrigine administration may cause increased side reactions of the central nervous system: dizziness, ataxia, diplopia, blurred vision and nausea.Reducing the dose of carbamazepine usually leads to the disappearance of complaints.

No effect on the plasma concentrations of other antiepileptic drugs on ethinyl estradiol and levonorgestrel concentration after taking oral contraceptives.

Lamotrigine does not reduce the clearance of drugs, especially those that are excreted through CYP2D6. Clozapine, phenelzine, risperidone, trazodone sertalin and apparently did not affect the clearance of lamotrigine.

Data on the effect of lamotrigine on the pharmacokinetics of other antiepileptic drugs and drug interactions between him and drugs, depending on CYP450. no.

Compatible with sedative, anxiolytic and antiepileptic agents.

Cautions
Evidence of inducing and inhibitory effects of lamotrigine on the enzymes of oxidation in the liver in clinically relevant amounts are not available. The ability of the drug to induce its own metabolism is low and probably has no clinical significance.

Do not assign Lamolep simultaneously with other containing lamotrigine, drugs.

If Lamolep provides good control of epilepsy, receiving other antiepileptic drugs can be stopped.

The objective criterion for the effectiveness of treatment is the ability to reduce the frequency of spikes in the EEG at 78-98%.

In the first 8 weeks of treatment may develop skin reactions. Skin rashes, usually are mild severity, disappear spontaneously, however, possible severe forms requiring hospitalization and discontinuation of lamotrigine eg, Stevens-Johnson syndrome and toxic epidermal necrolysis. High initial doses and accelerating the pace of increasing the dose prescribed lamotrigine, as well as the simultaneous reception of valproate contribute to the appearance of skin rash. To avoid the appearance of a skin rash should be strictly observe the specified dosage and rate of their increase.

Children are more likely to develop severe forms of skin reactions (incidence requiring hospitalization of children is 1: 300/1: 100).

Early symptoms of an allergic rash easily confused with an infectious rash, so if high fever and rash occur in the first 8 weeks of treatment, we must assume the development of drug reaction.

It is important to remember that early manifestations of hypersensitivity (eg, fever, lymphadenopathy) may occur without a rash. When a rash of each patient, regardless of age, should be buy primobolan depot immediately and thoroughly evaluated and lamotrigine stop treatment if symptoms develop can not be explained by another cause.

The appearance of the rash may be accompanied by a variety of systemic manifestations of hypersensitivity (fever, lymphadenopathy, facial edema, reactions on the part of the liver and hematopoietic system). The severity of hypersensitivity reactions may be different, and sometimes can be disseminated intravascular coagulopathy (CAAC) and the functional failure of multiple organs. It should be borne in mind that the early signs of hypersensitivity (eg, fever, lymphadenopathy) are not always accompanied by skin rash.

Abnormal liver function, generally, are part of the hypersensitivity syndrome, however, is not always accompanied by other symptoms of hypersensitivity.

Prolonged treatment lamotrigine can alter the metabolism of folic acid, as Lamotrigine is a weak inhibitor of dihydrofolate reductase. In this long, 12-month treatment lamotrigine does not significantly affect the level of hemoglobin, mean erythrocyte volume, folic acid concentrations in plasma and erythrocytes, after 5 years of treatment – the concentration of folic acid.

If lactose intolerance should be aware that Lamolepa 25 mg tablet contains 16.35 mg of lactose monohydrate, 50 mg tablet – 32.5 mg and 100 mg tablet – 65 mg.

Despite the fact that when taking oral contraceptives lamotrigine does not affect kontsetratsii ethinyl estradiol and levonorgestrel, changes during the menstrual cycle lamotrigine therapy taking oral contraceptives, requires close attention of the attending physician.

When treating patients with renal failure on hemodialysis, should be in the form of, on average, during a 4-hour hemodialysis of the body is derived 20% of lamotrigine.

Epilepsy: A sudden withdrawal of lamotrigine treatment provoke epileptic seizures, up to status epilepticus. Therefore, except in special cases (eg. The appearance of skin rash), requiring immediate treatment discontinuation, withdrawal of the drug should be carried out gradually, with a smooth, within 2 weeks, dose reduction.

