SUNLENCA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for SUNLENCA (SUNLENCA).
HIV-1 capsid inhibitor; binds to the HIV-1 capsid protein, interfering with multiple steps of the viral lifecycle including nuclear uptake, assembly, and release.
| Metabolism | Primarily metabolized by CYP3A4 and UGT1A1. |
| Excretion | Renal elimination predominantly as unchanged drug (~89% of dose); fecal elimination accounts for ~6% |
| Half-life | Terminal half-life approximately 14.5 days (range 10-18 days) due to slow release from the subcutaneous depot, enabling monthly dosing |
| Protein binding | >99.9% bound primarily to human serum albumin and alpha-1-acid glycoprotein |
| Volume of Distribution | Apparent Vd approximately 0.3 L/kg (total body water) suggesting limited tissue distribution |
| Bioavailability | Subcutaneous: approximately 87% (range 76-98%) relative to intravenous administration |
| Onset of Action | Subcutaneous: Steady-state viral load suppression achieved by week 4-6; first detectable decline in HIV RNA occurs within 24-48 hours post-injection |
| Duration of Action | Suppression maintained for up to 4 weeks after a single subcutaneous dose; clinical trials used monthly dosing |
600 mg subcutaneously every 6 months (2 injections of 300 mg/1.5 mL) for HIV pre-exposure prophylaxis (PrEP) with optional oral loading: 600 mg by mouth daily for 28 days prior to first injection.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (eGFR ≥15 mL/min). Not recommended for end-stage renal disease (eGFR <15 mL/min) or those on dialysis due to lack of data. |
| Liver impairment | No dose adjustment for mild (Child-Pugh A) or moderate (Child-Pugh B) hepatic impairment. Not recommended for severe hepatic impairment (Child-Pugh C) due to lack of data. |
| Pediatric use | Not approved for individuals weighing <35 kg. For ≥35 kg and age ≥12 years: same as adult dosing (600 mg SC every 6 months, with optional oral loading). |
| Geriatric use | No specific dose adjustment; limited data in patients >65 years. Monitor renal function and consider potential for decreased renal clearance due to age-related changes. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for SUNLENCA (SUNLENCA).
| Breastfeeding | It is not known whether lenacapavir is present in human breast milk, affects the breastfed infant, or affects milk production. In lactating rats, lenacapavir was excreted in milk at concentrations approximately 1.5% of maternal plasma levels. The M/P ratio is unknown in humans. Due to the potential for HIV transmission and adverse effects in the breastfed infant, breastfeeding is not recommended while taking SUNLENCA. |
| Teratogenic Risk | SUNLENCA (lenacapavir) is an HIV-1 capsid inhibitor. In animal reproductive studies, no evidence of fetal harm was observed at exposures up to 15 times the human exposure at the recommended dose. There are no adequate and well-controlled studies in pregnant women. Based on animal data, teratogenic risk is low, but potential fetal effects cannot be excluded, particularly in the first trimester. The drug should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. |
■ FDA Black Box Warning
None.
| Serious Effects |
["Concomitant administration with strong CYP3A4 inducers","History of hypersensitivity reaction to lenacapavir"]
| Precautions | ["Immune reconstitution syndrome","Risk of hepatitis B virus reactivation in patients co-infected with HBV and HIV","Potential for QT interval prolongation; use with caution with drugs that prolong QT interval or in patients with pre-existing QT prolongation","Severe injection site reactions including abscess, cellulitis, and nodule formation"] |
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| Fetal Monitoring | In pregnant women receiving SUNLENCA, monitor HIV-1 RNA viral load and CD4+ cell count regularly. Perform obstetric ultrasounds for fetal growth assessment given the lack of human safety data. Renal and hepatic function should be monitored as lenacapavir is primarily hepatically metabolized and renally excreted. No specific fetal monitoring is mandated, but standard prenatal care with attention to potential adverse effects is advised. |
| Fertility Effects | Animal studies showed no adverse effects on fertility in male or female rats at exposures up to 15 times the human exposure. There are no human data on fertility. Based on the mechanism of action, lenacapavir is not expected to impair human fertility; however, the effect on human fertility is unknown. |