Viramun, 50 mg/5 ml suspension, 240 ml

Viramune has an antiviral effect.

Nevirapine is a non-nucleoside reverse transcriptase inhibitor (NNRTI) of HIV-1. Nevirapine binds directly to reverse transcriptase (RT) and blocks RNA- and DNA-dependent DNA polymerase reactions by destroying the enzyme’s catalytic center. The action of nevirapine is not competitive against nucleosides and nucleoside triphosphates. The drug does not block HIV-2 reverse transcriptase and eukaryotic DNA polymerase (human DNA polymerase alpha, beta, gamma or delta).

Pharmacokinetics

It is well absorbed from the gastrointestinal tract, rapidly distributed to tissues and fluids, crosses the BBB, placental barrier, penetrates into breast milk. Absorption of nevirapine is not affected by intake of food, antacids and other drugs containing an alkaline buffer component (e.g., didanosine).

The absolute bioavailability after a single dose is approximately 93±9% for 200 mg tablets and 91±8% for suspension. C_max after a single 200 mg dose (2±0.4 mcg/ml) is reached after 4 h, with a linear increase in C_max in the dose range 200-400 mg/day is observed when taking a course of use. Binds to plasma proteins by approximately 60%.

It is biotransformed in the liver by cytochrome P450 enzymes to form several hydroxylated metabolites. It is excreted mainly in the urine as glucuronic acid-conjugated metabolites (only less than 5% of unchanged nevirapine is detected in the urine). T_1/2 after a single dose (200 mg) is 45 h, with course use (200-400 mg/day) decreases to 25-30 h, which is associated with the ability of nevirapine to induce cytochrome P450 metabolic enzymes.

Pharmacokinetic parameters in adults are not expected to vary with age (between 19-68 years) or ethnicity; they vary with age in children.

Indications

Treatment and prevention of HIV-1 infection.

When Viramun is prescribed as monotherapy, viral resistance develops quickly and almost always, so it should always be prescribed in combination with at least two other antiretroviral drugs.

Active ingredient

Composition

1 ml of oral suspension contains:

the active ingredient:

nevirapine 10 mg (which corresponds to 10.35 mg of nevirapine semihydrate),

excipients:

carbomer;

methylparahydroxybenzoate;

propylparahydroxybenzoate;

sorbitol;

sucrose;

polysorbate 80;

sodium hydroxide;

distilled water

How to take, the dosage

Viramun is taken orally.

Adults: 200 mg once daily for the first 14 days, then 200 mg twice daily in combination with at least two antiretrovirals. If there is a break of more than 7 days, treatment is resumed starting at a dose of 200 mg daily for the first 14 days, then the dose is increased to 200 mg twice daily.

In children: from 2 months to 8 years old – 4 mg/kg once daily for 2 weeks, then in a daily dose of 7 mg/kg in 2 doses; from 8 years old and over – 4 mg/kg once daily for 2 weeks, then in a dose of 4 mg/kg/day in 2 doses. The daily dose in patients of any age should not exceed 400 mg.

Preventing mother-to-child transmission of HIV: 200 mg once to the mother at delivery, followed by a single oral dose of 2 mg/kg to the newborn within 72 hours after birth.

Interaction

May decrease plasma concentrations of drugs that are actively metabolized by cytochrome P450 enzymes (dose adjustment may be required).

The dosing regimen does not need to be changed when using nevirapine in combination with nucleoside analogues (zidovudine, didanosine, zalcitabine); no clinically significant interaction with protease inhibitors (saquinavir, ritonavir, indinavir) has been established.

Decreases area under the concentration-time curve (AUC) and Cmax of ketoconazole, and ketoconazole increases nevirapine plasma concentration by 15-28% (should not be administered simultaneously, ketoconazole can be replaced with drugs with a renal excretion route, such as fluconazole).

The CYP cytochrome P450 isoenzyme inducers rifampicin and rifabutin decrease Cmax of nevirapine, but there are currently insufficient data to determine whether a dose change is necessary when they are used concomitantly. St. John’s wort reduces the blood concentrations of nevirapine and other NNRTIs (even to below therapeutic levels), so their concomitant use is not recommended (loss of efficacy and development of viral resistance are possible).

The CYP cytochrome P450 isoenzyme inhibitors, such as clarithromycin, increase (reciprocally) the AUC and Cmax, but it is not expected to change the dosing regimen with their simultaneous use.

Concomitant use with cimetidine increases the minimum steady-state plasma concentration of nevirapine.

It alters the pharmacokinetic parameters of oral contraceptives (decreases blood concentrations and accelerates excretion), so there is a risk of decreased effectiveness (if contraception is needed, switching to other methods such as barrier contraception is recommended, and if oral contraceptives are used for other indications, continued monitoring of therapeutic effectiveness is necessary).

Ketoconazole and erythromycin inhibit the formation of hydroxylated metabolites of nevirapine. There have been no clinical studies.

May decrease plasma concentrations of methadone by increasing its metabolism in the liver, which leads to development of narcotic withdrawal syndrome (treatment monitoring and dose adjustment if necessary are required).

Special Instructions

The treatment should be stopped immediately if the patient develops severe rashes, including those with signs of generalization of the process, with moderate or pronounced changes in liver activity (until normalization), with repeated changes in its functional state. Before and during therapy it is necessary to monitor the condition of the liver and skin (especially during the first 8 weeks of treatment).

Caution should be exercised when prescribing to patients with renal and hepatic insufficiency. The dose should be taken daily, as prescribed, and should not be changed without consulting a physician. If the next dose is missed, the next dose (without doubling it) should be taken as soon as possible. Viramun should only be combined with antiretrovirals (monotherapy develops resistance very quickly), preferably ones that have not been used previously.

Patients on nevirapine or other antiretrovirals may have progressive disease, including opportunistic infections associated with HIV-1 infection. Because of this, patients should be continuously monitored by physicians experienced in treating diseases associated with HIV-1 infection.

The long-term effects of the drug are currently unknown.

The risk of other people contracting HIV-1 infection is not reduced by therapy with the drug.

Patients with impaired renal function who are on dialysis are advised to take an additional dose of 200 mg after each dialysis treatment (no dose adjustment is required if creatinine Cl ≥20 mL/min).

In case of drowsiness, it is recommended to refrain from driving vehicles and operating machinery.

Contraindications

Hypersensitivity.

Side effects

Overdose

Symptoms (observed with doses of 800-1800 mg/day for up to 15 days): angioedema, erythema nodosa, fatigue, fever, headache, insomnia, nausea, lung infiltrate formation, rash, dizziness, vomiting, weight loss.

Treatment: there is no specific antidote. After withdrawal of the drug, reversal of all symptoms was noted.

Pregnancy use

The use of Viramun in pregnancy is possible only if the expected effect of therapy exceeds the potential risk to the fetus.

Breastfeeding should be stopped during treatment.