Severe seizures and status epilepticus buy primobolan depot may lead to rhabdomyolysis, multiple organ dysfunction and disseminated intravascular coagulopathy, sometimes fatal. Similar cases have occurred in connection with the use of lamotrigine.

bayer primobolan depot

Channels of the presynaptic membranes of neurons, inhibiting the excess release of glutamate bayer primobolan depot and associated with the latest distribution of effector impulses.
Lamotrigine is rapidly and completely absorbed from the intestines, almost without being first-pass metabolism of the first pass. Maximum plasma concentration is reached after about 2.5 hours after ingestion. Time to maximum concentration increases slightly after ingestion, but the degree of absorption is unchanged.There is considerable inter-individual fluctuations in the maximum concentration in an equilibrium state, but with occasional variations in each individual patient.Plasma protein binding is approximately . The bayer primobolan depot volume of distribution is. It is metabolized to the glucuronide, which are excreted in the urine . The clearance half-life, and do not depend on the dose. The half-life in adults is an average of 24-35 hours. In patients with Gilbert’s syndrome was observed decrease in clearance of the drug by, which, however, did not go 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”).

In children, the clearance of lamotrigine in the calculation of the body mass is higher than in adults (highest in children under 5 years). The half-life is usually shorter than that of adults. Its average value is equal to 7 hours, while the appointment of drugs that stimulate glucuronidation (phenytoin and carbamazepine) and bayer primobolan depot rises to an average of 45-50 hours, with a joint appointment with valproate (see. “Assigning and dose mode”, “Interaction with other drugs “).
no clinically significant differences in the clearance of lamotrigine in elderly patients compared to younger patients are not detected.
with a significant decrease in kidney function may need to reduce the dose of lamotrigine.
The doses of lamotrigine should be reduced in patients with moderate and severe hepatic insufficiency.

Indications

 

  • as adjunctive or monotherapy bayer primobolan depot 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 of a combination therapy, concomitant AEDs may be canceled and continued receiving lamotrigine as monotherapy;
  • Monotherapy of typical absence seizures.

Contraindications

Hypersensitivity to any component bayer primobolan depot of the drug, children under 3 years of age, pregnancy and lactation.

With caution : renal insufficiency.

Dosing and Administration

Inside. Because of the risk of rash should not exceed the initial dose and increase the dose recommended by the regime. If more precise dosing, such as part of complex therapy in children, used dosage forms containing lamotrigine in smaller dosages.

Epilepsy Monotherapy in adults and children over 12 years. The initial dose of 25 mg once a day for 2 weeks, followed bayer primobolan depot by increasing doses up to 50 mg once a day for 2 weeks. Thereafter, the dosage is 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 or without other AEDs them, the initial dose is 25 mg every other day for 2 weeks later – on 25 mg once a day 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 lamotrigine glucuronidation (in combination with other AEDs or without (except valproate)), the initial dose 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 doses. Some patients may require up to 700 mg / day. Patients who take oxcarbazepine in combination with any other inducers or inhibitors of glucuronidation or no lamotrigine them, the initial dose is 25 mg once a day for 2 weeks later – 50 mg / day at once in 2 weeks bayer primobolan depot. Then increase the maximum dose of 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. Monotherapy in children 3 to 12 years. The initial dose of lamotrigine in patients with typical absence seizures of 0.3 mg / kg / day in single or 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 0.15 mg / kg body weight 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 body weight every 1-2 weeks until the optimum therapeutic effect. The usual maintenance dose is 5.1 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)), an initial dose of 0.6 mg / kg per day in 2 hours 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 / day in 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. Typically, a maintenance dose is 1-10 mg / kg / day in one or two steps. The maximum dose is 200 mg / day. It is likely that children aged 3 to 6 years old will require the highest maintenance dose.

 

Bipolar disorders in adults
should be followed 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) Adjunctive therapy in patients taking lamotrigine glucuronidation inhibitors (e.g., valproate). The initial dose of lamotrigine is 25 mg every other day for two weeks, followed by 25 mg once a day for 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) Adjunctive 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 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 It should be maintained target dose of lamotrigine reached in the process of raising mode. d) Adjustment of lamotrigine daily dose following the addition of other drugs. The following recommendations (table 1) can be given on the basis of studies on the interaction of drugs.

 

Reappointment
The more time has passed after the last dose, the more caution should be increased to a maintenance dose. If the time after discontinuation of more than 5 half-lives, the lamotrigine dose should be increased to support, under the relevant scheme. It is not recommended to renew the appointment of lamotrigine patients who discontinued the drug due to the occurrence of rash, unless the potential benefit from the appointment of the drug, significantly, does not exceed the risk.

