Rilpivirine (Monograph)

Brand name: Edurant
Drug class: HIV Nonnucleoside Reverse Transcriptase Inhibitors

Medically reviewed by Drugs.com on Oct 26, 2023. Written by ASHP.

Introduction

Antiretroviral; HIV nonnucleoside reverse transcriptase inhibitor (NNRTI).

Uses for Rilpivirine

Treatment of HIV Infection

Treatment of HIV-1 infection in treatment-naïve and previously treated^{† [off-label]} adults and adolescents ≥12 years of age and weighing ≥35 kg with baseline plasma HIV-1 RNA levels ≤100,000 copies/mL; used in conjunction with other antiretrovirals (ARVs). Rilpivirine is included in various ARV regimens recommended in guidelines for treatment of HIV in adults and adolescents, pediatric patients, and pregnant patients. Fixed dose combinations containing rilpivirine and dolutegravir (Juluca), rilpivirine and cabotegravir (Cabenuva), rilpivirine, emtricitabine, and tenofovir disoproxil fumarate (DF, Complera), and rilpivirine, emtricitabine, and tenofovir alafenamide (Odefsey) are used in the treatment of HIV infection. See the full prescribing information for use of each of these combination products.

Short-term treatment of HIV-1 infection, in combination with oral cabotegravir, in adults and adolescents ≥12 years of age and weighing ≥35 kg who are virologically suppressed (HIV-1 RNA <50 copies/mL) on a stable regimen with no history of treatment failure and with no known or suspected resistance to either cabotegravir or rilpivirine.

Postexposure Prophylaxis following Occupational Exposure to HIV (PEP)

Postexposure prophylaxis of HIV infection following occupational exposure^{† [off-label]} (PEP) in health-care personnel and others exposed via percutaneous injury (e.g., needlestick, cut with sharp object) or mucous membrane or nonintact skin (e.g., chapped, abraded, dermatitis) contact with blood, tissue, or other body fluids that might contain HIV. Used in conjunction with other ARVs. Rilpivirine in combination with 2 NRTIs is among several alternative regimens recommended in guidelines for PEP when the preferred regimen cannot be used.

Postexposure Prophylaxis following Nonoccupational Exposure to HIV (nPEP)

Postexposure prophylaxis of HIV infection following nonoccupational exposure^{† [off-label]} (nPEP) in individuals exposed to blood, genital secretions, or other potentially infectious body fluids that might contain HIV when the exposure represents a substantial risk for HIV transmission. Used in conjunction with other ARVs. Rilpivirine in combination with 2 NRTIs is among several alternative regimens recommended in guidelines for nPEP. A fixed dose combination containing rilpivirine, emtricitabine, and tenofovir disoproxil fumarate (Complera) is used for nPEP in this setting. See the full prescribing information for use of Complera.

Rilpivirine Dosage and Administration

General

Pretreatment Screening

• Assess liver function tests prior to therapy initiation in patients with underlying hepatic disease such as hepatitis B (HBV) and/or C (HCV) co-infection or marked elevations in transaminase.

• Review concomitant medications for potential drug interactions prior to initiation of rilpivirine to avoid potential loss of virologic response.

Patient Monitoring

• Monitor liver function tests during therapy in patients with underlying hepatic disease such as HBV and/or HCV co-infection or marked elevations in transaminase. Consider monitoring liver function tests if no underlying hepatic dysfunction or risk factors.

• Review concomitant medications during therapy and consider potential for drug interactions with rilpivirine to avoid potential loss of virologic response.

Dispensing and Administration Precautions

• Rilpivirine is commercially available as a single entity and in various fixed-combination preparations containing additional ARV agents. Refer to the full prescribing information for specific, distinct uses of the combination products. Since the ARV agents contained in the fixed combination preparations also may be available in single-entity or other fixed-combination preparations, exercise care to ensure that therapy is not duplicated if a fixed combination is used in conjunction with other ARVs.

Administration

Oral Administration

Available as oral tablets.

Administer orally once daily with a meal. Use in conjunction with other ARVs.

Systemic exposure substantially decreased if rilpivirine given on empty stomach or with only a protein-rich nutritional drink.

Do not use single-entity rilpivirine (Edurant) and emtricitabine/rilpivirine/tenofovir alafenamide concomitantly.

Do not use single-entity rilpivirine (Edurant) and emtricitabine/rilpivirine/tenofovir DF (Complera) concomitantly, unless needed for adjustment of rilpivirine dosage (e.g., when fixed combination used concomitantly with rifabutin).

