Biktarvy

1 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 
 

 



2 

This medicinal product is subject to additional monitoring.  This will allow quick identification of 
new safety information.  Healthcare professionals are asked to report any suspected adverse reactions.  
See section 4.8 for how to report adverse reactions. 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Biktarvy 50 mg/200 mg/25 mg film-coated tablets 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each film-coated tablet contains bictegravir sodium equivalent to 50 mg of bictegravir, 200 mg of 
emtricitabine, and tenofovir alafenamide fumarate equivalent to 25 mg of tenofovir alafenamide. 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Film-coated tablet (tablet). 
 
Purplish-brown, capsule-shaped, film-coated tablet debossed with “GSI” on one side and “9883” on 
the other side of the tablet.  Each tablet is approximately 15 mm × 8 mm. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Biktarvy is indicated for the treatment of adults infected with human immunodeficiency virus-1 
(HIV-1) without present or past evidence of viral resistance to the integrase inhibitor class, 
emtricitabine or tenofovir (see section 5.1). 
 
4.2 Posology and method of administration 
 
Therapy should be initiated by a physician experienced in the management of HIV infection. 
 
Posology 
 
One tablet to be taken once daily. 
 
Missed doses 
If the patient misses a dose of Biktarvy within 18 hours of the time it is usually taken, the patient 
should take Biktarvy as soon as possible and resume the normal dosing schedule.  If a patient misses a 
dose of Biktarvy by more than 18 hours, the patient should not take the missed dose and simply 
resume the usual dosing schedule. 
 
If the patient vomits within 1 hour of taking Biktarvy another tablet should be taken.  If a patient 
vomits more than 1 hour after taking Biktarvy they do not need to take another dose of Biktarvy until 
the next regularly scheduled dose. 
 
Elderly 
No dose adjustment of Biktarvy is required in patients aged ≥ 65 years (see sections 4.8 and 5.2). 
 



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Renal impairment 
No dose adjustment of Biktarvy is required in patients with estimated creatinine clearance (CrCl) 
≥ 30 mL/min. 
 
No dose adjustment of Biktarvy is required in adult patients with end stage renal disease (estimated 
creatinine clearance < 15 mL/minute) who are receiving chronic haemodialysis.  However, Biktarvy 
should generally be avoided and only be used in these patients if the potential benefits are considered 
to outweigh the potential risks (see sections 4.4 and 5.2).  On days of haemodialysis, administer the 
daily dose of Biktarvy after completion of haemodialysis treatment. 
 
Initiation of Biktarvy should be avoided in patients with estimated creatinine clearance ≥15 mL/min 
and < 30 mL/min, or < 15 mL/min who are not receiving chronic haemodialysis, as the safety of 
Biktarvy has not been established in these populations (see section 5.2).  
 
Hepatic impairment 
No dose adjustment of Biktarvy is required in patients with mild (Child-Pugh Class A) or moderate 
(Child-Pugh Class B) hepatic impairment.  Biktarvy has not been studied in patients with severe 
hepatic impairment (Child-Pugh Class C), therefore Biktarvy is not recommended for use in patients 
with severe hepatic impairment (see sections 4.4 and 5.2). 
 
Paediatric population 
The safety and efficacy of Biktarvy in children under the age of 18 years have not yet been 
established.  No data are available. 
 
Method of administration 
 
Oral use 
Biktarvy can be taken with or without food (see section 5.2). 
The film-coated tablets should not be chewed, crushed or split. 
 
4.3 Contraindications 
 
Hypersensitivity to the active substances or to any of the excipients listed in section 6.1. 
 
Co-administration with rifampicin and St. John’s wort (Hypericum perforatum) (see section 4.5). 
 
4.4 Special warnings and precautions for use 
 
While effective viral suppression with antiretroviral therapy has been proven to substantially reduce 
the risk of sexual transmission, a residual risk cannot be excluded.  Precautions to prevent 
transmission should be taken in accordance with national guidelines. 
 
Patients co-infected with HIV and hepatitis B or C virus 
 
Patients with chronic hepatitis B or C treated with antiretroviral therapy are at an increased risk for 
severe and potentially fatal hepatic adverse reactions. 
 
There are limited safety and efficacy data for Biktarvy in patients co-infected with HIV-1 and 
hepatitis C virus (HCV).  
 
Biktarvy contains tenofovir alafenamide, which is active against hepatitis B virus (HBV). 
 
Discontinuation of Biktarvy therapy in patients co-infected with HIV and HBV may be associated 
with severe acute exacerbations of hepatitis.  Patients co-infected with HIV and HBV who discontinue 
Biktarvy should be closely monitored with both clinical and laboratory follow-up for at least several 
months after stopping treatment. 
 



4 

Liver disease 
 
The safety and efficacy of Biktarvy in patients with significant underlying liver disorders have not 
been established. 
 
Patients with pre-existing liver dysfunction, including chronic active hepatitis, have an increased 
frequency of liver function abnormalities during combination antiretroviral therapy (CART) and 
should be monitored according to standard practice.  If there is evidence of worsening liver disease in 
such patients, interruption or discontinuation of treatment must be considered. 
 
Weight and metabolic parameters 
 
An increase in weight and in levels of blood lipids and glucose may occur during antiretroviral 
therapy.  Such changes may in part be linked to disease control and life style.  For lipids, there is in 
some cases evidence for a treatment effect, while for weight gain there is no strong evidence relating 
this to any particular treatment.  For monitoring of blood lipids and glucose reference is made to 
established HIV treatment guidelines.  Lipid disorders should be managed as clinically appropriate. 
 
Mitochondrial dysfunction following exposure in utero 
 
Nucleos(t)ide analogues may impact mitochondrial function to a variable degree, which is most 
pronounced with stavudine, didanosine and zidovudine.  There have been reports of mitochondrial 
dysfunction in HIV negative infants exposed in utero and/or postnatally to nucleoside analogues; these 
have predominantly concerned treatment with regimens containing zidovudine.  The main adverse 
reactions reported are haematological disorders (anaemia, neutropenia) and metabolic disorders 
(hyperlactatemia, hyperlipasemia).  These events have often been transitory.  Late onset neurological 
disorders have been reported rarely (hypertonia, convulsion, abnormal behaviour).  Whether such 
neurological disorders are transient or permanent is currently unknown.  These findings should be 
considered for any child exposed in utero to nucleos(t)ide analogues, who present with severe clinical 
findings of unknown etiology, particularly neurologic findings.  These findings do not affect current 
national recommendations to use antiretroviral therapy in pregnant women to prevent vertical 
transmission of HIV. 
 
Immune Reactivation Syndrome 
 
In HIV infected patients with severe immune deficiency at the time of institution of CART, an 
inflammatory reaction to asymptomatic or residual opportunistic pathogens may arise and cause 
serious clinical conditions, or aggravation of symptoms.  Typically, such reactions have been observed 
within the first few weeks or months of initiation of CART.  Relevant examples include 
cytomegalovirus retinitis, generalised and/or focal mycobacterial infections, and Pneumocystis 
jirovecii pneumonia.  Any inflammatory symptoms should be evaluated and treatment instituted when 
necessary. 
 
Autoimmune disorders (such as Graves’ disease and autoimmune hepatitis) have also been reported to 
occur in the setting of immune reactivation; however, the reported time to onset is more variable and 
these events can occur many months after initiation of treatment. 
 
Opportunistic infections 
 
Patients should be advised that Biktarvy or any other antiretroviral therapy does not cure 
HIV infection and that they may still develop opportunistic infections and other complications of 
HIV infection.  Therefore patients should remain under close clinical observation by physicians 
experienced in the treatment of patients with HIV associated diseases. 
 



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Osteonecrosis 
 
Although the aetiology is considered to be multifactorial (including corticosteroid use, alcohol 
consumption, severe immunosuppression, higher body mass index), cases of osteonecrosis have been 
reported particularly in patients with advanced HIV disease and/or long-term exposure to CART.  
Patients should be advised to seek medical advice if they experience joint aches and pain, joint 
stiffness or difficulty in movement. 
 
Nephrotoxicity 
 
A potential risk of nephrotoxicity resulting from chronic exposure to low levels of tenofovir due to 
dosing with tenofovir alafenamide cannot be excluded (see section 5.3). 
 
Patients with end stage renal disease on chronic haemodialysis 
 
Biktarvy should generally be avoided but may be used in adults with end stage renal disease 
(estimated CrCl < 15 mL/min) on chronic haemodialysis if the potential benefits outweigh the 
potential risks (see section 4.2).  In a study of emtricitabine + tenofovir alafenamide in combination 
with elvitegravir + cobicistat as a fixed-dose combination tablet (E/C/F/TAF) in HIV-1 infected adults 
with end stage renal disease (estimated CrCl < 15 mL/min) on chronic haemodialysis, efficacy was 
maintained through 96 weeks but emtricitabine exposure was significantly higher than in patients with 
normal renal function.  Efficacy was also maintained in the extension phase of the study in which 10 
patients switched to Biktarvy for 48 weeks.  Although no additional adverse reactions were identified, 
the implications of increased emtricitabine exposure remain uncertain (see sections 4.8 and 5.2). 
 
Co-administration of other medicinal products 
 
Biktarvy should not be co-administered simultaneously with magnesium/aluminium-containing 
antacids or iron supplements under fasted conditions.  Biktarvy should be administered at least 2 hours 
before, or with food 2 hours after antacids containing magnesium and/or aluminium.  Biktarvy should 
be administered at least 2 hours before iron supplements, or taken together with food (see section 4.5). 
 
Some medicinal products are not recommended for co-administration with Biktarvy: atazanavir, 
carbamazepine, ciclosporin (IV or oral use), oxcarbazepine, phenobarbital, phenytoin, rifabutin, 
rifapentine, or sucralfate. 
 
Biktarvy should not be co-administered with other antiretroviral medicinal products. 
 
Excipients 
 
This medicine contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially 
‘sodium-free’. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
Interaction studies have only been performed in adults. 
 
Biktarvy should not be administered concomitantly with medicinal products containing tenofovir 
alafenamide, tenofovir disoproxil, lamivudine or adefovir dipivoxil used for the treatment of 
HBV infection. 
 
Bictegravir 
 
Bictegravir is a substrate of CYP3A and UGT1A1.  Co-administration of bictegravir and medicinal 
products that potently induce both CYP3A and UGT1A1, such as rifampicin or St. John’s wort, may 
significantly decrease plasma concentrations of bictegravir, which may result in a loss of therapeutic 
effect of Biktarvy and development of resistance, therefore co-administration is contraindicated (see 



6 

section 4.3).  Co-administration of bictegravir with medicinal products that potently inhibit both 
CYP3A and UGT1A1, such as atazanavir, may significantly increase plasma concentrations of 
bictegravir, therefore co-administration is not recommended.  
 
