Regast pills 400mg 30pcs

Composition

For 1 tablet:

Active ingredient:

Efavirenz 400.0 mg,

excipients:

Core: betadex (beta-cyclodextrin) – 8.0 mg; calcium stearate-4.0 mg; crospovidone-48.0 mg; sodium lauryl sulfate-14.0 mg; lactose monohydrate-248.0 mg; povidone K 25-16.0 mg; polysorbate-80 (Twin-80) – 6.0 mg, microcrystalline cellulose-36.0 mg.

Film shell: Ready-made water-soluble film shell-20.0 mg (Shell composition: hydroxypropylmethylcellulose (hypromellose)- 74.2%, polyethylene glycol 6000 (Macrogol 6000) – 14.3%, titanium dioxide-3.5%, talc-2.3%, iron oxide red dye-1.4%, iron oxide yellow dye-4.3%).

Pharmacological action

Pharmacotherapeutic group: Antiviral [HIV] agent. ATX code:

J05AG Non – nucleosides-reverse transcriptase INHIBITORJ05AG03 Efavirenz

Pharmacological properties

Pharmacodynamics

Efavirenz is a non-nucleoside reverse transcriptase (NNRTI)inhibitor HIV-1. Efavirenz is a non-competitive HIV-1 reverse transcriptase inhibitor and does not significantly inhibit HIV-2 reverse transcriptase and human cellular DNA polymerases (alpha, beta, gamma and delta).

HIV sensitivity in vitro. The clinical significance of HIV-1 sensitivity to efavirenz in vitro has not been established. The antiviral efficacy of efavirenz in vitro was evaluated on lymphoblastic cell lines, peripheral blood mononuclear cells, and macrophage/monocyte cultures. The efavirenz concentration required for 90-95% inhibition (IC90-95) of laboratory-adapted wild-type strains and clinical isolates resistant to zidovudine is in the range of 0.46 to 6.8 nmol/l.

Efavirenz demonstrated synergistic activity in cell culture in combination with the nucleoside reverse transcriptase inhibitors (NRTIs) zidovudine and didanosine and the protease inhibitor indinavir.

Stability. The antiviral efficacy of efavirenz in cell culture against viral varieties with amino acid substitutions in reverse transcriptase at positions 48,108,179,181 or 236, as well as against varieties with amino acid substitutions in protease, was similar to that for wild-type viral strains. The only substitutions that resulted in the highest efavirenz resistance in cell culture were the replacement of leucine with isoleucine at position 100 (L100I,17-22-fold resistance) and lysine with asparagine at position 103 (K103N,18-33-fold resistance). A more than 100-fold decrease in viral susceptibility to the drug was observed for HIV varieties expressing the K103N substitution in addition to other amino acid substitutions in reverse transcriptase.

K103N is the most commonly observed reverse transcriptase substitution in viral isolates obtained from patients who experienced a significant increase in the number of viral particles after discontinuation of treatment in clinical trials of efavirenz in combination with indinavir or in combination with zidovudine with lamivudine. Substitutions in reverse transcriptase at positions were also observed. 98,100,101,108,138,188,190 and 225, but less often and often only in combination with K103N. The type of reverse transcriptase amino acid substitutions associated with efavirenz resistance was independent of other antiviral drugs used in combination with efavirenz.

Cross-resistance. A study of the cross-resistance profiles of efavirenz, nevirapine, and delavirdine in cell cultures showed that K103N substitution leads to a loss of susceptibility to all three non-nucleoside reverse transcriptase inhibitors. Two of the three delavirdine-resistant clinical isolates studied were cross-resistant to efavirenz and contained the K103N replacement. The third isolate, which has a reverse transcriptase substitution at position 236, was not cross-resistant to efavirenz.

Viral isolates isolated from peripheral blood mononuclears of patients included in efavirenz clinical trials in whom therapy was ineffective (increased number of viral particles) were investigated for susceptibility to NNRTIs. Thirteen isolates that were previously characterized as resistant to efavirenz were also resistant to nevirapine and delavirdine. Five of these NNRTI-resistant isolates were found to contain a K103N substitution or a valine-isoleucine substitution at position 108 (V1081) in reverse transcriptase. Among the tested isolates after ineffective efavirenz therapy, three isolates remained sensitive to efavirenz in cell cultures, and also had sensitivity to nevirapine and delavirdine.

