Source: European Medicines Agency (EU) Revision Year: 2025 Publisher: Gilead Sciences Ireland UC, Carrigtohill, County Cork, T45 DP77, Ireland
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
Use in individuals with unknown HIV-1 status (see section 4.4).
Co-administration with strong inducers of CYP3A, P-gp, and UGT1A1, such as:
(see section 4.5).
Yeytuo should only be used to prevent HIV-1 acquisition in individuals confirmed to be HIV-negative. HIV-1 negative status should be confirmed prior to initiation of lenacapavir, and additionally as clinically appropriate in individuals receiving lenacapavir.
If recent (<1 month) exposures to HIV-1 are suspected or clinical symptoms consistent with acute HIV-1 infection are present, HIV-1 status should be reconfirmed.
Yeytuo should be used to prevent HIV-1 acquisition as part of a strategy to reduce the risk of sexually transmitted infections (STIs). Individuals should be identified for whom the required initiation and every 6-month continuation injection dosing schedule is appropriate. Nonadherence to the required initiation and continuation dosing schedule (see section 4.2) may lead to HIV-1 acquisition. Individuals should be counselled and supported on adhering to the lenacapavir administration schedule, on the use of other measures to prevent STIs, and on the importance of testing for HIV-1 and other STIs.
Mean lenacapavir plasma concentrations associated with significant antiviral activity were reached by Day 2 of the required initiation dosing and were maintained through the dosing interval of 26 weeks (see section 5.2). The exact time from initiation of lenacapavir for HIV-1 PrEP to maximal protection against HIV 1 infection is unknown.
Lenacapavir may not always be effective in preventing HIV-1 infection (see section 5.1). There is a risk of developing resistance to lenacapavir if an individual acquires HIV-1 either before or when receiving Yeytuo, or following discontinuation of Yeytuo. To minimise this risk, it is essential to confirm HIV-1 negative status before each subsequent injection, and additionally as clinically appropriate. Yeytuo alone does not constitute a complete regimen for HIV-1 treatment and mutations have emerged in some individuals with undetected HIV-1 infection who were only taking Yeytuo. Individuals who are confirmed to have HIV-1 must immediately begin a complete HIV-1 treatment regimen to reduce the risk of developing resistance.
Co-administration with medicinal products that are moderate inducers of CYP3A and P-gp is not recommended (see section 4.5).
Co-administration with medicinal products that are strong inhibitors of CYP3A, P-gp, and UGT1A1 together (i.e. all 3 pathways) is not recommended (see section 4.5).
This medicinal product contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially ‘sodium-free’.
Lenacapavir is a substrate of CYP3A, P-gp and UGT1A1. Strong inducers of CYP3A, P-gp, and UGT1A1 may significantly decrease plasma concentrations of lenacapavir which may result in reduced effectiveness of lenacapavir. Concomitant administration of lenacapavir with strong inducers of CYP3A, P-gp, and UGT1A1 is contraindicated (see section 4.3). Moderate inducers of CYP3A and P-gp may decrease plasma concentrations of lenacapavir. Concomitant administration of lenacapavir with moderate inducers of CYP3A and P-gp is not recommended (see section 4.4).
Strong inhibitors of CYP3A, P-gp and UGT1A1 together (i.e., all 3 pathways) may significantly increase plasma concentrations of lenacapavir, therefore co-administration is not recommended (see section 4.4).
Strong CYP3A4 inhibitors alone or strong inhibitors of CYP3A4 and P-gp together do not result in a clinically meaningful increase in lenacapavir exposure.
Lenacapavir is a moderate inhibitor of CYP3A and a P-gp inhibitor. Caution is advised if lenacapavir is co-administered with a sensitive CYP3A and/or P-gp substrate with a narrow therapeutic index. Lenacapavir is not a clinically meaningful inhibitor of BCRP and does not inhibit OATP.
Clinical drug interaction data for lenacapavir as victim are from studies with oral lenacapavir. Clinical drug interaction data for subcutaneous lenacapavir are not available.
