Yeztugo® (lenacapavir)

Drug Interaction Profile

This document is in response to your request for information regarding the drug interaction profile of Yeztugo® (lenacapavir [LEN]). This is not an exhaustive list of potential drug-drug interactions. Please refer to Section 7 Drug Interactions in the US FDA-approved Prescribing Information for more information. 

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.

Summary1

There are no contraindications to administering LEN with other drugs.

Based on drug interaction studies conducted with LEN, no clinically significant drug interactions have been observed with: atorvastatin, famotidine, pitavastatin, rosuvastatin, tenofovir alafenamide and voriconazole.

• Table 1: Summary of the Effect of Other Drugs on LEN
• Table 2: Drug-Drug Interaction Study: Effects of Select Drugs on LEN
• Figure 1: Dosing Recommendations for Individuals Receiving LEN and Initiating a Strong or Moderate CYP3A Inducer
• Table 3: Summary of the Effect of LEN on Other Drugs
• Table 4: Drug-Drug Interaction Study: Effects of LEN on Other Drugs

Effects of Other Drugs on LEN1

LEN is a substrate of P-gp, UGT1A1, and CYP3A.

Table 1. Summary of the Effect of Other Drugs on LEN1

Effects on Exposure of LEN When Coadministered With Select Drugs1

In a clinical drug-drug interaction study, select drugs were coadministered with a single dose of LEN 300 mg. The effects of the selected drugs on LEN PK parameters (Cmax, AUC) are summarized below in Table 2. Please refer to Section 12.3 Pharmacokinetics and Table 11. Effect of Other Drugs on LEN in the Prescribing Information for more information.

 Table 2. Drug-Drug Interaction Study: Effects of Select Drugs on LEN1

aBased on mean ratio of LEN PK parameters of Cmax and AUC, where no effect = 1.00. Refer to Table 11. Effect of Other Drugs on LEN in the Prescribing Information for more information
bNot applicable; was not described in the Prescribing Information.

Dosage Modifications for Coadministration with Strong or Moderate CYP3A Inducers1

Supplemental doses of LEN are recommended for individuals initiating therapy with either strong CYP3A inducers or moderate CYP3A inducers.

• Strong CYP3A inducers may be initiated starting at least 2 days after LEN is first initiated.
• Moderate CYP3A inducers may be started any time after LEN is first initiated.

Dosing recommendations are not available for the initiation of LEN in individuals already receiving strong or moderate CYP3A inducers, nor in individuals receiving the weekly oral dosage of LEN.

Figure 1 shows the dosing recommendations for individuals receiving LEN and initiating a strong or moderate CYP3A inducer. Please refer to Section 2.5 Dosage Modifications for Co-administration with Strong or Moderate CYP3A Inducers in the Prescribing Information for more information.

Figure 1. Dosing Recommendations for Individuals Receiving LEN and Initiating a Strong or Moderate CYP3A Inducer1

Effects of LEN on Other Drugs1

LEN is a moderate inhibitor of CYP3A and a P-gp inhibitor.

Table 3. Summary of the Effect of LEN on Other Drugs1

Effects on Exposure of Select Drugs When Coadministered With LEN1

In a clinical drug-drug interaction study, select drugs were coadministered following LEN 600 mg twice daily for 2 days. Single 600 mg doses of LEN were administered with each coadministered drug. The effects of LEN on the selected drugs PK parameters (Cmax,AUC) are summarized below in Table 4. Please refer to Section 12.3 Pharmacokinetics and Table 12. Effect of LEN on Other Drugs in the Prescribing Information for more information.

Table 4. Drug-Drug Interaction Study: Effects of LEN on Other Drugs1

aBased on mean ratio of coadministered drug PK parameters of Cmax and AUC, where no effect = 1.00. All no effect boundaries were 70% to 143%. See Table 12. Effect of LEN on Other Drugs in the Prescribing Information for more information.
bMajor active metabolite of midazolam.
cTenofovir alafenamide is converted to tenofovir in vivo.

Drugs Without Clinically Significant Interactions with LEN1

Based on drug interaction studies conducted with LEN, no clinically significant drug interactions have been observed with:

• Atorvastatin
• Famotidine
• Pitavastatin
• Rosuvastatin
• Tenofovir alafenamide
• Voriconazole

Reference

1. Enclosed, Gilead Sciences Inc. YEZTUGO® (lenacapavir) tablets, for oral use. YEZTUGO® (lenacapavir) injection, for subcutaneous use. U.S. Prescribing Information. Foster City, CA.

Abbreviations

AUC=area under the curve
BCRP=breast cancer resistance protein

Cmax=maximum plasma concentration
DDI=drug-drug interaction

LEN=lenacapavir

NA=not applicable
OATP=organic anion transporting polypeptide

P-gp=P-glycoprotein

PK=pharmacokinetic(s)
PrEP=pre-exposure prophylaxis
UGT=uridine 5’-diphospho- glucuronosyltransferase

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

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