Fixed Combinations Containing Rilpivirine

Rilpivirine hydrochloride is commercially available in fixed-combination tablets containing dolutegravir sodium and rilpivirine (Juluca); emtricitabine, rilpivirine, and tenofovir alafenamide (Odefsey); and emtricitabine, rilpivirine, and tenofovir disoproxil fumarate (Complera). Rilpivirine is also commercially available as an extended-release injectable suspension kit containing copackaged cabotegravir and rilpivirine (Cabenuva). See the full prescribing information for administration of each of these combination products.

Dosage

Available as rilpivirine hydrochloride; dosage expressed in terms of rilpivirine.

Pediatric Patients

Treatment of HIV Infection in Antiretroviral-naïve Pediatric Patients

Oral

Adolescents ≥12 years of age weighing ≥35 kg: 25 mg once daily.

Treatment of HIV Infection in Antiretroviral-experienced Pediatric Patients in Combination with Cabotegravir

Oral

Adolescents ≥12 years of age weighing ≥35 kg: 25 mg once daily.

Take in combination with cabotegravir (Vocabria) 30 mg once daily.

Use oral lead-in therapy with rilpivirine (Edurant) and cabotegravir (Vocabria) for 1 month (at least 28 days) to assess rilpivirine tolerability prior to cabotegravir/rilpivirine (Cabenuva) injections.

Administer last oral dose on same day cabotegravir/rilpivirine (Cabenuva) injection dosing initiated.

If scheduled monthly injection of cabotegravir/rilpivirine (Cabenuva) is planned to be missed by >7 days, daily oral rilpivirine (Edurant) and cabotegravir (Vocabria) can be taken together for up to 2 months to replace missed injections.

Recommended oral daily dose is one 25-mg tablet of rilpivirine and one 30-mg tablet of cabotegravir. Initiate first dose of oral therapy approximately same time as planned missed injection; continue until day injection dosing is restarted. For durations longer than 2 months, use alternative oral regimen.

If scheduled every-2-month injection of cabotegravir/rilpivirine (Cabenuva) is planned to be missed by >7 days, daily oral rilpivirine (Edurant) and cabotegravir (Vocabria) can be taken together for up to 2 months to replace 1 missed scheduled every-2-month injection.

Recommended oral daily dose is one 25-mg tablet of rilpivirine and one 30-mg tablet of cabotegravir. Initiate first dose of oral therapy approximately same time as planned missed injection; continue until day injection dosing is restarted. For durations longer than 2 months, use alternative oral regimen.

Treatment of HIV Infection in Pediatric Patients Receiving Rifabutin

Oral

Adolescents ≥12 years of age weighing ≥35 kg: 50 mg once daily. When rifabutin coadministration is stopped, decrease rilpivirine dose to 25 mg once daily.

Adults

Treatment of HIV Infection in Antiretroviral-naïve Adults

Oral

25 mg once daily.

Treatment of HIV Infection in Antiretroviral-experienced Adults in Combination with Cabotegravir

Oral

25 mg once daily.

Take in combination with cabotegravir (Vocabria) 30 mg once daily.

Use oral lead-in therapy with rilpivirine (Edurant) and cabotegravir (Vocabria) for 1 month (at least 28 days) to assess rilpivirine tolerability prior to cabotegravir/rilpivirine (Cabenuva) injections.

Administer last oral dose on same day cabotegravir/rilpivirine (Cabenuva) injection dosing initiated.

If scheduled monthly injection of cabotegravir/rilpivirine (Cabenuva) is planned to be missed by >7 days, daily oral rilpivirine (Edurant) and cabotegravir (Vocabria) can be taken together for up to 2 months to replace missed injections.

Recommended oral daily dose is one 25-mg tablet of rilpivirine and one 30-mg tablet of cabotegravir. Initiate first dose of oral therapy approximately same time as planned missed injection; continue until day injection dosing is restarted. For durations longer than 2 months, use alternative oral regimen.

If scheduled every-2-month injection of cabotegravir/rilpivirine (Cabenuva) is planned to be missed by >7 days, daily oral rilpivirine (Edurant) and cabotegravir (Vocabria) can be taken together for up to 2 months to replace 1 missed scheduled every-2-month injection.

Recommended oral daily dose is one 25-mg tablet of rilpivirine and one 30-mg tablet of cabotegravir. Initiate first dose of oral therapy approximately same time as planned missed injection; continue until day injection dosing is restarted. For durations longer than 2 months, use alternative oral regimen.

