Lenacapavir 300 Mg Tablet Gilead

Lenacapavir Gilead tablet is indicated in combination with safer sex practices for pre-exposure prophylaxis (PrEP) to prevent sexually acquired HIV-1 in adults and adolescents weighing at least 35 kg for:

• oral loading
• oral bridging (see sections 4.2 and 5.1).

All individuals must be screened for HIV-1 prior to initiating Lenacapavir Gilead and routinely thereafter as clinically appropriate (see sections 4.3 and 4.4). Individuals must have a negative HIV-1 test prior to initiating Lenacapavir Gilead.

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. Prior to starting Lenacapavir Gilead, healthcare professionals should select individuals for whom the required initiation and 6-monthly maintenance injection dosing schedule is appropriate, and counsel individuals about the importance of adherence to scheduled Lenacapavir Gilead dosing visits (see section 4.4).

Posology

The Lenacapavir Gilead 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 maintenance dosing (subcutaneous injections) (Table 1).

Initiation

On Day 1, the required dose is 927 mg of Lenacapavir Gilead administered by subcutaneous injection and 600 mg taken orally. On Day 2, the required dose is 600 mg taken orally.

Table 1: Dosing schedule for Lenacapavir Gilead initiation

Time

Dose of Lenacapavir Gilead: Initiation

Day 1 927 mg subcutaneous injection (2 x 1, 5 ml injections) 600 mg orally (2 x 300 mg tablets)

Day 2 600 mg orally (2 x 300 mg tablets)

a The complete initiation dosing schedule, consisting of subcutaneous injections and oral tablets, is required; the efficacy of Lenacapavir Gilead has only been established with this dosing schedule.

b Two injections, with the second injection at least 5 centimetres from the first injection (see Method of Administration in the Lenacapavir Gilead solution for injection Professional Information).

Missed initiation dose

If the Day 1 or Day 2 oral initiation dose (600 mg) is missed, it should be taken as soon as possible. Day 1 and Day 2 doses should not be taken on the same day.

Planned missed injections

During the maintenance dosing, if an individual plans to miss a scheduled 6-month injection visit by more than 2 weeks, Lenacapavir Gilead tablets may be used for oral bridging on an interim basis (for up to 6 months if needed), until injections resume. Oral bridging should be initiated within 26 to 28 weeks from the last injection. The dosing schedule is 300 mg (1 tablet) taken orally once every 7 days. Resume the maintenance injection dosage within 7 days after the last oral dose.

Vomiting

If the individual vomits within 3 hours of taking an oral dose of Lenacapavir Gilead, another oral dose should be taken. If the individual vomits more than 3 hours after taking an oral dose of Lenacapavir Gilead there is no need to take another oral dose of Lenacapavir Gilead, and the scheduled dosing regimen should continue.

Special populations

Elderly

No dose adjustment of Lenacapavir Gilead is required for elderly individuals (see section 5.2).

Renal impairment

No dose adjustment of Lenacapavir Gilead is required in individuals with mild, moderate, or severe renal impairment (creatinine clearance [CrCl] u2265 15 mL/min). Lenacapavir Gilead has not been studied in individuals with end stage renal disease (CrCl < 15 mL/min or on renal replacement therapy) (see section 5.2), therefore Lenacapavir Gilead should be used with caution in these individuals.

Hepatic impairment

No dose adjustment of Lenacapavir Gilead is required in individuals with mild or moderate hepatic impairment (Child-Pugh Class A or B). Lenacapavir Gilead has not been studied in individuals with severe hepatic impairment (Child-Pugh Class C) (see section 5.2), therefore Lenacapavir Gilead should be used with caution in these individuals.

Paediatric population

Safety and efficacy of Lenacapavir Gilead has been established in adolescents weighing at least 35 kg.

Method of administration

For oral use. Lenacapavir Gilead tablets should be taken orally with or without food (see section 5.2). The film-coated tablet should not be chewed, crushed, or split, because the effects on lenacapavir absorption have not been studied.

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, other than rifampicin, such as:

• anticonvulsants: carbamazepine, phenytoin
• herbal products: St. Johnu2019s wort (Hypericum perforatum) (see section 4.5).

Prevention strategy

Lenacapavir Gilead should only be used to prevent HIV-1 acquisition in individuals confirmed to be HIV-negative. Confirm HIV-1 negative status prior to initiation of Lenacapavir Gilead and routinely thereafter as clinically appropriate in individuals receiving Lenacapavir Gilead. Use Lenacapavir Gilead to prevent HIV-1 acquisition as part of a strategy to reduce the risk of sexually transmitted infections (STIs). Select individuals for whom the required initiation and every 6-month maintenance injection dosing schedule is appropriate. Non-adherence to the required initiation and maintenance dosing schedule (see section 4.2) may lead to HIV-1 acquisition. Counsel and support individuals on adhering to the Lenacapavir Gilead administration schedule, on the use of other measures to prevent STIs, and on the importance of testing for HIV-1 and other STIs.

