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

lactose monohydrate - 340.0 mg; cellulose microcrystalline - 212.0 mg; sodium carboxymethyl starch - 26.0 mg; poppedon-K30 - 6.0 mg; silicon dioxide colloidal - 8.0 mg; magnesium stearate - 8.0 mg.

Description:

Oval biconvex tablets, white or almost white in color. On one side of the tablet are engraving "C" and "35" and between the risk, on the other side of the tablet is only a risk.

Pharmacotherapeutic group:Antiviral | HIV | means

ATX: & nbsp

J.05.A.G.01 Nevirapine

Pharmacodynamics:

Nevirapine is a non-nucleoside reverse transcriptase inhibitor (NNRTI) of HIV-1. Nevirapine directly binds to reverse transcriptase and blocks the activity of RNA-dependent and DIC-dependent DNA polymerase, causing destruction of the catalytic site of this enzyme. Do not compete with matrix or nucleoside triphosphates. Nevirapine does not inhibit HIV-2 reverse transcriptase and DNA polymerase of eukaryotic cells (such as human DNA polymerase alpha, beta, gamma or sigma-DNA). In combination with other antiretroviral drugs, it reduces viral load and increases the number of CD4 + cells. With monotherapy, resistance develops rapidly. In vitro cross-resistance develops with other non-nucleoside reverse transcriptase inhibitors.

Pharmacokinetics:

Nevirapine is well (> 90%) absorbed after ingestion. Absolute bioavailability is 93%. After a single dose of 200 mg, the maximum concentration (Cmax) was 1.6 - 2.4 μg / ml, the time to reach the maximum concentration (TCmax) was 4 hours. After repeated administration of the drug at doses of 200 to 400 mg / day, the maximum concentration of nevirapine increased linearly depending on the dose.When taken 400 mg at day, the equilibrium Cmax of nevirapine was 7.44 μg / ml. area under the curve "concentration - time" (AUC) -109 μg / ml / h.

Nevirapine has a high lipophilicity and is practically not ionized at physiological pH. Nevirapine well penetrates the placental barrier and into breast milk. The binding of nevirapine to plasma proteins is about 60%. The concentration of nevirapine in the cerebrospinal fluid in humans is 45% of the plasma concentrations.

Nevirapine is intensively biotransformed by metabolism (oxidation reaction) with the participation of cytochrome P450 isoenzymes to several hydroxylated metabolites. Oxidative metabolism of nevirapine is carried out, mainly, with the help of cytochrome P450 isoenzymes from the family CYP3A, Additional isozymes may play an additional role. Further nevirapine is conjugated with glucuronidamine. Eliminated mainly by the kidneys - 70.2 - 92.4% (less than 3% in the form of unchanged substance), to a lesser extent the intestines - 8,6 - 11,6%. Nevirapine is the inducer of microsomal liver enzymes. As a result of the autoinduction of metabolism, the terminal period of the half-life (T_1/2) decreases from 45 hours (with a single dose) to 25-30 hours (with repeated administration).

Floor

Clearance in women is 13.8% lower than in men. The pharmacokinetics of nevirapine in HIV-1-infected adult patients does not change with age (range 18-68 years) or race (Negroid, Latin American or Europoid race).

Lack of kidney function

In patients with chronic renal failure (CRF), the pharmacokinetics do not change, but with terminal CRF, requiring dialysis, AUC nevirapine decreased by 43.5%. There is a cumulation of hydroxystabolites in the plasma, therefore, adult patients are recommended an auxiliary therapy with nevirapine, after using each dialysis session, an additional dose of 200 mg, which compensates for the effect of dialysis on the clearance of the drug.

Lack of liver function

Nevirapine should not be used in patients with severe severity of liver function disorders (Child-Pugh class C).

Patients with mild to moderate hepatic impairment (class A and B according to Child-Pugh classification) do not require dose selection, but such patients need careful monitoring to register unwanted drug reactions.

Indications:

Treatment of HIV 1 infection in adults (as part of combination therapy with other antiretroviral drugs).

