Rilpivirine

Rilpivirine is an antiviral drug [see Microbiology (12.4) ] .

• EDURANT and EDURANT PED are a human immunodeficiency virus type 1 (HIV-1) specific, non-nucleoside reverse transcriptase inhibitor (NNRTI) indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection in treatment-naïve patients 2 years of age and older and weighing at least 14 kg with HIV-1 RNA less than or equal to 100,000 copies/mL. ( 1.1 ).ICD-10: B20

• EDURANT and EDURANT PED are contraindicated for coadministration with the drugs in Table 2 for which significant decreases in rilpivirine plasma concentrations may occur due to CYP3A enzyme induction or gastric pH increase, which may result in loss of virologic response and possible resistance to EDURANT or EDURANT PED or to the class of NNRTIs [see Drug Interactions (7) and Clinical Pharmacology (12.3) ] . Table 2: Drugs That are Contraindicated with EDURANT and EDURANT PED Drug Class Contraindicated Drugs in Class Clinical Comment Anticonvulsants Carbamazepine Oxcarbazepine Phenobarbital Phenytoin Potential for significant decreases in rilpivirine plasma concentrations due to CYP3A enzyme induction, which may result in loss of virologic response.contraindicated

One 25 mg EDURANT tablet taken once daily with a meal for patients weighing at least 25 kg. ( 2.2 ) Pediatric patients 2 years of age and older and weighing at least 14 kg to less than 25 kg: Dosage of EDURANT PED is based on body weight. ( 2.3 ) EDURANT PED must be dispersed in drinking water and taken with a meal. ( 2.4 ) Do not substitute EDURANT tablets and EDURANT PED tablets for oral suspension on a milligram-per-milligram basis due to differing pharmacokinetic profiles. ( 2.1 , 5.6 ) See full prescribing information for dosing information when used in combination with cabotegravir. ( 2.6 ) For pregnant patients who are already on a stable EDURANT regimen prior to pregnancy and who are virologically suppressed (HIV-1 RNA less than 50 copies per mL) the recommended dosage in adults and pediatric patients weighing more than 25 kg is one 25 mg tablet once daily taken orally with a meal. ( 2.5 , 12.3 ) Rifabutin coadministration: Take two 25 mg tablets of EDURANT once daily with a meal for the duration of the rifabutin coadministration. ( 2.7 ) 2.1 Overview of Different Dosage Forms EDURANT is available in two dosage forms: EDURANT 25 mg film-coated tablets for adults and pediatric patients weighing at least 25 kg. EDURANT PED 2.5 mg tablets for oral suspension should only be given to pediatric patients weighing at least 14 kg to less than 25 kg [see Dosage and Administration (2.3) ] . Do not substitute EDURANT tablets and EDURANT PED tablets for oral suspension on a milligram-per-milligram basis due to differing pharmacokinetic profiles.

Skin and Hypersensitivity Reactions: Severe skin and hypersensitivity reactions have been reported during postmarketing experience, 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. ( 5.1 ) Hepatotoxicity: Hepatic adverse events have been reported in patients with underlying liver disease, including hepatitis B or C virus co-infection, or in patients with elevated baseline transaminases. A few cases of hepatotoxicity have occurred in patients with no pre-existing hepatic disease. Monitor liver function tests before and during treatment with EDURANT or EDURANT PED in patients with underlying hepatic disease, such as hepatitis B or C virus co-infection, or marked elevations in transaminase. Also consider monitoring liver functions tests in patients without pre-existing hepatic dysfunction or other risk factors. ( 5.2 ) Depressive Disorders: Severe depressive disorders have been reported. Immediate medical evaluation is recommended for severe depressive disorders. ( 5.3 ) Patients may develop immune reconstitution syndrome. ( 5.5 ) 5.1 Skin and Hypersensitivity Reactions Severe skin and hypersensitivity reactions have been reported during the postmarketing experience, including cases of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), with rilpivirine-containing regimens.

