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

Carbomir - 2,1 mg, polysorbate-80 - 0,5 mg, sorbitol-70 - 231,3 mg, sucrose - 150 mg, methylparahydroxybenzoate - 1,8 mg, propyl parahydroxybenzoate - 0.24 mg, sodium hydroxide - 0.35 mg, purified water - up to 1 ml.

Description:

White or almost white homogeneous suspension.

Pharmacotherapeutic group:Antiviral [HIV] agent

ATX: & nbsp

J.05.A.G.01 Nevirapine

Pharmacodynamics:

Nevirapine is a non-nucleoside reverse transcriptase inhibitor (NNRTI) of human immunodeficiency virus type 1 (HIV-1). Nevirapine directly binds to reverse transcriptase and blocks the activity of RNA-dependent and DNA-dependent DNA-polysmorph, causing destruction of the active center of this enzyme. Nevirapine Do not compete with matrix triphosphates or nucleoside triphosphates. Nevirapine does not inhibit HIV-2 reverse transcriptase and DNA polymerase of eukaryotic cells (such as human DNA polymerase α, β, γ or σ).

Nevirapine should not be used as a monotherapy for the treatment of HIV infection or added as a single drug to the regimen of therapy that is ineffective. When nevirapine is used as a monotherapy, the stability of the virus rapidly develops, which is typical for all other non-nucleoside and reverse transcriptase inhibitors.

When choosing new antiretroviral drugs, which are supposed to be used in combination with nevirapine, data should be taken into account the possibility of developing cross-resistance.

With the abolition of the antiretroviral regimen of therapy containing nevirapine, it is necessary to take into account the long half-life of this drug. If antiretroviral drugs with shorter half-lives are reduced at the same time, then due to low concentrations of nevirapine that persists for a week or more, resistance to HIV can develop.

Pharmacokinetics:

Adults

Nevirapine is well (> 90%) absorbed when taken orally. Absolute bioavailability after single dose application is 50 mg - 93 ± 9% for tablets and 91 ± 8% for oral solution. Maximum concentration (C_max) nevirapine in plasma after a single dose of the drug at a dose of 200 mg was determined after 4 hours and was 2 ± 0.4 μg / ml (7.5 μmol). After repeated administration of the drug in doses from 200 to 400 mg / day, the maximum concentration (C_max) of nevirapine increased linearly, depending on the magnitude of the dose. The equilibrium concentration when taking the drug at a dose of 400 mg / day was 4.5 ± 1.9 μg / ml (17 ± 7 μmol).

Nevirapine has a high lipophilicity and is practically not ionized at a physiological pH. After intravenous administration to healthy adult volunteers, the equilibrium volume of nevirapine distribution (Vdss) was 1.21 ± 0.09 l / kg, indicating a wide distribution of the drug in the tissues. Nevirapine well penetrates the placental barrier and is determined in breast milk. The binding of nevirapine to plasma proteins is about 60%, its plasma concentration varies from 1 to 10 μg / ml.The concentration of nevirapine in the cerebrospinal fluid in humans is 45% (± 5%) of plasma; this ratio approximately corresponds to the fraction of the drug unrelated to plasma proteins. The metabolism of nevirapine is carried out, mainly, with the help of cytochrome P450 isoenzymes from the family of isoenzymes CYP3A, Additional isozymes may play a role. Nevirapine biotransformiruetsya to several hydroxyl metabolites.

When a single dose (50 mg) of the isotope-labeled nevirapine ¹⁴With a steady state of pharmacokinetics, approximately 91.4 ± 10.5% isotope-labeled dose of the drug, mainly (81.3 ± 11.1%) by the kidneys and, to a lesser extent (10.1 ± 1.5%), by the intestine.

More than 80% ¹⁴C-nevirapine, found in urine, was associated with hydroxylated metabolites conjugates of glucuronide. Thus, the main path biotransformation and removal of nevirapine in humans consists in the metabolism involving cytochrome P450 isoenzymes, conjugation with glucuronides and excretion of metabolites associated with glucuronides, kidneys. Only a small proportion, less than 5% ¹⁴FROM -nevirapine (corresponding <3% of the total dose) was excreted by the kidneys in an unchanged state.

Nevirapine is an inducer of cytochrome GM50 isoenzymes in the liver.If after treatment with a single dose the treatment lasts for 2-4 weeks (taking 200-400 mg / day), the pharmacokinetics parameters are characterized by autoinduction: the clearance of nevirapine after ingestion increases about 1.5-2 times. Autoinduction also results in a corresponding reduction in the half-life of nevirapine: about 45 hours (after a single dose) to about 25-30 hours (after repeated administration of the drug at doses of 200-400 mg / day).

Floor

The nevirapine's clearance in women is 13.8% less than in men. This difference is not considered clinically significant.

