Efavirenz-Nanolek, 600 mg 30 pcs

Efavirenz should not be used as a single drug to treat HIV infection, nor should it be added as a single drug to an ineffective therapy regimen. As with other NNRTIs, viral resistance can develop rapidly when efavirenz is used in monotherapy. When selecting new antiretrovirals for use in combination with efavirenz, the possibility of cross-resistance of the virus should be considered (see section on Pharmacodynamics).

The use of efavirenz concomitantly with tablet medications with fixed combinations of efavirenz, emtricitabine and tenofovir disoproxil fumarate is not recommended unless a dose adjustment is required (for example, when concomitantly used with rifampicin).

The concomitant use of efavirenz with preparations based on Ginkgo biloba extract is not recommended.

When prescribing drugs for concomitant use with Efavirenz-NANOLEC®, the physician should refer to the instructions for medical use of these drugs.

With ART, the risk of transmission of HIV to others through sexual intercourse or blood cannot be ruled out. Because of this, appropriate precautions should be taken.

Companion antiretroviral therapy: If any antiretroviral drug in a combination ART regimen is withdrawn due to suspected intolerance, all antiretrovirals should be considered for simultaneous withdrawal. All antiretrovirals that have been discontinued should be restarted as soon as symptoms of intolerance have disappeared. Interrupted monotherapy and sequential re-treatment with antiretrovirals are not recommended because of the increased likelihood of emergence of therapy-resistant virus.

Skin rash: In clinical trials of efavirenz, mild to moderate rashes have been observed that usually disappear with continuation of therapy. Administration of appropriate H1-histamine receptor blockers and/or glucocorticosteroids may improve tolerability and contribute to the early disappearance of the skin rash. Severe skin rash accompanied by blistering, epithelial desquamation or ulcer formation has been observed in less than 1% of patients taking efavirenz. Erythema multiforme or Stevens-Johnson syndrome occurred in 0.1% of patients. If patients develop a severe rash accompanied by blistering, epithelial desquamation involving mucous membranes or fever, efavirenz should be stopped immediately. Efavirenz is not recommended in patients who have had a life-threatening skin reaction (e.g., Stevens-Johnson syndrome). If therapy with efavirenz is discontinued, discontinuation of other antiretrovirals should be considered in order to avoid the emergence of therapy-resistant virus. Cases of cutaneous rash were reported in 59 of 182 children (32%) treated with efavirenz in 3 clinical trials with an average duration of 123 weeks. In 6 children, the rash was severe. The median time to onset of rash in children was 27 days (3-1504 days). Appropriate antihistamine therapy as prophylaxis may be recommended before starting efavirenz therapy in children.

There is limited experience with efavirenz in patients who have had other NNRTI class antiretrovirals withdrawn (see side effects).

Efavirenz is not recommended in patients who have previously developed life-threatening skin reactions (e.g., Stevens-Johnson syndrome) while taking other NNRTIs.

Mental symptoms: There are data on the occurrence of mental adverse events in patients taking efavirenz. Patients with a history of mental disorders are at increased risk of serious mental adverse events. In particular, severe depression was most frequently observed in patients with a history of depression. There are also post-registration data on cases of severe depression, death by suicide, delirium, and psychosis-like behavior.

Patients should be warned that if they develop symptoms such as severe depression, psychosis, or suicidal ideation, they should inform their physician immediately. The physician should determine if these symptoms may be related to taking efavirenz, and if this relationship is confirmed, assess the balance between the risk to the patient of continuing therapy and the potential benefit of taking the drug (see Caution section). Hepatic adverse events: during the post-registration monitoring period there were a small number of reports of liver failure in patients with no history of liver disease and no other identified risk factors (see “Adverse effects”). In this regard, it is recommended to monitor the activity of “liver” enzymes even in patients without a history of hepatic dysfunction or other risk factors.

Effect of food: administration of Efavirenz-NANOLEC® during meals may increase exposure of efavirenz (see “Pharmacological properties”), which may lead to increased incidence of adverse reactions (see section “Adverse effects”). Therefore it is recommended to take Efavirenz-NANOLEC® on an empty stomach, preferably at bedtime.

The immune reconstitution syndrome: this syndrome has been observed in patients with severe immunodeficiency at any time after the start of combined ART. As a result of increased immune response due to therapy, an inflammatory response to inactive or residual opportunistic infections, such as cytomegalovirus rhinitis, generalized and/or focal mycobacterial infections, pneumonia caused by Pneumocystis jiroveci (formerly called Pneumocystis carinii) may develop within weeks or months of treatment initiation. Such inflammatory symptoms need further evaluation and appropriate treatment.

Autoimmune disorders (such as diffuse thyrotoxic goiter) have been observed against the background of immune reconstitution, but the timing of the initial manifestations varied greatly and the disease could occur many months after initiation of therapy.