Bictegravir is both a P-gp and a BCRP substrate.  The clinical relevance of this feature is not 
established.  Therefore, caution is recommended when bictegravir is combined with medicinal 
products known to inhibit P-gp and/or BCRP (e.g. macrolides, ciclosporin, verapamil, dronedarone, 
glecaprevir/pibrentasvir) (see also table below). 
 
Bictegravir inhibits organic cation transporter 2 (OCT2) and multidrug and toxin extrusion 
transporter 1 (MATE1) in vitro.  Co-administration of Biktarvy with the OCT2 and MATE1 substrate 
metformin did not result in a clinically significant increase in metformin exposure.  Biktarvy may be 
co-administered with substrates of OCT2 and MATE1.  
 
Bictegravir is not an inhibitor or inducer of CYP in vivo. 
 
Emtricitabine 
 
In vitro and clinical pharmacokinetic drug-drug interaction studies have shown that the potential for 
CYP-mediated interactions involving emtricitabine with other medicinal products is low.  
Co-administration of emtricitabine with medicinal products that are eliminated by active tubular 
secretion may increase concentrations of emtricitabine, and/or the co-administered medicinal product.  
Medicinal products that decrease renal function may increase concentrations of emtricitabine. 
 
Tenofovir alafenamide 
 
Tenofovir alafenamide is transported by P-glycoprotein (P-gp) and breast cancer resistance protein 
(BCRP).  Co-administration of Biktarvy with medicinal products that strongly affect P-gp and BCRP 
activity may lead to changes in tenofovir alafenamide absorption.  Medicinal products that induce 
P-gp activity (e.g. rifabutin, carbamazepine, phenobarbital) are expected to decrease the absorption of 
tenofovir alafenamide, resulting in decreased plasma concentration of tenofovir alafenamide, which 
may lead to loss of therapeutic effect of Biktarvy and development of resistance.  Co-administration of 
Biktarvy with other medicinal products that inhibit P-gp and BCRP may increase the absorption and 
plasma concentration of tenofovir alafenamide. 
 
Tenofovir alafenamide is not an inhibitor or inducer of CYP3A in vivo. 
 
Other interactions 
 
Interactions between Biktarvy or its individual component(s) and co-administered medicinal products 
are listed in Table 1 below (increase is indicated as “↑”, decrease as “↓” and no change as “↔”; all No 
Effect Boundaries are 70%-143%).  
 
Table 1: Interactions between Biktarvy or its individual component(s) and other medicinal 
products 
 

Medicinal product by 
therapeutic areas/possible 
mechanism of interaction 

Effects on medicinal product 
levels. 

Mean percent change in AUC, 
Cmax, Cmin 

Recommendation concerning 
co-administration with Biktarvy 

HERBAL PRODUCTS 
St. John’s wort (Hypericum 
perforatum) 
 
(Induction of CYP3A, UGT1A1, 
and P-gp) 

Interaction not studied with any of 
the components of Biktarvy. 
Co-administration may decrease 
bictegravir and tenofovir 
alafenamide plasma concentrations. 

Co-administration with St. John’s 
wort is contraindicated, due to the 
effect of St. John’s wort on the 
bictegravir component of Biktarvy. 



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Medicinal product by 
therapeutic areas/possible 
mechanism of interaction 

Effects on medicinal product 
levels. 

Mean percent change in AUC, 
Cmax, Cmin 

Recommendation concerning 
co-administration with Biktarvy 

ANTI-INFECTIVES 
Antimycobacterials 
Rifampicin (600 mg once daily),  
Bictegravir1 
 
(Induction of CYP3A, UGT1A1, 
and P-gp) 

Bictegravir: 
AUC: ↓ 75% 
Cmax: ↓ 28% 
 
Interaction not studied with 
tenofovir alafenamide.   
Co-administration of rifampicin 
may decrease tenofovir alafenamide 
plasma concentrations. 

Co-administration is 
contraindicated due to the effect of 
rifampicin on the bictegravir 
component of Biktarvy. 

Rifabutin (300 mg once daily),  
Bictegravir1 
 
(Induction of CYP3A and P-gp) 

Bictegravir: 
AUC: ↓ 38% 
Cmin: ↓ 56% 
Cmax: ↓ 20% 
 
Interaction not studied with 
tenofovir alafenamide. 
Co-administration of rifabutin may 
decrease tenofovir alafenamide 
plasma concentrations. 

Co-administration is not 
recommended due to the expected 
decrease of tenofovir alafenamide. 

Rifapentine 
 
(Induction of CYP3A and P-gp) 

Interaction not studied with any of 
the components of Biktarvy. 
Co-administration of rifapentine 
may decrease bictegravir and 
tenofovir alafenamide plasma 
concentrations. 

Co-administration is not 
recommended. 

HIV-1 antiviral agents 
Atazanavir (300 mg once daily), 
Cobicistat (150 mg once daily), 
Bictegravir1 
 
(Inhibition of CYP3A, UGT1A1, 
and P-gp/BCRP) 

Bictegravir: 
AUC: ↑ 306% 
Cmax: ↔ 

Co-administration is not 
recommended. 

Atazanavir (400 mg once daily), 
Bictegravir1 
 
(Inhibition of CYP3A and 
UGT1A1) 

Bictegravir: 
AUC: ↑ 315% 
Cmax: ↔ 



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Medicinal product by 
therapeutic areas/possible 
mechanism of interaction 

Effects on medicinal product 
levels. 

Mean percent change in AUC, 
Cmax, Cmin 

Recommendation concerning 
co-administration with Biktarvy 

Hepatitis C virus antiviral agents 
Ledipasvir/Sofosbuvir 
(90 mg/400 mg once daily), 
Bictegravir/Emtricitabine/ 
Tenofovir alafenamide2 

Bictegravir: 
AUC: ↔ 
Cmin: ↔ 
Cmax: ↔ 
 
Emtricitabine: 
AUC: ↔ 
Cmin: ↔ 
Cmax: ↔ 
 
Tenofovir alafenamide: 
AUC: ↔ 
Cmax: ↔ 
 
Ledipasvir: 
AUC: ↔ 
Cmin: ↔ 
Cmax: ↔ 
 
Sofosbuvir: 
AUC: ↔ 
Cmax: ↔ 
 
Sofosbuvir metabolite GS-331007: 
AUC: ↔ 
Cmin: ↔ 
Cmax: ↔ 

No dose adjustment is required 
upon co-administration. 



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Medicinal product by 
therapeutic areas/possible 
mechanism of interaction 

Effects on medicinal product 
levels. 

Mean percent change in AUC, 
Cmax, Cmin 

Recommendation concerning 
co-administration with Biktarvy 

Sofosbuvir/Velpatasvir/ 
Voxilaprevir 
(400/100/100 + 100 mg3 once 
daily), Bictegravir/Emtricitabine/ 
Tenofovir alafenamide 
 
(Inhibition of P-gp/BCRP) 

Bictegravir: 
AUC: ↔ 
Cmin: ↔ 
Cmax: ↔ 
 
Emtricitabine: 
AUC: ↔ 
Cmin: ↔ 
Cmax: ↔ 
 
Tenofovir alafenamide: 
AUC: ↑ 57% 
Cmax: ↑ 28% 
 
Sofosbuvir: 
AUC: ↔ 
Cmax: ↔ 
 
Sofosbuvir metabolite GS-331007: 
AUC: ↔ 
Cmin: ↔ 
Cmax: ↔ 
 
Velpatasvir: 
AUC: ↔ 
Cmin: ↔ 
Cmax: ↔ 
 
Voxilaprevir: 
AUC: ↔ 
Cmin: ↔ 
Cmax: ↔ 

No dose adjustment is required 
upon co-administration. 

Antifungals 
Voriconazole (300 mg twice daily), 
Bictegravir1 
 
(Inhibition of CYP3A) 

Bictegravir: 
AUC: ↑ 61% 
Cmax: ↔ 

No dose adjustment is required 
upon co-administration. 

Itraconazole 
Posaconazole  
 
(Inhibition of P-gp/BCRP) 

Interaction not studied with any of 
the components of Biktarvy.  
Co-administration of itraconazole 
or posaconazole may increase 
bictegravir plasma concentrations. 

Macrolides 
Azithromycin 
Clarithromycin 
 
(Inhibition of P-gp) 

Interaction not studied.  
Co-administration of azithromycin 
or clarithromycin may increase 
bictegravir plasma concentrations. 

Caution is recommended due to the 
potential effect of these agents on 
the bictegravir component of 
Biktarvy. 

ANTICONVULSANTS 
Carbamazepine (titrated from 
100 mg to 300 mg twice a day), 
Emtricitabine/Tenofovir 
alafenamide4 
 
(Induction of CYP3A, UGT1A1, 
and P-gp) 

Tenofovir alafenamide: 
AUC: ↓ 54% 
Cmax: ↓ 57% 
 
Interaction not studied with 
bictegravir.  
Co-administration of 
carbamazepine may decrease 
bictegravir plasma concentrations. 

Co-administration is not 
recommended. 



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Medicinal product by 
therapeutic areas/possible 
mechanism of interaction 

Effects on medicinal product 
levels. 

Mean percent change in AUC, 
Cmax, Cmin 

Recommendation concerning 
co-administration with Biktarvy 

Oxcarbazepine 
Phenobarbital 
Phenytoin 
 
(Induction of CYP3A, UGT1A1, 
and P-gp) 

Interaction not studied with any of 
the components of Biktarvy. 
Co-administration of 
oxcarbazepine, phenobarbital, or 
phenytoin may decrease bictegravir 
and tenofovir alafenamide plasma 
concentrations. 

Co-administration is not 
recommended. 

ANTACIDS, SUPPLEMENTS AND BUFFERED MEDICINES 
Magnesium/aluminium-containing 
antacid suspension (20 mL single 
dose5), Bictegravir 
 
(Chelation with polyvalent cations) 

Bictegravir (antacid suspension 
2 hours prior, fasted): 
AUC: ↓ 52% 
Cmax: ↓ 58% 
 
Bictegravir (antacid suspension 
after 2 hours, fasted): 
AUC: ↔ 
Cmax: ↔ 
 
Bictegravir (simultaneous 
administration, fasted): 
AUC: ↓ 79% 
Cmax: ↓ 80% 
 
Bictegravir (simultaneous 
administration with food): 
AUC: ↓ 47% 
Cmax: ↓ 49% 

Biktarvy should not be taken 
simultaneously with supplements 
containing magnesium and/or 
aluminium due to the expected 
substantial decrease of bictegravir 
exposure (see section 4.4). 
 