Lack of kidney function

Renal failure (mild - creatinine clearance 50 - 80 ml / min, moderate - creatinine clearance 30-50 ml / min or severe - creatinine clearance less than 30 ml / min) does not lead to significant changes in the pharmacokinetics of nevirapine. However, in patients with terminal stage of renal failure requiring dialysis, there was a decrease in the area under the concentration-time curve (AUC) by 43.5% and the accumulation of hydroxylated nevirapine metabolites in plasma, so Adult patients are recommended an auxiliary therapy with nevirapine, with an additional dose of 200 mg after each dialysis session,which compensates for the effect of dialysis on the clearance of the drug.

Lack of liver function

VIRAMUN should not be used in patients with severe impairment of liver function (Child-Pugh class C).

Patients with mild and moderate impairment of liver function do not need dose selection, but these patients need careful monitoring to register unwanted drug reactions.

Children (in clinical trials children from 3 months to 16 years old participated)

Nevirapine, used in doses of 4/7 mg / kg and 150 mg / m², was effective and safe when used in children who had not previously received antiretroviral therapy. With both dosing regimes, a significant increase in the percentage CD4 + cells to 48 weeks. Both dosing regimens also effectively reduced the viral load.

After oral administration of nevirapine, the clearance of the drug in children increased as the age of the patients increased, which coincided with an increase in the surface area of the body. Mean basal concentration of nevirapine after application of the drug at a dose of 150 mg / m² twice a day (after a two-week introductory period of 150 mg / m² once a day) was 4 to 6 μg / ml (which coincides with the data in adults).

Newborns

In neonates (born to HIV-1 infected mothers who once received 200 mg of nevirapine during labor), after a nevirapine suspension at a dose of 2 μ / kg for 72 hours after birth, the half-life of nevirapine was 47 hours. The concentration of nevirapine in the plasma during the first week of life was more than 100 ng / ml.

In children under 3 months of age, the concentration of nevirapine coincided with the concentration established in adults and in children of another age, but differed in greater variability, especially in children of the second month of life.

Indications:

Treatment of HIV-1 infection in combination antiretroviral therapy.

In order to prevent the transmission of HIV-1 from mother to child, in women who do not receive antiretroviral therapy during childbirth, VIRAMUN is indicated and can be used in the mother as monotherapy, as a single dose taken orally during childbirth, and in the child, also in the form of a single dose, used after birth.

Contraindications:

- Hypersensitivity to the active ingredient or any other component of the drug.

- VIRAMUN should not be re-assigned to patients who have previously,during therapy with nevirapine it was necessary to cancel it due to severe rash, hypersensitivity reactions or the development of clinically expressed hepatitis caused by taking the drug.

- Severe liver function disorders (Child-Pugh class C) or cases of initial increase in activity of aspartate aminotransferase (ACT) or alanine aminotransferase (ALT), more than 5 times the upper limit of the norm (until the ACT / ALT activity decreases steadily to less than 5 times the upper limit of the norm). VIRAMOUN should not be re-assigned to patients who previously had an increased activity ACT or ALT to a level more than 5 times the upper limit of the norm, or patients who, after repeated use of nevirapine, had a renewed liver function disorder.

- During the administration of nevirapine should not be used herbal preparations containing St. John's wort extract perforated (Hypericum perforatum), due to the risk of reducing nevirapine plasma concentrations and reducing its clinical effect.

- VIRAMUN is not recommended for use with efavirenz, rifampicin, ketoconazole,delavirdine, etravirine, rilpivirin, elvitegravir (together with the cobicystate), boceprevirov; as well as with fosamprenavir, saquinavir, atazanavir (when they are not used together with a low dose of ritonavir).

- Patients with rare hereditary disorders (fructose intolerance, pnukozo-galactose malabsorption, isomaltase deficiency) should not take VIRAMUN as a suspension, since the maximum recommended daily dose of the drug contains 6 g of sucrose and 6.5 g of sorbitol.

Carefully:

- Mild and moderate hepatic impairment

- Simultaneous therapy with telaprevir, rifabutin, warfarin, methadone, lopinavir / ritonavir, clarithromycin, fluconazole, itraconazole, ethynnestradiol, indinavir.

Pregnancy and lactation:

The safety and efficacy of the drug VIRAMUN, used to prevent the transmission of HIV-1 from mother to child, with the oral application of the drug once 200 mg by the mother during labor was established.

Adequate and well-controlled studies of HIV-1-infected pregnant women have not been conducted.

VIRAMOUN should be used during pregnancy only in those cases where the possible benefit to the mother is greater than the potential risk to the fetus.

