Yeztugo LENACAPAVIR SODIUM Kit
🆔 Identity & classification
Where does this data come from?
🏷️ RxNorm drug class
This medicine belongs to the Human Immunodeficiency Virus 1 Capsid Inhibitor class.
Where does this data come from?
🏭 Manufacturer & labeler
Where does this data come from?
🩺 Clinical
Lenacapavir injection is used to treat human immunodeficiency virus (HIV). Lenacapavir is also used along with practicing safer sex (e.g., condom use) to reduce the risk of HIV infection. Lenacapavir is in a class of medications called HIV capsid inhibitors. It works by decreasing the amount of HIV in the blood. Although lenacapavir does not cure HIV, it may decrease your chance of developing acquired immunodeficiency syndrome (AIDS) and HIV-related illnesses. Taking these medications along with practicing safer sex and making other life-style changes may decrease the risk of giving the HIV v...
Read the full MedlinePlus article ↗- Lenacapavir works by targeting the HIV virus's outer protein shell — called the capsid — which disrupts its ability to replicate. The oral tablets serve a specific purpose at the s...
- What exactly does lenacapavir do, and why do I need the tablets if there's also an injection?
- Yes, absolutely — this is one of the most important things to know. You must be tested for HIV-1 before every single injection using a sensitive FDA-approved test, not just when yo...
- I'm taking Yeztugo to prevent HIV — do I still need to get tested regularly?
Patient education
Supplement & herbal interactions
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Ask a licensed pharmacist directly — free, answered by our team.
💊 What it looks like
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🧪 Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
Where does this data come from?
IACT rows and label-wide narrative are kept separate; availability and product-level specificity depend on the submitted label.Inactive ingredient FAQ
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💲 Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per each | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | Not in the retail survey — common for institutional, discontinued, or low-volume packs. | |
| Medicaid paysCMS SDUD · 12 mo | $10,389.23 | — |
| Medicare drug plans payPart D · quarterly | No Part D plan price is available for this NDC in our data. | |
| Medicare Part B allowsASP · J0738 | $16.081 / J0738 unit | — |
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🧾 Billing & reimbursement
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🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Sunlenca 61958-3002-01 | Gilead | 1 kit | — | — | FDA listed | — |
| Sunlenca 61958-3005-01 | Gilead | 1 kit | — | — | FDA listed | — |
| Yeztugothis 61958-3402-01 | Gilead | 1 kit | — | — | FDA listed | — |
Where does this data come from?
⏳ Availability & generic status
We did not find an FDA-approved generic match for this exact strength, form and route. Patent/protection dates below may affect future generic timing.
Why the date isn’t exact: Generic timing can change because patents may be challenged, settled, licensed, added, removed, or worked around with a narrower label — and FDA approval does not always mean a pharmacy can get the generic today.
🛈 What do these terms mean?
- Patent
- Legal protection listed in the Orange Book that may delay generic approval or launch. Issued by the U.S. Patent & Trademark Office.
- Substance patent
- Covers the active drug molecule itself — the hardest to design around. A generic generally can’t launch until it expires.
- Formulation (product) patent
- Covers a specific formulation or dosage form. A generic can sometimes work around it with a different formulation.
- Method-of-use patent
- A patent covering one specific approved use of the drug — not necessarily the whole molecule. A generic can sometimes launch with a “skinny label” that carves out the protected use and keeps the others.
- Skinny label
- A generic label that omits a still-patented use when the FDA allows it — letting a generic reach the market for the unprotected uses.
- Exclusivity
- FDA-granted marketing protection, separate from patents — e.g. 5-yr new chemical entity, 7-yr orphan drug, or a +6-month pediatric extension.
- Paragraph IV
- A generic applicant’s formal challenge to a listed patent. It can potentially lead to earlier generic entry, but often involves litigation or a settlement.
- RLD / RS
- Reference Listed Drug — the brand product the FDA uses as the reference for generic applications. Reference Standard — the product the FDA expects generics to compare against in bioequivalence testing.
- TE / AB rating
- FDA therapeutic-equivalence rating. An AB rating generally means the FDA considers a generic therapeutically equivalent to — and substitutable for — the brand.
- LOE (loss of exclusivity)
- The latest patent or exclusivity currently listed — the loss-of-exclusivity / latest-listed-protection date shown on this page. Paragraph-IV challenges and settlements can move the real date earlier; FDA approval and a manufacturer’s decision to market can move it later.
Built from the FDA Orange Book. The bars above are scaled to each protection’s expiry; the red LOE marker is the last one to lapse.
| Patent | Type | Use code | Expires |
|---|---|---|---|
| US 11807625 ↗ | Method of use | U-4190 | Nov 25, 2040 |
| US 9951043 ↗ | Drug substance | U-4190 | Feb 28, 2034 |
| US 12594267 ↗ | Drug product | — | Jul 15, 2039 |
| US 11267799 ↗ | Drug substance | — | Aug 16, 2038 |
| US 10071985 ↗ | Drug substance | — | Aug 17, 2037 |
| Code | What it grants | Expires |
|---|---|---|
| NCE | New Chemical Entity (5-year) | Dec 22, 2027 |
| NP | New Product | Jun 18, 2028 |
Is there a generic version of YEZTUGO 463.5 MG/1.5 ML VIAL?
The FDA approved a generic — why can’t I get it at my pharmacy yet?
Why do different websites show different generic release dates?
What does “FDA listed” mean?
What does a patent or protection date mean here?
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Can a generic come out before the last patent expires?
Can a generic come out after the listed dates?
What is the difference between patents and exclusivity?
Why are there multiple patent dates?