The probability of cross-resistance between efavirenz and protease inhibitors is low due to the presence of different target enzymes. Cross-resistance between efavirenz and nucleoside reverse transcriptase inhibitors is also unlikely due to different target binding sites and different mechanisms of action.

Pharmacokinetics

Suction

In healthy volunteers, the maximum concentration (Cmax) of efavirenz in blood plasma of 1.6 – 9.1 microns was reached 5 hours after a single oral dose of the drug in doses from 100 mg to 1600 mg. A dose-dependent increase in the maximum concentration (Cmax) and area under the concentration-time curve was observed when taking the drug in doses up to 1600 mg; however, a proportional dependence of the degree of increase in these indicators on the dose was not achieved, from which it can be assumed that absorption decreases at higher doses. Time to reach Cmax in plasma (3-5 hours) It did not change after repeated use of the drug, and the equilibrium plasma concentration was reached after 6-7 days.

In HIV-infected patients in the period of stable condition, the average values of Cmax, minimum concentration (Cmin) and area under the concentration-time curve have a linear dependence on the daily dose. In 35 patients treated with efavirenz 600 mg once a day, the Cmax at steady-state concentration was 12.9 ± 3.7 µm, the Cmin was 5.6 ± 3.2 µm, and the area under the concentration-time curve was 184 ± 73 µm per hour.

Effect of food on absorption

Efavirenz can be taken regardless of food intake. Taking efavirenz with food can increase its effect and lead to an increase in the frequency of adverse reactions. The bioavailability of a single dose of efavirenz 600 mg in healthy volunteers increased by 22% and 17%, respectively, when taking the tablets together with food with a normal or high fat content, compared with taking the same dose of the drug on an empty stomach. Efavirenz is recommended to be taken before bedtime on an empty stomach.

Distribution

Efavirenz is highly bound to plasma proteins (approximately 99.5 – 99.75%), primarily to albumin. In HIV-infected patients (N = 9) who received efavirenz in doses from 200 to 600 mg once a day for at least one month, the concentration of the drug in the cerebrospinal fluid ranged from 0.26 to 1.19% (average 0.69%) of the corresponding plasma concentration. This indicator is approximately 3 times higher than the concentration of the non-protein (free) fraction of efavirenz in blood plasma.

Metabolism

Clinical and in vitro studies using human liver microsomes have shown that efavirenz is primarily metabolized by the cytochrome P450 system to hydroxylated derivatives, which then bind to glucuronic acid to form glucuronides. Basically, these metabolites are inactive against HIV-1. In vitro studies suggest that CYP3A4 and CYP2B6 are the main isoenzymes involved in efavirenz metabolism. In vitro studies have shown that efavirenz at concentrations corresponding to those in plasma inhibits the cytochrome P450 isoenzymes CYP2C9, CYP2C19, and CYP3A4. In vitro studies, efavirenz did not inhibit the CYP2E1 isoenzyme and inhibited the CYP206 and CYP1A2 isoenzymes only at concentrations much higher than those in clinical practice.

Efavirenz has been shown to induce cytochrome P450 enzymes, which leads to the induction of its own metabolism. With repeated use of 200-400 mg per day for 10 days, there was a lower degree of accumulation of the drug than expected (22-42% lower) and a shorter final half-life – 40-55 hours (the half-life of a single dose is 52-76 hours). The degree of induction of the CYP3A4 isoenzyme is similar with doses of efavirenz 400 mg and 600 mg. Pharmacokinetic interactive studies have shown that daily intake of 400 mg or 600 mg of efavirenz in combination with indinavir does not cause a further decrease in the area under the concentration-time curve of indinavir in comparison with cases when a dose of efavirenz 200 mg was prescribed.

Deduction

Efavirenz has a relatively long half-life, which ranges from 52 to 76 hours after a single dose and 40 to 55 hours after prolonged use. Approximately 14-34% of the isotope – labeled efavirenz dose is detected in the urine, and less than 1% of the efavirenz dose is excreted unchanged by the kidneys.