Treatment of HIV Infection in Adults Receiving Rifabutin

Oral

50 mg once daily. When rifabutin coadministration is stopped, decrease rilpivirine dose to 25 mg once daily.

Postexposure Prophylaxis following Occupational Exposure to HIV (PEP)† [off-label]

Oral

25 mg once daily. Use in conjunction with 2 NRTIs .

Initiate PEP as soon as possible following occupational exposure to HIV (preferably within hours); continue for 4 weeks, if tolerated.

Postexposure Prophylaxis following Nonoccupational Exposure to HIV (nPEP)† [off-label]

Oral

Emtricitabine/rilpivirine/tenofovir DF (Complera): 1 tablet (200 mg of emtricitabine, 25 mg of rilpivirine, and 300 mg of tenofovir DF) once daily. Use as a complete regimen for nPEP.

Initiate nPEP as soon as possible (within 72 hours) following nonoccupational exposure that represents a substantial risk for HIV transmission and continue for 28 days.

nPEP not recommended if exposed individual seeks care >72 hours after exposure.

Special Populations

Hepatic Impairment

Administer usual dosage in patients with mild or moderate hepatic impairment (Child-Pugh class A or B); not studied in those with severe hepatic impairment (Child-Pugh class C).

Renal Impairment

Administer usual dosage in patients with mild or moderate renal impairment. Manufacturer makes no specific dosage recommendations for those with severe renal impairment or end-stage renal disease (ESRD); use with caution.

Geriatric Patients

Select dosage with caution because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.

Cautions for Rilpivirine

Contraindications

• Concomitant use with drugs that induce CYP3A or elevate gastric pH contraindicated since substantially decreased plasma rilpivirine concentrations may occur and may result in loss of virologic response and development of resistance to rilpivirine and/or class resistance to other NNRTIs. This includes certain anticonvulsants (carbamazepine, oxcarbazepine, phenobarbital, phenytoin), certain antimycobacterials (rifampin, rifapentine), systemic dexamethasone (given in multiple doses), proton-pump inhibitors (esomeprazole, lansoprazole, omeprazole, pantoprazole, rabeprazole), and certain herbal supplements (St. John’s wort [Hypericum perforatum]).

Warnings/Precautions

Skin and Hypersensitivity Reactions

Severe skin and hypersensitivity reactions, including drug reaction with eosinophilia and systemic symptoms (DRESS), reported. Some skin reactions were accompanied by constitutional symptoms such as fever; others were associated with organ dysfunction, including elevated hepatic enzyme serum concentrations. Rash generally was grade 1 or 2 and occurred in the first 4–6 weeks of therapy.

Immediately discontinue rilpivirine if signs or symptoms of severe skin or hypersensitivity reactions develop (e.g., severe rash or rash accompanied by fever, blisters, mucosal involvement, conjunctivitis, facial edema, angioedema, hepatitis, or eosinophilia). Monitor clinical status, including laboratory parameters, and initiate appropriate therapy.

Hepatotoxicity

Adverse hepatic effects reported; hepatotoxicity reported in some patients without preexisting hepatic disease or other risk factors.

HIV-infected patients with HBV or HCV coinfection or marked elevations in aminotransferase concentrations prior to rilpivirine treatment may be at increased risk for development or worsening of aminotransferase concentration elevations.

In patients with underlying hepatic disease (e.g., HBV or HCV infection, elevated aminotransferase concentrations), perform laboratory tests to evaluate hepatic function prior to and during rilpivirine treatment (single entity or fixed combinations).

Consider liver enzyme monitoring in patients without preexisting hepatic disease or other risk factors.

Depressive Disorders

Depressive disorders (e.g., depressed mood, depression, dysphoria, major depression, altered mood, negative thoughts, suicide attempt, suicidal ideation) reported.

Advise patients experiencing severe depressive symptoms to seek immediate medical evaluation to determine the likelihood that symptoms are related to rilpivirine and to determine if benefits of continued rilpivirine outweigh risks.

Risk of Adverse Reactions or Loss of Virologic Response Due to Drug Interactions

Concomitant use with certain drugs (e.g., drugs that may reduce rilpivirine concentrations, drugs known to increase risk of torsade de pointes) is contraindicated or requires particular caution. Some drug interactions may lead to loss of virologic effect of rilpivirine and the possible development of resistance. Consider the potential for drug interactions with concomitant medications prior to, and during treatment with rilpivirine.

Immune Reconstitution Syndrome

During initial treatment, HIV-infected patients who respond to antiretroviral therapy may develop an inflammatory response to indolent or residual opportunistic infections (e.g., Mycobacterium avium, M. tuberculosis, cytomegalovirus [CMV], Pneumocystis jirovecii [formerly P. carinii]); this may necessitate further evaluation and treatment.

Autoimmune disorders (e.g., Graves' disease, polymyositis, Guillain-Barré syndrome, autoimmune hepatitis) also reported to occur in the setting of immune reconstitution; time to onset is more variable and can occur many months after initiation of ARV therapy.

Specific Populations

Pregnancy

Human data indicate no increased risk of birth defects. No dosage adjustments necessary in females stable on a rilpivirine-containing regimen prior to pregnancy and who are virologically suppressed (<50 copies/mL). Monitor viral load closely in pregnant females; lower rilpivirine exposures have been observed in pregnant individuals.

Antiretroviral Pregnancy Registry at 800-258-4263 or [Web].

Lactation

Not known whether rilpivirine distributed into human milk or effects on breastfed infant or milk production; distributed into milk in rats.

Instruct HIV-infected females not to breast-feed because of risk of HIV transmission and risk of adverse effects in the infant.

Pediatric Use

Safety, efficacy, and pharmacokinetics not established in pediatric patients <12 years of age or weighing <35 kg.

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether they respond differently than younger adults.

Select dosage with caution because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.

Hepatic Impairment

Not studied in patients with severe hepatic impairment (Child-Pugh class C).

Higher incidence of increased serum aminotransferase concentrations reported in HIV-infected patients coinfected with HBV and/or HCV compared with those without coinfection.

Renal Impairment

Use with caution and increased monitoring for adverse effects in patients with severe renal impairment or ESRD; increased rilpivirine concentrations possible due to alterations in absorption, distribution, or metabolism.

Common Adverse Effects

Adverse effects of at least moderate to severe intensity (≥2%): depressive disorders, insomnia, headache, rash.

Drug Interactions

Rilpivirine is metabolized by CYP3A.

The following drug interactions are based on studies using single-entity rilpivirine. When rilpivirine fixed combinations are used, interactions associated with each drug in the fixed combination should be considered.

Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes

CYP3A inducers: Possible decreased rilpivirine concentrations and possible loss of virologic response and development of resistance to rilpivirine or the NNRTI class.

CYP3A inhibitors: Possible increased rilpivirine concentrations.

CYP substrates: Recommended rilpivirine dosage (25 mg once daily) unlikely to have clinically important pharmacokinetic interactions.

Drugs that Increase Gastric pH

Possible decreased rilpivirine concentrations, loss of virologic response, and development of drug resistance or NNRTI class resistance.

Drugs that Prolong the QT Interval

Only limited data available to date regarding potential for pharmacodynamic interaction if used concomitantly with drugs known to prolong QT interval and increase the risk of torsade de pointes. In healthy individuals, rilpivirine dosages of 75 or 300 mg daily (substantially higher than recommended dosage) resulted in clinically important prolongation of QT_c interval.

Use caution if rilpivirine used concomitantly with drugs known to increase risk of torsade de pointes.

Specific Drugs

Rilpivirine Pharmacokinetics

Absorption

Bioavailability

Absolute oral bioavailability unknown.

Peak plasma rilpivirine concentrations attained within approximately 4–5 hours.

Food

Systemic exposure decreased by about 40–50% if rilpivirine administered under fasting conditions or with only a protein-rich nutritional drink (300 kcal) compared with administration with a meal.

Administration with a standard meal (533 kcal) or high-calorie meal (982 kcal) results in similar rilpivirine exposures.

Distribution

Extent

Distribution into compartments other than plasma (e.g., CSF, genital tract secretions) not evaluated.

Plasma Protein Binding

Approximately 99.7% (in vitro), principally albumin.

Approximately 99% during second and third trimesters and postpartum period.

Elimination

Metabolism

Metabolized principally in the liver by CYP3A.

Elimination Route

Following oral administration of a single dose, 85% of rilpivirine dose eliminated in feces (75% as metabolites) and 6% eliminated in urine (<1% as unchanged rilpivirine).

Because rilpivirine is highly bound to plasma proteins, clinically important removal by peritoneal dialysis or hemodialysis is unlikely.

Half-life

Terminal elimination half-life is about 50 hours.

Special Populations

Mild or moderate hepatic impairment (Child-Pugh class A or B) increases rilpivirine exposure by 47 or 5%, respectively.

Coinfection with HIV and HBV or HCV does not alter rilpivirine exposure.

Mild renal impairment does not alter rilpivirine exposure. Only limited data available for patients with moderate or severe renal impairment; rilpivirine concentrations may be increased as a result of altered absorption, distribution, or elimination.

Pharmacokinetics in treatment-naïve HIV-1-infected pediatric patients 12 to <18 years of age receiving rilpivirine 25 mg once daily is similar to those observed in treatment-naïve adult patients.

Gender differences in pharmacokinetics not observed.

Race not expected to affect rilpivirine exposure.

Total exposure to rilpivirine 30-40% lower in pregnant females. Not clinically relevant if virologically suppressed (<50 copies/mL).

Stability

Storage

Oral

Tablets

25°C (excursions permitted to 15–30°C); store in original container.

Actions and Spectrum

• Inhibits replication of HIV-1 by interfering with viral RNA- and DNA-directed polymerase activities of reverse transcriptase.

• Rilpivirine is a diarylpyrimidine NNRTI; structural flexibility of these drugs 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 emergence of some resistance mutations in HIV-1 reverse transcriptase.

• Active in vitro against wild-type HIV-1, but has limited activity against HIV type 2 (HIV-2). Active in vitro against some clinical HIV-1 isolates resistant to other commercially available NNRTIs (delavirdine, efavirenz, nevirapine).

• Rilpivirine-resistant strains have been selected in cell culture and have emerged during clinical use.

• Cross-resistance can occur between rilpivirine and other commercially available NNRTIs. Up to 90% of rilpivirine-resistant isolates that developed in patients receiving rilpivirine in clinical studies were resistant to etravirine.

• Patients in clinical studies experiencing virologic failure while receiving a rilpivirine regimen were more likely to develop NNRTI-class resistance and treatment-emergent resistance to NRTIs than patients receiving an efavirenz regimen.

Advice to Patients

• Advise patients of the critical nature of compliance with HIV therapy and importance of remaining under the care of a clinician. Importance of taking as prescribed; do not alter or discontinue antiretroviral regimen without consulting clinician.

• Counsel patients on the importance of using single-entity rilpivirine in conjunction with other antiretrovirals—not for monotherapy.

• Antiretroviral therapy is not a cure for HIV infection; opportunistic infections and other complications associated with HIV disease may still occur.

• Advise patients that sustained decreases in plasma HIV RNA have been associated with reduced risk of progression to acquired immunodeficiency disease (AIDS) and death.

• Advise patients that effective antiretroviral regimens can decrease HIV concentrations in blood and genital secretions and strict adherence to such regimens in conjunction with risk-reduction measures may decrease, but cannot absolutely eliminate, the risk of secondary transmission of HIV to others. Importance of continuing to practice safer sex (e.g., using latex or polyurethane condoms to minimize sexual contact with body fluids), never sharing personal items that can have blood or body fluids on them (e.g., toothbrushes, razor blades), and never reusing or sharing needles.

• Advise patients of the importance of reading patient information provided by the manufacturer.

• Advise patients of the importance of taking once daily with a meal; a protein drink alone does not constitute a meal. Food enhances absorption of rilpivirine.

• Counsel patients that if a missed dose of single-entity rilpivirine is remembered within 12 hours, take the dose with a meal as soon as possible and take next dose at regularly scheduled time. If the missed dose is remembered more than 12 hours after the scheduled time, omit the missed dose and take next dose at regularly scheduled time. Advise patients that doses that are larger or smaller than the prescribed dosage should not be taken at any time.

• Advise patients that skin reactions ranging from mild to severe, including DRESS, reported with rilpivirine-containing antiretroviral regimens. Instruct patients to immediately stop taking rilpivirine (single entity or fixed combinations) and contact a clinician if a rash develops and is also associated with fever, blisters, mucosal involvement, eye inflammation (conjunctivitis), swelling of the face, eyes, lips, mouth, tongue, or throat which may lead to difficulty swallowing or breathing, or any signs and symptoms of liver problems.

• Advise patients that depressive disorders (e.g., depressed mood, depression, dysphoria, major depression, altered mood, negative thoughts, suicide attempt, suicidal ideation) have been reported. Importance of immediately contacting clinician if depressive symptoms (e.g., feeling sad, hopeless, anxious, or restless; hurting oneself; having thoughts of hurting oneself) occur.

• Advise patients that hepatotoxicity has been reported in patients receiving rilpivirine.

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and herbal products (e.g., St. John’s wort), and any concomitant illnesses.

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.

• Importance of advising patients of other important precautionary information.

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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Frequently asked questions

• What is the difference between HIV treatments Odefsey and Complera?
• What drugs are contained in HIV treatment Juluca?

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