Lenacapavir

SUNLENCA

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Pronunciation: len-a-KAP-a-veer (sun-LEN-ka)

Lenacapavir ballicule: receptor binding, kinetics and half-life diagram — Mechanism of action: Lenacapavir ballicule

What it isFirst-in-class HIV capsid inhibitor; multidrug-resistant HIV and pre-exposure prophylaxis.

Why this oneFor PrEP it can replace a daily pill; in multidrug-resistant HIV it adds a new target when other classes have failed.

What limits itA long tail risks resistance if injections lapse. It is a moderate CYP3A4 inhibitor; injection-site nodules.

Lenacapavir molecular structure (skeletal formula) — Molecular structure: Lenacapavir

FDA-approved for

Multidrug-resistant HIV-1 (2022)
HIV-1 pre-exposure prophylaxis (2022)

FDA label

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FDA dosing	Population	Start	Target	Max
HIV-1, heavily treatment-experienced with multidrug-resistant HIV-1 (failing regimen due to resistance, intolerance, or safety), with other antiretroviral(s) — Initiation Option 1	Adults	Day 1: 927 mg SC (2 × 1.5 mL injections) + 600 mg PO (2 × 300 mg tablets); Day 2: 600 mg PO (2 × 300 mg)	Then maintenance 927 mg SC every 6 months (26 weeks) from date of last injection	927 mg SC every 6 months
HIV-1, heavily treatment-experienced with multidrug-resistant HIV-1, with other antiretroviral(s) — Initiation Option 2 (all-oral lead-in)	Adults	Day 1: 600 mg PO (2 × 300 mg); Day 2: 600 mg PO (2 × 300 mg); Day 8: 300 mg PO (1 × 300 mg); Day 15: 927 mg SC (2 × 1.5 mL injections)	Then maintenance 927 mg SC every 6 months (26 weeks) from date of last injection	927 mg SC every 6 months
HIV-1, heavily treatment-experienced — Maintenance (regardless of initiation option)	Adults	927 mg SC (2 × 1.5 mL injections) every 6 months (26 weeks) from date of last injection, ±2 weeks	927 mg SC every 6 months (26 weeks) ±2 weeks	927 mg SC every 6 months
HIV-1, heavily treatment-experienced — Oral bridging for planned missed injection (visit to be missed by >2 weeks)	Adults, 26–28 weeks since last injection	300 mg PO once every 7 days, for up to 6 months until injections resume	300 mg PO once every 7 days; resume maintenance injection within 7 days after last oral dose	300 mg PO every 7 days for up to 6 months
HIV-1, heavily treatment-experienced — Unplanned missed injection (>28 weeks since last injection, no oral bridging taken)	Adults	Clinically reassess (consider lenacapavir resistance testing); if appropriate, reinitiate with Option 1 or Option 2 from Day 1	Then continue maintenance 927 mg SC every 6 months	927 mg SC every 6 months
Oral loading as component of BIXLENVO (bictegravir/lenacapavir) initiation — virologically suppressed (HIV-1 RNA <50 copies/mL) on stable regimen, no known/suspected resistance to BIXLENVO components	Adults	Day 1: 600 mg PO (2 × 300 mg) + BIXLENVO 75 mg/50 mg 1 tablet; Day 2: 600 mg PO (2 × 300 mg) + BIXLENVO 1 tablet	Day 3 onward: BIXLENVO alone once daily; Sunlenca not used for BIXLENVO maintenance	600 mg PO daily × 2 days (Day 1 and Day 2 doses never on the same day)

Renal No adjustment needed for mild, moderate, or severe impairment (CrCl ≥15 mL/min); not studied in ESRD (CrCl <15 mL/min)

Hepatic No adjustment needed for mild (Child-Pugh A) or moderate (Child-Pugh B); not studied in severe (Child-Pugh C)

Maintenance injection every 6 months (26 weeks) ±2 weeks from last injection; residual drug persists up to 12 months or longer after last SC dose