Biktarvy should be administered at 
least 2 hours before, or with food 
2 hours after antacids containing 
magnesium and/or aluminium. 

Ferrous fumarate (324 mg single 
dose), Bictegravir 
 
(Chelation with polyvalent cations) 

Bictegravir (simultaneous 
administration, fasted): 
AUC: ↓ 63% 
Cmax: ↓ 71% 
 
Bictegravir (simultaneous 
administration with food): 
AUC: ↔ 
Cmax: ↓ 25% 

Biktarvy should be administered at 
least 2 hours before iron 
supplements, or taken together with 
food. 

Calcium carbonate (1,200 mg 
single dose), Bictegravir 
 
(Chelation with polyvalent cations) 

Bictegravir (simultaneous 
administration, fasted): 
AUC: ↓ 33% 
Cmax: ↓ 42% 
 
Bictegravir (simultaneous 
administration with food): 
AUC: ↔ 
Cmax: ↔ 

Biktarvy and calcium-containing 
supplements can be taken together, 
without regard to food. 

Sucralfate 
 
(Chelation with polyvalent cations) 

Interaction not studied with any of 
the components of Biktarvy. 
Co-administration may decrease 
bictegravir plasma concentrations. 

Co-administration not 
recommended. 



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Medicinal product by 
therapeutic areas/possible 
mechanism of interaction 

Effects on medicinal product 
levels. 

Mean percent change in AUC, 
Cmax, Cmin 

Recommendation concerning 
co-administration with Biktarvy 

ANTIDEPRESSANTS 
Sertraline (50 mg single dose), 
Tenofovir alafenamide6 

Tenofovir alafenamide: 
AUC: ↔ 
Cmax: ↔ 
 
Sertraline: 
AUC: ↔ 
Cmax: ↔ 
 
No interaction is expected with 
bictegravir and emtricitabine. 

No dose adjustment is required 
upon co-administration. 

IMMUNOSUPPRESSANTS 
Ciclosporin (IV or oral use) 
 
(P-gp inhibition) 

Interaction not studied with any of 
the components of Biktarvy.  
Co-administration of ciclosporin 
(IV or oral use) is expected to 
increase plasma concentrations of 
both bictegravir and tenofovir 
alafenamide. 

Co-administration of ciclosporin 
(IV or oral use) is not 
recommended.  If the combination 
is needed, clinical and biological 
monitoring, notably renal function, 
is recommended. 

ORAL ANTI-DIABETICS 
Metformin (500 mg twice daily), 
Bictegravir/Emtricitabine/ 
Tenofovir alafenamide 
 
(Inhibition of OCT2/MATE1) 

Metformin: 
AUC: ↑ 39% 
Cmin: ↑ 36% 
Cmax: ↔ 

No dose adjustment is required 
upon co-administration in patients 
with normal renal function. 
 
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 
(0.180/0.215/0.250 mg once daily)/ 
Ethinylestradiol (0.025 mg once 
daily), Bictegravir1 

Norelgestromin: 
AUC: ↔ 
Cmin: ↔ 
Cmax: ↔ 
 
Norgestrel: 
AUC: ↔ 
Cmin: ↔ 
Cmax: ↔ 
 
Ethinylestradiol: 
AUC: ↔ 
Cmin: ↔ 
Cmax: ↔ 

No dose adjustment is required 
upon co-administration. 

Norgestimate 
(0.180/0.215/0.250 mg once daily), 
Ethinylestradiol (0.025 mg once 
daily), Emtricitabine/Tenofovir 
alafenamide4 



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Medicinal product by 
therapeutic areas/possible 
mechanism of interaction 

Effects on medicinal product 
levels. 

Mean percent change in AUC, 
Cmax, Cmin 

Recommendation concerning 
co-administration with Biktarvy 

SEDATIVES/HYPNOTICS 
Midazolam (2 mg, oral syrup, 
single dose), 
Bictegravir/Emtricitabine/ 
Tenofovir alafenamide 

Midazolam: 
AUC: ↔ 
Cmax: ↔ 

No dose adjustment is required 
upon co-administration. 

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. 
 
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. 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
 
There are no or limited data (less than 300 pregnancy outcomes) from the use of bictegravir or 
tenofovir alafenamide in pregnant women.  A large amount of data on pregnant women (more than 
1,000 exposed outcomes) indicate no malformative nor foetal/neonatal toxicity associated with 
emtricitabine. 
 
Animal studies do not indicate direct or indirect harmful effects of emtricitabine with respect to 
fertility parameters, pregnancy, foetal development, parturition or postnatal development.  Studies of 
bictegravir and tenofovir alafenamide, administered separately, in animals have shown no evidence of 
harmful effects on fertility parameters, pregnancy, or foetal development (see section 5.3). 
 
Biktarvy should be used during pregnancy only if the potential benefit justifies the potential risk to 
the foetus. 
 
Breast-feeding 
 
It is not known whether bictegravir or tenofovir alafenamide is excreted in human milk.  Emtricitabine 
is excreted in human milk.  In animal studies, bictegravir was detected in the plasma of nursing rat 
pups likely due to the presence of bictegravir in milk, without effects on nursing pups.  In animal 
studies it has been shown that tenofovir is excreted in milk.   
 
There is insufficient information on the effects of all the components of Biktarvy in newborns/infants, 
therefore Biktarvy should not be used during breast-feeding. 
 
In order to avoid transmission of HIV to the infant it is recommended that HIV-infected women do not 
breast-feed their infants under any circumstances. 
 
Fertility 
 
No human data on the effect of Biktarvy on fertility are available.  Animal studies indicate no effects 
of bictegravir, emtricitabine or tenofovir alafenamide on mating or fertility (see section 5.3). 
 



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4.7 Effects on ability to drive and use machines 
 
Patients should be informed that dizziness has been reported during treatment with the components of 
Biktarvy (see section 4.8).  
 
4.8 Undesirable effects 
 
Summary of the safety profile 
 
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.  In clinical studies of treatment-naïve patients receiving 
Biktarvy through 144 weeks, the most frequently reported adverse reactions were headache (5%), 
diarrhoea (5%) and nausea (4%). 
 
Tabulated summary of adverse reactions 
 
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). 
 
Table 2: Tabulated list of adverse reactions1 
 
Frequency Adverse reaction 
Blood and lymphatic system disorders 
Uncommon: anaemia2 
Psychiatric disorders 
Common: depression, abnormal dreams 
Uncommon: suicidal behaviour, 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 
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 Phase 3 Biktarvy clinical 
studies in treatment-naïve patients through 144 weeks (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). 
 
Description of selected adverse reactions 
 
Metabolic parameters 
Weight and levels of blood lipids and glucose may increase during antiretroviral therapy (see 
section 4.4). 
 



14 

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). 
 
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). 
 
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 events through Week 144 in 
patients administered Biktarvy in clinical studies. 
 
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 events through Week 144 in Biktarvy clinical studies. 
 
Other special populations 
 
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). 
 
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.  
 
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). 
 



15 

Reporting of suspected adverse reactions 
 
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. 
 
4.9 Overdose 
 
If overdose occurs the patient must be monitored for evidence of toxicity (see section 4.8).  Treatment 
of overdose with Biktarvy consists of general supportive measures including monitoring of vital signs 
as well as observation of the clinical status of the patient. 
 
There is no specific antidote for overdose with Biktarvy.  As bictegravir is highly bound to plasma 
proteins, it is unlikely that it will be significantly removed by hemodialysis or peritoneal dialysis.  
Emtricitabine can be removed by hemodialysis, which removes approximately 30% of the 
emtricitabine dose over a 3-hour dialysis period starting within 1.5 hours of emtricitabine dosing.  
Tenofovir is efficiently removed by hemodialysis with an extraction coefficient of approximately 
54%.  It is not known whether emtricitabine or tenofovir can be removed by peritoneal dialysis.  
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: Antiviral for systemic use; antivirals for treatment of HIV infections, 
combinations, ATC code: J05AR20 
 
Mechanism of action and pharmacodynamic effects 
 
Bictegravir is an integrase strand transfer inhibitor (INSTI) that binds to the integrase active site and 
blocks the strand transfer step of retroviral deoxyribonucleic acid (DNA) integration which is essential 
for the HIV replication cycle.  Bictegravir has activity against HIV-1 and HIV-2. 
 
Emtricitabine is a nucleoside reverse transcriptase inhibitor (NRTI) and analogue of 2’-deoxycytidine.  
Emtricitabine is phosphorylated by cellular enzymes to form emtricitabine triphosphate.  Emtricitabine 
triphosphate inhibits HIV replication through incorporation into viral DNA by the HIV reverse 
transcriptase (RT), which results in DNA chain-termination.  Emtricitabine has activity against HIV-1, 
HIV-2 and HBV. 
 
Tenofovir alafenamide is a nucleotide reverse transcriptase inhibitor (NtRTI) and phosphonamidate 
prodrug of tenofovir (2’-deoxyadenosine monophosphate analogue).  Tenofovir alafenamide is 
permeable into cells and due to increased plasma stability and intracellular activation through 
hydrolysis by cathepsin A, tenofovir alafenamide is more efficient than tenofovir disoproxil in loading 
tenofovir into peripheral blood mononuclear cells (PBMCs) (including lymphocytes and other HIV 
target cells) and macrophages.  Intracellular tenofovir is subsequently phosphorylated to the 
pharmacologically active metabolite tenofovir diphosphate.  Tenofovir diphosphate inhibits HIV 
replication through incorporation into viral DNA by the HIV RT, which results in DNA chain-
termination.  Tenofovir has activity against HIV-1, HIV-2 and HBV.   
 
Antiviral activity in vitro 
 
The antiviral activity of bictegravir against laboratory and clinical isolates of HIV-1 was assessed in 
lymphoblastoid cell lines, PBMCs, primary monocyte/macrophage cells, and CD4+ T-lymphocytes.  
The 50% effective concentration (EC50) values for bictegravir were in the range of < 0.05 to 6.6 nM.  
The protein-adjusted EC95 of bictegravir was 361 nM (0.162 µg/mL) for wild type HIV-1 virus.  
Bictegravir displayed antiviral activity in cell culture against HIV-1 group (M, N, O), including 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


16 

subtypes A, B, C, D, E, F, and G (EC50 values ranged from < 0.05 to 1.71 nM), and activity against 
HIV-2 (EC50 = 1.1 nM). 
 
