Wirkstoffe & Arzneimittelsicherheit

Wechselwirkungen · Biktarvy

Biktarvy 30 mg/120 mg/15 mg film-coated tablets Biktarvy 50 mg/200 mg/25 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 11–12

HOS-139306 · Präparat HOS-098314

11  Medicinal product by Effects on medicinal product Recommendation concerning therapeutic areas/possible levels. co-administration with Biktarvy mechanism of interaction Mean percent change in AUC, Cmax, Cmin ORAL ANTI-DIABETICS Metformin (500 mg twice daily), Metformin: No dose adjustment is required Bictegravir/Emtricitabine/ AUC: ↑ 39% upon co-administration in patients Tenofovir alafenamide Cmin: ↑ 36% with normal renal function. Cmax: ↔ (Inhibition of OCT2/MATE1) In patients with moderate renal impairment, close monitoring should be considered when starting co-administration of bictegravir with metformin, due to the increased risk for lactic acidosis in these patients. A dose adjustment of metformin should be considered if required. ORAL CONTRACEPTIVES Norgestimate Norelgestromin: No dose adjustment is required (0.180/0.215/0.250 mg once daily)/ AUC: ↔ upon co-administration. Ethinylestradiol (0.025 mg once Cmin: ↔ daily), Bictegravir1 Cmax: ↔ Norgestimate (0.180/0.215/0.250 mg once daily), Norgestrel: Ethinylestradiol (0.025 mg once AUC: ↔ daily), Emtricitabine/Tenofovir Cmin: ↔ alafenamide4 Cmax: ↔

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) norgestimate (HOS-110544) norelgestromin (HOS-110295) metformin (HOS-091032) norgestrel (HOS-090613)

Wechselwirkungen · Biktarvy

Biktarvy 30 mg/120 mg/15 mg film-coated tablets Biktarvy 50 mg/200 mg/25 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 12

HOS-139307 · Präparat HOS-098314

Ethinylestradiol: AUC: ↔ Cmin: ↔ Cmax: ↔ SEDATIVES/HYPNOTICS Midazolam (2 mg, oral syrup, Midazolam: No dose adjustment is required single dose), AUC: ↔ upon co-administration. Bictegravir/Emtricitabine/ Cmax: ↔ Tenofovir alafenamide 1 This study was conducted using bictegravir 75 mg single dose. 2 This study was conducted using bictegravir/emtricitabine/tenofovir alafenamide 75/200/25 mg once daily. 3 Study conducted with additional voxilaprevir 100 mg to achieve voxilaprevir exposures expected in HCV infected patients. 4 This study was conducted using emtricitabine/tenofovir alafenamide 200/25 mg once daily. 5 Maximum strength antacid contained 80 mg aluminium hydroxide, 80 mg magnesium hydroxide, and 8 mg simethicone per mL. 6 This study was conducted using elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide 150/150/200/10 mg once 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): cobicistat (HOS-088111) magnesium hydroxide (HOS-088789) voxilaprevir (HOS-108930) elvitegravir (HOS-088110) simethicone (HOS-118210) midazolam (HOS-086167)

Wechselwirkungen · Biktarvy

Biktarvy 30 mg/120 mg/15 mg film-coated tablets Biktarvy 50 mg/200 mg/25 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 12

HOS-139309 · Präparat HOS-098314

Based on drug interaction studies conducted with Biktarvy or the components of Biktarvy, no clinically significant drug interactions are expected with: amlodipine, atorvastatin, buprenorphine, drospirenone, famciclovir, famotidine, fluticasone, methadone, naloxone, norbuprenorphine, omeprazole or rosuvastatin.

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): famciclovir (HOS-112681) fluticasone (HOS-108914) methadone (HOS-086198) atorvastatin (HOS-086304) amlodipine (HOS-086287) rosuvastatin (HOS-086307) famotidine (HOS-112087) buprenorphine (HOS-086193) drospirenone (HOS-116422) naloxone (HOS-109490) omeprazole (HOS-085912)

Nebenwirkungen · Biktarvy

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HOS-139310 · Präparat HOS-098314

Summary of the safety profile

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Nebenwirkungen · Biktarvy

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HOS-139311 · Präparat HOS-098314

In clinical studies of treatment-naïve patients receiving Biktarvy, the most frequently reported adverse reactions in the double-blind phase (Week 144) were headache (5%), diarrhoea (5%) and nausea (4%).

