Wirkstoffe & Arzneimittelsicherheit

Wechselwirkungen · Sunlenca

Sunlenca 464 mg solution for injection · Abschnitt 4.5 · PDF-Seite 8–9

HOS-148316 · Präparat HOS-099874

8 b This study was conducted using lenacapavir 300 mg single dose administered orally. c Evaluated as a strong inducer of CYP3A, and an inducer of P-gp and UGT. d Fed. e Evaluated as a strong inhibitor of CYP3A, and an inhibitor UGT1A1 and P-gp. f Evaluated as a moderate inducer of CYP3A and an inducer of P-gp. g Evaluated as a strong inhibitor of CYP3A and an inhibitor of P-gp. h Evaluated as a strong inhibitor of CYP3A, and an inhibitor and inducer of P-gp. i 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 with each co-administered medicinal product. j Evaluated as a P-gp substrate. k Tenofovir alafenamide is converted to tenofovir in vivo. l Evaluated as an OATP substrate. m Evaluated as an BCRP substrate. n Evaluated as a CYP3A substrate. o Major active metabolite of midazolam. p Evaluated as a strong inhibitor of CYP3A. q This study was conducted using voriconazole 400 mg loading dose twice daily for a day, followed by 200 mg maintenance dose twice daily.

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): tenofovir (HOS-088083) tenofovir alafenamide (HOS-110476) voriconazole (HOS-084524) midazolam (HOS-086167)

Wechselwirkungen · Sunlenca

Sunlenca 300 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 21

HOS-148330 · Präparat HOS-099874

Effect of other medicinal products on the pharmacokinetics of lenacapavir

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Wechselwirkungen · Sunlenca

Sunlenca 300 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 21

HOS-148331 · Präparat HOS-099874

Lenacapavir is a substrate of CYP3A, P-gp and UGT1A1. Strong inducers of CYP3A, P-gp, and UGT1A1, such as rifampicin, may significantly decrease plasma concentrations of lenacapavir resulting in loss of therapeutic effect and development of resistance, therefore co-administration is contraindicated (see section 4.3). Moderate inducers of CYP3A and P-gp, such as efavirenz, may also significantly decrease plasma concentrations of lenacapavir, therefore co-administration is not recommended (see section 4.4).

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): efavirenz (HOS-087947)

Wechselwirkungen · Sunlenca

Sunlenca 300 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 21–22

HOS-148332 · Präparat HOS-099874

21 Strong inhibitors of CYP3A, P-gp and UGT1A1 together (i.e., all 3 pathways), such as atazanavir/cobicistat, may significantly increase plasma concentrations of lenacapavir, therefore co-administration is not recommended (see section 4.4).

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): atazanavir (HOS-086180) cobicistat (HOS-088111)

Wechselwirkungen · Sunlenca

Sunlenca 300 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 22

HOS-148333 · Präparat HOS-099874

Strong CYP3A4 inhibitors alone (e.g. voriconazole) or strong inhibitors of CYP3A4 and P-gp together (e.g. cobicistat) do not result in a clinically meaningful increase in lenacapavir exposures.

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): cobicistat (HOS-088111) voriconazole (HOS-084524)