Contraindications:

- Increased sensitivity to nevirapine and / or drug components;

- Children under 18 and over 65;

- Weight less than 50 kg or body surface area less than 1.25 square meters;

- Violation of the liver function of severe severity (class C according to the Child-Pugh classification) or in the case of an initial increase in activity of aspartate aminotransferase (ACT) or alanine transferase (ALT), more than 5 times the upper limit of the norm, until the ACT / ALT activity decreases (steady) to a level that does not exceed the upper limit of the norm by a factor of 5:

- Re-appointment to patients who had previously, during treatment with nevirapine, required its withdrawal due to severe rash, hypersensitivity reactions or the development of clinically expressed hepatitis caused by nevirapine; there was an increase in activity ACT or ALT exceeding the upper limit of the norm more than 5 times, after repeated use of nevirapine, there was a renewal of liver function abnormalities;

- Simultaneous use with preparations of St. John's wort perfumed (Hypericum perforatum) (due to the risk of reducing plasma nevirapine and reducing its clinical effect); with rifampicin; with itraconazole, ketoconazole; with efavirenz, delaverdin, etravirine, rilpivirin, atazapavir / ritonavir, fosamprenavir, saquinavir, atazanavir (when not used together with low-dose ritonavir), bocepreviram, elvitegravir (together with cobicystate);

- Hereditary intolerance to galactose, deficiency of lactase or glucose-galactose malabsorption.

Carefully:

Violation of liver function of mild and moderate severity (class A and B according to the Child-Pugh classification); concomitant use with rifabutin, fluconazole, itraconazole, telaprevir, warfarin, methadone, lopinavir / ritonavir, clarritomycin, ethinylesteadiol, indinavir.

Pregnancy and lactation:

Comprehensive controlled studies of treatment in HIV-1-infected pregnant women have not been carried out to date. Nevirapine should be used during pregnancy only in cases where the potential benefit to the mother outweighs the potential risk to the fetus.

The safety and efficacy of nevirapine, used to prevent mother-to-child transmission of HIV-1, was established when the drug was used as part of a therapy regimen that included a single oral dose of 200 mg by the mother during labor.

According to the WHO recommendation, that HIV-infected mothers should not breast-feed newborns (to avoid the risk of postnatal HIV transmission), mothers who receive nevirapine, should stop breastfeeding.

Dosing and Administration:

Inside.

Nevirapine may be taken regardless of the intake of the food.

The drug should be taken only and combinations with at least two additional antiretroviral drugs (it is necessary to be guided by the information stated in the instructions for the use of a particular drug).

To reduce the incidence of skin rash, adults should take only one dose of the drug per day for the first 14 days ("introductory period"). If skin rash develops in this period, you should immediately consult a doctor for advice and do not raise the vine.

One tablet (200 mg) daily for the first 14 days (use of this initial period is necessary, since it is determined that the frequency of the development of the rash is reduced), and in the following, but one tablet (200 mg) 2 times a day. The maximum daily dose should not exceed 400 mg.

With XPS with creatinine clearance (CC) ≥ 20 ml / min, no dose adjustment is required. Patients with XPS, who undergo dialysis, are additionally assigned 200 mg after the procedure.

If the liver function is mild and moderate in severity (class A and B according to the Child-Pugh classification), dose adjustment is not required.

The dosage regimen in individuals. over 65 years of age is not established.

If the drug is missed for 8 hours, the patient should not double the next dose, the missed dose should be taken as soon as possible. If the dose is missed for more than 8 hours, the patient should take the next dose at the usual time.

Patients who, during the 14-day initial period of daily intake of the drug at a dose of 200 mg at day marked rash, should not increase the dose until then. until the rash disappears. However, more than 28 days nevirapine in a dose of 200 mg / day do not apply (alternative therapy is required).

Patients who stopped taking Nevirapine for more than 7 days should resume using the recommended regimen, that is, take the drug at a dose of 200 mg once a day (initial period), and then one tablet 200 mg 2 times a day.

Prevention transmission of HIV from mathoseRand to kid.

The following dosing regimen for pregnant women is recommended: a single dose of 200 mg as soon as possible after the onset of labor.

Patients with impaired renal function

Patients with a terminal stage of renal failure (creatinine clearance less than 20 ml / min) requiring dialysis are encouraged to use nevirapine supplementation with an additional 200 mg dose after each dialysis session. Patients who have creatinine clearance in excess of 20 ml / min do not need a dose adjustment for nevirapine.

Insufficiency of liver function

Patients with mild to moderate hepatic impairment (class A and B according to Child-Pugh classification) do not need a dose selection; careful monitoring is necessary for these patients to register unwanted drug reactions.

