Dolutegravir and Rilpivirine (Monograph)

Brand name: Juluca
Drug class: HIV Integrase Inhibitors

Medically reviewed by Drugs.com on Mar 10, 2025. Written by ASHP.

Introduction

Antiretroviral; fixed combination of dolutegravir and rilpivirine (dolutegravir/rilpivirine).¹ Dolutegravir is an HIV integrase strand transfer inhibitor (INSTI) and rilpivirine is an HIV nonnucleoside reverse transcriptase inhibitor (NNRTI).¹

Uses for Dolutegravir and Rilpivirine

Treatment of HIV Infection

Used as a complete regimen for the treatment of HIV-1 infection in antiretroviral-experienced (previously treated) adults to replace the current antiretroviral regimen in those who are virologically suppressed (i.e., plasma HIV-1 RNA levels <50 copies/mL) on a stable antiretroviral regimen for ≥6 months, have no known history of treatment failure, and are infected with HIV-1 with no known substitutions associated with resistance to dolutegravir or rilpivirine.^{1 2 6 11}

Selection of an antiretroviral regimen should be individualized based on factors such as virologic efficacy, toxicity, pill burden, dosing frequency, drug-drug interaction potential, resistance test results, comorbid conditions, access, and cost.^{200 201 202}

Dolutegravir and rilpivirine are available as a fixed-combination preparation (dolutegravir/rilpivirine) and as separate single-entity products.^{1 226 236} Refer to the full prescribing information of the single-entity products for information on specific uses.^{226 236}

Dolutegravir and Rilpivirine Dosage and Administration

General

Pretreatment Screening

• Perform testing for hepatitis B virus (HBV) infection prior to initiation of dolutegravir/rilpivirine.²⁰⁰

Patient Monitoring

• Monitor for hepatotoxicity during treatment with dolutegravir/rilpivirine.¹

• Monitor for signs or symptoms of severe skin or hypersensitivity reactions based on clinical status and laboratory parameters; discontinue dolutegravir/rilpivirine immediately if signs or symptoms develop.¹

• Evaluate patients with severe depressive symptoms to determine relationship to treatment with dolutegravir/rilpivirine and whether continued treatment is warranted.¹

• Monitor more frequently for adverse effects in patients with severe renal impairment (creatinine clearance <30 mL/minute) or end-stage renal disease.¹

Dispensing and Administration Precautions

• The Institute for Safe Medication Practices (ISMP) list of error-prone abbreviations, symbols, and dose designations states that the use of abbreviations for antiretroviral medications (e.g., DOR, TAF, TDF) during the medication use process should be avoided as their use has been associated with serious medication errors.²³⁷

Administration

Oral Administration

Administer orally once daily with a meal.¹ A protein drink alone does not constitute a meal.¹

Dosage

Available as fixed-combination tablets containing dolutegravir sodium and rilpivirine hydrochloride; dosages expressed in terms of dolutegravir and rilpivirine, respectively.¹

Each fixed-combination tablet contains 50 mg of dolutegravir and 25 mg of rilpivirine.¹

Adults

Treatment of HIV-1 Infection

Antiretroviral-experienced Adults

Oral

1 tablet of dolutegravir/rilpivirine (dolutegravir 50 mg and rilpivirine 25 mg) once daily with a meal.¹

Antiretroviral-experienced Adults Receiving Rifabutin

Oral

1 tablet of dolutegravir/rilpivirine (dolutegravir 50 mg and rilpivirine 25 mg) and a 25-mg tablet of single-entity rilpivirine once daily with a meal to provide a total rilpivirine dosage of 50 mg daily for the duration of rifabutin coadministration.¹

Special Populations

Hepatic Impairment

Mild or moderate hepatic impairment (Child-Pugh class A or B): Dosage adjustments not needed.¹

Severe hepatic impairment (Child-Pugh class C): No specific dosage recommendations.¹

Renal Impairment

Mild or moderate renal impairment (Cl_cr ≥30 mL/minute): Dosage adjustments not needed.¹

Severe renal impairment (Cl_cr <30 mL/minute) or end-stage renal disease: No specific dosage recommendations; increased monitoring for adverse effects recommended.¹