Pharmacokinetics in special patient groups

Liver failure

With a single dose of efavirenz, a twofold increase in its half-life was observed in one patient with severe hepatic insufficiency (Child-Pugh class C), which indicates an increased degree of accumulation in such cases.Repeated use of efavirenz did not reveal a significant effect of liver damage on the pharmacokinetics of efavirenz in patients with mild hepatic insufficiency (Child-Pugh class A) compared to patients in the control group. Currently, there are insufficient data to conclude whether moderate and severe hepatic insufficiency (Child-Pugh class B and C) affects the pharmacokinetics of efavirenz (see section “Contraindications”, “With caution”).

Renal insufficiency

The pharmacokinetics of efavirenz in patients with renal insufficiency have not been studied, but due to the fact that less than 1% of the efavirenz dose is excreted unchanged by the kidneys, impaired renal function should not significantly affect the elimination of efavirenz (see section “Special instructions”).

Gender and race

The pharmacokinetic parameters of efavirenz are similar in men and women, as well as in patients of different racial backgrounds.

Age group

There were no pharmacokinetic differences between patients 65 years and older and younger patients, although clinical studies of efavirenz did not include a sufficient number of patients 65 years and older.

Children

The use of efavirenz in children under 3 years of age and patients weighing less than 13 kg has not been studied. The pharmacokinetic parameters of efavirenz in children and adults were similar. In 49 children who received a dose of efavirenz equivalent to 600 mg (the dose was calculated based on body weight), Cmax was 14.2 microns, Cmin was 5.6 microns, and the area under the concentration-time curve was 218 microns per hour.

Indications

As part of combined antiviral therapy for the treatment of adults, adolescents and children over 3 years of age infected with the human immunodeficiency virus (HIV-1).

Use during pregnancy and lactation

Adequate and well-controlled studies of efavirenz in pregnant women have not been conducted. Efavirenz should not be used during pregnancy unless its use is necessary (the potential benefit to the mother outweighs the risk to the fetus, and there are no other appropriate therapeutic alternatives). Women taking efavirenz should avoid getting pregnant. In addition to oral or other hormonal contraceptives, other reliable methods of contraception should be used, including for 12 weeks after discontinuation of efavirenz treatment. It is not known whether efavirenz is excreted in human breast milk. Since data from animal studies indicate that the drug can pass into breast milk, women taking efavirenz during lactation are not recommended to breastfeed. In all circumstances, HIV-positive mothers are not recommended to breastfeed to avoid HIV transmission.

Contraindications

• hypersensitivity to any component of the drug;
• lactase deficiency, lactose intolerance, glucose-galactose malabsorption;
• hepatic failure, severe (class C classification for child – Pugh);
• children under 3 years or weighing less than 13 kg;
• simultaneous use with terfenadine, astemizole a, cisaprida with pimozide, bepridil with midazolam, triazolam and the ergot alkaloids, as a competitive interaction of efavirenz with CYP3A4 may lead to inhibition of metabolism of these drugs and the emergence of prerequisites for the occurrence of serious and/or life-threatening adverse events (e. g., cardiac arrhythmias, prolonged sedation or respiratory depression);
• simultaneous reception with saquinavir as the sole protease inhibitor in other non-nucleoside reverse transcriptase inhibitors (see section “Interaction with other medicines”);
• simultaneous reception of preparations containing St. John’s wort (Hypericum perforatum), since this may reduce the concentration of efavirenz in plasma and reducing its clinical effect.

With caution in

• patients with a history of psychiatric disorders are at increased risk for the development of serious adverse events on the part of the psyche;
• in the appointment of efavirenz to patients with impaired liver function of mild and moderate severity (grade A and b according to the classification of child-Pugh);
• in the appointment of efavirenz to patients with seizures (including in the anamnesis) (see “Special instructions”);
• patients receiving concomitant anticonvulsant drugs with predominant hepatic metabolism, such as phenytoin, carbamazepine and phenobarbital (it is necessary to perform periodic monitoring of concentrations in the blood)