The antiviral activity of emtricitabine against laboratory and clinical isolates of HIV-1 was assessed in 
lymphoblastoid cell lines, the MAGI CCR5 cell line, and PBMCs.  The EC50 values for emtricitabine 
were in the range of 0.0013 to 0.64 µM.  Emtricitabine displayed antiviral activity in cell culture 
against HIV-1 clades A, B, C, D, E, F, and G (EC50 values ranged from 0.007 to 0.075 µM) and 
showed activity against HIV-2 (EC50 values ranged from 0.007 to 1.5 µM). 
 
The antiviral activity of tenofovir alafenamide against laboratory and clinical isolates of HIV-1 
subtype B was assessed in lymphoblastoid cell lines, PBMCs, primary monocyte/macrophage cells, 
and CD4+ T-lymphocytes.  The EC50 values for tenofovir alafenamide were in the range of 2.0 to 
14.7 nM.  Tenofovir alafenamide displayed antiviral activity in cell culture against all HIV-1 groups 
(M, N, O), including subtypes A, B, C, D, E, F, and G (EC50 values ranged from 0.10 to 12.0 nM) and 
activity against HIV-2 (EC50 values ranged from 0.91 to 2.63 nM). 
 
Resistance 
 
In vitro 
HIV-1 isolates with reduced susceptibility to bictegravir have been selected in cell culture.  In one 
selection, amino acid substitutions M50I and R263K emerged and phenotypic susceptibility to 
bictegravir was reduced 1.3-, 2.2-, and 2.9-fold for M50I, R263K, and M50I + R263K, respectively.  
In a second selection, amino acid substitutions T66I and S153F emerged and phenotypic susceptibility 
to bictegravir was shifted 0.4-, 1.9-, and 0.5-fold for T66I, S153F, and T66I + S153F, respectively. 
 
HIV-1 isolates with reduced susceptibility to emtricitabine have been selected in cell culture and had 
M184V/I mutations in HIV-1 RT. 
 
HIV-1 isolates with reduced susceptibility to tenofovir alafenamide have been selected in cell culture 
and had the K65R mutation in HIV-1 RT; in addition, a K70E mutation in HIV-1 RT has been 
transiently observed.  HIV-1 isolates with the K65R mutation have low level reduced susceptibility to 
abacavir, emtricitabine, tenofovir, and lamivudine.  In vitro drug resistance selection studies with 
tenofovir alafenamide have shown no development of high-level resistance after extended culture. 
 
In treatment-naïve (Studies GS-US-380-1489 and GS-US-380-1490) and virologically-suppressed 
patients (Studies GS-US-380-1844 and GS-US-380-1878), no patient receiving Biktarvy had HIV-1 
with treatment-emergent genotypic or phenotypic resistance to bictegravir, emtricitabine, or tenofovir 
alafenamide in the final resistance analysis population (n = 11) with HIV-1 RNA ≥ 200 copies/mL at 
the time of confirmed virologic failure, at Week 48 or early study drug discontinuation (all studies) or 
at Week 96 or Week 144 (treatment naïve studies only).  At the time of study entry, one treatment-
naïve patient had pre-existing INSTI resistance-associated mutations Q148H + G140S and had HIV-1 
RNA < 50 copies/mL at Week 4 through Week 144. In addition, 6 patients had the pre-existing INSTI 
resistance-associated mutation T97A; all had HIV-1 RNA < 50 copies/mL at Week 144 or the last 
visit. 
 
Cross-resistance  
The susceptibility of bictegravir was tested against 64 INSTI-resistant clinical isolates (20 with single 
substitutions and 44 with 2 or more substitutions).  Of these, all single and double mutant isolates 
lacking Q148H/K/R and 10 of 24 isolates with Q148H/K/R with additional INSTI resistance 
associated substitutions had ≤ 2.5-fold reduced susceptibility to bictegravir; > 2.5-fold reduced 
susceptibility to bictegravir was found for 14 of the 24 isolates that contained G140A/C/S and 
Q148H/R/K substitutions in integrase.  Of those, 9 of the 14 isolates had additional mutations at 
L74M, T97A, or E138A/K.  In a separate study, site-directed mutants with G118R and T97A+G118R 
had 3.4- and 2.8-fold reduced susceptibility to bictegravir, respectively.  The relevance of these 
in vitro cross-resistance data remains to be established in clinical practice. 
 



17 

Bictegravir demonstrated equivalent antiviral activity against 5 nonnucleoside reverse transcriptase 
inhibitor (NNRTI)-resistant, 3 NRTI-resistant, and 4 protease inhibitor (PI)-resistant HIV-1 mutant 
clones compared with the wild-type strain. 
 
Emtricitabine-resistant viruses with the M184V/I substitution were cross-resistant to lamivudine, but 
retained sensitivity to didanosine, stavudine, tenofovir, and zidovudine.   
 
The K65R and K70E mutations result in reduced susceptibility to abacavir, didanosine, lamivudine, 
emtricitabine, and tenofovir, but retain sensitivity to zidovudine.  Multinucleoside resistant HIV-1 
with a T69S double insertion mutation or with a Q151M mutation complex including K65R showed 
reduced susceptibility to tenofovir alafenamide.   
 
Clinical data 
 
The efficacy and safety of Biktarvy in HIV-1 infected, treatment-naïve adults are based on 48-week 
and 144-week data from two randomised, double-blind, active-controlled studies, GS-US-380-1489 
(n = 629) and GS-US-380-1490 (n = 645). 
 
The efficacy and safety of Biktarvy in virologically-suppressed HIV-1 infected adults are based on 
48-week data from a randomised, double-blind, active-controlled study, GS-US-380-1844 (n = 563); 
and a randomised, open-label, active-controlled study, GS-US-380-1878 (n = 577). 
 
HIV-1 infected, treatment-naïve patients 
In Study GS-US-380-1489, patients were randomised in a 1:1 ratio to receive either 
bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) (n = 314) or 
abacavir/dolutegravir/lamivudine (600/50/300 mg) (n = 315) once daily.  In Study GS-US-380-1490, 
patients were randomised in a 1:1 ratio to receive either B/F/TAF (n = 320) or 
dolutegravir + emtricitabine/tenofovir alafenamide (50+200/25 mg) (n = 325) once daily. 
 
In Studies GS-US-380-1489 and GS-US-380-1490, the mean age was 35 years (range 18-77), 89% 
were male, 58% were White, 33% were Black, and 3% were Asian.  Twenty-four percent of patients 
identified as Hispanic/Latino.  The prevalence of different subtypes was comparable across all three 
treatment groups, with subtype B predominant in both groups; 11% were non-B subtypes.  The mean 
baseline plasma HIV-1 RNA was 4.4 log10 copies/mL (range 1.3-6.6).  The mean baseline CD4+ cell 
count was 460 cells/mm3 (range 0-1,636) and 11% had CD4+ cell counts less than 200 cells/mm3.  
Eighteen percent of patients had baseline viral loads greater than 100,000 copies/mL.  In both studies, 
patients were stratified by baseline HIV-1 RNA (less than or equal to 100,000 copies/mL, greater than 
100,000 copies/mL to less than or equal to 400,000 copies/mL, or greater than 400,000 copies/mL), by 
CD4+ cell count (less than 50 cells/µL, 50-199 cells/µL, or greater than or equal to 200 cells/µL), and 
by region (US or ex-US). 
 
Treatment outcomes of Studies GS-US-380-1489 and GS-US-380-1490 through Weeks 48 and 144 
are presented in Table 3. 
 
Table 3: Pooled virologic outcomes of Studies GS-US-380-1489 and GS-US-380-1490 at 
Weeks 48a and 144b 
 
 Week 48  Week 144  

 

B/F/TAF 
(n = 634)c 

ABC/DTG/
3TC 

(n = 315)d 

DTG + 
F/TAF 

(n = 325)e 

B/F/TAF 
(n = 634)c 

ABC/DTG/
3TC 

(n = 315)d 

DTG + 
F/TAF 

(n = 325)e 
HIV-1 RNA 
< 50 copies/mL  

91% 93% 93% 82% 84% 84% 

Treatment 
difference 
(95% CI) B/F/TAF 
vs Comparator 

- -2.1% 
(-5.9% to 

1.6%) 

-1.9% 
(-5.6% to 

1.8%) 

 
- 

-2.7% 
(-7.8% to 

2.4%) 

-1.9% 
(-7.0% to 

3.1%) 



18 

 Week 48  Week 144  

 

B/F/TAF 
(n = 634)c 

ABC/DTG/
3TC 

(n = 315)d 

DTG + 
F/TAF 

(n = 325)e 

B/F/TAF 
(n = 634)c 

ABC/DTG/
3TC 

(n = 315)d 

DTG + 
F/TAF 

(n = 325)e 
HIV-1 RNA 
≥ 50 copies/mLf 

3% 3% 1% 3% 3% 3% 

No virologic data at 
week 48 or 144 
window 

6% 4% 6% 16% 13% 13% 

Discontinued 
study drug due to 
AE or deathg 

<1% 1% 1% 2% 2% 3% 

Discontinued 
study drug due to 
other reasons and 
last available HIV-
1 RNA 
< 50 copies/mLh 

4% 3% 4% 13% 11% 9% 

Missing data 
during window but 
on study drug 

2% <1% 1% 1% <1% 1% 

Proportion (%) of 
patients with 
HIV-1 RNA 
< 50 copies/mL by 
subgroup 

      

By baseline viral load 
≤ 100,000 copies/
mL 
> 100,000 copies/
mL 

 
92% 
87% 

 
94% 
90% 

 
93% 
94% 

 
82% 
79% 

 
86% 
74% 

 
84% 
83% 

By baseline CD4+ cell 
count 

< 200 cells/mm3 
≥ 200 cells/mm3 

 
90% 
91% 

 
81% 
94% 

 
100% 
92% 

 
80% 
82% 

 
69% 
86% 

 
91% 
83% 

HIV-1 RNA 
< 20 copies/mL 

85% 87% 87% 78% 82% 79% 

ABC = abacavir DTG = dolutegravir 3TC = lamivudine F/TAF = emtricitabine/tenofovir alafenamide 
a Week 48 window was between Day 295 and 378 (inclusive). 
b Week 144 window was between Day 967 and 1050 (inclusive). 
c Pooled from Study GS-US-380-1489 (n = 314) and Study GS-US-380-1490 (n = 320). 
d Study GS-US-380-1489. 
e Study GS-US-380-1490. 
f Includes patients who had ≥ 50 copies/mL in the Week 48 or 144 window; patients who discontinued early due to lack or 

loss of efficacy (n = 0); patients who discontinued for reasons other than an adverse event (AE), death or lack or loss of 
efficacy (B/F/TAF n = 12 and 15; ABC/DTG/3TC n = 2 and 7; DTG+F/TAF n = 3 and 6, at Weeks 48 and 144, 
respectively) and at the time of discontinuation had a viral value of ≥ 50 copies/mL. 

g Includes patients who discontinued due to AE or death at any time point from Day 1 through the time window if this 
resulted in no virologic data on treatment during the specified window. 

h Includes patients who discontinued for reasons other than an AE, death or lack or loss of efficacy, e.g. withdrew consent, 
loss to follow-up, etc. 

