Nevirapine is intended for use only in combination antiretroviral (ARV) therapy, with at least two other drugs. Myotherapy with nevirapine, like other antiretroviral (ARV) drugs, is ineffective; the only result of monotherapy is the rapid development of resistance.
Contraindicated the inclusion of nevirapine in the combination of ARV drugs, which turned out to be ineffective.
Before starting therapy, all patients need to conduct laboratory tests to assess the likelihood of developing potentially dangerous side effects. Patients, previously received antiretroviral therapy, a genotypic analysis of the virus should be carried out.
It is recommended that all HIV-infected patients be tested for chronic hepatitis B before initiating antiretroviral therapy.
The patient should be informed that antiretroviral therapy does not prevent or reduce the risk of transmission of the immunodeficiency virus to healthy people through blood and through sexual contact. Nevirapine is not designed to prevent the transmission of the immunodeficiency virus, moreover,There are cases of serious adverse events in the use of nevirapine outside the approved indications (off-label); for example, there is evidence of cases of severe hepatic reactions that required liver transplantation. Combined antiretroviral therapy, including nevirapine, does not prevent diseases caused by progressive HIV infection, for example, opportunistic infections.
A patient must be is standardized, that an irregular intake of the drug leads to the development of virus resistance and a decrease in the effectiveness of treatment. If you miss a dose of the next dose should be as possible rather take a pill without waiting for the next appointment!
Do not double!
The most dangerous side effects - cutaneous (Stevens-Johnson syndrome and toxic epidermal necrolysis) and hepagotoxic reactions. By the time of development - the first 18 weeks of therapy are critical, the most dangerous of them are the first 6 weeks. Further, periodic monitoring of liver function parameters is recommended.
Hypersensitivity reactions
In patients who received nevirapine, there were serious and life-threatening skin reactions, including fatal - malignant exudative erythema (syndrome Stevens-Johnson), toxic epidermal necrolysis (syndrome Lyell), a syndrome of hypersensitivity - a combination of rash, common phenomena and damage to internal organs. Even in the case of isolated rash, careful monitoring is required. Hypersensitivity reactions can also be manifested by a combination of skin manifestations with hepatic reactions, eosinophilia, granulocytopenia, impaired renal function. The cases of development of rhabdomyolysis in combination with severe skin reactions of hypersensitivity and / or liver damage are described.
In case of development of generalized rash or rash in combination with common phenomena such as malaise, fever, mucosal lesions of the oral cavity (swelling, redness, tenderness, blisters), conjunctivitis, facial edema, blistering on the rut, joint and muscle pains - The drug should be discontinued and immediately consult a doctor. Repeated administration after severe hypersensitivity reactions is not allowed.
Prednisone and antihistamine preparations are ineffective; according to some data, with the preventive prescription of presidisone simultaneously with nevirapine in the first 14 days of therapy, even increases the incidence of rash.
Observance of the regimen of nevirapine (see the section "Dosage regimen") allows to minimize the likelihood of developing the rash. The risk of developing a drug rash against antiretroviral therapy, including nevirapine or not, higher in women. A serious risk factor for developing the rash is non-compliance with the dosage regimen of nevirapine, especially in the first 14 days of therapy.
If localized rash develops during the "introductory" period (the first 14 days of therapy, at 200 mg / day), an increase in the dose of nevirapine to 400 mg / day should be deferred until the rash disappears. In this case, the "introductory" period should not exceed 28 days (resistance develops). If the rash does not disappear within this period, respectively, it is not possible to achieve the recommended therapeutic dose of 400 mg / day, nevirapine should be canceled. The patient should be informed of the need to consult a doctor if any skin rash is found.
If suspicion of nevirapine skin reactions is necessary to assess liver function. Activity ACT and ALT, which exceeds VGN 5 times, is critical and serves as an indication for the withdrawal of the drug.
Reactions hypersensitivity and activity ACT and ALT, which exceeds VGN 5 times, are an absolute contraindication to the appointment of nevirapine.
Liver disorders
Severe life-threatening liver damage, including fulminant liver failure, are a response on nevirapine.
Immune-mediated hepatic reactions can be combined with skin reactions, rhabdomyolysis, and / or common phenomena such as fever, arthralgia, myalgia, malaise.
Any signs of development hepatotoxic reactions, as well as hypersensitivity reactions, are the indication of discontinuation of taking the drug and immediate medical treatment. Re-appointment not allowed. AT In some cases, liver symptoms increase, despite the withdrawal of nevirapine. Risk factors are HIV-1 viral load exceeding 50 copies / ml of plasma, female sex, initially high number CD4 cells, activity ACT and ALT, which exceeds GBH> 2.5 times, co-infection with the hepatitis C virus, alcohol abuse. In women, almost three times more than men develop hepatic, more often in combination with sypyo, reactions (5.8% vs 2.2%). In patients of both sexes who had not previously received ARV therapy, with detectable HIV-1 RNA and a high number CD4, also increased risk of developing liver reactions. When viral load> 50 copies / ml in women with the number of CD4 > 250 cells / mm3 compared with women who have CD4 <250 cells / mm3, the risk of development of hepatotoxic reactions is 12 times higher (11.0% vs 0.9%). In men with the same viral load, with the number of CD4 > 400 cells / mm3 the risk of developing hepatotoxic reactions is five times higher (6.3% vs 1.2%). Patients with similar indicators CD4, but in the absence of a viral load (less than 50 copies / ml, i.e., not detected in the blood plasma), ns belong to the group at high risk of developing liver reactions. Start treatment nevirapine of women CD4 > 250 cells / mm3 and men with the number of CD4 > 400 cells / mm3 It does not follow, unless the expected benefit substantially exceeds the possible risk.
Active monitoring of liver function parameters should be performed in patients who previously had complaints of dyspeptic phenomena, anorexia, nausea,discolored stool, pain in the liver, jaundice, bilirubinuria, hepatomegaly.
The patient should be informed that when complaints such as nausea, vomiting, anorexia, pain in the right upper quadrant, icteric skin, dark urine and discolored stools should be consulted immediately! Clinical and laboratory monitoring should be performed throughout the treatment period with nevirapine. During the first two months of nevirapine, liver tests should be performed every 2 weeks, then at the end of the third month of therapy, then somewhat less frequently, but regularly. Patients who had a history of symptoms indicative of a violation of liver function, as in the case of activity ACT or ALTs that exceed IGN more than 2.5 before or during treatment, need a relatively frequent examination, even with a good tolerability of the drug.
Asymptomatic increase in the activity of liver enzymes, like GGT, is often noted, but is not an indication for the withdrawal of nevirapine.
Nevirapine should not be given to patients who have initial activity ACT and / or ALT exceeds HHV more than 5 times. Increased activity ACT and / or ALT more than 5 times compared with eVGN with nevirapine therapy is an indication for immediate withdrawal of the drug. In the case of an asymptomatic increase in activity ACT and / or ALT - in the absence of complaints and / or symptoms of hepatitis or common symptoms that indicate a disruption of the function of internal bodies - use of nevirapine may be resumed.
The decision to resume is taken individually, based on clinical necessity. An indispensable condition is normalization activity of enzymes, stabilization. When reapplying nevirapine it is necessary to follow the recommended dosing regimen: an "introductory" period of 14 days - a dose of 200 mg / day, followed by an increase to 400 mg / day. Ensure thorough clinical and laboratory monitoring. In case of resumption of liver function disorders nevirapine must be canceled finally.
Diseases of the liver
The efficacy and safety of nevirapine in patients with underlying diseases liver ns installed. Heavy hepatic insufficiency - class C by The Child-Pyo scale is contraindication to the use nevirapine. Moderate hepatic Insufficiency - Class B on the Child-Pew requires use with caution.
Special surveillance is required for ARVs therapy of patients with HIV-infection with hepatitis B or C due to increased risk of developing severe, potentially fatal, hepatotoxic reactions. Required take into account recommendations and measures precautions used drugs.
In patients with initial dysfunction liver, including active chronic hepatitis, against the background of ARV therapy disorders liver function are noted for more often. This group of patients needs in close observation. When detection of clinical and / or laboratory signs of aggravation liver function disorders interrupt or discontinue therapy nevirapine.
Other undesirable reactions Redistribution of adipose tissue In patients who received antiretroviral therapy, observed fat redistribution / accumulation body tissues, including abdominal obesity, dorsocystvic fat deposition ("buffalo hump"), lipoatrophy on the limbs and face, breast augmentation and "cushingoid" type of obesity.Risk factors are metabolic disorders, the duration of antiretroviral therapy, and older patients. The mechanism of occurrence and long-term effects are not known. Causality with the use of ARV drugs has not been proven.
In clinical studies on the background of the use of nevirapine, there was an increase in high-density lipids and normalization of the ratio of high and low density lipids. The clinical significance of these facts is unknown, as there is no information about the possible effect of these on the degree of cardiovascular risk in HIV-infected patients.
Periodic monitoring of glucose and lipid levels in the blood is recommended; of necessity - an adequate pharmacological correction.
Osteonecrosis
It is possible to reduce the initial level of bone density, there are cases of osteonecrosis.
Etiology
multifactorial: simultaneous intake of corticosteroids, alcohol abuse, severe immunosuppression, high body mass index; the risk is higher patients with progressive HIV infection, and increases in direct proportion to the duration of therapy. The patient should be warned about the need to consult a doctor in case of complaints about restricted mobility of the joints, arthralgia of discomfort / difficulty in moving.
Immunodeficiency Syndrome
Immunodeficiency syndrome was reported in patients taking combined antiretroviral therapy. The immune reconstitution syndrome manifests itself as aggravation of sluggish and opportunistic infections, activation of the conditionally pathogenic flora; observed at the initial stage of treatment in HIV-infected patients with initial expressed immunosuppression.
Characteristic of the development of cytomegalovirus retinitis, localized or generalized mycobacterial infection, pneumocystis pneumonia.
Cases of autoimmune diseases, for example, Graves' disease (autoimmune thyroiditis) have been reported. In this case, infection caused by restoration of immunity is characterized by development during the first few weeks of treatment, while autoimmune diseases develop many months after the initiation of therapy.
Granulocytopenia as a complication of therapy with nevirapine, especially in combination with zidovudine, was detected in the postmarketing period. It is noted that in children this reaction develops much more often.
Other caveats. There are reports of the development of pancreatitis, peripheral neuropathy, thrombocytopenia against the use of nevirapine in combination with other antiretroviral drugs. These adverse reactions are often observed against the background of antiretroviral drugs, including when used in combination with nevirapine; nevertheless, their association with the use of nevirapine is questionable.
In women who previously received a single dose of nevirapine in order to prevent the transmission of HIV-1 from mother to child, the effectiveness of nevirapine in combination therapy may be reduced.