Vemlidy

1 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 



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This medicinal product is subject to additional monitoring.  This will allow quick identification of 
new safety information.  Healthcare professionals are asked to report any suspected adverse reactions.  
See section 4.8 for how to report adverse reactions. 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Vemlidy 25 mg film-coated tablets. 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each film-coated tablet contains tenofovir alafenamide fumarate equivalent to 25 mg of tenofovir 
alafenamide. 
 
Excipient with known effect 
 
Each tablet contains 95 mg lactose (as monohydrate). 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Film-coated tablet. 
 
Yellow, round, film-coated tablets, 8 mm in diameter, debossed with “GSI” on one side of the tablet 
and “25” on the other side of the tablet. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Vemlidy is indicated for the treatment of chronic hepatitis B in adults and adolescents (aged 12 years 
and older with body weight at least 35 kg) (see section 5.1). 
 
4.2 Posology and method of administration 
 
Therapy should be initiated by a physician experienced in the management of chronic hepatitis B. 
 
Posology 
 
Adults and adolescents (aged 12 years and older with body weight at least 35 kg): one tablet once 
daily. 
 
Treatment discontinuation 
Treatment discontinuation may be considered as follows (see section 4.4): 
 
• In HBeAg-positive patients without cirrhosis, treatment should be administered for at least 

6-12 months after HBe seroconversion (HBeAg loss and HBV DNA loss with 
anti-HBe detection) is confirmed or until HBs seroconversion or until there is loss of efficacy 
(see section 4.4).  Regular reassessment is recommended after treatment discontinuation to 
detect virological relapse. 

 
• In HBeAg-negative patients without cirrhosis, treatment should be administered at least until 

HBs seroconversion or until there is evidence of loss of efficacy.  With prolonged treatment for 



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more than 2 years, regular reassessment is recommended to confirm that continuing the selected 
therapy remains appropriate for the patient. 

 
Missed dose 
If a dose is missed and less than 18 hours have passed from the time it is usually taken, the patient 
should take Vemlidy as soon as possible and then resume their normal dosing schedule.  If more than 
18 hours have passed from the time it is usually taken, the patient should not take the missed dose and 
should simply resume the normal dosing schedule.  
 
If the patient vomits within 1 hour of taking Vemlidy, the patient should take another tablet.  If the 
patient vomits more than 1 hour after taking Vemlidy, the patient does not need to take another tablet. 
 
Special populations 
 
Elderly 
No dose adjustment of Vemlidy is required in patients aged 65 years and older (see section 5.2). 
 
Renal impairment 
No dose adjustment of Vemlidy is required in adults or adolescents (aged at least 12 years and of at 
least 35 kg body weight) with estimated creatinine clearance (CrCl) ≥ 15 mL/min or in patients with 
CrCl < 15 mL/min who are receiving haemodialysis. 
 
On days of haemodialysis, Vemlidy should be administered after completion of haemodialysis 
treatment (see section 5.2). 
 
No dosing recommendations can be given for patients with CrCl < 15 mL/min who are not receiving 
haemodialysis (see section 4.4). 
 
Hepatic impairment 
No dose adjustment of Vemlidy is required in patients with hepatic impairment (see sections 4.4 
and 5.2). 
 
Paediatric population 
The safety and efficacy of Vemlidy in children younger than 12 years of age, or weighing < 35 kg, 
have not yet been established.  No data are available. 
 
Method of administration 
 
Oral administration.  Vemlidy film-coated tablets should be taken with food. 
 
4.3 Contraindications 
 
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 
 
4.4 Special warnings and precautions for use 
 
HBV transmission 
 
Patients must be advised that Vemlidy does not prevent the risk of transmission of HBV to others 
through sexual contact or contamination with blood.  Appropriate precautions must continue to be 
used. 
 
