Rilpivirine

Indications

Rilpivirine is used for: HIV-1 Infection, Treatment of human immunodeficiency virus type 1 (HIV-1) infection in antiretroviral treatment-naïve patients 12 years of age and older and weighing at least 35 kg with plasma HIV-1 RNA less than or equal to 100,000 copies/mL at the start of therapy.

Adult Dose

HIV-1 Infection Indicated in combination with other antiretroviral agents for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in treatment-naïve adult patients with HIV-1 RNA <100,000 copies/mL 25 mg PO qDay; administer with a meal Dose during pregnancy May continue use for pregnant patients on a stable rilpivirine regimen before pregnancy and who are virologically suppressed (ie, HIV-1 RNA <50 copies/mL) 25 mg PO qDay; administer with a meal Lower exposures of rilpivirine were observed during pregnancy, therefore viral load should be monitored closely Hepatic impairment Mild-to-moderate hepatic impairment (Child-Pugh Classes A and B): No dose adjustment required Severe hepatic impairment (Child-Pugh Class C): Has not been studied

Child Dose

HIV-1 Infection Indicated in combination with other antiretroviral agents for treatment of HIV-1 infection in treatment-naïve adolescents aged 12-17 yr with HIV-1 RNA ?100,000 copies/mL <12 years: Safety and efficacy not established 12-17 years (weight ?35 kg): 25 mg PO qDay; administer with a meal

Renal Dose

Renal impairment Mild-to-moderate renal impairment: No dose adjustment required Severe renal impairment or ESRD: Used with caution and with increased monitoring for adverse effects, plasma concentrations may be increased because of altered drug absorption, distribution, and metabolism secondary to renal dysfunction Dialysis: Highly bound to plasma proteins, unlikely to be significantly removed by hemodialysis or peritoneal dialysis

Administration

Oral Administration Must administer with a meal Must be able to take with a meal of at least 500 calories on a regular schedule (a protein drink alone does not constitute a meal) If coadministered with antacids should only be administered either at least 2 hr before or at least 4 hr after rilpivirine

Contra Indications

Hypersensitivity Coadministration with drugs (eg, CYP inducers like phenobarbital, dexamethasone, oxcarbazepine, phenytoin, or carbamazepine) where significant decreases in rilpivirine plasma concentrations may occur, which may result in loss of virologic response and possible resistance and cross-resistance to other NNRTIs Contraindicated with drugs that increase gastric pH (eg, esomeprazole, lansoprazole, omeprazole, pantoprazole, rabeprazole) that may decrease rilpivirine absorption and result in decreased rilpivirine plasma concentrations

Precautions

Coadministration with other NNRTIs may either increase or decrease rilpivirine; avoid use with other NNRTIs May increase risk for depressive disorders Hepatic adverse effects reported; patients with underlying hepatitis B or C, or marked increased transaminases prior to treatment may be at increased risk; monitor for hepatotoxicity before initiating and during treatment Redistribution/accumulation of body fat, including central obesity, dorsocervical fat enlargement (buffalo hump), peripheral wasting, facial wasting, breast enlargement, and “cushingoid appearance” have been observed in patients receiving antiretroviral therapy Immune reconstitution syndrome: During initial phase of combination ART treatment, patients whose immune system responds may develop an inflammatory response to indolent or residual opportunistic infections (eg, Mycobacterium avium complex, CMV, Pneumocystis pneumonia, TB) Severe skin and hypersensitivity reactions reported, including cases of drug reaction with eosinophilia and systemic symptoms (DRESS), with rilpivirine-containing regimens; immediately discontinue treatment if hypersensitivity or rash with systemic symptoms or elevations in hepatic serum biochemistries develop and closely monitor clinical status, including hepatic serum biochemistries

Pregnancy-Lactation

Pregnancy Available data from the APR show no difference in the overall risk of birth defects for rilpivirine compared with the background rate for major birth defects of 2.7% in the Metropolitan Atlanta Congenital Defects Program (MACDP) reference population Lactation Unknown whether distributed in human breast milk The CDC recommends that women in the United States should not breastfeed their infants because of risk of the following Postnatal HIV transmission (in HIV-negative infants) Developing viral resistance (in HIV-positive infants) Adverse reactions in nursing infants

Interactions

Drugs that induce or inhibit CYP3A may affect clearance of rilpivirine Coadministration with CYP3A4 inducers may decrease plasma concentrations of rilpivirine and result in loss of virologic response and possible resistance to rilpivirine OR to non-nucleoside reverse transcriptase inhibitors (NNRTIs) Coadministration with CYP3A4 inhibitors may increase plasma concentrations of rilpivirine Coadministration with drugs that increase gastric pH may decrease plasma concentrations of rilpivirine and result in loss of virologic response and possible resistance to rilpivirine or to NNRTIs In healthy subjects, rilpivirine 75 mg PO qDay (3 times rilpivirine dose) and 300 mg PO qDay (12 times rilpivirine dose) have been shown to prolong the QTc interval; consider alternatives when coadministered with a drug with a known risk of torsade de pointes

Adverse Effects

Side effects of Rilpivirine : 1-10% Depressive disorders (4%) Insomnia (3%) Headache (3%) Rash (3%) Increased AST (2%; grade 3 or higher) ALT increased (19%) Abnormal dreams (1%) Nausea (1%) Suicidal ideation (4-8%) Abdominal pain (1%) Vomiting (1%) Fatigue (1%) Dizziness (1%)

Mechanism of Action

Antiviral agent; diarylpyrimidine non-nucleoside reverse transcriptase inhibitor (NNRTI) of HIV-1 Inhibits HIV-1 replication by noncompetitive inhibition of HIV-1 reverse transcriptase Does not inhibit the human cellular DNA polymerases alpha, beta, and gamma