Descovy

1 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 



 

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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 
 
Descovy 200 mg/10 mg film-coated tablets 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each tablet contains 200 mg of emtricitabine and tenofovir alafenamide fumarate equivalent to 10 mg 
of tenofovir alafenamide. 
 
 
3. PHARMACEUTICAL FORM 
 
Film-coated tablet. 
 
Grey, rectangular-shaped, film-coated tablet of dimensions 12.5 mm x 6.4 mm debossed with “GSI” 
on one side and “210” on the other side of the tablet. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Descovy is indicated in combination with other antiretroviral agents for the treatment of adults and 
adolescents (aged 12 years and older with body weight at least 35 kg) infected with human 
immunodeficiency virus type 1 (HIV-1) (see sections 4.2 and 5.1). 
 
4.2 Posology and method of administration 
 
Therapy should be initiated by a physician experienced in the management of HIV infection. 
 
Posology 
 
Adults and adolescents aged 12 years and older, weighing at least 35 kg 
Descovy should be administered as shown in Table 1. 
 
Table 1: Dose of Descovy according to third agent in the HIV treatment regimen 
 

Dose of Descovy Third agent in HIV treatment regimen 
(see section 4.5) 

Descovy 200/10 mg once 
daily 

Atazanavir with ritonavir or cobicistat 
Darunavir with ritonavir or cobicistat1 
Lopinavir with ritonavir 

Descovy 200/25 mg once 
daily 

Dolutegravir, efavirenz, maraviroc, 
nevirapine, rilpivirine, raltegravir 

1 Descovy 200/10 mg in combination with darunavir 800 mg and cobicistat 150 mg, administered as a fixed-dose 
combination tablet, was studied in treatment-naive subjects, see section 5.1. 

 
If the patient misses a dose of Descovy within 18 hours of the time it is usually taken, the patient 
should take Descovy as soon as possible and resume the normal dosing schedule.  If a patient misses a 
dose of Descovy by more than 18 hours, the patient should not take the missed dose and simply 
resume the usual dosing schedule. 
 



 

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If the patient vomits within 1 hour of taking Descovy another tablet should be taken. 
 
Elderly 
No dose adjustment of Descovy is required in elderly patients (see sections 5.1 and 5.2). 
 
Renal impairment 
No dose adjustment of Descovy is required in adults or adolescents (aged at least 12 years and of at 
least 35 kg body weight) with estimated creatinine clearance (CrCl) ≥ 30 mL/min. Descovy should be 
discontinued in patients with estimated CrCl that declines below 30 mL/min during treatment (see 
section 5.2).  
 
No dose adjustment of Descovy is required in adults with end stage renal disease (estimated 
CrCl < 15 mL/min) on chronic haemodialysis; however, Descovy should generally be avoided but 
may 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, Descovy should be administered after 
completion of haemodialysis treatment. 
 
Descovy should be avoided in patients with estimated CrCl ≥ 15 mL/min and < 30 mL/min, or 
< 15 mL/min who are not on chronic haemodialysis, as the safety of Descovy has not been established 
in these populations. 
 
No data are available to make dose recommendations in children less than 18 years with end stage 
renal disease. 
 
Hepatic impairment 
No dose adjustment of Descovy is required in patients with hepatic impairment.   
 
Paediatric population 
The safety and efficacy of Descovy in children younger than 12 years of age, or weighing < 35 kg, 
have not yet been established.  No data are available. 
 
Method of administration 
 
Descovy should be taken orally, once daily with or without food (see section 5.2).  The film-coated 
tablet 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. 
 
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. 
 
The safety and efficacy of Descovy in patients co-infected with HIV-1 and hepatitis C virus (HCV) 
have not been established. 
 
Tenofovir alafenamide is active against hepatitis B virus (HBV).  Discontinuation of Descovy 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 Descovy should be closely 



 

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monitored with both clinical and laboratory follow-up for at least several months after stopping 
treatment. 
 
Liver disease 
 
The safety and efficacy of Descovy in patients with significant underlying liver disorders have not 
been established (see sections 4.2 and 5.2). 
 
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. 
 
Patients with HIV-1 harbouring mutations 
 
Descovy should be avoided in antiretroviral-experienced patients with HIV-1 harbouring the K65R 
mutation (see section 5.1). 
 



 

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Triple nucleoside therapy 
 
There have been reports of a high rate of virological failure and of emergence of resistance at an early 
stage when tenofovir disoproxil was combined with lamivudine and abacavir as well as with 
lamivudine and didanosine as a once daily regimen.  Therefore, the same problems may be seen if 
Descovy is administered with a third nucleoside analogue. 
 
Opportunistic infections 
 
Patients receiving Descovy or any other antiretroviral therapy may continue to develop opportunistic 
infections and other complications of HIV infection, and, therefore, should remain under close clinical 
observation by physicians experienced in the treatment of patients with HIV associated diseases. 
 
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 
 
Descovy 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 48 weeks but emtricitabine exposure was significantly higher than in patients with 
normal renal function.  Although there were no new safety issues identified, the implications of 
increased emtricitabine exposure remain uncertain (see sections 4.8 and 5.2). 
 
Co-administration of other medicinal products 
 
The co-administration of Descovy is not recommended with certain anticonvulsants (e.g., 
carbamazepine, oxcarbazepine, phenobarbital and phenytoin), antimycobacterials (e.g., rifampicin, 
rifabutin, rifapentine), St. John’s wort and HIV protease inhibitors (PIs) other than atazanavir, 
lopinavir and darunavir (see section 4.5). 
 
Descovy should not be administered concomitantly with medicinal products containing tenofovir 
alafenamide, tenofovir disoproxil, emtricitabine, lamivudine or adefovir dipivoxil. 
 
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. 
 



 

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Descovy should not be administered concomitantly with medicinal products containing tenofovir 
alafenamide, tenofovir disoproxil, emtricitabine, lamivudine or adefovir dipivoxil. 
 
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).  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., rifampicin, 
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 Descovy and development of resistance.  Co-administration of Descovy 
with other medicinal products that inhibit P-gp and BCRP activity (e.g., cobicistat, ritonavir, 
ciclosporin) is expected to increase the absorption and plasma concentration of tenofovir alafenamide.  
Based on data from an in vitro study, co-administration of tenofovir alafenamide and xanthine oxidase 
inhibitors (e.g., febuxostat) is not expected to increase systemic exposure to tenofovir in vivo. 
 
Tenofovir alafenamide is not an inhibitor of CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, or 
CYP2D6 in vitro.  It is not an inhibitor or inducer of CYP3A in vivo.  Tenofovir alafenamide is a 
substrate of OATP1B1 and OATP1B3 in vitro.  The distribution of tenofovir alafenamide in the body 
may be affected by the activity of OATP1B1 and OATP1B3. 
 
Other interactions 
 
Tenofovir alafenamide is not an inhibitor of human uridine diphosphate glucuronosyltransferase 
(UGT) 1A1 in vitro.  It is not known whether tenofovir alafenamide is an inhibitor of other 
UGT enzymes.  Emtricitabine did not inhibit the glucuronidation reaction of a non-specific UGT 
substrate in vitro. 
 
Interactions between the components of Descovy and potential co-administered medicinal products are 
listed in Table 2 (increase is indicated as “↑”, decrease as “↓”, no change as “↔”).  The interactions 
described are based on studies conducted with Descovy, or the components of Descovy as individual 
agents and/or in combination, or are potential drug-drug interactions that may occur with Descovy. 
 
Table 2: Interactions between the individual components of Descovy and other medicinal 
products 
 

Medicinal product by 
therapeutic areas1 

Effects on medicinal product levels. 
Mean percent change in AUC, 

Cmax, Cmin2 

Recommendation concerning 
co-administration with Descovy 

ANTI-INFECTIVES 
Antifungals 
Ketoconazole 
Itraconazole 

Interaction not studied with either of 
the components of Descovy. 
 
Co-administration of ketoconazole or 
itraconazole, which are potent P-gp 
inhibitors, is expected to increase 
plasma concentrations of tenofovir 
alafenamide. 

The recommended dose of Descovy 
is 200/10 mg once daily. 



 

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Medicinal product by 
therapeutic areas1 

Effects on medicinal product levels. 
Mean percent change in AUC, 

Cmax, Cmin2 

Recommendation concerning 
co-administration with Descovy 

Fluconazole 
Isavuconazole 

Interaction not studied with either of 
the components of Descovy. 
 
Co-administration of fluconazole or 
isavuconazole may increase plasma 
concentrations of tenofovir 
alafenamide. 

Dose Descovy according to the 
concomitant antiretroviral (see 
section 4.2). 

Antimycobacterials 
Rifabutin 
Rifampicin 
Rifapentine 

Interaction not studied with either of 
the components of Descovy. 
 
Co-administration of rifampicin, 
rifabutin, and rifapentine, all of which 
are P-gp inducers, may decrease 
tenofovir alafenamide plasma 
concentrations, which may result in 
loss of therapeutic effect and 
development of resistance. 

Co-administration of Descovy and 
rifabutin rifampicin, or rifapentine 
is not recommended. 

Anti-hepatitis C virus medicinal products 
Ledipasvir (90 mg once daily)/ 
sofosbuvir (400 mg once daily), 
emtricitabine (200 mg once 
daily)/ tenofovir alafenamide 
(10 mg once daily) 3 

Ledipasvir: 
AUC: ↑ 79% 
Cmax: ↑ 65% 
Cmin: ↑ 93% 
 
Sofosbuvir: 
AUC: ↑ 47% 
Cmax: ↑ 29% 
 
Sofosbuvir metabolite GS-331007: 
AUC: ↑ 48% 
Cmax: ↔ 
Cmin: ↑ 66% 
 
Emtricitabine: 
AUC: ↔ 
Cmax: ↔ 
Cmin: ↔ 
 
Tenofovir alafenamide: 
AUC: ↔ 
Cmax: ↔ 

No dose adjustment of ledipasvir or 
sofosbuvir is required.  Dose 
Descovy according to the 
concomitant antiretroviral (see 
section 4.2). 



 

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Medicinal product by 
therapeutic areas1 

Effects on medicinal product levels. 
Mean percent change in AUC, 

Cmax, Cmin2 

Recommendation concerning 
co-administration with Descovy 

Ledipasvir (90 mg once daily)/ 
sofosbuvir (400 mg once daily), 
emtricitabine (200 mg once 
daily)/ tenofovir alafenamide 
(25 mg once daily) 4 

Ledipasvir: 
AUC: ↔ 
Cmax: ↔ 
Cmin: ↔ 
 
Sofosbuvir: 
AUC: ↔ 
Cmax: ↔ 
 
Sofosbuvir metabolite GS-331007: 
AUC: ↔ 
Cmax: ↔ 
Cmin: ↔ 
 
Emtricitabine: 
AUC: ↔ 
Cmax: ↔ 
Cmin: ↔ 
 
Tenofovir alafenamide: 
AUC: ↑ 32% 
Cmax: ↔ 

No dose adjustment of ledipasvir or 
sofosbuvir is required.  Dose 
Descovy according to the 
concomitant antiretroviral (see 
section 4.2). 

Sofosbuvir (400 mg once daily)/ 
velpatasvir (100 mg once daily), 
emtricitabine (200 mg once 
daily)/ tenofovir alafenamide  
(10 mg once daily)3 

Sofosbuvir: 
AUC: ↑ 37% 
Cmax: ↔ 
 
Sofosbuvir metabolite GS-331007: 
AUC: ↑ 48% 
Cmax: ↔ 
Cmin: ↑ 58% 
 
Velpatasvir: 
AUC: ↑ 50% 
Cmax: ↑ 30% 
Cmin: ↑ 60% 
 
Emtricitabine: 
AUC: ↔ 
Cmax: ↔ 
Cmin: ↔ 
 
Tenofovir alafenamide: 
AUC: ↔ 
Cmax: ↓ 20% 

No dose adjustment of sofosbuvir, 
velpatasvir or voxilaprevir is 
required.  Dose Descovy according 
to the concomitant antiretroviral 
(see section 4.2). 



 

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Medicinal product by 
therapeutic areas1 

Effects on medicinal product levels. 
Mean percent change in AUC, 

Cmax, Cmin2 

Recommendation concerning 
co-administration with Descovy 

Sofosbuvir/velpatasvir/ 
voxilaprevir 
(400 mg/100 mg/100 mg+100 mg 
once daily)7/  
emtricitabine (200 mg once 
daily)/ tenofovir alafenamide 
(10 mg once daily)3 

Sofosbuvir: 
AUC: ↔ 
Cmax: ↑ 27% 
 
Sofosbuvir metabolite GS-331007: 
AUC: ↑ 43% 
Cmax: ↔ 
 
Velpatasvir: 
AUC: ↔ 
Cmin: ↑ 46% 
Cmax: ↔ 
 
Voxilaprevir: 
AUC: ↑ 171% 
Cmin: ↑ 350% 
Cmax: ↑ 92% 
 
Emtricitabine: 
AUC: ↔ 
Cmin: ↔ 
Cmax: ↔ 
 
Tenofovir alafenamide: 
AUC: ↔ 
Cmax: ↓ 21% 

Sofosbuvir/velpatasvir/ 
voxilaprevir 
(400 mg/100 mg/100 mg+100 mg 
once daily)7/  
emtricitabine (200 mg once 
daily)/ tenofovir alafenamide 
(25 mg once daily)4 

Sofosbuvir: 
AUC: ↔ 
Cmax: ↔ 
 
Sofosbuvir metabolite GS-331007: 
AUC: ↔ 
Cmin: ↔ 
 
Velpatasvir: 
AUC: ↔ 
Cmin: ↔ 
Cmax: ↔ 
 
Voxilaprevir: 
AUC: ↔ 
Cmin: ↔ 
Cmax: ↔ 
 
Emtricitabine: 
AUC: ↔ 
Cmin: ↔ 
Cmax: ↔ 
 
Tenofovir alafenamide: 
AUC: ↑ 52% 
Cmax: ↑ 32% 

No dose adjustment of sofosbuvir, 
velpatasvir or voxilaprevir is 
required.  Dose Descovy according 
to the concomitant antiretroviral 
(see section 4.2). 



 

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Medicinal product by 
therapeutic areas1 

Effects on medicinal product levels. 
Mean percent change in AUC, 

Cmax, Cmin2 

Recommendation concerning 
co-administration with Descovy 

ANTIRETROVIRALS 
HIV protease inhibitors 
Atazanavir/cobicistat 
(300 mg/150 mg once daily), 
tenofovir alafenamide (10 mg)  

Tenofovir alafenamide: 
AUC: ↑ 75% 
Cmax: ↑ 80% 
 
Atazanavir: 
AUC: ↔ 
Cmax: ↔ 
Cmin: ↔ 

The recommended dose of Descovy 
is 200/10 mg once daily. 

Atazanavir/ritonavir (300/100 mg 
once daily), tenofovir 
alafenamide (10 mg) 

Tenofovir alafenamide: 
AUC: ↑ 91% 
Cmax: ↑ 77% 
 
Atazanavir: 
AUC: ↔ 
Cmax: ↔ 
Cmin: ↔ 

The recommended dose of Descovy 
is 200/10 mg once daily. 

Darunavir/cobicistat (800/150 mg 
once daily), tenofovir 
alafenamide (25 mg once daily)5 

Tenofovir alafenamide: 
AUC: ↔ 
Cmax: ↔ 
 
Tenofovir: 
AUC: ↑ 224% 
Cmax: ↑ 216% 
Cmin: ↑ 221% 
 
Darunavir: 
AUC: ↔ 
Cmax: ↔ 
Cmin: ↔ 

The recommended dose of Descovy 
is 200/10 mg once daily. 

Darunavir/ritonavir (800/100 mg 
once daily), tenofovir 
alafenamide (10 mg once daily) 

Tenofovir alafenamide: 
AUC: ↔ 
Cmax: ↔ 
 
Tenofovir: 
AUC: ↑ 105% 
Cmax: ↑ 142% 
 
Darunavir: 
AUC: ↔ 
Cmax: ↔ 
Cmin: ↔ 

The recommended dose of Descovy 
is 200/10 mg once daily. 

Lopinavir/ritonavir (800/200 mg 
once daily), tenofovir 
alafenamide (10 mg once daily) 

Tenofovir alafenamide: 
AUC: ↑ 47% 
Cmax: ↑ 119% 
 
Lopinavir: 
AUC: ↔ 
Cmax: ↔ 
Cmin: ↔ 

The recommended dose of Descovy 
is 200/10 mg once daily. 

Tipranavir/ritonavir Interaction not studied with either of 
the components of Descovy. 
 
Tipranavir/ritonavir results in P-gp 
induction.  Tenofovir alafenamide 
exposure is expected to decrease 
when tipranavir/ritonavir is used in 
combination with Descovy. 

Co-administration with Descovy is 
not recommended. 



 

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Medicinal product by 
therapeutic areas1 

Effects on medicinal product levels. 
Mean percent change in AUC, 

Cmax, Cmin2 

Recommendation concerning 
co-administration with Descovy 

Other protease inhibitors Effect is unknown. There are no data available to make 
dosing recommendations for 
co-administration with other 
protease inhibitors. 

Other HIV antiretrovirals 
Dolutegravir (50 mg once daily), 
tenofovir alafenamide (10 mg 
once daily)3 

Tenofovir alafenamide: 
AUC: ↔ 
Cmax: ↔ 
 
Dolutegravir: 
AUC: ↔ 
Cmax: ↔ 
Cmin: ↔ 

The recommended dose of Descovy 
is 200/25 mg once daily. 

Rilpivirine (25 mg once daily), 
tenofovir alafenamide (25 mg 
once daily) 

Tenofovir alafenamide: 
AUC: ↔ 
Cmax: ↔ 
 
Rilpivirine: 
AUC: ↔ 
Cmax: ↔ 
Cmin: ↔ 

The recommended dose of Descovy 
is 200/25 mg once daily. 

