Version May 2024
HIV-1 infection, treatment: Oral: 1 tablet (dolutegravir 50 mg/rilpivirine 25 mg) once daily. Note: Prior to switching to dolutegravir/rilpivirine, patients must be virologically suppressed on a stable antiretroviral regimen for ≥6 months with no history of treatment failure and no known resistance to dolutegravir or rilpivirine.
Dose adjustment for concomitant therapy with rifabutin: 1 tablet (dolutegravir 50 mg/rilpivirine 25 mg) once daily, with an additional rilpivirine 25 mg tablet once daily for the duration of rifabutin coadministration.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
CrCl ≥30 mL/minute: No dosage adjustment necessary.
CrCl <30 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling; use with caution and increased monitoring for adverse effects. In addition, dolutegravir concentrations may be decreased, resulting in loss of therapeutic effect and development of resistance to dolutegravir or other coadministered antiretroviral agents.
End-stage renal disease (ESRD), including hemodialysis: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Mild-to-moderate impairment (Child-Pugh class A or B): No dosage adjustment necessary.
Severe impairment (Child-Pugh class C): There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied). According to the Tivicay product labeling, use of dolutegravir is not recommended.
Refer to adult dosing.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Also see individual agents.
1% to 10%:
Endocrine & metabolic: Hyperglycemia (≤4%)
Gastrointestinal: Diarrhea (2%), increased serum lipase (2% to 5%)
Hepatic: Increased serum alanine aminotransferase (≤2%), increased serum bilirubin (2%)
Nervous system: Headache (2%)
Neuromuscular & skeletal: Decreased bone mineral density (2%), increased creatine phosphokinase in blood specimen (≤1%)
<1%:
Hepatic: Increased serum aspartate aminotransferase
Neuromuscular & skeletal: Bone fracture
Frequency not defined: Renal: Increased serum creatinine
Hypersensitivity to dolutegravir, rilpivirine, or any component of the formulation; concurrent use with dofetilide, carbamazepine, systemic dexamethasone (>1 dose), oxcarbazepine, phenobarbital, phenytoin, proton pump inhibitors (eg, esomeprazole, lansoprazole, omeprazole, pantoprazole, rabeprazole), rifampin, rifapentine, and/or St John's wort.
Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Canadian labeling: Additional contraindications (not in US labeling): Concurrent use with organic cation transporter 2 substrates with narrow therapeutic windows (eg, fampridine).
Concerns related to adverse effects:
• Depressive disorders: Rilpivirine may cause depression, depressed mood, dysphoria, mood changes, negative thoughts, suicide attempts, or suicidal ideation. Promptly evaluate patients with severe depressive symptoms and/or if changes are noted and reevaluate risk versus benefit of continued combination therapy.
• Hepatotoxicity: Hepatic adverse events, including elevated transaminases, hepatitis, and acute liver failure (sometimes requiring liver transplant) have been reported with regimens containing dolutegravir or rilpivirine. Risk may be increased in patients with significant transaminase elevations or hepatitis B or C prior to treatment, however, hepatotoxicity has been reported in patients with no preexisting hepatic disease or other risk factors. In some patients receiving dolutegravir-containing regimens, elevations in transaminases may be concurrent with development of immune reconstitution syndrome or hepatitis B reactivation (especially if antihepatitis therapy has been discontinued). Baseline and periodic laboratory LFT evaluation during therapy is recommended for patients with preexisting risk factors; also consider LFT monitoring in patients without identifiable hepatic disease risk.
• Hypersensitivity reactions: Rash, constitutional findings, and organ dysfunction (eg, liver injury) have been reported with dolutegravir. Hypersensitivity and severe skin reactions have been reported with rilpivirine, including severe rash or rash accompanied by fever, blisters, mucosal involvement, conjunctivitis, facial edema, angioedema, hepatitis or eosinophilia, or drug reaction with eosinophilia and systemic symptoms (DRESS). Most rashes were grade 1 or 2 and occurred within the first 4 to 6 weeks of therapy; no grade 4 rashes were reported. Discontinue treatment immediately if severe skin or hypersensitivity reactions occur; life-threatening reactions may occur if there is a delay in discontinuing therapy after onset of hypersensitivity. Monitor clinical status and liver function tests, and initiate supportive therapy as appropriate. Do not restart therapy with any dolutegravir or rilpivirine-containing product if hypersensitivity occurs.