Wechselwirkungen · Sunlenca

Sunlenca 300 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 22

HOS-148334 · Präparat HOS-099874

Effect of lenacapavir on the pharmacokinetics of other medicinal products

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Wechselwirkungen · Sunlenca

Sunlenca 300 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 22

HOS-148335 · Präparat HOS-099874

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

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Wechselwirkungen · Sunlenca

Sunlenca 300 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 22

HOS-148336 · Präparat HOS-099874

Table 2: Interactions between Sunlenca and other medicinal products

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Wechselwirkungen · Sunlenca

Sunlenca 300 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 22

HOS-148337 · Präparat HOS-099874

Medicinal product by therapeutic Effects on concentrations. Recommendation concerning areas Mean percent change in AUC, co-administration with Sunlenca Cmax ANTIMYCOBACTERIALS Rifampicina,b,c (600 mg once daily) Lenacapavir: Co-administration is AUC: ↓84% contraindicated (see section 4.3). Cmax: ↓55% Rifabutin Interaction not studied. Co-administration is not recommended (see section 4.4). Co-administration of rifabutin may decrease lenacapavir plasma concentrations, which may result in loss of therapeutic effect and development of resistance. ANTICONVULSANTS Carbamazepine Interaction not studied. Co-administration is Phenytoin contraindicated (see section 4.3) Co-administration of Oxcarbazepine carbamazepine, oxcarbazepine, Co-administration is not Phenobarbital phenobarbital, or phenytoin with recommended (see section 4.4). lenacapavir may decrease lenacapavir plasma concentrations, Alternative anticonvulsants should which may result in loss of be considered. therapeutic effect and development of resistance. HERBAL PRODUCTS St. John’s wort (Hypericum Interaction not studied. Co-administration is perforatum) contraindicated (see section 4.3). Co-administration of St. John’s wort may decrease lenacapavir plasma concentrations, which may result in loss of therapeutic effect and development of resistance.

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): phenobarbital (HOS-085617) carbamazepine (HOS-085618) rifabutin (HOS-086262) oxcarbazepine (HOS-110224) phenytoin (HOS-084531)

Wechselwirkungen · Sunlenca

Sunlenca 300 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 22–23

HOS-148338 · Präparat HOS-099874

22 Medicinal product by therapeutic Effects on concentrations. Recommendation concerning areas Mean percent change in AUC, co-administration with Sunlenca Cmax ANTIRETROVIRAL AGENTS Atazanavir/cobicistatb,d,e Lenacapavir: Co-administration is not (300 mg/150 mg once daily) AUC: ↑ 321% recommended (see section 4.4). Cmax: ↑ 560% Efavirenzb,d,f (600 mg once daily) Lenacapavir: AUC:↓ 56% Cmax:↓ 36% Etravirine Interaction not studied. Nevirapine Tipranavir/ritonavir Co-administration of etravirine, nevirapine, or tipranavir/ritonavir may decrease lenacapavir plasma concentrations, which may result in loss of therapeutic effect and development of resistance. Cobicistatb,d,g (150 mg once daily) Lenacapavir: No dose adjustment of lenacapavir AUC: ↑ 128% is required. Cmax:↑ 110% Darunavir/cobicistatb,d,h Lenacapavir: (800 mg/150 mg once daily) AUC:↑ 94% Cmax:↑ 130% Ritonavir Interaction not studied.

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): atazanavir (HOS-086180) etravirine (HOS-088088) darunavir (HOS-086181) nevirapine (HOS-088064) ritonavir (HOS-084521) tipranavir (HOS-086184)

Wechselwirkungen · Sunlenca

Sunlenca 300 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 23

HOS-148339 · Präparat HOS-099874

Co-administation of ritonavir may increase lenacapavir plasma concentrations. Tenofovir alafenamided,i,j (25 mg) Tenofovir alafenamide: No dose adjustment of tenofovir AUC:↑ 32% alafenamide is required. Cmax:↑ 24%

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): tenofovir (HOS-088083) tenofovir alafenamide (HOS-110476) ritonavir (HOS-084521)

Wechselwirkungen · Sunlenca

Sunlenca 300 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 23

HOS-148340 · Präparat HOS-099874

Tenofovirk: AUC:↑ 47% Cmax:↑ 23% ERGOT DERIVATIVES Dihydroergotamine Interaction not studied. Caution is warranted when Ergotamine dihydroergotamine or ergotamine, Plasma concentrations of these is co-administered with Sunlenca. medicinal products may be increased when co-administered with lenacapavir. PHOSPHODIESTERASE-5 (PDE-5) INHIBITORS Sildenafil Interaction not studied. Use of PDE-5 inhibitors for Tadalafil pulmonary arterial hypertension: Vardenafil Plasma concentration of PDE-5 Co-administration with tadalafil is inhibitors may be increased when not recommended. co-administered with lenacapavir. 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