Efavirenz (600 mg once daily), 
tenofovir alafenamide (40 mg 
once daily)4 

Tenofovir alafenamide: 
AUC: ↓ 14% 
Cmax: ↓ 22% 

The recommended dose of Descovy 
is 200/25 mg once daily. 

Maraviroc 
Nevirapine 
Raltegravir 

Interaction not studied with either of 
the components of Descovy. 
 
Tenofovir alafenamide exposure is 
not expected to be affected by 
maraviroc, nevirapine 
or raltegravir, nor is it expected to 
affect the metabolic and excretion 
pathways relevant to maraviroc, 
nevirapine or raltegravir. 

The recommended dose of Descovy 
is 200/25 mg once daily. 

ANTICONVULSANTS 
Oxcarbazepine 
Phenobarbital 
Phenytoin 

Interaction not studied with either of 
the components of Descovy. 
 
Co-administration of oxcarbazepine, 
phenobarbital, or phenytoin, all of 
which are P-gp inducers, may 
decrease tenofovir alafenamide 
plasma concentrations, which may 
result in loss of therapeutic effect and 
development of resistance. 

Co-administration of Descovy and 
oxcarbazepine, phenobarbital or 
phenytoin is not recommended. 

Carbamazepine (titrated from 
100 mg to 300 mg twice a day), 
emtricitabine/tenofovir 
alafenamide (200 mg/25 mg once 
daily) 5,6 

Tenofovir alafenamide: 
AUC: ↓ 55% 
Cmax: ↓ 57% 
 
Co-administration of carbamazepine, 
a P-gp inducer, decreases tenofovir 
alafenamide plasma concentrations, 
which may result in loss of 
therapeutic effect and development of 
resistance. 

Co-administration of Descovy and 
carbamazepine is not 
recommended. 



 

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Medicinal product by 
therapeutic areas1 

Effects on medicinal product levels. 
Mean percent change in AUC, 

Cmax, Cmin2 

Recommendation concerning 
co-administration with Descovy 

ANTIDEPRESSANTS 
Sertraline (50 mg once daily), 
tenofovir alafenamide (10 mg 
once daily)3 

Tenofovir alafenamide: 
AUC: ↔ 
Cmax: ↔ 
 
Sertraline: 
AUC: ↑ 9% 
Cmax: ↑ 14% 

No dose adjustment of sertraline is 
required.  Dose Descovy according 
to the concomitant antiretroviral 
(see section 4.2). 

HERBAL PRODUCTS 
St. John’s wort (Hypericum 
perforatum) 

Interaction not studied with either of 
the components of Descovy. 
 
Co-administration of St. John’s wort, 
a P-gp inducer, may decrease 
tenofovir alafenamide plasma 
concentrations, which may result in 
loss of therapeutic effect and 
development of resistance. 

Co-administration of Descovy with 
St. John’s wort is not 
recommended. 

IMMUNOSUPPRESSANTS 
Ciclosporin Interaction not studied with either of 

the components of Descovy. 
 
Co-administration of ciclosporin, a 
potent P-gp inhibitor, is expected to 
increase plasma concentrations of 
tenofovir alafenamide. 

The recommended dose of Descovy 
is 200/10 mg once daily. 

ORAL CONTRACEPTIVES 
Norgestimate 
(0.180/0.215/0.250 mg once 
daily), ethinylestradiol (0.025 mg 
once daily), 
emtricitabine/tenofovir 
alafenamide (200/25 mg once 
daily)5 

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

No dose adjustment of 
norgestimate/ethinylestradiol is 
required.  Dose Descovy according 
to the concomitant antiretroviral 
(see section 4.2). 

SEDATIVES/HYPNOTICS 
Orally administered midazolam 
(2.5 mg single dose), tenofovir 
alafenamide (25 mg once daily) 

Midazolam: 
AUC: ↔ 
Cmax: ↔ 

No dose adjustment of midazolam 
is required.  Dose Descovy 
according to the concomitant 
antiretroviral (see section 4.2). Intravenously administered 

midazolam (1 mg single dose), 
tenofovir alafenamide (25 mg 
once daily) 

Midazolam: 
AUC: ↔ 
Cmax: ↔ 

1 When doses are provided, they are the doses used in clinical drug-drug interaction studies. 
2 When data are available from drug-drug interaction studies. 
3 Study conducted with elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide fixed-dose combination tablet. 
4 Study conducted with emtricitabine/rilpivirine/tenofovir alafenamide fixed-dose combination tablet. 
5 Study conducted with Descovy. 
6 Emtricitabine/tenofovir alafenamide was taken with food in this study. 
7 Study conducted with additional voxilaprevir 100 mg to achieve voxilaprevir exposurers expected in HCV-infected 

patients. 
 



 

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4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
 
There are no adequate and well-controlled studies of Descovy or its components in pregnant women.  
There are no or limited data (less than 300 pregnancy outcomes) from the use of tenofovir alafenamide 
in pregnant women.  However, 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 
tenofovir alafenamide in animals have shown no evidence of harmful effects on fertility parameters, 
pregnancy, or foetal development (see section 5.3). 
 
Descovy should be used during pregnancy only if the potential benefit justifies the potential risk to 
the foetus. 
 
Breast-feeding 
 
It is not known whether tenofovir alafenamide is excreted in human milk.  Emtricitabine is excreted in 
human milk.  In animal studies it has been shown that tenofovir is excreted in milk. 
 
There is insufficient information on the effects of emtricitabine and tenofovir in newborns/infants.  
Therefore, Descovy 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 
 
There are no data on fertility from the use of Descovy in humans.  In animal studies there were no 
effects of emtricitabine and tenofovir alafenamide on mating or fertility parameters (see section 5.3). 
 
4.7 Effects on ability to drive and use machines 
 
Patients should be informed that dizziness has been reported during treatment with Descovy. 
 
4.8 Undesirable effects 
 
Summary of the safety profile 
 
Assessment of adverse reactions is based on safety data from across all Phase 2 and 3 studies in which 
3,112 HIV-1 infected patients received medicinal products containing emtricitabine and tenofovir 
alafenamide and from post-marketing experience.  In clinical studies of 866 treatment-naïve adult 
patients receiving emtricitabine and tenofovir alafenamide with elvitegravir and cobicistat as the fixed-
dose combination tablet elvitegravir 150 mg/cobicistat 150 mg/emtricitabine 200 mg/tenofovir 
alafenamide (as fumarate) 10 mg (E/C/F/TAF) through 144 weeks, the most frequently reported 
adverse reactions were diarrhoea (7%), nausea (11%), and headache (6%). 
 
Tabulated summary of adverse reactions 
 
The adverse reactions in Table 3 are listed by system organ class and frequency.  Frequencies are 
defined as follows: very common (≥ 1/10), common (≥ 1/100 to < 1/10) and uncommon (≥ 1/1,000 to 
< 1/100). 
 
Table 3: Tabulated list of adverse reactions1 
 



 

14 

Frequency Adverse reaction 
Blood and lymphatic system disorders 
Uncommon: anaemia2 
Psychiatric disorders 
Common: abnormal dreams 
Nervous system disorders 
Common: headache, dizziness 
Gastrointestinal disorders 
Very common: nausea 
Common: diarrhoea, vomiting, abdominal pain, flatulence 
Uncommon: dyspepsia 
Skin and subcutaneous tissue disorders 
Common: Rash 
Uncommon: angioedema3, 4, pruritus, urticaria4 
Musculoskeletal and connective tissue disorders 
Uncommon: arthralgia 
General disorders and administration site conditions 
Common: fatigue 
1 With the exception of angioedema, anaemia and urticaria (see footnotes 2,3 and 4), all adverse reactions were identified 

from clinical studies of F/TAF containing products.  The frequencies were derived from Phase 3 E/C/F/TAF clinical 
studies in 866 treatment-naïve adult patients through 144 weeks of treatment (GS-US-292-0104 and GS-US-292-0111). 

2 This adverse reaction was not observed in the clinical studies of F/TAF-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. 
 
Description of selected adverse reactions 
 
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 lipid laboratory tests 
In studies in treatment-naïve patients, increases from baseline were observed in both the tenofovir 
alafenamide fumarate and tenofovir disoproxil fumarate containing treatment groups for the fasting 
lipid parameters total cholesterol, direct low-density lipoprotein (LDL)- and high-density lipoprotein 
(HDL)-cholesterol, and triglycerides at Week 144.  The median increase from baseline for those 
parameters was greater in the E/C/F/TAF group compared with the elvitegravir 150 mg/cobicistat 
150 mg/emtricitabine 200 mg/tenofovir disoproxil (as fumarate) 245 mg (E/C/F/TDF) group at 
Week 144 (p < 0.001 for the difference between treatment groups for fasting total cholesterol, direct 
LDL- and HDL-cholesterol, and triglycerides).  The median (Q1, Q3) change from baseline in total 
cholesterol to HDL-cholesterol ratio at Week 144 was 0.2 (-0.3, 0.7) in the E/C/F/TAF group and 0.1 
(-0.4, 0.6) in the E/C/F/TDF group (p = 0.006 for the difference between treatment groups). 
 
In a study of virologically suppressed patients switching from emtricitabine/tenofovir disoproxil 
fumarate to Descovy while maintaining the third antiretroviral agent (Study GS-US-311-1089), 
increases from baseline were observed in the fasting lipid parameters total cholesterol, direct LDL 
cholesterol and triglycerides in the Descovy arm compared with little change in the 
emtricitabine/tenofovir disproxil fumarate arm (p ≤ 0.009 for the difference between groups in 
changes from baseline).  There was little change from baseline in median fasting values for HDL 



 

15 

cholesterol and glucose, or in the fasting total cholesterol to HDL cholesterol ratio in either treatment 
arm at Week 96.  None of the changes was considered clinically relevant. 
 
In a study of virologically suppressed adult patients switching from abacavir/lamivudine to Descovy 
while maintaining the third antiretroviral agent (Study GS-US-311-1717), there were minimal changes 
in lipid parameters.  
 
Metabolic parameters 
Weight and levels of blood lipids and glucose may increase during antiretroviral therapy (see 
section 4.4). 
 
Paediatric population 
 
The safety of emtricitabine and tenofovir alafenamide was evaluated through 48 weeks in an open-
label clinical study (GS-US-292-0106) in which HIV-1 infected, treatment-naïve paediatric patients 
aged 12 to < 18 years received emtricitabine and tenofovir alafenamide in combination with 
elvitegravir and cobicistat as a fixed-dose combination tablet.  The safety profile of emtricitabine and 
tenofovir alafenamide given with elvitegravir and cobicistat in 50 adolescent patients was similar to 
that in adults (see section 5.1). 
 
Other special populations 
 
Patients with renal impairment 
The safety of emtricitabine and tenofovir alafenamide was evaluated through 144 weeks in an open-
label clinical study (GS-US-292-0112) in which 248 HIV-1 infected patients who were either 
treatment-naïve (n = 6) or virologically suppressed (n = 242) with mild to moderate renal impairment 
(estimated glomerular filtration rate by Cockcroft-Gault method [eGFRCG]: 30-69 mL/min) received 
emtricitabine and tenofovir alafenamide in combination with elvitegravir and cobicistat as a fixed-dose 
combination tablet.  The safety profile in patients with mild to moderate renal impairment was similar 
to that in patients with normal renal function (see section 5.1). 
 
The safety of emtricitabine and tenofovir alafenamide was evaluated through 48 weeks 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 and tenofovir alafenamide in combination with elvitegravir and cobicistat as a fixed-dose 
combination tablet.  There were no new safety issues identified in patients with end stage renal disease 
on chronic haemodialysis receiving emtricitabine and tenofovir alafenamide, in combination with 
elvitegravir and cobicistat as a fixed-dose combination tablet (see section 5.2). 
 
Patients co-infected with HIV and HBV 
The safety of emtricitabine and tenofovir alafenamide in combination with elvitegravir and cobicistat 
as a fixed-dose combination tablet (elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide 
[E/C/F/TAF]) was evaluated in 72 HIV/HBV co-infected patients receiving treatment for HIV in an 
open-label clinical study (GS-US-292-1249), through Week 48, in which patients were switched from 
another antiretroviral regimen (which included tenofovir disoproxil fumarate [TDF] in 69 of 72 
patients) to E/C/F/TAF.  Based on these limited data, the safety profile of emtricitabine and tenofovir 
alafenamide in combination with elvitegravir and cobicistat as a fixed-dose combination tablet, in 
patients with HIV/HBV co-infection, was similar to that in patients with HIV-1 monoinfection (see 
section 4.4). 
 
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. 
 

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


 

16 

4.9 Overdose 
 
If overdose occurs the patient must be monitored for evidence of toxicity (see section 4.8).  Treatment 
of overdose with Descovy consists of general supportive measures including monitoring of vital signs 
as well as observation of the clinical status of the patient. 
 
Emtricitabine can be removed by haemodialysis, 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 haemodialysis 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: J05AR17. 
 
Mechanism of action 
 
Emtricitabine is a nucleoside reverse transcriptase inhibitor (NRTI) and nucleoside analogue of 
2’-deoxycytidine.  Emtricitabine is phosphorylated by cellular enzymes to form emtricitabine 
triphosphate.  Emtricitabine triphosphate inhibits HIV replication through incorporation into viral 
deoxyribonucleic acid (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 fumarate 
in concentrating tenofovir in peripheral blood mononuclear cells (PBMCs) or HIV target cells 
including lymphocytes 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 
 
Emtricitabine and tenofovir alafenamide demonstrated synergistic antiviral activity in cell culture. 
No antagonism was observed with emtricitabine or tenofovir alafenamide when combined with other 
antiretroviral agents. 
 
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 50% effective concentration 
(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 strain specific 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 



 

17 

(M, N, and O), including subtypes A, B, C, D, E, F, and G (EC50 values ranged from 0.10 to 12.0 nM) 
and showed strain specific activity against HIV-2 (EC50 values ranged from 0.91 to 2.63 nM). 
 
Resistance 
 
In vitro 
Reduced susceptibility to emtricitabine is associated with M184V/I mutations in HIV-1 RT. 
 
HIV-1 isolates with reduced susceptibility to tenofovir alafenamide express a K65R mutation in 
HIV-1 RT; in addition, a K70E mutation in HIV-1 RT has been transiently observed. 
 
In treatment-naïve patients 
In a pooled analysis of antiretroviral-naïve patients receiving emtricitabine and tenofovir alafenamide 
(10 mg) given with elvitegravir and cobicistat as a fixed-dose combination tablet in Phase 3 studies 
GS-US-292-0104 and GS-US-292-0111, genotyping was performed on plasma HIV-1 isolates from all 
patients with HIV-1 RNA ≥ 400 copies/mL at confirmed virological failure, at Week 144, or at the 
time of early study drug discontinuation.  Through Week 144, the development of one or more 
primary emtricitabine, tenofovir alafenamide, or elvitegravir resistance-associated mutations was 
observed in HIV-1 isolates from 12 of 22 patients with evaluable genotypic data from paired baseline 
and E/C/F/TAF treatment-failure isolates (12 of 866 patients [1.4%]) compared with 12 of 
20 treatment-failure isolates from patients with evaluable genotypic data in the E/C/F/TDF group (12 
of 867 patients [1.4%]).  In the E/C/F/TAF group, the mutations that emerged were M184V/I (n = 11) 
and K65R/N (n = 2) in RT and T66T/A/I/V (n = 2), E92Q (n = 4), Q148Q/R (n = 1), and N155H 
(n = 2) in integrase.  Of the HIV-1 isolates from 12 patients with resistance development in the 
E/C/F/TDF group, the mutations that emerged were M184V/I (n = 9), K65R/N (n = 4), and L210W (n 
= 1) in RT and E92Q/V (n = 4) and Q148R (n = 2), and N155H/S (n=3) in integrase.  Most 
HIV-1 isolates from patients in both treatment groups who developed resistance mutations to 
elvitegravir in integrase also developed resistance mutations to emtricitabine in RT. 
 
In patients co-infected with HIV and HBV 
In a clinical study of HIV virologically suppressed patients co-infected with chronic hepatitis B, who 
received emtricitabine and tenofovir alafenamide, given with elvitegravir and cobicistat as a 
fixed-dose combination tablet (E/C/F/TAF), for 48 weeks (GS-US-292-1249, n = 72), 2 patients 
qualified for resistance analysis.  In these 2 patients, no amino acid substitutions associated with 
resistance to any of the components of E/C/F/TAF were identified in HIV-1 or HBV. 
 
Cross-resistance in HIV-1 infected, treatment-naïve or virologically suppressed patients 
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 
 
There are no efficacy and safety studies conducted in treatment-naïve patients with Descovy. 
 
Clinical efficacy of Descovy was established from studies conducted with emtricitabine and tenofovir 
alafenamide when given with elvitegravir and cobicistat as the fixed-dose combination tablet 
E/C/F/TAF. 
 
HIV-1 infected, treatment-naïve patients 
In studies GS-US-292-0104 and GS-US-292-0111, patients were randomised in a 1:1 ratio to receive 
either emtricitabine 200 mg and tenofovir alafenamide 10 mg (n = 866) once daily or emtricitabine 



 

18 

200 mg + tenofovir disoproxil (as fumarate) 245 mg (n = 867) once daily, both given with elvitegravir 
150 mg + cobicistat 150 mg as a fixed-dose combination tablet.  The mean age was 36 years (range: 
18-76), 85% were male, 57% were White, 25% were Black, and 10% were Asian.  Nineteen percent of 
patients were identified as Hispanic/Latino.  The mean baseline plasma HIV-1 RNA was 
4.5 log10 copies/mL (range: 1.3-7.0) and 23% had baseline viral loads > 100,000 copies/mL.  The 
mean baseline CD4+ cell count was 427 cells/mm3 (range: 0-1,360) and 13% had a CD4+ cell count 
< 200 cells/mm3. 
 
E/C/F/TAF demonstrated statistical superiority in achieving HIV-1 RNA < 50 copies/mL when 
compared to E/C/F/TDF at Week 144.  The difference in percentage was 4.2% (95% CI: 0.6% to 
7.8%).  Pooled treatment outcomes at 48 and 144 weeks are shown in Table 4. 
 
Table 4: Pooled virological outcomes of Studies GS-US-292-0104 and GS-US-292-0111 at Weeks 
48 and 144a,b 
 

 Week 48 Week 144 
 E/C/F/TAF 

(n = 866) 
E/C/F/TDFe 

(n = 867) 
E/C/F/TAF 

(n = 866) 
E/C/F/TDF 

(n = 867) 
HIV-1 RNA < 50 copies/mL 92% 90% 84% 80% 

Treatment difference 2.0% (95% CI: -0.7% to 4.7%) 4.2% (95% CI: 0.6% to 7.8%) 
HIV-1 RNA ≥ 50 copies/mLc 4% 4% 5%  4%  
No virologic data at 
Week 48 or 144 window 

4% 6% 11% 16% 

Discontinued study drug 
due to AE or deathd 

1% 2% 1%  3% 

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

2% 4% 9% 11% 

Missing data during 
window but on study 
drug 

1% < 1% 1% 1%  

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

    

Age 
< 50 years 
≥ 50 years 

 
716/777 (92%) 
84/89 (94%) 

 
680/753 (90%) 
104/114 (91%) 

 
647/777 (83%) 
82/89 (92%)  

 
602/753 (80%) 
92/114 (81%)  

 
Sex 

Male 
Female 

 
674/733 (92%) 
126/133 (95%) 

 
673/740 (91%) 
111/127 (87%) 

 
616/733 (84%) 
113/133 (85%)  

 
603/740 (81%) 
91/127 (72%)  

 
Race 

Black 
Non-black 

 
197/223 (88%) 
603/643 (94%) 

 
177/213 (83%) 
607/654 (93%) 

 
168/223 (75%) 
561/643 (87%)  

 
152/213 (71%) 
542/654 (83%)  

 
Baseline viral load 

≤ 100,000 copies/mL 
> 100,000 copies/mL 

 
629/670 (94%) 
171/196 (87%) 

 
610/672 (91%) 
174/195 (89%) 

 
567/670 (85%) 
162/196 (83%)   

 
537/672 (80%) 
157/195 (81%)  

 
Baseline CD4+ cell count 

< 200 cells/mm3 
≥ 200 cells/mm3 

 
96/112 (86%) 
703/753 (93%) 

 
104/117 (89%) 
680/750 (91%) 

 
93/112 (83%) 
635/753 (84%)  

 
94/117 (80%) 
600/750 (80%)  

 
HIV-1 RNA < 20 copies/mL 84.4% 84.0% 81.1%  75.8%  

Treatment difference 0.4% (95% CI: -3.0% to 3.8%) 5.4% (95% CI: 1.5% to 9.2%)  



 

19 

E/C/F/TAF = elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide 
E/C/F/TDF = elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate 
a Week 48 window was between Day 294 and 377 (inclusive); Week 144 window was between Day 966 and 1049 

(inclusive). 
b In both studies, patients were stratified by baseline HIV-1 RNA (≤ 100,000 copies/mL, > 100,000 copies/mL to 

≤ 400,000 copies/mL, or > 400,000 copies/mL), by CD4+ cell count (< 50 cells/μL, 50-199 cells/μL, or ≥ 200 cells/μL), 
and by region (US or ex-US). 

c 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; patients who discontinued for reasons other than an adverse event (AE), death or lack or loss of efficacy 
and at the time of discontinuation had a viral value of ≥ 50 copies/mL. 

d 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. 

e 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. 

 
The mean increase from baseline in CD4+ cell count was 230 cells/mm3 in patients receiving 
E/C/F/TAF and 211 cells/mm3 in patients receiving E/C/F/TDF (p = 0.024) at Week 48, and 326 
cells/mm3 in E/C/F/TAF-treated patients and 305 cells/mm3 in E/C/F/TDF-treated patients (p = 0.06) 
at Week 144.  
 
Clinical efficacy of Descovy in treatment-naïve patients was also established from a study conducted 
with emtricitabine and tenofovir alafenamide (10 mg) when given with darunavir (800 mg) and 
cobicistat as a fixed-dose combination tablet (D/C/F/TAF).  In Study GS-US-299-0102, patients were 
randomised in a 2:1 ratio to receive either fixed-dose combination D/C/F/TAF once daily (n = 103) or 
darunavir and cobicistat and emtricitabine/tenofovir disoproxil fumarate once daily (n = 50).  The 
proportions of patients with plasma HIV-1 RNA < 50 copies/mL and < 20 copies/mL are shown in 
Table 5. 
 



 

20 

Table 5: Virological outcomes of Study GS-US-299-0102 at Week 24 and 48a 
 
 Week 24 Week 48 

 D/C/F/TAF 
(n = 103) 

Darunavir,  
cobicistat and 

emtricitabine/tenofovir 
disoproxil fumarate 

(n = 50) 

D/C/F/TAF 
(n = 103) 

Darunavir,  
cobicistat and 

emtricitabine/tenofovir 
disoproxil fumarate 

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

75% 74% 77% 84% 

Treatment difference 3.3% (95% CI: -11.4% to 18.1%) -6.2% (95% CI: -19.9% to 7.4%) 
HIV-1 RNA 
≥ 50 copies/mLb 

20% 24% 16% 12% 

No virologic data at 
Week 48 window 

5% 2% 8% 4% 

Discontinued study 
drug due to AE or 
deathc  

1% 0 1% 2% 

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

4% 2% 7% 2% 

Missing data during 
window but on study 
drug 

0 0 0 0 

HIV-1 RNA 
< 20 copies/mL 

55% 62% 63% 76% 

Treatment difference -3.5% (95% CI: -19.8% to 12.7%) -10.7% (95% CI: -26.3% to 4.8%) 
D/C/F/TAF = darunavir/cobicistat/emtricitabine/tenofovir alafenamide 
a Week 48 window was between Day 294 and 377 (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 an adverse event (AE), death or lack or loss of efficacy and at 
the time of discontinuation had a viral value of ≥ 50 copies/mL. 

c 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. 

d 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. 

 
HIV-1 infected virologically suppressed patients 
In Study GS-US-311-1089, the efficacy and safety of switching from emtricitabine/tenofovir 
disoproxil fumarate to Descovy while maintaining the third antiretroviral agent were evaluated in a 
randomised, double-blind study of virologically suppressed HIV-1 infected adults (n = 663).  Patients 
must have been stably suppressed (HIV-1 RNA < 50 copies/mL) on their baseline regimen for at least 
6 months and had HIV-1 with no resistance mutations to emtricitabine or tenofovir alafenamide prior 
to study entry.  Patients were randomised in a 1:1 ratio to either switch to Descovy (n = 333), or stay 
on their baseline emtricitabine/tenofovir disoproxil fumarate containing regimen (n = 330).  Patients 
were stratified by the class of the third agent in their prior treatment regimen.  At baseline, 46% of 
patients were receiving emtricitabine/tenofovir disoproxil fumarate in combination with a boosted PI 
and 54% of patients were receiving emtricitabine/tenofovir disoproxil fumarate in combination with an 
unboosted third agent. 
 
Treatment outcomes of Study GS-US-311-1089 through 48 and 96 weeks are presented in Table 6. 
 



 

21 

Table 6: Virological outcomes of Study GS-US-311-1089 at Weeks 48a and 96b 
 

 Week 48 Week 96 

 Descovy containing 
regimen 
(n = 333) 

 

Emtricitabine/tenofov
ir disoproxil fumarate 

containing regimen 
(n = 330) 

Descovy containing 
regimen 
(n = 333) 

Emtricitabine/tenofov
ir disoproxil fumarate 

containing regimen 
(n = 330) 

HIV-1 RNA 
< 50 copies/mL 

94% 93% 89% 89% 

Treatment 
difference 

1.3% (95% CI: -2.5% to 5.1%) -0.5% (95% CI: -5.3% to 4.4%) 

HIV-1 RNA 
≥ 50 copies/mLc 

< 1% 2% 2% 1% 

No virologic data 
at Week 48 or 96 
window 

5% 5% 9% 10% 

Discontinued 
study drug due 
to AE or 
deathd 

2% 1% 2% 2% 

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

3% 5% 

7% 9% 

Missing data 
during window 
but on study 
drug 

< 1% 0 0 <1% 

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

    

Boosted PIs 142/155 (92%) 140/151 (93%) 133/155 (86%) 133/151 (88%) 
Other third 
agents 

172/178 (97%) 167/179 (93%) 162/178 (91%)   161/179 (90%) 

PI = protease inhibitor 
a Week 48 window was between Day 294 and 377 (inclusive). 
b Week 96 window was between Day 630 and 713 (inclusive). 
c Includes patients who had ≥ 50 copies/mL in the Week 48 or Week 96 window; patients who discontinued early due to 

lack or loss of efficacy; patients who discontinued for reasons other than an adverse event (AE), death or lack or loss of 
efficacy and at the time of discontinuation had a viral value of ≥ 50 copies/mL. 

d 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. 

e 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. 

 
In Study GS-US-311-1717, patients who were virologically suppressed (HIV-1 RNA <50 copies/mL) 
on their abacavir/lamivudine containing regimen for at least 6 months were randomised in a 1:1 ratio 
to either switch to Descovy (N=280) while maintaining their third agent at baseline or stay on their 
baseline abacavir/lamivudine -containing regimen (N=276).  

Patients were stratified by the class of the third agent in their prior treatment regimen. At baseline, 
30% of patients were receiving abacavir/lamivudine in combination with a boosted protease inhibitor 
and 70% of patients were receiving abacavir/lamivudine in combination with an unboosted third agent. 
Virologic success rates at Week 48 were: Descovy Containing Regimen:  89.7% (227 of 253 subjects); 
Abacavir/lamivudine Containing Regimen: 92.7%% (230 of 248 subjects). At Week 48, switching to a 



 

22 

Descovy-containing regimen was non-inferior to staying on a baseline abacavir/lamivudine-containing 
regimen in maintaining HIV-1 RNA < 50 copies/mL  
 
HIV-1 infected patients with mild to moderate renal impairment 
In Study GS-US-292-0112, the efficacy and safety of emtricitabine and tenofovir alafenamide were 
evaluated in an open-label clinical study in which 242 HIV-1 infected patients with mild to moderate 
renal impairment (eGFRCG: 30-69 mL/min) were switched to emtricitabine and tenofovir alafenamide 
(10 mg) given with elvitegravir and cobicistat as a fixed-dose combination tablet.  Patients were 
virologically suppressed (HIV-1 RNA < 50 copies/mL) for at least 6 months before switching. 
 
The mean age was 58 years (range: 24-82), with 63 patients (26%) who were ≥ 65 years of age.  
Seventy-nine percent were male, 63% were White, 18% were Black, and 14% were Asian.  Thirteen 
percent of patients were identified as Hispanic/Latino.  At baseline, median eGFR was 56 mL/min, 
and 33% of patients had an eGFR from 30 to 49 mL/min.  The mean baseline CD4+ cell count was 
664 cells/mm3 (range: 126-1,813).  
 
At Week 144, 83.1% (197/237 patients) maintained HIV-1 RNA < 50 copies/mL after switching to 
emtricitabine and tenofovir alafenamide given with elvitegravir and cobicistat as a fixed-dose 
combination tablet.   
 
In Study GS-US-292-1825, the efficacy and safety of emtricitabine and tenofovir alafenamide, given 
with elvitegravir and cobicistat as a fixed-dose combination tablet were evaluated in a single arm, 
open-label clinical study in which 55 HIV-1 infected adults with end stage renal disease 
(eGFRCG < 15 mL/min) on chronic haemodialysis for at least 6 months before switching to 
emtricitabine and tenofovir alafenamide, given with elvitegravir and cobicistat as a fixed-dose 
combination tablet.  Patients were virologically suppressed (HIV-1 RNA < 50 copies/mL) for at least 
6 months before switching. 
 
The mean age was 48 years (range 23-64).  Seventy-six percent were male, 82% were Black and 18% 
were White.  Fifteen percent of patients identified as Hispanic/Latino.  The mean baseline CD4+ cell 
count was 545 cells/mm3 (range 205-1473).  At Week 48, 81.8% (45/55 patients) maintained HIV-1 
RNA < 50 copies/mL after switching to emtricitabine and tenofovir alafenamide, given with 
elvitegravir and cobicistat as a fixed-dose combination tablet.  There were no clinically significant 
changes in fasting lipid laboratory tests in patients who switched. 
 
Patients co-infected with HIV and HBV 
In open-label Study GS-US-292-1249, the efficacy and safety of emtricitabine and tenofovir 
alafenamide, given with elvitegravir and cobicistat as a fixed-dose combination tablet (E/C/F/TAF), 
were evaluated in adult patients co-infected with HIV-1 and chronic hepatitis B.  Sixty-nine of the 
72 patients were on prior TDF-containing antiretroviral therapy.  At the start of treatment with 
E/C/F/TAF, the 72 patients had been HIV-suppressed (HIV-1 RNA < 50 copies/mL) for at least 
6 months with or without suppression of HBV DNA and had compensated liver function.  The mean 
age was 50 years (range 28-67), 92% of patients were male, 69% were White, 18% were Black, and 
10% were Asian.  The mean baseline CD4+ cell count was 636 cells/mm3 (range 263-1498).  
Eighty-six percent of patients (62/72) were HBV suppressed (HBV DNA < 29 IU/mL) and 42% 
(30/72) were HBeAg positive at baseline. 
 
Of the patients who were HBeAg positive at baseline, 1/30 (3.3%) achieved seroconversion to 
anti-HBe at Week 48.  Of the patients who were HBsAg positive at baseline, 3/70 (4.3%) achieved 
seroconversion to anti-HBs Week 48. 
 
At Week 48, 92% of patients (66/72) maintained HIV-1 RNA < 50 copies/mL after switching to 
emtricitabine and tenofovir alafenamide, given with elvitegravir and cobicistat as a fixed-dose 
combination tablet.  The mean change from baseline in CD4+ cell count at Week 48 was -2 cells/mm3.  
Ninety-two percent (66/72 patients) had HBV DNA < 29 IU/mL using missing = failure analysis at 
Week 48.  Of the 62 patients who were HBV suppressed at baseline, 59 remained suppressed and 



 

23 

3 had missing data. Of the 10 patients who were not HBV suppressed at baseline 
(HBV DNA ≥ 29 IU/mL), 7 became suppressed, 2 remained detectable, and 1 had missing data. 
 
There are limited clinical data on the use of E/C/F/TAF in HIV/HBV co-infected patients who are 
treatment-naïve. 
 
Changes in measures of bone mineral density 
In studies in treatment-naïve patients, emtricitabine and tenofovir alafenamide given with elvitegravir 
and cobicistat as a fixed-dose combination tablet was associated with smaller reductions in bone 
mineral density (BMD) compared to E/C/F/TDF through 144 weeks of treatment as measured by dual 
energy X ray absorptiometry (DXA) analysis of hip (mean change: −0.8% vs −3.4%, p < 0.001) and 
lumbar spine (mean change: −0.9% vs −3.0%, p < 0.001). In a separate study, emtricitabine and 
tenofovir alafenamide given with  darunavir and cobicistat as a fixed-dose combination tablet was also 
associated with smaller reductions in BMD (as measured by hip and lumbar spine DXA analysis) 
through 48 weeks of treatment compared to darunavir, cobicistat, emtricitabine and tenofovir 
disoproxil fumarate.   
 
In a study in virologically suppressed adult patients, improvements in BMD were noted through 
96 weeks after switching to Descovy from a TDF containing regimen compared to minimal changes 
with maintaining the TDF containing regimen as measured by DXA analysis of hip (mean change 
from baseline of 1.9% vs -0.3%, p < 0.001) and lumbar spine (mean change from baseline of 2.2% vs 
-0.2%, p < 0.001). 
 
In a study in virologically suppressed adult patients, BMD did not change significantly through 48 
weeks after switching to Descovy from an abacavir/lamivudine containing regimen compared to 
maintaining the abacavir/lamivudine containing regimen as measured by DXA analysis of hip (mean 
change from baseline of 0.3% vs 0.2%, p = 0.55) and lumbar spine (mean change from baseline of 
0.1% vs < 0.1%, p = 0.78). 
 
Changes in measures of renal function 
In studies in treatment-naïve patients, emtricitabine and tenofovir alafenamide given with elvitegravir 
and cobicistat as a fixed-dose combination tablet through 144 weeks was associated with a lower 
impact on renal safety parameters (as measured after 144 weeks treatment by eGFRCG and urine 
protein to creatinine ratio and after 96 weeks treatment by urine albumin to creatinine ratio) compared 
to E/C/F/TDF. Through 144 weeks of treatment, no subject discontinued E/C/F/TAF due to a 
treatment-emergent renal adverse event compared with 12 subjects who discontinued E/C/F/TDF 
(p < 0.001).  
 
In a separate study in treatment-naïve patients, emtricitabine and tenofovir alafenamide given with 
darunavir and cobicistat as a fixed-dose combination tablet was associated with a lower impact on 
renal safety parameters through 48 weeks of treatment compared to darunavir and cobicistat given 
with emtricitabine/tenofovir disoproxil fumarate (see also section 4.4).  
 
In a study in virologically suppressed adult patients measures of tubular proteinuria were similar in 
patients switching to a regimen containing Descovy compared to patients who stayed on an 
abacavir/lamivudine containing regimen at baseline. At Week 48, the median percentage change in 
urine retinol binding protein to creatinine ratio was 4% in the Descovy group and 16% in those 
remaining on an abacavir/lamivudine containing regimen; and in urine beta-2 microglobulin to 
creatinine ratio it was 4% vs. 5%. 
 
Paediatric population 
 
In Study GS-US-292-0106, the efficacy, safety, and pharmacokinetics of emtricitabine and tenofovir 
alafenamide were evaluated in an open-label study in which 50 HIV-1 infected, treatment-naïve 
adolescents received emtricitabine and tenofovir alafenamide (10 mg) given with elvitegravir and 
cobicistat as a fixed-dose combination tablet.  Patients had a mean age of 15 years (range: 12-17), and 
56% were female, 12% were Asian, and 88% were Black.  At baseline, median plasma HIV-1 RNA 



 

24 

was 4.7 log10 copies/mL, median CD4+ cell count was 456 cells/mm3 (range: 95-1,110), and median 
CD4+% was 23% (range: 7-45%).  Overall, 22% had baseline plasma HIV-1 RNA 
> 100,000 copies/mL.  At 48 weeks, 92% (46/50) achieved HIV-1 RNA < 50 copies/mL, similar to 
response rates in studies of treatment-naïve HIV-1 infected adults.  The mean increase from baseline 
in CD4+ cell count at Week 48 was 224 cells/mm3.  No emergent resistance to E/C/F/TAF was 
detected through Week 48. 
 
The European Medicines Agency has deferred the obligation to submit the results of studies with 
Descovy in one or more subsets of the paediatric population in the treatment of HIV-1 infection (see 
section 4.2 for information on paediatric use). 
 
5.2 Pharmacokinetic properties 
 
Absorption 
 
Emtricitabine is rapidly and extensively absorbed following oral administration with peak plasma 
concentrations occurring at 1 to 2 hours post-dose.  Following multiple dose oral administration of 
emtricitabine to 20 HIV-1 infected subjects, the (mean ± SD) steady state plasma emtricitabine peak 
concentrations (Cmax) were 1.8 ± 0.7 μg/mL and the area-under the plasma concentration-time curve 
over a 24-hour dosing interval (AUC) was 10.0 ± 3.1 μg•h/mL.  The mean steady state plasma trough 
concentration at 24 hours post-dose was equal to or greater than the mean in vitro IC90 value for 
anti-HIV-1 activity. 
 
Emtricitabine systemic exposure was unaffected when emtricitabine was administered with food. 
 
Following administration of food in healthy subjects, peak plasma concentrations were observed 
approximately 1 hour post-dose for tenofovir alafenamide administered as F/TAF (25 mg) or 
E/C/F/TAF (10 mg).  The mean Cmax and AUClast, (mean ± SD) under fed conditions following a 
single 25 mg dose of tenofovir alafenamide administered in Descovy were 0.21 ± 0.13 μg/mL and 
0.25 ± 0.11 μg•h/mL, respectively.  The mean Cmax and AUClast following a single 10 mg dose of 
tenofovir alafenamide administered in E/C/F/TAF were 0.21 ± 0.10 μg/mL and 0.25 ± 0.08 μg•h/mL, 
respectively. 
 
Relative to fasting conditions, the administration of tenofovir alafenamide with a high fat meal 
(~800 kcal, 50% fat) resulted in a decrease in tenofovir alafenamide Cmax (15-37%) and an increase in 
AUClast (17-77%). 
 
Distribution 
 
In vitro binding of emtricitabine to human plasma proteins was < 4% and independent of 
concentration over the range of 0.02-200 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 
 
In vitro studies indicate that emtricitabine is not an inhibitor of human CYP enzymes.  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. 
 



 

25 

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 10 mg oral dose of tenofovir 
alafenamide (given with emtricitabine and elvitegravir and cobicistat) 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 (as fumarate) (given with 
emtricitabine and elvitegravir and cobicistat). 
 
In vitro, tenofovir alafenamide is not metabolised by CYP1A2, CYP2C8, CYP2C9, CYP2C19, or 
CYP2D6.  Tenofovir alafenamide is minimally metabolised by CYP3A4.  Upon co-administration 
with the moderate CYP3A inducer probe efavirenz, tenofovir alafenamide exposure was not 
significantly affected.  Following administration of tenofovir alafenamide, plasma [14C]-radioactivity 
showed a time-dependent profile with tenofovir alafenamide as the most abundant species in the initial 
few hours and uric acid in the remaining period. 
 
Elimination 
 
Emtricitabine is primarily excreted by the kidneys with complete recovery of the dose achieved in 
urine (approximately 86%) and faeces (approximately 14%).  Thirteen percent of the emtricitabine 
dose was recovered in urine as three metabolites.  The systemic clearance of emtricitabine averaged 
307 mL/min.  Following oral administration, the elimination half-life of emtricitabine is approximately 
10 hours. 
 
Renal excretion of intact tenofovir alafenamide is a minor pathway with < 1% of the dose eliminated 
in urine.  Tenofovir alafenamide is mainly 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 renally eliminated by both glomerular filtration and active tubular secretion. 
 
Pharmacokinetics in special populations 
 
Age, gender, and ethnicity 
No clinically relevant pharmacokinetic differences due to age, gender or ethnicity have been identified 
for emtricitabine, or tenofovir alafenamide. 
 
Paediatric population 
 
Exposures of emtricitabine and tenofovir alafenamide (given with elvitegravir and cobicistat) achieved 
in 24 paediatric patients aged 12 to < 18 years who received emtricitabine and tenofovir alafenamide 
given with elvitegravir and cobicistat in Study GS-US-292-0106 were similar to exposures achieved in 
treatment-naïve adults (Table 7). 
 



 

26 

Table 7: Pharmacokinetics of emtricitabine and tenofovir alafenamide in antiretroviral-naïve 
adolescents and adults 
 

 Adolescents Adults 
 FTCa TAFb TFVb FTCa TAFc TFVc 

AUCtau 
(ng•h/mL) 

14,424.4 
(23.9) 

242.8 
(57.8) 

275.8 
(18.4) 

11,714.1 
(16.6) 

206.4 
(71.8) 

292.6 
(27.4) 

Cmax 
(ng/mL) 

2,265.0 
(22.5) 

121.7 
(46.2) 

14.6 (20.0) 2,056.3 
(20.2) 

162.2 
(51.1) 

15.2 
(26.1) 

Ctau 
(ng/mL) 102.4 (38.9)

b N/A 10.0 (19.6) 95.2 (46.7) N/A 10.6 (28.5) 
E/C/F/TAF = elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide fumarate 
FTC = emtricitabine; TAF = tenofovir alafenamide fumarate; TFV = tenofovir 
N/A = not applicable 
Data are presented as mean (%CV). 
a n = 24 adolescents (GS-US-292-0106); n = 19 adults (GS-US-292-0102) 
b n = 23 adolescents (GS-US-292-0106, population PK analysis) 
c n = 539 (TAF) or 841 (TFV) adults (GS-US-292-0111 and GS-US-292-0104, population PK analysis) 
 
Renal impairment 
No clinically relevant differences in tenofovir alafenamide, or tenofovir pharmacokinetics were 
observed between healthy subjects and patients with severe renal impairment (estimated CrCl ≥ 15 
mL/min and < 30 mL/min) in a Phase 1 study of tenofovir alafenamide.  In a separate Phase 1 study of 
emtricitabine alone, mean systemic emtricitabine exposure was higher in patients with severe renal 
impairment (estimated CrCl < 30 mL/min) (33.7 μg•h/mL) than in subjects with normal renal function 
(11.8 μg•h/mL). The safety of emtricitabine and tenofovir alafenamide has not been established in 
patients with severe renal impairment (estimated CrCl ≥ 15 mL/min and < 30 mL/min). 
 
Exposures of emtricitabine and tenofovir in 12 patients with end stage renal disease (estimated 
CrCl < 15 mL/min) on chronic haemodialysis who received emtricitabine and tenofovir alafenamide in 
combination with elvitegravir and cobicistat as a fixed-dose combination tablet (E/C/F/TAF) 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.  
There were no new safety issues identified in patients with end stage renal disease on chronic 
haemodialysis receiving emtricitabine and tenofovir alafenamide, in combination with elvitegravir and 
cobicistat as a fixed-dose combination tablet (see section 4.8). 
 
There are no pharmacokinetic data on emtricitabine or tenofovir alafenamide in patients with end stage 
renal disease (estimated CrCl < 15 mL/min) not on chronic haemodialysis.  The safety of emtricitabine 
and tenofovir alafenamide has not been established in these patients. 
 
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 or moderate hepatic impairment.  In patients with 
severe hepatic impairment, total plasma concentrations of tenofovir alafenamide and tenofovir are 
lower than those seen in subjects with normal hepatic function.  When corrected for protein binding, 
unbound (free) plasma concentrations of tenofovir alafenamide in severe hepatic impairment and 
normal hepatic function are similar. 
 
Hepatitis B and/or hepatitis C virus co-infection 
The pharmacokinetics of emtricitabine and tenofovir alafenamide have not been fully evaluated in 
patients co-infected with HBV and/or HCV. 
 



 

27 

5.3 Preclinical safety data 
 
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 BMD in rats and dogs at tenofovir 
exposures at least four times greater than those expected after administration of Descovy.  A minimal 
infiltration of histiocytes was present in the eye in dogs at tenofovir alafenamide and tenofovir 
exposures of approximately 4 and 17 times greater, respectively, than those expected after 
administration of Descovy. 
 
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 fumarate, carcinogenicity studies and a rat peri-
postnatal study were conducted only with tenofovir disoproxil fumarate.  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 fumarate 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 
Macrogol 3350 
Talc 
Iron oxide black (E172) 
 
6.2 Incompatibilities 
 
Not applicable. 
 
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. 
 



 

28 

6.5 Nature and contents of container 
 
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 60 (2 bottles of 30) and 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/1/16/1099/001 
EU/1/16/1099/002 
EU/1/16/1099/005 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 21 April 2016 
 
 
10. DATE OF REVISION OF THE TEXT 
 
{MM/YYYY} 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu. 



 

29 

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 
 
Descovy 200 mg/25 mg film-coated tablets 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each tablet contains 200 mg of emtricitabine and tenofovir alafenamide fumarate equivalent to 25 mg 
of tenofovir alafenamide. 
 
 
3. PHARMACEUTICAL FORM 
 
Film-coated tablet. 
 
Blue, rectangular-shaped, film-coated tablet of dimensions 12.5 mm x 6.4 mm debossed with “GSI” 
on one side and “225” on the other side of the tablet. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Descovy is indicated in combination with other antiretroviral agents for the treatment of adults and 
adolescents (aged 12 years and older with body weight at least 35 kg) infected with human 
immunodeficiency virus type 1 (HIV-1) (see sections 4.2 and 5.1). 
 
4.2 Posology and method of administration 
 
Therapy should be initiated by a physician experienced in the management of HIV infection. 
 
Posology 
 
Adults and adolescents aged 12 years and older, weighing at least 35 kg 
Descovy should be administered as shown in Table 1. 
 
Table 1: Dose of Descovy according to third agent in the HIV treatment regimen 
 

Dose of Descovy Third agent in HIV treatment regimen 
(see section 4.5) 

Descovy 200/10 mg once 
daily 

Atazanavir with ritonavir or cobicistat 
Darunavir with ritonavir or cobicistat1 
Lopinavir with ritonavir 

Descovy 200/25 mg once 
daily 

Dolutegravir, efavirenz, maraviroc, 
nevirapine, rilpivirine, raltegravir 

1 Descovy 200/10 mg in combination with darunavir 800 mg and cobicistat 150 mg, administered as a fixed-dose 
combination tablet, was studied in treatment- naive subjects, see section 5.1. 

 
If the patient misses a dose of Descovy within 18 hours of the time it is usually taken, the patient 
should take Descovy as soon as possible and resume the normal dosing schedule.  If a patient misses a 
dose of Descovy by more than 18 hours, the patient should not take the missed dose and simply 
resume the usual dosing schedule. 
 



 

30 

If the patient vomits within 1 hour of taking Descovy another tablet should be taken. 
 
Elderly 
No dose adjustment of Descovy is required in elderly patients (see sections 5.1 and 5.2). 
 
Renal impairment 
No dose adjustment of Descovy is required in adults or adolescents (aged at least 12 years and of at 
least 35 kg body weight) with estimated creatinine clearance (CrCl) ≥ 30 mL/min. Descovy should be 
discontinued in patients with estimated CrCl that declines below 30 mL/min during treatment (see 
section 5.2). 
 
No dose adjustment of Descovy is required in adults with end stage renal disease (estimated 
CrCl < 15 mL/min) on chronic haemodialysis; however, Descovy should generally be avoided but 
may 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, Descovy should be administered after 
completion of haemodialysis treatment. 
 
Descovy should be avoided in patients with estimated CrCl ≥ 15 mL/min and < 30 mL/min, or 
< 15 mL/min who are not on chronic haemodialysis, as the safety of Descovy has not been established 
in these populations. 
 
No data are available to make dose recommendations in children less than 18 years with end stage 
renal disease. 
 
Hepatic impairment 
No dose adjustment of Descovy is required in patients with hepatic impairment.  
 
Paediatric population 
The safety and efficacy of Descovy in children younger than 12 years of age, or weighing < 35 kg, 
have not yet been established.  No data are available. 
 
Method of administration 
 
Descovy should be taken orally, once daily with or without food (see section 5.2).  The film-coated 
tablet 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. 
 
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. 
 
The safety and efficacy of Descovy in patients co-infected with HIV-1 and hepatitis C virus (HCV) 
have not been established. 
 
Tenofovir alafenamide is active against hepatitis B virus (HBV).  Discontinuation of Descovy 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 Descovy should be closely 



 

31 

monitored with both clinical and laboratory follow-up for at least several months after stopping 
treatment. 
 
Liver disease 
 
The safety and efficacy of Descovy in patients with significant underlying liver disorders have not 
been established (see sections 4.2 and 5.2). 
 
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. 
 
Patients with HIV-1 harbouring mutations 
 
Descovy should be avoided in antiretroviral-experienced patients with HIV-1 harbouring the K65R 
mutation (see section 5.1). 
 



 

32 

Triple nucleoside therapy 
 
There have been reports of a high rate of virological failure and of emergence of resistance at an early 
stage when tenofovir disoproxil was combined with lamivudine and abacavir as well as with 
lamivudine and didanosine as a once daily regimen.  Therefore, the same problems may be seen if 
Descovy is administered with a third nucleoside analogue. 
 
Opportunistic infections 
 
Patients receiving Descovy or any other antiretroviral therapy may continue to develop opportunistic 
infections and other complications of HIV infection, and, therefore, should remain under close clinical 
observation by physicians experienced in the treatment of patients with HIV associated diseases. 
 
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 
 
Descovy 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 48 weeks but emtricitabine exposure was significantly higher than in patients with 
normal renal function.  Although there were no new safety issues identified, the implications of 
increased emtricitabine exposure remain uncertain (see sections 4.8 and 5.2). 
 
Co-administration of other medicinal products 
 
The co-administration of Descovy is not recommended with certain anticonvulsants (e.g., 
carbamazepine, oxcarbazepine, phenobarbital and phenytoin), antimycobacterials (e.g., rifampicin, 
rifabutin, rifapentine), St. John’s wort and HIV protease inhibitors (PIs) other than atazanavir, 
lopinavir and darunavir (see section 4.5). 
 
Descovy should not be administered concomitantly with medicinal products containing tenofovir 
alafenamide, tenofovir disoproxil, emtricitabine, lamivudine or adefovir dipivoxil. 
 
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. 
 



 

33 

Descovy should not be administered concomitantly with medicinal products containing tenofovir 
alafenamide, tenofovir disoproxil, emtricitabine, lamivudine or adefovir dipivoxil. 
 
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).  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., rifampicin, 
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 Descovy and development of resistance.  Co-administration of Descovy 
with other medicinal products that inhibit P-gp and BCRP activity (e.g., cobicistat, ritonavir, 
ciclosporin) is expected to increase the absorption and plasma concentration of tenofovir alafenamide.  
Based on data from an in vitro study, co-administration of tenofovir alafenamide and xanthine oxidase 
inhibitors (e.g., febuxostat) is not expected to increase systemic exposure to tenofovir in vivo. 
 
Tenofovir alafenamide is not an inhibitor of CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, or 
CYP2D6 in vitro.  It is not an inhibitor or inducer of CYP3A in vivo.  Tenofovir alafenamide is a 
substrate of OATP1B1 and OATP1B3 in vitro.  The distribution of tenofovir alafenamide in the body 
may be affected by the activity of OATP1B1 and OATP1B3. 
 
Other interactions 
 
Tenofovir alafenamide is not an inhibitor of human uridine diphosphate glucuronosyltransferase 
(UGT) 1A1 in vitro.  It is not known whether tenofovir alafenamide is an inhibitor of other 
UGT enzymes.  Emtricitabine did not inhibit the glucuronidation reaction of a non-specific UGT 
substrate in vitro. 
 
Interactions between the components of Descovy and potential co-administered medicinal products are 
listed in Table 2 (increase is indicated as “↑”, decrease as “↓”, no change as “↔”).  The interactions 
described are based on studies conducted with Descovy, or the components of Descovy as individual 
agents and/or in combination, or are potential drug-drug interactions that may occur with Descovy. 
 
Table 2: Interactions between the individual components of Descovy and other medicinal 
products 
 

Medicinal product by 
therapeutic areas1 

Effects on medicinal product levels. 
Mean percent change in AUC, 

Cmax, Cmin2 

Recommendation concerning 
co-administration with Descovy 

ANTI-INFECTIVES 
Antifungals 
Ketoconazole 
Itraconazole 

Interaction not studied with either of 
the components of Descovy. 
 
Co-administration of ketoconazole or 
itraconazole, which are potent P-gp 
inhibitors, is expected to increase 
plasma concentrations of tenofovir 
alafenamide. 

The recommended dose of Descovy 
is 200/10 mg once daily. 



 

34 

Medicinal product by 
therapeutic areas1 

Effects on medicinal product levels. 
Mean percent change in AUC, 

Cmax, Cmin2 

Recommendation concerning 
co-administration with Descovy 

Fluconazole 
Isavuconazole 

Interaction not studied with either of 
the components of Descovy. 
 
Co-administration of fluconazole or 
isavuconazole may increase plasma 
concentrations of tenofovir 
alafenamide. 

Dose Descovy according to the 
concomitant antiretroviral (see 
section 4.2). 

Antimycobacterials 
Rifabutin 
Rifampicin 
Rifapentine 

Interaction not studied with either of 
the components of Descovy. 
 
Co-administration of rifampicin, 
rifabutin, and rifapentine, all of which 
are P-gp inducers, may decrease 
tenofovir alafenamide plasma 
concentrations, which may result in 
loss of therapeutic effect and 
development of resistance. 

Co-administration of Descovy and 
rifabutin rifampicin, or rifapentine 
is not recommended. 

Anti-hepatitis C virus medicinal products 
Ledipasvir (90 mg once daily)/ 
sofosbuvir (400 mg once daily), 
emtricitabine (200 mg once 
daily)/ tenofovir alafenamide 
(10 mg once daily)3 

Ledipasvir: 
AUC: ↑ 79% 
Cmax: ↑ 65% 
Cmin: ↑ 93% 
 
Sofosbuvir: 
AUC: ↑ 47% 
Cmax: ↑ 29% 
 
Sofosbuvir metabolite GS-331007: 
AUC: ↑ 48% 
Cmax: ↔ 
Cmin: ↑ 66% 
 
Emtricitabine: 
AUC: ↔ 
Cmax: ↔ 
Cmin: ↔ 
 
Tenofovir alafenamide: 
AUC: ↔ 
Cmax: ↔ 

No dose adjustment of ledipasvir or 
sofosbuvir is required.  Dose 
Descovy according to the 
concomitant antiretroviral (see 
section 4.2). 



 

35 

Medicinal product by 
therapeutic areas1 

Effects on medicinal product levels. 
Mean percent change in AUC, 

Cmax, Cmin2 

Recommendation concerning 
co-administration with Descovy 

Ledipasvir (90 mg once daily)/ 
sofosbuvir (400 mg once daily), 
emtricitabine (200 mg once 
daily)/ tenofovir alafenamide 
(25 mg once daily)4 

Ledipasvir: 
AUC: ↔ 
Cmax: ↔ 
Cmin: ↔ 
 
Sofosbuvir: 
AUC: ↔ 
Cmax: ↔ 
 
Sofosbuvir metabolite GS-331007: 
AUC: ↔ 
Cmax: ↔ 
Cmin: ↔ 
 
Emtricitabine: 
AUC: ↔ 
Cmax: ↔ 
Cmin: ↔ 
 
Tenofovir alafenamide: 
AUC: ↑ 32% 
Cmax: ↔ 

No dose adjustment of ledipasvir or 
sofosbuvir is required.  Dose 
Descovy according to the 
concomitant antiretroviral (see 
section 4.2). 

Sofosbuvir (400 mg once daily)/ 
velpatasvir (100 mg once daily), 
emtricitabine (200 mg once 
daily)/ tenofovir alafenamide  
(10 mg once daily)3 

Sofosbuvir: 
AUC: ↑ 37% 
Cmax: ↔ 
 
Sofosbuvir metabolite GS-331007: 
AUC: ↑ 48% 
Cmax: ↔ 
Cmin: ↑ 58% 
 
Velpatasvir: 
AUC: ↑ 50% 
Cmax: ↑ 30% 
Cmin: ↑ 60% 
 
Emtricitabine: 
AUC: ↔ 
Cmax: ↔ 
Cmin: ↔ 
 
Tenofovir alafenamide: 
AUC: ↔ 
Cmax: ↓ 20% 

No dose adjustment of sofosbuvir, 
velpatasvir or voxilaprevir is 
required.  Dose Descovy according 
to the concomitant antiretroviral 
(see section 4.2). 



 

36 

Medicinal product by 
therapeutic areas1 

Effects on medicinal product levels. 
Mean percent change in AUC, 

Cmax, Cmin2 

Recommendation concerning 
co-administration with Descovy 

Sofosbuvir/velpatasvir/ 
voxilaprevir 
(400 mg/100 mg/100 mg+100 mg 
once daily)7/  
emtricitabine (200 mg once 
daily)/ tenofovir alafenamide 
(10 mg once daily)3 

Sofosbuvir: 
AUC: ↔ 
Cmax: ↑ 27% 
 
Sofosbuvir metabolite GS-331007: 
AUC: ↑ 43% 
Cmax: ↔ 
 
Velpatasvir: 
AUC: ↔ 
Cmin: ↑ 46% 
Cmax: ↔ 
 
Voxilaprevir: 
AUC: ↑ 171% 
Cmin: ↑ 350% 
Cmax: ↑ 92% 
 
Emtricitabine: 
AUC: ↔ 
Cmin: ↔ 
Cmax: ↔ 
 
Tenofovir alafenamide: 
AUC: ↔ 
Cmax: ↓ 21% 

Sofosbuvir/velpatasvir/ 
voxilaprevir 
(400 mg/100 mg/100 mg+100 mg 
once daily)7/  
emtricitabine (200 mg once 
daily)/ tenofovir alafenamide 
(25 mg once daily)4 

Sofosbuvir: 
AUC: ↔ 
Cmax: ↔ 
 
Sofosbuvir metabolite GS-331007: 
AUC: ↔ 
Cmin: ↔ 
 
Velpatasvir: 
AUC: ↔ 
Cmin: ↔ 
Cmax: ↔ 
 
Voxilaprevir: 
AUC: ↔ 
Cmin: ↔ 
Cmax: ↔ 
 
Emtricitabine: 
AUC: ↔ 
Cmin: ↔ 
Cmax: ↔ 
 
Tenofovir alafenamide: 
AUC: ↑ 52% 
Cmax: ↑ 32% 

No dose adjustment of sofosbuvir, 
velpatasvir or voxilaprevir is 
required.  Dose Descovy according 
to the concomitant antiretroviral 
(see section 4.2). 



 

37 

Medicinal product by 
therapeutic areas1 

Effects on medicinal product levels. 
Mean percent change in AUC, 

Cmax, Cmin2 

Recommendation concerning 
co-administration with Descovy 

ANTIRETROVIRALS 
HIV protease inhibitors 
Atazanavir/cobicistat 
(300 mg/150 mg once daily), 
tenofovir alafenamide (10 mg) 

Tenofovir alafenamide: 
AUC: ↑ 75% 
Cmax: ↑ 80% 
 
Atazanavir: 
AUC: ↔ 
Cmax: ↔ 
Cmin: ↔ 

The recommended dose of Descovy 
is 200/10 mg once daily. 

Atazanavir/ritonavir (300/100 mg 
once daily), tenofovir 
alafenamide (10 mg) 

Tenofovir alafenamide: 
AUC: ↑ 91% 
Cmax: ↑ 77% 
 
Atazanavir: 
AUC: ↔ 
Cmax: ↔ 
Cmin: ↔ 

The recommended dose of Descovy 
is 200/10 mg once daily. 

Darunavir/cobicistat (800/150 mg 
once daily), tenofovir 
alafenamide (25 mg once daily)5 

Tenofovir alafenamide: 
AUC: ↔ 
Cmax: ↔ 
 
Tenofovir: 
AUC: ↑ 224% 
Cmax: ↑ 216% 
Cmin: ↑ 221% 
 
Darunavir: 
AUC: ↔ 
Cmax: ↔ 
Cmin: ↔ 

The recommended dose of Descovy 
is 200/10 mg once daily. 

Darunavir/ritonavir (800/100 mg 
once daily), tenofovir 
alafenamide (10 mg once daily) 

Tenofovir alafenamide: 
AUC: ↔ 
Cmax: ↔ 
 
Tenofovir: 
AUC: ↑ 105% 
Cmax: ↑ 142% 
 
Darunavir: 
AUC: ↔ 
Cmax: ↔ 
Cmin: ↔ 

The recommended dose of Descovy 
is 200/10 mg once daily. 

Lopinavir/ritonavir (800/200 mg 
once daily), tenofovir 
alafenamide (10 mg once daily) 

Tenofovir alafenamide: 
AUC: ↑ 47% 
Cmax: ↑ 119% 
 
Lopinavir: 
AUC: ↔ 
Cmax: ↔ 
Cmin: ↔ 

The recommended dose of Descovy 
is 200/10 mg once daily. 

Tipranavir/ritonavir Interaction not studied with either of 
the components of Descovy. 
 
Tipranavir/ritonavir results in P-gp 
induction.  Tenofovir alafenamide 
exposure is expected to decrease 
when tipranavir/ritonavir is used in 
combination with Descovy. 

Co-administration with Descovy is 
not recommended. 



 

38 

Medicinal product by 
therapeutic areas1 

Effects on medicinal product levels. 
Mean percent change in AUC, 

Cmax, Cmin2 

Recommendation concerning 
co-administration with Descovy 

Other protease inhibitors Effect is unknown. There are no data available to make 
dosing recommendations for 
co-administration with other 
protease inhibitors. 

Other HIV antiretrovirals 
Dolutegravir (50 mg once daily), 
tenofovir alafenamide (10 mg 
once daily)3 

Tenofovir alafenamide: 
AUC: ↔ 
Cmax: ↔ 
 
Dolutegravir: 
AUC: ↔ 
Cmax: ↔ 
Cmin: ↔ 

The recommended dose of Descovy 
is 200/25 mg once daily. 

Rilpivirine (25 mg once daily), 
tenofovir alafenamide (25 mg 
once daily) 

Tenofovir alafenamide: 
AUC: ↔ 
Cmax: ↔ 
 
Rilpivirine: 
AUC: ↔ 
Cmax: ↔ 
Cmin: ↔ 

The recommended dose of Descovy 
is 200/25 mg once daily. 

Efavirenz (600 mg once daily), 
tenofovir alafenamide (40 mg 
once daily)4 

Tenofovir alafenamide: 
AUC: ↓ 14% 
Cmax: ↓ 22% 

The recommended dose of Descovy 
is 200/25 mg once daily. 

Maraviroc 
Nevirapine 
Raltegravir 

Interaction not studied with either of 
the components of Descovy. 
 
Tenofovir alafenamide exposure is 
not expected to be affected by 
maraviroc, nevirapine 
or raltegravir, nor is it expected to 
affect the metabolic and excretion 
pathways relevant to maraviroc, 
nevirapine or raltegravir. 

The recommended dose of Descovy 
is 200/25 mg once daily. 

ANTICONVULSANTS 
Oxcarbazepine 
Phenobarbital 
Phenytoin 

Interaction not studied with either of 
the components of Descovy. 
 
Co-administration of oxcarbazepine, 
phenobarbital, or phenytoin, all of 
which are P-gp inducers, may 
decrease tenofovir alafenamide 
plasma concentrations, which may 
result in loss of therapeutic effect and 
development of resistance. 

Co-administration of Descovy and 
oxcarbazepine, phenobarbital or 
phenytoin is not recommended. 

Carbamazepine (titrated from 
100 mg to 300 mg twice a day), 
emtricitabine/tenofovir 
alafenamide (200 mg/25 mg once 
daily)5,6 

Tenofovir alafenamide: 
AUC: ↓ 55% 
Cmax: ↓ 57% 
 
Co-administration of carbamazepine, 
a P-gp inducer, decreases tenofovir 
alafenamide plasma concentrations, 
which may result in loss of 
therapeutic effect and development of 
resistance. 

Co-administration of Descovy and 
carbamazepine is not 
recommended. 



 

39 

Medicinal product by 
therapeutic areas1 

Effects on medicinal product levels. 
Mean percent change in AUC, 

Cmax, Cmin2 

Recommendation concerning 
co-administration with Descovy 

ANTIDEPRESSANTS 
Sertraline (50 mg once daily), 
tenofovir alafenamide (10 mg 
once daily)3 

Tenofovir alafenamide: 
AUC: ↔ 
Cmax: ↔ 
 
Sertraline: 
AUC: ↑ 9% 
Cmax: ↑ 14% 

No dose adjustment of sertraline is 
required.  Dose Descovy according 
to the concomitant antiretroviral 
(see section 4.2). 

HERBAL PRODUCTS 
St. John’s wort (Hypericum 
perforatum) 

Interaction not studied with either of 
the components of Descovy. 
 
Co-administration of St. John’s wort, 
a P-gp inducer, may decrease 
tenofovir alafenamide plasma 
concentrations, which may result in 
loss of therapeutic effect and 
development of resistance. 

Co-administration of Descovy with 
St. John’s wort is not 
recommended. 

IMMUNOSUPPRESSANTS 
Ciclosporin Interaction not studied with either of 

the components of Descovy. 
 
Co-administration of ciclosporin, a 
potent P-gp inhibitor, is expected to 
increase plasma concentrations of 
tenofovir alafenamide. 

The recommended dose of Descovy 
is 200/10 mg once daily. 

ORAL CONTRACEPTIVES 
Norgestimate 
(0.180/0.215/0.250 mg once 
daily), ethinylestradiol (0.025 mg 
once daily), 
emtricitabine/tenofovir 
alafenamide (200/25 mg once 
daily)5 

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

No dose adjustment of 
norgestimate/ethinylestradiol is 
required.  Dose Descovy according 
to the concomitant antiretroviral 
(see section 4.2). 

SEDATIVES/HYPNOTICS 
Orally administered midazolam 
(2.5 mg single dose), tenofovir 
alafenamide (25 mg once daily) 

Midazolam: 
AUC: ↔ 
Cmax: ↔ 

No dose adjustment of midazolam 
is required.  Dose Descovy 
according to the concomitant 
antiretroviral (see section 4.2). Intravenously administered 

midazolam (1 mg single dose), 
tenofovir alafenamide (25 mg 
once daily) 

Midazolam: 
AUC: ↔ 
Cmax: ↔ 

1 When doses are provided, they are the doses used in clinical drug-drug interaction studies.  
2     When data are available from drug-drug interaction studies. 
3 Study conducted with elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide fixed-dose combination tablet. 
4 Study conducted with emtricitabine/rilpivirine/tenofovir alafenamide fixed-dose combination tablet. 
5 Study conducted with Descovy. 
6 Emtricitabine/tenofovir alafenamide was taken with food in this study. 
7 Study conducted with additional voxilaprevir 100 mg to achieve voxilaprevir exposurers expected in HCV-infected 

patients. 
 



 

40 

4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
 
There are no adequate and well-controlled studies of Descovy or its components in pregnant women.  
There are no or limited data (less than 300 pregnancy outcomes) from the use of tenofovir alafenamide 
in pregnant women.  However, 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 
tenofovir alafenamide in animals have shown no evidence of harmful effects on fertility parameters, 
pregnancy, or foetal development (see section 5.3). 
 
Descovy should be used during pregnancy only if the potential benefit justifies the potential risk to  
the foetus. 
 
Breast-feeding 
 
It is not known whether tenofovir alafenamide is excreted in human milk.  Emtricitabine is excreted in 
human milk.  In animal studies it has been shown that tenofovir is excreted in milk. 
 
There is insufficient information on the effects of emtricitabine and tenofovir in newborns/infants.  
Therefore, Descovy 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 
 
There are no data on fertility from the use of Descovy in humans.  In animal studies there were no 
effects of emtricitabine and tenofovir alafenamide on mating or fertility parameters (see section 5.3). 
 
4.7 Effects on ability to drive and use machines 
 
Patients should be informed that dizziness has been reported during treatment with Descovy. 
 
4.8 Undesirable effects 
 
Summary of the safety profile 
 
Assessment of adverse reactions is based on safety data from across all Phase 2 and 3 studies in which 
3,112 HIV-1 infected patients received medicinal products containing emtricitabine and tenofovir 
alafenamide and from post-marketing experience.  In clinical studies of 866 treatment-naïve adult 
patients receiving emtricitabine and tenofovir alafenamide with elvitegravir and cobicistat as the fixed-
dose combination tablet elvitegravir 150 mg/cobicistat 150 mg/emtricitabine 200 mg/tenofovir 
alafenamide (as fumarate) 10 mg (E/C/F/TAF) through 144 weeks, the most frequently reported 
adverse reactions were diarrhoea (7%), nausea (11%), and headache (6%). 
 
Tabulated summary of adverse reactions 
 
The adverse reactions in Table 3 are listed by system organ class and frequency.  Frequencies are 
defined as follows: very common (≥ 1/10), common (≥ 1/100 to < 1/10) and uncommon (≥ 1/1,000 to 
< 1/100). 
 
Table 3: Tabulated list of adverse reactions1 
 



 

41 

Frequency Adverse reaction 
Blood and lymphatic system disorders 
Uncommon: anaemia2 
Psychiatric disorders 
Common: abnormal dreams 
Nervous system disorders 
Common: headache, dizziness 
Gastrointestinal disorders 
Very common: nausea 
Common: diarrhoea, vomiting, abdominal pain, flatulence 
Uncommon: dyspepsia 
Skin and subcutaneous tissue disorders 
Common: rash 
Uncommon: angioedema3,4, pruritus, urticaria4 
Musculoskeletal and connective tissue disorders 
Uncommon: arthralgia 
General disorders and administration site conditions 
Common: fatigue 
1 With the exception of angioedema, anaemia and urticaria (see footnotes 2, 3 and 4), all adverse reactions were identified 

from clinical studies of F/TAF containing products.  The frequencies were derived from Phase 3 E/C/F/TAF clinical 
studies in 866 treatment-naïve adult patients through 144 weeks of treatment (GS-US-292-0104 and GS-US-292-0111). 

2 This adverse reaction was not observed in the clinical studies of F/TAF-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. 
 
Description of selected adverse reactions 
 
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 lipid laboratory tests 
In studies in treatment- naïve patients, increases from baseline were observed in both the tenofovir 
alafenamide fumarate and tenofovir disoproxil fumarate containing treatment groups for the fasting 
lipid parameters total cholesterol, direct low-density lipoprotein (LDL)- and high-density lipoprotein 
(HDL)-cholesterol, and triglycerides at Week 144.  The median increase from baseline for those 
parameters was greater in the E/C/F/TAF group compared with the elvitegravir 150 mg/cobicistat 
150 mg/emtricitabine 200 mg/tenofovir disoproxil (as fumarate) 245 mg (E/C/F/TDF) group at 
Week 144 (p < 0.001 for the difference between treatment groups for fasting total cholesterol, direct 
LDL- and HDL-cholesterol, and triglycerides).  The median (Q1, Q3) change from baseline in total 
cholesterol to HDL-cholesterol ratio at Week 144 was 0.2 (-0.3, 0.7) in the E/C/F/TAF group and 0.1 
(-0.4, 0.6) in the E/C/F/TDF group (p = 0.006 for the difference between treatment groups). 
 
In a study of virologically suppressed patients switching from emtricitabine/tenofovir disoproxil 
fumarate to Descovy while maintaining the third antiretroviral agent (Study GS-US-311-1089), 
increases from baseline were observed in the fasting lipid parameters total cholesterol, direct LDL 
cholesterol and triglycerides in the Descovy arm compared with little change in the 
emtricitabine/tenofovir disproxil fumarate arm (p ≤ 0.009 for the difference between groups in 
changes from baseline).  There was little change from baseline in median fasting values for HDL 



 

42 

cholesterol and glucose, or in the fasting total cholesterol to HDL cholesterol ratio in either treatment 
arm at Week 96.  None of the changes was considered clinically relevant. 
 
In a study of virologically suppressed adult patients switching from abacavir/lamivudine to Descovy 
while maintaining the third antiretroviral agent (Study GS-US-311-1717), there were minimal changes 
in lipid parameters.  
 
Metabolic parameters 
Weight and levels of blood lipids and glucose may increase during antiretroviral therapy (see 
section 4.4). 
 
Paediatric population 
 
The safety of emtricitabine and tenofovir alafenamide was evaluated through 48 weeks in an open-
label clinical study (GS-US-292-0106) in which HIV-1 infected, treatment-naïve paediatric patients 
aged 12 to < 18 years received emtricitabine and tenofovir alafenamide in combination with 
elvitegravir and cobicistat as a fixed-dose combination tablet.  The safety profile of emtricitabine and 
tenofovir alafenamide given with elvitegravir and cobicistat in 50 adolescent patients was similar to 
that in adults (see section 5.1). 
 
Other special populations 
 
Patients with renal impairment 
The safety of emtricitabine and tenofovir alafenamide was evaluated through 144 weeks in an open-
label clinical study (GS-US-292-0112) in which 248 HIV-1 infected patients who were either 
treatment-naïve (n = 6) or virologically suppressed (n = 242) with mild to moderate renal impairment 
(estimated glomerular filtration rate by Cockcroft-Gault method [eGFRCG]: 30-69 mL/min) received 
emtricitabine and tenofovir alafenamide in combination with elvitegravir and cobicistat as a fixed-dose 
combination tablet.  The safety profile in patients with mild to moderate renal impairment was similar 
to that in patients with normal renal function (see section 5.1). 
 
The safety of emtricitabine and tenofovir alafenamide was evaluated through 48 weeks 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 and tenofovir alafenamide in combination with elvitegravir and cobicistat as a fixed-dose 
combination tablet.  There were no new safety issues identified in patients with end stage renal disease 
on chronic haemodialysis receiving emtricitabine and tenofovir alafenamide, in combination with 
elvitegravir and cobicistat as a fixed-dose combination tablet (see section 5.2). 
 
Patients co-infected with HIV and HBV 
The safety of emtricitabine and tenofovir alafenamide in combination with elvitegravir and cobicistat 
as a fixed-dose combination tablet (elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide 
[E/C/F/TAF]) was evaluated in 72 HIV/HBV co-infected patients receiving treatment for HIV in an 
open-label clinical study (GS-US-292-1249), through Week 48, in which patients were switched from 
another antiretroviral regimen (which included tenofovir disoproxil fumarate [TDF] in 69 of 72 
patients) to E/C/F/TAF.  Based on these limited data, the safety profile of emtricitabine and tenofovir 
alafenamide in combination with elvitegravir and cobicistat as a fixed-dose combination tablet, in 
patients with HIV/HBV co-infection, was similar to that in patients with HIV-1 monoinfection (see 
section 4.4). 
 
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. 
 

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


 

43 

4.9 Overdose 
 
If overdose occurs the patient must be monitored for evidence of toxicity (see section 4.8).  Treatment 
of overdose with Descovy consists of general supportive measures including monitoring of vital signs 
as well as observation of the clinical status of the patient. 
 
Emtricitabine can be removed by haemodialysis, 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 haemodialysis 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: J05AR17. 
 
Mechanism of action 
 
Emtricitabine is a nucleoside reverse transcriptase inhibitor (NRTI) and nucleoside analogue of 
2’-deoxycytidine.  Emtricitabine is phosphorylated by cellular enzymes to form emtricitabine 
triphosphate.  Emtricitabine triphosphate inhibits HIV replication through incorporation into viral 
deoxyribonucleic acid (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 fumarate 
in concentrating tenofovir in peripheral blood mononuclear cells (PBMCs) or HIV target cells 
including lymphocytes 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 
 
Emtricitabine and tenofovir alafenamide demonstrated synergistic antiviral activity in cell culture. 
No antagonism was observed with emtricitabine or tenofovir alafenamide when combined with other 
antiretroviral agents. 
 
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 50% effective concentration 
(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 strain specific 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 



 

44 

(M, N, and O), including subtypes A, B, C, D, E, F, and G (EC50 values ranged from 0.10 to 12.0 nM) 
and showed strain specific activity against HIV-2 (EC50 values ranged from 0.91 to 2.63 nM). 
 
Resistance 
 
In vitro 
Reduced susceptibility to emtricitabine is associated with M184V/I mutations in HIV-1 RT. 
 
HIV-1 isolates with reduced susceptibility to tenofovir alafenamide express a K65R mutation in 
HIV-1 RT; in addition, a K70E mutation in HIV-1 RT has been transiently observed. 
 
In treatment-naïve patients 
In a pooled analysis of antiretroviral-naïve patients receiving emtricitabine and tenofovir alafenamide 
(10 mg) given with elvitegravir and cobicistat as a fixed-dose combination tablet in Phase 3 studies 
GS-US-292-0104 and GS-US-292-0111, genotyping was performed on plasma HIV-1 isolates from all 
patients with HIV-1 RNA ≥ 400 copies/mL at confirmed virological failure, at Week 144, or at the 
time of early study drug discontinuation.  Through Week 144, the development of one or more 
primary emtricitabine, tenofovir alafenamide, or elvitegravir resistance-associated mutations was 
observed in HIV-1 isolates from 12 of 22 patients with evaluable genotypic data from paired baseline 
and E/C/F/TAF treatment-failure isolates (12 of 866 patients [1.4%]) compared with 12 of 
20 treatment-failure isolates from patients with evaluable genotypic data in the E/C/F/TDF group (12 
of 867 patients [1.4%]).  In the E/C/F/TAF group, the mutations that emerged were M184V/I (n = 11) 
and K65R/N (n = 2) in RT and T66T/A/I/V (n = 2), E92Q (n = 4), Q148Q/R (n = 1), and N155H 
(n = 2) in integrase.  Of the HIV-1 isolates from 12 patients with resistance development in the 
E/C/F/TDF group, the mutations that emerged were M184V/I (n = 9), K65R/N (n = 4), and L210W (n 
= 1) in RT and E92Q/V (n = 4) and Q148R (n = 2), and N155H/S (n=3) in integrase.  Most 
HIV-1 isolates from patients in both treatment groups who developed resistance mutations to 
elvitegravir in integrase also developed resistance mutations to emtricitabine in RT. 
 
In patients co-infected with HIV and HBV  
In a clinical study of HIV virologically suppressed patients co-infected with chronic hepatitis B, who 
received emtricitabine and tenofovir alafenamide, given with elvitegravir and cobicistat as a 
fixed-dose combination tablet (E/C/F/TAF), for 48 weeks (GS-US-292-1249, n = 72), 2 patients 
qualified for resistance analysis.  In these 2 patients, no amino acid substitutions associated with 
resistance to any of the components of E/C/F/TAF were identified in HIV-1 or HBV. 
 
Cross-resistance in HIV-1 infected, treatment-naïve or virologically suppressed patients 
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 
 
There are no efficacy and safety studies conducted in treatment-naïve patients with Descovy. 
 
Clinical efficacy of Descovy was established from studies conducted with emtricitabine and tenofovir 
alafenamide when given with elvitegravir and cobicistat as the fixed-dose combination tablet 
E/C/F/TAF. 
 
HIV-1 infected, treatment-naïve patients 
In studies GS-US-292-0104 and GS-US-292-0111, patients were randomised in a 1:1 ratio to receive 
either emtricitabine 200 mg and tenofovir alafenamide 10 mg (n = 866) once daily or emtricitabine 



 

45 

200 mg + tenofovir disoproxil (as fumarate) 245 mg (n = 867) once daily, both given with elvitegravir 
150 mg + cobicistat 150 mg as a fixed-dose combination tablet.  The mean age was 36 years (range: 
18-76), 85% were male, 57% were White, 25% were Black, and 10% were Asian.  Nineteen percent of 
patients were identified as Hispanic/Latino.  The mean baseline plasma HIV-1 RNA was 
4.5 log10 copies/mL (range: 1.3-7.0) and 23% had baseline viral loads > 100,000 copies/mL.  The 
mean baseline CD4+ cell count was 427 cells/mm3 (range: 0-1,360) and 13% had a CD4+ cell count 
< 200 cells/mm3. 
 
E/C/F/TAF demonstrated statistical superiority in achieving HIV-1 RNA < 50 copies/mL when 
compared to E/C/F/TDF at Week 144.  The difference in percentage was 4.2% (95% CI: 0.6% to 
7.8%).  Pooled treatment outcomes at 48 and 144 weeks are shown in Table 4. 
 
Table 4: Pooled virological outcomes of Studies GS-US-292-0104 and GS-US-292-0111 at 
Weeks 48 and 144a,b 
 
 Week 48 Week 144 
 E/C/F/TAF 

(n = 866) 
E/C/F/TDFe 

(n = 867) 
E/C/F/TAF 

(n = 866) 
E/C/F/TDF 

(n = 867) 
HIV-1 RNA < 50 copies/mL 92% 90% 84% 80% 

Treatment difference 2.0% (95% CI: -0.7% to 4.7%) 4.2% (95% CI: 0.6% to 7.8%) 
HIV-1 RNA ≥ 50 copies/mLc 4% 4% 5%  4%  
No virologic data at 
Week 48 or 144 window 

4% 6% 11% 16% 

Discontinued study drug 
due to AE or deathd 

1% 2% 1%  3% 

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

2% 4% 9% 11% 

Missing data during 
window but on study 
drug 

1% < 1% 1% 1%  

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

    

Age 
< 50 years 
≥ 50 years 

 
716/777 (92%) 
84/89 (94%) 

 
680/753 (90%) 
104/114 (91%) 

 
647/777 (83%) 
82/89 (92%)  

 
602/753 (80%) 
92/114 (81%)  

 
Sex 

Male 
Female 

 
674/733 (92%) 
126/133 (95%) 

 
673/740 (91%) 
111/127 (87%) 

 
616/733 (84%) 
113/133 (85%)  

 
603/740 (81%) 
91/127 (72%)  

 
Race 

Black 
Non-black 

 
197/223 (88%) 
603/643 (94%) 

 
177/213 (83%) 
607/654 (93%) 

 
168/223 (75%) 
561/643 (87%)  

 
152/213 (71%) 
542/654 (83%)  

 
Baseline viral load 

≤ 100,000 copies/mL 
> 100,000 copies/mL 

 
629/670 (94%) 
171/196 (87%) 

 
610/672 (91%) 
174/195 (89%) 

 
567/670 (85%) 
162/196 (83%)   

 
537/672 (80%) 
157/195 (81%)  

 
Baseline CD4+ cell count 

< 200 cells/mm3 
≥ 200 cells/mm3 

 
96/112 (86%) 
703/753 (93%) 

 
104/117 (89%) 
680/750 (91%) 

 
93/112 (83%) 
635/753 (84%)  

 
94/117 (80%) 
600/750 (80%)  

 
HIV-1 RNA < 20 copies/mL 84.4% 84.0% 81.1%  75.8%  

Treatment difference 0.4% (95% CI: -3.0% to 3.8%) 5.4% (95% CI: 1.5% to 9.2%)  



 

46 

E/C/F/TAF = elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide 
E/C/F/TDF = elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate 
a Week 48 window was between Day 294 and 377 (inclusive); Week 144 window was between Day 966 and 1049 

(inclusive). 
b In both studies, patients were stratified by baseline HIV-1 RNA (≤ 100,000 copies/mL, > 100,000 copies/mL to 

≤ 400,000 copies/mL, or > 400,000 copies/mL), by CD4+ cell count (< 50 cells/μL, 50-199 cells/μL, or ≥ 200 cells/μL), 
and by region (US or ex-US). 

c 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; patients who discontinued for reasons other than an adverse event (AE), death or lack or loss of efficacy 
and at the time of discontinuation had a viral value of ≥ 50 copies/mL. 

d 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. 

e 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. 

 
The mean increase from baseline in CD4+ cell count was 230 cells/mm3 in patients receiving 
E/C/F/TAF and 211 cells/mm3 in patients receiving E/C/F/TDF (p = 0.024) at Week 48, and 326 
cells/mm3 in E/C/F/TAF-treated patients and 305 cells/mm3 in E/C/F/TDF-treated patients (p = 0.06) 
at Week 144.  
 
Clinical efficacy of Descovy in treatment-naïve patients was also established from a study conducted 
with emtricitabine and tenofovir alafenamide (10 mg) when given with darunavir (800 mg) and 
cobicistat as a fixed-dose combination tablet (D/C/F/TAF).  In Study GS-US-299-0102, patients were 
randomised in a 2:1 ratio to receive either fixed-dose combination D/C/F/TAF once daily (n = 103) or 
darunavir and cobicistat and emtricitabine/tenofovir disoproxil fumarate once daily (n = 50).  The 
proportions of patients with plasma HIV-1 RNA < 50 copies/mL and < 20 copies/mL are shown in 
Table 5. 
 



 

47 

Table 5: Virological outcomes of Study GS-US-299-0102 at Week 24 and 48a 
 
 Week 24 Week 48 

 D/C/F/TAF 
(n = 103) 

Darunavir,  
cobicistat and 

emtricitabine/tenofovir 
disoproxil fumarate 

(n = 50) 

D/C/F/TAF 
(n = 103) 

Darunavir,  
cobicistat and 

emtricitabine/tenofovir 
disoproxil fumarate 

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

75% 74% 77% 84% 

Treatment difference 3.3% (95% CI: -11.4% to 18.1%) -6.2% (95% CI: -19.9% to 7.4%) 
HIV-1 RNA 
≥ 50 copies/mLb 

20% 24% 16% 12% 

No virologic data at 
Week 48 window 

5% 2% 8% 4% 

Discontinued study 
drug due to AE or 
deathc  

1% 0 1% 2% 

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

4% 2% 7% 2% 

Missing data during 
window but on study 
drug 

0 0 0 0 

HIV-1 RNA 
< 20 copies/mL 

55% 62% 63% 76% 

Treatment difference -3.5% (95% CI: -19.8% to 12.7%) -10.7% (95% CI: -26.3% to 4.8%) 
D/C/F/TAF = darunavir/cobicistat/emtricitabine/tenofovir alafenamide 
a Week 48 window was between Day 294 and 377 (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 an adverse event (AE), death or lack or loss of efficacy and at 
the time of discontinuation had a viral value of ≥ 50 copies/mL. 

c 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. 

d 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. 

 
HIV-1 infected virologically suppressed patients 
In Study GS-US-311-1089, the efficacy and safety of switching from emtricitabine/tenofovir 
disoproxil fumarate to Descovy while maintaining the third antiretroviral agent were evaluated in a 
randomised, double-blind study of virologically suppressed HIV-1 infected adults (n = 663).  Patients 
must have been stably suppressed (HIV-1 RNA < 50 copies/mL) on their baseline regimen for at least 
6 months and had HIV-1 with no resistance mutations to emtricitabine or tenofovir alafenamide prior 
to study entry.  Patients were randomised in a 1:1 ratio to either switch to Descovy (n = 333), or stay 
on their baseline emtricitabine/tenofovir disoproxil fumarate containing regimen (n = 330).  Patients 
were stratified by the class of the third agent in their prior treatment regimen.  At baseline, 46% of 
patients were receiving emtricitabine/tenofovir disoproxil fumarate in combination with a boosted PI 
and 54% of patients were receiving emtricitabine/tenofovir disoproxil fumarate in combination with an 
unboosted third agent. 
 
Treatment outcomes of Study GS-US-311-1089 through 48 and 96 weeks are presented in Table 6. 



 

48 

Table 6: Virological outcomes of Study GS-US-311-1089 at Weeks 48a and 96b 
 
 Week 48 Week 96 

 Descovy containing 
regimen 
(n = 333) 

 

Emtricitabine/tenofov
ir disoproxil fumarate 

containing regimen 
(n = 330) 

Descovy containing 
regimen 
(n = 333) 

Emtricitabine/tenofov
ir disoproxil fumarate 

containing regimen 
(n = 330) 

HIV-1 RNA 
< 50 copies/mL 

94% 93% 89% 89% 

Treatment 
difference 

1.3% (95% CI: -2.5% to 5.1%) -0.5% (95% CI: -5.3% to 4.4%) 

HIV-1 RNA 
≥ 50 copies/mLc 

< 1% 2% 2% 1% 

No virologic data 
at Week 48 or 96 
window 

5% 5% 9% 10% 

Discontinued 
study drug due 
to AE or 
deathd 

2% 1% 2% 2% 

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

3% 5% 

7% 9% 

Missing data 
during window 
but on study 
drug 

< 1% 0 0 <1% 

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

    

Boosted PIs 142/155 (92%) 140/151 (93%) 133/155 (86%) 133/151 (88%) 
Other third 
agents 

172/178 (97%) 167/179 (93%) 162/178 (91%)   161/179 (90%) 

PI = protease inhibitor 
a Week 48 window was between Day 294 and 377 (inclusive). 
b Week 96 window was between Day 630 and 713 (inclusive). 
c Includes patients who had ≥ 50 copies/mL in the Week 48 or Week 96 window; patients who discontinued early due to 

lack or loss of efficacy; patients who discontinued for reasons other than an adverse event (AE), death or lack or loss of 
efficacy and at the time of discontinuation had a viral value of ≥ 50 copies/mL. 

d 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. 

e 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. 

 
In Study GS-US-311-1717, patients who were virologically suppressed (HIV-1 RNA <50 copies/mL) 
on their abacavir/lamivudine containing regimen for at least 6 months were randomised in a 1:1 ratio 
to either switch to Descovy (N=280) while maintaining their third agent at baseline or stay on their 
baseline abacavir/lamivudine -containing regimen (N=276).  

Patients were stratified by the class of the third agent in their prior treatment regimen. At baseline, 
30% of patients were receiving abacavir/lamivudine in combination with a boosted protease inhibitor 
and 70% of patients were receiving abacavir/lamivudine in combination with an unboosted third agent. 
Virologic success rates at Week 48 were: Descovy Containing Regimen:  89.7% (227 of 253 subjects); 
Abacavir/lamivudine Containing Regimen: 92.7%% (230 of 248 subjects). At Week 48, switching to a 



 

49 

Descovy-containing regimen was non-inferior to staying on a baseline abacavir/lamivudine-containing 
regimen in maintaining HIV-1 RNA < 50 copies/mL  
 
HIV-1 infected patients with mild to moderate renal impairment 
In Study GS-US-292-0112, the efficacy and safety of emtricitabine and tenofovir alafenamide were 
evaluated in an open-label clinical study in which 242 HIV-1 infected patients with mild to moderate 
renal impairment (eGFRCG: 30-69 mL/min) were switched to emtricitabine and tenofovir alafenamide 
(10 mg) given with elvitegravir and cobicistat as a fixed-dose combination tablet.  Patients were 
virologically suppressed (HIV-1 RNA < 50 copies/mL) for at least 6 months before switching. 
 
The mean age was 58 years (range: 24-82), with 63 patients (26%) who were ≥ 65 years of age.  
Seventy-nine percent were male, 63% were White, 18% were Black, and 14% were Asian.  Thirteen 
percent of patients were identified as Hispanic/Latino.  At baseline, median eGFR was 56 mL/min, 
and 33% of patients had an eGFR from 30 to 49 mL/min.  The mean baseline CD4+ cell count was 
664 cells/mm3 (range: 126-1,813). 
 
At Week 144, 83.1% (197/237 patients) maintained HIV-1 RNA < 50 copies/mL after switching to 
emtricitabine and tenofovir alafenamide given with elvitegravir and cobicistat as a fixed-dose 
combination tablet. 
 
In Study GS-US-292-1825, the efficacy and safety of emtricitabine and tenofovir alafenamide, given 
with elvitegravir and cobicistat as a fixed-dose combination tablet were evaluated in a single arm, 
open-label clinical study in which 55 HIV-1 infected adults with end stage renal disease 
(eGFRCG < 15 mL/min) on chronic haemodialysis for at least 6 months before switching to 
emtricitabine and tenofovir alafenamide, given with elvitegravir and cobicistat as a fixed-dose 
combination tablet.  Patients were virologically suppressed (HIV-1 RNA < 50 copies/mL) for at least 
6 months before switching. 
 
The mean age was 48 years (range 23-64).  Seventy-six percent were male, 82% were Black and 18% 
were White.  Fifteen percent of patients identified as Hispanic/Latino.  The mean baseline CD4+ cell 
count was 545 cells/mm3 (range 205-1473).  At Week 48, 81.8% (45/55 patients) maintained HIV-1 
RNA < 50 copies/mL after switching to emtricitabine and tenofovir alafenamide, given with 
elvitegravir and cobicistat as a fixed-dose combination tablet.  There were no clinically significant 
changes in fasting lipid laboratory tests in patients who switched. 
 
Patients co-infected with HIV and HBV 
In open-label Study GS-US-292-1249, the efficacy and safety of emtricitabine and tenofovir 
alafenamide, given with elvitegravir and cobicistat as a fixed-dose combination tablet (E/C/F/TAF), 
were evaluated in adult patients co-infected with HIV-1 and chronic hepatitis B.  Sixty-nine of the 
72 patients were on prior TDF-containing antiretroviral therapy.  At the start of treatment with 
E/C/F/TAF, the 72 patients had been HIV-suppressed (HIV-1 RNA < 50 copies/mL) for at least 
6 months with or without suppression of HBV DNA and had compensated liver function.  The mean 
age was 50 years (range 28-67), 92% of patients were male, 69% were White, 18% were Black, and 
10% were Asian.  The mean baseline CD4+ cell count was 636 cells/mm3 (range 263-1498).  
Eighty-six percent of patients (62/72) were HBV suppressed (HBV DNA < 29 IU/mL) and 42% 
(30/72) were HBeAg positive at baseline. 
 
Of the patients who were HBeAg positive at baseline, 1/30 (3.3%) achieved seroconversion to 
anti-HBe at Week 48.  Of the patients who were HBsAg positive at baseline, 3/70 (4.3%) achieved 
seroconversion to anti-HBs Week 48. 
 
At Week 48, 92% of patients (66/72) maintained HIV-1 RNA < 50 copies/mL after switching to 
emtricitabine and tenofovir alafenamide, given with elvitegravir and cobicistat as a fixed-dose 
combination tablet.  The mean change from baseline in CD4+ cell count at Week 48 was -2 cells/mm3.  
Ninety-two percent (66/72 patients) had HBV DNA < 29 IU/mL using missing = failure analysis at 
Week 48.  Of the 62 patients who were HBV suppressed at baseline, 59 remained suppressed and 



 

50 

3 had missing data. Of the 10 patients who were not HBV suppressed at baseline 
(HBV DNA ≥ 29 IU/mL), 7 became suppressed, 2 remained detectable, and 1 had missing data. 
 
There are limited clinical data on the use of E/C/F/TAF in HIV/HBV co-infected patients who are 
treatment-naïve. 
 
Changes in measures of bone mineral density 
In studies in treatment-naïve patients, emtricitabine and tenofovir alafenamide given with elvitegravir 
and cobicistat as a fixed-dose combination tablet was associated with smaller reductions in bone 
mineral density (BMD) compared to E/C/F/TDF through 144 weeks of treatment as measured by dual 
energy X ray absorptiometry (DXA) analysis of hip (mean change: −0.8% vs −3.4%, p < 0.001) and 
lumbar spine (mean change: −0.9% vs −3.0%, p < 0.001). In a separate study, emtricitabine and 
tenofovir alafenamide given with  darunavir and cobicistat as a fixed-dose combination tablet was also 
associated with smaller reductions in BMD (as measured by hip and lumbar spine DXA analysis) 
through 48 weeks of treatment compared to darunavir, cobicistat, emtricitabine and tenofovir 
disoproxil fumarate.   
 
In a study in virologically suppressed adult patients, improvements in BMD were noted through 
96 weeks after switching to Descovy from a TDF containing regimen compared to minimal changes 
with maintaining the TDF containing regimen as measured by DXA analysis of hip (mean change 
from baseline of 1.9% vs -0.3%, p < 0.001) and lumbar spine (mean change from baseline of 2.2% vs 
-0.2%, p < 0.001). 
 
In a study in virologically suppressed adult patients, BMD did not change significantly through 48 
weeks after switching to Descovy from an abacavir/lamivudine containing regimen compared to 
maintaining the abacavir/lamivudine containing regimen as measured by DXA analysis of hip (mean 
change from baseline of 0.3% vs 0.2%, p = 0.55) and lumbar spine (mean change from baseline of 
0.1% vs < 0.1%, p = 0.78). 
 
Changes in measures of renal function 
In studies in treatment-naïve patients, emtricitabine and tenofovir alafenamide given with elvitegravir 
and cobicistat as a fixed-dose combination tablet through 144 weeks was associated with a lower 
impact on renal safety parameters (as measured after 144 weeks treatment by eGFRCG and urine 
protein to creatinine ratio and after 96 weeks treatment by urine albumin to creatinine ratio) compared 
to E/C/F/TDF. Through 144 weeks of treatment, no subject discontinued E/C/F/TAF due to a 
treatment-emergent renal adverse event compared with 12 subjects who discontinued E/C/F/TDF 
(p < 0.001).  
 
In a separate study in treatment-naïve patients, emtricitabine and tenofovir alafenamide given with 
darunavir and cobicistat as a fixed-dose combination tablet was associated with a lower impact on 
renal safety parameters through 48 weeks of treatment compared to darunavir and cobicistat given 
with emtricitabine/tenofovir disoproxil fumarate (see also section 4.4).  
 
In a study in virologically suppressed adult patients measures of tubular proteinuria were similar in 
patients switching to a regimen containing Descovy compared to patients who stayed on an 
abacavir/lamivudine containing regimen at baseline. At Week 48, the median percentage change in 
urine retinol binding protein to creatinine ratio was 4% in the Descovy group and 16% in those 
remaining on an abacavir/lamivudine containing regimen; and in urine beta-2 microglobulin to 
creatinine ratio it was 4% vs. 5%. 
 
Paediatric population 
 
In Study GS-US-292-0106, the efficacy, safety, and pharmacokinetics of emtricitabine and tenofovir 
alafenamide were evaluated in an open-label study in which 50 HIV-1 infected, treatment-naïve 
adolescents received emtricitabine and tenofovir alafenamide (10 mg) given with elvitegravir and 
cobicistat as a fixed-dose combination tablet.  Patients had a mean age of 15 years (range: 12-17), and 
56% were female, 12% were Asian, and 88% were Black.  At baseline, median plasma HIV-1 RNA 



 

51 

was 4.7 log10 copies/mL, median CD4+ cell count was 456 cells/mm3 (range: 95-1,110), and median 
CD4+% was 23% (range: 7-45%).  Overall, 22% had baseline plasma HIV-1 RNA 
> 100,000 copies/mL.  At 48 weeks, 92% (46/50) achieved HIV-1 RNA < 50 copies/mL, similar to 
response rates in studies of treatment-naïve HIV-1 infected adults.  The mean increase from baseline 
in CD4+ cell count at Week 48 was 224 cells/mm3.  No emergent resistance to E/C/F/TAF was 
detected through Week 48. 
 
The European Medicines Agency has deferred the obligation to submit the results of studies with 
Descovy in one or more subsets of the paediatric population in the treatment of HIV-1 infection (see 
section 4.2 for information on paediatric use). 
 
5.2 Pharmacokinetic properties 
 
Absorption 
 
Emtricitabine is rapidly and extensively absorbed following oral administration with peak plasma 
concentrations occurring at 1 to 2 hours post-dose.  Following multiple dose oral administration of 
emtricitabine to 20 HIV-1 infected subjects, the (mean ± SD) steady state plasma emtricitabine peak 
concentrations (Cmax) were 1.8 ± 0.7 μg/mL and the area-under the plasma concentration-time curve 
over a 24-hour dosing interval (AUC) was 10.0 ± 3.1 μg•h/mL.  The mean steady state plasma trough 
concentration at 24 hours post-dose was equal to or greater than the mean in vitro IC90 value for 
anti-HIV-1 activity. 
 
Emtricitabine systemic exposure was unaffected when emtricitabine was administered with food. 
 
Following administration of food in healthy subjects, peak plasma concentrations were observed 
approximately 1 hour post-dose for tenofovir alafenamide administered as F/TAF (25 mg) or 
E/C/F/TAF (10 mg).  The mean Cmax and AUClast, (mean ± SD) under fed conditions following a 
single 25 mg dose of tenofovir alafenamide administered in Descovy were 0.21 ± 0.13 μg/mL and 
0.25 ± 0.11 μg•h/mL, respectively.  The mean Cmax and AUClast following a single 10 mg dose of 
tenofovir alafenamide administered in E/C/F/TAF were 0.21 ± 0.10 μg/mL and 0.25 ± 0.08 μg•h/mL, 
respectively. 
 
Relative to fasting conditions, the administration of tenofovir alafenamide with a high fat meal 
(~800 kcal, 50% fat) resulted in a decrease in tenofovir alafenamide Cmax (15-37%) and an increase in 
AUClast (17-77%). 
 
Distribution 
 
In vitro binding of emtricitabine to human plasma proteins was < 4% and independent of 
concentration over the range of 0.02-200 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 
 
In vitro studies indicate that emtricitabine is not an inhibitor of human CYP enzymes.  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. 
 



 

52 

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 10 mg oral dose of tenofovir 
alafenamide (given with emtricitabine and elvitegravir and cobicistat) 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 (as fumarate) (given with 
emtricitabine and elvitegravir and cobicistat). 
 
In vitro, tenofovir alafenamide is not metabolised by CYP1A2, CYP2C8, CYP2C9, CYP2C19, or 
CYP2D6.  Tenofovir alafenamide is minimally metabolised by CYP3A4.  Upon co-administration 
with the moderate CYP3A inducer probe efavirenz, tenofovir alafenamide exposure was not 
significantly affected.  Following administration of tenofovir alafenamide, plasma [14C]-radioactivity 
showed a time-dependent profile with tenofovir alafenamide as the most abundant species in the initial 
few hours and uric acid in the remaining period. 
 
Elimination 
 
Emtricitabine is primarily excreted by the kidneys with complete recovery of the dose achieved in 
urine (approximately 86%) and faeces (approximately 14%).  Thirteen percent of the emtricitabine 
dose was recovered in urine as three metabolites.  The systemic clearance of emtricitabine averaged 
307 mL/min.  Following oral administration, the elimination half-life of emtricitabine is approximately 
10 hours. 
 
Renal excretion of intact tenofovir alafenamide is a minor pathway with < 1% of the dose eliminated 
in urine.  Tenofovir alafenamide is mainly 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 renally eliminated by both glomerular filtration and active tubular secretion. 
 
Pharmacokinetics in special populations 
 
Age, gender, and ethnicity 
No clinically relevant pharmacokinetic differences due to age, gender or ethnicity have been identified 
for emtricitabine, or tenofovir alafenamide. 
 
Paediatric population 
 
Exposures of emtricitabine and tenofovir alafenamide (given with elvitegravir and cobicistat) achieved 
in 24 paediatric patients aged 12 to < 18 years who received emtricitabine and tenofovir alafenamide 
given with elvitegravir and cobicistat in Study GS-US-292-0106 were similar to exposures achieved in 
treatment-naïve adults (Table 7). 
 



 

53 

Table 7: Pharmacokinetics of emtricitabine and tenofovir alafenamide in antiretroviral-naïve 
adolescents and adults 
 

 Adolescents Adults 
 FTCa TAFb TFVb FTCa TAFc TFVc 

AUCtau 
(ng•h/mL) 

14,424.4 
(23.9) 

242.8 
(57.8) 

275.8 
(18.4) 

11,714.1 
(16.6) 

206.4 
(71.8) 

292.6 
(27.4) 

Cmax 
(ng/mL) 

2,265.0 
(22.5) 

121.7 
(46.2) 

14.6 (20.0) 2,056.3 
(20.2) 

162.2 
(51.1) 

15.2 
(26.1) 

Ctau 
(ng/mL) 102.4 (38.9)

b N/A 10.0 (19.6) 95.2 (46.7) N/A 10.6 (28.5) 
E/C/F/TAF = elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide fumarate 
FTC = emtricitabine; TAF = tenofovir alafenamide fumarate; TFV = tenofovir 
N/A = not applicable 
Data are presented as mean (%CV). 
a n = 24 adolescents (GS-US-292-0106); n = 19 adults (GS-US-292-0102) 
b n = 23 adolescents (GS-US-292-0106, population PK analysis) 
c n = 539 (TAF) or 841 (TFV) adults (GS-US-292-0111 and GS-US-292-0104, population PK analysis) 
 
Renal impairment 
No clinically relevant differences in tenofovir alafenamide, or tenofovir pharmacokinetics were 
observed between healthy subjects and patients with severe renal impairment (estimated CrCl > 15 
mL/min and < 30 mL/min) in a Phase 1 study of tenofovir alafenamide.  In a separate Phase 1 study of 
emtricitabine alone, mean systemic emtricitabine exposure was higher in patients with severe renal 
impairment (estimated CrCl < 30 mL/min) (33.7 μg•h/mL) than in subjects with normal renal function 
(11.8 μg•h/mL). The safety of emtricitabine and tenofovir alafenamide has not been established in 
patients with severe renal impairment (estimated CrCl ≥ 15 mL/min and < 30 mL/min). 
 
Exposures of emtricitabine and tenofovir in 12 patients with end stage renal disease (estimated 
CrCl < 15 mL/min) on chronic haemodialysis who received emtricitabine and tenofovir alafenamide in 
combination with elvitegravir and cobicistat as a fixed-dose combination tablet (E/C/F/TAF) 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.  
There were no new safety issues in patients with end stage renal disease on chronic haemodialysis 
receiving emtricitabine and tenofovir alafenamide, in combination with elvitegravir and cobicistat as a 
fixed-dose combination tablet (see section 4.8). 
 
There are no pharmacokinetic data on emtricitabine or tenofovir alafenamide in patients with end stage 
renal disease (estimated CrCl < 15 mL/min) not on chronic haemodialysis.  The safety of emtricitabine 
and tenofovir alafenamide has not been established in these patients. 
 
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 or moderate hepatic impairment.  In patients with 
severe hepatic impairment, total plasma concentrations of tenofovir alafenamide and tenofovir are 
lower than those seen in subjects with normal hepatic function.  When corrected for protein binding, 
unbound (free) plasma concentrations of tenofovir alafenamide in severe hepatic impairment and 
normal hepatic function are similar. 
 
Hepatitis B and/or hepatitis C virus co-infection 
The pharmacokinetics of emtricitabine and tenofovir alafenamide have not been fully evaluated in 
patients co-infected with HBV and/or HCV. 
 



 

54 

5.3 Preclinical safety data 
 
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 BMD in rats and dogs at tenofovir 
exposures at least four times greater than those expected after administration of Descovy.  A minimal 
infiltration of histiocytes was present in the eye in dogs at tenofovir alafenamide and tenofovir 
exposures of approximately 4 and 17 times greater, respectively, than those expected after 
administration of Descovy. 
 
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 fumarate, carcinogenicity studies and a rat peri-
postnatal study were conducted only with tenofovir disoproxil fumarate.  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 fumarate 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 
Macrogol 3350 
Talc 
Indigo carmine aluminium lake (E132) 
 
6.2 Incompatibilities 
 
Not applicable. 
 
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. 
 



 

55 

6.5 Nature and contents of container 
 
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 60 (2 bottles of 30) and 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/1/16/1099/003 
EU/1/16/1099/004 
EU/1/16/1099/006 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 21 April 2016 
 
 
10. DATE OF REVISION OF THE TEXT 
 
{MM/YYYY} 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu. 



 

56 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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 



 

57 

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 
 
The requirements for submission of periodic safety update reports 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. 
 
The marketing authorisation holder shall submit the first periodic safety update report for this product 
within 6 months following authorisation. 
 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 
 
• Risk Management Plan (RMP) 
 
The 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. 



 

58 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 



 

59 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 



 

60 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING AND THE IMMEDIATE 
PACKAGING 
 
BOTTLE AND CARTON LABELLING 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Descovy 200 mg/10 mg film-coated tablets 
emtricitabine/tenofovir alafenamide 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each film-coated tablet contains 200 mg of emtricitabine and tenofovir alafenamide fumarate 
equivalent to 10 mg of tenofovir alafenamide. 
 
 
3. LIST OF EXCIPIENTS 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
30 film-coated tablets 
 
60 (2 bottles of 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. 
 
 



 

61 

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/1/16/1099/001 30 film-coated tablets 
EU/1/16/1099/002 90 (3 bottles of 30) film-coated tablets 
EU/1/16/1099/005 60 (2 bottles of 30) film-coated tablets 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Descovy 200 mg/10 mg [Outer packaging only] 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC: {number} 
SN: {number} 
NN: {number}  
 



 

62 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING AND THE IMMEDIATE 
PACKAGING 
 
BOTTLE AND CARTON LABELLING 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Descovy 200 mg/25 mg film-coated tablets 
emtricitabine/tenofovir alafenamide 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each film-coated tablet contains 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 
 
60 (2 bottles of 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. 
 
 



 

63 

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/1/16/1099/003 30 film-coated tablets 
EU/1/16/1099/004 90 (3 bottles of 30) film-coated tablets 
EU/1/16/1099/006 60 (2 bottles of 30) film-coated tablets 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Descovy 200 mg/25 mg [Outer packaging only] 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC: {number} 
SN: {number} 
NN: {number}  
 



 

64 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 



 

65 

Package leaflet: Information for the user 
 

Descovy 200 mg/10 mg film-coated tablets 
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 Descovy is and what it is used for 
2. What you need to know before you take Descovy 
3. How to take Descovy 
4. Possible side effects 
5. How to store Descovy 
6. Contents of the pack and other information 
 
 
1. What Descovy is and what it is used for 
 
Descovy contains two active substances: 
 
• 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) 
 
Descovy blocks the action of the reverse transcriptase enzyme, which is essential for the virus to 
multiply.  Descovy therefore reduces the amount of HIV in your body. 
 
Descovy in combination with other medicines is for the treatment of human immunodeficiency 
virus 1 (HIV-1) infection in adults and adolescents 12 years of age and older, who weigh at least 
35 kg. 
 
 
2. What you need to know before you take Descovy 
 
Do not take Descovy: 
• If you are allergic to emtricitabine, tenofovir alafenamide or any of the other ingredients of 

this medicine (listed in section 6 of this leaflet). 
 
Warnings and precautions 
 
You must remain under the care of your doctor while taking Descovy. 
 
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 



 

66 

people.  This medicine is not a cure for HIV infection.  While taking Descovy you may still develop 
infections or other illnesses associated with HIV infection. 
 
Talk to your doctor before taking Descovy: 
 
• If you have liver problems or have suffered 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 liver problems may become worse after you stop taking Descovy.  Do 
not stop taking Descovy without talking to your doctor: see section 3, Do not stop taking 
Descovy. 

 
• Your doctor may not prescribe Descovy to you if the virus has a K65R mutation. 
 
While you are taking Descovy 
 
Once you start taking Descovy, 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 Descovy, there is a possibility that you may 
experience kidney problems when taking Descovy over a long period of time. 
 
Children and adolescents 
 
Do not give this medicine to children aged 11 years or under, or weighing less than 35 kg.  The use 
of Descovy in children aged 11 years or under has not yet been studied. 
 
Other medicines and Descovy 
 
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 
medicines.  Descovy may interact with other medicines.  As a result, the amounts of Descovy 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 used in treating hepatitis B infection: 
You should not take Descovy with medicines containing: 
• tenofovir alafenamide 
• tenofovir disoproxil 
• lamivudine 
• adefovir dipivoxil 
 
 Tell your doctor if you are taking any of these medicines. 
 
Other types of medicine: 
Talk to your doctor if you are taking: 
• antibiotics, used to treat bacterial infections including tuberculosis, containing: 

- rifabutin, rifampicin, and rifapentine 



 

67 

• antiviral medicines used to treat HIV: 
- emtricitabine and tipranavir 

• anticonvulsants, used to treat epilepsy, such as: 
- carbamazepine, oxcarbazepine, phenobarbital and phenytoin 

• herbal remedies used to treat depression and anxiety containing: 
- St. John’s wort (Hypericum perforatum) 

 
 Tell your doctor if you are taking these or any other medicines.  Do not stop your treatment 

without contacting your doctor. 
 
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 Descovy 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 
NRTIs during pregnancy, the benefit from the protection against HIV outweighed the risk of side 
effects. 
 
Do not breast-feed during treatment with Descovy.  This is because one of the active substances in 
this medicine passes into breast milk.  It is recommended that you do not breast-feed to avoid passing 
the virus to the baby through breast milk. 
 
Driving and using machines 
Descovy can cause dizziness.  If you feel dizzy when taking Descovy, do not drive and do not use any 
tools or machines. 
 
Descovy contains sodium 
This medicine contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially 
‘sodium-free’. 
 
 
3. How to take Descovy 
 
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 
Adolescents 12 years of age and older, who weigh at least 35 kg: one tablet each day with or 
without food 
 
Do not chew, crush or split the tablet. 
 
Always take the dose recommended by your doctor.  This is to make sure that your medicine is 
fully effective, and to reduce the risk of developing resistance to the treatment.  Do not change the 
dose unless your doctor tells you to. 
 
If you are on dialysis, take your daily dose of Descovy following completion of dialysis. 
 



 

68 

If you take more Descovy than you should 
 
If you take more than the recommended dose of Descovy 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 the tablet bottle 
with you so that you can show what you have taken. 
 
If you forget to take Descovy 
 
It is important not to miss a dose of Descovy. 
 
If you do miss a dose: 
• If you notice within 18 hours of the time you usually take Descovy, 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 Descovy, 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 Descovy, take another tablet. 
 
Do not stop taking Descovy 
 
Do not stop taking Descovy without talking to your doctor.  Stopping Descovy can seriously affect 
how well future treatment works.  If Descovy is stopped for any reason, speak to your doctor before 
you restart taking Descovy tablets. 
 
When your supply of Descovy 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 very important not to stop taking Descovy 
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 may lead to 
worsening of 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. 
 
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 serious side effects: tell a doctor immediately 
 
• Any signs of inflammation or infection.  In some patients with advanced HIV infection 

(AIDS) and who have had opportunistic infections in the past (infections that occur in people 
with a weak immune system), signs and symptoms of inflammation from previous infections 
may occur soon after antiretroviral 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. 



 

69 

• Autoimmune disorders (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 the side effects described above, tell your doctor immediately. 
 
Very common side effects 
(may affect more than 1 in 10 people) 
• feeling sick (nausea) 
 
Common side effects 
(may affect up to 1 in 10 people) 
• abnormal dreams 
• headache 
• dizziness 
• diarrhoea 
• vomiting 
• stomach pain 
• wind (flatulence) 
• rash 
• tiredness (fatigue) 
 
Uncommon side effects 
(may affect up to 1 in 100 people) 
• low red blood cell count (anaemia) 
• problems with digestion resulting in discomfort after meals (dyspepsia) 
• swelling of the face, lips, tongue or throat (angioedema) 
• itching (pruritus) 
• hives (urticaria) 
• joint pain (arthralgia) 
 
 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 Descovy 

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. 
 



 

70 

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 Descovy 
 
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 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. 
 
 
6. Contents of the pack and other information 
 
What Descovy contains 
 
The active substances are emtricitabine and tenofovir alafenamide.  Each Descovy film-coated tablet 
contains 200 mg of emtricitabine and tenofovir alafenamide fumarate equivalent to 10 mg of tenofovir 
alafenamide. 
 
The other ingredients are 
 
Tablet core: 
Microcrystalline cellulose, croscarmellose sodium, magnesium stearate. 
 
Film-coating: 
Polyvinyl alcohol, titanium dioxide, macrogol 3350, talc, iron oxide black (E172). 
 
What Descovy looks like and contents of the pack 
 
Descovy film-coated tablets are grey, rectangular-shaped tablets, debossed on one side with “GSI” and 
the number “210” on the other side of the tablet. 
 
Descovy comes in bottles of 30 tablets (with 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. 
 
The following pack sizes are available: outer cartons containing 1 bottle of 30 film-coated tablets and 
outer cartons containing 60 (2 bottles of 30) and 90 (3 bottles of 30) film-coated tablets.  Not all pack 
sizes may be marketed. 
 
Marketing Authorisation Holder: 
Gilead Sciences Ireland UC 
Carrigtohill 
County Cork, T45 DP77 
Ireland  
 

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


 

71 

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 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: + 420 910 871 986 
 

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

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 22 262 8702 
 

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

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

Österreich 
Gilead Sciences GesmbH 
Tel: + 43 1 260 830 
 

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

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

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

Portugal 
Gilead Sciences, Lda. 
Tel: + 351 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 
 



 

72 

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

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

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: + 30 210 8930 100 
 

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

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

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

 
This leaflet was last revised in <{MM/YYYY}> <{month YYYY}>. 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu. 



 

73 

Package leaflet: Information for the user 
 

Descovy 200 mg/25 mg film-coated tablets 
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 Descovy is and what it is used for 
2. What you need to know before you take Descovy 
3. How to take Descovy 
4. Possible side effects 
5. How to store Descovy 
6. Contents of the pack and other information 
 
 
1. What Descovy is and what it is used for 
 
Descovy contains two active substances: 
 
• 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) 
 
Descovy blocks the action of the reverse transcriptase enzyme, which is essential for the virus to 
multiply.  Descovy therefore reduces the amount of HIV in your body. 
 
Descovy in combination with other medicines is for the treatment of human immunodeficiency 
virus 1 (HIV-1) infection in adults and adolescents 12 years of age and older, who weigh at least 
35 kg. 
 
 
2. What you need to know before you take Descovy 
 
Do not take Descovy: 
• If you are allergic to emtricitabine, tenofovir alafenamide or any of the other ingredients of 

this medicine (listed in section 6 of this leaflet). 
 
Warnings and precautions 
 
You must remain under the care of your doctor while taking Descovy. 
 
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 



 

74 

people.  This medicine is not a cure for HIV infection.  While taking Descovy you may still develop 
infections or other illnesses associated with HIV infection. 
 
Talk to your doctor before taking Descovy: 
 
• If you have liver problems or have suffered 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 liver problems may become worse after you stop taking Descovy.  Do 
not stop taking Descovy without talking to your doctor: see section 3, Do not stop taking 
Descovy. 

 
• Your doctor may not prescribe Descovy to you if the virus has a K65R mutation. 
 
While you are taking Descovy 
 
Once you start taking Descovy, 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 Descovy, there is a possibility that you may 
experience kidney problems when taking Descovy over a long period of time. 
 
Children and adolescents 
 
Do not give this medicine to children aged 11 years or under, or weighing less than 35 kg.  The use 
of Descovy in children aged 11 years or under has not yet been studied. 
 
Other medicines and Descovy 
 
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 
medicines.  Descovy may interact with other medicines.  As a result, the amounts of Descovy 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 used in treating hepatitis B infection: 
You should not take Descovy with medicines containing: 
• tenofovir alafenamide 
• tenofovir disoproxil 
• lamivudine 
• adefovir dipivoxil 
 
 Tell your doctor if you are taking any of these medicines. 
 
Other types of medicine: 
Talk to your doctor if you are taking: 
• antibiotics, used to treat bacterial infections including tuberculosis, containing: 

- rifabutin, rifampicin, and rifapentine 



 

75 

• antiviral medicines used to treat HIV: 
- emtricitabine and tipranavir 

• anticonvulsants, used to treat epilepsy, such as: 
- carbamazepine, oxcarbazepine, phenobarbital and phenytoin 

• herbal remedies used to treat depression and anxiety containing: 
- St. John’s wort (Hypericum perforatum) 

 
 Tell your doctor if you are taking these or any other medicines.  Do not stop your treatment 

without contacting your doctor. 
 
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 Descovy 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 
NRTIs during pregnancy, the benefit from the protection against HIV outweighed the risk of side 
effects. 
 
Do not breast-feed during treatment with Descovy.  This is because one of the active substances in 
this medicine passes into breast milk.  It is recommended that you do not breast-feed to avoid passing 
the virus to the baby through breast milk. 
 
Driving and using machines 
Descovy can cause dizziness.  If you feel dizzy when taking Descovy, do not drive and do not use any 
tools or machines. 
 
Descovy contains sodium 
This medicine contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially 
‘sodium-free’. 
 
 
3. How to take Descovy 
 
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 
Adolescents 12 years of age and older, who weigh at least 35 kg: one tablet each day with or 
without food 
 
Do not chew, crush or split the tablet. 
 
Always take the dose recommended by your doctor.  This is to make sure that your medicine is 
fully effective, and to reduce the risk of developing resistance to the treatment.  Do not change the 
dose unless your doctor tells you to. 
 
If you are on dialysis, take your daily dose of Descovy following completion of dialysis. 
 



 

76 

If you take more Descovy than you should 
 
If you take more than the recommended dose of Descovy 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 the tablet bottle 
with you so that you can show what you have taken. 
 
If you forget to take Descovy 
 
It is important not to miss a dose of Descovy. 
 
If you do miss a dose: 
• If you notice within 18 hours of the time you usually take Descovy, 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 Descovy, 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 Descovy, take another tablet. 
 
Do not stop taking Descovy 
 
Do not stop taking Descovy without talking to your doctor.  Stopping Descovy can seriously affect 
how well future treatment works.  If Descovy is stopped for any reason, speak to your doctor before 
you restart taking Descovy tablets. 
 
When your supply of Descovy 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 very important not to stop taking Descovy 
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 may lead to 
worsening of 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. 
 
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 serious side effects: tell a doctor immediately 
 
• Any signs of inflammation or infection.  In some patients with advanced HIV infection 

(AIDS) and who have had opportunistic infections in the past (infections that occur in people 
with a weak immune system), signs and symptoms of inflammation from previous infections 
may occur soon after antiretroviral 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. 



 

77 

• Autoimmune disorders (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 the side effects described above, tell your doctor immediately. 
 
Very common side effects 
(may affect more than 1 in 10 people) 
• feeling sick (nausea) 
 
Common side effects 
(may affect up to 1 in 10 people) 
• abnormal dreams 
• headache 
• dizziness 
• diarrhoea 
• vomiting 
• stomach pain 
• wind (flatulence) 
• rash 
• tiredness (fatigue) 
 
Uncommon side effects 
(may affect up to 1 in 100 people) 
• low red blood cell count (anaemia) 
• problems with digestion resulting in discomfort after meals (dyspepsia) 
• swelling of the face, lips, tongue or throat (angioedema) 
• itching (pruritus) 
• hives (urticaria) 
• joint pain (arthralgia) 
 
 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 Descovy 

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. 
 



 

78 

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 Descovy 
 
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 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. 
 
 
6. Contents of the pack and other information 
 
What Descovy contains 
 
The active substances are emtricitabine and tenofovir alafenamide.  Each Descovy film-coated tablet 
contains 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, macrogol 3350, talc, indigo carmine aluminium lake (E132). 
 
What Descovy looks like and contents of the pack 
 
Descovy film-coated tablets are blue, rectangular-shaped tablets, debossed on one side with “GSI” and 
the number “225” on the other side of the tablet. 
 
Descovy comes in bottles of 30 tablets (with 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. 
 
The following pack sizes are available: outer cartons containing 1 bottle of 30 film-coated tablets and 
outer cartons containing 60 (2 bottles of 30) and 90 (3 bottles of 30) film-coated tablets.  Not all pack 
sizes may be marketed. 
 
Marketing Authorisation Holder: 
Gilead Sciences Ireland UC 
Carrigtohill 
County Cork, T45 DP77 
Ireland  
 

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


 

79 

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 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: + 420 910 871 986 
 

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

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 22 262 8702 
 

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

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

Österreich 
Gilead Sciences GesmbH 
Tel: + 43 1 260 830 
 

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

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

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

Portugal 
Gilead Sciences, Lda. 
Tel: + 351 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 
 



 

80 

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

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

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: + 30 210 8930 100 
 

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

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

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

 
This leaflet was last revised in <{MM/YYYY}> <{month YYYY}>. 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
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