Pregnant women

In studies it was shown that at the time of delivery in HIV-1-infected women, the half-life of the drug VIRAMUN, after a single oral intake at a dose of 200 mg, is prolonged (up to 60-70 hours), and the clearance significantly varies (2.1 ± 1 , 5 l / h), which depends on the degree of physiological stress during childbirth. Nevirapine quickly penetrates the placental barrier. Concentration of nevirapine at of the blood of the umbilical cord, after the mother took a dose of 200 mg, exceeded 100 ng / ml, and the ratio of blood concentrations in the umbilical cord and in the mother's blood was 0.84 ± 0.19.

Mothers breastfeeding
HIV-infected mothers should not breast-feed newborns to avoid the risk of postnatal HIV transmission. Mothers who receive VIRAMUN should give up breastfeeding. the drug is found in breast milk.

Dosing and Administration:

Inside. Shake the bottle before use.

VIRAMOUN can be taken regardless of food intake.

The drug should be taken only in combination with at least two additional antiretroviral drugs, except for the use of the drug to prevent the transmission of HIV-1 from mother to child once, during childbirth, or, within 72 hours after birth, in a newborn.

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

Adults:

200 mg once daily for the first 14 days, then you should take the usual dose of 200 mg twice daily.

Children:

The total daily dose should not exceed 400 mg. VIRAMOUN can be dosed in children either taking into account the body surface area (PPT), or taking into account the body weight.

When taking into account the surface area of the body using formula Mosteller the recommended dose for oral administration in children of any age is 150 mg / m² once a day for 14 days, then 150 mg / m² twice a day.

Calculation of the volume of the suspension for oral administration (50 mg / 5 ml), taking into account the surface area of the body is carried out as follows:

Range of PPT (m²)	Volume (ml)
0,08 - 0,25	2,5
0,25 - 0,42	5
0,42 - 0,58	7,5
0,58 - 0,75	10
0,75 - 0,92	12,5
0,92- 1,08	15
1,08-1,25	17,5
1,25+	20

Formula Mostcllcr: PPT (m²) =

When taking into account the body weight, the recommended dose for ingestion in children under 8 years is 4 mg / kg once a day for 14 days, then 7 mg / kg twice a day. In children 8 and older 4 mg / kg once a day for 14 days, then 4 mg / kg twice daily.

Calculation of the volume of the oral suspension (50 mg / 5 ml), after a two-week introductory period, is carried out as follows:

Body weight range (kg) for patients under the age of 8 years, receiving 7 mg / kg with regard to body weight.	Body weight range (kg) for patients aged 8 years and older receiving 4 mg / kg with regard to body weight.	Volume (ml)
1,79-5,36	3,13-9,38	2,5
5,36-8,93	9,38- 15,63	5
8,93- 12,50	15,63-21,88	7,5
12,50- 16,07	21,88 -28,12	10
16,07-19,64	28,12 -34,37	12,5
19,64-23,21	34,37 -40,62	15
23,21 -26,79	40,62- 46,88	17,5
26,79+	46,88+	20

General recommendations. VIRAMUN should be taken daily according to the instructions for use. In case of skipping the drug should not double the next dose, but you need to take the next dose as soon as possible.

Prior to taking the drug and at appropriate intervals during therapy, biochemical blood tests, including liver function tests, should be performed.

Patients who have a skin rash during the 14-day introductory period of daily dosing at a dose of 200 mg per day should not increase the dose until the rash disappears. Dosing regimen using 200 mg of the drug once a day should not last more than 28 days, then alternative therapies should be selected.

Patients who stopped taking the drug VIRAMUN for more than 7 days, with the resumption of therapy should again repeat the recommended mode of use, using a two-week introductory period.

Prevention of mother-to-child transmission of HIV

The following dosing regimen is recommended for pregnant women and their newborns:

Pregnant: 200 mg as soon as possible after the onset of labor. Newborns: 2 mg / kg once during 72 hours after birth. If the mother received VIRAMUN less than two hours before the birth, the newborn should be given the first dose (2 mg / kg) immediately after birth, and the second dose (2 mg / kg) - within 24-72 hours after the first.

Patients with impaired renal function

Adult patients with terminal renal failure (creatinine clearance less than 20 ml / min) requiring dialysis,It is recommended to use auxiliary therapy with nevirapine, with an additional dose of 200 mg after each dialysis session. Patients who have creatinine clearance in excess of 20 ml / min do not need a dose adjustment for nevirapine.

Children who are on hemodialysis are recommended to use auxiliary therapy with nevirapine, after each dialysis session, an additional dose of 50% of the recommended daily dose, which compensates for the effect of dialysis on the clearance of the drug.

Patients with impaired hepatic function

Patients with mild and moderate impairment of liver function are not required to select a dose, but such patients need careful monitoring to register unwanted drug reactions.