Patients with decompensated liver disease 
 
There are no data on the safety and efficacy of Vemlidy in HBV infected patients with decompensated 
liver disease and who have a Child Pugh Turcotte (CPT) score > 9 (i.e. class C).  These patients may 



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be at higher risk of experiencing serious hepatic or renal adverse reactions. Therefore, hepatobiliary 
and renal parameters should be closely monitored in this patient population (see section 5.2). 
 
Exacerbation of hepatitis 
 
Flares on treatment  
Spontaneous exacerbations in chronic hepatitis B are relatively common and are characterised by 
transient increases in serum alanine aminotransferase (ALT).  After initiating antiviral therapy, 
serum ALT may increase in some patients.  In patients with compensated liver disease, these increases 
in serum ALT are generally not accompanied by an increase in serum bilirubin concentrations or 
hepatic decompensation.  Patients with cirrhosis may be at a higher risk for hepatic decompensation 
following hepatitis exacerbation, and therefore should be monitored closely during therapy. 
 
Flares after treatment discontinuation 
Acute exacerbation of hepatitis has been reported in patients who have discontinued treatment for 
hepatitis B, usually in association with rising HBV DNA levels in plasma.  The majority of cases are 
self-limited but severe exacerbations, including fatal outcomes, may occur after discontinuation of 
treatment for hepatitis B.  Hepatic function should be monitored at repeated intervals with both clinical 
and laboratory follow-up for at least 6 months after discontinuation of treatment for hepatitis B.  If 
appropriate, resumption of hepatitis B therapy may be warranted. 
 
In patients with advanced liver disease or cirrhosis, treatment discontinuation is not recommended 
since post-treatment exacerbation of hepatitis may lead to hepatic decompensation.  Liver flares are 
especially serious, and sometimes fatal in patients with decompensated liver disease. 
 
Renal impairment 
 
Patients with creatinine clearance < 30 mL/min 
The use of Vemlidy once daily in patients with CrCl ≥ 15 mL/min but < 30 mL/min and in patients 
with CrCl < 15 mL/min who are receiving haemodialysis is based on very limited pharmacokinetic 
data and on modelling and simulation.  There are no safety data on the use of Vemlidy to treat 
HBV infected patients with CrCl < 30 mL/min. 
 
The use of Vemlidy is not recommended in patients with CrCl < 15 mL/min who are not receiving 
haemodialysis (see section 4.2). 
 
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 co-infected with HBV and hepatitis C or D virus 
 
There are no data on the safety and efficacy of Vemlidy in patients co-infected with hepatitis C or D 
virus.  Co-administration guidance for the treatment of hepatitis C should be followed (see 
section 4.5). 
 
Hepatitis B and HIV co-infection 
 
HIV antibody testing should be offered to all HBV infected patients whose HIV-1 infection status is 
unknown before initiating therapy with Vemlidy.  In patients who are co-infected with HBV and HIV, 
Vemlidy should be co-administered with other antiretroviral agents to ensure that the patient receives 
an appropriate regimen for treatment of HIV (see section 4.5). 
 



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Co-administration with other medicinal products 
 
Vemlidy should not be co-administered with medicinal products containing tenofovir alafenamide, 
tenofovir disoproxil or adefovir dipivoxil. 
 
Co-administration of Vemlidy with certain anticonvulsants (e.g. carbamazepine, oxcarbazepine, 
phenobarbital and phenytoin), antimycobacterials (e.g. rifampicin, rifabutin and rifapentine) or 
St. John’s wort, all of which are inducers of P-glycoprotein (P-gp) and may decrease tenofovir 
alafenamide plasma concentrations, is not recommended. 
 
Co-administration of Vemlidy with strong inhibitors of P-gp (e.g. itraconazole and ketoconazole) may 
increase tenofovir alafenamide plasma concentrations.  Co-administration is not recommended. 
 
Lactose intolerance 
 
Vemlidy contains lactose monohydrate. Patients with rare hereditary problems of galactose 
intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicinal 
product. 
 
Excipients 
 
This medicine contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially 
‘sodium-free’. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
Interaction studies have only been performed in adults. 
 