Side effects

Efavirenz is generally well tolerated. Side effects possibly causally related to the use of the drug are presented below. The frequency of events is determined using the following assumption: very often (>1/10); often (>>1/100, >><1/10); infrequently (>1/1000, <1/10); infrequently (><1/100); rarely (>1/10000, <1/100); rarely (><1/1 000); very rarely (Immune system disorders: Infrequently: hypersensitivity reactions. Mental disorders: Common: abnormal dreams, anxiety, depression, insomnia. Infrequently: tendency to affect, aggressiveness, confusion, euphoria, hallucinations, mania, paranoid behavior, psychosis, suicidal intentions, suicide attempt. Rare: delirium, neurosis, death due to suicide. Nervous system disorders: Common: cerebellar coordination and balance disorders, attention disorders, dizziness, headaches, drowsiness. Infrequently: anxious agitation, amnesia, ataxia, impaired coordination of movements, convulsions, impaired thinking, tremor. Endocrine system disorders: Infrequently: gynecomastia. Metabolic disorders: Common: hypertriglyceridemia. Infrequently: hypercholesterolemia. Visual disturbances: Infrequently: blurred vision. Hearing disorders and labyrinth disorders: Infrequently: vertigo, tinnitus. From the respiratory system: Rarely-shortness of breath. From the cardiovascular system: Rarely-palpitation sensation. Gastrointestinal disorders: Common: abdominal pain, diarrhea, nausea, vomiting. Infrequently: pancreatitis, asymptomatic increase in serum amylase activity. Liver and biliary tract disorders: Common: increased activity of aspartate aminotransferase (ACT), alanine aminotransferase (ALT) and gamma-glutamyltransferase (GGT). Infrequently: acute hepatitis. Rare: liver failure. Musculoskeletal disorders: Infrequently: myalgia, arthralgia, myopathy, osteonecrosis. Skin and subcutaneous tissue disorders: Very common: a rash. Common: pruritus of the skin. Infrequently: erythema multiforme, Stevens-Johnson syndrome. Rare: photoallergic dermatitis. Common disorders: Often: increased fatigue. Infrequently: asthenia, “hot flashes” of blood to the skin of the face. Immune recovery syndrome In HIV-infected patients with severe immunodeficiency during the initiation of combined antiretroviral therapy, the risk of inflammatory reactions to asymptomatic or residual opportunistic infections may increase. Autoimmune diseases (for example, Graves ‘ disease) were observed against the background of immune recovery, but the time of initial manifestations varied, and the disease could occur many months after the start of therapy. Lipodystrophy and metabolic disorders Combined antiretroviral therapy is associated with redistribution of body fat (lipodystrophy) in HIV-infected patients, including depletion of peripheral and facial subcutaneous fat, its accumulation in the intraperitoneal space, internal organs, the back of the neck (“buffalo hump”) and hypertrophy of the mammary glands. Combined antiretroviral therapy can cause metabolic disorders such as hypertriglyceridemia, hypercholesterolemia, insulin resistance, hyperglycemia, and hyperlactatemia. Children and adolescents The type and frequency of adverse events in children is generally similar to that in adults, with the exception of rash, which is more common in children than in adults and is more pronounced. Prescribing appropriate H%^%1-histamine receptor blockers to children prior to efavirenz therapy to prevent rash may be appropriate.

Interaction

Efavirenz in vivo is an inducer of the isoenzymes CYP3A4, CYP2B6 and UDP-GT%^% 1%^%A%^% 1. The plasma concentration of compounds that are substrates for these isoenzymes may decrease with simultaneous use with efavirenz. Efavirenz may be an inducer of the CYP2C19 and CYP2C9 isoenzymes, but in vitro inhibition of these isoenzymes has also been observed. The effect of concomitant use of efavirenz with compounds that are substrates for these isoenzymes is not fully clear. Exposure to efavirenz may decrease when the drug is used simultaneously with certain medications (for example, ritonavir) or foods (for example, grapefruit juice) that inhibit the isoenzymes CYP3A4 or CYP2B6. Compounds or herbal preparations (for example, those containing Gingo Biloba extract, as well as St. John’s wort) that induce these isoenzymes can lead to a decrease in the concentration of efavirenz in blood plasma. Concomitant use with drugs containing St. John’s wort is contraindicated. Concomitant use with Gingo Biloba extracts is not recommended.Concomitant use of efavirenz with terfenadine, astemizole, cisapride, pimozide, bepridil, midazolam, triazolam, and ergot alkaloids (e. g., ergotamine, dihydroergotamine, ergonovine, or methylergonovine) is contraindicated, since inhibition of their metabolism by efavirenz can cause serious, life-threatening consequences (see “Contraindications”).. Hypericum perforatum: the use of preparations / products containing St. John’s wort in patients taking efavirenz is contraindicated. The concentration of efavirenz in blood plasma may decrease with simultaneous use with St. John’s wort, since it induces the induction of enzymes and / or transport proteins responsible for drug metabolism. If the patient is already taking medications / products containing St. John’s wort, then the use of the latter should be discontinued, check the concentration of the virus in the blood and, if possible, the concentration of efavirenz in the blood. After discontinuation of drugs/products containing St. John’s wort, the concentration of efavirenz may increase and then a dose adjustment of efavirenz will be required. The effect of St. John’s wort associated with the induction of enzymes may persist for at least 2 weeks after its withdrawal (see “Contraindications”). Other interactions between efavirenz and HIV protease inhibitors, other antiretroviral drugs other than HIV protease inhibitors, as well as between efavirenz and drugs that do not belong to the group of antiretroviral drugs are indicated in table 2 below. An increase in the indicator value is indicated by an arrow “↑”, a decrease in the value – by an arrow”↓”, if the indicator remains unchanged-by an arrow”↔”. If necessary, the 90% and 95% confidence intervals are shown in parentheses. Usually, studies were conducted on healthy volunteers, unless other information is specifically specified.