Side effects:

From the side of the blood and lymphatic system:

Granulotsigoneniya, anemia.

From the immune system:

Drug reaction accompanied by eosinophilia and systemic symptoms, anaphylactic reaction, hypersensitivity (including anaphylactic reaction, angioedema, hives).

From the nervous system:

Headache.

From the gastrointestinal tract:

Diarrhea, abdominal pain, nausea, vomiting.

Co side of the liver and bile ducts:

Hepatitis (including serious and life-threatening hepatoxicity), fulminant hepatitis (which can lead to death), jaundice.

From the skin and subcutaneous tissues:

Skin rash, Stevens-Johnson syndrome / toxic epidermal necrolysis (which can lead to death), angioedema, hives.

From the musculoskeletal system and connective tissue:

Arthralgia, myalgia.

Impact on laboratory and instrumental research results: violation of functional liver samples (increased activity of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, gamma-glutamyltransferase and hyperbilirubinemia), lowering blood phosphorus, increasing blood pressure.

Other:

Pyrexia, fatigue.

In the prevention of vertical transmission of HIV infection, a low incidence of adverse events was observed. Serious dermatological or hepatologic reactions, which would be regarded as associated with taking the drug, were not observed. Post-marketing experience: severe hepatitis, hepatic insufficiency, kidney damage. On combination antiretroviral therapy was noted redistribution of subcutaneous tissue (thinning of the subcutaneous tissue of the face and limbs and increase in subcutaneous tissue in the abdomen, internal organs, breasts and abdomen, mammary gland hypertrophy); hypertriglyceridemia, hypercholesterolemia, insulin resistance, hyperglycemia and hyperlactatemia; pancreatitis, peripheral neuropathy, thrombocytopenia; immune reconstitution syndrome; osteonecrosis.

Overdose:

There were reported cases of overdose with VIRAMUN (taking 800 to 6000 mg per day for up to 15 days). Symptoms: edema, erythema nodosum, fatigue, fever, headache, insomnia, nausea, lung infiltrates, rash, dizziness, vomiting, increased activity of "liver" transaminases and weight loss.

Treatment: cancellation of the drug. The antidote is not known.

Interaction:

It is shown that VIRAMUN is an inducer of cytochrome P450 isoenzymes of the liver (CYP3A, CYP2B6) and can lead to a decrease in plasma concentrations of other concomitantly used drugs that are heavily metabolized by isoenzymes CYP3A or CYP2B6. Therefore, if a patient who previously had a dosing regimen for a drug metabolized by 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.

Antiretrovirals:

NRTI (Nukteosid analogues of reverse transcriptase inhibitors)

When VIRAMUNA is used in combination with didanosine (at a dose of 100 to 150 mg twice daily), dose adjustment is not required.

When VIRAMUNA is used in combination with emtricitabnom and abakivor, which are not inhibitors of cytochrome P450 isoenzymes, dose adjustment is not required.

When VIRAMUNA is used in combination with lamivudine (at a dose of 150 mg twice daily), dose adjustment is not required.

When VIRAMUN is used in combination with stavudine (30-40 mg twice daily), dose adjustment is not required.

When VIRAMUNA is used in combination with tenofovir (300 mg once daily) and zidovudine (100-200 mg three times daily), which do not affect the pharmacokinetics of nevirapine; correction of the dose is not required.

When VIRAMUNA is used in combination with zalcitabine (0.125-0.25 mg three times daily), dose adjustment is not required.

NNRTI (Non-nucleoside analogues of reverse transcriptase inhibitors)

It is not recommended simultaneous use of efavirenz (600 mg per day) and nevirapine, tk. this combination can lead to an increased risk of adverse reactions, resulting in a cumulation of toxicity. In addition, this combination does not increase the effectiveness compared to monotherapy with non-nucleoside analogues of reverse transcriptase inhibitors (there is a decrease AUC, C_min and C_maxefavirenz).

It is not recommended simultaneous use of nevirapine with delavirdine and rilpivirin (since the combined use of these drugs has not been studied); it is not recommended joint use of nevirapine with etravirine, as the combined use of these drugs can lead to a significant decrease in the concentration of etravirin in the plasma and reduce its effectiveness.

IP (Protease Inhibitors)

When using atazanavir in combination with nevirapine, atazanavir should be administered at a dose of 400 mg together with ritonavir in a low dose of 100 mg. When using this combination (nevirapine with atazanavir / ritonavir in a dose of 400/100 mg 2 times a day) there is a decrease AUC, C_min, Ataxanavir seeds and increase AUC, C_min, C_max nevirapine.

With the simultaneous use of nevirapine with darunavir / ritonavir (400/100 mg twice daily), darupavir / ritonavir inhibits CYP3A4 and thus increases the concentration of nevirapine. Since a change in the concentration of nevirapine is not considered clinically meaningful, dose adjustment is not required.