Geriatric Patients

No specific dosage recommendations; use with caution because of age-related decreases in hepatic, renal, and/or cardiac function and potential for concomitant disease and drug therapy.¹

Cautions for Dolutegravir and Rilpivirine

Contraindications

• Previous hypersensitivity reaction to dolutegravir or rilpivirine.¹

• Concomitant use with dofetilide due to potential for serious and/or life-threatening adverse effects resulting from increased dofetilide plasma concentrations.¹

• Concomitant use with drugs that induce CYP3A or drugs that elevate gastric pH since substantially decreased plasma rilpivirine concentrations may occur and may result in loss of virologic response; these drugs include certain anticonvulsants (carbamazepine, oxcarbazepine, phenobarbital, phenytoin), certain antimycobacterials (rifampin, rifapentine), systemic dexamethasone (given in multiple doses), proton-pump inhibitors (e.g., esomeprazole, lansoprazole, omeprazole, pantoprazole, rabeprazole), and St. John’s wort (Hypericum perforatum).¹

Warnings/Precautions

Skin and Hypersensitivity Reactions

Hypersensitivity reactions (e.g., rash, constitutional findings, and sometimes organ dysfunction including liver injury) reported in patients receiving dolutegravir.¹

Severe skin and hypersensitivity reactions, including cases of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), reported during postmarketing experience with rilpivirine-containing regimens.¹ Some skin reactions were accompanied by constitutional symptoms; other skin reactions were associated with organ dysfunction, including elevated hepatic enzyme concentrations.¹

Immediately discontinue dolutegravir/rilpivirine if signs or symptoms of severe skin or hypersensitivity reactions occur (including, but not limited to, severe rash or rash accompanied by fever, general malaise, fatigue, muscle or joint aches, blisters or peeling of the skin, mucosal involvement [oral blisters or lesions], conjunctivitis, facial edema, hepatitis, eosinophilia, angioedema, difficulty breathing).¹ Monitor clinical status, including laboratory parameters with liver aminotransferases, and initiate appropriate therapy.¹

Delay in stopping dolutegravir/rilpivirine treatment after onset of hypersensitivity reaction may result in a life-threatening reaction.¹

Hepatotoxicity

Adverse hepatic effects reported in patients receiving dolutegravir- or rilpivirine-containing regimens.¹

HIV-infected patients with HBV or HCV coinfection or markedly elevated serum aminotransferase concentrations prior to initiation of dolutegravir/rilpivirine may be at increased risk for development or worsening of aminotransferase elevations.¹ In some patients receiving a dolutegravir-containing regimen, serum aminotransferase elevations were consistent with immune reconstitution syndrome or HBV reactivation, particularly in the setting where HBV therapy had been discontinued.¹

Cases of hepatic toxicity, including elevated serum liver biochemistries and hepatitis, also reported in patients receiving dolutegravir- or rilpivirine-containing regimens who had no preexisting hepatic disease or other identifiable risk factors.¹

Drug-induced liver injury leading to acute liver failure reported with dolutegravir-containing regimens; drug-induced liver injury leading to liver transplant reported with the fixed combination of abacavir, dolutegravir, and lamivudine (abacavir/dolutegravir/lamivudine).¹

Monitor for hepatotoxicity in patients receiving dolutegravir/rilpivirine.¹

Depressive Disorders

Depressive disorders (depressed mood, depression, dysphoria, major depression, altered mood, negative thoughts, suicide attempt, suicidal ideation) reported in patients receiving dolutegravir and/or rilpivirine.¹

Promptly evaluate patients experiencing severe depressive symptoms to determine the likelihood that symptoms are related to dolutegravir/rilpivirine and to determine if benefits of continued dolutegravir/rilpivirine therapy outweigh risks.¹

Drug Interactions

Concomitant use with certain drugs may result in drug interactions.¹ May lead to loss of therapeutic effects and possible development of resistance or possible adverse effects from increased exposures of concomitant drugs.¹

Because rilpivirine may prolong QT interval corrected for rate (QT_c), consider alternatives to dolutegravir/rilpivirine in patients receiving drugs with known risk of torsades de pointes.¹

Consider potential for drug interactions prior to and during treatment with dolutegravir/rilpivirine and monitor for adverse effects associated with concomitant drugs.¹

Use of Fixed Combinations

Consider cautions, precautions, contraindications, and interactions associated with both components of dolutegravir/rilpivirine.¹

Consider cautionary information applicable to specific populations (e.g., pregnant or nursing women, individuals with hepatic or renal impairment, geriatric patients) for each drug in the fixed combination.¹

Specific Populations

Pregnancy

Antiretroviral Pregnancy Registry (APR) monitors pregnancy outcomes in women exposed to dolutegravir/rilpivirine during pregnancy.¹ Clinicians encouraged to register patients in the APR by calling 800-258-4263 or visiting [Web].¹

Lactation

Dolutegravir distributed into human milk.¹ Unknown whether rilpivirine distributed into human milk;²²⁶ detected in milk of lactating rats.¹

Not known whether dolutegravir or rilpivirine affects human milk production or affects breast-fed infant.^{1 226}

Per HHS perinatal HIV transmission guideline, inform patients that feeding with appropriate formula or pasteurized donor human milk from a milk bank eliminates postnatal HIV transmission risk to the infant.²⁰² Additionally, achieving and maintaining viral suppression with antiretroviral therapy during pregnancy and postpartum reduces risk of breastfeeding HIV transmission to <1%, but not does not completely eliminate risk.²⁰² Replacement feeding with formula or banked pasteurized donor milk is recommended when patients with HIV are not on antiretroviral therapy and/or do not have a suppressed viral load during pregnancy (at a minimum throughout the third trimester), as well as at delivery.²⁰²

Pediatric Use

Safety and efficacy not established in pediatric patients.¹ Pharmacokinetics not evaluated.¹

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether they respond differently to dolutegravir/rilpivirine compared with younger adults.¹ Population pharmacokinetic analyses indicate age has no clinically important effect on pharmacokinetics of dolutegravir or rilpivirine.¹

Caution advised because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.¹

Hepatic Impairment

Dosage adjustments not needed in patients with mild or moderate hepatic impairment (Child-Pugh class A or B).¹

Effect of severe hepatic impairment on pharmacokinetics not known.¹

Renal Impairment

Dosage adjustments not needed in patients with mild or moderate renal impairment (Cl_cr ≥30 mL/minute).¹

Increased monitoring for adverse effects recommended in patients with severe renal impairment (Cl_cr <30 mL/minute) or end-stage renal disease.¹

Common Adverse Effects

Common adverse effects (≥2%): diarrhea, headache, nausea.¹

Drug Interactions

CYP3A plays minor role in dolutegravir metabolism; rilpivirine primarily metabolized by CYP3A4.¹

Dolutegravir: Does not inhibit CYP1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, or 3A; does not induce CYP1A2, 2B6, or 3A4.¹

Dolutegravir: Metabolized by UGT1A1; substrate for UGT1A3 and UGT1A9.¹ Does not inhibit UGT1A1 or UGT2B7.¹

Dolutegravir: Substrate of P-glycoprotein (P-gp) transport system and breast cancer resistance protein (BCRP); does not inhibit P-gp or BCRP.¹

Dolutegravir: Inhibits multidrug and toxin extrusion transporter (MATE) 1.¹

Dolutegravir: Inhibits renal organic anion transporter (OAT) 1 and OAT3.¹ Does not inhibit organic anion transporter polypeptide (OATP) 1B1 or OATP1B3; not a substrate of OATP1B1 or 1B3.¹

Dolutegravir: Inhibits renal organic cation transporter (OCT) 2; does not inhibit OCT1.¹

Dolutegravir: Does not inhibit bile salt export pump (BSEP) or multidrug resistance protein (MRP) 2 or MRP4.¹

The following drug interactions are based on studies using the individual components of dolutegravir/rilpivirine or are predicted to occur with the fixed combination.¹ When dolutegravir/rilpivirine is used, consider interactions associated with both drugs in the fixed combination.¹

Drugs Affecting Hepatic Microsomal Enzymes

CYP3A inducers: Possible decreased dolutegravir and rilpivirine plasma concentrations; may lead to decreased therapeutic effect of the drugs and resistance to rilpivirine or other HIV NNRTIs.¹

CYP3A inhibitors: Possible increased dolutegravir and rilpivirine plasma concentrations.¹

Drugs Affecting UGT

UGT1A1, 1A3, or 1A9 inducers: Possible decreased dolutegravir plasma concentrations and decreased therapeutic effect of dolutegravir.¹

UGT1A1 inhibitors: Possible increased dolutegravir concentrations.¹

Drugs Affecting P-glycoprotein Transport

P-gp inducers: Possible decreased dolutegravir plasma concentrations and decreased therapeutic effects of dolutegravir.¹

P-gp inhibitors: Possible increased dolutegravir plasma concentrations.¹

Drugs Affecting Breast Cancer Resistance Protein

BCRP inducers: Possible decreased dolutegravir plasma concentrations.¹

BCRP inhibitors: Possible increased dolutegravir plasma concentrations.¹

Drugs Affected by Multidrug and Toxin Extrusion Transporter

Drugs eliminated by MATE1: Dolutegravir may increase plasma concentrations of MATE1 substrates.¹

Drugs Affected by Renal Organic Cation Transporters

Drugs eliminated by OCT2: Dolutegravir may increase plasma concentrations of OCT2 substrates.¹

Specific Drugs

Dolutegravir and Rilpivirine Pharmacokinetics

Absorption

Bioavailability

Dolutegravir: Absolute bioavailability not established.²³⁶

Rilpivirine: Absolute bioavailability not established.²²⁶

Food

Dolutegravir: Administration with moderate- or high-fat meal increases AUC by approximately 1.9-fold; not considered clinically important.¹

Rilpivirine: Administration with moderate- or high-fat meal increases AUC by approximately 1.6- or 1.7-fold, respectively.¹ If taken with only a protein-rich nutritional drink, exposures are 50% lower than when taken with a meal.¹

Plasma Concentrations

Dolutegravir: Peak plasma concentrations attained 3 hours after a dose.¹

Rilpivirine: Peak plasma concentrations attained 4 hours after a dose.¹

Distribution

Extent

Dolutegravir: Crosses placenta.¹ Distributed into human milk.¹

Rilpivirine: Crosses placenta.²⁰² Not known whether distributed into human milk;²²⁶ distributed into milk in rats.¹

Plasma Protein Binding

Dolutegravir: Approximately 99%.¹

Rilpivirine: Approximately 99%.¹

Elimination

Metabolism

Dolutegravir: Primarily metabolized by UGT1A1; CYP3A plays only minor role.¹

Rilpivirine: Primarily metabolized by CYP3A.¹

Elimination Route

Dolutegravir: 64% of an oral dose eliminated in feces (53% as unchanged drug); 31% eliminated in urine (<1% as unchanged drug).¹

Rilpivirine: 85% of an oral dose eliminated in feces (25% as unchanged drug); 6.5% eliminated in urine (<1% as unchanged drug).¹

Half-life

Dolutegravir: 14 hours.¹

Rilpivirine: 50 hours.¹

Special Populations

Mild hepatic impairment (Child-Pugh class A): Rilpivirine exposures 47% higher than matched controls.¹

Moderate hepatic impairment (Child-Pugh class B): Dolutegravir exposures similar to those in healthy individuals; rilpivirine exposures 5% higher than matched controls.¹

Severe hepatic impairment (Child-Pugh class C): Effect on dolutegravir and rilpivirine pharmacokinetics not evaluated.¹

Mild renal impairment: No clinically important effect on dolutegravir or rilpivirine pharmacokinetics.¹

Moderate renal impairment: No clinically important effect on dolutegravir pharmacokinetics; effect on rilpivirine pharmacokinetics not known.¹

Severe renal impairment: Dolutegravir AUC, peak plasma concentrations, and plasma concentrations measured 24 hours after dosing are 40, 23, and 43% lower, respectively, compared with healthy individuals; effect on rilpivirine pharmacokinetics not known.¹

End-stage renal disease: Effect on rilpivirine pharmacokinetics not known.¹

Dialysis: Effect on dolutegravir or rilpivirine pharmacokinetics not known.¹

Race, gender: No clinically important effects on dolutegravir or rilpivirine pharmacokinetics.¹

HCV coinfection: No clinically important effects on dolutegravir or rilpivirine exposures.¹

Pregnancy: Rilpivirine exposure approximately 30–40% lower during pregnancy (similar for second and third trimesters) compared with postpartum (6–12 weeks after delivery).¹ Protein binding of rilpivirine similar during second trimester, third trimester, and postpartum period.¹

Stability

Storage

Oral

Tablets

20–25°C (excursions permitted between 15–30°C).¹

Store and dispense in original package;¹ do not remove desiccant and protect from moisture.¹

Actions and Spectrum

• Dolutegravir/rilpivirine is a fixed-combination antiretroviral containing dolutegravir and rilpivirine.¹

• Dolutegravir is an HIV INSTI.^{1 3 5} The drug binds to the active site of HIV integrase and blocks the strand transfer step of retroviral DNA integration, which is essential for HIV replication.^{1 3 5} Active against HIV-1;¹ also has in vitro activity against HIV type 2 (HIV-2).²⁰⁰

• Rilpivirine is a diarylpyrimidine HIV NNRTI.^{1 3 5} The drug noncompetitively inhibits HIV-1 reverse transcriptase.^{1 3 5} Active against HIV-1;¹ HIV-2 intrinsically resistant to NNRTIs.²⁰⁰

• HIV-1 resistance to dolutegravir or rilpivirine produced in vitro and has emerged during clinical use.^{1 2}

• In clinical studies evaluating 2-drug regimen of dolutegravir and rilpivirine in antiretroviral-experienced adults, virologic failure during treatment with the regimen reported.¹ Isolates showed genotypic and/or phenotypic resistance to rilpivirine with emergent NNRTI resistance substitutions or evidence of dolutegravir resistance substitutions.¹

• Cross-resistance occurs among HIV NNRTIs; cross-resistance to efavirenz, etravirine, and/or nevirapine likely after virologic failure and development of resistance to rilpivirine.¹

• No in vitro evidence of antagonistic anti-HIV effects between dolutegravir and rilpivirine.¹

Advice to Patients

• Inform patients about the critical nature of compliance with HIV therapy and importance of remaining under the care of a clinician.²⁰⁰ Inform patients to take the antiretroviral regimen as prescribed, and to not alter or discontinue the antiretroviral regimen without consulting a clinician.^{1 200}

• Advise patients to take dolutegravir/rilpivirine once daily with a meal; a protein drink alone does not constitute a meal.¹

• If a dose of dolutegravir/rilpivirine is missed, inform patients to take the dose with a meal as soon as it is remembered.¹ Inform patients not to double their next dose to make up for a missed dose.¹

• Advise patients to immediately discontinue dolutegravir/rilpivirine and seek medical attention if rash occurs and is associated with fever, generally ill feeling, extreme tiredness, muscle or joint aches, breathing difficulty, blisters or peeling skin, oral blisters or lesions, eye inflammation or redness, swelling of the face, eyes, lips, or mouth, and/or signs and symptoms of liver problems (e.g., yellowing of skin or whites of the eyes, dark or tea-colored urine, pale stools/bowel movements, nausea, vomiting, loss of appetite, or pain, aching, or sensitivity on right side of the abdomen below ribs).¹ Advise patients that close monitoring and appropriate laboratory testing or treatment may be required if a hypersensitivity reaction occurs.¹

• Advise patients that depressive disorders (depressed mood, depression, dysphoria, major depression, altered mood, negative thoughts, suicide attempt, suicidal ideation) have been reported in patients receiving the components of dolutegravir/rilpivirine.¹ Inform patients to immediately contact their clinician if depressive symptoms (e.g., feeling sad, hopeless, anxious, or restless; hurting oneself; having thoughts of hurting oneself) occur.¹

• Advise patients that hepatotoxicity has been reported in patients receiving the components of dolutegravir/rilpivirine and that monitoring for hepatotoxicity is recommended.¹

• Advise women to inform their clinician if they plan to become pregnant, or if pregnancy is confirmed, during treatment with dolutegravir/rilpivirine.¹ Inform patients that a registry exists that monitors outcomes in women exposed to dolutegravir/rilpivirine during pregnancy.¹

• Advise women to inform their clinician if they plan to breast-feed.¹

• Advise patients of the potential for serious drug interactions and to inform their clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs and herbal products, and any concomitant illnesses.¹

• Advise patients of other important precautionary information.¹

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.

Frequently asked questions

• What drugs are contained in HIV treatment Juluca?

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