• Immune reconstitution syndrome: Patients may develop immune reconstitution syndrome resulting in the occurrence of an inflammatory response to an indolent or residual opportunistic infection during initial HIV treatment or activation of autoimmune disorders (eg, Graves’ disease, polymyositis, Guillain-Barré syndrome) later in therapy; further evaluation and treatment may be required.
• QTc prolongation: In healthy subjects, supratherapeutic doses of rilpivirine (ie, 75 mg daily, 300 mg daily) have been associated with QTc prolongation; use caution and/or consider alternative therapy when coadministering with a drug with a known risk of torsades de pointes.
Disease-related concerns:
• Hepatic impairment: Not recommended for use in patients with severe hepatic impairment (has not been studied). Patients with underlying hepatic disease (such as hepatitis B or C coinfection) may be at increased risk of development or worsening of transaminase elevations; use with caution. Monitor transaminases at baseline and during therapy.
• Renal impairment: Use with caution and increased monitoring for adverse reactions in patients with CrCl <30 mL/minute or end-stage renal disease (ESRD). In addition, in INSTI-experienced patients with severe renal impairment, decreases in dolutegravir concentrations were observed and may result in loss of therapeutic effect and development of resistance to dolutegravir or other coadministered antiretroviral agents.
Other warnings/precautions:
• Appropriate use: Indicated for virologically suppressed patients with no history of treatment failure and/or resistance to dolutegravir or rilpivirine; has not been studied as initial or salvage therapy for patients with detectable HIV-1 viral load.
• Changes in serum creatinine: Dolutegravir and rilpivirine may increase serum creatinine due to inhibition of tubular secretion of creatinine without affecting renal glomerular function or effective renal plasma flow (Gutierrez 2014). Increased serum creatinine occurred within the first 4 weeks of treatment with dolutegravir and rilpivirine and remained stable through 48 weeks of treatment.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Juluca: Dolutegravir 50 mg and rilpivirine 25 mg
No
Tablets (Juluca Oral)
50-25 mg (per each): $140.49
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Juluca: Dolutegravir 50 mg and rilpivirine 25 mg
Administer with a meal; a protein supplement drink alone does not replace a meal. Administer 4 hours before or 6 hours after cation-containing antacids or laxatives, sucralfate, oral supplements containing iron or calcium, or buffered medications. Alternatively, may be administered with supplements containing calcium or iron at the same time if administered together with food.
HIV-1 infection, treatment: Treatment of HIV-1 infection in adults virologically suppressed on a stable antiretroviral regimen for ≥6 months with no history of treatment failure and no known resistance to the individual components
Refer to individual components.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Aluminum Hydroxide: May decrease the serum concentration of Dolutegravir. Management: Administer dolutegravir at least 2 hours before or 6 hours after oral aluminum hydroxide. Administer the dolutegravir/rilpivirine combination product at least 4 hours before or 6 hours after oral aluminum hydroxide. Risk D: Consider therapy modification
Antacids: May decrease the serum concentration of Rilpivirine. Management: Administer antacids at least 2 hours before or 4 hours after oral rilpivirine when used with most rilpivirine products. However, administer antacids at least 6 hours before or 4 hours after the rilpivirine/dolutegravir combination product. Risk D: Consider therapy modification
Antidiabetic Agents: Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy
Antihepaciviral Combination Products: May increase the serum concentration of Rilpivirine. Risk X: Avoid combination
Betibeglogene Autotemcel: Antiretroviral Agents may diminish the therapeutic effect of Betibeglogene Autotemcel. Risk X: Avoid combination
Calcium Salts: May decrease the serum concentration of Dolutegravir. Management: Administer dolutegravir at least 2 hours before or 6 hours after oral calcium. Administer dolutegravir/rilpivirine at least 4 hours before or 6 hours after oral calcium salts. Alternatively, dolutegravir and oral calcium can be taken together with food. Risk D: Consider therapy modification
CarBAMazepine: May decrease the serum concentration of Rilpivirine. Risk X: Avoid combination
