EDURANT

Indications

• HIV-1 infection
• Antiretroviral therapy in treatment-naive patients
• Combination therapy with other antiretroviral agents

Dosage

Children: For paediatric patients aged 12 years and older, rilpivirine is recommended in combination with other antiretroviral medications. Specific dosing should be referred to in the BNF for Children.

Adults: The recommended initial dose is 900 mg administered as an intramuscular injection at month 2, following a lead-in period. Maintenance doses are 600 mg every month from month 3 onwards. For oral administration, the usual initial dose is 25 mg once daily.

Mechanism of action

Rilpivirine binds non-competitively to the reverse transcriptase enzyme of HIV-1. This binding inhibits the RNA and DNA-dependent DNA polymerase activities, effectively blocking HIV-1 replication. Its structural flexibility allows it to adapt to changes in the non-nucleoside RT binding pocket, making it less susceptible to resistance mutations compared to other NNRTIs.

Pharmacodynamics

As an NNRTI, rilpivirine inhibits the replication of HIV-1. It has a long duration of action, which permits once-daily oral dosing or monthly intramuscular injections. Patients are advised about potential side effects, including hypersensitivity reactions, hepatotoxicity, and mood disorders, alongside the possibility of body fat redistribution.

Pharmacokinetics

Rilpivirine exhibits variable absorption and a half-life that supports once-daily dosing. It is metabolized primarily by the liver, with a significant interaction profile that necessitates monitoring of liver function, especially during the initial treatment phase. Renal and hepatic impairment may affect drug clearance, requiring caution in these populations.

Contra-indications

• Severe hepatic impairment
• Severe renal impairment

Adverse effects

• Rash
• Depression
• Dizziness
• Drowsiness
• Gastrointestinal discomfort
• Headache
• Nausea
• Sleep disorders
• Vomiting
• Anxiety
• Asthenia
• Diarrhoea
• Fever
• Malaise
• Myalgia
• Weight increase
• General malaise
• Hypersensitivity reactions

Interactions

• Mitotane (unknown effect on rilpivirine exposure)
• Dabrafenib (unknown effect on rilpivirine exposure)

Precautions

• Monitor liver function closely during the first 18 weeks of treatment
• Monitor for skin reactions during the first 18 weeks
• Caution in patients with hepatic disease or co-infection with hepatitis B or C
• Patients should be informed about the risk of hypersensitivity reactions

Pregnancy

Use during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

It is unknown whether rilpivirine is excreted in human milk; caution should be exercised when administering to breastfeeding women.

Storage

Store in a cool, dry place, away from light. Do not freeze.

Formulations

• Rilpivirine hydrochloride 25 mg tablet (Edurant)
• Rilpivirine intramuscular injection (long-acting formulation)

Mechanism of action

Rilpivirine is a non-competitive NNRTI that binds to reverse transcriptase. Its binding results in the blockage of RNA and DNA- dependent DNA polymerase activities, like HIV-1 replication. It does not present activity against human DNA polymerases α, β and γ. Rilpivirine's flexible structure around the aromatic rings allows the adaptation to changes in the non-nucleoside RT binding pocket, reducing the likelihood of viral mutations conferring resistance. Rilpivirine, a diarylpyrimidine nonnucleoside reverse transcriptase inhibitor (NNRTI), inhibits replication of human immunodeficiency virus type 1 (HIV-1) by interfering with viral RNA- and DNA-directed polymerase activities of reverse transcriptase. Diarylpyrimidine NNRTIs (e.g., rilpivirine, etravirine) are capable of adapting to mutations in HIV-1 reverse transcriptase because of structural flexibility that allows for binding to the allosteric NNRTI binding pocket in a variety of conformations. Unlike other currently available NNRTIs, rilpivirine contains a cyanovinyl group that contributes to potency and maintains the drug's binding ability, despite the emergence of some resistance mutations.

Pharmacodynamics

Rilpivirine is a non-nucleoside reverse transcriptase inhibitor that inhibits the replication of HIV-1. It has a long duration of action as the oral tablet is given daily and the intramuscular suspension is given monthly. Patients should be counselled regarding the risk of hypersensitivity reactions, hepatotoxicity, depressive disorders, and the redistribution or accumulation of body fat.