The following adverse reactions are discussed below and in other sections of the labeling: Skin and Hypersensitivity Reactions [see Warnings and Precautions (5.1) ] Hepatotoxicity [see Warnings and Precautions (5.2) ] Depressive Disorders [see Warnings and Precautions (5.3) ] The most common adverse reactions to EDURANT or EDURANT PED (incidence >2%) of at least moderate to severe intensity (≥ Grade 2) were depressive disorders, headache, insomnia and rash. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Janssen Products, LP at 1-800-526-7736 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. Clinical Trials Experience in Adults The safety assessment is based on the Week 96 pooled data from 1368 patients in the Phase 3 controlled trials TMC278-C209 (ECHO) and TMC278-C215 (THRIVE) in antiretroviral treatment-naïve HIV-1 infected adult patients, 686 of whom received EDURANT (25 mg once daily) [see Clinical Studies (14.1) ] . The median duration of exposure for patients in the EDURANT arm and efavirenz arm was 104.3 and 104.1 weeks, respectively. Most adverse reactions occurred in the first 48 weeks of treatment. The proportion of subjects who discontinued treatment with EDURANT or efavirenz due to adverse reaction, regardless of severity, was 2% and 4%, respectively.

Pregnancy: Total rilpivirine exposures were generally lower during pregnancy compared to the postpartum period. ( 2.5 , 8.1 , 12.3 ) 8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to EDURANT during pregnancy. Healthcare providers are encouraged to register patients by calling the Antiretroviral Pregnancy Registry (APR) 1-800-258-4263. Risk Summary 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 (see Data ) . The rate of miscarriage is not reported in the APR. The estimated background rate of miscarriage in clinically recognized pregnancies in the U.S. general population is 15% to 20%. The background risk for major birth defects and miscarriage for the indicated population is unknown. Methodologic limitations of the APR include the use of MACDP as the external comparator group. The MACDP population is not disease-specific, evaluates women and infants from a limited geographic area, and does not include outcomes for births that occurred at <20 weeks gestation. In a clinical trial, total rilpivirine exposures were generally lower during pregnancy compared to the postpartum period (see Data ) .

Metabolism

Pharmacokinetics in Adults The pharmacokinetic properties of rilpivirine have been evaluated in adult healthy subjects and in adult antiretroviral treatment-naïve HIV-1-infected subjects. Exposure to rilpivirine was generally lower in HIV-1 infected subjects than in healthy subjects.

There is no specific antidote for overdose with EDURANT or EDURANT PED. Human experience of overdose with EDURANT or EDURANT PED is limited. Treatment of overdose with EDURANT or EDURANT PED consists of general supportive measures including monitoring of vital signs and ECG (QT interval) as well as observation of the clinical status of the patient. It is advisable to contact a poison control center to obtain the latest recommendations for the management of an overdose. Since rilpivirine is highly bound to plasma protein, dialysis is unlikely to result in significant removal of the active substance.

• May 20, 2011NDANDA202022Janssen Prods
• Aug 10, 2011NDANDA202123Gilead Sciences Inc
• Mar 1, 2016NDANDA208351Gilead Sciences Inc
• Nov 21, 2017NDANDA210192Viiv Hlthcare
• Jan 21, 2021NDANDA212888Viiv Hlthcare
• Mar 15, 2024NDANDA219016Janssen Prods
• May 20, 2025ANDAANDA208452Mylan
• Jan 29, 2026ANDAANDA218798Somerset Theraps Llc

1. 1Bone Density Decreased4,41318%
2. 2Renal Injury3,21313%
3. 3Skeletal Injury2,97712%
4. 4Chronic Kidney Disease2,69711%
5. 5Pain2,63911%
6. 6Tooth Loss2,4029.9%
7. 7Renal Failure2,1558.9%
8. 8Anxiety2,0698.5%
9. 9Emotional Distress2,0308.4%
10. 10Tooth Injury1,9768.2%
11. 11Bone Loss1,9448.0%
12. 12Osteonecrosis1,8987.8%
13. 13Multiple Fractures1,8807.8%
14. 14Osteoporosis1,8707.7%
15. 15Anhedonia1,8027.4%

Recent PubMed references pinned to Rilpivirine as a MeSH major topic. Citations link to pubmed.ncbi.nlm.nih.gov.