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

Nebenwirkungen · Biktarvy

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HOS-139312 · Präparat HOS-098314

13 Tabulated list of adverse reactions

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Nebenwirkungen · Biktarvy

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HOS-139313 · Präparat HOS-098314

The assessment of adverse reactions is based on safety data from across all Phase 2 and 3 studies with Biktarvy and from post-marketing experience. The adverse reactions in Table 2 are listed by system organ class and frequency. Frequencies are defined as follows: common (≥ 1/100 to < 1/10) uncommon (≥ 1/1 000 to < 1/100) and rare (≥ 1/10 000 to < 1/1 000).

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

Nebenwirkungen · Biktarvy

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HOS-139314 · Präparat HOS-098314

Table 2: Tabulated list of adverse reactions1

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Nebenwirkungen · Biktarvy

Biktarvy 30 mg/120 mg/15 mg film-coated tablets Biktarvy 50 mg/200 mg/25 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 14

HOS-139315 · Präparat HOS-098314

Frequency Adverse reaction Blood and lymphatic system disorders Uncommon: anaemia2 Psychiatric disorders Common: depression, abnormal dreams suicidal ideation, suicide attempt (particularly in patients with a pre-existing history Uncommon: of depression or psychiatric illness), anxiety, sleep disorders Nervous system disorders Common: headache, dizziness Gastrointestinal disorders Common: diarrhoea, nausea Uncommon: vomiting, abdominal pain, dyspepsia, flatulence Hepatobiliary disorders Uncommon: hyperbilirubinaemia Skin and subcutaneous tissue disorders Uncommon: angioedema3,4, rash, pruritus, urticaria4 Rare: Stevens-Johnson syndrome5 Musculoskeletal and connective tissue disorders Uncommon: arthralgia General disorders and administration site conditions Common: Fatigue Investigations Common: weight increased 1 With the exception of angioedema, anaemia, urticaria and Stevens-Johnson syndrome (see footnotes 2-5), all adverse reactions were identified from Biktarvy clinical studies. The frequencies were derived from the double-blind phase (Week 144) of Phase 3 Biktarvy clinical studies in treatment-naïve patients (GS-US-380-1489 and GS-US-380-1490). 2 This adverse reaction was not observed in the clinical studies of emtricitabine + tenofovir alafenamide-containing products but identified from clinical studies or post-marketing experience for emtricitabine when used with other antiretrovirals. 3 This adverse reaction was identified through post-marketing surveillance for emtricitabine-containing products. 4 This adverse reaction was identified through post-marketing surveillance for tenofovir alafenamide-containing products. 5 This adverse reaction was identified through post-marketing surveillance for Biktarvy. The frequency has been calculated using 3/X, where X represent the cumulative number of subjects exposed to Biktarvy in clinical trials (N=3963).

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

Nebenwirkungen · Biktarvy

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HOS-139316 · Präparat HOS-098314

Description of selected adverse reactions

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Nebenwirkungen · Biktarvy

Biktarvy 30 mg/120 mg/15 mg film-coated tablets Biktarvy 50 mg/200 mg/25 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 14

HOS-139317 · Präparat HOS-098314

Metabolic parameters Weight and levels of blood lipids and glucose may increase during antiretroviral therapy (see section 4.4).

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

Nebenwirkungen · Biktarvy

Biktarvy 30 mg/120 mg/15 mg film-coated tablets Biktarvy 50 mg/200 mg/25 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 14

HOS-139318 · Präparat HOS-098314

Immune Reactivation Syndrome In HIV infected patients with severe immune deficiency at the time of initiation of CART, an inflammatory reaction to asymptomatic or residual opportunistic infections may arise. Autoimmune disorders (such as Graves’ disease and autoimmune hepatitis) have also been reported; however, the reported time to onset is more variable and these events can occur many months after initiation of treatment (see section 4.4).

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

Nebenwirkungen · Biktarvy

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HOS-139319 · Präparat HOS-098314

Osteonecrosis Cases of osteonecrosis have been reported, particularly in patients with generally acknowledged risk factors, advanced HIV disease or long-term exposure to CART. The frequency of this is unknown (see section 4.4).

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

Nebenwirkungen · Biktarvy

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HOS-139320 · Präparat HOS-098314

14 Changes in serum creatinine Bictegravir has been shown to increase serum creatinine due to inhibition of tubular secretion of creatinine, however these changes are not considered to be clinically relevant since they do not reflect a change in glomerular filtration rate. Increases in serum creatinine occurred by Week 4 of treatment and remained stable through Week 144. In Studies GS-US-380-1489 and GS-US-380-1490, median (Q1, Q3) serum creatinine increased by 0.11 (0.03, 0.19) mg/dL (9.7 [2.7, 16.8] µmol/L), 0.11 (0.04, 0.19) mg/dL (9.7 [3.5, 16.8] µmol/L), and 0.12 (0.06, 0.21) mg/dL (10.6 [5.3, 18.6] μmol/L) from baseline to Week 144 in the Biktarvy, abacavir/dolutegravir/lamivudine, and dolutegravir + emtricitabine/tenofovir alafenamide groups, respectively. There were no discontinuations due to renal adverse reactions through Week 144 in patients administered Biktarvy in clinical studies.

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

Nebenwirkungen · Biktarvy

Biktarvy 30 mg/120 mg/15 mg film-coated tablets Biktarvy 50 mg/200 mg/25 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 15

HOS-139321 · Präparat HOS-098314

Changes in bilirubin In Studies GS-US-380-1489 and GS-US-380-1490, total bilirubin increases were observed in 17% of treatment-naïve patients administered Biktarvy through Week 144. Increases were primarily Grade 1 (12%) and Grade 2 (4%) (≥1.0 to 2.5 x Upper Limit of Normal [ULN]), and were not associated with hepatic adverse reactions or other liver related laboratory abnormalities. Five patients administered Biktarvy (1%) had grade 3 bilirubin increases that were not considered related to study drug. There were no discontinuations due to hepatic adverse reactions through Week 144 in Biktarvy clinical studies.

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

Nebenwirkungen · Biktarvy

Biktarvy 30 mg/120 mg/15 mg film-coated tablets Biktarvy 50 mg/200 mg/25 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 15

HOS-139322 · Präparat HOS-098314

Paediatric population The safety of Biktarvy was evaluated in 50 HIV-1 infected adolescents aged 12 to < 18 years and weighing ≥ 35 kg through Week 96 (48-week main phase and 48-week extension), in 50 children aged 6 to < 12 years and weighing ≥ 25 kg through Week 96 (48-week main phase and 48-week extension), and in 22 children ≥ 2 years of age and weighing ≥ 14 to < 25 kg through Week 24 in an open-label clinical study (GS-US-380-1474). In this study, no new adverse reactions have been observed in paediatric subjects aged 2 years and older living with HIV-1 as compared to adult subjects living with HIV-1. Bone mineral density data were not collected in this study. Reductions in BMD of the spine and of the TBLH ≥ 4% have been reported in paediatric patients receiving other tenofovir alafenamide containing products for 48 weeks (see section 4.4).

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

Nebenwirkungen · Biktarvy

Biktarvy 30 mg/120 mg/15 mg film-coated tablets Biktarvy 50 mg/200 mg/25 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 15

HOS-139323 · Präparat HOS-098314

Other special populations

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

Nebenwirkungen · Biktarvy

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HOS-139324 · Präparat HOS-098314

Patients co-infected with hepatitis B In 16 HIV/HBV co-infected adults administered Biktarvy (8 HIV/HBV treatment-naïve adults in Study GS-US-380-1490; 8 HIV/HBV suppressed adults in Study GS-US-380-1878), the safety profile of Biktarvy was similar to that in patients with HIV-1 monoinfection (see section 5.1).

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

Nebenwirkungen · Biktarvy

Biktarvy 30 mg/120 mg/15 mg film-coated tablets Biktarvy 50 mg/200 mg/25 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 15

HOS-139325 · Präparat HOS-098314

Elderly Studies GS-US-380-1844, GS-US-380-1878 and the dedicated Study GS-US-380-4449 in patients ≥ 65 years old (evaluation of 86 HIV-1 infected, virologically-suppressed subjects ≥ 65 years old) included 111 patients aged ≥ 65 years who received Biktarvy. In these patients, no differences in the safety profile of Biktarvy were observed.

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

Nebenwirkungen · Biktarvy

Biktarvy 30 mg/120 mg/15 mg film-coated tablets Biktarvy 50 mg/200 mg/25 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 15

HOS-139326 · Präparat HOS-098314

Patients with renal impairment The safety of emtricitabine + tenofovir alafenamide was evaluated in a single arm, open-label clinical study (GS-US-292-1825), in which 55 virologically-suppressed HIV-1 infected patients with end stage renal disease (eGFRCG < 15 mL/min) on chronic haemodialysis received emtricitabine + tenofovir alafenamide in combination with elvitegravir + cobicistat as a fixed-dose combination tablet for 96 weeks. In an extension phase of Study GS-US-292-1825, 10 patients switched to Biktarvy for 48 weeks. No additional adverse reactions were identified in patients with end stage renal disease on chronic haemodialysis in this study (see sections 4.4 and 5.2).

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