Side effects:

The most frequent adverse events were rash, allergic reactions, change in the indication function liver, nausea, fatigue, fever, headache, vomiting, diarrhea, abdominal pain and myalgia.

Adverse events probably associated with nevirapine therapy occurred with the following frequency: very often (≥1 / 10). often (≥1 / 100; <1/10); infrequently (≥1 / 1000; <1/100), rarely (≥1 / 10000: 1/1000). very rarely (<1/10000).

From the laboratory indicators:

Often: changes in liver function (increased activity ACT, ALT, GGT, increased total bilirubin, alkaline phosphatase); infrequently - hypophosphatemia;

From the system of blood and blood-forming organs:

Often: granulocytopenia

Infrequently: anemia:

From the nervous system:

Often: headache;

From the side digestive systems:

Often: nausea, vomiting, diarrhea, abdominal pain;

From the skin and subcutaneous fat:

Very common: rash

Infrequently: the syndrome (Ctivens-Johnson / toxic epidermal necrolysis (which can lead to death), angioedema, hives;

From the side musculoskeletal system:

Often: myalgia

Infrequently: arthralgia:

From the immune system:

Often: allergic reactions (including angioedema, hives); rarely - medicinal rash, accompanied by eosinophilia and general symptoms, anaphylaxis;

From the hepatobiliary system:

Often: hepatitis, including serious and life-threatening hepatotoxicity;

Infrequently: jaundice

Rarely: fulminant hepatitis (including fatal outcome);

From the side of the cardiovascular system:

Infrequent - increased blood pressure;

Other:

Often: fever, fatigue:

Against the background of combination antiretroviral therapy observed redistribution of subcutaneous fat (thinning of the subcutaneous tissue of the face and in the periphery, and its increase in the abdomen and internal organs, breast and abdomen, hypertrophy of the mammary glands): Metabolic disorders: hypertriglyceridemia, hypercholesterolemia, nnsulniorezistentnost, hyperglycemia and hyperlactatemia, pancreatitis , peripheral neuropaththia, thrombocytopenia, neutropenia.

Postmarketing an experience: drowsiness; vomiting; jaundice, severe hepatitis, hepatic insufficiency, liver necrosis: anemia, eosinophilia, neutropenia; hypophosphatemia; arthralgia, rhabdomyolysis; paresthesia; kidney damage; increased blood pressure; a syndrome of reactivity of immunity; osteonecrosis.

Overdose:

Symptoms: edema, erythema nodosum. fatigue, fever, headache, insomnia, nausea, pulmonary infiltrates, rashes, vertigo, vomiting, increased activity of "liver" transaminases, weight loss.

Treatment: withdrawal of nevirapine, antidote is not known.

Interaction:

Is the inducer of isofermings CYP3A and potentially isoenzymes CYP2B6, maximum induction is observed within 2-4 weeks after initiation of therapy. It can lead to a decrease in plasma concentrations of other concomitantly used drugs, which are intensely destabilized by isoenzymes and CYP3A or isoenzymes CYP2B6.Esland in a patient who has previously been treated with a dosage regimen of a drug metabolized with an isoenzyme CYP3A or CYP2B6, treatment with nevirapine begins, it may be necessary to adjust the dose of this drug. Maximum induction is observed within 2-4 weeks after the initiation of therapy.

The intake of food, antanids and preparations with alkaline buffer medium does not affect the absorption of nevirapine.

NucleosideMr.th Analogues. With the simultaneous use of nevirapine with nucleoside reverse transcriptase inhibitors (didanosine 100-150 mg twice a day; Limivudio 150 ml 2 times a day, stavudine 30/40 mg 2 times a day, tenofovir 300 mg per day, zidovudine 100-200 mg 3 times a day; zalcitabine 0,125 - 0.25 mg 3 times a day, emtricitabine and abacavir) correction of the dosage regimen of nevirapine is not required.

Nenukleoanalogues. It is not recommended simultaneous use with the following non-nucleoside reverse transcriptase inhibitors: efavirenz 600 mg / day (accumulation of toxicity, lack of additive effect, decrease AUC, minimal concentrates (Cmin) and Cmax efavirenz), delavirdine, etravirine (a significant decrease in etravirin in the plasma and a decrease in its effectiveness), rilpivirin.