How to take, course of use and dosage

Inside, the drug is recommended to be taken before bedtime on an empty stomach.

Therapy should be prescribed by a doctor who has experience in treating HIV infection.

Adults: 600 mg once daily in combination therapy with protease inhibitors and / or nucleoside reverse transcriptase inhibitors (NRTIs).

Combination therapy:

When used concomitantly with rifampicin in patients weighing 50 kg or more, the efavirenz dose should be increased to 800 mg / day. When administered concomitantly with efavirenz, no dose adjustment of rifampicin is required.

When efavirenz and voriconazole are co-administered, the maintenance dose of voriconazole should be increased to 400 mg every 12 hours and the efavirenz dose should be reduced to 300 mg once a day (see section “Interactions with other medicinal products”). After discontinuation of voriconazole therapy, the initial dose of efavirenz (600 mg) should be used.

Concomitant antiretroviral therapy: efavirenz should be used in combination therapy with other antiretroviral drugs.

Adolescents and children with a body weight of 40 kg or more: 600 mg once a day in combination therapy with a protease inhibitor and / or NRTI. Children aged 3 years and older with a body weight of 13 to 40 kg: Recommendations for the use of efavirenz with a protease inhibitor and / or NRTIs are given in Table 1.

Table 1. Doses for children prescribed efavirenz once a day

The use of efavirenz in children under 3 years of age and patients weighing less than 13 kg has not been studied.

Patients with renal insufficiency

The pharmacokinetics of efavirenz in patients with renal insufficiency have not been studied, but due to the fact that less than 1% of the efavirenz dose is excreted unchanged by the kidneys, impaired renal function should not significantly affect the elimination of efavirenz (see section “Special instructions”).

Patients with hepatic insufficiency

In patients with mild hepatic impairment, no dose adjustment of efavirenz is required. At the same time, patients should be monitored for timely detection of dose-dependent adverse reactions, especially from the nervous system (see the section “Special instructions”).

In patients with moderate hepatic impairment, the use of the drug is not recommended, since at this time there is insufficient data to determine whether a dose adjustment is necessary in such cases.

Overdose

Some patients who accidentally took efavirenz at a dose of 600 mg 2 times a day experienced increased symptoms from the nervous system. One patient experienced involuntary muscle contractions. In the case of an overdose of efavirenz, treatment should consist of general supportive measures, including monitoring of the main vital signs of the body and monitoring the patient’s clinical condition. Activated carbon can be used to remove the unabsorbed drug. There is no specific antidote for treating efavirenz overdose. Since efavirenz actively binds to proteins, it is unlikely that dialysis can significantly remove the drug from the blood.

Special instructions

Efavirenz should not be used as the sole treatment for HIV infection, nor should it be added as the sole treatment to an ineffective treatment regimen.

During therapy, the risk of HIV transmission to others during sexual contact or through blood cannot be excluded. In this regard, appropriate precautions should be observed.

