Nevirapine

Nevirapine is an antiviral drug.

[1], [2], [3], [4], [5],

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 undergo antiretroviral therapy during childbirth).

[6], [7]

Release form

The release is sold in tablets with a volume of 0.2 grams, in polyethylene bottles, 30 or 60 pieces each. The box contains 1 bottle.

[8], [9], [10], [11]

Pharmacodynamics

Nevirapine is a non-nucleotidic substance that slows the revertase of the HIV-1 type. It is directly connected with the revertase, while blocking the activity of polymerases, dependent on DNA along with RNA. As a result, destruction takes place, affecting the catalytic region of the enzyme.

The drug does not compete with nucleoside or matrix 3-phosphates, nor does it slow down the activity of human DNA polymerase (types α, β and γ or δ) and HIV-2 revertase.

The combination with didanosine or zidovudine causes a reduction in the number of viruses inside the serum and increases the number of cells of the CD4 + type.

[12], [13], [14], [15], [16]

Pharmacokinetics

When administered orally, nevirapine is absorbed at a high rate (greater than 90%) in both volunteers and people infected with HIV. After a 1-time dose of 0.2 g, plasma Cmax values are recorded after 4 hours and are approximately 2 ± 0.4 μg / ml (equal to 7.5 μmol). After the course use, there was a linear increase in the plasma indices of Cmax nevirapine in the interval of 0.2-0.4 g portions per day.

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

Nevirapine is a lipophilic component that almost does not ionize when the physiological pH level is affected. When intravenously injected into a healthy adult, the Vd level is approximately 1.21 ± 0.09 l / kg, indicating a good distribution of drugs within the tissues. The indices of the drug inside the CSF are 45% (± 5%) of its plasma values.

At plasma indices in the range of 1-10 μg / ml, the substance is synthesized with the protein by 60%.

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

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

Drug excretion occurs through the kidneys (approximately 80%) in the form of metabolic products conjugated with glucuronic acid, as well as a small part of the substance in the unmodified state.

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

After oral use in a dose of 0.2 g 2 times a day for 0.5-1 month, the level of apparent drug clearance is 1.5-2 times higher than in a 1-time dose in the same dose. Term half-life at the terminal stage is reduced from 45 hours after a single application to 25-30 hours after the course use. These parameters vary due to pharmacokinetic self-induction.

In HIV-1 infected children, the AUC and Cmax levels increased in proportion to the increase in the portion. After completion of the absorption of the substance, the plasma values of nevirapine decreased linearly with time.

The clearance of the drug when recalculating for weight shows the maximum in infants at the age of 1-2 years, after which it decreases in proportion to the growth of a person. The level of drug clearance in people under 8 years of age is half that of adults. The half-life after reaching the Css mark is approximately 25.9 ± 9.6 hours on average (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 varies with age and has the following indicators:

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

[17], [18], [19], [20]

Dosing and administration

After oral intake of 0.2 g of LS, 1-fold per day by an adult, every day during the first 2 weeks (the introductory phase), a portion increases to 0.2 g with a 2-fold intake per day every day (in combination with a minimum 2 antiretroviral drugs).

Children in the range from 2 months to 8 years of age need to apply in the first 2 weeks of 4 mg / kg of substance 1-fold for a day, and later - 7 mg / kg 2 times a day. Children, whose age is more than 8 years, are prescribed in the first 2 weeks to take 4 mg / kg 1-fold per day, and later - 4 mg / kg 2 times a day.

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

People who have had rashes during the 2-week introductory phase of using the medication should not increase their dosage until this rash completely disappears.

To prevent the transmission of HIV from the pregnant to the baby, it is necessary to take 0,2 g of substance at birth and then 2-mg / kg of the drug to the newborn for 1 72 hours after the birth.

In the case of a moderate change in liver function values (except GGT), Nevirapine should be discontinued until the data return to the baseline, after which the drug is used in a dose of 0.2 g per day. Further increase in dosage (0.2 g 2 times a day) should be performed very carefully, after a long period of monitoring the patient's condition. If the hepatic values have changed again, the therapy must be finally canceled.

In people who did not take the drug for more than 7 days, the therapy should be restarted, starting with a portion of 0.2 g per day, for 2 weeks, and then increase it to 2 times the same amount per day.

[23], [24], [25], [26], [27], [28],

Use Nevirapine during pregnancy

Appropriate clinical safety tests for the use of medication during pregnancy, which would be strictly controlled, were not performed. There is evidence that the substance easily passes through the placenta. Prescribe Nevirapine to pregnant women is allowed only in situations where it is more likely that it will be useful for a woman than harm the fetus.

The medicine is excreted with the mother's milk, so if you need to take it with lactation, you must first stop breastfeeding.

As a preventive substance preventing the transmission of HIV-1 from a pregnant woman to her child, the drug demonstrated its safety and therapeutic effectiveness when administered orally during the delivery of a 1-time dose of 0.2 grams, as well as a 1-fold dose of 2 mg / kg given to a newborn in the period up to 72 hours from the moment of birth.

During therapy it is necessary to use contraceptive means of barrier type.

Experiments conducted on animals did not show the presence of teratogenic properties in the preparation. A decrease in fertility in female rats after the use of drugs in portions at which the active element enters the circulatory system was demonstrated (they were determined by means of the AUC level, which is approximately the same as it accumulates when the recommended therapeutic dosages of the drug are administered).

Contraindications

Contraindicated use of the medicine in the presence of intolerance in his relationship.

[21]

Side effects Nevirapine

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

• disorders that are dermatological: rashes on the skin that have erythematous maculopular nature, against which sometimes there is itching (usually appear on the face, trunk or extremities). Often, such rashes occur during the first 28 days of treatment;
• defeat of the allergic nature: may develop myalgia or arthralgia, febrile condition and lymphadenopathy, in which the following signs appear (eosinophilia, hepatitis or granulocytopenia, as well as a disorder in the functioning of the kidneys and manifestations indicative of the defeat of other internal organs). Also develops urticaria, anaphylactic symptoms, Stevens-Johnson syndrome, edema Quincke and TEN (occasionally they cause death);
• disorders of the digestive function: often there is an increase in GGT activity. There may be an increase in the total bilirubin and AC activity with AST and ALT, as well as the development of diarrhea, abdominal pain and vomiting with nausea. It was reportedly reported on the appearance of hepatotoxic signs in the severe stage or jaundice;
• symptoms associated with the hematopoietic system: the development of granulocytopenia (often in children);
• problems in the CNS: headaches and a feeling of severe fatigue or drowsiness.

[22],

Overdose

Signs of intoxication are noted when using a daily dose of 0.8-6 g of the drug for 15 days. They manifest in the form of allergy symptoms (such as Quincke edema, nodular type erythema and eruptions on the epidermis), pulmonary infiltrate, short-term dizziness, weight loss, increased transaminases and the development of general signs of a state of health disorder (such as headaches, vomiting, feeling drowsiness or fatigue, as well as nausea and fever).

The medicine does not have an antidote. To eliminate the disorders, gastrointestinal lavage is performed, enterosorbents (such as activated charcoal) and symptomatic procedures are prescribed.

[29], [30], [31]

Interactions with other drugs

After combined use with the drug, there may be a decrease in plasma hormone OC values, which is why their therapeutic efficacy is weakened.

Combination of the drug with ketoconazole leads to a decrease in the level of Cmax and AUC of the latter. In this case, ketoconazole increases the values of nevirapine inside the plasma by about 15-28%. Therefore, these drugs can not be used at the same time.

The combination with cimetidine results in an increase in the minimum plasma Css values of the substance, compared to its use without the use of cimetidine.

Erythromycin with ketoconazole can significantly weaken the formation of hydroxylated metabolic products of Nevirapine.

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

Because the drug induces the activity of the isoenzymes CYP3A and CYP2B6, if it is combined with medicaments that are subject to active metabolism with the enzymes mentioned above, a decrease in the plasma indices of these agents may be noted.

Combined use of medicines with medicines containing St. John's wort may lead to a reduction in NVP below the drug mark, which will make the virological effect of the drug disappear and the virus become resistant to the drug. In this regard, you need to abandon such a drug combination.

The drug can lower the plasma values of methadone. This is due to the peculiarities of the metabolism of the latter - Nevirapine enhances hepatic metabolism of methadone. People who took these medicines at the same time experienced cases with the emergence of withdrawal syndrome, which is of a narcotic nature. Because of this, when using this combination, you need to monitor the patient's condition and change the portion of methadone in time.

[32], [33], [34]

Storage conditions

Nevirapine should be kept at temperature values not exceeding 30 ° C.

[35], [36], [37]

Shelf life

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

[38], [39], [40]

Analogues

The analog of the therapeutic drug is medicament Viramun.

[41], [42], [43], [44], [45], [46],

Reviews

Nevirapine is considered an effective drug that fully fulfills its therapeutic function. People who strictly observe medical recommendations do not have any negative symptoms and a good tolerability of drugs.

According to the doctors, the most serious negative property of the medicine is that it damages the liver. In connection with this, during the therapy the patient should regularly undergo medical examinations and take tests - this instruction must be adhered to rigorously to avoid the development of severe consequences.