lenacapavir

Absorption: 6–10% absorbed following oral administration; 91% absorbed following SUBQ administration.

Distribution: Extensively distributed to tissues.

Protein Binding: >98.5%.

Metabolism/Excretion: Primarily metabolized by the liver with some metabolism by the CYP3A isoenzyme and UGT1A1. Primarily excreted in feces (33% as unchanged drug), with <1% excreted in urine.

Half-Life: Oral: 10–12 days; SUBQ: 8–12 wk.

Time/Action Profile ⬆ ⬇

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
PO	unknown	4 hr	unknown
SUBQ	unknown	77–84 days	unknown

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Concurrent use of strong CYP3A inducers (Sunlenca only);
Unknown or positive HIV status (Yeztugo only);
End-stage renal disease;
Severe hepatic impairment;
Lactation: Breastfeeding not recommended for patients with HIV (Sunlenca only).

Use Cautiously in:

OB: Safety not established in pregnancy; not a recommended antiretroviral agent in pregnancy (Sunlenca only);
Lactation: Use while breastfeeding only if potential maternal benefit justifies potential risk to infant (Yeztugo only);
Pedi: Safety and effectiveness not established in children <18 yr (Sunlenca) or <35 kg (Yeztugo).

Adv. Reactions/Side Effects ⬆ ⬇

Endo: hyperglycemia

GI: ↑liver enzymes, diarrhea, nausea, vomiting

GU: ↑serum creatinine, glycosuria, proteinuria

Local: injection site reactions

Neuro: dizziness, headache

Misc: immune reconstitution syndrome

Interactions ⬆ ⬇

Because of long half-life of SUBQ lenacapavir, levels and risk of toxicity of CYP3A substrates initiated within 9 mo of last SUBQ dose may remain elevated.

Drug-drug:

Strong CYP3A inducers, including carbamazepine, phenytoin, or rifampin, significantly ↓ levels and effectiveness; concurrent use with Sunlenca contraindicated; administer supplemental Yeztugo doses.
Moderate CYP3A inducers, including efavirenz, nevirapine, oxcarbazepine, phenobarbital, rifabutin, rifapentine, and tipranavir/ritonavir, may ↓ levels and effectiveness; concurrent use with Sunlenca not recommended; administer supplemental Yeztugo doses.
Combined p-glycoprotein, UGT1A1, and strong CYP3A inhibitors, including atazanavir, cobicistat, darunavir, ergot derivatives, ritonavir, and voriconazole, may ↑ levels and risk of toxicity; concurrent use not recommended.
May ↑ levels and risk of toxicity of digoxin; monitor levels closely.
May ↑ levels and risk of bleeding of dabigatran, edoxaban, and rivaroxaban.
May ↑ levels and risk of toxicity of buprenorphine, dexamethasone, fentanyl, hydrocortisone, lovastatin, methadone, oxycodone, simvastatin, tramadol, and triazolam.
May ↑ levels and risk of toxicity of naloxegol; avoid concurrent use, if possible. If concurrent use is unavoidable, ↓ naloxegol dose.
May ↑ levels and risk of toxicity of sildenafil, tadalafil, and vardenafil; concurrent use with tadalafil for pulmonary arterial hypertension not recommended.

Drug-Natural Products:

St. John's wort significantly ↓ levels and effectiveness; concurrent use contraindicated.

Route/Dosage ⬆ ⬇

Sunlenca

Treatment can be initiated with either the 2-day or 15-day initiation regimen.
2-Day Initiation Regimen
PO SC (Adults ): Day 1: 600 mg orally as single dose AND 927 mg SUBQ as single dose. Day 2: 600 mg orally as single dose. Maintenance dosing: Starting 6 mo following date of last injection, administer 927 mg SUBQ every 6 mo (26 wk ± 2 wk).
15-Day Initiation Regimen
PO SC (Adults ): Day 1: 600 mg orally as single dose. Day 2: 600 mg orally as single dose. Day 8: 300 mg orally as single dose. Day 15: 927 mg SUBQ as single dose.Maintenance dosing: Starting 6 mo following date of last injection, administer 927 mg SUBQ every 6 mo (26 wk ± 2 wk).

Yeztugo

PO SC (Adults and Children ≥35 kg): Initiation (Day 1): 927 mg SUBQ as single dose AND 600 mg orally as single dose; Initiation (Day 2): 600 mg orally as single dose; Continuation: Starting 6 mo following date of last injection, administer 927 mg SUBQ every 6 mo (26 wk ± 2 wk). Concurrent use of strong CYP3A inducer: Continue to administer 927 mg SUBQ every 6 mo as previously scheduled PLUS administer the following supplemental doses: On day strong CYP3A inducer initiated (should be ≥2 days after Yeztugo 1st initiated): Step 1: Administer 927 mg SUBQ as single dose AND 600 mg orally as single dose; On day after strong CYP3A inducer initiated: Step 2: Administer 600 mg orally as single dose; If strong CYP3A inducer coadministered for >6 mo: Every 6 mo from initiation of strong CYP3A inducer, continue to administer supplemental doses as outlined above in Steps 1 and 2. Concurrent use of moderate CYP3A inducer: Continue to administer 927 mg SUBQ every 6 mo as previously scheduled PLUS administer the following supplemental doses; On day moderate CYP3A inducer initiated: Administer 463.5 mg SUBQ as single dose; If moderate CYP3A inducer coadministered for >6 mo: Every 6 mo from initiation of moderate CYP3A inducer, continue to administer a supplemental dose.