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): tadalafil (HOS-086316) sildenafil (HOS-086162) ergotamine (HOS-086154) dihydroergotamine (HOS-086152) vardenafil (HOS-086163)

Wechselwirkungen · Sunlenca

Sunlenca 300 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 23–24

HOS-148341 · Präparat HOS-099874

23 Medicinal product by therapeutic Effects on concentrations. Recommendation concerning areas Mean percent change in AUC, co-administration with Sunlenca Cmax CORTICOSTEROIDS (systemic) Cortisone/hydrocortisone Interaction not studied. Co-administration of Sunlenca with Dexamethasone corticosteroids whose exposures Plasma concentrations of are significantly increased by corticosteroids may be increased CYP3A inhibitors can increase the when co-administered with risk for Cushing's syndrome and lenacapavir. adrenal suppression. Initiate with the lowest starting dose and titrate Plasma concentrations of carefully while monitoring for lenacapavir may decrease when co- safety. administered with systemic dexamethasone, which may result Caution is warranted when in loss of therapeutic effect and systemic dexamethasone is development of resistance. co-administered with Sunlenca, particularly for long-term use. Alternative corticosteroids should be considered. HMG-CoA REDUCTASE INHIBITORS Lovastatin Interaction not studied. Initiate lovastatin and simvastatin Simvastatin with the lowest starting dose and Plasma concentrations of these titrate carefully while monitoring medicinal products may be for safety (e.g. myopathy). Atorvastatin increased when co-administered No dose adjustment of atorvastatin with lenacapavir. is required. Pitavastatin (2 mg single dose; d,i,l Pitavastatin: No dose adjustment of pitavastatin simultaneous or 3 days after AUC:↔ and rosuvastatin is required. lenacapavir) Cmax:↔ Rosuvastatind,i,m (5 mg single dose) Rosuvastatin: AUC:↑ 31% Cmax:↑ 57% ANTIARRHYTHMICS Digoxin Interaction not studied. Caution is warranted and therapeutic concentration Plasma concentration of digoxin monitoring of digoxin is may be increased when recommended. co-administered with lenacapavir. SEDATIVES/HYPNOTICS Midazolamd,i,n (2.5 mg single dose; Midazolam: Caution is warranted when oral; simultaneous administration) AUC: ↑ 259% midazolam or triazolam, is Cmax: ↑ 94% co-administered with Sunlenca.

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): cortisone (HOS-114161) lovastatin (HOS-086157) atorvastatin (HOS-086304) simvastatin (HOS-086158) rosuvastatin (HOS-086307) digoxin (HOS-086172) dexamethasone (HOS-084535) hydrocortisone (HOS-148307) triazolam (HOS-086168) midazolam (HOS-086167) pitavastatin (HOS-125743)

Wechselwirkungen · Sunlenca

Sunlenca 300 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 24

HOS-148342 · Präparat HOS-099874

1-hydroxymidazolamo: AUC: ↓ 24% Cmax: ↓ 46% Midazolamd,i,n (2.5 mg single dose; Midazolam: oral; 1 day after lenacapavir) AUC: ↑ 308% Cmax: ↑ 116%

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): midazolam (HOS-086167)

Wechselwirkungen · Sunlenca

Sunlenca 300 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 24

HOS-148343 · Präparat HOS-099874

1-hydroxymidazolamo: AUC: ↓ 16% Cmax: ↓ 48% Triazolam Interaction not studied.

