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

Clinical and pharmacological group: & nbsp

Means for the treatment of HIV infection

Included in the formulation

Lakonivir

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FARMASINTEZ, JSC (Irkutsk) Russia

Eduardant®

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Johnson & Johnson, LLC Russia

АТХ:

J.05.A.G. Non-nucleosides - reverse transcriptase inhibitors

J.05.A.G.05 Rilpivirine

Pharmacodynamics:

Rilpivirin is a diaryl pyrimidine non-nucleoside inhibitor of HIV-1 reverse transcriptase. The activity of rilpivirin is mediated by the non-competitive inhibition of HIV-1 reverse transcriptase. Rilpivirine does not inhibit human alpha, beta, gamma-DNA polymerase. Rilpivirine has additive antiviral activity in combination with nucleotide / nucleoside reverse transcriptase inhibitors (abacavir, didanosine, emtricitabine, stavudine and tenofovir), with protease inhibitors (amprenavir, atazanavir, darunavir, indinavir, lopinavir, nelfinavir, ritonavir, tipranavir and saquinavir), with non-nucleoside reverse transcriptase inhibitors (efavirenzem, etravirine and nevirapine), as well as in combination with a fusion inhibitor-enfuvirtide and a CCR 5 co-receptor antagonist-maravi eye. Rilpivirine gives a synergistic or additive antiviral effect in combination with nucleoside reverse transcriptase inhibitors lamivudine and zidovudine, as well as an integrase inhibitor raltegravir.

Pharmacokinetics:

After ingestion C_max rilpivirin in the blood plasma was achieved within 4-5 hours. Absolute bioavailability of rilpivirin is unknown.

Exposure rilpivirina was about 40% lower when taking the drug on an empty stomach than when taking with meals the usual caloric intake (533 kcal) or with food high in fat (928 kcal). When rilpivirine taken with a drink enriched with proteins, the exposure of the drug was 50% lower than when it was simultaneously reception with food. Final half-liferilpivirin is approximately 45 hours. After taking a single dose of 14C-rilpivirin by mouth, about 85% and 6.1% of the dose containing the radioactive label was found in feces and urine, respectively.

The amount of rilpivirine found in the stool in unchanged form averaged 25% of the administered dose. In urine, only a small amount of unchanged rilpivirin was detected (less than 1% of the dose taken).

Indications:

In combination with other antiretroviral drugs as first-line therapy for the treatment of infection caused by human immunodeficiency virus type 1 (HIV-1) in adult patients.

ICD-10

I.B20-B24 Disease caused by the human immunodeficiency virus [HIV]

Contraindications:

Children under 18 years old (at the moment there is insufficient data on the safety and effectiveness of the drug rilpivirine in children under 18; therefore, while clinical data on the safety and efficacy of the drug in children will not be obtained, it is not recommended to use the drug in this category of patients);

Severe hepatic impairment (at the moment there is insufficient data on the safety and effectiveness of the drug rilpivirine in patients with severe impairment of liver function (class C on the Child-Pugh scale); Therefore, until clinical data on the safety and efficacy of the drug in patients with severe impairment of liver function are not obtained, it is not recommended to use the drug in this category of patients).

Simultaneous reception with drugs, significantly lowering the concentration of rilpivirin in the plasma, as this may lead to a loss of the virologic response or to the development of resistance to rilpivirin or to the entire class of non-nucleoside reverse transcriptase inhibitors.A significant decrease in the concentrations of rilpivirin in plasma can occur when the drugs taken simultaneously with rilpivirin are metabolized via the CYP3A isoenzyme or increase the pH level in the stomach:

anticonvulsants - carbamazepine, oxcarbazepine, phenobarbital, phenytoin;

antituberculous agents - rifabutin, rifampicin, rifapentin; proton pump inhibitors - such as esomeprazole, lansoprazole, omeprazole, pantoprazole, rabeprazole;

Systemic SCS - dexamethasone (when taken more than 1 time);

preparations based on St. John's wort (Hypericum perforatum);

Lactose intolerance, deficiency of lactase, glucose-galactose malabsorption.

Hypersensitivity to rilpivirin or any other components of the drug.

Carefully:

Carefully should be applied rilpivirine in combination with drugs that can cause a polymorphic ventricular tachycardia such as "pirouette". Data on the potential interaction of rilpivirin and drugs that extend the QT interval are limited. In a study involving healthy volunteers, it was found that rilpivirine in high doses (75 mg once a day and 300 mg once a day) prolongs the QT interval on the ECG.

Pregnancy and lactation:

Adequate and well-controlled clinical or pharmacokinetic studies of drug use with pregnant women have not been conducted. There was no evidence of embryotoxicity or reproductive effects in animals. Rilpivirine should be used during pregnancy only if the possible benefit to the mother exceeds the potential risk to the fetus.

It is not known whether the rilpivirine in the breast milk of nursing women. In connection with the risk of contracting HIV infection and the possible development of adverse events in infants who are breastfeeding, it is not recommended to perform breastfeeding while taking the drug.

Due to the lack of adequate and well-controlled clinical trials of rilpivirin in pregnant women, women of childbearing age are advised to use effective contraceptive during the administration of the drug.