 
B/F/TAF was non-inferior in achieving HIV-1 RNA < 50 copies/mL at both Weeks 48 and 144 when 
compared to abacavir/dolutegravir/lamivudine and to dolutegravir + emtricitabine/tenofovir 
alafenamide, respectively.  Treatment outcomes between treatment groups were similar across 
subgroups by age, sex, race, baseline viral load, baseline CD4+ cell count, and region. 
 
In Studies GS-US-380-1489 and GS-US-380-1490, the mean increase from baseline in CD4+ cell 
count at Week 144 was 288, 317, and 289 cells/mm3 in the pooled B/F/TAF, 
abacavir/dolutegravir/lamivudine, and dolutegravir + emtricitabine/tenofovir alafenamide groups, 
respectively. 
 



19 

HIV-1 infected, virologically -suppressed patients 
In Study GS-US-380-1844, the efficacy and safety of switching from a regimen of 
dolutegravir + abacavir/lamivudine or abacavir/dolutegravir/lamivudine to B/F/TAF were evaluated in 
a randomised, double-blind study of virologically-suppressed (HIV-1 RNA < 50 copies/mL) HIV-1 
infected adults (n = 563).  Patients must have been stably suppressed (HIV-1 RNA < 50 copies/mL) on 
their baseline regimen for at least 3 months prior to study entry.  Patients were randomised in a 1:1 
ratio to either switch to B/F/TAF at baseline (n = 282), or stay on their baseline antiretroviral regimen 
(n = 281).  Patients had a mean age of 45 years (range 20-71), 89% were male, 73% were White, and 
22% were Black.  Seventeen percent of patients identified as Hispanic/Latino.  The prevalence of 
different HIV-1 subtypes was comparable between treatment groups, with subtype B predominant in 
both groups; 5% were non-B subtypes.  The mean baseline CD4+ cell count was 723 cells/mm3 
(range 124-2,444).  
 
In Study GS-US-380-1878, the efficacy and safety of switching from either abacavir/lamivudine or 
emtricitabine/tenofovir disoproxil fumarate (200/300 mg) plus atazanavir or darunavir (boosted by 
either cobicistat or ritonavir) to B/F/TAF were evaluated in a randomised, open-label study of 
virologically-suppressed HIV-1 infected adults (n = 577).  Patients must have been stably suppressed 
on their baseline regimen for at least 6 months and must not have been previously treated with any 
INSTI.  Patients were randomised in a 1:1 ratio to either switch to B/F/TAF (n = 290), or stay on their 
baseline antiretroviral regimen (n = 287).  Patients had a mean age of 46 years (range 20-79), 83% 
were male, 66% were White, and 26% were Black.  Nineteen percent of patients identified as 
Hispanic/Latino.  The mean baseline CD4+ cell count was 663 cells/mm3 (range 62-2,582).  The 
prevalence of different subtypes was comparable across treatment groups, with subtype B predominant 
in both groups; 11% were non-B subtypes.  Patients were stratified by prior treatment regimen.  At 
screening, 15% of patients were receiving abacavir/lamivudine plus atazanavir or darunavir (boosted 
by either cobicistat or ritonavir) and 85% of patients were receiving emtricitabine/tenofovir disoproxil 
fumarate plus atazanavir or darunavir (boosted by either cobicistat or ritonavir).  
 
Treatment outcomes of Studies GS-US-380-1844 and GS-US-380-1878 through Week 48 are 
presented in Table 4. 
 
Table 4: Virologic outcomes of Studies GS-US-380-1844 and GS-US-380-1878 at Week 48a 
 
 Study GS-US-380-1844 Study GS-US-380-1878 

 

B/F/TAF 
(n = 282) 

ABC/DTG/3TC 
(n = 281) 

B/F/TAF 
(n = 290) 

Baseline ATV- 
or DRV-based 

regimen 
(n = 287) 

HIV-1 RNA < 50 copies/mL  94% 95% 92% 89% 
Treatment difference (95% CI) -1.4% (-5.5% to 2.6%) 3.2% (-1.6% to 8.2%) 

HIV-1 RNA ≥ 50 copies/mLb 1% < 1% 2% 2% 
Treatment difference (95% CI) 0.7% (-1.0% to 2.8%) 0.0% (-2.5% to 2.5%) 

No virologic data at Week 48 
window 5% 5% 6% 9% 

Discontinued study drug due to 
AE or death and last available 
HIV-1 RNA < 50 copies/mL 

2% 1% 1% 1% 

Discontinued study drug due to 
other reasons and last available 
HIV-1 RNA < 50 copies/mLc 

2% 3% 3% 7% 

Missing data during window but 
on study drug 2% 1% 2% 2% 

ABC = abacavir ATV = atazanavir DRV = darunavir DTG = dolutegravir 3TC = lamivudine 
a Week 48 window was between Day 295 and 378 (inclusive). 
b Includes patients who had ≥ 50 copies/mL in the Week 48 window; patients who discontinued early due to lack or loss of 

efficacy; patients who discontinued for reasons other than lack or loss of efficacy and at the time of discontinuation had a 
viral value of ≥ 50 copies/mL. 

c Includes patients who discontinued for reasons other than an AE, death or lack or loss of efficacy, e.g. withdrew consent, 
loss to follow-up, etc. 



20 

 
B/F/TAF was non-inferior to the control regimen in both studies.  Treatment outcomes between 
treatment groups were similar across subgroups by age, sex, race, and region. 
 
In GS-US-380-1844, the mean change from baseline in CD4+ cell count at Week 48 was 
-31 cells/mm3 in patients who switched to B/F/TAF and 4 cells/mm3 in patients who stayed on 
abacavir/dolutegravir/lamivudine.  In GS-US-380-1878, the mean change from baseline in CD4+ cell 
count at Week 48 was 25 cells/mm3 in patients who switched to B/F/TAF and 0 cells/mm3 in patients 
who stayed on their baseline regimen. 
 
Patients co-infected with HIV and HBV 
The number of patients co-infected with HIV and HBV treated with B/F/TAF is limited.  In 
Study GS-US-380-1490, 8 patients with HIV/HBV co-infection at baseline were randomised to 
receive B/F/TAF. At Week 48, 7 patients were HBV suppressed (HBV DNA < 29 IU/mL) and had 
HIV-1 RNA < 50 copies/mL.  One patient had missing HBV DNA data at Week 48.  At Week 144, 5 
patients were HBV suppressed and had HIV-1 RNA < 50 copies/mL.  Three patients had missing 
HBV DNA data at Week 144 (1 lost to follow-up from Week 48, 1 lost to follow-up after Week 72, 
and 1 lost to follow-up after Week 120). 
 
In Study GS-US-380-1878, at Week 48, 100% (8/8) of the patients co-infected with HIV/HBV at 
baseline in the B/F/TAF arm maintained HBV DNA < 29 IU/mL (missing = excluded analysis) and 
HIV RNA < 50 copies/mL. 
 
Paediatric population 
 
The European Medicines Agency has deferred the obligation to submit the results of studies with 
Biktarvy in one or more subsets of the paediatric population in the treatment of human 
HIV-1 infection (see section 4.2 for information on paediatric use). 
 
5.2 Pharmacokinetic properties 
 
Absorption 
 
Bictegravir is absorbed following oral administration with peak plasma concentrations occurring at 
2.0-4.0 hours after administration of B/F/TAF.  Relative to fasting conditions, the administration of 
B/F/TAF with either a moderate fat (~600 kcal, 27% fat) or high fat meal (~800 kcal, 50% fat) 
resulted in an increase in bictegravir AUC (24%).  This modest change is not considered clinically 
meaningful and B/F/TAF can be administered with or without food. 
 
Following oral administration of B/F/TAF with or without food in HIV-1 infected adults, the multiple 
dose mean (CV%) pharmacokinetic parameters of bictegravir were Cmax = 6.15 µg/mL (22.9%), 
AUCtau = 102 µg•h/mL (26.9%), and Ctrough = 2.61 µg/mL (35.2%). 
 
Emtricitabine is rapidly and extensively absorbed following oral administration with peak plasma 
concentrations occurring at 1.5-2.0 hours after administration of B/F/TAF.  The mean absolute 
bioavailability of emtricitabine from 200 mg hard capsules was 93%.  Emtricitabine systemic exposure 
was unaffected when emtricitabine was administered with food and B/F/TAF can be administered with 
or without food. 
 
Following oral administration of B/F/TAF with or without food in HIV-1 infected adults, the multiple 
dose mean (CV%) pharmacokinetic parameters of emtricitabine were Cmax = 2.13 µg/mL (34.7%), 
AUCtau = 12.3 µg•h/mL (29.2%), and Ctrough = 0.096 µg/mL (37.4%). 
 
Tenofovir alafenamide is rapidly absorbed following oral administration with peak plasma 
concentrations occurring at 0.5-2.0 hours after administration of B/F/TAF.  Relative to fasting 
conditions, the administration of tenofovir alafenamide with a moderate fat meal (~600 kcal, 27% fat) 
and a high fat meal (~800 kcal, 50% fat) resulted in an increase in AUClast by 48% and 63%, 



21 

respectively.  These modest changes are not considered clinically meaningful and B/F/TAF can be 
administered with or without food.  
 
Following oral administration of B/F/TAF with or without food in HIV-1 infected adults, the multiple 
dose mean (CV%) pharmacokinetic parameters of tenofovir alafenamide were Cmax = 0.121 µg/mL 
(15.4%), and AUCtau = 0.142 µg•h/mL (17.3%). 
 
Distribution 
 
In vitro binding of bictegravir to human plasma proteins was > 99% (free fraction ~0.25%).  The 
in vitro human blood to plasma bictegravir concentration ratio was 0.64. 
 
In vitro binding of emtricitabine to human plasma proteins was < 4% and independent of 
concentration over the range of 0.02 to 200 µg/mL.  At peak plasma concentration, the mean plasma to 
blood drug concentration ratio was ~1.0 and the mean semen to plasma drug concentration ratio was 
~4.0. 
 