IngebHIV protease inhibitors. Simultaneous application atazanavir / ritonavir in combination with nevirapine is contraindicated. When using this combination (nevirapine with atazanavir / ritonavir in a dose of 400/100 mg 2 times a day) there is a decrease AUC, Cmin and C max atazanavir and an increase AUC, Cmin and Cmax nevirapine.

The simultaneous use of nevirapine with fosamprenavir 1400 mg 2 times a day leads to a decrease AUC, Cmin and Cmax fosamprenavir, increasing AUC, Cmin and Cmax of nevirapine, therefore simultaneous application of this combination is contraindicated in the case of the treasure, it is not used in conjunction with a low dose of ritonavir.

When used concomitantly with the following non-nucleoside reverse transcriptase inhibitors: dronavir / ritonavir 400/100 mg twice a day; fosamprenavir / ritonavir 700/100 mg twice a day; nelfinavir 750 mg 3 times a day; ritonavir 600 mg 2 times at day; saquinavir / ritonavir, tipranavir /ritonavir 500/200 mg 2 times a day correction, dosing regimen is not required.

When used simultaneously with lopinavir / ritonavir 400/100 mg 2 times a day, they need to be increased dose to 533/133 mg (4 capsules) or 500/125 mg (5 tablets of 100/25 mg) 2 times a day, dosage adjustment of nevirapine is not required.

IngibitorIntegrationShl. When used simultaneously with HIV integrase inhibitors (raltegravir 400 mg twice a day) correction of the dosing regimen is not required.

Joint use of nevirapine and elvitegravir (in combination with a cobicystate)but. Kobitsystat is an inhibitor of cytochrome P4503A, so joint use is likely to lead to a change in the concentration of the cobicystate and nevirapine at plasma.

Inghibitters mergers. With simultaneous application of fusion inhibitors (enfuvirtide, miroviroc 300 mg/ day) correction of the dosing regimen is not required.

Inghibitors ncompanyBasics. When used simultaneously with indinavir there is a decrease in its concentration, there are no corresponding doses for this combination, but an increase in the dose of indinavir may be necessary.

Other antiviral drugsratas.

Boceprevir is partially metabolized by isoferments CYP3A4, so the simultaneous use Bocetrevir with drugs that are inducers or inhibitors CYP3A4 may lead to an increase or decrease in the exposure of bocestrevir. There was a decrease in plasma concentrations of boceprevir with simultaneous administration with NNRTIs having the same metabolic pathways as nevirapine. The clinical significance of reducing the concentrations of bocetrephir was not assessed. The simultaneous use of boceprevir and nevirapine is not recommended.

Adefovir. In vilro identified a weak antagonism between nevirapine and adefovir. In clinical trials, this interaction is not confirmed, a decrease in efficacy is not expected. Adefovir does not affect the cytochrome P450 isoenzymes involved in the metabolism of drugs, and is excreted by the kidneys. It is not expected clinically significant interaction with the simultaneous administration of nevirapine and adefovir. Correction of the dosing regimen is not required.

Entecavir. Taking into account the peculiarities of metabolism (entecavir is not a substrate, an inductor or an inhibitor isoenzymes of cytochrome P450), clinically significant pharmacokinetic interactions between entecavir and nevirapine are not expected. At the same time, the administration of nevirapine and entecavir does not require correction of the dosing regimen.

Ribavirin. Ribavirin is an inducer or inhibitor of cytochrome P450 isoenzymes, clinically significant pharmacokinetic interactions between ribavirin and nevirapine are not expected. With simultaneous use of nevirapine and ribavirip, correction of the dosing regimen is not required.

Telaprevir. Telaprevir is mainly metabolized in the liver by isophosphate CYP3A4, and is also a substrate of P-glycoprotein. Medicines that are inducers CYP3A4 or P-glycoprotein, can reduce the concentration of telaprevir in the blood plasma. When concomitant use of telaprevir with other NNRTIs having the same pathways metabolism, as nevirapine (eg, efavirenzem), there is a decrease in the concentration of telaprevir in plasma. With simultaneous use of nevirapine with telaprevir, care should be taken, correction of doses of telaprevir is possible.