Lipodystrophy and metabolic disorders: Combination ART is associated with redistribution of subcutaneous body fat (lipodystrophy) in HIV-infected patients. Long-term consequences of this phenomenon are still unknown, and the mechanism of its development has not been sufficiently studied.

The association between visceral lipomatosis and the use of protease inhibitors and lipoatrophy and the use of NIOT has been suggested. The increased risk of lipodystrophy may be due to both individual factors, such as advanced age, and drug-related factors, such as prolonged ART and associated metabolic abnormalities. Therefore, during the clinical examination of a patient, a physical examination should be performed, paying attention to the redistribution of subcutaneous fat, as well as determining the fasting serum lipid concentration and blood glucose concentration. Lipid metabolism disorders should be corrected according to clinical manifestations.

Osteonecrosis: although the etiology of this disease is recognized as multifactorial (including corticosteroid use, alcohol abuse, severe immunosuppression, increased body mass index), cases of osteonecrosis have been observed primarily in patients with long-term HIV infection and/or in patients who have received long-term combination ART. Patients should see a physician immediately if they experience joint pain, decreased joint mobility, or difficulty walking.

Patients with liver disease: Efavirenz is contraindicated in patients with severe hepatic impairment (Child-Pugh class C) (see sections “Contraindications”; “Pharmacological properties”) and is not recommended in patients with moderate liver disease because there are insufficient data to determine whether dose adjustments are necessary in these cases. Because of intensive metabolism of efavirenz by cytochrome P450 system and limited experience of clinical use of the drug in patients with chronic liver disease, caution should be exercised when prescribing Efavirenz-NANOLEC® in patients with mild liver disease. Patients should be under observation for timely detection of dose-dependent adverse reactions, especially in nervous system. Laboratory tests should also be performed at intervals to assess the liver condition.

Safety and efficacy of efavirenz have not been confirmed in patients with a history of significant liver dysfunction. Patients with chronic hepatitis B or C taking combination ART are at risk of serious adverse liver reactions that may be fatal. In patients with a history of liver dysfunction, including chronic active hepatitis, the incidence of liver dysfunction during combination ART increases, so such patients should be monitored according to the standard regimen. In patients with worsening liver disease or with a sustained increase in serum transaminases greater than 5-fold IUF, the benefit of continued efavirenz therapy should be weighed against the possible risk of hepatotoxicity. In these patients, consideration should be given to whether to discontinue or withdraw ART.

When concomitant use of other drugs with known hepatotoxicity, monitoring of “liver” enzyme activity is recommended. Patients with hepatitis B or C should also follow the hepatitis B or C medication administration guidelines when prescribing combined antiviral therapy.

Patients with renal impairment: Pharmacokinetics of efavirenz in patients with renal impairment have not been studied, but due to the fact that less than 1% of the dose of efavirenz is excreted unchanged by kidneys, renal function impairment should not significantly affect excretion of efavirenz (see section “Pharmacological properties”). There is no experience of using efavirenz in patients with severe renal impairment; therefore, the safety of the drug should be closely monitored in such patients.

Elderly patients: Because the clinical studies have included a small number of elderly patients, there is no reason to believe that the effect of the drug in elderly patients is different from that in younger patients.

Children: The use of efavirenz in children younger than 3 months of age or weighing less than 3.5 kg has not been studied.

No studies have been conducted to evaluate the effect on the ability to drive and operate machinery. Efavirenz may cause dizziness, impaired attention, insomnia and other adverse CNS reactions. Patients should be warned that if they experience any of these symptoms, they should avoid driving or operating machinery.

– Hypersensitivity to any of the components of the drug;

– Severe hepatic impairment (Child-Pugh functional class C) (see sections “Pharmacological properties” and “Pharmacokinetics of special patient groups. Pharmacological properties” and “Pharmacokinetics in special patient groups”);

– children with a body weight less than 40 kg (for the given dosage form and dosage form);

– concomitant use with terfenadine, astemizole, cisapride, midazolam, triazolam, pimozide, bepridil, ergot alkaloids (e.g. ergotamine, dihydroergotamine, ergonovine or methyl ergonovine), since competitive interaction of efavirenz with the CYP3A4 isoenzyme may inhibit the metabolism of these drugs and lead to serious and/or life-threatening adverse reactions (e.g. arrhythmias, prolonged sedation or respiratory depression) (see section “Interaction with other drugs”).

– concomitant use with preparations/ herbal products containing Hypericum perforatum, since plasma concentrations of efavirepz are reduced and, consequently, the clinical effect (see “Interaction with other medicinal products”).

Lactase deficiency, lactose intolerance, glucose-galactose malabsorption.

– Patients with a history of psychiatric disorders who are at high risk of developing serious adverse psychiatric events;

Patients with a history of mild to moderate liver disease;

Patients with a history of seizures/patients taking concomitant anticonvulsants that are metabolized preferentially in the liver, such as phenytoin, carbamazepine, and phenobarbital (periodic monitoring of their blood concentrations is necessary);

– when concomitant use of efavirenz and artemether/lumefantrine.