With simultaneous administration of nevirapine with fosamprenavir / ritonavir (700/100 mg 2 times a day) dose changes are not required.

VIRAMUN should not be used together with fosamprnavir (in a dose of 1400 mg 2 times a day), if simultaneously with them is not applied ritonavir.

With the simultaneous administration of nevirapine with nelfinavir (750 mg 3 times a day) there are no clinically significant changes in the pharmacokinetics of nevirapine and nelfinavir, so dose adjustment is not required.

With simultaneous administration of nevirapine with ritonavir (600 mg twice daily), plasma concentrations of nevirapine and ritonavir do not change significantly, dose adjustment is not required.

With simultaneous administration of nevirapine with saquinavir / ritonavir, dose changes are not required.

VIRAMUN should not be used together with saquinavir (600 mg dose 3 times a day), if not simultaneously applied ritonavir.

With simultaneous administration of nevirapine with tipranavir / ritonavir (500/200 mg twice daily), clinically significant changes in pharmacokinetics are not expected, dose adjustment is not required.

With regard to the potential consequences of the combined use of nevirapine and indinavir (800 mg every 8 hours), certain clinical findings have been made. Clinical data on the interaction of nevirapine with iidinavir / ritonavir are limited.

When taking nevirapine simultaneously with lopinavir / ritonavir, an increase in the dose of lopinavir / ritovir is recommended to 533/133 mg (4 capsules) twice daily with meals.

Inhibitors of fusion of the HIV virus and cells

Clinically significant pharmacokinetic interactions between enfuvirtide and simultaneously used drugs metabolized by isoenzymes CYP450, not expected. With simultaneous use of enfuvirtide with nevirapine, dose changes are not required.

With simultaneous application of maraviroc (at a dose of 300 mg once a day) with nevirapine, dose adjustment is not required.

Integrase inhibitors

If raltegravir is used together (at a dose of 400 mg 2 times a day), no change in dose is required with nevirapine.

The combined use of nevirapine and elvitegravir (in combination with a cobicystate) is not recommended.Kobitsystat, is an inhibitor of cytochrome P450 OA, so joint use is likely to lead to a change in the concentration of cobicystate and nevirapine in plasma.

Antiviral drugs for the treatment of hepatitis B and C

Interferons (pegylated interferons alpha-2a and alpha-2b) do not affect isoenzymes CYP FOR4 and CYP 2B6. Clinically significant interactions between interferons and nevirapine are not expected. Dose changes are not required.

Entecavir is not a substrate, inducer or inhibitor of cytochrome P450 isoenzymes (CYP450). Clinically significant interactions between entecavir and nevirapine are not expected. Dose changes are not required.

Telbivudine is not a substrate, inducer or inhibitor of cytochrome P450 isoenzymes (CYP450). Clinically significant interactions between telbivuridine and nevirapine are not expected. Dose changes are not required.

Research results in vitro showed that there is a weak antagonism between nevirapine and adefovir. However, this has not been confirmed in clinical studies, therefore, the reduction in the efficacy of nevirapine and adefovir in their combined use is not expected.Adefovir does not affect known isoenzymes CYP. Dose changes in the combined use of adefovir and nevirapine are required.

Research results in vitro showed that there is a weak antagonism between nevirapine and ribavirin. However, this has not been confirmed in clinical studies, therefore, a decrease in efficacy in the combined use of nevirapine and ribavirin is not expected. Ribavirin does not affect cytochrome P450 isoenzymes. Dose changes with the combined use of nevirapine and ribavirin are not required.

Bocepreviir is partially metabolized by isoenzymes CYP3A4 and CYP3A5. The joint use of boceprevir with NNRTIs, in which the metabolic pathway is the same as in nevirapine, led to a decrease in the basal concentration of bocepreviir. The clinical result of a decrease in the basal concentration of boceprevir is unknown. Joint use of nevirapine and boceprevir is not recommended.

Telaprevir is metabolized in the liver with the participation of isoenzyme CYP3A and is a substrate for glycoprotein-P. Other isoenzymes may also participate in the metabolism of the drug. The joint use of telaprevir and drugs that induce isoenzyme CYP3A and / or glycoprotein-P, can lead to a decrease in the concentration of telaprevir in the plasma.Studies of the interaction of the body with nevirapine have not been conducted, but studies of the interaction of telaprevir with NNRTIs, which have the same metabolic pathway as nevirapine, have shown that the concentrations of both drugs decrease. Caution should be exercised in the combined use of nevirapine and telaprevir, as it may require a change in the dose of telaprevir.

Antibiotics

With the simultaneous use of nevirapine and clarithromycin (500 mg 2 times a day) dose adjustment of any of these drugs is not required. Nevertheless, careful monitoring of liver function is necessary.

