rilpivirine (Rx)

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%)

Posmarketing reports

Severe skin and hypersensitivity reactions including DRESS (Drug Reaction with Eosinophilia and Systemic Symptoms)

Contraindications

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

Cautions

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

Healthcare providers are encouraged to register patients by call the Antiretroviral Pregnancy Registry (APR) 1-800-258-4263

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

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  

Absorption

Bioavailability: Absolute bioavailability unknown

Peak Plasma Time: 4-5 hr

Peak Plasma Concentration: 80 ng/mL (mean)

AUC: 2397 ng•h/mL (mean)

Food: Exposure ~40% lower when taken in a fasted condition as compared to a normal caloric meal (533 kcal) or high-fat high-caloric meal (928 kcal); when taken with only a protein-rich nutritional drink, exposures were 50% lower than when taken with a meal

Distribution

Protein Bound: 99.7% (primarily to albumin)

Metabolism

Metabolized primarily by CYP3A

Elimination

Half-life: 50 hr

Excretion: feces (85%), urine (6.1%) bile, other

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