Clofarabine: OCT2 Inhibitors may increase the serum concentration of Clofarabine. Risk C: Monitor therapy
CYP3A4 Inducers (Moderate): May decrease the serum concentration of Rilpivirine. Risk C: Monitor therapy
CYP3A4 Inducers (Strong): May decrease the serum concentration of Rilpivirine. Management: Consider alternatives to this combination whenever possible. If combined, monitor closely for reduced rilpivirine efficacy (eg, loss of virologic response or resistance). Risk X: Avoid combination
CYP3A4 Inhibitors (Strong): May increase the serum concentration of Rilpivirine. Risk C: Monitor therapy
Dalfampridine: OCT2 Inhibitors may increase the serum concentration of Dalfampridine. Management: Consider alternatives to this combination. Carefully weigh the risk of seizures against the benefit of combining OCT2 inhibitors with dalfampridine. Risk D: Consider therapy modification
DexAMETHasone (Systemic): May decrease the serum concentration of Rilpivirine. Risk X: Avoid combination
Didanosine: Rilpivirine may decrease the absorption of Didanosine. Didanosine may decrease the absorption of Rilpivirine. More specifically, simultaneous coadministration of these drugs creates a conflict between recommendations to administer with (rilpivirine) and without (didanosine) food. Management: Administer didanosine on an empty stomach at least 2 hours before or 4 hours after rilpivirine, due to the requirement that rilpivirine be administered with food. Risk D: Consider therapy modification
Dofetilide: Dolutegravir may increase the serum concentration of Dofetilide. Risk X: Avoid combination
Elivaldogene Autotemcel: Antiretroviral Agents may diminish the therapeutic effect of Elivaldogene Autotemcel. Management: Avoid use of antiretroviral medications for at least one month, or for the amount of time required for elimination of the retroviral medication, prior to stem cell mobilization and until the all apheresis cycles are finished Risk X: Avoid combination
Ergonovine: Reverse Transcriptase Inhibitors (Non-Nucleoside) may increase the serum concentration of Ergonovine. Specifically, this would be most likely with delavrdine, while other Non-Nucleoside Reverse Transcriptase Inhibitors may be more likely to decrease the concentration of Ergonovine. Risk X: Avoid combination
Fosamprenavir: May decrease the serum concentration of Dolutegravir. Specifically, Fosamprenavir/Ritonavir may decrease the serum concentration of Dolutegravir. The individual contributions of Fosamprenavir and Ritonavir to this effect are unknown. Management: Increase dolutegravir to 50 mg twice/day in adults. Increase weight-based dose to twice daily in pediatric patients. Recommendations vary for combo products; see interaction monograph for details. Not recommended with Dovato or Juluca brand combos. Risk D: Consider therapy modification
Fosphenytoin: May decrease the serum concentration of Rilpivirine. Risk X: Avoid combination
Haloperidol: QT-prolonging Agents (Indeterminate Risk - Avoid) may enhance the QTc-prolonging effect of Haloperidol. Risk C: Monitor therapy
Histamine H2 Receptor Antagonists: May decrease the serum concentration of Rilpivirine. Management: Administer histamine H2 receptor antagonists (H2RAs) at least 12 hours before or 4 hours after oral rilpivirine. Risk D: Consider therapy modification
Inhibitors of the Proton Pump (PPIs and PCABs): May decrease the serum concentration of Rilpivirine. Risk X: Avoid combination
Iron Preparations: May decrease the serum concentration of Dolutegravir. Management: Administer dolutegravir at least 2 hours before or 6 hours after oral iron. Administer dolutegravir/rilpivirine at least 4 hours before or 6 hours after oral iron. Alternatively, dolutegravir and oral iron can be taken together with food. Risk D: Consider therapy modification
Isoniazid: Dolutegravir may enhance the adverse/toxic effect of Isoniazid. Dolutegravir may increase the serum concentration of Isoniazid. Risk C: Monitor therapy
Ketoconazole (Systemic): May increase the serum concentration of Rilpivirine. Rilpivirine may decrease the serum concentration of Ketoconazole (Systemic). Risk C: Monitor therapy
Levoketoconazole: QT-prolonging Agents (Indeterminate Risk - Avoid) may enhance the QTc-prolonging effect of Levoketoconazole. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Levomethadone: Reverse Transcriptase Inhibitors (Non-Nucleoside) may decrease the serum concentration of Levomethadone. Management: Levomethadone dosage adjustments will likely be required with efavirenz and nevirapine, and may be necessary with rilpivirine as well. Risk C: Monitor therapy