In the treatment of patients with infections caused by mycobacterium avium-intracellularc complex, it is necessary to take into account alternative clarithromycin therapy, since the active metabolite of the drug in this case is ineffective.

With the simultaneous use of rifabutin (150 - 300 mg once a day) and nevirapine, dose changes are not required. Due to the high interindividual variability in some patients, the risk of rifabutin toxicity may increase. Therefore, when combined, care must be taken.

VIRAMUN should not be used in combination with rifampicin (600 mg once a day). Clinical data on the need for dose adjustment for nevirapine when used concomitantly with rifampicin are limited. If it is necessary to treat patients with tuberculosis and apply a regimen of therapy that includes VIRAMUN, an alternative drug should be used rifabutin.

Erythromycin significantly inhibits the formation of hydroxylated nevirapine metabolites.

Antifungal drugs

As a result of the increase AUC, C_min and C_max nevirapine 2 times, with simultaneous use of nevirapine with fluconazole (200 mg once a day) should be careful and carefully monitor the condition of patients.

With simultaneous use of nevirapine with itraconazole (200 mg / day), an increase in the dose of the latter may be required.

Ketocobalase and nevirapine should not be used together, since ketoconazole significantly inhibits the formation of hydroxylated nevirapine metabolites.

Antacids

With the simultaneous use of cimetidine and nevirapine, a dose change ns is required. The intake of food, antacids and preparations with an alkaline buffer does not affect the absorption of nevirapine.

Antithrombotics

The interaction between nevirapine and antithrombotic drug warfarin has a complex character, while the simultaneous use of these drugs, there is the possibility of both an increase, hack and a decrease in blood coagulation time.

During the first weeks of simultaneous application and after the withdrawal of the drug VIRAMUN, the final result of the interaction may change, so it is advisable to carefully monitor the indices of the blood coagulation system.

Contraceptive means

With simultaneous use of nevirapine with medrokeiprogesterone (depot form, 150 mg every 3 months), dose changes are not required. The simultaneous use of the drug VIRAMUN does not interfere with the suppressing effect of medroxyprogesterone on ovulation. Oral hormonal contraceptives (ex. ethinyl estradiol, 0.035 mg) should not be used as the only method of contraception in women taking VIRAMUN. Adequate doses for hormonal contraceptive preparations (oral or other dosage forms), except for medroxyprogesterone, for combination with VIRAMUN are not established with regard to safety and efficacy.

Analgesics / opioids

In patients who received both VIRAMUN and methadone, a withdrawal syndrome was reported. Patients receiving methadone maintenance doses and initiating nevirapine therapy should be observed for signs of withdrawal syndrome and the need for a corresponding dose change in methadone in these cases.

Vegetable preparations

Herbal preparations containing the herb extract of St. John's wort perfumed (Hypericum perforatum), should not be used together with nevirapine. If the patient is already taking these drugs, you should check the concentration of nevirapine and, if possible, the concentration 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 VIRAMUN. After discontinuing the administration of preparations containing St. John's Wort extract, the inductive effect may persist for at least 2 weeks.

Special instructions:

With monotherapy with VIRAMUN, resistant strains of the virus quickly and practically always appear. Therefore VIRAMOUN should always be used in combination, at least,with two other antiretroviral drugs, except for the use of the drug to prevent the transmission of HIV-1 from mother to child once, during childbirth and at the newborn within 72 hours after birth.

Important is the first 18 weeks of therapy. During this period, careful monitoring of patients to identify possible severe and life-threatening skin reactions (including Stevens-Johnson syndrome and toxic epidermal necrolysis), hepatitis or liver failure is required.

The greatest risk of hepatological and dermatological reactions exists in the first 6 weeks of therapy. However, the risk of unwanted reactions from the liver remains in the future, so the need for observation remains.

The risk of adverse events from the liver is elevated in patients with a higher number Cd4+ cells at the beginning of therapy. Given the pronounced and life-threatening gspatotoxicity, VIRAMUN ns should be given to women with a number Cd4+ lymphocytone more than 250 in 1 mm³, and men with a number Cd4+ lymphocytes more than 400 in 1 mm³, in which plasma HIV-1 RNA is determined in the plasma, unless the benefit of taking the drug does not exceed the risk of side effects.

In some cases, a violation of liver function may persist, and after the drug is discontinued.

In case of signs or symptoms of hepatitis, serious skin reactions or hypersensitivity reactions, patients should stop taking the drug and immediately go to a medical facility for examination.

VIRAMOUN can not be re-administered to patients who have experienced severe liver, skin, or hypersensitivity reactions when taking this medication.