In vitro binding of tenofovir to human plasma proteins is < 0.7% and is independent of concentration 
over the range of 0.01-25 µg/mL.  Ex vivo binding of tenofovir alafenamide to human plasma proteins 
in samples collected during clinical studies was approximately 80%.   
 
Biotransformation 
 
Metabolism is the major clearance pathway for bictegravir in humans.  In vitro phenotyping studies 
showed that bictegravir is primarily metabolised by CYP3A and UGT1A1.  Following a single dose 
oral administration of [14C]-bictegravir, ~60% of the dose from faeces included unchanged parent, 
desfluoro-hydroxy-BIC-cysteine-conjugate, and other minor oxidative metabolites.  Thirty-five 
percent of the dose was recovered from urine and consisted primarily of the glucuronide of bictegravir 
and other minor oxidative metabolites and their phase II conjugates.  Renal clearance of the unchanged 
parent was minimal. 
 
Following administration of [14C]-emtricitabine, complete recovery of the emtricitabine dose was 
achieved in urine (~86%) and faeces (~14%).  Thirteen percent of the dose was recovered in the urine 
as three putative metabolites.  The biotransformation of emtricitabine includes oxidation of the thiol 
moiety to form the 3’-sulfoxide diastereomers (~9% of dose) and conjugation with glucuronic acid to 
form 2’-O-glucuronide (~4% of dose).  No other metabolites were identifiable. 
 
Metabolism is a major elimination pathway for tenofovir alafenamide in humans, accounting for 
> 80% of an oral dose.  In vitro studies have shown that tenofovir alafenamide is metabolised to 
tenofovir (major metabolite) by cathepsin A in PBMCs (including lymphocytes and other HIV target 
cells) and macrophages; and by carboxylesterase-1 in hepatocytes.  In vivo, tenofovir alafenamide is 
hydrolysed within cells to form tenofovir (major metabolite), which is phosphorylated to the active 
metabolite, tenofovir diphosphate.  In human clinical studies, a 25 mg oral dose of tenofovir 
alafenamide resulted in tenofovir diphosphate concentrations > 4-fold higher in PBMCs and > 90% 
lower concentrations of tenofovir in plasma as compared to a 245 mg oral dose of tenofovir disoproxil. 
 
Elimination 
 
Bictegravir is primarily eliminated by hepatic metabolism.  Renal excretion of intact bictegravir is a 
minor pathway (~1% of dose).  The plasma bictegravir half-life was 17.3 hours.  
 
Emtricitabine is primarily excreted by the kidneys by both glomerular filtration and active tubular 
secretion.  The plasma emtricitabine half-life was approximately 10 hours. 
 
Tenofovir alafenamide is eliminated following metabolism to tenofovir.  Tenofovir alafenamide and 
tenofovir have a median plasma half-life of 0.51 and 32.37 hours, respectively.  Tenofovir is 



22 

eliminated by the kidneys by both glomerular filtration and active tubular secretion.  Renal excretion 
of intact tenofovir alafenamide is a minor pathway with less than 1% of the dose eliminated in urine.   
 
Linearity 
 
The multiple dose pharmacokinetics of bictegravir are dose proportional over the dose range of 25 to 
100 mg.  The multiple dose pharmacokinetics of emtricitabine are dose proportional over the dose 
range of 25 to 200 mg.  Tenofovir alafenamide exposures are dose proportional over the dose range of 
8 mg to 125 mg. 
 
Other special populations 
 
Renal impairment: 
Severe Renal Impairment (estimated creatinine clearance ≥ 15 and < 30 mL/minute) 
No clinically relevant differences in bictegravir, tenofovir alafenamide, or tenofovir pharmacokinetics 
were observed between healthy subjects and subjects with severe renal impairment (estimated 
CrCl ≥ 15 mL/min and < 30 mL/min) in Phase 1 Studies.  In a separate Phase 1 study of emtricitabine 
alone, mean systemic emtricitabine exposure was higher in patients with severe renal impairment 
(CrCl < 30 mL/min) (33.7 µg•h/mL) than in subjects with normal renal function (11.8 µg•h/mL).  The 
safety of Biktarvy has not been established in subjects with estimated creatinine 
clearance ≥ 15 mL/min and < 30 mL/min. 
 
End Stage Renal Disease (estimated creatinine clearance < 15 mL/minute) 
Exposures of emtricitabine and tenofovir in 12 patients with end stage renal disease (estimated 
CrCl < 15 mL/min) on chronic haemodialysis who received emtricitabine + tenofovir alafenamide in 
combination with elvitegravir + cobicistat as a fixed dose combination tablet in Study GS-US-292-
1825 were significantly higher than in patients with normal renal function.  No clinically relevant 
differences in tenofovir alafenamide pharmacokinetics were observed in patients with end stage renal 
disease on chronic haemodialysis as compared to those with normal renal function.  In the extension 
phase of Study GS-US-292-1825, lower bictegravir Ctrough was observed in patients with end stage 
renal disease who received Biktarvy compared to patients with normal renal function, but this 
difference was not considered clinically relevant.  No additional adverse reactions were identified in 
patients with end stage renal disease on chronic haemodialysis in this study (see section 4.8). 
 
There are no pharmacokinetic data on bictegravir, emtricitabine or tenofovir alafenamide in patients 
with end stage renal disease (estimated CrCl < 15 mL/min) not on chronic haemodialysis.  The safety 
of Biktarvy has not been established in these patients. 
 
Hepatic impairment 
Clinically relevant changes in the pharmacokinetics of bictegravir were not observed in subjects with 
moderate hepatic impairment.  The pharmacokinetics of emtricitabine have not been studied in 
subjects with hepatic impairment; however, emtricitabine is not significantly metabolised by liver 
enzymes, so the impact of liver impairment should be limited.  Clinically relevant changes in the 
pharmacokinetics of tenofovir alafenamide or its metabolite tenofovir were not observed in patients 
with mild, moderate, or severe hepatic impairment. 
 
Age, gender and race 
Pharmacokinetics of bictegravir, emtricitabine, and tenofovir have not been fully evaluated in the 
elderly (≥ 65 years of age).  Population analyses using pooled pharmacokinetic data from adult studies 
did not identify any clinically relevant differences due to age, gender or race on the exposures of 
bictegravir, emtricitabine, or tenofovir alafenamide. 
 
5.3 Preclinical safety data 
 
Bictegravir was not mutagenic or clastogenic in conventional genotoxicity assays. 

Bictegravir was not carcinogenic in a 6-month rasH2 transgenic mouse study (at doses of up to 
100 mg/kg/day in males and 300 mg/kg/day in females, which resulted in exposures of approximately 



23 

15 and 23 times, in males and females, respectively, the exposure in humans at the recommended 
human dose) nor in a 2-year rat study (at doses of up to 300 mg/kg/day, which resulted in exposures of 
approximately 31 times the exposure in humans).  
 
Studies of bictegravir in monkeys revealed the liver as the primary target organ of toxicity.  
Hepatobiliary toxicity was described in a 39-week study at a dosage of 1,000 mg/kg/day, which 
resulted in exposures of approximately 16 times the exposure in humans at the recommended human 
dose, and was partially reversible after a 4-week recovery period.  
 
Studies in animals with bictegravir have shown no evidence of teratogenicity or an effect on 
reproductive function.  In offspring from rat and rabbit dams treated with bictegravir during 
pregnancy, there were no toxicologically significant effects on developmental endpoints. 
 
Non-clinical data on emtricitabine reveal no special hazard for humans based on conventional studies 
of safety pharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential, toxicity to 
reproduction and development.  Emtricitabine has demonstrated low carcinogenic potential in mice 
and rats. 
 
Non-clinical studies of tenofovir alafenamide in rats and dogs revealed bone and kidney as the primary 
target organs of toxicity.  Bone toxicity was observed as reduced bone mineral density in rats and dogs 
at tenofovir exposures at least 43 times greater than those expected after administration of B/F/TAF.  
A minimal infiltration of histiocytes was present in the eye in dogs at tenofovir alafenamide and 
tenofovir exposures of approximately 14 and 43 times greater, respectively, than those expected after 
administration of B/F/TAF. 
 
Tenofovir alafenamide was not mutagenic or clastogenic in conventional genotoxicity assays. 
 
Because there is a lower tenofovir exposure in rats and mice after the administration of tenofovir 
alafenamide compared to tenofovir disoproxil, carcinogenicity studies and a rat peri-postnatal study 
were conducted only with tenofovir disoproxil.  No special hazard for humans was revealed in 
conventional studies of carcinogenic potential and toxicity to reproduction and development.  
Reproductive toxicity studies in rats and rabbits showed no effects on mating, fertility, pregnancy or 
foetal parameters.  However, tenofovir disoproxil reduced the viability index and weight of pups in a 
peri-postnatal toxicity study at maternally toxic doses. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Tablet core 
Microcrystalline cellulose 
Croscarmellose sodium 
Magnesium stearate 
 
Film-coating 
Polyvinyl alcohol 
Titanium dioxide (E171) 
Macrogol 
Talc 
Iron oxide red (E172) 
Iron oxide black (E172) 
 
6.2 Incompatibilities 
 
Not applicable. 
 



24 

6.3 Shelf life 
 
3 years 
 
6.4 Special precautions for storage 
 
Store in the original package in order to protect from moisture.  Keep the bottle tightly closed.  Do not 
use if seal over bottle opening is broken or missing. 
 
6.5 Nature and contents of container 
 
White, high density polyethylene (HDPE) bottle with a polypropylene continuous-thread, 
child-resistant cap, lined with an induction activated aluminium foil liner containing 30 film-coated 
tablets.  Each bottle contains silica gel desiccant and polyester coil. 
 
The following pack sizes are available: outer cartons containing 1 bottle of 30 film-coated tablets and 
outer cartons containing 90 (3 bottles of 30) film-coated tablets. 
 
Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal 
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Gilead Sciences Ireland UC 
Carrigtohill 
County Cork, T45 DP77 
Ireland 
 
 
8. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/18/1289/001 
EU/1/18/1289/002 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 21 June 2018 
 
 
10. DATE OF REVISION OF THE TEXT 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu. 

http://www.ema.europa.eu/


25 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX II 
 

A. MANUFACTURER(S) RESPONSIBLE FOR BATCH 
RELEASE 

 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY 

AND USE 
 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE 

MARKETING AUTHORISATION 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO 

THE SAFE AND EFFECTIVE USE OF THE MEDICINAL 
PRODUCT 



26 

A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE 
 
Name and address of the manufacturer(s) responsible for batch release 
 
Gilead Sciences Ireland UC 
IDA Business & Technology Park 
Carrigtohill 
County Cork 
Ireland 
 
 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 
 
Medicinal product subject to restricted medical prescription (see Annex I: Summary of Product 
Characteristics, section 4.2). 
 