Vemlidy should not be co-administered with medicinal products containing tenofovir disoproxil, 
tenofovir alafenamide or adefovir dipivoxil. 
 
Medicinal products that may affect tenofovir alafenamide 
 
Tenofovir alafenamide is transported by P-gp and breast cancer resistance protein (BCRP).  Medicinal 
products that are P-gp inducers (e.g., rifampicin, rifabutin, carbamazepine, phenobarbital or 
St. John’s wort) are expected to decrease plasma concentrations of tenofovir alafenamide, which may 
lead to loss of therapeutic effect of Vemlidy.  Co-administration of such medicinal products with 
Vemlidy is not recommended. 
 
Co-administration of tenofovir alafenamide with medicinal products that inhibit P-gp and BCRP may 
increase plasma concentrations of tenofovir alafenamide.  Co-administration of strong inhibitors of 
P-gp with tenofovir alafenamide is not recommended. 
 
Tenofovir alafenamide is a substrate of OATP1B1 and OATP1B3 in vitro.  The distribution of 
tenofovir alafenamide in the body may be affected by the activity of OATP1B1 and/or OATP1B3. 
 
Effect of tenofovir alafenamide on other medicinal products 
 
Tenofovir alafenamide is not an inhibitor of CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, or 
CYP2D6 in vitro.  It is not an inhibitor or inducer of CYP3A in vivo. 
 
Tenofovir alafenamide is not an inhibitor of human uridine diphosphate glucuronosyltransferase 
(UGT) 1A1 in vitro.  It is not known whether tenofovir alafenamide is an inhibitor of other 
UGT enzymes. 
 
Drug interaction information for Vemlidy with potential concomitant medicinal products is 
summarised in Table 1 below (increase is indicated as “↑”, decrease as “↓”, no change as “↔”; twice 



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daily as “b.i.d.”, single dose as “s.d.”, once daily as “q.d.”; and intravenously as “IV”).  The drug 
interactions described are based on studies conducted with tenofovir alafenamide, or are potential drug 
interactions that may occur with Vemlidy. 
 
Table 1: Interactions between Vemlidy and other medicinal products 
 
Medicinal product by 
therapeutic areas 

Effects on drug levels.a,b 
Mean ratio (90% 
confidence interval) for 
AUC, Cmax, Cmin 

Recommendation concerning co-administration 
with Vemlidy 

ANTICONVULSANTS 
Carbamazepine 
(300 mg orally, b.i.d.) 
 
Tenofovir alafenamidec 
(25 mg orally, s.d.) 

Tenofovir alafenamide 
↓ Cmax 0.43 (0.36, 0.51) 
↓ AUC 0.45 (0.40, 0.51) 
 
Tenofovir 
↓ Cmax 0.70 (0.65, 0.74) 
↔ AUC 0.77 (0.74, 0.81) 

Co-administration is not recommended. 

Oxcarbazepine 
Phenobarbital 
 

Interaction not studied. 
Expected: 
↓ Tenofovir alafenamide 

Co-administration is not recommended. 

Phenytoin Interaction not studied. 
Expected: 
↓ Tenofovir alafenamide 

Co-administration is not recommended. 

Midazolamd 
(2.5 mg orally, s.d.) 
 
Tenofovir alafenamidec 
(25 mg orally, q.d.) 

Midazolam 
↔ Cmax 1.02 (0.92, 1.13) 
↔ AUC 1.13 (1.04, 1.23) 

No dose adjustment of midazolam (administered 
orally or IV) is required. 

Midazolamd 
(1 mg IV, s.d.) 
 
Tenofovir alafenamidec 
(25 mg orally, q.d.) 

Midazolam 
↔ Cmax 0.99 (0.89, 1.11) 
↔ AUC 1.08 (1.04, 1.14) 

ANTIDEPRESSANTS 
Sertraline 
(50 mg orally, s.d.) 
 