Table 2. Interactions between Yeytuo and other medicinal products:
| Medicinal product by therapeutic areas | Effects on concentrations. Mean percent change in AUC, Cmax | Recommendation concerning co-administration with Yeytuo |
|---|---|---|
| ANTIMYCOBACTERIALS | ||
| Rifampicina,b (600 mg once daily) (strong inducer of CYP3A, and an inducer of P-gp and UGT) | Lenacapavir: AUC: ↓ 84% Cmax: ↓ 55% | Co-administration is contraindicated (see section 4.3). |
| Rifabutin Rifapentine | Interaction not studied. Co-administration of rifabutin or rifapentine may decrease lenacapavir plasma concentrations. | Co-administration is not recommended (see section 4.4). |
| ANTICONVULSANTS | ||
| Carbamazepine Phenytoin | Interaction not studied. Co-administration of carbamazepine, oxcarbazepine, phenobarbital, or phenytoin with lenacapavir may decrease lenacapavir plasma concentrations. | Co-administration is contraindicated (see section 4.3). |
| Oxcarbazepine Phenobarbital | Co-administration is not recommended (see section 4.4). Alternative anticonvulsants should be considered. | |
| HERBAL PRODUCTS | ||
| St. John’s wort (Hypericum perforatum) | Interaction not studied. Co-administration of St. John’s wort may decrease lenacapavir plasma concentrations. | Co-administration is contraindicated (see section 4.3). |
| ANTIRETROVIRAL AGENTS | ||
| Atazanavir/cobicistatb,c,d (300 mg/150 mg once daily) (strong inhibitor of CYP3A, and an inhibitor UGT1A1 and P-gp) | Lenacapavir: AUC: ↑ 321% Cmax: ↑ 560% | Co-administration of lenacapavir and strong inhibitors of CYP3A, P-gp, and UGT1A1 is not recommended (see section 4.4). |
| Efavirenzb,c,d (600 mg once daily) (moderate inducer of CYP3A and an inducer of P-gp) | Lenacapavir: AUC: ↓ 56% Cmax: ↓ 36% | Co-administration is not recommended (see section 4.4). |
| Cobicistatb,c,d (150 mg once daily) (strong inhibitor of CYP3A and an inhibitor of P-gp) | Lenacapavir: AUC: ↑ 128% Cmax: ↑ 110% | No dose adjustment of lenacapavir is required. |
| Darunavir/cobicistatb,c,d (800 mg/150 mg once daily) (strong inhibitor of CYP3A, and an inhibitor and inducer of P-gp) | Lenacapavir: AUC: ↑ 94% Cmax: ↑ 130% | |
| Tenofovir alafenamidec,e (25 mg) (substrate of P-gp) | Tenofovir alafenamide: AUC: ↑ 32% Cmax: ↑ 24% Tenofovirf: AUC: ↑ 47% Cmax: ↑ 23% | No dose adjustment of tenofovir alafenamide is required. |
| ERGOT DERIVATIVES | ||
| Dihydroergotamine Ergotamine | Interaction not studied. Plasma concentrations of these medicinal products may be increased when co-administered with lenacapavir. | Caution is warranted when dihydroergotamine or ergotamine, is co-administered with lenacapavir. |
| PHOSPHODIESTERASE-5 (PDE-5) INHIBITORS | ||
| Sildenafil Tadalafil Vardenafil | Interaction not studied. Plasma concentration of PDE-5 inhibitors may be increased when co-administered with lenacapavir. | Use of PDE-5 inhibitors for pulmonary arterial hypertension: Co-administration with tadalafil is not recommended. Use of PDE-5 inhibitors for erectile dysfunction: Sildenafil: A starting dose of 25 mg is recommended. Vardenafil: No more than 5 mg in a 24-hour period. Tadalafil: • For use as needed: no more than 10 mg every 72 hours • For once daily use: dose not to exceed 2.5 mg |
| CORTICOSTEROIDS (systemic) | ||
| Dexamethasone Hydrocortisone/cortisone | Interaction not studied. Plasma concentrations of corticosteroids may be increased when co-administered with lenacapavir. Plasma concentrations of lenacapavir may decrease when co-administered with systemic dexamethasone. | Co-administration of lenacapavir with corticosteroids whose exposures are significantly increased by CYP3A inhibitors can increase the risk for Cushing’s syndrome and adrenal suppression. Initiate with the lowest starting dose and titrate carefully while monitoring for safety. Caution is warranted when systemic dexamethasone is co-administered with lenacapavir, particularly for long-term use. Alternative corticosteroids should be considered. |
| HMG-CoA REDUCTASE INHIBITORS | ||
| Lovastatin Simvastatin | Interaction not studied. Plasma concentrations of these medicinal products may be increased when co-administered with lenacapavir. | Initiate lovastatin and simvastatin with the lowest starting dose and titrate carefully while monitoring for safety (e.g. myopathy). |
| Atorvastatin | No dose adjustment of atorvastatin is required. | |
| Pitavastatinc,e (2 mg single dose; simultaneous or 3 days after lenacapavir) (substrate of OATP) | Pitavastatin: AUC: ↔ Cmax: ↔ | No dose adjustment of pitavastatin and rosuvastatin is required. |
| Rosuvastatinc,e (5 mg single dose) (substrate of BCRP and OATP) | Rosuvastatin: AUC: ↑ 31% Cmax: ↑ 57% | |
| ANTIARRHYTHMICS | ||
| Digoxin | Interaction not studied. Plasma concentration of digoxin may be increased when co-administered with lenacapavir. | Caution is warranted and therapeutic concentration monitoring of digoxin is recommended. |
| SEDATIVES/HYPNOTICS | ||