• Safety and efficacy of deltoid intramuscular long-acting cabotegravir and rilpivirine, a case series.
  Antiviral therapy · 2026 · Pannecoucke C, Valin N, Peytavin G, et al.
  PMID 42125948DOI 10.1177/13596535261436877
• Feasibility, Fidelity, and Effectiveness of Administering Long-Acting Cabotegravir + Rilpivirine in Infusion Centers in the United States: Findings From the Phase 4 GLACIER Implementation Study.
  Journal of the International Association of Providers of AIDS Care · 2026 · Gutner CA, Harrington C, Bontempo G, et al.
  PMID 42117620DOI 10.1177/23259582261439585
• Long-acting injectable ART: Promise for adherence, but persistent gaps in global access.
  Med (New York, N.Y.) · 2026 · Jennings L, Bekker LG
  PMID 42105739DOI 10.1016/j.medj.2026.101137
• Real-World Patterns of Discontinuation and Virologic Failure with Long-Acting Cabotegravir-Rilpivirine.
  AIDS research and human retroviruses · 2026 · Hockney S, Mueller D, Phillbrick A, et al.
  PMID 42087552DOI 10.1177/08892229261449867
• Real-world adherence, persistence, and health care resource utilization among people with HIV receiving long-acting cabotegravir plus rilpivirine compared with oral antiretroviral therapy in the United States: The ABOVE Study.
  Journal of managed care & specialty pharmacy · 2026 · Garris C, DerSarkissian M, Chang R, et al.
  PMID 42043923DOI 10.18553/jmcp.2026.32.5.584
• Effectiveness and Persistence of Long-Acting Injectable Cabotegravir and Rilpivirine in Migrant Individuals Living With HIV in Spain: Substudy of the RELATIVITY Cohort.
  Journal of the International AIDS Society · 2026 · Llenas-García J, Arcos Rueda MDM, Calderón Hernaiz R, et al.
  PMID 42011965DOI 10.1002/jia2.70106
• Virological outcomes of PWH who discontinued cabotegravir/rilpivirine long-acting therapy in a real-world context.
  International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases · 2026 · Gagliardini R, Tavelli A, Mazzotta V, et al.
  PMID 41997417DOI 10.1016/j.ijid.2026.108704
• The plasma and intracellular exposure of intramuscularly administered long-acting cabotegravir and rilpivirine in people with HIV.
  The Journal of antimicrobial chemotherapy · 2026 · Ferrara M, Maccario V, Barrera F, et al.
  PMID 41937337DOI 10.1093/jac/dkag113