Concomitant use of efavirenz with fixed combinations containing efavirenz, emtricitabine and tenofovir disoproxil fumarate is not recommended unless a dose adjustment is required (for example, when used concomitantly with rifampicin). When prescribing medications that should be taken simultaneously with efavirenz, the doctor should refer to the relevant “Instructions for Medical Use” for these drugs. If the use of any antiretroviral drug in combination therapy is discontinued due to suspected intolerance, consideration should be given to the possibility of simultaneous discontinuation of all antiretroviral drugs. All discontinued antiretroviral medications should be resumed as soon as the symptoms of intolerance disappear.

Intermittent monotherapy with subsequent repeated doses of antiretroviral drugs is not recommended due to the increased probability of selection of mutagenic viruses that are resistant to therapy.

The use of efavirenz with Gingo Biloba extracts is not recommended.

Taking efavirenz with food can increase its effect and lead to an increase in the frequency of adverse reactions. Therefore, the drug is recommended to be used before bedtime on an empty stomach.

Skin rash: Mild to moderate skin rashes have been reported in clinical studies of efavirenz, which usually disappear with continued therapy. Taking appropriate H1-histamine receptor blockers and / or glucocorticosteroid medications may improve tolerability and contribute to the rapid disappearance of the rash. A severe rash, accompanied by blisters, desquamation, or ulceration, was observed in less than 1% of patients taking efavirenz. Multimorphic exudative erythema or Stevens-Johnson syndrome occurred in 0.14% of cases. If patients develop a severe rash accompanied by blisters, mucosal desquamation, or fever, efavirenz should be discontinued immediately. If efavirenz therapy is discontinued, consideration should be given to discontinuing other antiretroviral drugs to avoid the emergence of a therapy-resistant virus.

Rash was observed in 26 children out of 57 (46%) treated with efavirenz for 48 weeks, and three patients had a severe rash. Prescribing H1-histamine receptor blockers prior to efavirenz therapy in children to prevent the occurrence of rash may be appropriate.

Psychiatric symptoms: There are reports of psychiatric adverse events in patients treated with efavirenz. Patients with a history of psychiatric disorders are at an increased risk of developing serious adverse events on the part of the psyche. There are also post-registration data on cases of suicide, delusions, and psychosis-like behavior. Patients should be warned that if they develop these symptoms, they should contact their doctor immediately. The physician should determine whether these symptoms may be related to efavirenz use and, if confirmed, assess the patient’s risk ratio for continuing therapy and the potential benefit of taking the drug (see section “With caution”).

Nervous system symptoms: patients receiving efavirenz 600 mg once daily in clinical trials often experience the following symptoms: dizziness, insomnia, drowsiness, decreased concentration, dream pathology, and other undesirable phenomena.Symptoms from the nervous system are usually observed during the first or second day of therapy and in most cases disappear after the first 2-4 weeks. Patients should be informed that such symptoms, if they appear, usually disappear with continued therapy and are not a sign of possible mental disorders, which are less common.

Immune recovery syndrome: HIV-infected patients with severe immunodeficiency may develop an inflammatory response to asymptomatic or residual opportunistic infections during the initiation of antiretroviral therapy, which may lead to a serious deterioration of the condition or aggravation of symptoms. As a rule, such reactions are observed in the first weeks or months after the start of antiretroviral therapy. The most significant examples are cytomegalovirus retinitis, generalized and / or focal mycobacterial infection, and pneumonia caused by Pneumocystis jiroveci (formerly known as Pneumocystis carinii). Any symptoms of inflammation should be identified and, if necessary, treatment should be prescribed.

Autoimmune diseases (for example, Graves ‘ disease) were observed against the background of immune recovery, but the time of initial manifestations varied, and the disease could occur many months after the start of therapy. Lipodystrophy and metabolic disorders Combined antiretroviral therapy is associated with redistribution of body fat (lipodystrophy) in HIV-infected patients, including depletion of peripheral and facial subcutaneous fat, its accumulation in the intraperitoneal space, internal organs, the back of the neck (“buffalo hump”) and hypertrophy of the mammary glands. Combined antiretroviral therapy can cause metabolic disorders such as hypertriglyceridemia, hypercholesterolemia, insulin resistance, hyperglycemia, and hyperlactatemia.

Osteonecrosis

Cases of osteonecrosis have been reported, especially in patients with generally accepted risk factors (corticosteroid use, alcohol consumption, acute immunosuppression, elevated body mass index), late-stage HIV infection, or long-term combination antiretroviral therapy. Patients should be advised to consult a doctor if they experience joint pain, stiffness in the joints, or difficulty moving.