Availability ⬆ ⬇

Tablets: 300 mg
Solution for SUBQ injection: 463.5 mg/1.5 mL

Assessment ⬆ ⬇

Assess for change in severity of HIV symptoms during therapy.
Assess for immune reconstitution syndrome. Monitor for signs and symptoms of fever, localized inflammation, confusion, and respiratory issues and for symptoms of opportunistic infections during therapy.
Assess SUBQ injection sites for reactions (erythema, pain, induration, nodules).

Lab Test Considerations:

Obtain baseline HIV RNA levels.
Monitor viral load and CD4 count.
Obtain baseline ALT, AST, and bilirubin. May cause hepatotoxicity.
Monitor serum creatinine during routine assessment.
Monitor for metabolic abnormalities such as lipid or glucose changes.
Yeztugo: Perform HIV-1 screening before starting, before each subsequent injection, and as clinically appropriate. Do not initiate therapy unless negative infection status is confirmed.

Implementation ⬆ ⬇

PO: Administer with or without food.
SC: Use aseptic technique. Visually inspect the solution in the vials and prepared syringe for particulate matter and discoloration before administration. Solution is a yellow color. Do not use if the solution is discolored or contains particulate matter. Withdraw 1.5 mL from each vial using provided syringes and withdrawal needles or vial access devices; two 1.5-mL injections are required for each dose. Prepared syringes should be administered as soon as possible. Discard any solution remaining in vial.
- Administer each injection at separate sites apart in the abdomen (≥2 in from the navel). Do not administer intradermally due to risk of serious injection site reactions.
- Planned missed injections: If a patient plans to miss a scheduled 6-mo injection visit by >2 wk during the maintenance period, lenacapavir 300 mg orally once every 7 days may be taken for up to 6 mo until injections resume. Resume maintenance injection dosage within 7 days after the last PO dose.
- Unplanned missed Sunlenca injections: If >28 wk since the last injection during the maintenance period, if lenacapavir oral tablets have not been taken, and if clinically appropriate to continue treatment, restart starting dosage regimen from Day 1, using either 2-day or 15-day initiation. Unplanned missed Yeztugo injection: If >28 wk since the last injection and tablets have not been taken, restart initiation from Day 1, if clinically appropriate.
- Discontinuation of therapy: Residual concentrations of lenacapavir long-acting injection may remain in the systemic circulation of patients for ≥12 mo; consider this if therapy is discontinued. To minimize the potential risk of resistance development, an alternative fully suppressive antiretroviral regimen should be initiated when possible, no later than 28 wk after final injection.
- Yeztugo: Missed PO Initiation Dose: If Day 2 PO initiation dose (600 mg) is missed, take it as soon as possible. Do not take Day 1 and Day 2 PO initiation doses on the same day.

Patient/Family Teaching ⬆ ⬇

Explain purpose and side effects of medication. Advise patient to read Patient Information before starting therapy. Advise patient to contact health care provider if dose is missed or plan to miss a scheduled injection visit and that oral therapy may be used for up to 6 mo to replace missed injections.
Advise patient to notify health care provider of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care provider before taking other medications, especially St. John’s wort. If therapy is discontinued, advise patient that lenacapavir may remain in the body and affect certain other drugs for up to 9 mo after receiving the last injection.
Advise patient to inform their health care provider immediately of any symptoms of infection; signs and symptoms of inflammation from previous infections may occur soon after anti-HIV treatment is started.
Advise patient that injection site reactions (swelling, pain, erythema, nodule, induration, pruritus, extravasation, mass) may occur. Nodules and indurations at the injection site may take longer to resolve than other reactions and may be persistent.
Advise patient about the importance of continued medication adherence and scheduled visits to maintain viral suppression and to ↓ risk of loss of virologic response and development of resistance. Advise patient to contact health care provider immediately if they stop taking therapy or any other drug in their antiretroviral regimen.
Advise patient taking Yeztugo about the potential risk of developing resistance to lenacapavir if HIV-1 is acquired either before or when receiving or following discontinuation of therapy. Advise that testing will be done before each injection and additionally as clinically appropriate to confirm HIV-1 negative status. If HIV-1 is acquired while receiving Yeztugo, discontinue therapy, and treatment should be changed to a full HIV-1 regimen.
Advise patient taking Yeztugo on adhering to the required initiation and continuation dosing schedule, safe sex practices (condoms), and other measures to reduce the risk of sexually transmitted infections.
Rep: Advise women of reproductive potential to notify health care provider if pregnancy is planned or suspected and to avoid breastfeeding during therapy. Enroll all patients exposed to antiretroviral medications as early in pregnancy as possible in the Antiretroviral Pregnancy Registry (1-800-258-4263).

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