Telbivudine. Taking into account the peculiarities of metabolism (telbivudine is not a substrate, inducer or inhibitor of cytochrome P450 isoenzymes), clinically significant pharmacokinetic interactions between telbivudine and nevirapine are not expected. With simultaneous use of nevirapine and telbivudine correction of the dosing regimen is not required.

Pegulterated iterferons alfa-2a and alpha-2b. No effect of interferons on isomer activity CYP2B6, CYP3A4. Therefore, clinically significant interaction between pegylated interferons alpha-2a and alpha-2b and nevirapine is not expected. With the simultaneous use of nevirapine with these drugs, correction of the dosing regimen is not required.

Indusisofermentation agents CYP450. Has no significant effect on the pharmacokinetic parameters rifabutin (150 mg / day or 300 mg / day), however, due to high fluctuations in the concentration of the latter in different individuals, there may be a significant increase in AUC, which requires caution in the simultaneous use of rifabutin and nevirapine. Simultaneous application with rifampicin (600 mg / day) is not recommended and offor a significant reduction AUC, Cmin and Cmax nevirapine, it is recommended to switch to rifabuin.

Inghiisoenzyme inhibitors CYP 450. Significantly reduces AUC, Cmin and Cmax clerkicicle (500 mg twice a day) and increases AUC and Cmax of its metabolite - 14 - hydroxyclatromycin: since the latter shows less activity with respect to the complex Mycobacterium aviumintracellulare, It is necessary to consider the possibility of switching to azithromycin; it is additionally recommended to monitor liver function.

As a result of the increase AUC, Cmin and Cmax nevirapine in 2 times with simultaneous application with fluconazole (200 mg / day) should be careful. When used simultaneously with itraconazole (200 mg / day) may require an increase in the dose of the latter. Nevirapine and itraconazole It should not be administered concomitantly with a potential decrease in plasma concentration itraconazole . Simultaneous application with ketoconazole (400 mg / day) is not recommended (decrease AUC, Cmin and Cmax ketoconazole and an increase in these parameters in nevirapine). Ketoconazole and erythromycin significantly inhibit the formation of hydroxylated nevirapine metabolites.

At simultaneous application with antacids / cimetidine correction of the dosing regimen is not required.

AntIcoagulants. When used simultaneously with warfarin it is necessary to strengthen control over blood coagulation indicators.

Medroxyprogesterone. With the simultaneous use of e-medroxyprogesterone (depot form, 150 mg every 3 months), correction of the dosing regimen is not required.

Oral contraceptives. When used concomitantly with oral contraceptives containing ethinyl estradiol (0.035 mg) or norethisterone (1 mg / day), additional contraceptive methods should be used. With simultaneous use of nevirapine with medroxyprogesterone (depot form, 150 mg every 3 months), dose changes are not required.

Methadone. When concomitant use with methadone should be borne in mind the possibility of development of withdrawal syndrome, which may require a dose adjustment for methadone.

Delayed perforated. Simultaneous use with drugs containing St. John's Wort is contraindicated. If the patient is already taking these medications, you should check the concentration of nevirapine and, if possible, the activity of the virus, and stop using preparations containing St. John's Wort extract. After their withdrawal, the concentration of nevirapine may increase. You may need to change the dose of the drug Nevirapine. After discontinuation of medications containing the herb extract of St. John's Wort, the inductive effect may persist for as long as min. 2 weeks.

Special instructions:

Nevirapine does not cure HIV-1 infection; patients may have diseases associated with the progression of HIV-1 infection, including. infections caused by opportunistic flora.

No reduces the risk of infection of other persons with HIV-1 during sexual contact or in case of ingestion virus in the blood.

It is necessary to take the drug every day.If the drug is missed for 8 hours, the patient should not double the next dose, the missed dose should be taken as soon as possible. If the dose is missed for more than 8 hours, the patient should take the next dose at the usual time.

Nevirapine should not be used as a monotherapy for the treatment of HIV infection or should be added as a single drug to a regimen of therapy that is not effective (rapid development of resistance).

When selecting new antiretroviral drugs, which are use in combination with nevirapine, the possibility of developing cross-resistance should be taken into account. In the event of the cancellation of antiretroviral therapy containing nevirapine, it is necessary to bear in mind its long T_1/2.