Lovotibeglogene Autotemcel: Antiretroviral Agents may diminish the therapeutic effect of Lovotibeglogene Autotemcel. Risk X: Avoid combination
Macrolide Antibiotics: May increase the serum concentration of Rilpivirine. Management: Consider the use of azithromycin or another non-macrolide alternative when appropriate to avoid this potential interaction. Risk D: Consider therapy modification
Magnesium Salts: May decrease the serum concentration of Dolutegravir. Management: Administer dolutegravir at least 2 hours before or 6 hours after oral magnesium salts. Administer the dolutegravir/rilpivirine combination product at least 4 hours before or 6 hours after oral magnesium salts. Risk D: Consider therapy modification
MetFORMIN: Dolutegravir may increase the serum concentration of MetFORMIN. Management: Consider alternatives to this combination or use of lower metformin doses. Carefully weigh the risk of metformin toxicities (including lactic acidosis) against the benefit of combining dolutegravir with metformin. Risk D: Consider therapy modification
Methadone: Reverse Transcriptase Inhibitors (Non-Nucleoside) may increase the metabolism of Methadone. Management: Methadone dosage adjustments will likely be required with efavirenz and nevirapine, and may be necessary with rilpivirine as well. Risk C: Monitor therapy
Mitapivat: May decrease the serum concentration of UGT1A1 Substrates. Risk C: Monitor therapy
Multivitamins/Minerals (with ADEK, Folate, Iron): May decrease the serum concentration of Dolutegravir. Management: Administer dolutegravir at least 2 hours before or 6 hours after multivitamins. Administer the dolutegravir/rilpivirine product at least 4 hours before or 6 hours multivitamins. Alternatively, dolutegravir and multivitamins can be taken together with food Risk D: Consider therapy modification
Multivitamins/Minerals (with AE, No Iron): May decrease the serum concentration of Dolutegravir. Management: Administer dolutegravir at least 2 hours before or 6 hours after multivitamins. Administer the dolutegravir/rilpivirine product at least 4 hours before or 6 hours multivitamins. Alternatively, dolutegravir and multivitamins can be taken together with food Risk D: Consider therapy modification
Nevirapine: May decrease the serum concentration of Dolutegravir. Risk X: Avoid combination
Orlistat: May decrease the serum concentration of Antiretroviral Agents. Risk C: Monitor therapy
OXcarbazepine: May decrease the serum concentration of Rilpivirine. Risk X: Avoid combination
OXcarbazepine: May decrease the serum concentration of Dolutegravir. Risk X: Avoid combination
PHENobarbital: May decrease the serum concentration of Rilpivirine. Risk X: Avoid combination
PHENobarbital: May decrease the serum concentration of Dolutegravir. Risk X: Avoid combination
Phenytoin: May decrease the serum concentration of Rilpivirine. Risk X: Avoid combination
Primidone: May decrease the serum concentration of Rilpivirine. Risk X: Avoid combination
Primidone: May decrease the serum concentration of Dolutegravir. Specifically, the Primidone metabolite phenobarbital may decrease Dolutegravir serum concentrations. Risk X: Avoid combination
QT-prolonging Agents (Highest Risk): QT-prolonging Agents (Indeterminate Risk - Avoid) may enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Reverse Transcriptase Inhibitors (Non-Nucleoside): May enhance the adverse/toxic effect of other Reverse Transcriptase Inhibitors (Non-Nucleoside). Reverse Transcriptase Inhibitors (Non-Nucleoside) may decrease the serum concentration of other Reverse Transcriptase Inhibitors (Non-Nucleoside). Specifically, efavirenz and nevirapine may decrease the serum concentrations of other non-nucleoside reverse transcriptase inhibitors. Reverse Transcriptase Inhibitors (Non-Nucleoside) may increase the serum concentration of other Reverse Transcriptase Inhibitors (Non-Nucleoside). Specifically, delavirdine may increase the serum concentration of etravirine. Risk X: Avoid combination
Rifabutin: May decrease the serum concentration of Rilpivirine. Management: Increase rilpivirine dose to 50 mg/day during rifabutin treatment. Use of rifabutin with emtricitabine/rilpivirine/tenofovir alafenamide product is not recommended. Use with IV cabotegravir/rilpivirine is contraindicated. Risk D: Consider therapy modification
RifAMPin: May decrease the serum concentration of Rilpivirine. Risk X: Avoid combination
Rifapentine: May decrease the serum concentration of Rilpivirine. Risk X: Avoid combination