Where does this data come from?
🗺️ Medicaid utilization & spend
📊 Medicare Part D spend CMS · PART D · 2026 (Q1)
📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 61958-3402-01 You're viewing this | 1 KIT in 1 CARTON (61958-3402-1) * 1.5 mL in 1 VIAL (61958-3403-1) | 2025-06-18 | Active |
🧭 About this NDC listing & data coverage
Kit / multi-component package
This NDC identifies a kit — a package containing more than one component. Structured data (pricing, ingredients, equivalents) is often reported per component rather than for the kit NDC itself, which can make this page look thinner than the components' own pages.
What data is (and isn’t) available for this NDC — tap to expand
| NDC identity (package / product / labeler codes) | ✓ Available |
| Labeler | ✓ Available |
| Product & package description | ✓ Available |
| Marketing category & status | ✓ Available |
| Active ingredient / dosage form / route | ✓ Available |
| FDA label (SPL via DailyMed) | ✓ Available |
| Package photos | ✓ Available |
| Inactive ingredients (structured) | — Not published for this NDC The labeler did not submit a structured excipient list, or no SPL is available. |
| NADAC pharmacy acquisition price (CMS) | — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey. |
| Orange Book / therapeutic-equivalence data | ✓ Available |
| HCPCS J-code billing crosswalk | ✓ Available |
| Medicaid utilization (CMS SDUD) | ✓ Available |
Questions about this listing
Why is there no price listed?
Is the NDC printed on the package the same as the 11-digit billing NDC?
What do the three segments of this NDC mean?
Is this package still being marketed?
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Do I need a prescription for this product?
Does this product have a billing J-code?
Where does this data come from?
📄 Full prescribing information FDA SPL
🚨 Boxed Warning ▾
WARNING: RISK OF DRUG RESISTANCE WITH USE OF YEZTUGO FOR HIV-1 PRE-EXPOSURE PROPHYLAXIS (PrEP) IN UNDIAGNOSED HIV-1 INFECTION Individuals must be tested for HIV-1 infection prior to initiating YEZTUGO, and with each subsequent injection of YEZTUGO, using a test approved or cleared by the FDA for the diagnosis of acute or primary HIV-1 infection. Drug-resistant HIV-1 variants have been identified with use of YEZTUGO by individuals with undiagnosed HIV-1 infection. Do not initiate YEZTUGO unless negative infection status is confirmed.
Individuals who acquire HIV-1 while receiving YEZTUGO must transition to a complete HIV-1 treatment regimen [see Dosage and Administration (2.1) , Contraindications (4) , Warnings and Precautions (5.1 , 5.2) ]. WARNING: RISK OF DRUG RESISTANCE WITH USE OF YEZTUGO FOR HIV-1 PRE-EXPOSURE PROPHYLAXIS (PrEP) IN UNDIAGNOSED HIV-1 INFECTION See full prescribing information for complete boxed warning. Individuals must be tested for HIV-1 infection prior to initiating YEZTUGO, and with each subsequent injection of YEZTUGO, using a test approved or cleared by the FDA for the diagnosis of acute or primary HIV-1 infection.
Drug-resistant HIV-1 variants have been identified with use of YEZTUGO by individuals with undiagnosed HIV-1 infection. Do not initiate YEZTUGO unless negative infection status is confirmed. Individuals who acquire HIV-1 while receiving YEZTUGO must transition to a complete HIV-1 treatment regimen ( 2.1 , 4 , 5.1 , 5.2 ).
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE YEZTUGO is indicated for pre‑exposure prophylaxis (PrEP) to reduce the risk of sexually acquired HIV-1 in adults and adolescents weighing at least 35 kg who are at risk for HIV-1 acquisition. Individuals must have a negative HIV-1 test prior to initiating YEZTUGO [see Dosage and Administration (2.1) and Warnings and Precautions (5.1) ]. YEZTUGO, a human immunodeficiency virus type 1 (HIV-1) capsid inhibitor, is indicated for pre‑exposure prophylaxis (PrEP) to reduce the risk of sexually acquired HIV-1 in adults and adolescents weighing at least 35 kg who are at risk for HIV-1 acquisition.
Individuals must have a negative HIV-1 test prior to initiating YEZTUGO. ( 1 )
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION HIV-1 screening: Screen all individuals for HIV-1 infection prior to initiating YEZTUGO, prior to each injection of YEZTUGO, and additionally as clinically appropriate. ( 2.1 ) Dosing schedule: Initiation dosing (injection and tablets) followed by once every 6-months continuation injection dosing. Tablets may be taken without regard to food.
( 2.3 ) Initiation Day 1 927 mg by subcutaneous injection (2 x 1.5 mL injections) and 600 mg orally (2 x 300 mg tablets) Day 2 600 mg orally (2 x 300 mg tablets) Continuation 927 mg by subcutaneous injection (2 x 1.5 mL injections) every 6-months (26 weeks) from the date of the last injection +/-2 weeks. Anticipated delayed injections: If scheduled injection is anticipated to be delayed by more than 2 weeks, YEZTUGO tablets may be used on an interim basis (for up to 6 months if needed) until injections resume. Dosing schedule for delayed injection is 300 mg orally once every 7 days.
( 2.4 ) Missed injections: If more than 28 weeks have elapsed since last injection and tablets have not been taken, restart initiation from Day 1 if clinically appropriate. ( 2.4 ) Dosage modifications (supplemental doses) of YEZTUGO are recommended when initiating strong or moderate CYP3A inducers. ( 2.5 ) YEZTUGO injection is for subcutaneous administration only.
