Yeztugo® (lenacapavir)
Use in Hepatic Impairment
Gilead Sciences, Inc. is providing this document to you, a US Healthcare Professional, in response to your unsolicited request for medical information.
Gilead Sciences, Inc. is providing this document to you, a US Healthcare Professional, in response to your unsolicited request for medical information.
Yeztugo® (lenacapavir)
Use in Hepatic Impairment
This document is in response to your request for information regarding Yeztugo® (lenacapavir [LEN]) and use in individuals with hepatic impairment.
Some data may be outside of the US FDA-approved prescribing information. In providing this data, Gilead Sciences, Inc. is not making any representation as to its clinical relevance or to the use of any Gilead product(s). For information about the approved conditions of use of any Gilead drug product, please consult the FDA-approved prescribing information.
The full indication, important safety information, and boxed warning are available at:
www.gilead.com/-/media/files/pdfs/medicines/hiv/yeztugo/yeztugo_pi.
Product Labeling1
Use in Specific Populations
Hepatic impairment
No dosage adjustment of LEN is recommended in individuals with mild (Child-Pugh Class A) or moderate (Child-Pugh Class B) hepatic impairment. LEN has not been studied in patients with severe hepatic impairment (Child-Pugh Class C).
Clinical Pharmacology
PK
Specific populations
There were no clinically significant differences in the PK of LEN based on moderate hepatic impairment (Child-Pugh Class B). The effect of severe hepatic impairment (Child‑Pugh Class C) on the PK of LEN is unknown.
Clinical Data on the Use of LEN in Participants With Moderate Hepatic Impairment
PK Study in Participants With Moderate Hepatic Impairment2
Study design and demographics
A phase 1, open‑label, parallel‑group, single‑dose study evaluated the PK and safety of oral LEN in participants with moderate hepatic impairment (CPT Class B: score, 7–9). Participants with stable, moderate hepatic impairment for >6 months (n=10) were matched to healthy volunteers (n=10) according to age (±10 years), sex, race, and BMI (±20%). Safety assessments included physical examinations, ECGs, clinical laboratory tests, and incidence of AEs.
Figure 1. PK Study Design (Jogiraju et al)2
Abbreviation: PO=by mouth.
Table 1. Baseline Demographics and Disease Characteristics (Jogiraju et al)2
Key Demographics and Characteristics | LEN 300 mg | ||
Moderate Hepatic Impairment | Normal Hepatic Function | ||
Age, median (range), years | 56 (39–71) | 55 (31–69) | |
Male, n (%) | 7 (70) | 7 (70) | |
White, n (%) | 10 (100) | 10 (100) | |
Hispanic/Latinx, n (%) | 7 (70) | 5 (50) | |
ALT, median (range), U/L | 23 (11–312) | 17 (8–32) | |
AST, median (range), U/L | 33 (14–129) | 17 (11–19) | |
BMI, median (range), kg/m2 | 31.9 (23.5–37.8) | 29.5 (25–36.1) | |
CPT score, n (%) | 7 | 7 (70) | – |
8 | 3 (30) | – | |
PK results
After a single oral dose of LEN 300 mg, the AUCinf GMR was 1.47-fold higher and the Cmax GMR was 2.61-fold higher in participants with moderate hepatic impairment than in healthy volunteers with normal hepatic function (Table 2). The authors described the difference in exposure to LEN between groups as modest and not clinically significant. No significant relationships between LEN exposure (AUC and Cmax) and additional hepatic function measures (CPT score, albumin and total bilirubin levels, prothrombin time, and INR) were observed. Plasma protein binding of LEN was >99% overall and did not differ between groups.
Table 2. Summary of PK Parameters (Jogiraju et al)2
PK Parameter | Moderate Hepatic Impairment (n=10) | Normal Hepatic Function (n=10) | GMR |
AUCinf, GM (range), h·ng/mL | 12,000 (4990–29,600) | 8180 (3150–20,700) | 1.47 (0.947–2.27) |
AUClast, GM (range), h·ng/mL | 11,900 (4940–29,200) | 7590 (3050–20,500) | 1.57 (1.01–2.43) |
Cmax, GM (range), ng/mL | 61.1 (21–229) | 23.4 (9.7–55.2) | 2.61 (1.51–4.52) |
CL/F, GM (range), L/h | 25 (10.1–60.2) | 36.6 (14.5–95.3) | – |
Tmax, median (range), h | 6 (2–48) | 4 (4–12) | – |
t1/2, median (range), days | 12.6 (9.74–17.1) | 13.1 (10.7–17) | – |
Vz/F, GM (range), L | 10,800 (4060–23,000) | 17,000 (6970–49,800) | – |
Abbreviations: AUClast=area under the curve from time zero to last quantifiable plasma concentration; CL/F=apparent oral clearance; GM=geometric mean; t1/2=terminal half‑life; Tmax=time to peak concentration; Vz/F=apparent volume of distribution.
Safety results
A single oral dose of LEN 300 mg was generally well tolerated in participants with moderate hepatic impairment. All treatment emergent AEs were Grade 1 or 2, and all AEs were reported as resolved. There were no serious AEs and no AEs that led to study discontinuation. No deaths were reported.
Table 3. Summary of Safety Parameters (Jogiraju et al)3
Safety Outcomes, n (%) | Moderate Hepatic Impairment (n=10) | Normal Hepatic Function (n=10) |
Any AE | 3 (30) | 3 (30) |
Headache | 2 (20) | 1 (10) |
Anxiety | 1 (10) | 0 |
Dizziness | 1 (10) | 0 |
Hyponatremia | 1 (10) | 0 |
Malaise | 1 (10) | 0 |
Skin abrasion | 1 (10) | 0 |
Type 2 diabetes mellitus | 1 (10) | 0 |
Constipation | 0 | 1 (10) |
Hyperglycemia | 0 | 1 (10) |
Any drug-related AE | 1a (10) | 1b (10) |
a Grade 2. b Grade 1.
The authors noted that the results did not indicate a safety risk or warrant dose adjustment of LEN in patients with moderate hepatic impairment.
References
- Enclosed, Gilead Sciences Inc. YEZTUGO® (lenacapavir) tablets, for oral use. YEZTUGO® (lenacapavir) injection, for subcutaneous use. U.S. Prescribing Information. Foster City, CA.
- Jogiraju V, Weber E, Hindman J, et al. Pharmacokinetics of long-acting lenacapavir in participants with hepatic or renal impairment. Antimicrob Agents Chemother. 2024;68(4):e0134423.
- Jogiraju V, Weber E, Hindman J, et al. Pharmacokinetics of long-acting lenacapavir in participants with hepatic or renal impairment. [Supplementary Tables]. Antimicrob Agents Chemother. 2024;68(4):e0134423.
Abbreviations
Page 1 of 4
AE=adverse event
AUC=area under the curve
AUCinf=area under the curve from 0 to infinity
Cmax=peak concentration
CPT=Child-Pugh-Turcotte GMR=geometric least squares mean ratio
LEN=lenacapavir
PK=pharmacokinetic(s)
Product Label
For the full indication, important safety information, and boxed warning, please refer to the Yeztugo US Prescribing Information available at:
www.gilead.com/-/media/files/pdfs/medicines/hiv/yeztugo/yeztugo_pi.
Follow-Up
For any additional questions, please contact Gilead Medical Information at:
☎1‐866‐MEDI‐GSI (1‐866‐633‐4474) or www.askgileadmedical.com
Adverse Event Reporting
Please report all adverse events to:
Gilead Global Patient Safety ☎ 1-800-445-3235, option 3 or
www.gilead.com/utility/contact/report-an-adverse-event
FDA MedWatch Program by ☎ 1-800-FDA-1088 or MedWatch, FDA, 5600 Fishers Ln, Rockville, MD 20852 or www.accessdata.fda.gov/scripts/medwatch
Data Privacy
The Medical Information service at Gilead Sciences may collect, store and use your personal information to provide a response to your medical request. We may share your information with other Gilead Sciences colleagues to ensure that your request is addressed appropriately. If you report an adverse event or concern about the quality of a Gilead or Kite product, we will need to use the information you have given us in order to meet our regulatory requirements in relation to the safety of our medicines.
It may be necessary for us to share your information with Gilead’s affiliates, business partners, service providers and regulatory authorities located in countries besides your own. Gilead Sciences has implemented measures to protect the personal information you provide. Please see the Gilead Privacy Statement (www.gilead.com/privacy-statements) for more information about how Gilead handles your personal information and your rights. If you have any further questions about the use of your personal information, please contact privacy@gilead.com.
YEZTUGO, GILEAD, and the GILEAD logo are registered trademarks of Gilead Sciences, Inc., or its related companies.
© 2025 Gilead Sciences, Inc.