Juluca - Drug Monograph

Introduction

Juluca (dolutegravir/rilpivirine) is a fixed-dose combination antiretroviral medication approved for the treatment of HIV-1 infection in adults. It represents the first complete single-tablet regimen containing only two drugs rather than the traditional three or more drugs, marking a significant advancement in HIV treatment simplification.

Mechanism of Action

Juluca combines two antiretroviral agents with different mechanisms of action:

• Dolutegravir: An integrase strand transfer inhibitor (INSTI) that blocks HIV integrase, preventing the insertion of viral DNA into the host genome
• Rilpivirine: A non-nucleoside reverse transcriptase inhibitor (NNRTI) that binds to reverse transcriptase, inhibiting RNA-dependent and DNA-dependent DNA polymerase activities

This dual mechanism provides potent suppression of HIV replication through complementary pathways, effectively reducing viral load and maintaining immunologic function.

Indications

Juluca is indicated for the treatment of HIV-1 infection in adults who:

• Are virologically suppressed (HIV-1 RNA <50 copies/mL) on a stable antiretroviral regimen for at least 6 months
• Have no history of treatment failure
• Have no known substitutions associated with resistance to dolutegravir or rilpivirine

Dosage and Administration

• Renal impairment: No dosage adjustment required
• Hepatic impairment: No dosage adjustment required for mild to moderate impairment; not recommended for severe hepatic impairment
• Elderly: No dosage adjustment required, but consider age-related renal impairment
• Pregnancy: Use only if potential benefit justifies potential risk
• Pediatrics: Not approved for patients under 18 years

Pharmacokinetics

• Dolutegravir: Tmax 2-3 hours; bioavailability ~74%
• Rilpivirine: Tmax 4-5 hours; bioavailability increased by ~40% with food

• Dolutegravir: Protein binding ~99%; Vd 17.4 L
• Rilpivirine: Protein binding ~99.7%; Vd ~4 L

• Dolutegravir: Primarily metabolized via UGT1A1 with some CYP3A involvement
• Rilpivirine: Primarily metabolized by CYP3A

• Dolutegravir: Terminal half-life ~14 hours; excreted primarily in feces (53%) and urine (31%)
• Rilpivirine: Terminal half-life ~50 hours; excreted primarily in feces (85%) and urine (6%)

Contraindications

• Concomitant use with drugs that significantly reduce rilpivirine plasma concentrations:

- Carbamazepine, oxcarbazepine, phenobarbital, phenytoin - Rifampin, rifapentine - Proton pump inhibitors - St. John's wort (Hypericum perforatum)

• Known hypersensitivity to any component of the formulation

Warnings and Precautions

Drug Interactions

• Antacids: Separate Juluca administration by at least 4 hours
• Cation-containing products (Ca, Fe, Mg, Al): Separate administration by at least 4 hours
• CYP3A inducers: Avoid coadministration (rifampin, carbamazepine, etc.)
• CYP3A inhibitors: May increase rilpivirine concentrations
• Methadone: No dosage adjustment needed
• Oral contraceptives: No significant interactions documented

Adverse Effects

• Headache (3%)
• Diarrhea (2%)
• Nausea (2%)
• Fatigue (2%)
• Insomnia (2%)

• Hepatotoxicity
• Depressive disorders
• Skin reactions including severe rash
• QT interval prolongation

Monitoring Parameters

• HIV-1 RNA levels: At initiation, every 4-8 weeks until suppressed, then every 3-6 months
• CD4+ cell count: Baseline and periodically
• Liver function tests: Baseline and clinically indicated
• Renal function: Baseline assessment
• Serum creatinine: Baseline and periodically (dolutegravir may cause increases)
• Mental health screening: Regular assessment for depressive symptoms
• ECG monitoring: In patients with cardiac risk factors

Patient Education

• Take exactly as prescribed with a meal to ensure adequate absorption
• Do not miss doses to prevent development of resistance
• Report any signs of liver problems (jaundice, dark urine, abdominal pain)
• Report mood changes, depression, or suicidal thoughts immediately
• Inform all healthcare providers about Juluca use before starting new medications
• Use effective contraception; discuss pregnancy plans with healthcare provider
• Do not stop taking without medical supervision
• Store at room temperature in original container

References

1. FDA prescribing information: Juluca (dolutegravir and rilpivirine) tablets. 2017. 2. Llibre JM, et al. Efficacy, safety, and tolerability of dolutegravir-rilpivirine for the maintenance of virological suppression in adults with HIV-1: phase 3, randomised, non-inferiority SWORD-1 and SWORD-2 studies. Lancet. 2018;391(10123):839-849. 3. Cahn P, et al. Dolutegravir plus rilpivirine dual therapy versus continuing antiretroviral therapy in HIV-1-infected adults with virological suppression (SWORD): week 48 results. J Acquir Immune Defic Syndr. 2018;78(3):319-328. 4. Mills AM, et al. Pharmacokinetics, safety, and efficacy of dolutegravir/rilpivirine as a switch option in HIV-infected adults. Expert Opin Pharmacother. 2018;19(14):1605-1613. 5. EACS Guidelines version 11.0, October 2021.