The 10 most recently updated of 179 ClinicalTrials.gov registrations naming Rilpivirine as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• Long-Acting Cabotegravir and Rilpivirine in People Living With HIV-1 Subtype A6: A Real-World Retrospective Study
  Recruiting · Observational · 250 enrolled · Pomeranian Medical University Szczecin
  NCT07370649updated 2026-06-11
• Targeted Therapies for Immunological Non-Responders in People With HIV: A Multicenter Clinical Study
  Not yet recruiting · Phase 2 · Interventional · 21 enrolled · Beijing 302 Hospital
  NCT07637877updated 2026-06-10
• Cabotegravir & Rilpivirine Antiretroviral Therapy in Pregnancy
  Not yet recruiting · Observational · 40 enrolled · International Maternal Pediatric Adolescent AIDS Clinical Trials Group
  NCT07637942updated 2026-06-10
• A Roll-over Study With Rilpivirine for Human Immunodeficiency Virus Type 1 (HIV-1) Infected Participants Who Participated in Rilpivirine Pediatric Studies
  Active not recruiting · Phase 2 · Interventional · 48 enrolled · Janssen Sciences Ireland UC
  NCT02494986updated 2026-06-05
• Study to Compare an Oral Weekly Islatravir/Lenacapavir Regimen With Standard of Care in Virologically Suppressed People With HIV-1
  Active not recruiting · Phase 3 · Interventional · 600 enrolled · Gilead Sciences
  NCT06630299updated 2026-05-29
• A Study to Evaluate the Effectiveness of Long-acting (LA) Cabotegravir (CAB) + Rilpivirine (RPV) LA When Given to Participants With Detectable HIV-1
  Recruiting · Phase 3 · Interventional · 332 enrolled · ViiV Healthcare
  NCT06694805updated 2026-05-27
• A Study to Evaluate the Efficacy, Safety, Participant Choice and Preference of an Oral Once-daily Regimen or a Long-acting Injectable Regimen Every Two Months for Treatment of Human Immunodeficiency Virus (HIV-1) in Adults Who Have Not Previously Taken Antiretroviral Therapy
  Completed · Phase 3 · Interventional · 171 enrolled · ViiV Healthcare
  NCT05917509updated 2026-05-27
• Study of Oral and Long-Acting Injectable Cabotegravir and Rilpivirine in Virologically Suppressed Children Living With HIV-1, Two to Less Than 12 Years of Age
  Recruiting · Phase 1 · Phase 2 · Interventional · 90 enrolled · National Institute of Allergy and Infectious Diseases (NIAID)
  NCT05660980updated 2026-05-19
• A Study of a Rilpivirine Extended-Release Suspension in Healthy Participants
  Completed · Phase 1 · Interventional · 126 enrolled · Janssen Research & Development, LLC
  NCT05112939updated 2026-05-12
• PERsistance of Long-Acting inJEctable CAB+RPV in a Cohort of Virologically-suppressed PLWH: a Real-life Study
  Not yet recruiting · Observational · 200 enrolled · Fondazione Policlinico Universitario Agostino Gemelli IRCCS
  NCT07579546updated 2026-05-12

Frequently asked questions

How does Rilpivirine work?

Rilpivirine is an antiviral drug [see Microbiology (12.4) ] .

What is Rilpivirine used for?

According to FDA labeling, Rilpivirine carries indications including: EDURANT and EDURANT PED are a human immunodeficiency virus type 1 (HIV-1) specific, non-nucleoside reverse transcriptase inhibitor (NNRTI) indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection in treatment-naïve patients 2 years of age and older and weighing at least 14 kg with HIV-1 RNA less than or equal to 100,000 copies/mL. ( 1.1 ).. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Rilpivirine?

Rilpivirine is classified as Non-nucleoside reverse transcriptase inhibitors, Human Immunodeficiency Virus 1 Non-Nucleoside Analog Reverse Transcriptase Inhibitor, Cytochrome P450 3A Inhibitors, Non-Nucleoside Reverse Transcriptase Inhibitors, Decreased Reverse Transcription to DNA, Stimulation Gastric Acid Secretion.

What are the brand names for Rilpivirine?

Rilpivirine is marketed under brand names including Complera, Edurant, Juluca, Odefsey.

What are the contraindications for Rilpivirine?

Rilpivirine labeling lists contraindications including: EDURANT and EDURANT PED are contraindicated for coadministration with the drugs in Table 2 for which significant decreases in rilpivirine plasma concentrations may occur due to CYP3A enzyme induction or gastric pH increase, which may result in loss of virologic response and possible resistance to EDURANT or EDURANT PED or to the class of NNRTIs [see Drug Interactions (7) and Clinical Pharmacology (12.3) ] . Table 2: Drugs That are Contraindicated with EDURANT and EDURANT PED Drug Class Contraindicated Drugs in Class Clinical Comment Anticonvulsants Carbamazepine Oxcarbazepine Phenobarbital Phenytoin Potential for significant decreases in rilpivirine plasma concentrations due to CYP3A enzyme induction, which may result in loss of virologic response.. Always consult the full prescribing information and a clinician.