Monotherapy with the drug VIRAMUN is accompanied by the development of resistance to non-nucleoside analogs of reverse transcriptase inhibitors. In women who previously received a single dose of VIRAMUN drug in order to prevent the transmission of HIV-1 from mother to child, the effectiveness of VIRAMUN, used in combination therapy, may decrease. Where other antiretroviral drugs are available, the single-dose regimen of VIRAMUN should be combined with additional effective antiretroviral drugs (in accordance with existing international guidelines).

It is necessary to adhere strictly to the recommended dosage regimen.

Reactions from the skin:

VIRAMOUN should be withdrawn from any patient in the event of a severe rash or rash accompanied by common symptoms (fever, blistering, changes in the oral mucosa, conjunctivitis, facial edema, joint and muscle pain, general malaise), with Stevens-Johnson syndrome or toxic epidermal necrolysis. VIRAMOUN should be withdrawn and should not be administered again to any patient in the event of development of hypersensitivity reactions characterized by a rash and general symptoms of internal organ damage such as hepatitis, eosinophilia, granulocytopenia and renal dysfunction, as well as other changes in the function of the internal organs.

Patients should be informed that the main manifestation of the toxicity of the drug VIRAMUN is a rash. To reduce the incidence of rash, an initial initial treatment period should be used. In most cases, the rash associated with taking the drug occurs in the first six weeks of therapy, so it is during this period that patients should be closely monitored for dermatological reactions.Patients should be informed that if any rash develops during the initial treatment start-up period, the dose should not be increased to two times a day 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.

In rare cases, in patients with skin and liver reactions associated with the use of nevirapine, rhabdomyolysis was observed.

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, may increase the frequency of dermatological reactions during the first 6 weeks of therapy.

Among the risk factors for the development of 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 introductory initial treatment period. The risk of serious complications of dermatological reactions increases in the event of delay in seeking medical advice after the onset of symptoms. The risk of developing rash in women is higher than that of men, as in the case of nevirapine, and in the case of therapy that does not contain nevirapine.

Reactions from the liver:

It is necessary to inform the patient that reactions from the liver are the main manifestation of the toxicity of the drug VIRAMUN. Patients who are symptomatic of hepatitis should stop taking the drug and immediately go to a medical facility for examination, which should include an assessment of liver function.

Postexposure prophylaxis of people who have not been infected with HIV is not considered an approved indication for the use of the drug and is therefore strongly discouraged. With repeated use of the drug VIRAMUN for the purpose of post-exposure prophylaxis of persons who have not been infected with HIV, serious manifestations of hepatotoxicity, incl. on the development of liver failure, requiring liver transplantation.

A high risk of adverse reactions from the liver during any antiretroviral therapy (including during therapy including nevirapine) is noted at the initial increase in the activity of enzymes ACT or ALT more than 2.5 times compared with the upper limit of the norm, and / or in the presence of hepatitis B and / or C.

Monitoring the liver

The asymptomatic increase in the activity of liver enzymes and gamma-glutamyltransferase (GGT) is often described and ns is an unconditional contraindication for the use of VIRAMUN. Strict monitoring of liver function indicators at short intervals is recommended, depending on the clinical condition of the patient, especially during the first 18 weeks of treatment. Clinical and laboratory monitoring should continue throughout the treatment period. Doctors and patients should be wary of such prodromal signs or symptoms of hepatitis such as anorexia, nausea, jaundice, bilirubinemia, fecal staining, hepatomegaly or liver soreness. Patients should be informed of the need to seek medical advice in such cases. In the case of increased activity of enzymes ACT or ALT more than 2.5 times the upper limit of the norm before or during treatment, liver function indicators should be monitored more often during regular examinations. VIRAMOUN should not be administered to patients with initial activity ACT or ALT is more than 5 times higher than the upper limit of the norm (until it steadily decreases to a level less than 5 times the upper limit of the norm). If the activity of enzymes ACT or ALT rises more than 5-fold compared with the upper limit of the norm during treatment, VIRAMOON should be immediately withdrawn. If the activity of enzymes ACT and ALT levels returned to baseline values and if the patient does not experience any symptoms of hepatitis or general simtomy or other phenomena, indicating dysfunction of internal organs, the use of the drug Viramune may be renewed (if there is a clinical need). The decision on this should be taken in each individual case, based on clinical necessity. Reassignment Viramune preparation should be conducted in conditions of high clinical and laboratory alertness in an initial dose of 200 mg / dei (within 14 days), followed by its increase up to 400 mg / day. If violations of the liver function are resumed, VIRAMUN should be finally canceled.

In the case of the development of hepatitis, accompanied by such clinical manifestations as anorexia,nausea, vomiting, jaundice, and changes in laboratory indicators (moderate or significant changes in liver function, without taking into account the activity of gamma-glutamyltransferase); nevirapine must be canceled finally. VIRAMOUN should not be given again to those patients who required its withdrawal because of the development of clinically expressed hepatitis caused by nevirapine.