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): triazolam (HOS-086168)

Wechselwirkungen · Sunlenca

Sunlenca 300 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 24

HOS-148344 · Präparat HOS-099874

Plasma concentration of triazolam may be increased when co-administered with lenacapavir. ANTICOAGULANTS Direct Oral Anticoagulants Interaction not studied. Due to potential bleeding risk, dose (DOACs) adjustment of DOAC may be

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): triazolam (HOS-086168)

Wechselwirkungen · Sunlenca

Sunlenca 300 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 24–25

HOS-148345 · Präparat HOS-099874

24 Medicinal product by therapeutic Effects on concentrations. Recommendation concerning areas Mean percent change in AUC, co-administration with Sunlenca Cmax Rivaroxaban Plasma concentration of DOAC required. Consult the Summary of Dabigatran may be increased when Product Characteristics of the Edoxaban co-administered with lenacapavir. DOAC for further information on use in combination with moderate CYP3A inhibitors and/or P-gp inhibitors. ANTIFUNGALS Voriconazolea,b,p,q (400 mg twice Lenacapavir: No dose adjustment of lenacapavir daily/200 mg twice daily) AUC:↑ 41% is required. Cmax:↔ Itraconazole Interaction not studied. Ketoconazole Plasma concentration of lenacapavir may be increased when co-administered with itraconazole or ketoconazole. H2-RECEPTOR ANTAGONISTS Famotidinea,b (40 mg once daily, 2 Famotidine: No dose adjustment of famotidine hours before lenacapavir) AUC:↑ 28% is required. Cmax:↔ ORAL CONTRACEPTIVES Ethinylestradiol Interaction not studied. No dose adjustment of Progestins ethinylestradiol and progestins is Plasma concentrations of required. ethinylestradiol and progestins may be increased when co-administered with lenacapavir. GENDER AFFIRMING HORMONES 17β-estradiol Interaction not studied. No dose adjustment of these gender Anti-androgens affirming hormones is required. Progestogen Plasma concentrations of these Testosterone 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 Evaluated as a strong inducer of CYP3A, and an inducer of P-gp and UGT. d Fed. e Evaluated as a strong inhibitor of CYP3A, and an inhibitor UGT1A1 and P-gp. f Evaluated as a moderate inducer of CYP3A and an inducer of P-gp. g Evaluated as a strong inhibitor of CYP3A and an inhibitor of P-gp. h Evaluated as a strong inhibitor of CYP3A, and an inhibitor and inducer of P-gp. i 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 with each co-administered medicinal product. j Evaluated as a P-gp substrate. k Tenofovir alafenamide is converted to tenofovir in vivo. l Evaluated as an OATP substrate. m Evaluated as an BCRP substrate. n Evaluated as a CYP3A substrate. o Major active metabolite of midazolam. p Evaluated as a strong inhibitor of CYP3A. q This study was conducted using voriconazole 400 mg loading dose twice daily for a day, followed by 200 mg maintenance dose twice daily.

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): tenofovir (HOS-088083) ketoconazole (HOS-084513) tenofovir alafenamide (HOS-110476) estradiol (HOS-090751) famotidine (HOS-112087) dabigatran (HOS-112096) rivaroxaban (HOS-086236) voriconazole (HOS-084524) itraconazole (HOS-084516) testosterone (HOS-144014) edoxaban (HOS-086234) midazolam (HOS-086167)

Nebenwirkungen · Sunlenca

Sunlenca 464 mg solution for injection · Abschnitt 4.8 · PDF-Seite 9

HOS-148317 · Präparat HOS-099874

Summary of the safety profile

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Nebenwirkungen · Sunlenca

Sunlenca 464 mg solution for injection · Abschnitt 4.8 · PDF-Seite 9

HOS-148318 · Präparat HOS-099874

The most common adverse reactions in heavily treatment-experienced adult participants with HIV were ISRs (76%) and nausea (6%).

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Nebenwirkungen · Sunlenca

Sunlenca 464 mg solution for injection · Abschnitt 4.8 · PDF-Seite 9

HOS-148319 · Präparat HOS-099874

Tabulated list of adverse reactions

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.