Tenofovir alafenamidee 
(10 mg orally, q.d.) 

Tenofovir alafenamide 
↔ Cmax 1.00 (0.86, 1.16) 
↔ AUC 0.96 (0.89, 1.03) 
 
Tenofovir 
↔ Cmax 1.10 (1.00, 1.21) 
↔ AUC 1.02 (1.00, 1.04) 
↔ Cmin 1.01 (0.99, 1.03) 

No dose adjustment of Vemlidy or sertraline is 
required. 

Sertraline 
(50 mg orally, s.d.) 
 
Tenofovir alafenamidee 
(10 mg orally, q.d.) 

Sertraline 
↔ Cmax 1.14 (0.94, 1.38) 
↔ AUC 0.93 (0.77, 1.13) 

ANTIFUNGALS 
Itraconazole 
Ketoconazole 

Interaction not studied. 
Expected: 
↑ Tenofovir alafenamide 

Co-administration is not recommended. 

ANTIMYCOBACTERIALS 
Rifampicin 
Rifapentine 

Interaction not studied. 
Expected: 
↓ Tenofovir alafenamide 

Co-administration is not recommended. 

Rifabutin Interaction not studied. 
Expected: 
↓ Tenofovir alafenamide 

Co-administration is not recommended. 



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Medicinal product by 
therapeutic areas 

Effects on drug levels.a,b 
Mean ratio (90% 
confidence interval) for 
AUC, Cmax, Cmin 

Recommendation concerning co-administration 
with Vemlidy 

HCV ANTIVIRAL AGENTS 
Sofosbuvir (400 mg orally, 
q.d.) 

Interaction not studied. 
Expected: 
↔ Sofosbuvir 
↔ GS-331007 

No dose adjustment of Vemlidy or sofosbuvir is 
required. 

Ledipasvir/sofosbuvir 
(90 mg/400 mg orally, q.d.) 
 
Tenofovir alafenamidef 
(25 mg orally, q.d.) 

Ledipasvir 
↔ Cmax 1.01 (0.97, 1.05) 
↔ AUC 1.02 (0.97, 1.06) 
↔ Cmin 1.02 (0.98, 1.07) 
 
Sofosbuvir 
↔ Cmax 0.96 (0.89, 1.04) 
↔ AUC 1.05 (1.01, 1.09) 
 
GS-331007g 
↔ Cmax 1.08 (1.05, 1.11) 
↔ AUC 1.08 (1.06, 1.10) 
↔ Cmin 1.10 (1.07, 1.12) 
 
Tenofovir alafenamide 
↔ Cmax 1.03 (0.94, 1.14) 
↔ AUC 1.32 (1.25, 1.40) 
 
Tenofovir 
↑ Cmax 1.62 (1.56, 1.68) 
↑ AUC 1.75 (1.69, 1.81) 
↑ Cmin 1.85 (1.78, 1.92) 

No dose adjustment of Vemlidy or 
ledipasvir/sofosbuvir is required. 

Sofosbuvir/velpatasvir 
(400 mg/100 mg orally, 
q.d.) 

Interaction not studied. 
Expected: 
↔ Sofosbuvir 
↔ GS-331007 
↔ Velpatasvir 
↑ Tenofovir alafenamide 

No dose adjustment of Vemlidy or 
sofosbuvir/velpatasvir is required. 

Sofosbuvir/velpatasvir/ 
voxilaprevir 
(400 mg/100 mg/ 
100 mg + 100 mgi orally, 
q.d.) 
 
Tenofovir alafenamidef 
(25 mg orally, q.d.) 