Special patient groups

Liver diseases: efavirenz is contraindicated in patients with severe hepatic insufficiency (Child-Pugh Class C) (see section “Contraindications”) and is not recommended in patients with moderate hepatic impairment, as there is currently insufficient data to determine whether a dose adjustment is necessary in such cases. Due to the intensive metabolism of efavirenz under the action of the cytochrome P 450 system and limited clinical experience with the use of efavirenz in patients with chronic liver disease, the drug should be prescribed with caution to patients with mild hepatic impairment (see the section “With caution”). At the same time, patients should be monitored for timely detection of dose-dependent adverse reactions, especially from the nervous system. Also, laboratory tests should be performed at certain intervals to assess the condition of the liver.

The safety and efficacy of efavirenz have not been confirmed in patients with a history of significant hepatic impairment. Patients with chronic hepatitis B and C taking combination antiretroviral therapy (ART) are at risk of developing severe adverse liver reactions that can lead to death. Patients with a history of hepatic impairment, including chronic active hepatitis, have an increased incidence of hepatic impairment in combination ART, so these patients should be monitored according to the standard regimen. In patients with a worsening course of liver disease or with a sustained increase in serum transaminase activity exceeding more than 5 times the upper limit of normal, the benefit of continuing efavirenz therapy should be compared with the possible risk of hepatotoxicity. In such patients, consideration should be given to discontinuing or discontinuing ART.

With the simultaneous use of other drugs with known hepatotoxicity, it is recommended to monitor the activity of” liver ” enzymes. Patients with hepatitis B or C should also follow the instructions for use of the prescribed drugs for the treatment of hepatitis B or C when prescribing combined antiviral therapy.

Renal insufficiency: the pharmacokinetics of efavirenz in patients with renal insufficiency have not been studied, however, due to the fact that less than 1% of the amount of efavirenz is excreted unchanged by the kidneys, impaired renal function should not significantly affect the elimination of efavirenz.

There is no experience of use in patients with severe renal insufficiency, so monitoring is recommended for this group of patients when using the drug in order to assess the safety of therapy.

Elderly patients: since a small number of elderly patients were included in clinical trials, it is not possible to assume that the effect of the drug on elderly patients differs from that in young patients (see section Pharmacokinetics).

Children: the use of efavirenz in children under 3 years of age or weighing less than 13 kg has not been studied. There is evidence that the pharmacokinetics of efavirenz may be altered in very young children.

Seizures: Seizures were extremely rare in patients treated with efavirenz, including patients with a history of seizures. In patients receiving concomitant anticonvulsants with a predominant metabolism in the liver, such as phenytoin, carbamazepine and phenobarbital, their plasma concentrations should be periodically monitored. Caution should be exercised when prescribing the drug to patients with a history of seizures (see sections “With caution” and “Side effects”).

“Liver “enzymes: in patients with a history of diagnosed or suspected hepatitis B and C and patients taking drugs associated with toxic effects on the liver, it is recommended to regularly monitor the activity of” liver ” enzymes. In patients with a sustained increase in serum transaminase activity exceeding 5 times the upper limit of normal, the benefit of continuing efavirenz therapy should be compared with the possible risk of hepatotoxicity (see section “Side effects”).

Cholesterol: Blood cholesterol levels should be monitored in patients taking efavirenz (see section “Side effects”).

Interaction with the cannabinoid test: efavirenz does not bind to cannabinoid receptors, but there have been reports of false-positive urinalysis results for cannabinoids in uninfected volunteers treated with efavirenz. False positive test results were observed only when performing the CEDIA DAU Multi-Level TIS assay, which is used for screening, and were not observed when performing other cannabinoid tests, including tests used to confirm positive results.

Influence on the ability to drive vehicles and mechanisms

No studies have been conducted to investigate the impact on the ability to drive a car and work with devices. Efavirenz may cause dizziness, impaired attention, and / or insomnia. Patients should be warned that if they develop any of these symptoms, they should avoid driving a car or operating devices.

Storage conditions

In the original manufacturer’s packaging at a temperature not exceeding 25 °C. Keep out of reach of children.

Shelf

life is 2 years. Do not use after the expiration date indicated on the package.

Active ingredient

Efavirenz

Conditions of release from pharmacies

By prescription

Dosage form

Tablets