Data on the effects of rilpivirin on reproductive function are not available.

Category FDA recommendations are not defined.

Dosing and Administration:

The recommended dose of the drug is 25 mg (1 tab.) Orally 1 time / day during meals.

If the delay in taking the drug is less than 12 hours, the patient should take a tablet of rilpivirin as soon as possible with the food, the next tablet is taken at the usual time. If the delay in taking the drug is more than 12 hours, the missed dose should not be taken; the next tablet is taken at the usual time.

Side effects:

From the digestive system: often - decreased appetite, pain in the abdomen, vomiting, nausea; infrequently - discomfort in the abdomen.

From the side of the central nervous system: often - depression, insomnia, unusual dreams, sleep disorder, dizziness, headache; infrequent - a decrease in mood, drowsiness.

From the skin and subcutaneous tissue: often - a rash.

From the laboratory indicators: often - increased activity of transaminases. There were also cases of a decrease in the concentration of hemoglobin, platelets, leukocytes, increased activity of AST, ALT, pancreatic amylase, lipase, increased bilirubin, total cholesterol, LDL and triglycerides.The mean change in total cholesterol concentration (fasting) was 2 mg / dL, HDL (fasting) 4 mg / dL, LDL fast (1 mg / dL) and triglycerides (fasting) 7 mg / dl.

Are common: often fatigue.

Description of individual adverse reactions

Redistribution of subcutaneous fat (FFA)

Combined antiretroviral therapy causes the redistribution of PLN (lipodystrophy) in HIV-infected patients and is manifested by loss of subcutaneous fat on the periphery (upper and lower extremities) and the facial area, increased levels of fat in the intraperitoneal and visceral regions, mammary hypertrophy and accumulation of subcutaneous fat in the dorsocervical region (the "buffalo hump").

Immunodeficiency Syndrome

In HIV-infected patients with severe form of immunodeficiency, who have just begun to receive combined antiretroviral therapy, the inflammatory response to the presence of opportunistic agents with the appearance or exacerbation of symptoms of a disease previously asymptomatic (immune reconstitution syndrome) may develop on the background of restoration of the immune system.

Patients who are co-infected with hepatitis B and / or hepatitis C virus

In patients co-infected with the hepatitis B or C virus, who received rilpivirine, the frequency of increase in the level of hepatic enzymes was higher than in patients with only HIV infection. The pharmacokinetic effect of rilpivirin in co-infected patients is comparable to that of patients without co-infection.

The increase in serum creatinine was observed during the first four weeks of therapy and remained stable until the 48th week. The mean change after 48 weeks of therapy was 0.09 mg / dL (range: -0.20 mg / dl to 0.62 mg / dL). In patients with mild to moderate renal insufficiency, this increase in serum creatinine levels was comparable to an increase in serum creatinine in patients with normal renal function. These changes were regarded as clinically insignificant, and no patient discontinued therapy due to an increase in serum creatinine levels.

Overdose:No data.

Interaction:

Rilpivirin is metabolized with cytochrome P450 (CYP) 3A isoenzymes, so drugs that induce or inhibit CYP3A affect the excretion of rilpivirin.

Simultaneous reception rilpivirina and drugs capable of inducing CYP3A, can lead to a decrease in the concentration of rilpivirin in the blood plasma and reduce the therapeutic effect of rilpivirin.

Simultaneous reception rilpivirina and medicinal drugs that inhibit CYP3A, can lead to an increase in the concentration of rilpivirin in the blood plasma.

Simultaneous reception rilpivirina and drugs that raise the pH level in the stomach, can lead to a decrease in the concentration of rilpivirin in the blood plasma and to a possible decrease in the therapeutic effect of rilpivirin.

Probability decrease in efficiency oral contraceptives with simultaneous admission with rilpivirinom low. Correction of the dose of contraceptives based on estrogen and / or progesterone while taking with rilpivirin is not required.

Data on potential interaction rilpivirine and drugs that extend the QT interval, are bounded. In a study involving healthy volunteers, it was found that rilpivirine in high doses (75 mg once a day and 300 mg 1 time / day) prolongs the QT interval on the ECG. Concerning rilpivirine should be used with caution in combination with drugs that can cause a polymorphic ventricular tachycardia such as "pirouette".

Special instructions:

Patients should be informed that, with current antiretroviral therapy, HIV infection can not be cured, nor can HIV infection be prevented through blood or through sexual contact. Take the necessary precautions to prevent HIV infection.

Before starting therapy with the drug rilpivirine should take into account the following: the participants in the study who received rilpivirine, with an HIV-1 RNA of more than 100,000 copies / ml at the time of initiation of therapy, the absence of a virologic response was more likely than in patients who had HIV-1 RNA values less than 100,000 at the time of initiation of therapy. The observed virological inefficiency in the treatment with rilpivirin resulted in a higher incidence of resistance to NNRTIs. In patients with observed virologic failure receiving rilpivirin therapy, resistance to lamivudine / emtricitabine was more likely than in patients with observed virological inefficiency who received the drug efavirenz.

Instructions

Rilpivirine (Rilpivirinum)