 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 
 
• Periodic safety update reports (PSURs) 
 
The requirements for submission of PSURs for this medicinal product are set out in the list of Union 
reference dates (EURD list) provided for under Article 107c(7) of Directive 2001/83/EC and any 
subsequent updates published on the European medicines web-portal. 
 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 
 
• Risk management plan (RMP) 
 
The marketing authorisation holder (MAH) shall perform the required pharmacovigilance activities 
and interventions detailed in the agreed RMP presented in Module 1.8.2 of the marketing authorisation 
and any agreed subsequent updates of the RMP. 
 
An updated RMP should be submitted: 
• At the request of the European Medicines Agency; 
• Whenever the risk management system is modified, especially as the result of new information 

being received that may lead to a significant change to the benefit/risk profile or as the result of 
an important (pharmacovigilance or risk minimisation) milestone being reached. 



27 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 



28 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 



29 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING AND THE IMMEDIATE 
PACKAGING 
 
BOTTLE AND CARTON LABELLING 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Biktarvy 50 mg/200 mg/25 mg film-coated tablets 
bictegravir/emtricitabine/tenofovir alafenamide 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each film-coated tablet contains bictegravir sodium equivalent to 50 mg of bictegravir, 200 mg of 
emtricitabine and tenofovir alafenamide fumarate equivalent to 25 mg of tenofovir alafenamide. 
 
 
3. LIST OF EXCIPIENTS 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
30 film-coated tablets 
 
90 (3 bottles of 30) film-coated tablets 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
 
Oral use 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in the original package in order to protect from moisture.  Keep the bottle tightly closed. 
 
 



30 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Gilead Sciences Ireland UC 
Carrigtohill 
County Cork, T45 DP77 
Ireland 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/18/1289/001 30 film-coated tablets 
EU/1/18/1289/002 90 (3 bottles of 30) film-coated tablets 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Biktarvy [Outer packaging only] 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. [Outer packaging only] 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC {number} 
SN {number} 
NN {number} 
[Outer packaging only] 



31 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 



32 

Package leaflet: Information for the user 
 

Biktarvy 50 mg/200 mg/25 mg film-coated tablets 
bictegravir/emtricitabine/tenofovir alafenamide 

 
This medicine is subject to additional monitoring.  This will allow quick identification of new 

safety information.  You can help by reporting any side effects you may get.  See the end of section 4 
for how to report side effects. 
 
Read all of this leaflet carefully before you start taking this medicine because it contains 
important information for you. 
- Keep this leaflet.  You may need to read it again. 
- If you have any further questions, ask your doctor or pharmacist. 
- This medicine has been prescribed for you only.  Do not pass it on to others.  It may harm them, 

even if their signs of illness are the same as yours. 
- If you get any side effects, talk to your doctor or pharmacist.  This includes any possible side 

effects not listed in this leaflet.  See section 4. 
 
What is in this leaflet 
 
1. What Biktarvy is and what it is used for 
2. What you need to know before you take Biktarvy 
3. How to take Biktarvy 
4. Possible side effects 
5. How to store Biktarvy 
6. Contents of the pack and other information 
 
 
1. What Biktarvy is and what it is used for 
 
Biktarvy contains three active substances: 
• bictegravir, an antiretroviral medicine known as an integrase strand transfer inhibitor (INSTI) 
• emtricitabine, an antiretroviral medicine of a type known as a nucleoside reverse transcriptase 

inhibitor (NRTI) 
• tenofovir alafenamide, an antiretroviral medicine of a type known as a nucleotide reverse 

transcriptase inhibitor (NtRTI) 
 
Biktarvy is a single tablet for the treatment of human immunodeficiency virus 1 (HIV-1) infection in 
adults. 
 
Biktarvy reduces the amount of HIV in your body.  This will improve your immune system and reduce 
the risk of developing illnesses linked to HIV infection. 
 
 
2. What you need to know before you take Biktarvy 
 
Do not take Biktarvy 
 
• If you are allergic to bictegravir, emtricitabine, tenofovir alafenamide or any of the other 

ingredients of this medicine (listed in section 6). 
 
• If you are currently taking any of the following medicines: 

- rifampicin used to treat some bacterial infections such as tuberculosis 
- St. John’s wort (Hypericum perforatum), a herbal remedy used for depression and 

anxiety, or products that contain it. 
 
 If any of these apply to you, do not take Biktarvy and tell your doctor immediately. 



33 

 
Warnings and precautions 
 
Talk to your doctor before taking Biktarvy: 
 
• If you have liver problems or a history of liver disease, including hepatitis.  Patients with 

liver disease including chronic hepatitis B or C, who are treated with antiretrovirals, have a 
higher risk of severe and potentially fatal liver complications.  If you have hepatitis B infection, 
your doctor will carefully consider the best treatment regimen for you. 
 

• If you have hepatitis B infection.  Liver problems may become worse after you stop taking 
Biktarvy.  

 Do not stop taking Biktarvy if you have hepatitis B.  Talk to your doctor first.  For more details, see 
section 3, Do not stop taking Biktarvy. 

 
While you are taking Biktarvy 
 
Once you start taking Biktarvy, look out for: 
 
• Signs of inflammation or infection 
• Joint pain, stiffness or bone problems 
 
 If you notice any of these symptoms, tell your doctor immediately.  For more information see 

section 4, Possible side effects. 
 
Although kidney problems have not been observed with Biktarvy, there is a possibility that you may 
experience kidney problems when taking Biktarvy over a long period of time. 
 
You can still pass on HIV when taking this medicine, although the risk is lowered by effective 
antiretroviral therapy.  Discuss with your doctor the precautions needed to avoid infecting other 
people.  This medicine is not a cure for HIV infection.  While taking Biktarvy you may still develop 
infections or other illnesses associated with HIV infection. 
 
Children and adolescents 
 
Do not give this medicine to children and adolescents under 18 years of age.  The use of Biktarvy 
in children and adolescents under 18 years of age has not yet been studied. 
 
Other medicines and Biktarvy 
 
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 
medicines.  Biktarvy may interact with other medicines.  As a result, the amounts of Biktarvy or other 
medicines in your blood may change.  This may stop your medicines from working properly, or may 
make any side effects worse.  In some cases, your doctor may need to adjust your dose or check your 
blood levels. 
 
Medicines that must never be taken with Biktarvy: 
• rifampicin used to treat some bacterial infections such as tuberculosis 
• St. John’s wort (Hypericum perforatum), a herbal remedy used for depression and anxiety, or 

products that contain it. 
 
 If you are taking any of these medicines, do not take Biktarvy and tell your doctor immediately. 
 



34 

Talk to your doctor if you are taking: 
 
• medicines used for treating HIV and/or hepatitis B, containing: 

- adefovir dipivoxil, atazanavir, bictegravir, emtricitabine, lamivudine, tenofovir 
alafenamide, or tenofovir disoproxil 

• antibiotics used to treat bacterial infections, containing: 
- azithromycin, clarithromycin, rifabutin or rifapentine 

• anticonvulsants used to treat epilepsy, containing: 
- carbamazepine, oxcarbazepine, phenobarbital or phenytoin 

• immunosuppressants used to control your body’s immune response after a transplant, 
containing ciclosporin 

• ulcer-healing medicines containing sucralfate 
 
 Tell your doctor if you are taking any of these medicines.  Do not stop your treatment without 

contacting your doctor. 
 
Get advice from a doctor or pharmacist if you are taking: 
• antacids to treat stomach ulcers, heartburn, or acid reflux, containing aluminium and/or 

magnesium hydroxide  
• mineral supplements or vitamins containing magnesium or iron 
 
 Get advice from your doctor or pharmacist before taking Biktarvy if you are taking any of 

these medicines. 
Antacids and magnesium supplements: you will need to take Biktarvy at least 2 hours before 
antacids or supplements containing aluminium and/or magnesium.  Or you can take Biktarvy with 
food at least 2 hours after. 
Iron supplements: you will need to take Biktarvy at least 2 hours before iron supplements, or you 
can take them together with food. 

 
Pregnancy and breast-feeding 
 
• If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, 

ask your doctor or pharmacist for advice before taking this medicine. 
• Tell your doctor immediately if you become pregnant and ask about the potential benefits and 

risks of your antiretroviral therapy to you and your child. 
 
If you have taken Biktarvy during your pregnancy, your doctor may request regular blood tests and 
other diagnostic tests to monitor the development of your child.  In children whose mothers took 
nucleoside reverse transcriptase inhibitors (NRTIs) during pregnancy, the benefit from the protection 
against HIV outweighed the risk of side effects. 
 
Do not breast-feed during treatment with Biktarvy.  This is because some of the active substances 
in this medicine pass into human breast milk.  It is also recommended that you do not breast-feed to 
avoid passing the virus to the baby in breast milk.  If you really want to breastfeed, talk to your doctor 
first. 
 
Driving and using machines 
 
Biktarvy can cause dizziness.  If you feel dizzy when taking Biktarvy, do not drive and do not use any 
tools or machines. 
 
Biktarvy contains sodium 
 
This medicine contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially 
‘sodium-free’. 
 
 



35 

3. How to take Biktarvy 
 
Always take this medicine exactly as your doctor has told you.  Check with your doctor or pharmacist 
if you are not sure. 
 
The recommended dose is: 
 
Adults: one tablet each day with or without food 
 
Do not chew, crush or split the tablet. 
 
 Get advice from a doctor or pharmacist if you are taking: 
• antacids to treat stomach ulcers, heartburn, or acid reflux, containing aluminium and/or 

magnesium hydroxide 
• mineral supplements or vitamins containing magnesium or iron 
 See section 2 for more information on taking these medicines with Biktarvy. 
 
If you are on dialysis, take your daily dose of Biktarvy following completion of dialysis. 
 
If you take more Biktarvy than you should 
 
If you take more than the recommended dose of Biktarvy you may be at higher risk of side effects of 
this medicine (see section 4, Possible side effects). 
 
Contact your doctor or nearest emergency department immediately for advice.  Keep or take the tablet 
bottle with you so that you can easily describe what you have taken. 
 
If you forget to take Biktarvy 
 
It is important not to miss a dose of Biktarvy. 
 