Two 1.5 mL injections are required for complete dose. ( 2.6 )
2.1HIV-1 Screening for Individuals Receiving YEZTUGO for HIV-1 Pre-Exposure Prophylaxis Screen all individuals for HIV-1 infection prior to initiating YEZTUGO, prior to each subsequent injection of YEZTUGO, and additionally as clinically appropriate, using a test approved or cleared by the FDA for the diagnosis of acute or primary HIV-1 infection. When screening for HIV-1 infection prior to initiating YEZTUGO, if an antigen/antibody-specific test is used and provides negative results, then such negative results should be confirmed using an RNA-specific assay, even if the results of the RNA-assay are available after YEZTUGO initiation.
When screening for HIV-1 infection prior to continuing YEZTUGO, negative results from a rapid, point-of-care antigen/antibody test should be confirmed using a more sensitive assay [see Indications and Usage (1) , Contraindications (4) , Warnings and Precautions (5.1 , 5.2) and Clinical Studies (14) ].
2.2Adherence to YEZTUGO Prior to starting YEZTUGO, healthcare providers should select individuals who agree to the required testing and every 6 month injection dosing schedule, and counsel individuals about the importance of adherence to scheduled YEZTUGO dosing visits to help reduce the risk of acquiring HIV-1 infection and development of resistance [see Dosage and Administration (2.1) , Warnings and Precautions (5.1 , 5.2) , and Microbiology (12.4) ] .
2.3Recommended Dosage The YEZTUGO dosing schedule in adults and adolescents weighing at least 35 kg consists of a required initiation dosing (subcutaneous injections and oral tablets) followed by once every 6-months continuation dosing (subcutaneous injections) ( Table 1 ). YEZTUGO oral tablets may be taken with or without food [see Clinical Pharmacology (12.3) ] . Table 1.
Dosing Schedule for YEZTUGO Initiation and Continuation in Adults and Adolescents Weighing at Least 35 kg Time Dosage of YEZTUGO: Initiation The complete initiation dosing schedule, consisting of subcutaneous injections and oral tablets, is required; the efficacy of YEZTUGO has only been established with this dosing schedule. Day 1 927 mg by subcutaneous injection (2 x 1.5 mL injections) and 600 mg orally (2 x 300 mg tablets) Day 2 600 mg orally (2 x 300 mg tablets) Dosage of YEZTUGO: Continuation Every 6-months (26 weeks) From the date of the last injection. +/-2 weeks 927 mg by subcutaneous injection (2 x 1.5 mL injections)
2.4Dosing Schedule for Missed Dose Missed Oral Initiation Dose If the Day 2 oral initiation dose (600 mg; see Table 1 ) is missed, take it as soon as possible. Do not take Day 1 and Day 2…
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS Tablets: 300 mg of lenacapavir Injection: 463.5 mg/1.5 mL (309 mg/mL) of lenacapavir in single-dose vials. ( 3 ) YEZTUGO tablets: Each tablet contains 300 mg of lenacapavir (present as 306.8 mg of lenacapavir sodium). The tablets are beige, capsule-shaped, film-coated, and debossed with ‘GSI’ on one side of the tablet and ‘62L’ on the other side of the tablet.
YEZTUGO injection: Each single-dose vial contains 463.5 mg/1.5 mL (309 mg/mL) of lenacapavir (present as 473.1 mg/1.5 mL of lenacapavir sodium). The lenacapavir injectable solution is sterile, preservative-free, clear, and yellow with no visible particles.
⛔ Contraindications ▾
4 CONTRAINDICATIONS YEZTUGO is contraindicated in individuals with unknown or positive HIV-1 status [see Warnings and Precautions (5.1) ]. Unknown or positive HIV-1 status. ( 4 )
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS Comprehensive management to reduce the risk of HIV-1 acquisition. ( 5.1 ) Potential risk of developing resistance to lenacapavir if an individual acquires HIV-1 either before or when receiving YEZTUGO, or following discontinuation of YEZTUGO. Test before each injection and additionally as clinically appropriate to confirm HIV-1 negative status ( 5.2 ) Residual concentrations of lenacapavir may remain in systemic circulation for up to 12 months or longer.
( 5.3 ) Improper administration (intradermal injection) has been associated with serious injection site reactions. ( 5.4 )
5.1Comprehensive Management to Reduce the Risk of HIV-1 Infection and Other Sexually Acquired Infections Use YEZTUGO to reduce the risk of HIV-1 acquisition as part of a comprehensive prevention strategy including adherence to the administration schedule and safer sex practices, including condoms, to reduce the risk of sexually transmitted infections (STIs). YEZTUGO is not always effective in preventing HIV-1 acquisition [see Clinical Studies (14) ]. The time from initiation of YEZTUGO for HIV-1 PrEP to maximal protection against HIV-1 infection is unknown.
Risk for HIV-1 acquisition includes behavioral, biological, or epidemiologic factors including, but not limited to, condomless sex, past or current STIs, self-identified HIV risk, having sexual partners of unknown HIV-1 viremic status, or sexual activity in a high prevalence area or network. Counsel individuals on the use of other prevention measures (e.g., consistent and correct condom use; knowledge of partner(s)’ HIV-1 status, including viral suppression status; regular testing for STIs that can facilitate HIV-1 transmission).
Inform individuals about and support their efforts in reducing sexual behaviors associated with HIV-1 acquisition risk. Use YEZTUGO to reduce the risk of HIV-1 acquisition only in individuals confirmed to be HIV-1 negative [see Contraindications (4) ] . Evaluate for current or recent signs or symptoms consistent with acute HIV-1 infection (e.g., fever, fatigue, myalgia, skin rash).
Confirm HIV-1 negative status prior to initiating YEZTUGO, prior to each subsequent injection of YEZTUGO, and additionally as clinically appropriate (e.g., upon diagnosis of other sexually transmitted infections or if clinical symptoms consistent with acute HIV-1 infection are present) using a test approved or cleared by the FDA for the diagnosis of acute or primary HIV-1 infection [see Dosage and Administration (2.1) ] . Counsel and support individuals on adhering to the YEZTUGO administration schedule, on the use of other measures to reduce the risk of STIs, and on the importance of routine testing for HIV-1 and other STIs.
Some individuals, such as adolescents, may benefit from additional counseling and appointment reminders to support adherence to the dosing and testing schedule [see Use in Specific Populations (8.4) ] .
5.2Potential Risk of Resistance with YEZTUGO There is a potential risk of developing resistance to YEZTUGO if an individual acquires HIV-1 either before or when receiving YEZTUGO, or following discontinuation of YEZTUGO. HIV-1 resistance substitutions may emerge in individuals with undiagnosed HIV-1 infection who are taking only YEZTUGO because YEZTUGO alone does not constitute a complete regimen for HIV-1 treatment [see Microbiology (12.4) ] . To minimize this risk, it is essential to test before each injection and additionally as clinically appropriate (e.g., upon diagnosis of other sexually transmitted infections or if clinical symptoms consistent with acute HIV-1 infection are present) to confirm HIV-1 negative status using a test approved or cleared by the FDA for the diagnosis of acute or primary HIV-1 infection.
Individuals who are confirmed to have HIV-1 must immediately begin a complete HIV-1 treatment regimen to reduce the risk of developing resistance. In addition, due to the long-acting properties of YEZTUGO, alternative forms of PrEP shou…
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS The following adverse reactions are discussed in other sections of the labeling: Serious Injection Site Reactions with Improper Administration [see Warnings and Precautions (5.4) ]. Most common adverse reactions (incidence greater than or equal to 5%, all grades) are injection site reactions, headache, and nausea. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Gilead Sciences, Inc. at 1-800-GILEAD-5 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
6.1Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The primary safety assessment of YEZTUGO is based on data from two randomized, double-blind, active-controlled trials, PURPOSE 1 and PURPOSE 2, in which a total of 8616 adult and adolescent participants received YEZTUGO (N=4323), DESCOVY (emtricitabine [FTC]/tenofovir alafenamide [TAF]; N=2135) once daily, or TRUVADA (FTC/tenofovir disoproxil fumarate [TDF]; N=2158) once daily for HIV-1 PrEP.
In PURPOSE 1, the median duration of exposure to YEZTUGO, DESCOVY, and TRUVADA was 43, 42, and 41 weeks, respectively. In PURPOSE 2, the median duration of exposure to both YEZTUGO and TRUVADA was 39 weeks. The most common adverse reactions (all Grades) reported in at least 5% of participants receiving YEZTUGO in either PURPOSE 1 or PURPOSE 2 were injection site reactions, headache, and nausea.
In PURPOSE 1, <1% of participants in the groups receiving YEZTUGO, DESCOVY or TRUVADA, discontinued due to adverse events (all causality). In PURPOSE 2, 1% of participants in the group receiving YEZTUGO and <1% of participants receiving TRUVADA discontinued due to adverse events (all causality). Table 6 presents the frequency of adverse reactions (all Grades) in at least 2% of participants receiving YEZTUGO in either PURPOSE 1 or PURPOSE 2.
Table 6. Adverse Drug Reactions (All Grades) Reported in ≥2% Frequencies of adverse reactions are based on all adverse events attributed to study drug (or to the procedure for injection site reactions) by the investigator. of Participants Receiving YEZTUGO in PURPOSE 1 or PURPOSE 2 PURPOSE 1 PURPOSE 2 Adverse Reaction YEZTUGO N=2140 TRUVADA Participants received placebo subcutaneous injections (polyethylene glycol 400). N=1070 YEZTUGO N=2183 TRUVADA N=1088 Injection Site Reactions 69% 34% 83% 69% Headache 7% 8% 2% 2% Nausea 5% 11% 2% 4% Dizziness 4% 6% <1% 1% Vomiting 4% 7% <1% 1% Diarrhea 4% 4% 2% 2% Injection-Associated Adverse Reactions Local Injection Site Reactions (ISRs) The most frequent adverse reactions associated with lenacapavir injection for subcutaneous use in PURPOSE 1 and PURPOSE 2 were ISRs.
The most commonly reported ISRs (all grades) in at least 2% of participants who received YEZTUGO in either PURPOSE 1 or PURPOSE 2 are presented in Table 7 . PURPOSE 1 In PURPOSE 1, 69% of participants receiving YEZTUGO experienced ISRs, compared to 35% of participants receiving placebo injections (and DESCOVY or TRUVADA). Most participants who received YEZTUGO had mild (Grade 1, 50%) or moderate (Grade 2, 19%) severity ISRs.
Grade 3 ISRs were reported in 4 (0.2%) participants, and included ulcer and nodule. YEZTUGO was discontinued due to ISRs in 4 (0.2%) participants. None of the ISRs were serious.
The incidence of reported ISRs decreased with subsequent injections. Nodules: Injection site nodule was reported in 64% of participants who received YEZTUGO and resolved more slowly than other ISRs. The median duration of nodules associated with the first injections of YEZTUGO was 350 (interquartile range: 182, 470) days.
The median of the maximum observed nodule diameter from each participant was 3.0 (interquartile range: 2.0, 3.5) cm. Other ISRs: The other ISRs reported in more than 2% of participants who received YEZTUGO were pain (31%), swelling (4…
🔄 Drug Interactions ▾
7 DRUG INTERACTIONS Consult the Full Prescribing Information for important drug interactions with YEZTUGO. ( 7 , 12.3 )
7.1Effect of Other Drugs on YEZTUGO Lenacapavir is a substrate of P-gp, UGT1A1, and CYP3A. Strong or Moderate CYP3A Inducers Drugs that are strong or moderate inducers of CYP3A may significantly decrease plasma concentrations of lenacapavir, which may reduce the effectiveness of YEZTUGO. Therefore, dosage modifications (supplemental doses) of YEZTUGO are recommended when initiating strong or moderate CYP3A inducers [see Dosage and Administration (2.5) and Clinical Pharmacology (12.3) ] .
Combined P-gp, UGT1A1, and Strong CYP3A Inhibitors Combined P-gp, UGT1A1, and strong CYP3A inhibitors may significantly increase plasma concentrations of YEZTUGO. Concomitant administration of YEZTUGO with these inhibitors is not recommended.
7.2Effect of YEZTUGO on Other Drugs CYP3A and P-gp Substrates Lenacapavir is a moderate inhibitor of CYP3A and a P-gp inhibitor. The co-administration of YEZTUGO with sensitive substrates of CYP3A or P-gp may increase the concentrations of these substrates and result in the increased risk of their adverse events. See the prescribing information of these sensitive substrates for dosing recommendations or appropriate monitoring of safety.
Due to the long half-life of lenacapavir following subcutaneous administration, YEZTUGO may increase the exposure of drugs primarily metabolized by CYP3A [see Clinical Pharmacology (12.3) ] initiated within 9 months after the last subcutaneous dose of YEZTUGO.
7.3Drugs without Clinically Significant Interactions with YEZTUGO Based on drug interaction studies conducted with YEZTUGO, no clinically significant drug interactions have been observed with: atorvastatin, famotidine, pitavastatin, rosuvastatin, tenofovir alafenamide, and voriconazole.
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS
8.1Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in individuals exposed to YEZTUGO during pregnancy. Healthcare providers are encouraged to register individuals by calling the Antiretroviral Pregnancy Registry (APR) at 1-800-258-4263. Risk Summary Available data from a randomized, controlled trial (PURPOSE 1) with YEZTUGO use during pregnancy have not identified a drug-associated risk for miscarriage, or adverse maternal or fetal outcomes when compared to the active control (see Data ) .
The rate of major birth defects in YEZTUGO-exposed pregnancies did not exceed the background prevalence rates. The risk estimates are imprecise due to small numbers of exposed pregnancies (see Data ) . There is an increased risk of HIV-1 transmission from the mother to the child during acute HIV-1 infection (see Clinical Considerations ).
In animal reproduction studies, no adverse developmental effects were observed when lenacapavir was administered to rats and rabbits at exposures (AUC) ≥7 times the exposure in humans at the recommended human dose (RHD) of YEZTUGO ( see Data ). The APR has been established to monitor for birth defects following prenatal exposure to antiretrovirals. The APR uses the Metropolitan Atlanta Congenital Defects Program (MACDP) as the U.S. reference population for birth defects in the general population.
The background rate for major birth defects is 2.7% in the MACDP. The rate of miscarriage for individual drugs is not reported in the APR. In the U.S. general population, the estimated background risk of miscarriage in clinically recognized pregnancies is 15–20%.
The MACDP evaluates mothers and infants from a limited geographic area and does not include outcomes for births that occurred at < 20 weeks gestation. Clinical Considerations Disease-associated maternal and/or embryo/fetal risk Published studies indicate an increased risk of HIV-1 infection during pregnancy and an increased risk of mother to child transmission during acute HIV-1 infection. In women at risk of acquiring HIV-1, consideration should be given to methods to prevent acquisition of HIV-1, including continuing or initiating YEZTUGO for HIV-1 PrEP, during pregnancy.
Data Human Data In a randomized, controlled trial in Uganda and South Africa (PURPOSE 1), there were 208 pregnancies exposed to YEZTUGO with known outcomes and 132 deliveries (both live and non-live). In the active control arm of PURPOSE 1, there were 109 pregnancies exposed to TRUVADA with known outcomes and 61 deliveries (both live and non-live). The adverse pregnancy outcomes of spontaneous abortion, stillbirth, preterm birth, and small for gestational age were similar across both treatment groups.
There were two major birth defects in the YEZTUGO arm. Both were ventricular septal defects. This resulted in a rate of major birth defects that fell within the background prevalence rate for major birth defects.
Concentrations of YEZTUGO during each trimester of pregnancy and postpartum were comparable to those in non-pregnant participants [see Clinical Pharmacology (12.3) ]. Animal Data Lenacapavir was administered intravenously to pregnant rabbits (up to 20 mg/kg/day on gestation days (GD) 7 to 19), orally to rats (up to 300 mg/kg/day on GD 6 to 17), and subcutaneously to rats (up to 300 mg/kg on GD 6). No significant toxicological effects on embryo-fetal (rats and rabbits) or pre/postnatal (rats) development were observed at exposures (AUC) approximately 21 times (rats) and 170 times (rabbits) the exposure in humans at the RHD of YEZTUGO.
8.2Lactation Risk Summary Lenacapavir is present in human milk. Lenacapavir was detected at very low levels in infants who were breastfed by individuals who became pregnant while receiving YEZTUGO (see Data ) . No adverse effects of lenacapavir in breastfed infants have been observed. It is not known if YEZTUGO affects milk production. In women without HIV-1…
🤰 Pregnancy ▾
8.1Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in individuals exposed to YEZTUGO during pregnancy. Healthcare providers are encouraged to register individuals by calling the Antiretroviral Pregnancy Registry (APR) at 1-800-258-4263. Risk Summary Available data from a randomized, controlled trial (PURPOSE 1) with YEZTUGO use during pregnancy have not identified a drug-associated risk for miscarriage, or adverse maternal or fetal outcomes when compared to the active control (see Data ) .
The rate of major birth defects in YEZTUGO-exposed pregnancies did not exceed the background prevalence rates. The risk estimates are imprecise due to small numbers of exposed pregnancies (see Data ) . There is an increased risk of HIV-1 transmission from the mother to the child during acute HIV-1 infection (see Clinical Considerations ).
In animal reproduction studies, no adverse developmental effects were observed when lenacapavir was administered to rats and rabbits at exposures (AUC) ≥7 times the exposure in humans at the recommended human dose (RHD) of YEZTUGO ( see Data ). The APR has been established to monitor for birth defects following prenatal exposure to antiretrovirals. The APR uses the Metropolitan Atlanta Congenital Defects Program (MACDP) as the U.S. reference population for birth defects in the general population.
The background rate for major birth defects is 2.7% in the MACDP. The rate of miscarriage for individual drugs is not reported in the APR. In the U.S. general population, the estimated background risk of miscarriage in clinically recognized pregnancies is 15–20%.
The MACDP evaluates mothers and infants from a limited geographic area and does not include outcomes for births that occurred at < 20 weeks gestation. Clinical Considerations Disease-associated maternal and/or embryo/fetal risk Published studies indicate an increased risk of HIV-1 infection during pregnancy and an increased risk of mother to child transmission during acute HIV-1 infection. In women at risk of acquiring HIV-1, consideration should be given to methods to prevent acquisition of HIV-1, including continuing or initiating YEZTUGO for HIV-1 PrEP, during pregnancy.
Data Human Data In a randomized, controlled trial in Uganda and South Africa (PURPOSE 1), there were 208 pregnancies exposed to YEZTUGO with known outcomes and 132 deliveries (both live and non-live). In the active control arm of PURPOSE 1, there were 109 pregnancies exposed to TRUVADA with known outcomes and 61 deliveries (both live and non-live). The adverse pregnancy outcomes of spontaneous abortion, stillbirth, preterm birth, and small for gestational age were similar across both treatment groups.
There were two major birth defects in the YEZTUGO arm. Both were ventricular septal defects. This resulted in a rate of major birth defects that fell within the background prevalence rate for major birth defects.
Concentrations of YEZTUGO during each trimester of pregnancy and postpartum were comparable to those in non-pregnant participants [see Clinical Pharmacology (12.3) ]. Animal Data Lenacapavir was administered intravenously to pregnant rabbits (up to 20 mg/kg/day on gestation days (GD) 7 to 19), orally to rats (up to 300 mg/kg/day on GD 6 to 17), and subcutaneously to rats (up to 300 mg/kg on GD 6). No significant toxicological effects on embryo-fetal (rats and rabbits) or pre/postnatal (rats) development were observed at exposures (AUC) approximately 21 times (rats) and 170 times (rabbits) the exposure in humans at the RHD of YEZTUGO.
🧒 Pediatric Use ▾
8.4Pediatric Use The safety and effectiveness of YEZTUGO for HIV-1 PrEP in adolescents weighing at least 35 kg who are at risk for HIV-1 acquisition is supported by 2 adequate and well-controlled trials, PURPOSE 1 and PURPOSE 2, that enrolled both adults and adolescents [see Adverse Reactions (6.1) , Clinical Pharmacology (12.3) , and Clinical Studies (14) ] . PURPOSE 1 and PURPOSE 2 enrolled a total of 128 adolescent participants. In the 59 adolescents who received YEZTUGO, the safety data were comparable to the safety data reported in adults receiving YEZTUGO.
HIV-1 testing should be conducted prior to initiating YEZTUGO, prior to each subsequent injection of YEZTUGO, and additionally as clinically appropriate, using a test approved or cleared by the FDA for the diagnosis of acute or primary HIV-1 infection. Adolescents may benefit from additional counseling and appointment reminders to support adherence to the dosing and testing schedule [see Dosage and Administration (2.2) , Warnings and Precautions (5.1) ] . The safety, effectiveness, and pharmacokinetics of YEZTUGO in pediatric populations weighing less than 35 kg have not been established.
🧓 Geriatric Use ▾
8.5Geriatric Use Clinical studies of YEZTUGO did not include sufficient numbers of participants aged 65 and over to determine whether they respond differently from younger individuals. In general, caution should be exercised in administration of YEZTUGO in elderly individuals, reflecting greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy [see Clinical Pharmacology (12.3) ] .
🆘 Overdosage ▾
10 OVERDOSAGE No data are available on overdose of YEZTUGO. If overdose occurs, monitor the individual for evidence of toxicity. Treatment of overdose with YEZTUGO consists of general supportive measures including monitoring of vital signs as well as observation of the clinical status of the individual. As lenacapavir is highly bound to plasma proteins, it is unlikely to be significantly removed by dialysis.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action YEZTUGO is an HIV-1 antiretroviral agent with long-acting properties [see Microbiology (12.4) ].
12.2Pharmacodynamics Cardiac Electrophysiology At supratherapeutic exposures of lenacapavir (16-fold higher than the therapeutic exposures of YEZTUGO), YEZTUGO does not prolong the QTcF interval to any clinically relevant extent.
12.3Pharmacokinetics The pharmacokinetic (PK) properties of lenacapavir are provided in Table 8 . The population PK parameter estimates of YEZTUGO after oral and subcutaneous administration to adults are provided in Table 9 . Similar exposures are achieved when YEZTUGO is administered subcutaneously in the abdomen or thigh.
Table 8. Pharmacokinetic Properties of Lenacapavir Oral Subcutaneous Absorption % Absolute bioavailability 4 to 7 91 Values reflect absolute bioavailability following subcutaneous administration of the 927 mg dose. T max Values reflect administration of lenacapavir with or without food.
4 hours 77 to 84 days Subcutaneously administered lenacapavir forms a drug depot whereby lenacapavir is slowly released from the site of administration. Effect of Food Effect of low-fat meal (relative to fasting) Values refer to geometric mean ratio [low-fat meal/fasting] in PK parameters and (90% confidence interval). Low fat meal is approximately 400 kcal, 25% fat.
AUC inf ratio 98.6 (58.2,167.2) - C max ratio 115.8 (55.4, 242.1) - Effect of high-fat meal (relative to fasting) Values refer to geometric mean ratio [high-fat meal/fasting] in PK parameters and (90% confidence interval). High fat meal is approximately 1000 kcal, 50% fat. AUC inf ratio 115.2 (72.0, 184.5) - C max ratio 145.2 (77.9, 270.5) - Distribution Steady state volume of distribution (L) 1657 % bound to human plasma proteins >98.5 Blood-to-plasma ratio 0.5 to
0.7Values reflect the blood-to-plasma ratio of lenacapavir following a single dose intravenous administration of [ 14 C] lenacapavir through 336 hours postdose. Elimination Apparent t 1/2 10 to 12 days 8 to 12 weeks Clearance (L/h) 3.4 % of dose of unchanged drug in plasma Dosing in mass balance studies: single dose intravenous administration of [ 14 C] lenacapavir to participants. 69 Metabolism Metabolic pathway(s) CYP3A UGT1A1 (minor) Excretion Major routes of elimination Excretion of unchanged drug into feces Metabolized via oxidation, N-dealkylation, hydrogenation, amide hydrolysis, glucuronidation, hexose conjugation, pentose conjugation, and glutathione conjugation; via CYP3A and UGT1A1 and no single circulating metabolite accounted for >10% of plasma drug-related exposure. % of dose excreted in urine <1 % of dose excreted in feces (% unchanged) 76 (33) Table 9.
Pharmacokinetic Parameters of Lenacapavir Following Oral and Subcutaneous Administration to Adult Participants Receiving YEZTUGO Parameter Mean (%CV) Day 1 to end of Month 6 Steady State CV = coefficient of variation C max (ng/mL) 73.8 (48.6) 82.4 (40.4) AUC tau (h•ng/mL) 188108 (41.0) 257334 (38.7) C trough (ng/mL) 27.0 (51.1) 36.9 (53.5) Specific Populations There were no clinically significant differences in the pharmacokinetics of lenacapavir based on age, sex assigned at birth, gender identity, ethnicity, race, body weight, severe renal impairment (creatinine clearance of 15 to less than 30 mL per minute, estimated by Cockroft-Gault method), or moderate hepatic impairment (Child-Pugh Class B).
The effect of end-stage renal disease (including dialysis), or severe hepatic impairment (Child-Pugh Class C), on the pharmacokinetics of lenacapavir is unknown. As lenacapavir is greater than 98.5% protein bound, dialysis is not expected to alter exposures of lenacapavir [see Use in Specific Populations (8.6 , 8.7) ]. Pediatrics The population PK parameter estimates of YEZTUGO after oral and subcutaneous administration to adolescents (weighing at least 35 kg) are provided in Table 10 .
Table 10. Pharmacokinetic Parameters of Lenacapavir Following Oral and Subcutaneous A…
🧬 Mechanism of Action ▾
12.1Mechanism of Action YEZTUGO is an HIV-1 antiretroviral agent with long-acting properties [see Microbiology (12.4) ].
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING YEZTUGO tablets, 300 mg are beige, capsule-shaped, and film-coated with “GSI” debossed on one side and “62L” on the other side. Each YEZTUGO bottle contains 4 tablets (NDC 61958-3401-1), a silica gel desiccant, polyester coil, and is closed with a child resistant closure. Do not remove the desiccant packet.
Keep bottle tightly closed. Store bottle at 20 °C – 25 °C (68 °F – 77 °F), excursions permitted to 15 °C – 30 °C (59 °F – 86 °F) (see USP Controlled Room Temperature). Dispense and store only in original container.
YEZTUGO injection is packaged in a dosing kit (NDC 61958-3402-1) containing: 2 single-dose clear glass vials, each containing sufficient volume to allow withdrawal of 463.5 mg/1.5 mL (309 mg/mL) of lenacapavir. The injection solution is sterile, preservative-free, clear, and yellow with no visible particles. Vials are sealed with a stopper and aluminum overseal with flip-off cap.
2 disposable syringes, 2 withdrawal needles (18-gauge, 1½ inch; may be supplied with or without a safety shield), and 2 injection safety needles for subcutaneous injection (22-gauge, ½ inch). The vial stoppers are not made with natural rubber latex. Store at 20 °C – 25 °C (68 °F – 77 °F), excursions permitted to 15 °C – 30 °C (59 °F – 86 °F).
Keep the vials in the original carton until just prior to preparation of the injections in order to protect from light. Once the solution has been drawn into the syringes, the injections should be administered as soon as possible. Discard any unused portion of the solution.
📋 Description ▾
11 DESCRIPTION YEZTUGO tablets and YEZTUGO injection contain lenacapavir sodium, a capsid inhibitor. The chemical name of lenacapavir sodium is: Sodium (4-chloro-7-(2-(( S )-1-(2-((3b S ,4a R )-5,5-difluoro-3-(trifluoromethyl)-3b,4,4a,5-tetrahydro-1 H -cyclopropa[3,4]cyclopenta[1,2- c ]pyrazol-1-yl)acetamido)-2-(3,5-difluorophenyl)ethyl)-6-(3-methyl-3-(methylsulfonyl)but-1-yn-1-yl)pyridin-3-yl)-1-(2,2,2-trifluoroethyl)-1 H -indazol-3-yl)(methylsulfonyl)amide. Lenacapavir sodium has a molecular formula of C 39 H 31 ClF 10 N 7 NaO 5 S 2, a molecular weight of 990.3, and the following structural formula: Lenacapavir sodium is a light yellow to yellow solid and is practically insoluble in water.
Chemical Structure YEZTUGO tablets are for oral administration. Each film-coated tablet contains 300 mg of lenacapavir (present as 306.8 mg lenacapavir sodium) and the following inactive ingredients: copovidone, croscarmellose sodium, magnesium stearate, mannitol, microcrystalline cellulose, and poloxamer 407. The tablets are film-coated with a coating material containing iron oxide black, iron oxide red, iron oxide yellow, polyethylene glycol, polyvinyl alcohol, talc, and titanium dioxide.
YEZTUGO injection is for subcutaneous administration. Each single-dose vial contains 463.5 mg/1.5 mL (309 mg/mL) of lenacapavir (present as 473.1 mg/1.5 mL of lenacapavir sodium) as a sterile, preservative-free, clear, yellow solution and the following inactive ingredients: 896.3 mg of polyethylene glycol 300 (as solvent) and water for injection. The apparent pH range of the injection is 9.0-10.2.
The vial stoppers are not made with natural rubber latex.
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Advise the individual to read the FDA-approved patient labeling ( Patient Information ). Important Information for Individuals Receiving YEZTUGO for HIV-1 PrEP Advise individuals about the following [see Warnings and Precautions (5.1) ] : YEZTUGO should be used for PrEP as part of an overall HIV-1 prevention strategy, including adherence to the administration schedule and safer sex practices, including condoms, to reduce the risk of STIs. YEZTUGO is not always effective in preventing HIV-1 acquisition [see Clinical Studies (14) ] .
The time from initiation of YEZTUGO for HIV-1 PrEP to maximal protection against HIV-1 infection is unknown. Counsel individuals on the use of other prevention measures (e.g., knowledge of partner HIV-1 status, testing for STIs, condom use). Inform individuals about and support their efforts in reducing sexual behaviors associated with HIV-1 acquisition risk.
YEZTUGO should be used to reduce the risk of HIV-1 acquisition only in individuals confirmed to be HIV-1 negative. Individuals must have a negative HIV-1 test prior to initiating YEZTUGO, prior to each subsequent injection of YEZTUGO, and additionally as clinically appropriate, with a test approved or cleared by the FDA as an aid in the diagnosis of acute or primary HIV-1 infection [see Dosage and Administration (2.1) , Contraindications (4) , and Warnings and Precautions (5.1, 5.2) ]. Counsel and support individuals on adhering to the required initiation and continuation dosing schedule, on the use of other measures to reduce the risk of STIs, and on the importance of testing for HIV-1 and other STIs.
Some individuals, such as adolescents, may benefit from additional counseling and appointment reminders to support adherence. Risk of Resistance Advise individuals that there is a risk of developing resistance to YEZTUGO if HIV-1 is acquired either before or when receiving YEZTUGO, or following discontinuation of YEZTUGO. HIV-1 resistance substitutions may emerge in individuals with undiagnosed HIV-1 infection who are taking only YEZTUGO, because YEZTUGO alone does not constitute a complete regimen for HIV-1 treatment [see Warnings and Precautions (5.2) ] .
Inform individuals that YEZTUGO can remain in the body for up to 12 months or longer after receiving their last injection [see Warnings and Precautions (5.3) ] . To minimize this risk, it is essential that individuals are routinely tested to confirm HIV-1 negative status. Advise individuals that if they are confirmed to have HIV-1, they must immediately be transitioned to a complete HIV-1 treatment regimen [see Warnings and Precautions (5.2) ] .
Inform individuals that alternative forms of PrEP should be considered and initiated within 28 weeks of the last YEZTUGO injection [see Warnings and Precautions (5.2) ] . Anticipated Delayed Injections Advise individuals to contact their healthcare provider if the scheduled 6-month injection is anticipated to be delayed by more than 2 weeks. Advise that YEZTUGO tablets may be taken for up to 6 months, if needed, until injections resume.
Advise individuals that oral dosing should be used on an interim basis only and that the continuation injection dosage should be resumed at the earliest possible opportunity [see Dosage and Administration (2.4) ] . Injection Site Reactions Inform individuals that a subcutaneous drug depot forms following YEZTUGO injection. Advise that, in some individuals, this may lead to a nodule at the injection site [see Adverse Reactions (6.1) and Clinical Pharmacology (12.3) ].
Drug Interactions YEZTUGO may interact with certain drugs; therefore, advise individuals to report to their healthcare provider the use of any other prescription or non-prescription medication or herbal products [see Drug Interactions (7) ] . If YEZTUGO is discontinued, advise individuals that YEZTUGO may remain in the body and affect certain other drugs for up to 9 months after receiving their last injection [see Drug Inte…