Instructions

Tablets with or without food
Injection: subcutaneous only, into the abdomen, by a healthcare provider; do NOT give intradermally (serious injection site reactions incl. necrosis/ulcer)
Two 1.5 mL injections (463.5 mg/1.5 mL each) required for a complete 927 mg dose; administer as soon as possible after withdrawal from vials; discard if discolored or particulate (normal solution is yellow)
Before starting (HTE): select patients who agree to every-6-month injection schedule; counsel on adherence to injection visits and concomitant oral ART
Maintenance injection window: every 6 months (26 weeks) from date of last injection ±2 weeks
Planned missed injection (>2 weeks late): 300 mg PO once every 7 days starting at 26–28 weeks since last injection, up to 6 months; resume injection within 7 days of last oral dose
Unplanned missed injection (>28 weeks, no oral bridging): reassess, consider resistance testing; reinitiate with Option 1 or 2 if clinically appropriate
BIXLENVO oral loading: missed Day 1 or Day 2 600 mg dose — take as soon as possible; never take Day 1 and Day 2 doses on the same day
Strong CYP3A inducers contraindicated (decreased lenacapavir levels → loss of effect, resistance)
Lenacapavir is a moderate CYP3A inhibitor: CYP3A-metabolized drugs started within 9 months after last SC dose may have increased exposure/adverse reactions
If discontinued: start an alternative fully suppressive ART regimen no later than 28 weeks after final injection; if virologic failure, switch regimen if possible

Available strengths

tab 300 mg
inj 463.5 mg/1.5 mL (SC, single-dose vial (2 vials = 927 mg dose))

Contraindications

Coadministration with strong CYP3A inducers (decreased lenacapavir concentrations → loss of therapeutic effect and resistance)

Cautions

Long-acting properties: residual lenacapavir for up to 12 months or longer after last SC dose; missed/late injections risk loss of virologic response and resistance
Moderate CYP3A inhibitor — increased exposure to CYP3A substrates initiated within 9 months after last SC dose
On discontinuation, start alternative fully suppressive ART no later than 28 weeks after final injection; switch regimen if virologic failure
Injection site reactions; nodules and indurations may persist (30% of nodules, 13% of indurations unresolved at median 553 days); intradermal administration linked to necrosis and ulcer
Immune reconstitution syndrome (opportunistic-infection inflammatory response; autoimmune disorders with variable, later onset)

Adverse reactions

Injection site reactions 65% (CAPELLA, N=72): swelling 36%, pain 31%, erythema 31%, nodule 25%, induration 15%, pruritus 6%, extravasation 3%, mass 3%; Grade 3 ISR 4%
Nausea 4%
Median ISR resolution 5 days (excluding nodules/indurations); nodules median 148 days, indurations median 70 days
Discontinuation for adverse events 1%
Grade 3–4 lab abnormalities (causality not established): creatinine 13%, glycosuria 6%, fasting hyperglycemia 5%, proteinuria 4%, ALT 3%, AST 3%, direct bilirubin 3%
Postmarketing: injection site necrosis

Pregnancy Randomized controlled trial data (individuals without HIV-1; 208 exposed pregnancies) show no drug-associated risk of miscarriage or adverse maternal/fetal outcomes vs active control; major birth defect rate within background (2 VSDs); estimates imprecise; animal studies no adverse developmental effects at ≥16× human exposure; Antiretroviral Pregnancy Registry 1-800-258-4263

Lactation Present in human milk (median milk:plasma ratio 0.63); detected at very low levels in breastfed infants (median infant:mother plasma ratio 0.06); no adverse effects observed in infants; risks include HIV-1 transmission, viral resistance in infants with HIV-1, and adult-type adverse reactions

Cost

Lenacapavir (SUNLENCA)

Strength		#/mo	generic $/unit	CostPlus
300 mg	tab	per unit		not offered
463.5 mg/1.5 mL	inj	per unit		not offered

NADAC is a voluntary CMS survey of what retail community pharmacies pay for the drugs they stock. Lenacapavir is administered under clinical supervision and dispensed outside retail pharmacies, so it rarely appears on surveyed invoices.

Other forms: Lenacapavir (PrEP) (YEZTUGO)

NO BOXED WARNINGS

No boxed warning for the HIV treatment indication, but the pre-exposure prophylaxis indication carries a boxed warning for drug-resistant HIV-1 if started during undiagnosed infection.

Principal riskA long tail risks resistance if injections lapse