Included in the formulation
Included in the list (Order of the Government of the Russian Federation No. 2782-r of 30.12.2014):VED
АТХ:J.05.A.G. Non-nucleosides - reverse transcriptase inhibitors
J.05.A.G.03 Efavirenz
Pharmacodynamics:An antiviral agent. A non-nucleoside reverse transcriptase inhibitor of human immunodeficiency virus type 1 (HIV-1).
Pharmacokinetics:It is subjected to intensive metabolism in the liver with the participation of enzymes of the CYP system. Based on research in vitro it is considered that CYP3A4 and CYP2B6 are the main isoenzymes responsible for the metabolism of efavirenz. According to a number of studies, depending on the dose efavirenz is an inhibitor or inducer of CYP3A4.
Less than 1% is excreted in the urine unchanged.
Indications:Infections caused by HIV-1 (as part of combination therapy).
I.B20-B24.B24 Disease caused by human immunodeficiency virus [HIV], unspecified
Contraindications:Hypersensitivity.Simultaneous application with terfenadine, astemizole, cisapride, midazolam or trizolam; increased sensitivity to efavirenz.
Carefully:Clinical experience with efavirenz in patients with chronic liver disease is limited. Use with caution in patients with severe impairment of liver function (since efavirenz is subjected to intensive metabolism in the liver with the participation of enzymes of the CYP system).
During the period of treatment it is recommended to constantly monitor the activity of hepatic transaminases in patients with hepatitis B or C or suspected of these infections in the anamnesis and in patients receiving other drugs that can have hepatotoxic effect. In case of acute persistent increase in transaminase activity to a level more than 5 times higher than the upper limit of the norm, one should compare the advantages of continuing treatment with the risk of a significant hepatotoxic effect.
In children under 3 years of age or body weight less than 13 kg, the safety and efficacy of efavirenz have not been studied.
Pregnancy and lactation:Pregnancy should be excluded from women receiving efavirenz (in experiments on primates efavirenz passed through the placenta and had a teratogenic effect). Before starting treatment, women of childbearing age should be tested for pregnancy and during treatment always use barrier methods of contraception in conjunction with other methods (eg, oral or other hormonal contraceptives).
In the case of pregnancy, the use of efavirenz is allowed only in cases when the potential benefit justifies the potential risk to the fetus (adequate and well-controlled studies in pregnant women has not been).
Action category for the fetus by FDA - D.
Breastfeeding is not recommended because of the potential risk of transmission of the virus, and although it is not known whether efavirenz with human milk, it should be discontinued because of the possible serious side effects of efavirenz in infants. Studies in rats have shown that efavirenz excreted with milk.
Dosing and Administration:Used in combination therapy with other antiretroviral drugs (protease inhibitors and / or nucleoside - reverse transcriptase inhibitors).
When ingested for adults and children weighing more than 40 kg, the recommended dose is 600 mg per day.
For children and adolescents (3 to 17 years), depending on the age of the dose is 200-400 mg per day. The recommended dose for children weighing more than 40 kg is 600 mg per day.
Frequency of admission - 1 time per day, regardless of food intake.
Efavirenz capsules are prescribed only to children who are able to easily swallow capsules.
Side effects:Dermatological reactions: often (especially in children) - maculopapular rash; in isolated cases - a severe rash, accompanied by blisters, wetting peeling and ulcers.
From the side digestive system: often - nausea; possible diarrhea.
From the side CNS: possible dizziness, headache, insomnia, fatigue, decreased concentration of attention.
Allergic reactions: in isolated cases - erythema multiforme, Stevens-Johnson syndrome.
From the side laboratory indicators: increased activity of ALT, AST, GGT, amylases, increase in the level of total bilirubin, increase in the concentration of glucose in the blood.
Overdose:An increase in neurologic symptoms in patients with a random dose of 600 mg twice a day was reported. One patient had involuntary muscle contractions.
Treatment: general supportive measures, including monitoring vital signs and monitoring the clinical condition of the patient. To accelerate the removal of an unabsorbed drug, Activated carbon. The specific antidote is not known. The efficacy of dialysis is unlikely (efavirenz actively binds to proteins).
Interaction:With simultaneous use of efavirenz with terfenadine, astemizole, cisapride, midazolam or trizolam, competitive drug interaction for the isoenzyme CYP3A4 is observed, which can lead to inhibition of the metabolism of these drugs and create the possibility of serious and / or life-threatening consequences - severe arrhythmias, prolonged sedation or oppression respiration).
Under the influence of efavirenz it is possible to reduce the concentration in the plasma of preparations that are substrates of the isoenzyme CYP3A4.
Special instructions:When choosing new antiretroviral drugs for combination therapy, the possibility of cross-resistance of the virus should be considered.
With the withdrawal of efavirenz should also consider the possibility of canceling treatment with other antiretroviral drugs,to avoid the emergence of resistant viruses.
During the treatment period, the level of cholesterol should be constantly monitored.
In children under 3 years of age or body weight less than 13 kg, the safety and efficacy of efavirenz have not been studied.