Critical importance first 18 weeks of therapy with nevirapine. During this period, careful monitoring of patients is required to identify possible severe and life-threatening skin reactions (including Stevens-Johnson syndrome and toxic epidermal necrolysis) or severe hepatitis / liver failure. The greatest risk gephatological and dermatological reactions exist in the first 6 weeks of therapy. The risk of adverse events on the part of the liver is increased in women and in patients with a higher number Cd4+ cells. It is necessary to strictly adhere to the recommended regimen of therapy, especially during the initial 14-day period.

Reactions about the skin side. In patients who received nevirapine, there were serious and life-threatening dermatological reactions, including fatalities. There were cases of the syndrome Stevensa-Johnson (SDS), toxic epidermal necrosis (TEN) and hypersensitivity syndrome, characterized by a rash, general reactions and internal organs damage. Careful observation of patients during the first 18 weeks of treatment is necessary. Careful observation is required in the case of development of an isolated rash. Nevirapine must abrogate Any patient who develops a severe rash or rash accompanied by common symptoms (fever, blistering, changes in the oral cavity, conjunctivitis, facial swelling, joint or muscle pain, general malaise), Stevens-Johnson syndrome or toxic epidermal necrolysis. Nevirapine should be withdrawn and should not be prescribed again in any patient in the case of development of hypersensitivity reactions characterized by a rash and general symptoms, as well as changes in internal organs, including hepatitis, eosinophilia, granulocytopenia and renal dysfunction, or other signs of failure of internal bodies.

Patients should be informed that the main manifestation of the toxicity of nevirapine is a rash. An initial treatment period should be used, since it is determined that this reduces the incidence of the rash. In most cases, a rash that is associated with taking a nepiscine occurs in the first 6 weeks of therapy. Therefore, during this period, careful monitoring of patients with dermatological reactions. Patients should be informed that if any rash develops during the initial treatment period, the dose should not be increased until the rash disappears. The dosage regimen using 200 mg of the drug once a day should not last more than 28 days, at which point a different regimen should be developed.

It was shown that simultaneous application of prednisone (40 mg / day, during the first 14 days of taking nevirapine) does not reduce the incidence of rash, but, on the contrary, it can increase dermatological reactions during the first 6 weeks of therapy.

Among the actors at risk of developing serious skin reactions is a violation of the recommendation on the use of the drug at a dose of 200 mg per day during the initial period of therapy. The risk of developing more serious outcomes of dermatological reactions increases in the case of delayed treatment za medical advice after the onset of symptoms.

Reactions from the liver. Patients treated with nevirapine experienced serious or life-threatening hepatotoxicity, including fatal fulminant hepatitis. Critical is the first 18 weeks of treatment, during which careful monitoring is necessary. The highest risk of reactions from the liver is noted in the first 6 weeks of therapy. An increased risk of unwanted hepatological reactions is observed in women and patients with a higher number Cd4 cells. This risk persists in the future, so frequent monitoring should continue throughout the treatment.It is necessary to inform patients that reactions from the liver are the main type of nevirapine toxicity and that the appearance of signs indicating the development of hepatitis should be an occasion for prompt consultation with the doctor.

A higher risk of unwanted reactions from the liver during any antiretroviral therapy, including during the application of regimens that include nevirapine, is noted at the initial increase in activity ACT or ALT by more than 2.5 times compared with the upper limit of the norm and / or in the presence of hepatitis B and / or C. The risk of developing typological reactions associated with a rash in women is three times higher than that of men. The risk of developing hepatological reactions associated with a rash in the treatment of nevirapine may also be higher in patients with a higher number Cd4+ cells. According to a retrospective analysis, in women with a number Cd4+ cells more than 250 cells / mm³, the risk of hepatological reactions associated with a rash was 9 times higher than in women with a number Cd4+ cells less than 250 cells / mm³ . Increased risk was observed in men with a number Cd4+ cells> 400 cells / mm³ compared with men with a number Cd4+ cells <400 cells / mm³. Nevirapine should not be given to women with a number of CB4 + lymphocytes more than 250 in 1 mm³, and men with a number Cd4+ lymphocytes more than 400 in 1 mm³, in which the plasma is determined RNA HIV-1, unless the benefit of taking the drug does not exceed the risk of developing side effects.

Monitoring the liver. With the use of nevirapine, it was reported changes in liver function indicators, sometimes occurring in the first weeks of therapy. The asymptomatic increase in the activity of liver enzymes is described often and is not an unconditional contraindication for the use of nevirapine. Asymptomatic increase in the activity of gamma-glutamyl transferase is not a contraindication to the continuation of therapy.