Risk of resistance

There is a risk of developing resistance to lenacapavir if an individual acquires HIV-1 either before or when receiving Lenacapavir Gilead, or following discontinuation of Lenacapavir Gilead. Lenacapavir Gilead alone does not constitute a complete regimen for HIV-1 treatment. Individuals who are confirmed to have HIV-1 must immediately begin a complete HIV-1 treatment regimen to reduce the risk of developing resistance.

Long-acting properties

Residual concentrations of lenacapavir may remain in the systemic circulation of individuals for prolonged periods (up to 12 months or longer). If Lenacapavir Gilead is discontinued and it is clinically appropriate to continue PrEP, alternative forms of PrEP should be considered and initiated within 28 weeks of the last Lenacapavir Gilead injection.

Co-administration of other medicines

Co-administration with medicinal products that are moderate inducers of CYP3A and P-gp, other than rifabutin, 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).

Excipients

This medicinal product contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially u2018sodium-freeu2019.

Effect of other medicinal products on the pharmacokinetics of lenacapavir

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 Gilead. Concomitant administration of Lenacapavir Gilead with strong inducers of CYP3A, P-gp, and UGT1A1, other than rifampicin, is contraindicated (see section 4.3); dose adjustment of Lenacapavir Gilead is required if rifampicin is co-administered (see Table 2). Moderate inducers of CYP3A and P-gp may decrease plasma concentrations of lenacapavir. Concomitant administration of Lenacapavir Gilead with moderate inducers of CYP3A and P-gp, other than rifabutin, is not recommended (see section 4.4); dose adjustment of Lenacapavir Gilead is required if rifabutin is co-administered (see Table 2). 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.

Effect of lenacapavir on the pharmacokinetics of other medicines

Lenacapavir is a moderate inhibitor of CYP3A and a P-gp inhibitor. Caution is advised if Lenacapavir Gilead 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.

Table 2: Interactions between Lenacapavir Gilead and other medicines

Medicinal product by therapeutic areas

Effects on concentrations.

Mean percent change in AUC, C max

Recommendation concerning co-administration with Lenacapavir Gilead

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. Johnu2019s wort (Hypericum perforatum)

Interaction not studied. Co-administration of St. Johnu2019s wort may decrease lenacapavir plasma concentrations. Co-administration is contraindicated (see section 4.3).

ANTIMYCOBACTERIALS

Rifampicin a,b (600 mg once daily) (strong inducer of CYP3A, and an inducer of P-gp and UGT)

Lenacapavir: AUC: u219384 % C max : u219355 % If rifampicin or rifabutin is co-administered, maintain the usual Lenacapavir Gilead dosing schedule and administer additional dose(s) of Lenacapavir Gilead as follows: Rifampicin:

u2022 In individuals receiving Lenacapavir Gilead, rifampicin may be co-administered starting at least 2 days after Lenacapavir Gilead is first initiated.

u2022 On the day rifampicin is initiated, administer 927 mg of Lenacapavir Gilead subcutaneously (2 x 1, 5 ml injections) and 600 mg of Lenacapavir Gilead orally (2 x 300 mg tablets), and

u2022 On the day after rifampicin initiation, administer 600 mg of Lenacapavir Gilead orally (2 x 300 mg tablets).

u2022 If rifampicin is co-administered for longer than 6 months, continue to administer additional doses of Lenacapavir Gilead as described above, every 6 months following the day of rifampicin initiation.

Rifabutin

Rifapentine

Interaction not studied. Co-administration of rifabutin and rifapentine may decrease lenacapavir plasma concentrations.

Pregnancy

A moderate amount of data on pregnant women (369 pregnancy outcomes) indicate no malformative or feto/neonatal toxicity of lenacapavir. The rates of adverse pregnancy outcomes in participants who received Lenacapavir Gilead were similar to reported background rates. Lenacapavir exposures during each trimester of pregnancy and postpartum were comparable to those in non-pregnant participants (see section 5.2).

Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, foetal development, parturition or postnatal development (see section 5.3). The use of Lenacapavir Gilead may be considered during pregnancy, if clinically appropriate.

Breast-feeding

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 Lenacapavir Gilead (see section 5.2). No adverse effects of lenacapavir in breastfed infants have been observed. Lenacapavir Gilead can be used during breast-feeding.

Fertility

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).

Lenacapavir Gilead is expected to have no or negligible influence on the ability to drive and use machines.

No adverse reactions to Lenacapavir Gilead taken orally were identified in adults or adolescents in PURPOSE 1 and PURPOSE 2.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicine is important. It allows continued monitoring of the benefit/risk balance of the medicine. Health care professionals are asked to report any suspected adverse reactions to SAHPRA via the Med Safety APP (Medsafety X SAHPRA) and eReporting reporting platform (who-umc.org) found on SAHPRA website.

If overdose occurs the individual must be monitored for signs or symptoms of adverse reactions (see section 4.8). Treatment of overdose with Lenacapavir Gilead 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 protein bound, it is unlikely to be significantly removed by dialysis.