JULUCA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for JULUCA (JULUCA).
Dolutegravir is an integrase strand transfer inhibitor (INSTI) that inhibits the catalytic activity of HIV-1 integrase, preventing integration of viral DNA into host chromosomal DNA. Lamivudine is a nucleoside reverse transcriptase inhibitor (NRTI) that inhibits HIV-1 reverse transcriptase via incorporation into viral DNA, causing chain termination.
| Metabolism | Dolutegravir is primarily metabolized by UGT1A1 with minor contribution from CYP3A4. Lamivudine is phosphorylated intracellularly to its active triphosphate moiety; it is not extensively metabolized in the liver and is largely excreted unchanged in urine. |
| Excretion | Dolutegravir: 64% fecal (as unchanged drug), 32% renal (as glucuronide conjugate); <1% unchanged in urine. Lamivudine: 70% renal (as unchanged drug) via glomerular filtration and active tubular secretion; 5-10% as trans-sulfoxide metabolite. |
| Half-life | Dolutegravir: ~14 hours (terminal; supports once-daily dosing). Lamivudine: ~13-19 hours (terminal; supports once-daily dosing; prolonged in renal impairment). |
| Protein binding | Dolutegravir: >99% bound to plasma proteins (mainly albumin and alpha-1-acid glycoprotein). Lamivudine: <36% bound (minimal protein binding). |
| Volume of Distribution | Dolutegravir: ~12.5 L (0.18 L/kg based on ~70 kg); indicates extensive tissue distribution. Lamivudine: ~1.3 L/kg (91 L); distributes into total body water and penetrates CSF (ratio 0.04-0.13). |
| Bioavailability | Dolutegravir: ~53% (oral, fasted); 75% with high-fat meal (food increases exposure). Lamivudine: ~86% (oral, fasted); food delays absorption slightly but does not reduce extent. |
| Onset of Action | Oral: Dolutegravir achieves virologic suppression within 2-4 weeks; lamivudine antiviral effect begins within hours but maximal suppression requires weeks. |
| Duration of Action | Oral: 24 hours (maintained by once-daily dosing); clinical effect persists throughout dosing interval; missed dose may reduce suppression. |
| Molecular Weight | 571.68 Da |
One tablet orally once daily, each tablet containing dolutegravir 50 mg and rilpivirine 25 mg.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (CrCl ≥30 mL/min). Avoid use in severe renal impairment (CrCl <30 mL/min) or end-stage renal disease due to lack of data; rilpivirine exposure may increase. |
| Liver impairment | No dose adjustment required for mild to moderate hepatic impairment (Child-Pugh A or B). Not recommended for severe hepatic impairment (Child-Pugh C) due to lack of data. |
| Pediatric use | Approved for children weighing ≥40 kg: one tablet (dolutegravir 50 mg/rilpivirine 25 mg) once daily. Not recommended for children weighing <40 kg due to insufficient data. |
| Geriatric use | No specific dose adjustments; limited data in patients aged 65 years and older. Use with caution due to potential age-related renal impairment and comorbidities. |
| 1st trimester | Insufficient human data; based on animal studies, avoid use unless benefit outweighs risk. Dolutegravir has been associated with neural tube defects when used at conception. |
| 2nd trimester | Limited data; may be used if clearly needed. Monitor for maternal toxicity and fetal growth. |
| 3rd trimester | Limited data; may be used if clearly needed. Monitor for adverse effects on fetus/neonate. |
Clinical note
Comprehensive clinical and safety monograph for JULUCA (JULUCA).
| Placental transfer | Both dolutegravir and lamivudine cross the placenta; dolutegravir reaches cord blood concentrations similar to maternal plasma; lamivudine reaches higher concentrations in cord blood. |
| Breastfeeding | Transfer into human milk is expected. Avoid breastfeeding due to potential for HIV transmission and adverse effects in the infant. |
■ FDA Black Box Warning
None
| Serious Effects |
Hypersensitivity to dolutegravir, lamivudine, or any componentConcomitant use with dofetilide
| Precautions | Hepatotoxicity: Cases of hepatic injury have been reported, including in patients with hepatitis B or C coinfection., Immune reconstitution syndrome: May occur during initial treatment., Risk of lamivudine-resistant hepatitis B virus (HBV) in patients with HBV coinfection if lamivudine is discontinued., Lactic acidosis and severe hepatomegaly with steatosis have been reported with nucleoside analogues., Hypersensitivity reactions: Discontinue immediately if signs/symptoms appear. |
| Food/Dietary | Take JULUCA with a meal; food increases rilpivirine absorption. A meal of at least 400 kcal is recommended. Avoid taking with calcium, iron, magnesium, or aluminum-containing products (e.g., antacids, supplements) within 6 hours before or after dosing. Proton pump inhibitors are contraindicated. H2-receptor antagonists should be taken at least 12 hours before or 4 hours after JULUCA. |
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| Lactation Rating | L5 (Contraindicated) |
| Teratogenic Risk | Dolutegravir: limited human data in first trimester show neural tube defects (NTDs) with a prevalence of 0.3% vs 0.1% background; risk highest with periconceptional exposure. Avoid in first trimester unless no alternative. Second/third trimester: no evidence of increased malformations. Lamivudine: extensive human data show no increased risk of birth defects. Overall: dolutegravir-containing regimen carries small increased NTD risk in first trimester; lamivudine is safe. |
| Fetal Monitoring | Maternal: HIV viral load every 1-2 months during pregnancy; CD4 count at baseline and each trimester; hepatic/renal function tests at baseline and periodically; folic acid supplementation (0.4-4 mg/day) recommended with dolutegravir in first trimester. Fetal/neonatal: first trimester ultrasound for NTD screening at 18-20 weeks; neonatal HIV testing per protocol; monitor for anemia (lamivudine-related) and hepatic toxicity (rare). |
| Fertility Effects | Neither dolutegravir nor lamivudine have known clinically significant effects on female or male fertility based on animal and human data. No evidence of altered menstrual cycles, ovarian function, or spermatogenesis. Dolutegravir has been associated with small increases in total testosterone but not with impaired fertility. |
| Clinical Pearls | Dolutegravir/rilpivirine is a complete regimen for HIV-1 treatment; do not use with other antiretrovirals. Avoid in patients with prior virologic failure or resistance to NNRTIs or integrase inhibitors. Must be taken with a meal to ensure adequate rilpivirine absorption. Check renal function before initiation; avoid if CrCl <50 mL/min. Monitor for hepatotoxicity, especially in patients with HBV/HCV coinfection. Use with caution in patients with depression or suicidal ideation due to rilpivirine CNS effects. Dolutegravir may cause small increases in serum creatinine due to inhibition of tubular secretion, not renal injury. |
| Patient Advice | Take one tablet daily with a meal; do not take on an empty stomach. · Swallow tablet whole; do not crush, chew, or split. · Inform all healthcare providers that you take JULUCA. · Avoid taking with antacids or supplements containing calcium, iron, magnesium, or aluminum; separate by at least 6 hours if needed. · Report any signs of liver problems: yellow skin/eyes, dark urine, right upper quadrant pain, or unexplained fatigue. · Notify your doctor if you become pregnant or plan to become pregnant. · Do not stop taking JULUCA without consulting your doctor; missing doses may lead to viral resistance. · Store at room temperature away from moisture and heat. |