It is recommended to strictly monitor liver function indicators at short intervals, at depending on the clinical condition of the patients, especially during the first 18 weeks of treatment. Clinical and laboratory monitoring should continue throughout the treatment period with nevirapine. Doctors and patients should be wary of such prodromal signs or symptoms of hepatitis, as anorexia, nausea, jaundice, bilirubinemia, achiolic stool, hepatogemia or liver tenderness.Patients should be informed of the need to seek medical advice in such cases.

In case of increased activity ACT or ALT is more than 2.5 times higher than the upper limit of the norm before or during treatment, liver function indicators should be checked more often during regular clinical visits.

Nevirapine should not be given to patients who have a baseline ACT or ALT more than 5 times exceeds the upper limit of the norm (until it steadily decreases to a level less than 5 times that of UGN).

If AST or ALT increase more than 5 times higher than ULN during treatment, nevirapine must be immediately canceled. Level ACT and ALT return to baseline values and if the patient does not experience any clinical signs or symptoms of hepatitis, general symptoms, or other phenomena that indicate impairment of function internal organs, the use of nevirapine may be resumed (herwhether there is a clinical need). A decision on this should be made in each case, based on clinical considerations.Repeated administration of nevirapine should be performed under conditions of increased clinical and laboratory alertness, at an initial dose of 200 mg / day (for 14 days), followed by her increase to 400 mg / dei. If violations of liver function are resumed, nevirapine must be finally canceled.

If hepatitis occurs, accompanied by clinical manifestations such as anorexia, nausea, vomiting, jaundice, and laboratory disorders (moderate or significant changes indicators of liver function, without GGT), nevirapine must be canceled finally. Nevirapine should not be given again to those patients who required his withdrawal because of the development of clinically expressed hepatitis caused by nevirapine.

Diseases of the liver.

Nevirapine is extensively metabolized in the liver, and nevirapine metabolites are excreted mainly by the kidneys. The results of pharmacokinetic studies indicate the need for caution in the appointment of nevirapine to patients with impaired liver function of moderate severity (class B according to the Child-Pugh classification). Nevirapine should not be administered to patients with severe liver failure (class C according to Child-Pugh classification).

The risk of hepatoxic effect of antiretroviral prenaracters in patients with co-infected HIV infection and the hepatitis B or C virus is higher than in the presence of only HIV infection. Therefore, patients with chronic hepatitis B or C who at the same time take antiretroviral drugs are in the group of increased adverse effects on the liver with possible fatal outcome. these patients should be carefully monitored, both clinical and laboratory.

A higher risk of adverse reactions from the liver during any antiretroviral therapy, incl. and during the application of regimes including nevirapine, are observed in patients with underlying liver diseases receiving nevirapine in combination antiretroviral therapy, careful monitoring should be conducted; if signs of impaired liver function appear, consideration should be given to the possibility of interrupting or canceling therapy.

Rhabdomyolysis. In rare cases, in patients with skin and liver reactions associated with the use of nevirapine, rhabdomyolysis was observed. Patients should be warned that at the first sign of muscle pain and weakness or darkening of urine, stop taking the medication immediately and consult your doctor to determine activity of creatine kinase in the blood.

Osteonecrosis. Although the etiology of osteonecrosis is multifactorial, there are reports of such cases, especially in patients with progressive HIV infection /or long-term antiretroviral therapy. Patients should seek medical advice from a physician if symptoms such as lethargy, stiffness, joint pain or difficulty with movement occur.

Lipodystrophy. In patients receiving antiretroviral therapy, there was a redistribution / titration of fatty tissue, including obesity of the central type, an increase in the deposition of fatty tissue in the dorsocervical region ("buffalo buffalo"), a decrease in the volume of peripheral adipose tissue, a reduction in subcutaneous fat in the face, mammary hypertrophy, and a "cushingoid appearance."The mechanism of development and the long-term consequences of these effects are currently unknown, their causal relationship with the use of certain anti-retroviral drugs are not established.

Recovery Syndrome immunity. At the beginning of treatment with antiretroviral agents HIV-infected patients with severe immunodeficiency may exacerbate the inflammatory process against a background of asymptomatic opportunistic infection or its residual phenomena, which can cause serious deterioration of the condition or exacerbation of symptoms. Usually such reactions are observed during the first weeks or months after initiation of antiretroviral therapy. For example, a cytomegalovirus retinitis, generalized and / or focal mycobacterial and pneumocytosistnpneumonia (P.Carinii). Any symptoms of inflammation should be immediately identified and if necessary begin treatment.

Autoimmune diseases (such as Graves' disease, polymyositis and Guillain-Barre syndrome) were observed against the background of restoration of immunity, however, the time of primary manifestation varied, and the disease could occur many months after initiation of therapy and have an atypical course.

Other caveats. In the case of the use of nevirapine in combination with other antiretroviral drugs, the development of such undesirable reactions as pancreatitis, peripheral neuropathy, and thrombocytopenia has also been reported. These phenomena are often associated with other antiretroviral drugs. Their occurrence can be expected with the use of nevirapine in combination with other drugs; The likelihood of communication of any reactions with the use of nevirapine is low.

In patients receiving nevirapine or any other antiretroviral therapy, can continue to develop opportunistic infections and other complications of HIV infection. Therefore, such patients should remain under close clinical supervision of physicians with experience in the treatment of diseases associated with HIV infection. Information on the ability of nevirapine to reduce the risk of horizontal transmission of HIV-1 to others is not available.

Despite the fact that the ability of nevirapine to prevent mother-to-child transmission of HIV-1 is established (in women who have not received other antiretroviral drugs) to minimize the possible and transmit HIV-1 to a child,It is recommended more intensive treatment of the mother before delivery with the use of combinations of antiretroviral drugs (where possible).

In women receiving nevirapine, oral contraceptives and other hormonal methods should not be used as the main contraceptive method, since nevirapine can reduce the concentration of these drugs in the plasma. In addition, if oral contraceptives are used during therapy with nevirapine, gOrmal regulation, control over the therapeutic effect of hormonal treatment is necessary.

Pharmacokinetic studies performed in patients with impaired renal function on hemodialysis showed that adjuvant therapy with nevirapine supplemented with a dose of 200 mg after each dialysis session can help offset the effect of dialysis on nevirapine clearance. Thus, in patients with creatinine clearance greater than 20 ml / min, no dosage changes of nevirapine are required.

(Existing data of pharmacokinetic studies indicate the inexpediency of simultaneous use of rifampicin and nevirapine.If it is necessary to treat concomitant tuberculosis in patients receiving treatment, including nevirapine, can consider the possibility of riabutin. Riabutyne and nevirapine can be used together without changing the dosing.

Granulocytopenia. The risk of developing granulocytopenia is increased in patients receiving concomitantly nevirapine and zidovudine (especially in patients receiving zidovudine in high doses and patients with a reduced reserve of bone marrow). Such patients need careful monitoring of hematological parameters.

Effect on the ability to drive transp. cf. and fur:

Special studies in relation to the ability to drive vehicles and management of theMami was not conducted. If patients experience fatigue, they should avoid management vehicles and other potentially dangerous species activities that require increased concentration of attention and speed psychomoreactions.

Form release / dosage:

Tablets 200 mg.

Packaging:

For 60 tablets in white polyethylene bottles,Sealed with a screwed polypropylene lid on the inner side of the center with a round cylindrical cavity with tight paper, and sealed with aluminum foil. Each bottle contains a sealant made of cotton wool. One bottle together with the instruction for use is placed in a cardboard box.

For 10 tablets blister of PVC film / aluminum foil. Two blisters together with instructions for use are placed in a cardboard box.

Storage conditions:

In a dry place protected from light, at a temperature not exceeding 30⁰FROM. Keep out of the reach of children.

Shelf life:3 years. Do not use after the expiry date.

Terms of leave from pharmacies:On prescription

Registration number:LP-003018

Date of registration:02.06.2015

Expiration Date:02.06.2020

The owner of the registration certificate:Aurobindo Pharma Co., Ltd.Aurobindo Pharma Co., Ltd. India

Manufacturer: & nbsp

AUROBINDO PHARMA, Ltd. India

Representation: & nbspAurobindo Pharma, ZAOAurobindo Pharma, ZAO

Information update date: & nbsp26.06.2018

Illustrated instructions

Instructions

Nevirapine (Nevirapine)