General dosing recommendations for lamotrigine in special patient groups

Women taking hormonal contraceptives a) Appointment of lamotrigine to patients already receiving hormonal contraceptives: no need for a correction recommended regimens increase lamotrigine dose. B) The appointment of hormonal contraceptives to patients already receiving maintenance doses of lamotrigine and NOT receiving inductors glucuronidation of lamotrigine: you may need to increase the maintenance dose lamotrigine, but not more than 2-fold, depending on the individual clinical response. c) Stopping hormonal contraceptives patients already receiving maintenance doses of lamotrigine and nOT receiving inductors glucuronidation of lamotrigine: you may need to decrease the dose of lamotrigine to 2 times, depending on the individual clinical effect.

 

Elderly patients (over 65)
Changes in recruitment scheme doses are required.

Abnormal liver function
An initial, growing and maintenance dose should be reduced by approximately 50% and 75% in patients with moderate (stage B) and severe (stage C) degrees of hepatic impairment, respectively. Growing and maintenance doses should be adjusted depending on clinical response.

Renal impairment
Patients with severely reduced renal function may be recommended maintenance dose reduction.

Side effect

Violations of the skin and subcutaneous tissue: skin rash. Rash, mainly maculopapular, usually appears during the first 8 weeks of the start of therapy and disappears after discontinuation bayer primobolan depot of the drug. There are reports of rare cases of severe, potentially life-threatening skin lesions, including Stevens-Johnson syndrome and toxic epidermal necrolysis (Lyell’s syndrome). Although in most cases to remove the drug occurred regression of symptoms, some patients were permanent scars on the skin; known single cases of fatal lesions. Largely increased risk of dermatological complications associated with impaired recommended mode titration doses (exceeding the initial dose or exceeding the rate of increase of doses), as well as with an increase in half-life of lamotrigine when co-administered with drugs valproic acid (see “Dosage and administration”.; “Interactions with other medicinal products”). Due to the fact that almost all cases of skin rashes occurred within the first 8 weeks of treatment with lamotrigine can not be considered duration of therapy as a risk prediction tool of dermatological complications. Development of the rash may also be seen as a manifestation of a hypersensitivity syndrome. In children, the risk of serious skin rashes is higher than that of adults. The blood and lymphatic system: neutropenia, leukopenia, anemia, thrombocytopenia, pancytopenia, aplastic anemia, agranulocytosis. Hematologic abnormalities may or may not be associated with a syndrome of hypersensitivity. Violations of the immune system: Hypersensitivity syndrome (including symptoms such as skin rash, fever, lymphadenopathy, swelling of the face, blood disorders and liver function, dissiminirovannoy intravascular syndrome coagulation (DIC), multiple organ disorders). The early manifestations of hypersensitivity (eg fever, lymphadenopathy) may occur even in the absence of clear signs of a rash. With the development of these symptoms, the patient should be immediately examined by a doctor and, if not installed another cause of symptoms, lamotrigine should be abolished. Nervous system disorders: headache, dizziness, nystagmus, tremor, ataxia, drowsiness, insomnia, aggressiveness, irritability, tics, hallucinations, confusion, agitation, unsteadiness, movement disorders, worsening of Parkinson’s disease, extrapyramidal disorder, choreoathetosis, increase in the frequency of seizures. Visual impairment:diplopia, blurred vision, conjunctivitis. Gastrointestinal disorders: nausea, diarrhea. Hepato-biliary disorders : increased levels of liver enzymes, abnormal liver function, hepatic failure. Violations of the liver usually develop in conjunction with symptoms of hyperactivity, but in a few cases were noted in the absence of overt signs of hypersensitivity. Violations of the muscle and connective tissue: lupus-like syndrome, arthralgia. General Disorders: fatigue, pain in the body and limbs.

Overdose

It reported on single dose of doses in excess of the maximum therapeutic 10-20 times. Overdose manifested symptoms including nystagmus, ataxia, impaired consciousness and coma.
Treatment: gastric lavage, hospitalization and symptomatic therapy.

special instructions

Skin rash
in children initial manifestations of rash can be mistaken for an infection, so doctors must take into account the possibility of the reaction of children to the drug manifested development of rash and fever during the first 8 weeks of therapy.
When a rash all patients (adults and children) should be rapidly examined by a doctor. Acceptance of lamotrigine should be discontinued immediately except in cases where it is obvious that the development of the rash is not related to the drug intake. It is not recommended to resume receiving lamotrigine when his previous appointment was canceled due to the development of a skin reaction. DihydrofolateLamotrigine is a weak inhibitor of dihydrofolate, so it is likely the influence of the drug on the metabolism of folate in its long-term appointment. However, it was shown that lamotrigine did not cause significant changes in hemoglobin concentration, mean corpuscular volume, at a concentration of folate erythrocytes destination duration serum preparation to 1 year or reduced folate bayer primobolan depot concentration in erythrocytes in the appointment of lamotrigine for up to 5 years. Epilepsy Abrupt withdrawal receiving lamotrigine as and other AEDs, can provoke seizures develop. If abrupt discontinuation of therapy is not a safety requirement (for example, the appearance of the rash), the dose of lamotrigine should be reduced gradually over a period of 2 weeks. There are reports in the literature that severe convulsive seizures including status epilepticus may lead to rhabdomyolysis, multiple organ disorders and disseminated intravascular coagulation, sometimes with fatal outcome. Such cases were observed in the treatment of patients with lamotrigine. Bipolar Disorder The possibility of suicide attempt is a characteristic feature of bipolar disorder, therefore the treatment of such patients should be under close supervision.

 

Interactions with other drugs

The average half-life is reduced to approximately 14 hours, while the appointment of drugs that stimulate glucuronidation, such as carbamazepine and phenytoin and is increased to an average of 70 hours at a joint appointment with valproate.
Uridine diphosphate (UDP) glucuronyl is the main metabolizing enzyme lamotrigine. No Information about the ability of lamotrigine to cause clinically significant inhibition or induction of oxidative liver enzymes. In this regard, the interaction between lamotrigine and drugs metabolized by cytochrome P450 enzyme system, it is unlikely. Lamotrigine can stimulate its own metabolism but the effect is moderate and does not have clinically significant consequences.
Valproate has a strong inhibitory effect on glucuronidation of lamotrigine.
Carbamazepine, phenytoin, primidone, phenobarbital, rifampin combined preparation etiniloestradiol / levonorgestrel – have a stimulating effect on the glucuronidation of lamotrigine. The influence of other oral contraceptives and hormone replacement therapy has not been studied, though they may have a similar effect on the pharmacokinetic parameters of lamotrigine.
Lithium drugs, bupropion, olanzapine, oxcarbazepine – no significant inhibitory effect on glucuronidation of lamotrigine.

Interactions with AEDs
Valproate, which inhibits the glucuronidation of lamotrigine, reduces the rate of its metabolism and lengthens its average half-life of almost 2 times.
Certain antiepileptic drugs (such as phenytoin, carbamazepine, fenabarbital and primidone) which stimulate the system of the liver metabolizing enzymes accelerate the glucuronidation of lamotrigine and its metabolism. It reported on the development of adverse effects to the central nervous system, include dizziness, ataxia, diplopia, blurred vision and nausea in patients taking carbamazepine who started on the background of lamotrigine therapy. These symptoms usually resolve after reduction of the dose of carbamazepine. A similar effect was observed in the appointment of lamotrigine and oxcarbazepine in healthy volunteers, the result of reducing the dose has not been investigated.
Lamotrigine does not displace other AEDs from their association with plasma proteins.
When concomitant administration of lamotrigine 200 mg and oxcarbazepine at a dose of 1200 mg or oxcarbazepine and no lamotrigine not violate the metabolism of each other.

Interactions involving other psychoactive drugs
lamotrigine at 100 mg / day does not cause disturbances pharmacokinetics anhydrous gluconate lithium (2 g, 2 times a day for 6 days) when coadministered.
Multiple assignment bupropion inside had no statistically significant effect on the pharmacokinetics of a single dose of lamotrigine and causes a slight increase in the AUC (area under the curve, “concentration-time”) of lamotrigine glucuronide.
Alanzapin 15 mg reduces AUC and Cmax of lamotrigine by an average of 24% and 20% respectively. Changes of this level is not usually require clinical significance. Lamotrigine at 200 mg did not alter alanzapina kinetics.
Inhibition of lamotrigine amitriptyline, bupropion, clonazepam, fluoxetine, haloperidol or lorazepam has bayer primobolan depot minimal effect on the formation of the primary metabolite of lamotrigine, 2-N-glucuronide. The study of metabolism bufuralola microsomal liver enzymes isolated from human, allows us to conclude that lamotrigine does not reduce the clearance of drugs eliminated predominantly isoenzymes CYP2D6. The results of in vitro studies also suggest that clozapine, phenelzine, risperidone, sertraline and trazodone are unlikely to affect the clearance of lamotrigine.

Interactions with hormonal contraceptives
Effect of hormonal contraceptives on the pharmacokinetics of lamotrigine.
Receiving combined oral contraceptive containing 30 .mu.g etiniloestradiola and 150 .mu.g levonorgestrel is approximately two-fold increase in clearance of lamotrigine (after oral administration), which leads to a decrease in AUC and Cmax of lamotrigine by an average of 52 % and 39% respectively. During the week of receiving the free active drug, there is an increase plasma concentrations of lamotrigine, wherein the concentration of lamotrigine, measured at the end of this week before administering the next dose, the average is 2 times higher than that in the active therapy.

The influence on the pharmacokinetics of lamotrigine hormonal contraceptives
equilibrium concentrations of lamotrigine Period 300 mg did not affect the pharmacokinetics etiniloestradiola – component of combined oral contraceptives. Observed slight increase in the clearance of the second component of oral contraceptives – levonorgestrel that resulted in lower Cmax and AUC of levonorgestrel at 19% and 12% respectively. Measurement of serum FSH, LH and oestradiol during the study showed a slight decrease in suppression of ovarian hormonal activity in some women, although measurement of plasma progesterone, none of the 16 women showed no hormonal evidence of ovulation.Effect of moderate increase in levonorgestrel clearance and changes in plasma levels of FSH and LH on ovarian ovulatory activity is not found. Interactions with other drugs
Rifampicin increases the clearance of lamotrigine and reduces its half-life due to the stimulation of hepatic enzymes bayer primobolan depot responsible for glucuronidation. Patients receiving rifampicin as co-therapy, the appointment of lamotrigine treatment must comply with the scheme recommended by a joint appointment of lamotrigine and means of stimulating glucuronidation.

primobolan depot bayer

 

Terbinafine gives derived primobolan depot bayer ergosterol synthesis in fungi by inhibiting squalene epoxidase enzyme located on the cell membrane of the fungus. This leads to a deficiency of ergosterol and to an intracellular accumulation of squalene, which causes death of fungal cells.
Food does not affect the bioavailability.After a single dose of terbinafine into the maximum drug concentration achieved after 2 hours of blood plasma. The drug was well absorbed when administered orally ,  rapidly penetrates into the dermal layer of the skin and accumulate in the stratum corneum and nail plates provide fungicidal action. Quickly penetrates into sebum, leading to the creation of a high concentration in the hair follicles, the hair, the skin, subcutaneous tissue.Biotransformiroetsa in the liver to inactive metabolites; about 70% of the dose is excreted in the urine.The half-life is 17 hours. The half-life in the terminal phase -. 200-400 hours not cumulated in the body. There primobolan depot bayer were no changes in the equilibrium concentration of terbinafine in dependence of age, in patients with renal insufficiency or in patients with hepatic cirrhosis rate of excretion of the drug may be slowed, resulting in higher concentrations of terbinafine in plasma.

Indications

– Onychomycosis;
– fungal infections of the scalp (trihofitia, mikrosporiya)
– fungal diseases of smooth skin – treatment of common tinea trunk and extremities;
– candidiasis skin and mucous membranes, caused by fungi of the genus of Candida – in cases where the localization or distribution process determine the feasibility of oral therapy.

Contraindications
: Hypersensitivity to terbinafine or any other components of the drug.
Precautions – alcoholism, blood diseases, cancer primobolan depot bayer, metabolic diseases, pathology limbs. Children’s age – up to 2 years.

Dosing and Administration
Duration of treatment and dosage regimen is established individually and depends on the process of localization and severity of the disease.

Adults are usually administered orally after a meal to 250 mg once a day.

Patients with hepatic and renal insufficiency – 125 mg 1 time per day.

Fungal infections of the skin

The recommended duration of treatment:
Tinea pedis (interdigital, plantar or type “socks”): 2-6 weeks
Tinea trunk, extremities – 2-4nedeli,
skin and mucosal candidiasis – 2-4 weeks.

Complete disappearance of the clinical manifestations of the disease there are usually a few weeks after mycological cure.

Fungal infections of the scalp

The recommended duration of treatment:
. Mycosis of the scalp – about 4 weeks
Mycosis of the scalp occurs mainly in children.

onychomycosis

The duration of drug treatment for most patients is 6-12 weeks. In onychomycosis brushes in most cases it is 6 weeks, and at onychomycosis a stop – 12 weeks. Some patients who have a decreased rate of nail growth, may require longer treatment. The optimal clinical effect is seen some months after mycological cure and cessation of therapy. This is determined by the period of time that is required for regrowth of healthy nail.

Use of the drug in children

Children drug designate to two years. The dose depends on the body weight of the child and of:
for children weighing 20 kg dog – 62.5 mg / day
from 20 kg to 40 kg – 125 mg / day;
more than 40 kg – 250 mg / day.

Data on drug use among children primobolan depot bayer aged up to two years (with a body weight less than 12 kg) are not available.

Side effects
Lamikan generally well tolerated. Side effects usually are mild or moderate and transient in nature are.

If ingestion may occur:
– the part of the gastrointestinal tract and liver: dyspepsia, abdominal pain, feeling of fullness, nausea, loss of appetite, diarrhea; sometimes taste disturbance, including their loss (restored several weeks after cessation of treatment).
– From the musculoskeletal system: muscle pain, joint pain.
– From the hematopoietic system: neutropenia, agranulocytosis, thrombocytopenia, rarely – lymphopenia.
– Allergic reactions: skin rash in the form of spots, blisters, seldom – toxic epidermal necrolysis, Stevens-Johnson syndrome, anaphylactoid reactions.

Overdose
orally in recommended doses is not described Until now, cases of overdose when taking terbinafine. In acute overdose of the drug may develop nausea, vomiting, pain in the epigastric region.

Treatment: gastric lavage, followed by the appointment of activated carbon; if necessary – symptomatic supportive therapy.

Interaction with other medicinal products
Terbinafine in vitro has a very low ability to alter the clearance of most drugs that are metabolized with participation of cytochrome P450 (eg tsoklosporina, terfenadine, tolbutamide, triazolam or oral contraceptives).

In women, while taking terbinafine and oral contraceptives, may experience irregular menstruation. The total clearance of terbinafine may be accelerated by drugs that cause induction of cytochrome P450 enzymes (such as rifampicin) and may slow down drugs – inhibitors of the cytochrome P450 system (eg, cimetidine), if necessary, the simultaneous use of these drugs may require dose adjustment.

Caffeine clearance reduces by 20%.
Terbinafine does not affect the clearance of antipyrine, digoxin, warfarin.
Ethanol and other hepatotoxic drugs increases the risk of hepatotoxicity.

Cautions
Irregular use or premature ending primobolan depot bayer of treatment increases the risk of relapse.

If after 2 weeks of treatment, no improvement in the state, it is necessary to re-determine the causative agent and its sensitivity to the drug.

Care should be taken when appointing Lamikana into patients with impaired hepatic function and (or) of the kidneys. If any symptoms suggestive of liver dysfunction (lack of appetite, fatigue, persistent nausea, jaundice, dark urine), you need to remove the drug. Patients with chronic disorders of the liver and kidney primobolan depot bayer function should be given half the usual recommended dose of the drug and monitor indicators of liver and kidney function during treatment.

primobolan depot

Allylamine which has a broad spectrum of activity against fungi which cause diseases of the skin, hair and nails, including dermatophytes such as primobolan depot and Pityrosporum. At low concentrations of terbinafine has fungicidal activity against dermatophytes, molds and certain dimorphic fungi. Activity against yeast fungi, depending on their type, may be a fungicidal or fungistatic,primobolan depot specifically inhibits the early stage of the biosynthesis of sterols in fungal cells. This leads to a deficiency of ergosterol and to an intracellular accumulation of squalene, which causes death of fungal cells. Terbinafine action effected by inhibition of the enzyme squalene epoxidase in the cell membrane of the fungus. This enzyme does not belong to the cytochrome primobolan depot system.When assigning primobolan depot inside the skin, hair and nails are drug concentration providing fungicidal activity.

Pharmacokinetics

After oral administration, terbinafine is well absorbed (> 70%); the absolute bioavailability of terbinafine due to the effect of “first pass” is about 50%. After receiving a single oral dose of terbinafine 250 mg its maximum concentration is reached after 1.5 hours in plasma (Cmax) and is 1.3 ug / ml. When it postoyannno receiving terbinafine Cmax increased on average by 25%, compared to a single dose; AUC increased 2.3-fold. Based on the increased AUC, we can calculate the effective half-life (30 hours). Ingestion marginally affects drug bioavailability (AUC is increased by at least 20%), and therefore requires no dose adjustment Lamizila® while taking with food.

Terbinafine largely bound to plasma proteins (99%). It quickly penetrates the dermal layer of the skin, and concentrates in the lipophilic stratum corneum. Terbinafine is also penetrates the sebum, which results in a high concentration in the hair primobolan depot follicles, the hair and the skin rich in sebaceous glands. We also show that terbinafine penetrates the nail plate in the first few weeks after beginning therapy.

Terbinafine is metabolised rapidly primobolan depot and substantially, with the participation of at least seven isoenzymes of cytochrome P450, with the main role is played isoenzymes CYP2C9, CYP1A2, CYP3A4, CYP2C8 and CYP2C19. The resulting biotransformation terbinafine metabolites formed without having antifungal activity and can be output primarily with urine.

There were no changes in the equilibrium plasma concentrations of terbinafine, depending on age.

In pharmacokinetic studies, single dose Lamizila® in patients with underlying renal impairment (creatinine clearance <50 mL / min) and liver disease have shown the possibility of reducing the clearance of the drug by 50%.

INDICATIONS

 

  • Onychomycosis caused by dermatophytes fungi.
  • Fungal infections of the scalp.
  • Fungal skin infections – treatment of primobolan depot tinea of the body, legs, feet, and yeast infections of the skin caused by fungi of the genus of Candida (eg, of Candida albicans) – in cases where localization, severity or prevalence of infection determine the feasibility of oral therapy.Note: unlike Lamizila® topical terbinafine oral not effective in pityriasis versicolor.CONTRAINDICATIONS

    Increased sensitivity to terbinafine or to any ingredient of the drug.

    CAREFULLY

    Terbinafine is not recommended for patients with chronic or active liver disease. Prior to his appointment Lamizila® tablets need to determine whether the patient’s previous liver disease. Hepatotoxicity may occur in patients with liver diseases previous or without them. Patients who are prescribed terbinafine should be warned that you should immediately inform your doctor of the occurrence primobolan depot in patients receiving the drug symptoms such as persistent nausea, anorexia, fatigue, vomiting, right upper quadrant pain, jaundice, dark urine or light cal. In the event of such symptoms should immediately stop taking the drug and to conduct a study of liver function.

    Pregnancy and lactation

    These experimental studies do not suggest the presence of adverse events in relation to fertility and of toxic effects on the fetus. Since clinical experience Lamizila® in pregnant women is very limited, you should not use the drug during pregnancy except in cases where the expected benefits of therapy outweighs the potential risk.

    Terbinafine is excreted in breast milk, therefore women receiving terbinafine into, should not breastfeed.

    DOSAGE AND ADMINISTRATION

    The duration of treatment depends on the indication and the severity of the disease.

    Children

    Data on the use of the drug in children primobolan depot younger than 2 years (body weight which is usually less than 12 kg) are not available.

    The drug is administered 1 time per day. Single dose depends on the body weight and is: for children weighing less than 20 kg – 62.5 mg; from 20 to 40 kg – 125 mg; 40 kg – 250 mg. In children older than 2 years Lamizila® tolerability of oral good.

    Adults

    250 mg 1 time per day.

    Infections of the skin

    The recommended duration of treatment:
    Tinea pedis (interdigital, plantar or by type of socks): 2-6 weeks.
    Tinea torso, legs: 2-4 weeks.
    Skin Candidiasis: 2-4 weeks.

    Complete disappearance of the manifestations of infection and complaints associated with it, may occur no earlier than a few weeks after mycological cure.

    Infections hair and scalp

    The recommended duration of treatment:
    Mycosis of the scalp:. 4 weeks
    Fungal infections of the scalp mostly seen in children.

    Onychomycosis

    The duration of treatment in most patients is 6 to 12 weeks. When onychomycosis brushes in most cases enough to 6 weeks of treatment. When onihomi goat-stop in most cases quite 12 weeks of treatment. Some patients who have a decreased rate of nail growth, may require longer treatment. The optimal clinical effect is seen some months after mycological cure and cessation of therapy. This is determined by the period of time that is required for regrowth of healthy nail.

    Use in patients with impaired renal function

    Patients with renal impairment (creatinine clearance less than 50 mL / min and concentration of serum creatinine 300 umol / L), the dose should be reduced by 2 times.

    Use in the elderly

    There is no reason to assume that the elderly need to change the drug dosage regimen, or that they have marked side effects that differ from those of younger patients. In the case of use in this age group of the drug in tablets should consider the possibility of concomitant abnormal liver or renal function.

    SIDE EFFECT

    Terbinafine generally well tolerated. Side effects are usually mild or moderately expressed and are transient in nature. Below are the adverse events observed in clinical trials or after the drug on the market.

    In assessing the incidence of adverse events following grading used: “very often” (> 1/10), “often” (from> / 100 <1/10), “sometimes” (> 1/1000 <1/100), ” rarely “(> 1/10000 <1/1000),” very rarely “(<1/10000), including isolated posts.

    From hemopoiesis system: very rarely – neutropenia, agranulocytosis, thrombocytopenia.

    Immune system: very rare – anaphylactoid reactions (including angioedema), cutaneous and systemic lupus erythematosus

    From the nervous system: often – headache; sometimes primobolan depot – a violation of taste sensations, including their loss (typically recovery occurs within a few weeks after cessation of treatment). There are some reports of cases of prolonged taste disturbance. In some cases in patients receiving the drug showed a decrease in food intake, which resulted in a significant reduction in weight.

    Liver: rare – hepatobiliary dysfunction (primarily cholestatic nature), including very rare cases of serious liver failure (some with a fatal outcome, or requiring liver transplant). In most cases, when developed liver failure, patients had serious concomitant systemic disease and the causal link of liver failure with reception Lamizila® was questionable.

    On the part of the gastrointestinal tract (GIT): very often – a sense of fullness, loss of appetite, dyspepsia, nausea, mild abdominal pain, diarrhea. Skin and subcutaneous tissue: very often – not heavy skin reactions (rash, urticaria) very seldom – serious skin reactions (including Stevens-Johnson syndrome, toxic epidermal necrolysis); psoriasiform rash or exacerbation of psoriasis. Very rarely, there have been cases of hair loss, although a causal link with the administration of the drug has not been established. If progressive skin rash develops, treatment should be discontinued Lamizilom®.

    From the musculoskeletal system: very often – arthralgia, myalgia.

    Other: very rarely – fatigue.

    OVERDOSE

    There are reports of a few cases of overdose (accepted dose was 5 g), in which the observed headache, nausea, epigastric pain and dizziness.

    Recommended in case of overdose, treatment includes measures to eliminate the drug, primarily by the appointment of activated charcoal and gastric lavage; if necessary, symptomatic and supportive therapy.

    interaction with other medicinal products and other forms of

    INTERACTION

    Effect of other medicinal products on terbinafine

    The plasma clearance of terbinafine may be accelerated under the influence of drugs – inducers of metabolism and suppressed under the influence of inhibitors of cytochrome P450. If necessary, the simultaneous application of the above drugs and Lamizila® and may require appropriate correction dosing regime of the latter.

    Cimetidine may increase the effects of terbinafine or increase its concentration in plasma. Cimetidine reduces the clearance of terbinafine by 33%.

    Rifampicin may impair the action of terbinafine or reduce its concentration in plasma. Rifampicin increased the clearance of terbinafine by 100%.

    Effect of terbinafine on other drugs

    Studies conducted in vitro and in healthy primobolan depot volunteers show that terbinafine has little capacity to inhibit or enhance the clearance of most drugs that are metabolized by the participation of cytochrome P450 (eg, terfenadine, triazolam, tolbutamide or oral contraceptives), except for those which are metabolized by the CYP2D6.

    Terbinafine does not influence the clearance of antipyrine or digoxin.

    There are reports of several cases of violation of the menstrual cycle in patients taking terbinafine, together with oral contraceptives, although the incidence of these disorders is not higher than the average rate of such disorders in patients taking only oral contraceptives.

    Terbinafine may increase the effects of caffeine or increase its concentration in plasma. Terbinafine decreases the clearance of caffeine administered intravenously by 19%.

    In studies in vivo and in vitro have shown that terbinafine inhibits metabolism mediated by the enzyme 2D6 (CYP2D6). These data may be clinically important for those drugs that are metabolized primarily by the enzyme: tricyclic antidepressants, beta-blockers, selective serotonin reuptake inhibitor, antiarrhythmic drugs of class 1C and inhibitors mono-oxidase type B – in case applied simultaneously preparation It has a small range of therapeutic concentrations.