Saquinavir: Rilpivirine may enhance the arrhythmogenic effect of Saquinavir. Saquinavir may increase the serum concentration of Rilpivirine. Risk X: Avoid combination
Selenium: May decrease the serum concentration of Dolutegravir. Management: Administer dolutegravir at least 2 hours before or 6 hours after oral selenium. Administer the dolutegravir/rilpivirine combination product at least 4 hours before or 6 hours after oral selenium. Risk D: Consider therapy modification
St John's Wort: May decrease the serum concentration of Dolutegravir. Risk X: Avoid combination
St John's Wort: May decrease the serum concentration of Rilpivirine. Risk X: Avoid combination
Sucralfate: May decrease the serum concentration of Dolutegravir. Management: Administer dolutegravir at least 2 hours before or 6 hours after sucralfate. Administer the dolutegravir/rilpivirine combination product at least 4 hours before or 6 hours after sucralfate. Risk D: Consider therapy modification
Tipranavir: May decrease the serum concentration of Dolutegravir. Specifically, Tipranavir/Ritonavir may decrease the serum concentration of Dolutegravir. The individual contributions of Tipranavir and Ritonavir to this effect are unknown. Management: Increase dolutegravir to 50 mg twice/day in adults. Increase weight-based dose to twice daily in pediatric patients. Recommendations vary for combo products; see interaction monograph for details. Not recommended with Dovato or Juluca brand combos. Risk D: Consider therapy modification
Valproate Products: May decrease the serum concentration of Dolutegravir. Risk C: Monitor therapy
Zinc Salts: May decrease the serum concentration of Dolutegravir. Management: Administer dolutegravir at least 2 hours before or 6 hours after oral zinc salts. Administer the dolutegravir/rilpivirine combination product at least 4 hours before or 6 hours after oral zinc salts. Risk D: Consider therapy modification
Exposure is increased when taken with a moderate to high fat meal; when taken with a protein supplement drink alone, exposures were 50% lower compared to taking with a meal. Management: Administer with a meal (not a protein supplement drink alone).
Evaluate pregnancy status prior to use in patients who may become pregnant.
Contraception is not required to initiate or continue antiretroviral therapy (HHS [perinatal] 2023). However, the manufacturer recommends consistent use of effective contraception during therapy.
The Health and Human Services (HHS) perinatal HIV guidelines do not recommend use of this fixed-dose 2-drug combination as a complete regimen in patients with HIV who are not yet pregnant but are trying to conceive (HHS [perinatal] 2023).
Refer to individual monographs for additional information.
The Health and Human Services (HHS) perinatal HIV guidelines do not recommend use of this fixed-dose, 2-drug combination as a complete regimen in pregnant patients with HIV who are antiretroviral-naive, who have had antiretroviral therapy (ART) in the past but are restarting, or who require a new ART regimen (due to poor tolerance or poor virologic response of current regimen). Although data are not available for use of 2-drug oral regimens in pregnancy, use may continue in patients who are virologically suppressed and present with this combination as a 2-drug regimen while pregnant; frequent viral load monitoring (every 1 to 2 months) is recommended (HHS [perinatal] 2023).
Refer to individual monographs for additional information.
Dolutegravir is present in breast milk. It is not known if rilpivirine is present in breast milk.
Refer to individual monographs for additional information.
Take with a meal (not a protein supplement drink alone). Take 4 hours before or 6 hours after cation-containing antacids or laxatives, sucralfate, oral supplements containing iron or calcium, or buffered medications. Alternatively, may be taken with supplements containing calcium or iron at the same time if taken together with food.
HIV viral load, CD4 count, lipid profile, hepatic transaminases (baseline and during therapy), signs of skin rash, fever, and/or hypersensitivity reactions, signs and symptoms of infection. Evaluate pregnancy status prior to use in patients who may become pregnant.
Dolutegravir, an integrase inhibitor, inhibits HIV integrase by binding to the integrase active site and blocking the strand transfer step of retroviral DNA integration. Rilpivirine, a non-nucleoside reverse transcriptase inhibitor, binds to reverse transcriptase and blocks the RNA-dependent and DNA-dependent polymerase activities, including HIV-1 replication.
See individual agents.
آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟
