Odefsey

1 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 



2 

This medicinal product is subject to additional monitoring.  This will allow quick identification of 
new safety information.  Healthcare professionals are asked to report any suspected adverse reactions.  
See section 4.8 for how to report adverse reactions. 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Odefsey 200 mg/25 mg/25 mg film-coated tablets 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each film-coated tablet contains 200 mg of emtricitabine, rilpivirine hydrochloride equivalent to 
25 mg of rilpivirine and tenofovir alafenamide fumarate equivalent to 25 mg of tenofovir alafenamide. 
 
Excipients with known effect 
 
Each tablet contains 189.8 mg lactose monohydrate. 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Film-coated tablet. 
 
Grey, capsule-shaped, film-coated tablets, of dimensions 15 mm x 7 mm, debossed with “GSI” on one 
side of the tablet and “255” on the other side of the tablet. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Odefsey is indicated for the treatment of adults and adolescents (aged 12 years and older with body 
weight at least 35 kg) infected with human immunodeficiency virus-1 (HIV-1) without known 
mutations associated with resistance to the non-nucleoside reverse transcriptase inhibitor (NNRTI) 
class, tenofovir or emtricitabine and with a viral load ≤ 100,000 HIV-1 RNA copies/mL (see 
sections 4.2, 4.4 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 
One tablet to be taken once daily with food (see section 5.2). 
 
If the patient misses a dose of Odefsey within 12 hours of the time it is usually taken, the patient 
should take Odefsey with food as soon as possible and resume the normal dosing schedule.  If a 
patient misses a dose of Odefsey by more than 12 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 4 hours of taking Odefsey another tablet should be taken with food.  If a 
patient vomits more than 4 hours after taking Odefsey they do not need to take another dose of 
Odefsey until the next regularly scheduled dose. 
 
Elderly 
No dose adjustment of Odefsey is required in elderly patients (see section 5.2). 
 
Renal impairment 
No dose adjustment of Odefsey is required in adults or in adolescents (aged at least 12 years and of at 
least 35 kg body weight) with estimated creatinine clearance (CrCl) ≥ 30 mL/min.  Odefsey should be 
discontinued in patients with estimated CrCl that declines below 30 mL/min during treatment (see 
section  5.2). 
 
No dose adjustment of Odefsey is required in adults with end stage renal disease (estimated 
CrCl < 15 mL/min) on chronic haemodialysis; however, Odefsey should generally be avoided but may 
be used with caution 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, Odefsey should be administered after 
completion of haemodialysis treatment. 
 
Odefsey 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 Odefsey 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 Odefsey is required in patients with mild (Child Pugh Class A) or moderate 
(Child Pugh Class B) hepatic impairment.  Odefsey should be used with caution in patients with 
moderate hepatic impairment.  Odefsey has not been studied in patients with severe hepatic 
impairment (Child Pugh Class C); therefore, Odefsey is not recommended for use in patients with 
severe hepatic impairment (see sections 4.4 and 5.2). 
 
Paediatric population 
The safety and efficacy of Odefsey in children younger than 12 years of age, or weighing < 35 kg, 
have not yet been established.  No data are available. 
 
Pregnancy 
Lower exposures of rilpivirine (one of the components of Odefsey) were observed during pregnancy; 
therefore viral load should be monitored closely.  Alternatively, switching to another antiretroviral 
regimen could be considered (see sections 4.4, 4.6, 5.1 and 5.2). 
 
Method of administration 
 
Odefsey should be taken orally, once daily with 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. 
 
Odefsey should not be co-administered with medicinal products that can result in significant decreases 
in rilpivirine plasma concentrations (due to cytochrome P450 [CYP]3A enzyme induction or gastric 
pH increase), which may result in loss of therapeutic effect of Odefsey (see section 4.5), including: 
 
• carbamazepine, oxcarbazepine, phenobarbital, phenytoin 
• rifabutin, rifampicin, rifapentine 



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• omeprazole, esomeprazole, dexlansoprazole, lansoprazole, pantoprazole, rabeprazole 
• dexamethasone (oral and parenteral doses), except as a single dose treatment 
• St. John’s wort (Hypericum perforatum) 
 
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. 
 
Virologic failure and development of resistance 
 
There are insufficient data to justify the use in patients with prior NNRTI failure.  Resistance testing 
and/or historical resistance data should guide the use of Odefsey (see section 5.1). 
 
In the pooled efficacy analysis from the two Phase 3 clinical studies in adults (C209 [ECHO] and 
C215 [THRIVE]) through 96 weeks, patients treated with emtricitabine/tenofovir disoproxil 
fumarate + rilpivirine with a baseline viral load > 100,000 HIV-1 RNA copies/mL had a greater risk of 
virologic failure (17.6% with rilpivirine versus 7.6% with efavirenz) compared to patients with a 
baseline viral load ≤ 100,000 HIV-1 RNA copies/mL (5.9% with rilpivirine versus 2.4% with 
efavirenz).  The virologic failure rate in patients treated with emtricitabine/tenofovir disoproxil 
fumarate + rilpivirine at Week 48 and Week 96 was 9.5% and 11.5% respectively, and 4.2% and 5.1% 
in the emtricitabine/tenofovir disoproxil fumarate + efavirenz arm.  The difference in the rate of new 
virologic failures from the Week 48 to Week 96 analysis between rilpivirine and efavirenz arms was 
not statistically significant.  Patients with a baseline viral load > 100,000 HIV-1 RNA copies/mL who 
experienced virologic failure exhibited a higher rate of treatment-emergent resistance to the NNRTI 
class.  More patients who failed virologically on rilpivirine than who failed virologically on efavirenz 
developed lamivudine/emtricitabine associated resistance (see section 5.1). 
 
Findings in adolescents (12 to less than 18 years of age) in Study C213 were generally in line with 
these data (for details see section 5.1). 
 
Only adolescents deemed likely to have good adherence to antiretroviral therapy should be treated 
with rilpivirine, as suboptimal adherence can lead to development of resistance and the loss of future 
treatment options. 
 
Cardiovascular 
 
At supratherapeutic doses (75 mg once daily and 300 mg once daily), rilpivirine has been associated 
with prolongation of the QTc interval of the electrocardiogram (ECG) (see sections 4.5 and 4.9).  
Rilpivirine at the recommended dose of 25 mg once daily is not associated with a clinically relevant 
effect on QTc.  Odefsey should be used with caution when co-administered with medicinal products 
with a known risk of Torsade de Pointes. 
 
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 Odefsey 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 Odefsey 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 Odefsey should be closely 
monitored with both clinical and laboratory follow-up for at least several months after stopping 
treatment. 



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



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Osteonecrosis 
 
Although the aetiology is considered to be multifactorial (including corticosteroid use, alcohol 
consumption, severe immunosuppression, higher body mass index), cases of osteonecrosis have been 
reported particularly in patients with advanced HIV disease and/or long-term exposure to CART.  
Patients should be advised to seek medical advice if they experience joint aches and pain, joint 
stiffness or difficulty in movement. 
 
Nephrotoxicity 
 
A potential risk of nephrotoxicity resulting from chronic exposure to low levels of tenofovir due to 
dosing with tenofovir alafenamide cannot be excluded (see section 5.3). 
 
Patients with end stage renal disease on chronic haemodialysis 
 
Odefsey should generally be avoided but may be used with caution 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). 
 
Pregnancy 
 
Lower exposures of rilpivirine were observed when rilpivirine 25 mg once daily was taken during 
pregnancy.  In the Phase 3 studies (C209 and C215), lower rilpivirine exposure, similar to that seen 
during pregnancy, has been associated with an increased risk of virological failure, therefore viral load 
should be monitored closely (see sections 4.6, 5.1 and 5.2).  Alternatively, switching to another 
antiretroviral regimen could be considered. 
 
Co-administration of other medicinal products 
 
Some medicinal products should not be co-administered with Odefsey (see sections 4.3 and 4.5). 
 
Odefsey should not be co-administered with other antiretroviral medicinal products (see section 4.5). 
 
Odefsey should not be co-administered with other medicinal products containing tenofovir 
alafenamide, lamivudine, tenofovir disoproxil or adefovir dipivoxil (see section 4.5). 
 
Excipients 
 
Odefsey contains lactose monohydrate.  Patients with rare hereditary problems of galactose 
intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicinal 
product. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
Odefsey is indicated for use as a complete regimen for the treatment of HIV-1 infection and should not 
be co-administered with other antiretroviral medicinal products.  Therefore, information regarding 
drug-drug interactions with other antiretroviral medicinal products is not provided.  Interaction studies 
have only been performed in adults. 
 



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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. 
 
Rilpivirine 
 
Rilpivirine is primarily metabolised by CYP3A.  Medicinal products that induce or inhibit CYP3A 
may thus affect the clearance of rilpivirine (see section 5.2).  Rilpivirine inhibits P-glycoprotein (P-gp) 
in vitro (50% inhibitory concentration [IC50] is 9.2 µM).  In a clinical study, rilpivirine did not 
significantly affect the pharmacokinetics of digoxin.  Additionally, in a clinical drug-drug interaction 
study with tenofovir alafenamide, which is more sensitive to intestinal P-gp inhibition, rilpivirine did 
not affect tenofovir alafenamide exposures when administered concurrently, indicating that rilpivirine 
is not a P-gp inhibitor in vivo. 
 
Rilpivirine is an in vitro inhibitor of the transporter MATE-2K with an IC50 of < 2.7 nM.  The clinical 
implications of this finding are currently unknown. 
 
Tenofovir alafenamide 
 
Tenofovir alafenamide is transported by P-gp and breast cancer resistance protein (BCRP).  Medicinal 
products that affect P-gp and BCRP activity may lead to changes in tenofovir alafenamide absorption 
(see Table 1).  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 
Odefsey and development of resistance.  Co-administration of Odefsey with other medicinal products 
that inhibit P-gp and BCRP activity (e.g., ketoconazole, fluconazole, itraconazole, posaconazole, 
voriconazole, 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.  Tenofovir alafenamide is not an inhibitor or inducer of CYP3A in vivo.  Tenofovir 
alafenamide is a substrate of organic anion transporting polypeptide (OATP) 1B1 and OATP1B3 
in vitro.  The distribution of tenofovir alafenamide in the body may be affected by the activity of 
OATP1B1 and OATP1B3. 
 
Concomitant use contraindicated 
 
Co-administration of Odefsey and medicinal products that induce CYP3A has been observed to 
decrease the plasma concentrations of rilpivirine which could potentially lead to loss of virologic 
response to Odefsey (see section 4.3) and possible resistance to rilpivirine and to the NNRTI class. 
 
Co-administration of Odefsey with proton pump inhibitors has been observed to decrease the plasma 
concentrations of rilpivirine (due to an increase in gastric pH) which could potentially lead to loss of 
virologic response to Odefsey (see section 4.3) and possible resistance to rilpivirine and to the 
NNRTI class. 
 
Concomitant use where caution is recommended 
 
CYP enzyme inhibitors 
Co-administration of Odefsey with medicinal products that inhibit CYP3A enzyme activity has been 
observed to increase rilpivirine plasma concentrations. 



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QT prolonging medicinal products 
Odefsey should be used with caution when co-administered with a medicinal product with a known 
risk of Torsade de Pointes (see section 4.4). 
 
Other interactions 
 
Tenofovir alafenamide is not an inhibitor of human uridine diphosphate glucuronosyltransferase 
(UGT) 1A1 in vitro.  It is not known whether emtricitabine, or tenofovir alafenamide are inhibitors of 
other UGT enzymes.  Emtricitabine did not inhibit the glucuronidation reaction of a non-specific UGT 
substrate in vitro. 
 
Interactions between Odefsey or its individual component(s) and co-administered medicinal products 
are listed in Table 1 below (increase is indicated as “↑”, decrease as “↓” and no change as “↔”). 
 
Table 1: Interactions between Odefsey or its individual component(s) and other medicinal 
products 
 

Medicinal product by therapeutic 
areas 

Effects on medicinal product 
levels. 

Mean percent change in AUC, 
Cmax, Cmin 

Recommendation concerning 
co-administration with 

Odefsey 

ANTI-INFECTIVES 
Antifungals 
Ketoconazole (400 mg once daily)/ 
Rilpivirine1 

Ketoconazole: 
AUC: ↓ 24% 
Cmin: ↓ 66% 
Cmax: ↔ 
 
Rilpivirine: 
AUC: ↑ 49% 
Cmin: ↑ 76% 
Cmax: ↑ 30% 
Inhibition of CYP3A 
 
Expected: 
Tenofovir alafenamide: 
AUC: ↑ 
Cmax: ↑ 
Inhibition of P-gp 
 
Interaction not studied with 
tenofovir alafenamide.  
Co-administration of ketoconazole 
is expected to increase plasma 
concentrations of tenofovir 
alafenamide (inhibition of P-gp). 

Co-administration is not 
recommended. 

Fluconazole 
Itraconazole 
Posaconazole 
Voriconazole 

Interaction not studied with any of 
the components of Odefsey.  
Co-administration of these 
antifungal agents is expected to 
increase plasma concentrations of 
rilpivirine (inhibition of CYP3A) 
and tenofovir alafenamide 
(inhibition of P-gp). 

Co-administration is not 
recommended. 



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Medicinal product by therapeutic 
areas 

Effects on medicinal product 
levels. 

Mean percent change in AUC, 
Cmax, Cmin 

Recommendation concerning 
co-administration with 

Odefsey 

Antimycobacterials 
Rifampicin/ Rilpivirine Rifampicin: 

AUC: ↔ 
Cmin: N/A 
Cmax: ↔ 
 
25-desacetyl-rifampicin: 
AUC: ↓ 9% 
Cmin: N/A 
Cmax: ↔ 
 
Rilpivirine: 
AUC: ↓ 80% 
Cmin: ↓ 89% 
Cmax: ↓ 69% 
Induction of CYP3A 
 
Expected: 
Tenofovir alafenamide: 
AUC: ↓ 
Cmax: ↓ 
Induction of P-gp 
 
Interaction not studied with 
tenofovir alafenamide.  
Co-administration is likely to cause 
significant decreases in the plasma 
concentrations of tenofovir 
alafenamide (induction of P-gp). 

Co-administration is 
contraindicated. 

Rifapentine Interaction not studied with any of 
the components of Odefsey.  
Co-administration is likely to cause 
significant decreases in the plasma 
concentrations of rilpivirine 
(induction of CYP3A) and 
tenofovir alafenamide (induction of 
P-gp). 

Co-administration is 
contraindicated. 



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Medicinal product by therapeutic 
areas 

Effects on medicinal product 
levels. 

Mean percent change in AUC, 
Cmax, Cmin 

Recommendation concerning 
co-administration with 

Odefsey 

Rifabutin (300 mg once daily)/ 
Rilpivirine1 
 
 
 
 
 
 
 
 
Rifabutin (300 mg once daily)/ 
Rilpivirine 

Rifabutin: 
AUC: ↔ 
Cmin: ↔ 
Cmax: ↔ 
 
25-O-desacetyl-rifabutin: 
AUC: ↔ 
Cmin: ↔ 
Cmax: ↔ 
 
Rilpivirine: 
AUC: ↓ 42% 
Cmin: ↓ 48% 
Cmax: ↓ 31% 
Induction of CYP3A 
 
Expected: 
Tenofovir alafenamide: 
AUC: ↓ 
Cmax: ↓  
Induction of P-gp 
 
Interaction not studied with 
tenofovir alafenamide.  
Co-administration is likely to cause 
significant decreases in the plasma 
concentrations of tenofovir 
alafenamide (induction of P-gp). 

Co-administration is 
contraindicated. 

Macrolide antibiotics 
Clarithromycin 
Erythromycin 

Interaction not studied with any of 
the components of Odefsey.  The 
combination of Odefsey with these 
macrolide antibiotics may cause an 
increase in the plasma 
concentrations of rilpivirine 
(inhibition of CYP3A) and 
tenofovir alafenamide (inhibition 
of P-gp). 

Co-administration is not 
recommended. 

Antiviral agents 
Ledipasvir/Sofosbuvir 
(90 mg/400 mg once daily)/ 
Rilpivirine 

Ledipasvir: 
AUC: ↑ 2% 
Cmin: ↑ 2% 
Cmax: ↑ 1% 
 
Sofosbuvir: 
AUC: ↑ 5% 
Cmax: ↓ 4% 
 
Sofosbuvir metabolite GS-331007: 
AUC: ↑ 8% 
Cmin: ↑ 10% 
Cmax: ↑ 8% 
 
Rilpivirine: 
AUC: ↓ 5% 
Cmin: ↓ 7% 
Cmax: ↓ 3% 

No dose adjustment is required. 



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Medicinal product by therapeutic 
areas 

Effects on medicinal product 
levels. 

Mean percent change in AUC, 
Cmax, Cmin 

Recommendation concerning 
co-administration with 

Odefsey 

Ledipasvir/Sofosbuvir 
(90 mg/400 mg once daily)/ 
Tenofovir alafenamide 

Tenofovir alafenamide: 
AUC: ↑ 32% 
Cmax: ↑ 3% 

Sofosbuvir/Velpatasvir  
(400 mg/100 mg once daily)/ 
Rilpivirine2 

Sofosbuvir: 
AUC: ↔ 
Cmax: ↔ 
 
Sofosbuvir metabolite GS-331007: 
AUC: ↔ 
Cmin: ↔ 
Cmax: ↔ 
 
Velpatasvir: 
AUC: ↔ 
Cmin: ↔ 
Cmax: ↔ 
 
Rilpivirine: 
AUC: ↔ 
Cmin: ↔ 
Cmax: ↔ 

No dose adjustment is required. 

Sofosbuvir/Velpatasvir/Voxilaprevir  
(400 mg/100 mg/100 mg + 100 mg 
once daily)3/ 
Emtricitabine/Rilpivirine/Tenofovir 
alafenamide (200 mg/25 mg/25 mg 
once daily) 

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

No dose adjustment is required. 



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Medicinal product by therapeutic 
areas 

Effects on medicinal product 
levels. 

Mean percent change in AUC, 
Cmax, Cmin 

Recommendation concerning 
co-administration with 

Odefsey 

Sofosbuvir (400 mg once daily)/ 
Rilpivirine (25 mg once daily) 

Sofosbuvir: 
AUC: ↔ 
Cmax: ↑ 21% 
 
Sofosbuvir metabolite GS-331007: 
AUC: ↔ 
Cmax: ↔ 
 
Rilpivirine: 
AUC: ↔ 
Cmin: ↔ 
Cmax: ↔ 

No dose adjustment is required. 

ANTICONVULSANTS 
Carbamazepine 
Oxcarbazepine 
Phenobarbital 
Phenytoin 

Interaction not studied with any of 
the components of Odefsey.  
Co-administration may cause 
significant decreases in the plasma 
concentrations of rilpivirine 
(induction of CYP3A) and 
tenofovir alafenamide (induction of 
P-gp). 

Co-administration is 
contraindicated. 

GLUCOCORTICOIDS 
Dexamethasone (systemic, except 
for single dose use) 

Interaction not studied with any of 
the components of Odefsey.  
Significant dose dependent 
decreases in rilpivirine plasma 
concentrations are expected 
(induction of CYP3A). 

Co-administration is 
contraindicated. 

PROTON PUMP INHIBITORS 
Omeprazole (20 mg once daily)/ 
Rilpivirine1 

Omeprazole: 
AUC: ↓ 14% 
Cmin: N/A 
Cmax: ↓ 14% 
 
Rilpivirine: 
AUC: ↓ 40% 
Cmin: ↓ 33% 
Cmax: ↓ 40% 
Reduced absorption, increase in 
gastric pH 

Co-administration is 
contraindicated. 

Lansoprazole 
Rabeprazole 
Pantoprazole 
Esomeprazole 
Dexlansoprazole 

Interaction not studied with any of 
the components of Odefsey.  
Significant decreases in rilpivirine 
plasma concentrations are expected 
(reduced absorption, increase in 
gastric pH). 

Co-administration is 
contraindicated. 

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

Interaction not studied with any of 
the components of Odefsey.  
Co-administration may cause 
significant decreases in the plasma 
concentrations of rilpivirine 
(induction of CYP3A) and 
tenofovir alafenamide (induction of 
P-gp). 

Co-administration is 
contraindicated.  



13 

Medicinal product by therapeutic 
areas 

Effects on medicinal product 
levels. 

Mean percent change in AUC, 
Cmax, Cmin 

Recommendation concerning 
co-administration with 

Odefsey 

H2-RECEPTOR ANTAGONISTS 
Famotidine (40 mg single dose 
taken 12 hours before rilpivirine)/ 
Rilpivirine1 
 
 
Famotidine (40 mg single dose 
taken 2 hours before rilpivirine)/ 
Rilpivirine1 
 
 
 
 
Famotidine (40 mg single dose 
taken 4 hours after rilpivirine)/ 
Rilpivirine1 

Rilpivirine: 
AUC: ↓ 9% 
Cmin: N/A 
Cmax: ↔ 
 
Rilpivirine: 
AUC: ↓ 76% 
Cmin: N/A 
Cmax: ↓ 85% 
Reduced absorption, increase in 
gastric pH 
 
Rilpivirine: 
AUC: ↑ 13% 
Cmin: N/A 
Cmax: ↑ 21% 

Only H2-receptor antagonists that 
can be dosed once daily should 
be used.  A strict dosing schedule 
with intake of the H2-receptor 
antagonists at least 12 hours 
before or at least 4 hours after 
Odefsey should be used. 

Cimetidine 
Nizatidine 
Ranitidine 

Interaction not studied with any of 
the components of Odefsey.  
Co-administration may cause 
significant decreases in rilpivirine 
plasma concentrations (reduced 
absorption, increase in gastric pH). 

ANTACIDS 
Antacids (e.g., aluminium or 
magnesium hydroxide, calcium 
carbonate) 

Interaction not studied with any of 
the components of Odefsey.  
Co-administration may cause 
significant decreases in rilpivirine 
plasma concentrations (reduced 
absorption, increase in gastric pH). 

Antacids should only be 
administered either at least 
2 hours before or at least 4 hours 
after Odefsey. 

ORAL CONTRACEPTIVES 
Ethinylestradiol (0.035 mg once 
daily)/ Rilpivirine 
 
 
 
Norethindrone (1 mg once daily)/ 
Rilpivirine 

Ethinylestradiol: 
AUC: ↔ 
Cmin: ↔ 
Cmax: ↑ 17% 
 
Norethindrone: 
AUC: ↔ 
Cmin: ↔ 
Cmax: ↔ 
 
Rilpivirine: 
AUC: ↔* 
Cmin: ↔* 
Cmax: ↔* 
*based on historic controls 

No dose adjustment is required. 



14 

Medicinal product by therapeutic 
areas 

Effects on medicinal product 
levels. 

Mean percent change in AUC, 
Cmax, Cmin 

Recommendation concerning 
co-administration with 

Odefsey 

Norgestimate 
(0.180/0.215/0.250 mg once daily)/ 
Ethinylestradiol (0.025 mg once 
daily)/ Emtricitabine/Tenofovir 
alafenamide (200/25 mg once daily) 

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

No dose adjustment is required. 

NARCOTIC ANALGESICS 
Methadone (60-100 mg once daily, 
individualised dose)/ Rilpivirine 

R(-) methadone: 
AUC: ↓ 16% 
Cmin: ↓ 22% 
Cmax: ↓ 14% 
 
S(+) methadone: 
AUC: ↓ 16% 
Cmin: ↓ 21% 
Cmax: ↓ 13% 
 
Rilpivirine: 
AUC: ↔* 
Cmin: ↔* 
Cmax: ↔* 
*based on historic controls 

No dose adjustments are 
required. 
 
Clinical monitoring is 
recommended as methadone 
maintenance therapy may need 
to be adjusted in some patients. 

ANALGESICS 
Paracetamol (500 mg single dose)/ 
Rilpivirine1 

Paracetamol: 
AUC: ↔ 
Cmin: N/A 
Cmax: ↔ 
 
Rilpivirine: 
AUC: ↔ 
Cmin: ↑ 26% 
Cmax: ↔ 

No dose adjustment is required. 

ANTIARRHYTHMICS 
Digoxin/ Rilpivirine Digoxin: 

AUC: ↔ 
Cmin: N/A 
Cmax: ↔ 

No dose adjustment is required. 

ANTICOAGULANTS 
Dabigatran etexilate Interaction not studied with any of 

the components of Odefsey. 
A risk for increases in dabigatran 
plasma concentrations cannot be 
excluded (inhibition of intestinal 
P-gp). 

Co-administration should be 
used with caution. 



15 

Medicinal product by therapeutic 
areas 

Effects on medicinal product 
levels. 

Mean percent change in AUC, 
Cmax, Cmin 

Recommendation concerning 
co-administration with 

Odefsey 

IMMUNOSUPPRESSANTS 
Ciclosporin Interaction not studied with any of 

the components of Odefsey.  
Co-administration of ciclosporin is 
expected to increase plasma 
concentrations of rilpivirine 
(inhibition of CYP3A) and 
tenofovir alafenamide (inhibition 
of P-gp). 

Co-administration is not 
recommended. 

ANTIDIABETICS 
Metformin (850 mg single dose)/ 
Rilpivirine 

Metformin: 
AUC: ↔ 
Cmin: N/A 
Cmax: ↔ 

No dose adjustment is required. 

HMG CO-A REDUCTASE INHIBITORS 
Atorvastatin (40 mg once daily)/ 
Rilpivirine1 

Atorvastatin: 
AUC: ↔ 
Cmin: ↓ 15% 
Cmax: ↑ 35% 
 
Rilpivirine: 
AUC: ↔ 
Cmin: ↔ 
Cmax: ↓ 9% 

No dose adjustment is required. 

PHOSPHODIESTERASE TYPE 5 (PDE-5) INHIBITORS 
Sildenafil (50 mg single dose)/ 
Rilpivirine1 

Sildenafil: 
AUC: ↔ 
Cmin: N/A 
Cmax: ↔ 
 
Rilpivirine: 
AUC: ↔ 
Cmin: ↔ 
Cmax: ↔ 

No dose adjustment is required. 

Vardenafil 
Tadalafil 

Interaction not studied with any of 
the components of Odefsey.  These 
are medicinal products within class 
where similar interactions could be 
predicted. 

No dose adjustment is required. 

HYPNOTICS/SEDATIVES 
Midazolam (2.5 mg, orally, single 
dose)/ Tenofovir alafenamide 
 
 
 
Midazolam (1 mg, intravenously, 
single dose)/ Tenofovir alafenamide 

Midazolam: 
AUC: ↑ 12% 
Cmin: N/A 
Cmax: ↑ 2% 
 
Midazolam: 
AUC: ↑ 8% 
Cmin: N/A 
Cmax: ↓ 1% 

No dose adjustment is required. 

N/A = not applicable 
1 This interaction study has been performed with a dose higher than the recommended dose for rilpivirine hydrochloride 

assessing the maximal effect on the co-administered medicinal product.  The dosing recommendation is applicable to the 
recommended dose of rilpivirine of 25 mg once daily. 

2 Study conducted with emtricitabine/rilpivirine/tenofovir disoproxil fumarate fixed-dose combination tablet. 
3 Study conducted with additional voxilaprevir 100 mg to achieve voxilaprevir exposures expected in HCV infected 

patients. 
 



16 

Studies conducted with other medicinal products 
 
Based on drug-drug interaction studies conducted with the components of Odefsey, no clinically 
significant interactions are expected when Odefsey is combined with the following medicinal 
products: buprenorphine, naloxone and norbuprenorphine. 
 
4.6 Fertility, pregnancy and lactation 
 
Women of childbearing potential/contraception in males and females 
 
The use of Odefsey should be accompanied by the use of effective contraception. 
 
Pregnancy 
 
There are no adequate and well-controlled studies of Odefsey or its components in pregnant women. 
 
There is a limited amount of data (less than 300 pregnancy outcomes) from the use of tenofovir 
alafenamide in pregnant women.  A moderate amount of data on pregnant women (between 300-1,000 
pregnancy outcomes) indicate no malformative or foetal/neonatal toxicity of rilpivirine (see 
sections 4.4, 5.1 and 5.2).  Lower exposures of rilpivirine were observed during pregnancy; therefore 
viral load should be monitored closely.  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 with respect to reproductive toxicity 
(see section 5.3) with the components of Odefsey. 
 
Odefsey should be used during pregnancy only if the potential benefit justifies the potential risk to the 
foetus. 
 
Breast-feeding 
 
Emtricitabine is excreted in human milk.  It is not known whether rilpivirine or tenofovir alafenamide 
are excreted in human milk.  In animal studies it has been shown that tenofovir is excreted in milk.  
Rilpivirine is excreted in the milk of rats. 
 
There is insufficient information on the effects of all the components of Odefsey in newborns/infants. 
 
Because of both the potential for HIV transmission and the potential for adverse reactions in breastfed 
infants, women should be instructed not to breast-feed if they are receiving Odefsey. 
 
Fertility 
 
No human data on the effect of Odefsey on fertility are available.  Animal studies do not indicate 
harmful effects of emtricitabine, rilpivirine hydrochloride or tenofovir alafenamide on fertility (see 
section 5.3). 
 
4.7 Effects on ability to drive and use machines 
 
Patients should be informed that fatigue, dizziness and somnolence have been reported during 
treatment with the components of Odefsey (see section 4.8).  This should be considered when 
assessing a patient’s ability to drive or operate machinery. 
 



17 

4.8 Undesirable effects 
 
Summary of the safety profile 
 
The most frequently reported adverse reactions in clinical studies of treatment-naïve patients taking 
emtricitabine + tenofovir alafenamide in combination with elvitegravir + cobicistat were nausea 
(11%), diarrhoea (7%), and headache (6%).  The most frequently reported adverse reactions in clinical 
studies of treatment-naïve patients taking rilpivirine hydrochloride in combination with 
emtricitabine + tenofovir disoproxil fumarate were nausea (9%), dizziness (8%), abnormal dreams 
(8%), headache (6%), diarrhoea (5%) and insomnia (5%). 
 
No new adverse reactions were identified through Week 96 in 2 clinical studies of virologically 
suppressed patients who switched from emtricitabine/rilpivirine/tenofovir disoproxil fumarate 
(FTC/RPV/TDF) to Odefsey (Study GS-US-366-1216) or from efavirenz/emtricitabine/tenofovir 
disoproxil fumarate (EFV/FTC/TDF) to Odefsey (Study GS-US-366-1160). 
 
Tabulated summary of adverse reactions 
 
Assessment of adverse reactions is based on safety data from across all Phase 2 and 3 studies in which 
2,396 patients received emtricitabine + tenofovir alafenamide given with elvitegravir + cobicistat as a 
fixed-dose combination tablet, pooled data from 686 patients who received rilpivirine 25 mg once 
daily in combination with other antiretroviral medicinal products in the controlled studies 
TMC278-C209 and TMC278-C215, 754 patients who received Odefsey in Studies GS-US-366-1216 
and GS-US-366-1160, and post-marketing experience. 
 
The adverse reactions in Table 2 are listed by system organ class and highest frequency observed.  
Frequencies are defined as follows: very common (≥ 1/10), common (≥ 1/100 to < 1/10) or uncommon 
(≥ 1/1,000 to < 1/100). 
 
Table 2: Tabulated list of adverse reactions 
 

Frequency Adverse reaction 
Blood and lymphatic system disorders 

Common: decreased white blood cell count
1, decreased haemoglobin1, decreased 

platelet count1 
Uncommon: anaemia2 
Immune system disorders 
Uncommon: immune reactivation syndrome1 
Metabolism and nutrition disorders 
Very common: increased total cholesterol (fasted)1, increased LDL-cholesterol (fasted)1 
Common: decreased appetite1, increased triglycerides (fasted)1 
Psychiatric disorders 
Very common: insomnia1 
Common: depression1, abnormal dreams1, 3, sleep disorders1, depressed mood1 
Nervous system disorders 
Very common: headache1, 3, dizziness1, 3 
Common: somnolence1 
Gastrointestinal disorders 
Very common: nausea1, 3, increased pancreatic amylase1 

Common: abdominal pain
1, 3, vomiting1, 3, increased lipase1, abdominal discomfort1, dry 

mouth1, flatulence3, diarrhoea3 
Uncommon: dyspepsia3 
Hepatobiliary disorders 
Very common: increased transaminases (AST and/or ALT)1 
Common: increased bilirubin1 
Skin and subcutaneous tissue disorders 
Common: rash1, 3 

Uncommon: severe skin reactions with systemic symptoms
4, angioedema5, 6, pruritus3, 

urticaria6 



18 

Frequency Adverse reaction 
Musculoskeletal and connective tissue disorders 
Uncommon: arthralgia3 
General disorders and administration site conditions 
Common: fatigue1, 3 

1 Adverse reactions identified from rilpivirine clinical studies. 
2 This adverse reaction was not observed in the Phase 3 studies of emtricitabine + tenofovir alafenamide in combination 

with elvitegravir + cobicistat or in the Phase 3 studies with Odefsey but identified from clinical studies or post-marketing 
experience of emtricitabine when used with other antiretrovirals. 

3 Adverse reactions identified from clinical studies of emtricitabine + tenofovir alafenamide-containing products. 
4 Adverse reaction identified through post-marketing surveillance of emtricitabine/rilpivirine/tenofovir disoproxil 

fumarate. 
5 Adverse reaction identified through post-marketing surveillance for emtricitabine-containing products.  
6 Adverse reaction identified through post-marketing surveillance for tenofovir alafenamide-containing products. 
 
Laboratory abnormalities 
 
Changes in serum creatinine for rilpivirine-containing regimens 
The pooled data from the Phase 3 TMC278-C209 and TMC278-C215 studies of treatment-naïve 
patients also demonstrate that serum creatinine increased and estimated glomerular filtration rate 
(eGFR) decreased over 96 weeks of treatment with rilpivirine.  Most of this increase in creatinine and 
decrease in eGFR occurred within the first four weeks of treatment.  Over 96 weeks of treatment with 
rilpivirine mean changes of 0.1 mg/dL (range: -0.3 mg/dL to 0.6 mg/dL) for creatinine 
and -13.3 mL/min/1.73 m2 (range: -63.7 mL/min/1.73 m2 to 40.1 mL/min/1.73 m2) for eGFR were 
observed.  In patients who entered the studies with mild or moderate renal impairment, the serum 
creatinine increase observed was similar to that seen in patients with normal renal function.  These 
increases do not reflect a change in actual glomerular filtration rate (GFR). 
 
Changes in lipid laboratory tests 
In studies in treatment-naïve patients receiving emtricitabine + tenofovir alafenamide (FTC + TAF) or 
emtricitabine + tenofovir disoproxil fumarate (FTC + TDF), both given with elvitegravir + cobicistat 
as a fixed-dose combination tablet, increases from baseline were observed in both 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 
these parameters was greater in patients receiving FTC + TAF compared with patients receiving 
FTC + TDF (p < 0.001 for the difference between treatment groups for fasting total cholesterol, direct 
LDL- and HDL-cholesterol, and triglycerides).  Median (Q1, Q3) change from baseline at Week 144 
in total cholesterol to HDL-cholesterol ratio was 0.2 (-0.3, 0.7) in patients receiving FTC + TAF and 
0.1 (-0.4, 0.6) in patients receiving FTC + TDF (p = 0.006 for the difference between treatment 
groups). 
 
Switching from a TDF-based regimen to Odefsey may lead to slight increases in lipid parameters.  In a 
study of virologically suppressed patients switching from FTC/RPV/TDF to Odefsey (Study 
GS-US-366-1216), increases from baseline were observed in fasting values of total cholesterol, direct 
LDL-cholesterol, HDL-cholesterol, and triglycerides in the Odefsey arm; and no clinically relevant 
changes from baseline in median fasting values for total cholesterol to HDL-cholesterol ratio were 
observed in either treatment arm at Week 96.  In a study of virologically suppressed patients switching 
from EFV/FTC/TDF to Odefsey (Study GS-US-366-1160), decreases from baseline were observed in 
the fasting values of total cholesterol and HDL-cholesterol in the Odefsey arm; no clinically relevant 
changes from baseline in median fasting values for total cholesterol to HDL-cholesterol ratio, direct 
LDL-cholesterol or triglycerides were observed in either treatment arm at Week 96. 
 
Cortisol 
In the pooled Phase 3 TMC278-C209 and TMC278-C215 studies of treatment-naïve patients, at 
Week 96, there was an overall mean change from baseline in basal cortisol of -19.1 
(-30.85; -7.37) nmol/L in the rilpivirine arm and of -0.6 (-13.29; 12.17) nmol/L in the efavirenz arm.  
At Week 96, the mean change from baseline in ACTH-stimulated cortisol levels was lower in the 
rilpivirine arm (+18.4 ± 8.36 nmol/L) than in the efavirenz arm (+54.1 ± 7.24 nmol/L).  Mean values 
for the rilpivirine arm for both basal and ACTH-stimulated cortisol at Week 96 were within the normal 



19 

range.  These changes in adrenal safety parameters were not clinically relevant.  There were no clinical 
signs or symptoms suggestive of adrenal or gonadal dysfunction in adults. 
 
Description of selected adverse reactions 
 
Metabolic parameters 
Weight and levels of blood lipids and glucose may increase during antiretroviral therapy (see 
section 4.4). 
 
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). 
 
Severe skin reactions 
Severe skin reactions with systemic symptoms have been reported during post-marketing experience 
of emtricitabine/rilpivirine/tenofovir disoproxil fumarate including rashes accompanied by fever, 
blisters, conjunctivitis, angioedema, elevated liver function tests, and/or eosinophilia. 
 
Paediatric population 
 
The safety of emtricitabine + tenofovir alafenamide was evaluated through 48 weeks in an open-label 
clinical study (GS-US-292-0106) in which 50 HIV-1 infected, treatment-naïve paediatric patients aged 
12 to < 18 years received emtricitabine + tenofovir alafenamide in combination with 
elvitegravir + cobicistat as a fixed-dose combination tablet.  In this study, the safety profile in 
adolescent patients was similar to that in adults (see section 5.1). 
 
The safety assessment of rilpivirine is based on Week 48 data from one single-arm open-label study 
(TMC278-C213) in 36 paediatric patients 12 to < 18 years and weighing at least 32 kg.  No patients 
discontinued rilpivirine due to adverse reactions.  No new adverse reactions were identified compared 
to those seen in adults.  Most adverse reactions were Grade 1 or 2.  Adverse reactions (all grades) of 
very common frequency were headache, depression, somnolence and nausea.  No Grade 3-4 
laboratory abnormalities for AST/ALT or Grade 3-4 adverse reactions of transaminase increased were 
reported (see section 5.1). 
 
Other special populations 
 
Patients with renal impairment 
The safety of emtricitabine + 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 + tenofovir alafenamide in combination with elvitegravir + 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 + 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 + tenofovir alafenamide in combination with elvitegravir + cobicistat as a fixed-dose 



20 

combination tablet.  There were no new safety issues identified in patients with end stage renal disease 
on chronic haemodialysis receiving emtricitabine + tenofovir alafenamide, given with elvitegravir + 
cobicistat as a fixed-dose combination tablet (see section 5.2). 
 
Patients co-infected with HIV and HBV 
The safety of emtricitabine + 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 TDF in 69 of 72 patients) to E/C/F/TAF.  Based on 
these limited data, the safety profile of emtricitabine + 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. 
 
In patients co-infected with hepatitis B or C virus receiving rilpivirine, the incidence of hepatic 
enzyme elevation was higher than in patients receiving rilpivirine who were not co-infected.  The 
pharmacokinetic exposure of rilpivirine in co-infected patients was comparable to that in patients 
without co-infection. 
 
Reporting of suspected adverse reactions 
 
Reporting suspected adverse reactions after authorisation of the medicinal product is important.  
It allows continued monitoring of the benefit/risk balance of the medicinal product.  Healthcare 
professionals are asked to report any suspected adverse reactions via the national reporting system 
listed in Appendix V. 
 
4.9 Overdose 
 
If overdose occurs the patient must be monitored for evidence of toxicity (see section 4.8), and 
standard supportive treatment applied as necessary including observation of the clinical status of the 
patient and monitoring of vital signs and ECG (QT interval). 
 
There is no specific antidote for overdose with Odefsey.  Up to 30% of the emtricitabine dose can be 
removed by haemodialysis.  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.  Since rilpivirine is highly protein bound, dialysis is unlikely to result in 
significant removal of the active substance.  Further management should be as clinically indicated or 
as recommended by the national poisons centre, where available. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: Antiviral for systemic use; antivirals for treatment of HIV infections, 
combinations, ATC code: J05AR19 
 
Mechanism of action and pharmacodynamic effects 
 
Emtricitabine is a nucleoside reverse transcriptase inhibitor (NRTI) and analogue of 2’-deoxycytidine.  
Emtricitabine is phosphorylated by cellular enzymes to form emtricitabine triphosphate.  Emtricitabine 
triphosphate competitively inhibits HIV-1 reverse transcriptase (RT), resulting in deoxyribonucleic 
acid (DNA) chain termination.  Emtricitabine has activity against HIV-1, HIV-2, and HBV. 
 
Rilpivirine is a diarylpyrimidine NNRTI of HIV-1.  Rilpivirine activity is mediated by 
non-competitive inhibition of HIV-1 RT.  Rilpivirine does not inhibit the human cellular DNA 
polymerases α, β and mitochondrial DNA polymerase γ. 

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


21 

 
Tenofovir alafenamide is a nucleotide reverse transcriptase inhibitor (NtRTI) and prodrug of tenofovir 
(2’-deoxyadenosine monophosphate analogue).  Due to increased plasma stability and intracellular 
activation through hydrolysis by cathepsin A, tenofovir alafenamide is more efficient than tenofovir 
disoproxil fumarate in loading tenofovir into peripheral blood mononuclear cells (PBMCs) (including 
lymphocytes and other HIV target cells) and macrophages.  Intracellular tenofovir is subsequently 
phosphorylated to the active metabolite tenofovir diphosphate.  Tenofovir diphosphate inhibits 
HIV RT, resulting in DNA chain termination.  Tenofovir has activity against HIV-1, HIV-2 and HBV. 
 
Antiviral activity in vitro 
 
The combinations of emtricitabine, rilpivirine, and tenofovir alafenamide were not antagonistic and 
showed synergistic effects with each other in cell culture combination antiviral activity assays. 
 
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 subtype A, B, C, D, E, F, and G (EC50 values ranged 
from 0.007 to 0.075 µM) and showed activity against HIV-2 (EC50 values ranged from 0.007 to 
1.5 µM). 
 
Rilpivirine exhibited activity against laboratory strains of wild-type HIV-1 in an acutely infected 
T-cell line with a median EC50 value for HIV-1/IIIB of 0.73 nM (0.27 ng/mL).  Rilpivirine also 
demonstrated antiviral activity against a broad panel of HIV-1 group M (subtype A, B, C, D, F, G, H) 
primary isolates with EC50 values ranging from 0.07 to 1.01 nM (0.03 to 0.37 ng/mL), group O 
primary isolates with EC50 values ranging from 2.88 to 8.45 nM (1.06 to 3.10 ng/mL), and showed 
limited in vitro activity against HIV-2 with EC50 values ranging from 2,510 to 10,830 nM (920 to 
3,970 ng/mL). 
 
The antiviral activity of tenofovir alafenamide against laboratory and clinical isolates of HIV-1 
subtype B was assessed in lymphoblastoid cell lines, PBMCs, primary monocyte/macrophage cells, 
and CD4+ T-lymphocytes.  The EC50 values for tenofovir alafenamide were in the range of 2.0 to 
14.7 nM.  Tenofovir alafenamide displayed antiviral activity in cell culture against all HIV-1 groups 
(M, N, O), including subtypes A, B, C, D, E, F, and G (EC50 values ranged from 0.10 to 12.0 nM) and 
showed activity against HIV-2 (EC50 values ranged from 0.91 to 2.63 nM). 
 
Resistance 
 
Considering all of the available in vitro data and data generated in treatment-naïve patients, the 
following resistance-associated mutations in HIV-1 RT, when present at baseline, may affect the 
activity of Odefsey: K65R, K70E, K101E, K101P, E138A, E138G, E138K, E138Q, E138R, V179L, 
Y181C, Y181I, Y181V, M184I, M184V, Y188L, H221Y, F227C, M230I, M230L and the 
combination of L100I and K103N. 
 
A negative impact by NNRTI mutations other than those listed above (e.g., mutations K103N or L100I 
as single mutations) cannot be excluded, since this was not studied in vivo in a sufficient number of 
patients. 
 
As with other antiretroviral medicinal products, resistance testing and/or historical resistance data 
should guide the use of Odefsey (see section 4.4). 
 
In vitro 
Reduced susceptibility to emtricitabine is associated with M184V/I mutations in HIV-1 RT. 
 
Rilpivirine-resistant strains were selected in cell culture starting from wild-type HIV-1 of different 
origins and subtypes as well as NNRTI-resistant HIV-1.  The most commonly observed amino acid 



22 

substitutions that emerged included: L100I, K101E, V108I, E138K, V179F, Y181C, H221Y, F227C, 
and M230I. 
 
HIV-1 isolates with reduced susceptibility to tenofovir alafenamide expressed a K65R mutation in 
HIV-1 RT; in addition, a K70E mutation in HIV-1 RT has been transiently observed. 
 
In treatment-naïve adult patients 
In the Week 144 pooled analysis of antiretroviral-naïve patients receiving 
elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) in the Phase 3 studies 
GS-US-292-0104 and GS-US-292-0111, the development of one or more primary 
resistance-associated mutations was observed in HIV-1 isolates from 12 of 866 (1.4%) patients treated 
with E/C/F/TAF.  Among these 12 HIV-1 isolates, 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. 
 
In the Week 96 pooled analysis for patients receiving emtricitabine/tenofovir disoproxil fumarate 
(FTC/TDF) + rilpivirine hydrochloride in the Phase 3 clinical studies TMC278-C209 and 
TMC278-C215, HIV-1 isolates from 43 patients had an amino acid substitution associated with 
NNRTI (n = 39) or NRTI (n = 41) resistance.  The NNRTI resistance-associated mutations that 
developed most commonly were: V90I, K101E, E138K/Q, V179I, Y181C, V189I, H221Y and F227C.  
The presence of V90I and V189I at baseline did not affect the response.  Fifty-two percent of HIV-1 
isolates with emergent resistance in the rilpivirine arm developed concomitant NNRTI and NRTI 
mutations, most frequently E138K and M184V.  The mutations associated with NRTI resistance that 
developed in 3 or more patient isolates were: K65R, K70E, M184V/I and K219E. 
 
Through Week 96, fewer patients in the rilpivirine arm with baseline viral load ≤ 100,000 copies/mL 
had emerging resistance-associated substitutions and/or phenotypic resistance to rilpivirine (7/288) 
than patients with baseline viral load > 100,000 copies/mL (30/262).  
 
In virologically suppressed patients 
One patient with emergent resistance (M184M/I) was identified in a clinical study of virologically 
suppressed patients who switched from a regimen containing emtricitabine + tenofovir disoproxil 
fumarate to E/C/F/TAF in a fixed-dose combination (FDC) tablet (GS-US-292-0109, n = 959). 
 
Through Week 96, in patients who switched to Odefsey from emtricitabine/rilpivirine/tenofovir 
disoproxil fumarate (FTC/RPV/TDF) or efavirenz/emtricitabine/tenofovir disoproxil fumarate 
(EFV/FTC/TDF) (Studies GS-US-366-1216 and GS-US-366-1160; n = 754), no treatment-emergent 
resistance-associated mutations were detected.  
 
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 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 
 
Emtricitabine-resistant viruses with the M184V/I substitution were cross-resistant to lamivudine, but 
retained sensitivity to didanosine, stavudine, tenofovir, and zidovudine. 
 
In a panel of 67 HIV-1 recombinant laboratory strains with one resistance-associated mutation at RT 
positions associated with NNRTI resistance, the only single resistance-associated mutations associated 
with a loss of susceptibility to rilpivirine were K101P and Y181V/I.  The K103N substitution alone 
did not result in reduced susceptibility to rilpivirine, but the combination of K103N and L100I resulted 
in a 7-fold reduced susceptibility to rilpivirine.  In another study, the Y188L substitution resulted in a 
reduced susceptibility to rilpivirine of 9-fold for clinical isolates and 6-fold for site-directed mutants. 
 



23 

In patients receiving rilpivirine hydrochloride in combination with FTC/TDF in Phase 3 studies 
(TMC278-C209 and TMC278-C215 pooled data), most HIV-1 isolates with emergent phenotypic 
resistance to rilpivirine had cross-resistance to at least one other NNRTI (28/31).  
 
The K65R and also the K70E substitution result in reduced susceptibility to abacavir, didanosine, 
lamivudine, emtricitabine, and tenofovir, but retain sensitivity to zidovudine. 
 
Clinical data 
 
Clinical efficacy of Odefsey was established from studies conducted with emtricitabine + tenofovir 
alafenamide when given with elvitegravir + cobicistat as an E/C/F/TAF FDC tablet, from studies 
conducted with rilpivirine when given with FTC/TDF as individual components or as a 
FTC/RPV/TDF FDC tablet, and from studies conducted with Odefsey. 
 
Emtricitabine + tenofovir alafenamide containing regimens 
Treatment-naïve and virologically suppressed HIV-1 infected adult patients 
In Study GS-US-292-0104 and Study GS-US-292-0111, patients received either E/C/F/TAF (n = 866) 
or elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (E/C/F/TDF) (n = 867) once 
daily, both given as FDC tablets. 
 
The mean age was 36 years (range 18-76), 85% were male, 57% were White, 25% were Black, and 
10% were Asian.  The mean baseline plasma HIV-1 RNA was 4.5 log10 copies/mL (range 1.3-7.0) and 
23% of patients 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 CD4+ cell counts < 200 cells/mm3. 
 
In Studies GS-US-292-0104 and GS-US-292-0111, 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 3. 
 
In Study GS-US-292-0109, the efficacy and safety of switching from either EFV/FTC/TDF, FTC/TDF 
plus atazanavir (boosted by either cobicistat or ritonavir), or E/C/F/TDF to E/C/F/TAF FDC tablet 
were evaluated in a randomised, open-label study of virologically suppressed (HIV-1 RNA 
< 50 copies/mL) HIV-1 infected adults (n = 959 switching to E/C/F/TAF, n = 477 Stayed on Baseline 
Regimen [SBR]).  Patients had a mean age of 41 years (range 21-77), 89% were male, 67% were 
White, and 19% were Black.  The mean baseline CD4+ cell count was 697 cells/mm3 (range 
79-1,951). 
 
In Study GS-US-292-0109, switching from a tenofovir disoproxil fumarate-based regimen to 
E/C/F/TAF was superior in maintaining HIV-1 RNA < 50 copies/mL compared to staying on the 
baseline regimen.  Pooled treatment outcomes at 48 weeks are shown in Table 3. 
 



24 

Table 3: Virologic outcomes of Studies GS-US-292-0104, GS-US-292-0111 at Week 48 and 
Week 144a, and GS-US-292-0109 at Week 48a 
 

 Treatment-naïve adults in Studies GS-US-292-0104 and 
GS-US-292-0111b 

Virologically suppressed 
adults in Study 

GS-US-292-0109 
 Week 48 Week 144 Week 48 
 E/C/F/TAF 

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

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

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

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

(n = 959) 
Baseline 
regimen 
(n = 477) 

HIV-1 RNA 
< 50 copies/mL 

92% 90% 84% 80% 97% 93% 

Treatment 
difference 

2.0% (95% CI: -0.7% to 4.7%) 4.2% (95% CI: 0.6% to 7.8%) 4.1% (95% CI: 1.6% to 
6.7%, p < 0.001c) 

HIV-1 RNA 
≥ 50 copies/mLd 

4% 4% 5% 4% 1% 1% 

No virologic data in 
Week 48 or 
144 window 

4% 6% 11% 16% 2% 6% 

Discontinued 
study drug due 
to AE or deathe 

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

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

2% 4% 9% 11% 1% 4% 

Missing data 
during window 
but on study 
drug 

1% < 1% 1% 1% 0% < 1% 

HIV-1 RNA 
< 20 copies/mL 

84% 84% 81% 76%   

Treatment 
difference 

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

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

      

EFV/FTC/TDF     96% 90% 
FTC/TDF plus 
boosted 
atazanavir 

    97% 92% 

E/C/F/TDF     98% 97% 
a Week 48 window was between Day 294 and 377 (inclusive); Week 144 window was between Day 966 and 1,049 

(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 P-value for the superiority test comparing the percentages of virologic success was from the CMH 
(Cochran-Mantel-Haenszel) test stratified by the prior treatment regimen (EFV/FTC/TDF, FTC/TDF plus boosted 
atazanavir, or E/C/F/TDF). 

d Includes patients who had ≥ 50 copies/mL in the Week 48 or Week 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. 

e 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. 

f 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. 



25 

 
In Studies GS-US-292-0104 and GS-US-292-0111, the rate of virologic success was similar across 
patient subgroups (age, gender, race, baseline HIV-1 RNA, or baseline CD4+ cell count). 
 
The mean increase from baseline in CD4+ cell count was 230 cells/mm3 in E/C/F/TAF-treated patients 
and 211 cells/mm3 in E/C/F/TDF-treated patients (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. 
 
Rilpivirine-containing regimens 
Treatment-naïve HIV-1 infected adult patients 
The efficacy of rilpivirine is based on the analyses of 96 weeks data from two randomised, 
double-blind, controlled studies in treatment-naïve patients (TMC278-C209 and 
emtricitabine + tenofovir disoproxil fumarate subset of TMC278-C215). 
 
In the pooled analysis for TMC278-C209 and TMC278-C215 of 1,096 patients who received a 
background regimen (BR) of FTC/TDF, demographic and baseline characteristics were balanced 
between the rilpivirine and efavirenz (EFV) arms.  The median age was 36 years, 78% were male and 
62% White and 24% Black/African American.  Median plasma HIV-1 RNA was 5.0 log10 copies/mL 
and median CD4+ cell count was 255 cells/mm3. 
 
Overall response and a subgroup analysis of the virologic response (< 50 HIV-1 RNA copies/mL) at 
both 48 weeks and 96 weeks, and virologic failure by baseline viral load (pooled data from the two 
Phase 3 clinical studies, TMC278-C209 and TMC278-C215, for patients receiving the FTC/TDF BR) 
are presented in Table 4. 
 



26 

Table 4: Virologic outcomes of randomised treatment of Studies TMC278-C209 and 
TMC278-C215 (pooled data for patients receiving rilpivirine hydrochloride or efavirenz in 
combination with FTC/TDF) at Week 48 (primary) and Week 96 
 

 RPV + FTC/TDF 
(n = 550) 

EFV + FTC/TDF 
(n = 546) 

RPV + FTC/TDF 
(n = 550) 

EFV + FTC/TDF 
(n = 546) 

 Week 48 Week 96 
Overall response 
(HIV-1 RNA 
< 50 copies/mL 
(TLOVRa))b 

83.5% (459/550) 82.4% (450/546) 76.9% (423/550) 77.3% (422/546) 

By baseline viral load (copies/mL) 
    ≤ 100,000 89.6% (258/288) 84.8% (217/256) 83.7% (241/288) 80.8% (206/255) 
    > 100,000 76.7% (201/262) 80.3% (233/290) 69.5% (182/262) 74.2% (216/291) 
Non-response 
Virologic failure 
(all patients) 

9.5% (52/550) 4.2% (23/546) 11.5% (63/550)c 5.1% (28/546)d 

By baseline viral load (copies/mL) 
    ≤ 100,000 4.2% (12/288) 2.3% (6/256) 5.9% (17/288) 2.4% (6/255) 
    > 100,000 15.3% (40/262) 5.9% (17/290) 17.6% (46/262) 7.6% (22/291) 
Death 0 0.2% (1/546) 0 0.7% (4/546) 
Discontinued due 
to adverse event 
(AE) 

2.2% (12/550) 7.1% (39/546) 3.6% (20/550) 8.1% (44/546) 

Discontinued for 
non-AE reasone 

4.9% (27/550) 6.0% (33/546) 8% (44/550) 8.8% (48/546) 

EFV = efavirenz; RPV = rilpivirine 
a ITT TLOVR = Intention to treat time to loss of virologic response. 
b The difference of response rate at Week 48 is 1% (95% confidence interval -3% to 6%) using normal approximation. 
c There were 17 new virologic failures between the Week 48 primary analysis and Week 96 (6 patients with baseline viral 

load ≤ 100,000 copies/mL and 11 patients with baseline viral load > 100,000 copies/mL).  There were also 
reclassifications in the Week 48 primary analysis with the most common being reclassification from virologic failure to 
discontinued for non-AE reasons. 

d There were 10 new virologic failures between the Week 48 primary analysis and Week 96 (3 patients with baseline viral 
load ≤ 100,000 copies/mL and 7 patients with baseline viral load > 100,000 copies/mL).  There were also 
reclassifications in the Week 48 primary analysis with the most common being reclassification from virologic failure to 
discontinued for non-AE reasons. 

e e.g., lost to follow up, non-compliance, withdrew consent. 
 
FTC/TDF + rilpivirine hydrochloride was non-inferior in achieving HIV-1 RNA < 50 copies/mL 
compared to FTC/TDF + efavirenz. 
 
Odefsey regimen 
Virologically suppressed HIV-1 infected adult patients 
In Study GS-US-366-1216, the efficacy and safety of switching from FTC/RPV/TDF to Odefsey were 
evaluated in a randomised, double-blind study of virologically suppressed HIV-1 infected adults.  
Patients had a mean age of 45 years (range 23-72), 90% were male, 75% were White, and 19% were 
Black.  The mean baseline CD4+ cell count was 709 cells/mm3 (range 104-2,527). 
 
In Study GS-US-366-1160, the efficacy and safety of switching from EFV/FTC/TDF to Odefsey were 
evaluated in a randomised, double-blind study of virologically suppressed HIV-1 infected adults.  
Patients had a mean age of 48 years (range 19-76), 87% were male, 67% were White, and 27% were 
Black.  The mean baseline CD4+ cell count was 700 cells/mm3 (range 140-1,862). 
 
Treatment outcomes of Studies GS-US-366-1216 and GS-US-366-1160 are presented in Table 5. 
 



27 

Table 5: Virologic outcomes of Studies GS-US-366-1216 and GS-US-366-1160 at Weeks 48a and 
96b 
 

 GS-US-366-1216 GS-US-366-1160 
 Week 48 Week 96 Week 48 Week 96 
 ODE 

(n = 316) 
FTC/RPV

/TDF 
(n = 313)c 

ODE 
(n = 316) 

FTC/RPV
/TDF 

(n = 313)c 

ODE 
(n = 438) 

EFV/FTC 
/TDF 

(n = 437) 

ODE 
(n = 438) 

EFV/FTC
/TDF 

(n = 437) 
HIV-1 RNA 
< 50 copies/mL 

94% 94% 89% 88% 90% 92% 85% 85% 

Treatment 
difference 

-0.3% 
(95% CI: -4.2% to 

3.7%) 

0.7% (95% CI:  
-4.3% to 5.8%) 

-2.0% (95% CI:  
-5.9% to 1.8%) 

0% (95% CI:  
-4.8% to 4.8%) 

HIV-1 RNA 
≥ 50 copies/mLd 

1% 0% 1% 1% 1% 1% 1% 1% 

No virologic data 
in Week 48 or 96 
window 

6% 6% 10% 11% 9% 7% 14% 14% 

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

2% 1% 2% 3% 3% 1% 4% 3% 

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

4% 4% 8% 8% 5% 5% 10% 11% 

Missing data 
during window 
but on study drug 

< 1% 1% 1% 0 1% 1% < 1% 0 

ODE = Odefsey 
a Week 48 window was between Day 295 and 378 (inclusive). 
b Week 96 window was between Day 631 and 714 (inclusive). 
c One patient who was not on FTC/RPV/TDF prior to screening was excluded from the analysis. 
d 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 lack or loss of efficacy and at the time of 
discontinuation had a viral value of ≥ 50 copies/mL. 

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

 
At Week 96, switching to Odefsey was non-inferior in maintaining HIV-1 RNA < 50 copies/mL when 
compared to patients who stayed on FTC/RPV/TDF or on EFV/FTC/TDF in respective studies. 
 
In Study GS-US-366-1216, the mean change from baseline in CD4+ cell count at Week 96 was 
12 cells/mm3 in patients who switched to Odefsey and 16 cells/mm3 in those who remained on 
FTC/RPV/TDF.  In Study GS-US-366-1160, the mean change from baseline in CD4+ cell count at 
Week 96 was 12 cells/mm3 in patients who switched to Odefsey and 6 cells/mm3 in those who stayed 
on EFV/FTC/TDF. 
 
HIV-1 infected adult patients with mild to moderate renal impairment 
In Study GS-US-292-0112, the efficacy and safety of E/C/F/TAF FDC tablet were evaluated in an 
open-label clinical study of 242 HIV-1 infected, virologically suppressed patients with mild to 
moderate renal impairment (eGFRCG: 30-69 mL/min).  
 
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.  Thirty-five 
percent of patients were on a treatment regimen that did not contain tenofovir disoproxil fumarate.  At 



28 

baseline, median eGFRCG was 56 mL/min, and 33% of patients had an eGFRCG 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 
E/C/F/TAF FDC tablet. 
 
In Study GS-US-292-1825, the efficacy and safety of E/C/F/TAF 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 E/C/F/TAF 
FDC 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 E/C/F/TAF.  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 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 263-1,498).  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 at Week 48. 
 
At Week 48, 92% of patients (66/72) maintained HIV-1 RNA < 50 copies/mL after switching to 
E/C/F/TAF.  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 
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.  
Alanine aminotransferase (ALT) normalisation was achieved in 40% (4/10) of subjects with ALT 
greater than upper limit of normal (ULN) at baseline. 
 
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 adult patients, E/C/F/TAF 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% versus -3.4%, p < 0.001) 
and lumbar spine (mean change: -0.9% versus -3.0%, p < 0.001). 
 
Small improvements in BMD were noted at 48 weeks after switching to E/C/F/TAF compared to 
maintaining the tenofovir disoproxil fumarate-containing regimen. 
 
In Odefsey studies in virologically suppressed adult patients, increases in BMD were noted at 
96 weeks after switching to Odefsey compared to minimal changes with maintaining FTC/RPV/TDF 
or EFV/FTC/TDF at the hip (mean change 1.6% for Odefsey versus -0.6% for FTC/RPV/TDF, 
p < 0.001; 1.8% for Odefsey versus -0.6% for EFV/FTC/TDF, p < 0.001) and the spine (mean change 



29 

2.0% for Odefsey versus -0.3% for FTC/RPV/TDF, p < 0.001; 1.7% for Odefsey versus 0.1% for 
EFV/FTC/TDF, p < 0.001). 
 
Changes in measures of renal function 
In studies in treatment-naïve adult patients, E/C/F/TAF was associated with lower impact on renal 
safety parameters (as measured after 144 weeks treatment by eGFRCG and urine protein to creatinine 
ratio [UPCR] and after 96 weeks treatment by urine albumin to creatinine ratio [UACR]) 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 studies in virologically suppressed adult patients, through 96 weeks of treatment there 
were minimal changes or decreases in albuminuria (UACR) in patients receiving Odefsey compared 
with increases from baseline in patients who stayed on FTC/RPV/TDF or EFV/FTC/TDF.  See also 
section 4.4. 
 
Paediatric population 
 
Emtricitabine + tenofovir alafenamide regimen 
In Study GS-US-292-0106, the efficacy, safety, and pharmacokinetics of E/C/F/TAF FDC tablet were 
evaluated in an open-label study of 50 HIV-1 infected, treatment-naïve adolescents.  Patients had a 
mean age of 15 years (range 12-17), were 56% female, 12% Asian, and 88% Black.  At baseline, 
median plasma HIV-1 RNA was 4.7 log10 copies/mL, median CD4+ cell count was 456 cells/mm3 
(range 95 to 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.  No emergent resistance to E/C/F/TAF was detected through 
Week 48. 
 
Rilpivirine-containing regimen 
The pharmacokinetics, safety, tolerability, and efficacy of rilpivirine 25 mg once daily, in combination 
with an investigator-selected BR containing two NRTIs, were evaluated in Study TMC278-C213, a 
single-arm, open-label Phase 2 study in antiretroviral-naïve HIV-1 infected paediatric patients 12 to 
< 18 years of age and weighing at least 32 kg.  The median duration of exposure for patients was 
63.5 weeks. 
 
Thirty-six patients had a median age of 14.5 years and were 55.6% female, 88.9% Black, and 11.1% 
Asian.  The median baseline plasma HIV-1 RNA was 4.8 log10 copies/mL, and the median baseline 
CD4+ cell count was 414 cells/mm3.  The proportion of patients with HIV-1 RNA < 50 copies/mL at 
Week 48 (TLOVR) was 72.2% (26/36).  The combination of NRTIs most frequently used together 
with rilpivirine was FTC/TDF (24 subjects [66.7%]). 
 
The proportion of responders was higher in subjects with a baseline viral load ≤ 100,000 copies/mL 
(78.6%, 22/28) as compared to those with a baseline viral load > 100,000 copies/mL (50.0%, 4/8).  
The proportion of virologic failures was 22.2% (8/36). 
 
The European Medicines Agency has deferred the obligation to submit the results of studies with 
Odefsey in one or more subsets of the paediatric population in the treatment of human HIV-1 infection 
(see section 4.2 for information on paediatric use). 
 
Pregnancy 
 
Rilpivirine (one of the components of Odefsey) in combination with a background regimen was 
evaluated in Study TMC114HIV3015 in 19 pregnant women during the 2nd and 3rd trimesters, and 
postpartum.  The pharmacokinetic data demonstrate that total exposure (AUC) to rilpivirine as a part 
of an antiretroviral regimen was approximately 30% lower during pregnancy compared with 
postpartum (6-12 weeks).  The virologic response was generally preserved throughout the study: of the 
12 patients that completed the study, 10 patients were suppressed at the end of the study; in the other 



30 

2 patients an increase in viral load was observed only postpartum, for at least 1 patient due to 
suspected suboptimal adherence.  No mother to child transmission occurred in all 10 infants born to 
the mothers who completed the study and for whom the HIV status was available.  Rilpivirine was 
well tolerated during pregnancy and postpartum.  There were no new safety findings compared with 
the known safety profile of rilpivirine in HIV-1 infected adults (see sections 4.2, 4.4 and 5.2). 
 
5.2 Pharmacokinetic properties 
 
Absorption 
 
Odefsey: Emtricitabine and tenofovir alafenamide exposures were bioequivalent when comparing one 
Odefsey 200/25/25 mg film-coated tablet to elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide 
(150/150/200/10 mg) fixed-dose combination tablet following single dose administration to healthy 
subjects (n = 82) under fed conditions.  Rilpivirine exposures were bioequivalent when comparing 
Odefsey 200/25/25 mg to one rilpivirine (as hydrochloride) 25 mg film-coated tablet following single 
dose administration to healthy subjects (n = 95) under fed conditions. 
 
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) area-under the plasma 
concentration-time curve over a 24-hour dosing interval (AUC) was 10.0 ± 3.1 h•µg/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.  The absolute bioavailability of emtricitabine from 200 mg 
hard capsules was estimated to be 93%.  Emtricitabine systemic exposure was unaffected when 
emtricitabine was administered with food. 
 
After oral administration, the maximum plasma concentration of rilpivirine is generally achieved 
within 4 to 5 hours.  The absolute bioavailability of rilpivirine is unknown.  Relative to fasting 
conditions, the administration of Odefsey to healthy adult subjects with food resulted in increased 
rilpivirine exposure (AUC) by 13-72%. 
 
Tenofovir alafenamide is rapidly absorbed following oral administration, with peak plasma 
concentrations occurring at 15-45 minutes post-dose.  Relative to fasting conditions, the administration 
of Odefsey to healthy adult subjects with food resulted in increased tenofovir alafenamide exposure 
(AUC) by 45-53%. 
 
It is recommended that Odefsey be taken with food. 
 
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. 
 
In vitro binding of rilpivirine to human plasma proteins is approximately 99.7%, primarily to albumin. 
 
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 
 
The biotransformation of emtricitabine includes oxidation of the thiol moiety to form the 3’-sulfoxide 
diastereomers (approximately 9% of dose) and conjugation with glucuronic acid to form 
2’-O-glucuronide (approximately 4% of dose).  Emtricitabine did not inhibit in vitro drug metabolism 
mediated by any of the major human CYP isoforms involved in drug biotransformation.  Also, 
emtricitabine did not inhibit uridine-5’-diphosphoglucuronyl transferase (UGT), the enzyme 
responsible for glucuronidation. 



31 

 
In vitro experiments indicate that rilpivirine hydrochloride primarily undergoes oxidative metabolism 
mediated by the CYP3A system. 
 
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, cobicistat and elvitegravir 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, 
cobicistat and elvitegravir. 
 
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. 
 
The terminal elimination half-life of rilpivirine is approximately 45 hours.  After single dose oral 
administration of [14C]-rilpivirine, on average 85% and 6.1% of the radioactivity could be retrieved in 
faeces and urine, respectively.  In faeces, unchanged rilpivirine accounted for on average 25% of the 
administered dose.  Only trace amounts of unchanged rilpivirine (< 1% of dose) were detected in 
urine. 
 
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 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, rilpivirine or tenofovir alafenamide. 
 
Paediatric population 
The pharmacokinetics of rilpivirine in antiretroviral-naïve HIV-1 infected paediatric patients 12 to 
< 18 years of age receiving rilpivirine 25 mg once daily was comparable to that in treatment-naïve 
HIV-1 infected adults receiving rilpivirine 25 mg once daily.  There was no impact of body weight on 
rilpivirine pharmacokinetics in paediatric patients in Study C213 (33 to 93 kg), similar to what was 
observed in adults.  The pharmacokinetics of rilpivirine in paediatric patients < 12 years of age is 
under investigation. 
 
Exposures of emtricitabine and tenofovir alafenamide given with elvitegravir + cobicistat achieved in 
24 paediatric patients aged 12 to < 18 years were similar to exposures achieved in treatment-naïve 
adults (Table 6). 



32 

 
Table 6: Pharmacokinetics of emtricitabine and tenofovir alafenamide in antiretroviral-naïve 
adolescents and adults 
 

 

Adolescents Adults 
Emtricitabine + tenofovir alafenamide 

 
Emtricitabine + tenofovir alafenamide 

 
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) 

FTC = emtricitabine; TAF = tenofovir alafenamide; 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 + 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 + tenofovir alafenamide in 
combination with elvitegravir + 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 + tenofovir alafenamide, given with elvitegravir + 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. 
 
The pharmacokinetics of rilpivirine have not been studied in patients with renal insufficiency.  Renal 
elimination of rilpivirine is negligible.  In patients with severe renal impairment or end-stage renal 
disease, plasma concentrations may be increased due to alteration of drug absorption, distribution 
and/or metabolism secondary to renal dysfunction.  As rilpivirine is highly bound to plasma proteins, 
it is unlikely that it will be significantly removed by haemodialysis or peritoneal dialysis (see 
section 4.9). 
 
Hepatic impairment 
The pharmacokinetics of emtricitabine have not been studied in patients with varying degrees of 
hepatic insufficiency; however emtricitabine is not significantly metabolised by liver enzymes, so the 
impact of liver impairment should be limited. 
 
Rilpivirine hydrochloride is primarily metabolised and eliminated by the liver.  In a study comparing 
8 patients with mild hepatic impairment (Child-Pugh Class A) to 8 matched controls and 8 patients 
with moderate hepatic impairment (Child-Pugh Class B) to 8 matched controls, the multiple dose 
exposure of rilpivirine was 47% higher in patients with mild hepatic impairment and 5% higher in 



33 

patients with moderate hepatic impairment.  However, it may not be excluded that the 
pharmacologically active, unbound, rilpivirine exposure is significantly increased in moderate 
impairment.  Rilpivirine has not been studied in patients with severe hepatic impairment (Child Pugh 
Class C) (see section 4.2). 
 
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, rilpivirine and tenofovir alafenamide have not been fully 
evaluated in patients co-infected with hepatitis B and/or C virus. 
 
Pregnancy and postpartum 
After taking rilpivirine 25 mg once daily as part of an antiretroviral regimen, the total exposure of 
rilpivirine was lower during pregnancy (similar for the 2nd and 3rd trimester) compared with 
postpartum.  The decrease in the unbound free fraction of rilpivirine exposure (i.e., active) during 
pregnancy compared to postpartum was less pronounced than for total exposure of rilpivirine. 
 
In women receiving rilpivirine 25 mg once daily during the 2nd trimester of pregnancy, mean intra-
individual values for total rilpivirine Cmax, AUC24h and Cmin values were 21%, 29% and 35% lower, 
respectively, as compared to postpartum; during the 3rd trimester of pregnancy, Cmax, AUC24h and Cmin 
values were 20%, 31% and 42% lower, respectively, as compared to postpartum. 
 
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. 
 
Non-clinical data on rilpivirine hydrochloride reveal no special hazard for humans based on studies of 
safety pharmacology, drug disposition, genotoxicity, carcinogenic potential, toxicity to reproduction 
and development.  Liver toxicity associated with liver enzyme induction was observed in rodents.  In 
dogs cholestasis-like effects were noted. 
 
Carcinogenicity studies with rilpivirine in mice and rats revealed tumorigenic potential specific for 
these species, but are regarded as of no relevance for humans. 
 
Non-clinical studies of tenofovir alafenamide in rats and dogs revealed bone and kidney as the primary 
target organs of toxicity.  Bone toxicity was observed as reduced bone mineral density in rats and dogs 
at tenofovir exposures at least four times greater than those expected after administration of Odefsey.  
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 Odefsey. 
 
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. 



34 

 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Tablet core 
 
Croscarmellose sodium 
Lactose (as monohydrate) 
Magnesium stearate 
Microcrystalline cellulose 
Polysorbate 20 
Povidone 
 
Film-coating 
 
Macrogol 
Polyvinyl alcohol 
Talc 
Titanium dioxide (E171) 
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. 
 
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 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. 
 
 



35 

7. MARKETING AUTHORISATION HOLDER 
 
Gilead Sciences Ireland UC 
Carrigtohill 
County Cork, T45 DP77 
Ireland 
 
 
8. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/16/1112/001 
EU/1/16/1112/002 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 21 June 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. 
  



36 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX II 
 

A. MANUFACTURER 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 



37 

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

AUTHORISATION 
 
• Periodic safety update reports (PSURs) 
 
The requirements for submission of PSURs for this medicinal product are set out in the list of Union 
reference dates (EURD list) provided for under Article 107c(7) of Directive 2001/83/EC and any 
subsequent updates published on the European medicines web-portal. 
 
The marketing authorisation holder (MAH) shall submit the first PSUR 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. 

 
  



38 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 
  



39 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 



40 

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

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



41 

 
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/1/16/1112/001 30 film-coated tablets 
EU/1/16/1112/002 90 (3 bottles of 30) film-coated tablets 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Odefsey [Outer packaging only] 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. [Outer packaging only] 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC: {number} 
SN: {number} 
NN: {number} 
[Outer packaging only] 
 
  



42 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 



43 

Package leaflet: Information for the user 
 

Odefsey 200 mg/25 mg/25 mg film-coated tablets 
emtricitabine/rilpivirine/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 Odefsey is and what it is used for 
2. What you need to know before you take Odefsey 
3. How to take Odefsey 
4. Possible side effects 
5. How to store Odefsey 
6. Contents of the pack and other information 
 
 
1. What Odefsey is and what it is used for 
 
Odefsey is an antiviral medicine used to treat infection by the Human Immunodeficiency 
Virus (HIV).  It is a single tablet that contains a combination of three active substances: 
emtricitabine, rilpivirine and tenofovir alafenamide.  Each of these active substances works by 
interfering with an enzyme called ‘reverse transcriptase’, which is essential for the HIV-1 virus to 
multiply. 
 
Odefsey reduces the amount of HIV in your body.  This will improve your immune system and reduce 
the risk of developing illnesses linked to HIV infection. 
 
Odefsey is used in adults and adolescents aged 12 years and older, who weigh at least 35 kg. 
 
 
2. What you need to know before you take Odefsey 
 
Do not take Odefsey 
 
• If you are allergic to emtricitabine, rilpivirine, tenofovir alafenamide or any of the other 

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

- carbamazepine, oxcarbazepine, phenobarbital and phenytoin (used to treat epilepsy 
and prevent seizures) 

- rifabutin, rifampicin and rifapentine (used to treat some bacterial infections such as 
tuberculosis) 

- omeprazole, dexlansoprazole, lansoprazole, rabeprazole, pantoprazole and 
esomeprazole (used to prevent and treat stomach ulcers, heartburn, acid reflux disease) 



44 

- dexamethasone (a corticosteroid medicine used to treat inflammation and suppress the 
immune system) when taken by mouth or injected (except as a single dose treatment) 

- products that contain St. John’s wort (Hypericum perforatum) (a herbal remedy used 
for depression and anxiety) 

 
 If this applies to you, do not take Odefsey and tell your doctor immediately. 
 
Warnings and precautions 
 
You must remain under the care of your doctor while taking Odefsey. 
 
You can still pass on HIV when taking this medicine, although the risk is lowered by effective 
antiretroviral therapy.  Discuss with your doctor the precautions needed to avoid infecting other 
people.  This medicine is not a cure for HIV infection.  While taking Odefsey you may still develop 
infections or other illnesses associated with HIV infection. 
 
Talk to your doctor before taking Odefsey: 
 
• If you have liver problems or a history of liver disease, including hepatitis.  Patients with 

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

 
If you have hepatitis B infection, liver problems may become worse after you stop taking 
Odefsey.  It is important not to stop taking Odefsey without talking to your doctor: see 
section 3, Do not stop taking Odefsey. 
 

• If you are taking any medicines that may cause a life-threatening irregular heartbeat (Torsades 
de Pointes). 

 
While you are taking Odefsey 
 
Once you start taking Odefsey, 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. 
 
It is possible that in the future, long-term users of Odefsey may get kidney problems. 
 
Children and adolescents 
 
Do not give this medicine to children aged 11 years or under, or weighing less than 35 kg.  The 
use of Odefsey in children aged 11 years or under or weighing less than 35 kg has not yet been 
studied. 
 
Other medicines and Odefsey 
 
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 
medicines.  Odefsey may interact with other medicines.  As a result, the amounts of Odefsey or other 
medicines in your blood may be affected.  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. 
 



45 

Medicines that must never be taken with Odefsey: 
 

- carbamazepine, oxcarbazepine, phenobarbital and phenytoin (used to treat epilepsy 
and prevent seizures) 

- rifabutin, rifampicin and rifapentine (used to treat some bacterial infections such as 
tuberculosis) 

- omeprazole, dexlansoprazole, lansoprazole, rabeprazole, pantoprazole and 
esomeprazole (used to prevent and treat stomach ulcers, heartburn, acid reflux disease) 

- dexamethasone (a corticosteroid medicine used to treat inflammation and suppress the 
immune system) when taken by mouth or injected (except as a single dose treatment) 

- products that contain St. John’s wort (Hypericum perforatum) (a herbal remedy used 
for depression and anxiety) 

 
 If you are taking any of these medicines, do not take Odefsey and tell your doctor immediately. 
 
Other types of medicine: 
 
Talk to your doctor if you are taking: 
 
• Any medicines used for treating HIV 

 
• Any medicines containing: 

- tenofovir alafenamide 
- tenofovir disoproxil 
- lamivudine 
- adefovir dipivoxil 

 
• Antibiotics used to treat bacterial infections containing: 

- clarithromycin 
- erythromycin 
These medicines can increase the amount of rilpivirine and tenofovir alafenamide (components 
of Odefsey) in your blood.  Your doctor will give you a different medicine. 

 
• Antifungal medicines used to treat fungal infections: 

- ketoconazole 
- fluconazole 
- itraconazole 
- posaconazole 
- voriconazole 
These medicines can increase the amount of rilpivirine and tenofovir alafenamide (components 
of Odefsey) in your blood.  Your doctor will give you a different medicine. 

 
• Medicines for stomach ulcers, heartburn or acid reflux such as: 

- antacids (aluminium/magnesium hydroxide or calcium carbonate) 
- H2-antagonists (famotidine, cimetidine, nizatidine or ranitidine) 
These medicines can decrease the amount of rilpivirine (a component of Odefsey) in your 
blood.  If you are taking one of these medicines your doctor will either give you a different 
medicine, or recommend how and when you take that medicine: 

 
- If you are taking an antacid, take it at least 2 hours before or at least 4 hours after 

Odefsey. 
 

- If you are taking an H2-antagonist, take it at least 12 hours before or at least 4 hours 
after Odefsey.  H2-antagonists can only be taken once a day if you take Odefsey.  
H2-antagonists should not be taken in a twice a day regimen.  Talk to your doctor about 
an alternative regimen (see How to take Odefsey). 

 



46 

• Ciclosporin, a medicine used to reduce the strength of the body’s immune system: 
This medicine can increase the amount of rilpivirine and tenofovir alafenamide (components of 
Odefsey) in your blood.  Your doctor will give you a different medicine. 
 

• Methadone, a medicine used to treat opiate addiction, as your doctor may need to change your 
methadone dose. 

 
• Dabigatran etexilate, a medicine used to treat heart conditions, as your doctor may need to 

monitor the levels of this medicine in your blood. 
 

 Tell your doctor if you are taking any of these 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 for advice before taking this medicine. 
• Use effective contraception while taking Odefsey. 
 
Ask your doctor or pharmacist for advice before taking any medicine when pregnant. 
 
If you have taken Odefsey during your pregnancy, your doctor may request regular blood tests and 
other diagnostic tests to monitor the development of your child.  In children whose mothers took 
nucleoside reverse transcriptase inhibitors (NRTIs) during pregnancy, the benefit from the protection 
against HIV outweighed the risk of side effects. 
 
Do not breast-feed during treatment with Odefsey.  This is because some of the active substances 
in this medicine pass into human breast milk.  It is also recommended that you do not breast-feed to 
avoid passing the virus to the baby in breast milk. 
 
Driving and using machines 
 
Do not drive or operate machines if you feel tired, sleepy or dizzy after taking your medicine. 
 
Odefsey contains lactose and sodium 
 
If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor 
before taking this medicine. 
 
This medicine contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially ‘sodium-
free’. 
 
 If any of these applies to you, talk to your doctor before taking Odefsey. 
 
 
3. How to take Odefsey 
 
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 food 
Adolescents 12 years of age and older, who weigh at least 35 kg: one tablet each day with food 
 
Do not chew, crush or split the tablet. 
 



47 

If you are taking an antacid such as aluminium/magnesium hydroxide, or calcium carbonate, take it 
at least 2 hours before or at least 4 hours after Odefsey. 
 
If you are taking an H2-antagonist such as famotidine, cimetidine, nizatidine or ranitidine, take it at 
least 12 hours before or at least 4 hours after Odefsey.  H2-antagonists can only be taken once a day if 
you take Odefsey.  H2-antagonists should not be taken twice a day.  Talk to your doctor about an 
alternative regimen. 
 
If you are on dialysis, take your daily dose of Odefsey following completion of dialysis. 
 
If you take more Odefsey than you should 
 
If you accidentally take more than the recommended dose of Odefsey you may be at increased risk of 
experiencing possible side effects with this medicine (see section 4, Possible side effects). 
 
Contact your doctor or nearest emergency department immediately for advice.  Keep or take the tablet 
bottle with you so that you can easily describe what you have taken. 
 
If you forget to take Odefsey 
 
It is important not to miss a dose of Odefsey. 
 
If you do miss a dose: 
• If you notice within 12 hours of the time you usually take Odefsey, you must take the tablet as 

soon as possible.  Always take the tablet with food.  Then take the next dose as usual. 
• If you notice 12 hours or more after the time you usually take Odefsey, then do not take the 

missed dose.  Wait and take the next dose, with food, at your usual time. 
 
If you vomit less than 4 hours after taking Odefsey, take another tablet with food.  If you vomit 
more than 4 hours after taking Odefsey you do not need to take another tablet until your next 
regularly scheduled tablet. 
 
Do not stop taking Odefsey 
 
Do not stop taking Odefsey without talking to your doctor.  Stopping Odefsey can seriously affect 
your response to future treatment.  If Odefsey is stopped for any reason, speak to your doctor before 
you restart taking Odefsey tablets. 
 
When your supply of Odefsey starts to run low, get more from your doctor or pharmacist.  This is 
very important because the amount of virus may start to increase if the medicine is stopped for even a 
short time.  The disease may then become harder to treat. 
 
If you have both HIV infection and hepatitis B, it is especially important not to stop your Odefsey 
treatment without talking to your doctor first.  You may require blood tests for several months after 
stopping treatment.  In some patients with advanced liver disease or cirrhosis, stopping treatment is 
not recommended as this may lead to worsening of your hepatitis, which may be life-threatening. 
 
 Tell your doctor immediately about new or unusual symptoms after you stop treatment, 

particularly symptoms you associate with hepatitis B infection. 
 
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. 
 



48 

Possible side effects: tell a doctor immediately 
 
• Any signs of inflammation or infection.  In some patients with advanced HIV infection 

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

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

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

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

 
Very common side effects 
(may affect more than 1 in 10 people) 
• difficulty sleeping (insomnia) 
• headache 
• dizziness 
• feeling sick (nausea) 
 
Tests may also show: 
• increased levels of cholesterol and/or pancreatic amylase (a digestive enzyme) in the blood 
• increased levels of liver enzymes in the blood 
 
Common side effects 
(may affect up to 1 in 10 people) 
• decreased appetite 
• depression 
• abnormal dreams 
• sleep disorders 
• depressed mood 
• feeling sleepy (somnolence) 
• tiredness 
• stomach pain or discomfort 
• being sick (vomiting) 
• feeling bloated 
• dry mouth 
• wind (flatulence) 
• diarrhoea 
• rash 
 
Tests may also show: 
• low white blood cell count (a reduced white blood cell count can make you more prone to 

infection) 
• low platelet count (a type of blood cell involved in clotting blood) 
• decrease in haemoglobin in your blood 
• increased fatty acids (triglycerides), bilirubin or lipase in the blood 
 



49 

Uncommon side effects 
(may affect up to 1 in 100 people) 
• signs or symptoms of inflammation or infection 
• low red blood cell count (anaemia) 
• severe skin reactions including rash accompanied by fever, swelling and liver problems 
• problems with digestion resulting in discomfort after meals 
• 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 Odefsey 

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

 If you notice any of these symptoms tell your doctor. 
 
During HIV therapy there may be an increase in weight and in levels of blood lipids and glucose.  This 
is partly linked to restored health and life style, and in the case of blood lipids sometimes to the HIV 
medicines themselves.  Your doctor will test for these changes. 
 
Reporting of side effects 
If you get any side effects, talk to your doctor or pharmacist.  This includes any possible side effects 
not listed in this leaflet.  You can also report side effects directly via the national reporting system 
listed in Appendix V.  By reporting side effects you can help provide more information on the safety 
of this medicine. 
 
 
5. How to store Odefsey 
 
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. 
 
 

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


50 

6. Contents of the pack and other information 
 
What Odefsey contains 
 
The active substances are emtricitabine, rilpivirine and tenofovir alafenamide.  Each Odefsey tablet 
contains 200 mg of emtricitabine, rilpivirine hydrochloride equivalent to 25 mg of rilpivirine and 
tenofovir alafenamide fumarate equivalent to 25 mg of tenofovir alafenamide. 
 
The other ingredients are 
 
Tablet core: 
Croscarmellose sodium, lactose (as monohydrate), magnesium stearate, microcrystalline cellulose, 
polysorbate 20, povidone. 
 
Film-coating: 
Macrogol, polyvinyl alcohol, talc, titanium dioxide (E171), iron oxide black (E172). 
 
What Odefsey looks like and contents of the pack 
 
Odefsey is a grey, capsule-shaped, film-coated tablet debossed on one side with “GSI” and “255” on 
the other side.  Odefsey comes in bottles of 30 tablets and in packs made up of 3 bottles, each 
containing 30 tablets.  Each bottle contains a silica gel desiccant that must be kept in the bottle to help 
protect your tablets.  The silica gel desiccant is contained in a separate sachet or canister and should 
not be swallowed. 
 
Not all pack sizes may be marketed. 
 
Marketing Authorisation Holder 
Gilead Sciences Ireland UC 
Carrigtohill 
County Cork, T45 DP77 
Ireland 
 
Manufacturer 
Gilead Sciences Ireland UC 
IDA Business and 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 
 



51 

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 
 

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 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