Oxcarbazepine - instructions for use, dose, side effects, contraindications

Clinical and pharmacological group: & nbsp

Antiepileptic agents

Included in the formulation

Trileptal®

pills inwards

Novartis Pharma AG Switzerland

Trileptal®

suspension inwards

Novartis Pharma AG Switzerland

Included in the list (Order of the Government of the Russian Federation No. 2782-r of 30.12.2014):

VED

ONLS

АТХ:

N.03.A.F.02 Oxcarbazepine

Pharmacodynamics:

Antiepileptic agent. The mechanism of action of oxcarbazepine and its metabolite monohydroxy derivative is mainly associated with blockade of potential-dependent sodium channels, which leads to stabilization of overexcited neuronal membranes, inhibition of serial neuronal discharges, and a decrease in synaptic impulses.

The realization of anticonvulsant action is facilitated by an increase in the conductivity of potassium ions and modulation of calcium channels activated by a high membrane potential.

Pharmacokinetics:

It is well absorbed, metabolized in the liver to form the active metabolite of the 10-monohydroxy derivative. The association with the plasma proteins of the active metabolite of the drug is 40%. The half-life is 2 hours for the drug, 9 hours for the active metabolite. Excreted by the kidneys by 95% and through the gastrointestinal tract by 4%.

Indications:

Generalized tonic-clonic epileptic seizures (age from 2 years).

Complex and simple partial epileptic seizures (with loss or loss of consciousness), with / without secondary generalization (age from 1 month and older).

Monotherapy (as a first-choice drug), as well as in combination therapy. With incomplete relief of epileptic seizures, it is possible to replace other anticonvulsants with oxcarbazepine.

ICD-10

VI.G40-G47.G40 Epilepsy

Contraindications:

Hypersensitivity.

Lactation.

Carefully:

Allergic reactions to the drug in the anamnesis.

Pregnancy.

Age to 2 years.

Pregnancy and lactation:

Category FDA - C. The available reports indicate a possible association of oxcarbazepine in pregnancy with the development of birth defects (for example, the wolf mouth).

If the patient plans to become pregnant or becomes pregnant during the application of oxcarbazepine, and if there is a question about the use of oxcarbazepine in pregnancy, carefully compare the expected benefits of therapy and the possible risk to the fetus, especially in the first trimester of pregnancy.

When pregnancy should be used oxcarbazepine in the minimum effective dose.

It is known that a deficiency of folic acid develops during pregnancy. Antiepileptic drugs can increase this deficit, which is one of the possible causes of fetal development disorders, therefore, an additional intake of folic acid preparations is recommended.

At application at pregnancy it is necessary to consider, that the physiological changes occurring in an organism of the pregnant woman, can lead to gradual decrease in concentration of the active metabolite in a blood plasma. To achieve maximum control of the symptoms of the disease, it is necessary to regularly evaluate the clinical effect of oxcarbazepine and determine the concentration of the metabolite in the blood plasma. Determination of the concentration of monohydroxy derivative in the blood plasma is also recommended to be carried out in the postpartum period, especially if the dose of oxcarbazepine is increased in pregnancy.

There are reports that the use of antiepileptic drugs in pregnancy can lead to increased bleeding in newborns. As a precaution, the appointment of vitamin K₁ in the last few weeks of pregnancy, as well as to newborns whose mothers received oxcarbazepine.

Oxcarbazepine and monohydroxy derivatives penetrate the placental barrier and are excreted in breast milk. Since the impact on newborns of oxcarbazepine and monohydroxy derivatives, received with the mother's milk, is not known, one should not apply oxcarbazepine in the period of breastfeeding.

Dosing and Administration:

Take orally, regardless of food intake, with a small amount of liquid. The suspension may be taken undiluted directly from the syringe or diluted with a small amount of water.

The first dose 600 mg /day (8-10 mg per kg per day), divided into 2 doses. The further dose is adjusted in accordance with the patient's clinical indicators, based on the effectiveness of treatment, kidney function.

Under steady-state conditions, a rapid dose increase of up to 2,400 mg per day can be achieved within 48 hours.

The recommended initial dose for children over 2 years is 8-10 mg / kg body weight per day, divided into 2 doses, both in monotherapy and in combination therapy.In combination with other antiepileptic drugs an adequate therapeutic effect is observed with a maintenance dose of 30 mg / kg of body weight per day. To achieve the desired therapeutic response, a gradual increase in the dose of 10 mg / kg per day per week to a maximum daily dose of 46 mg / kg body weight is possible.

Side effects:

Organism as a whole: increased fatigue, asthenia, angioedema, polyorganism hypersensitivity reactions (rash, fever, lymphadenopathy, increased liver samples, eosinophilia, arthralgia).

On the part of the immune system: allergic reactions, angioedema, abnormal liver function, anaphylactic reactions, urticaria, Stevens-Johnson syndrome, etc.

From the side CAS: very rarely - arrhythmia, atrioventricular blockade.

From the hematopoiesis: oppression of bone marrow hematopoiesis, thrombocytopenia, neutropenia, pancytopenia, agranulocytosis, aplastic anemia.

From the side of water-electrolyte metabolism: often - asymptomatic hyponatremia; very rarely - clinically manifested hyponatremia (convulsions, confusion, encephalopathy, blurred vision, nausea, vomiting).

On the part of the digestive system and liver: dyspeptic phenomena, increased activity of hepatic transaminases, hepatitis, constipation, diarrhea, pancreatitis, increased concentrations of alkaline phosphatase in the blood.

From the nervous system: headache, drowsiness, dizziness, impaired vision, diplopia, vertigo, emotional lability, agitation, apathy, amnesia, agitation, depression, attention deficit disorder, disorientation, nystagmus, ataxia, tremor.

From the skin: acne, alopecia, rash.

Overdose:

Dizziness, drowsiness, hyponatremia, hypokinesia, nystagmus, ataxia, vomiting, nausea. Treatment: symptomatic and supportive. Gastric lavage and administration of activated charcoal to reduce absorption (in the case of a recent drug administration). There is no specific antidote.

Interaction:

The drug and its active metabolite are inhibitors of cytochrome CYP2C19, osimultaneous administration of high doses of oxcarbazepine and medicines, metabolized CYP2C19 (phenobarbital, phenytoin), can lead to interaction

The drug and its active metabolite are inducers CYP3A4, CYP3A5 and CYP2B, involved in the metabolism of dihydropyridine derivatives of calcium channel blockers, oral contraceptives and antiepileptic medicines (including carbamazepine). Simultaneous administration of oxcarbazepine and substrates CYP3A4 and CYP3A5 can reduce the concentration of the latter in blood plasma.

Oxcarbazepine can reduce the carbamazepine concentration by 22%; in the same time carbamazepine can reduce the concentration of oxcarbazepine by 40%.

Valproic acid can reduce the concentration of oxcarbazepine by 18%.

The drug enhances the sedative effect of ethanol.

Special instructions:

Allergic reactions can develop in patients without a history of hypersensitivity to carbamazepine. In case of allergic reactions, the drug should be immediately canceled.

Hyponatremia (serum Na concentration⁺ below 125 mmol / l) is usually clinically not manifested and does not require correction of the dosing regimen, observed in 2.7% of patients. The Na concentration⁺ It is normalized with the abolition (decrease in the dose) of oxcarbazepine or restriction of fluid intake. In patients with impaired renal function associated with hyponatremia, or with simultaneous therapy with diuretics, drugs, affecting the secretion ADH, before the initiation of oxcarbazepine therapy, the concentration of Na⁺ in blood plasma, and after 2 weeks after the start of therapy, and then monthly or as needed. If it is necessary to simultaneously prescribe saluretics and other medicines that cause hyponatremia, the same recommendations should be followed. When clinical symptoms of hyponatremia appear, serum Na concentration should be determined⁺.

During the period of treatment, it is necessary to control body weight in patients with chronic heart failure for the timely detection of fluid retention. In case of fluid retention or progression of symptoms of chronic heart failure, serum Na⁺. In the case of hyponatremia, the amount of fluid consumed should be limited.

During the period of treatment, careful monitoring of patients with a history of rhythm and conduction disorder is necessary.

If the suspected development of hepatitis during treatment, the drug should be canceled.

Women of childbearing age who take oral contraceptives should be warned,that simultaneous prescription of the drug can reduce their effectiveness, therefore additional use of non-hormonal methods of contraception is recommended.

Impact on the ability to drive vehicles and manage mechanisms

May cause dizziness, drowsiness. During the drug intake it is necessary to refrain from driving and performing work associated with increased concentration of attention.

Instructions

Oxcarbazepine (Oxcarbazepinum)