Other caveats

In the use of nevirapine in combination with other antiretroviral drugs, adverse events such as pancreatitis, peripheral neuropathy, and thrombocytopenia have been reported. These phenomena are often associated with the use of other antiretroviral drugs. These conditions can develop with the use of nevirapine in combination with other drugs; The likelihood of the connection of these reactions with the use of the drug VIRAMUN is low.

Patients receiving VIRAMUI or any other antiretroviral therapy may continue to develop opportunistic infections and other complications of HIV infection. Therefore, such patients should remain under the close supervision of a physician with experience in the treatment of diseases,associated with HIV infection. Information about the ability of nevirapine to reduce the risk of horizontal transmission of HIV 1 to each other is not available to them.

Despite the fact that the ability of the drug VIRAMUN to prevent the transmission of HIV-1 infection from a mother who had not previously received other antiretroviral drugs, the child has been established to minimize the possibility of HIV-1 transmission to a child, more intensive mother treatment before delivery with antiretroviral this is possible).

In women who previously received a single dose of nevirapine to prevent mother-to-child transmission of HIV-1, the effectiveness of VIRAMUN, used in the combination therapy that these women receive for treatment, may be reduced.

In women receiving nevirapine, oral contraceptives and other hormonal methods should not be used as the main contraceptive method, since nevirapine can reduce their concentration. In addition, when using oral contraceptives during therapy with nevirapine for the purpose of hormonal regulation, it is necessary to monitor the therapeutic effects of hormonal treatment.

Osteopecrosis: The etiology of osteonecrosis is multifactorial (use of glucocorticosteroids, alcohol consumption, severe immunosuppression, increased body mass index), cases of osteonecrosis have been observed in patients with advanced HIV infection and / or long-term combined antiretroviral therapy. Patients should be warned about the need to consult a doctor in case of aches and pains in the joints, joint stiffness or difficulty in moving.

Immunodeficiency Syndrome: In patients infected with HIV-1, in the presence of significant immunodeficiency during the onset of combined antiretroviral therapy, an inflammatory response to asymptomatically existing or residual opportunistic infectious microorganisms may occur (or increase), leading to severe clinical conditions. Typically, such reactions are observed during the first few weeks or months after the onset of combined antiretroviral therapy. Typical examples are cytomegalovirus retinitis, generalized and / or local infections caused by mycobacteria, and pneumonia caused by Pneumocystic. Autoimmune diseases (eg, Based's disease) can also be noted in the case of immune reconstitution syndrome. However, such diseases can occur several months after the start of treatment. You should analyze any symptoms of inflammation and, if necessary, conduct appropriate treatment.

It is not recommended to use VIRAMUN together with efavirenz, rifampicin, ketoconazole, delavirdine, etravirine, rilpivirin, elvitegravir (in combination with cobicystag), boceprevir; if not simultaneously applied ritonavir in a small dose: with fosamprenavir, saquinavir, atazanavir.

The drug contains methyl parahydroxybenzoate and propyl lar hydroxy benzoate, these substances can cause allergic reactions (possibly delayed type).

VIRAMUN is also available in the form of tablets (200 mg), which are convenient for adults, older children and adolescents whose weight is more than 50 kg or for children with a body surface area of more than 1.25 square meters.

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

Special studies on the ability to drive vehicles and management mechanisms have not been conducted.However, patients should be informed that during treatment with VIRAMUN, undesirable reactions such as fatigue and headache are possible. Therefore, while driving the car or controlling the mechanisms should be recommended to be careful. If the patient feels fatigue or complains of a headache, then potentially hazardous activities such as driving or managing machinery should be avoided.

Form release / dosage:

Suspension for oral administration 50 mg / 5 ml.

Packaging:To 240 ml in a plastic bottle. Each vial, sealed with a plastic screw cap with an opening control from children, with instructions for use, a plastic measuring syringe and an additional lid is placed in a cardboard box.

Storage conditions:

Store at a temperature not exceeding 30 ° C.

Keep out of the reach of children.

Shelf life:

The drug should be used within 6 months from the time the vial is opened.

Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:П N011661 / 01

Date of registration:26.08.2010 / 01.11.2016

Expiration Date:Unlimited

The owner of the registration certificate:Boehringer Ingelheim International GmbHBoehringer Ingelheim International GmbH Germany

Manufacturer: & nbsp

West-Ward Columbus Inc. USA

Representation: & nbspBehringer Ingelheim, LLCBehringer Ingelheim, LLC

Information update date: & nbsp19.02.2017

Illustrated instructions

Instructions

Viramune® (Viramune®)