| Midazolamc,e (2.5 mg single dose; oral; simultaneous administration) (substrate of CYP3A) | Midazolam: AUC: ↑ 259% Cmax: ↑ 94% 1-hydroxymidazolamg: AUC: ↓ 24% Cmax: ↓ 46% | Caution is warranted when midazolam or triazolam, is co-administered with lenacapavir. |
| Midazolamc,e (2.5 mg single dose; oral; 1 day after lenacapavir) (substrate of CYP3A) | Midazolam: AUC: ↑ 308% Cmax: ↑ 116% 1-hydroxymidazolamg: AUC: ↓ 16% Cmax: ↓ 48% | |
| Triazolam | Interaction not studied. Plasma concentration of triazolam may be increased when co-administered with lenacapavir. | |
| ANTICOAGULANTS | ||
| Direct Oral Anticoagulants (DOACs) Rivaroxaban Dabigatran Edoxaban | Interaction not studied. Plasma concentration of DOAC may be increased when co-administered with lenacapavir. | Due to potential bleeding risk, dose adjustment of DOAC may be required. Consult the Summary of Product Characteristics of the DOAC for further information on use in combination with moderate CYP3A inhibitors and/or P-gp inhibitors. |
| ANTIFUNGALS | ||
| Voriconazolea,b,h (400 mg twice daily/200 mg twice daily) (strong CYP3A inhibitor) | Lenacapavir: AUC: ↑ 41% Cmax: ↔ | No dose adjustment of lenacapavir is required. |
| Itraconazole Ketoconazole | Interaction not studied. Plasma concentration of lenacapavir may be increased when co-administered with itraconazole or ketoconazole. | |
| H2-RECEPTOR ANTAGONISTS | ||
| Famotidinea,b (40 mg once daily, 2 hours before lenacapavir) | Famotidine: AUC: ↑ 28% Cmax: ↔ | No dose adjustment of famotidine is required. |
| ORAL OR LONG-ACTING CONTRACEPTIVES | ||
| Long-acting contraceptives: Medroxyprogesterone acetate Etonogestrel Norethisterone enanthate | Observed data does not indicate clinically relevant changes in the exposure of long-acting contraceptives. | No dose adjustment of oral or long- acting contraceptives is required. |
| Oral contraceptives: Ethinylestradiol Progestins | Interaction not studied. Plasma concentrations of oral contraceptives may be increased when co-administered with lenacapavir. | |
| GENDER AFFIRMING HORMONES (feminising or masculinising) | ||
| Estradiol Testosterone | Observed data does not indicate clinically relevant changes in the exposure of estradiol and testosterone. | No dose adjustment of these gender affirming hormones is required. |
| Anti-androgens Progestogen | Interaction not studied. Plasma concentrations of these medicinal products may be increased when co-administered with lenacapavir. | |
a Fasted.
b This study was conducted using lenacapavir 300 mg single dose administered orally.
c Fed.
d These antiretroviral medicinal products are probes for the referenced enzymes/transporters and are not to be co-administered with lenacapavir for PrEP.
e This study was conducted using lenacapavir 600 mg single dose following a loading regimen of 600 mg twice daily for 2 days, single 600 mg doses of lenacapavir were administered orally with each co-administered medicinal product.
f Tenofovir alafenamide is converted to tenofovir in vivo.
g Major active metabolite of midazolam.
h This study was conducted using voriconazole 400 mg loading dose twice daily for a day, followed by 200 mg maintenance dose twice daily.
Individuals of childbearing potential should be counselled about the long-acting properties of lenacapavir injection.
If an individual plans a pregnancy, the benefits and the risks of initiating or continuing Yeytuo during pregnancy should be discussed.
There are limited data (130 birth outcomes) from the use of lenacapavir in pregnant women. The rates of adverse pregnancy outcomes in participants who received Yeytuo were similar to reported background rates.
Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity (see section 5.3).
Yeytuo may be considered during pregnancy if the expected benefit outweighs the potential risk to the foetus.
Lenacapavir is present in human milk. Lenacapavir was detected at low levels in infants who were breastfed by individuals who became pregnant while receiving Yeytuo (see section 5.2). There is insufficient information on the effects of lenacapavir in newborns/infants.
Yeytuo may be considered during breastfeeding if the expected benefit outweighs the potential risk to the child.
There are no data on the effects of lenacapavir on human male or female fertility. Animal studies indicate no effects of lenacapavir on male or female fertility (see section 5.3).
Yeytuo is expected to have no or negligible influence on the ability to drive and use machines.
No adverse reactions to lenacapavir taken orally were identified in adults or adolescents in PURPOSE 1 and PURPOSE 2.
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.
Not applicable.
© All content on this website, including data entry, data processing, decision support tools, "RxReasoner" logo and graphics, is the intellectual property of RxReasoner and is protected by copyright laws. Unauthorized reproduction or distribution of any part of this content without explicit written permission from RxReasoner is strictly prohibited. Any third-party content used on this site is acknowledged and utilized under fair use principles.