If you do miss a dose: 
• If you notice within 18 hours of the time you usually take Biktarvy, you must take the tablet as 

soon as possible.  Then take the next dose as usual. 
• If you notice 18 hours or more after the time you usually take Biktarvy, then do not take the 

missed dose.  Wait and take the next dose at your usual time. 
 
If you vomit less than 1 hour after taking Biktarvy, take another tablet.  If you vomit more than 1 hour 
after taking Biktarvy you do not need to take another tablet until your next regularly scheduled tablet. 
 
Do not stop taking Biktarvy 
 
Do not stop taking Biktarvy without talking to your doctor.  Stopping Biktarvy can seriously affect 
how future treatment works.  If Biktarvy is stopped for any reason, speak to your doctor before you 
restart taking Biktarvy tablets. 
 
When your supply of Biktarvy starts to run low, get more from your doctor or pharmacist.  This is 
very important because the amount of virus may start to increase if the medicine is stopped for even a 
short time.  The disease may then become harder to treat. 
 
If you have both HIV infection and hepatitis B, it is especially important not to stop your Biktarvy 
treatment without talking to your doctor first.  You may require blood tests for several months after 
stopping treatment.  In some patients with advanced liver disease or cirrhosis, stopping treatment is 
not recommended as this may lead to worsening of your hepatitis, which may be life-threatening. 
 
 Tell your doctor immediately about new or unusual symptoms after you stop treatment, 

particularly symptoms you associate with hepatitis B infection. 



36 

 
If you have any further questions on the use of this medicine, ask your doctor or pharmacist. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
Possible side effects: tell a doctor immediately 
 
• Any signs of inflammation or infection.  In some patients with advanced HIV infection 

(AIDS) and a history of opportunistic infections (infections that occur in people with a weak 
immune system), signs and symptoms of inflammation from previous infections may occur soon 
after HIV treatment is started.  It is thought that these symptoms are due to an improvement in 
the body’s immune response, enabling the body to fight infections that may have been present 
with no obvious symptoms. 

 
• Autoimmune disorders, when the immune system attacks healthy body tissue, may also occur 

after you start taking medicines for HIV infection.  Autoimmune disorders may occur many 
months after the start of treatment.  Look out for any symptoms of infection or other symptoms 
such as: 
- muscle weakness 
- weakness beginning in the hands and feet and moving up towards the trunk of the body 
- palpitations, tremor or hyperactivity 
 

 If you notice these or any symptoms of inflammation or infection, tell your doctor 
immediately. 

 
Common side effects 
(may affect up to 1 in 10 people) 
• depression 
• abnormal dreams 
• headache 
• dizziness 
• diarrhoea 
• feeling sick (nausea) 
• tiredness (fatigue) 
 
Uncommon side effects 
(may affect up to 1 in 100 people) 
• anaemia 
• vomiting 
• stomach pain 
• problems with digestion resulting in discomfort after meals (dyspepsia) 
• wind (flatulence) 
• swelling of the face, lips, tongue or throat (angioedema) 
• itching (pruritus) 
• rash 
• hives (urticaria) 
• joint pain (arthralgia) 
• suicidal behaviour 
• anxiety 
• sleep disorders 
 



37 

Rare side effects  
(may affect up to 1 in 1000 people) 
• Stevens-Johnson syndrome (SJS) is a serious life-threatening condition which usually starts 

with flu- like symptoms. A few days later other symptoms appear including: 
- Painful red or purple skin that looks burned and peels off 
- Blisters on your skin, mouth, nose, and genitals 
- Red, painful, watery eyes 

 If you have any of these symptoms, stop your medicine immediately and tell your doctor 
straight away. 

Blood tests may also show: 
• higher levels of substances called bilirubin and/or serum creatinine in the blood 
 
 If any of the side effects get serious, tell your doctor. 
 
Other effects that may be seen during HIV treatment 
 
The frequency of the following side effects is not known (frequency cannot be estimated from the 
available data). 
 
• Bone problems.  Some patients taking combination antiretroviral medicines such as Biktarvy 

may develop a bone disease called osteonecrosis (death of bone tissue caused by loss of blood 
supply to the bone).  Taking this type of medicine for a long time, taking corticosteroids, 
drinking alcohol, having a very weak immune system, and being overweight, may be some of 
the many risk factors for developing this disease.  Signs of osteonecrosis are: 
- joint stiffness 
- joint aches and pains (especially of the hip, knee and shoulder) 
- difficulty with movement 

 If you notice any of these symptoms tell your doctor. 
 
During HIV therapy there may be an increase in weight and in levels of blood lipids and glucose.  This 
is partly linked to restored health and life style, and in the case of blood lipids sometimes to the HIV 
medicines themselves.  Your doctor will test for these changes. 
 
Reporting of side effects 
If you get any side effects, talk to your doctor or pharmacist.  This includes any possible side effects 
not listed in this leaflet.  You can also report side effects directly via the national reporting system 
listed in Appendix V.  By reporting side effects you can help provide more information on the safety 
of this medicine. 
 
 
5. How to store Biktarvy 
 
Keep this medicine out of the sight and reach of children. 
 
Do not use this medicine after the expiry date which is stated on the carton and bottle after {EXP}.  
The expiry date refers to the last day of that month. 
 
Store in the original package in order to protect from moisture.  Keep the bottle tightly closed.  Do not 
use if the seal over the bottle opening is broken or missing. 
 
Do not throw away any medicines via wastewater or household waste.  Ask your pharmacist how to 
throw away medicines you no longer use.  These measures will help protect the environment. 
 
 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


38 

6. Contents of the pack and other information 
 
What Biktarvy contains 
 
The active substances are bictegravir, emtricitabine and tenofovir alafenamide.  Each Biktarvy tablet 
contains bictegravir sodium equivalent to 50 mg of bictegravir, 200 mg of emtricitabine and tenofovir 
alafenamide fumarate equivalent to 25 mg of tenofovir alafenamide. 
 
The other ingredients are 
 
Tablet core 
Microcrystalline cellulose, croscarmellose sodium, magnesium stearate. 
 
Film-coating 
Polyvinyl alcohol, titanium dioxide (E171), macrogol, talc, iron oxide red (E172), iron oxide black 
(E172). 
 
What Biktarvy looks like and contents of the pack 
 
Biktarvy film-coated tablets are purplish-brown, capsule-shaped, film-coated tablets debossed on one 
side with “GSI” and “9883” on the other side.  Biktarvy comes in bottles of 30 tablets and in packs 
made up of 3 bottles, each containing 30 tablets.  Each bottle contains a silica gel desiccant that must 
be kept in the bottle to help protect your tablets.  The silica gel desiccant is contained in a separate 
sachet or canister and should not be swallowed. 
 
Not all pack sizes may be marketed. 
 
Marketing Authorisation Holder 
Gilead Sciences Ireland UC 
Carrigtohill 
County Cork, T45 DP77 
Ireland 
 
Manufacturer 
Gilead Sciences Ireland UC 
IDA Business & Technology Park 
Carrigtohill 
County Cork 
Ireland 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien 
Gilead Sciences Belgium SPRL-BVBA 
Tél/Tel: + 32 (0) 24 01 35 50 
 

Lietuva 
Gilead Sciences Poland Sp. z o.o. 
Tel.: + 48 (0) 22 262 8702 
 

България 
Gilead Sciences Ireland UC 
Тел.: + 353 (0) 1 686 1888 
 

Luxembourg/Luxemburg 
Gilead Sciences Belgium SPRL-BVBA 
Tél/Tel: + 32 (0) 24 01 35 50 
 

Česká republika 
Gilead Sciences s.r.o. 
Tel: + 420 (0) 910 871 986 
 

Magyarország 
Gilead Sciences Ireland UC 
Tel.: + 353 (0) 1 686 1888 
 



39 

Danmark 
Gilead Sciences Sweden AB 
Tlf: + 46 (0) 8 5057 1849 
 

Malta 
Gilead Sciences Ireland UC 
Tel: + 353 (0) 1 686 1888 
 

Deutschland 
Gilead Sciences GmbH 
Tel: + 49 (0) 89 899890-0 
 

Nederland 
Gilead Sciences Netherlands B.V. 
Tel: + 31 (0) 20 718 36 98 
 

Eesti 
Gilead Sciences Poland Sp. z o.o. 
Tel.: +48 (0) 22 262 8702 

Norge 
Gilead Sciences Sweden AB 
Tlf: + 46 (0) 8 5057 1849 
 

Ελλάδα 
Gilead Sciences Ελλάς Μ.ΕΠΕ. 
Τηλ: + 30 (0) 210 8930 100 
 

Österreich 
Gilead Sciences GesmbH 
Tel: + 43 (0) 1 260 830 
 

España 
Gilead Sciences, S.L. 
Tel: + 34 (0) 91 378 98 30 
 

Polska 
Gilead Sciences Poland Sp. z o.o. 
Tel.: + 48 (0) 22 262 8702 
 

France 
Gilead Sciences 
Tél: + 33 (0) 1 46 09 41 00 
 

Portugal 
Gilead Sciences, Lda. 
Tel: + 351 (0) 21 7928790 
 

Hrvatska 
Gilead Sciences Ireland UC 
Tel: + 353 (0) 1 686 1888 
 

România 
Gilead Sciences Ireland UC 
Tel: + 353 (0) 1 686 1888 
 

Ireland 
Gilead Sciences Ireland UC 
Tel: + 353 (0) 214 825 999 
 

Slovenija 
Gilead Sciences Ireland UC 
Tel: + 353 (0) 1 686 1888 
 

Ísland 
Gilead Sciences Sweden AB 
Sími: + 46 (0) 8 5057 1849 
 

Slovenská republika 
Gilead Sciences Slovakia s.r.o. 
Tel: + 421 (0) 232 121 210 
 

Italia 
Gilead Sciences S.r.l. 
Tel: + 39 02 439201 
 

Suomi/Finland 
Gilead Sciences Sweden AB 
Puh/Tel: + 46 (0) 8 5057 1849 
 

Κύπρος 
Gilead Sciences Ελλάς Μ.ΕΠΕ. 
Τηλ: + 30 (0) 210 8930 100 
 

Sverige 
Gilead Sciences Sweden AB 
Tel: + 46 (0) 8 5057 1849 
 

Latvija 
Gilead Sciences Poland Sp. z o.o. 
Tel.: + 48 (0) 22 262 8702 
 

United Kingdom 
Gilead Sciences Ltd. 
Tel: + 44 (0) 8000 113 700 
 

 
This leaflet was last revised in . 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu. 

http://www.ema.europa.eu/

	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET