Nevirapine

Nevirapine is an antiviral medication.

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Indications Nevirapine

It is used for therapy in people with HIV-1 infection (taken in combination with at least 2 antiretroviral drugs).

In addition, the drug is used to prevent the transmission of HIV-1 from a pregnant woman to her child (in those mothers who did not receive antiretroviral therapy during childbirth).

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Release form

The product is available in 0.2 g tablets in polyethylene bottles of 30 or 60 pieces. The box contains 1 bottle.

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Pharmacodynamics

Nevirapine is a non-nucleotide substance that inhibits HIV-1 type revertase. It is directly linked to revertase, thereby blocking the activity of polymerases dependent on DNA and RNA. As a result, destruction occurs, affecting the catalytic region of the enzyme.

The drug does not compete with nucleoside or matrix 3-phosphates, and does not inhibit the activity of human DNA polymerase (types α, β and γ or δ) and HIV-2 reverse transcriptase.

Combination with didanosine or zidovudine causes a decrease in the number of viruses in the serum and increases the number of CD4+ cells.

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Pharmacokinetics

When administered orally, nevirapine is absorbed at a high rate (more than 90%) in both volunteers and HIV-infected individuals. After a single dose of 0.2 g, plasma Cmax values are observed after 4 hours and are approximately 2±0.4 μg/ml (equal to 7.5 μmol). After a course of use, a linear increase in plasma Cmax values of nevirapine was observed in the range of doses of 0.2-0.4 g per day.

The consumption of food, antacids and other medications that contain an alkaline buffer element (for example, didanosine) does not affect the extent of absorption of the drug.

Nevirapine is a lipophilic component that is almost not ionized when exposed to physiological pH. When injected intravenously into a healthy adult, the Vd is approximately 1.21±0.09 L/kg, indicating good distribution of the drug within tissues. The drug levels in the cerebrospinal fluid are 45% (±5%) of its plasma values.

With plasma levels within the range of 1-10 μg/ml, the substance is synthesized with protein by 60%.

The Cssmin values of the drug are approximately 4.5±1.9 μg/ml and are achieved with a dose of 0.4 g of the substance per day.

Metabolic processes occur with the help of microsomal liver enzymes of the hemoprotein P450 system (mainly CYP3A isoenzymes). As a result, several hydroxylated metabolic products are formed.

Excretion of the drug occurs through the kidneys (approximately 80%) in the form of metabolic products conjugated with the participation of glucuronic acid, as well as a small portion of the substance in an unchanged state.

Nevirapine is an element that induces microsomal enzymes of the CYP system.

After oral administration of 0.2 g twice a day for 0.5-1 month, the apparent clearance of the drug increases by 1.5-2 times compared to a single dose of the same dose. The half-life at the terminal stage decreases from 45 hours after a single dose to 25-30 hours after a course of use. These parameters change due to pharmacokinetic self-induction.

In HIV-1 infected children, AUC and Cmax increased proportionally with increasing dose. Once absorption was complete, plasma nevirapine levels decreased linearly over time.

The drug clearance when converted to weight demonstrates the maximum value in infants aged 1-2 years, after which it decreases proportionally to the person's maturation. The drug clearance level in individuals under 8 years of age is half that of adults. The half-life after reaching the Css mark is on average approximately 25.9±9.6 hours (in the category of infants with HIV-1, whose average age is 11 months).

After prolonged use, the half-life of the drug at the terminal stage changes depending on age and has the following indicators:

• infants 2-12 months – 32 hours;
• children 1-4 years old – 21 hours;
• children 4-8 years old – 18 hours;
• over 8 years of age – 28 hours.

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Dosing and administration

After oral administration of 0.2 g of the drug once a day by an adult, every day during the first 2 weeks (introductory phase), the dose is increased to 0.2 g with 2 doses per day every day (in combination with at least 2 antiretroviral drugs).

Children aged 2 months to 8 years are required to take 4 mg/kg of the substance once a day during the first 2 weeks, and later – 7 mg/kg twice a day. Children over 8 years of age are prescribed 4 mg/kg once a day during the first 2 weeks, and later – 4 mg/kg twice a day.

People of any age can take a maximum of 0.4 g of the drug per day.

People who develop a rash during the 2-week introductory phase of using the medication should not have their dosage increased until the rash has completely cleared up.

To prevent the transmission of HIV from a pregnant woman to her child, it is necessary to take 0.2 g of the substance once during childbirth, and then, over the next 72 hours from the moment of birth, administer 2 mg/kg of the drug orally to the newborn once.

In case of moderate changes in liver function values (except GGT), Nevirapine should be discontinued until these values return to the initial level, after which the drug is used in a dose of 0.2 g per day. A further increase in dosage (0.2 g 2 times per day) should be done very carefully, after a long period of monitoring the patient's condition. If liver values change again, therapy should be permanently discontinued.

For people who have not taken the drug for more than 7 days, therapy should be resumed, starting with a dose of 0.2 g per day, for 2 weeks, and then increasing it to 2 times the same dose per day.

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Use Nevirapine during pregnancy

There have been no adequate clinical tests of the safety of the drug during pregnancy that would be strictly controlled. There is evidence that the substance easily crosses the placenta. Nevirapine may only be prescribed to pregnant women in situations where it is more likely to be beneficial to the woman than to harm the fetus.

The drug is excreted in breast milk, so if you need to take it during lactation, you must first stop breastfeeding.

As a prophylactic agent preventing the transmission of HIV-1 from a pregnant woman to her child, the drug has demonstrated its safety and therapeutic efficacy when administered orally during labor in a single dose of 0.2 g, as well as in a single dose of 2 mg/kg given to a newborn within 72 hours of birth.

During therapy, it is necessary to use barrier contraceptives.

Experiments conducted on animals have not shown the presence of teratogenic properties in the drug. A decrease in fertility in female rats was demonstrated after the use of the drug in doses at which the active element enters the bloodstream (they were determined by the AUC level, which is approximately the same as it accumulates when introducing the recommended therapeutic doses of the drug).

Contraindications

It is contraindicated to use the medicine if you have an intolerance to it.

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Side effects Nevirapine

Taking capsules can lead to the development of some side effects:

• disorders of a dermatological nature: skin rashes of an erythematous maculopapular nature, against which itching sometimes appears (usually appear on the face, trunk or limbs). Often such rashes appear during the first 28 days of treatment;
• allergic lesions: myalgia or arthralgia, fever and lymphadenopathy may occur, with the following signs (eosinophilia, hepatitis or granulocytopenia, as well as renal dysfunction and manifestations indicating damage to other internal organs). Urticaria, anaphylactic symptoms, Stevens-Johnson syndrome, Quincke's edema and TEN (rarely they cause death) also develop;
• digestive disorders: an increase in GGT activity is often observed. An increase in total bilirubin and alkaline phosphatase activity with AST and ALT may be observed, as well as the development of diarrhea, abdominal pain and vomiting with nausea. There have been isolated reports of the appearance of hepatotoxic signs in a severe stage or jaundice;
• symptoms associated with the hematopoietic system: development of granulocytopenia (often in children);
• problems with the central nervous system: headaches and a feeling of extreme fatigue or drowsiness.

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Overdose

Signs of intoxication are observed when using a daily dose of 0.8-6 g of the drug for 15 days. They manifest themselves in the form of allergy symptoms (such as Quincke's edema, nodular erythema and rashes on the epidermis), pulmonary infiltrate, short-term dizziness, weight loss, increased transaminase levels and the development of general signs of malaise (such as headaches, vomiting, a feeling of drowsiness or fatigue, as well as nausea and fever).

The drug has no antidote. To eliminate the disorders, gastrointestinal lavage is performed, enterosorbents (such as activated carbon) are prescribed, and symptomatic procedures are performed.

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Interactions with other drugs

After combined use with the drug, a decrease in plasma levels of hormonal oral contraceptives may occur, due to which their therapeutic effectiveness is weakened.

Combination of the drug with ketoconazole leads to a decrease in the Cmax and AUC levels of the latter. At the same time, ketoconazole increases the values of nevirapine in plasma by approximately 15-28%. Therefore, these drugs cannot be used simultaneously.

Combination with cimetidine leads to an increase in the minimum plasma Css values of the substance, compared to its use without cimetidine.

Erythromycin with ketoconazole are able to significantly weaken the processes of formation of hydroxylated metabolic products of Nevirapine.

The drug does not affect the pharmacokinetic characteristics of rifampicin, but at the same time rifampicin leads to a significant decrease in the AUC level and Cmin values of the drug. Combined use with rifabutin leads to a decrease in nevirapine values. Currently, there is too little information to determine the need to change the dose of the drug when it is combined with rifabutin or rifampicin.

Since the drug induces the activity of CYP3A and CYP2B6 isoenzymes, in the case of its combination with drugs that undergo active metabolism with the help of the above enzymes, a decrease in plasma levels of these drugs may be observed.

Combined use of the drug with drugs that contain St. John's wort may lead to a decrease in nevirapine levels below the drug mark, due to which the virological effect of the drug will disappear, and the virus will become resistant to the drug. In this regard, such a drug combination should be abandoned.

The drug can reduce plasma levels of methadone. This is due to the peculiarities of the latter's metabolism - Nevirapine increases the hepatic metabolism of methadone. In people taking these medications simultaneously, there have been cases of withdrawal syndrome of a narcotic nature. Because of this, when using such a combination, it is necessary to monitor the patient's condition and change the methadone dose in time.

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Storage conditions

Nevirapine should be kept at temperatures not exceeding 30°C.

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Shelf life

Nevirapine is allowed to be used within 36 months from the date of release of the drug.

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Analogues

An analogue of the therapeutic drug is the medication Viramun.

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Reviews

Nevirapine is considered an effective drug that fully performs its therapeutic function. People who strictly follow the doctor's recommendations do not experience any negative symptoms and have good tolerance of the drug.

According to doctors, the most serious negative property of the drug is that it damages the liver. In this regard, during therapy, the patient should undergo regular medical examinations and tests - this instruction must be strictly followed to avoid the development of serious consequences.