Sofosbuvir 
↔ Cmax 0.95 (0.86, 1.05) 
↔ AUC 1.01 (0.97, 1.06) 
 
GS-331007g 
↔ Cmax 1.02 (0.98, 1.06) 
↔ AUC 1.04 (1.01, 1.06) 
 
Velpatasvir 
↔ Cmax 1.05 (0.96, 1.16) 
↔ AUC 1.01 (0.94, 1.07) 
↔ Cmin 1.01 (0.95, 1.09) 
 
Voxilaprevir 
↔ Cmax 0.96 (0.84, 1.11) 
↔ AUC 0.94 (0.84, 1.05) 
↔ Cmin 1.02 (0.92, 1.12) 
 
Tenofovir alafenamide 
↑ Cmax 1.32 (1.17, 1.48) 
↑ AUC 1.52 (1.43, 1.61) 

No dose adjustment of Vemlidy or 
sofosbuvir/velpatasvir/voxilaprevir is required. 



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Medicinal product by 
therapeutic areas 

Effects on drug levels.a,b 
Mean ratio (90% 
confidence interval) for 
AUC, Cmax, Cmin 

Recommendation concerning co-administration 
with Vemlidy 

HIV ANTIRETROVIRAL AGENTS – PROTEASE INHIBITORS 
Atazanavir/cobicistat 
(300 mg/150 mg orally, 
q.d.) 
 
Tenofovir alafenamidec 
(10 mg orally, q.d.) 

Tenofovir alafenamide 
↑ Cmax 1.80 (1.48, 2.18) 
↑ AUC 1.75 (1.55, 1.98) 
 
Tenofovir 
↑ Cmax 3.16 (3.00, 3.33) 
↑ AUC 3.47 (3.29, 3.67) 
↑ Cmin 3.73 (3.54, 3.93) 
 
Atazanavir 
↔ Cmax 0.98 (0.94, 1.02) 
↔ AUC 1.06 (1.01, 1.11) 
↔ Cmin 1.18 (1.06, 1.31) 
 
Cobicistat 
↔ Cmax 0.96 (0.92, 1.00) 
↔ AUC 1.05 (1.00, 1.09) 
↑ Cmin 1.35 (1.21, 1.51) 

Co-administration is not recommended. 

Atazanavir/ritonavir 
(300 mg/100 mg orally, 
q.d.) 
 
Tenofovir alafenamidec 
(10 mg orally, s.d.) 

Tenofovir alafenamide 
↑ Cmax 1.77 (1.28, 2.44) 
↑ AUC 1.91 (1.55, 2.35) 
 
Tenofovir 
↑ Cmax 2.12 (1.86, 2.43) 
↑ AUC 2.62 (2.14, 3.20) 
 
Atazanavir 
↔ Cmax 0.98 (0.89, 1.07) 
↔ AUC 0.99 (0.96, 1.01) 
↔ Cmin 1.00 (0.96, 1.04) 

Co-administration is not recommended. 

Darunavir/cobicistat 
(800 mg/150 mg orally, 
q.d.) 
 
Tenofovir alafenamidec 
(25 mg orally, q.d.) 

Tenofovir alafenamide 
↔ Cmax 0.93 (0.72, 1.21) 
↔ AUC 0.98 (0.80, 1.19) 
 
Tenofovir 
↑ Cmax 3.16 (3.00, 3.33) 
↑ AUC 3.24 (3.02, 3.47) 
↑ Cmin 3.21 (2.90, 3.54) 
 
Darunavir 
↔ Cmax 1.02 (0.96, 1.09) 
↔ AUC 0.99 (0.92, 1.07) 
↔ Cmin 0.97 (0.82, 1.15) 
 
Cobicistat 
↔ Cmax 1.06 (1.00, 1.12) 
↔ AUC 1.09 (1.03, 1.15) 
↔ Cmin 1.11 (0.98, 1.25) 

Co-administration is not recommended. 



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Medicinal product by 
therapeutic areas 

Effects on drug levels.a,b 
Mean ratio (90% 
confidence interval) for 
AUC, Cmax, Cmin 

Recommendation concerning co-administration 
with Vemlidy 

Darunavir/ritonavir 
(800 mg/100 mg orally, 
q.d.) 
 
Tenofovir alafenamidec 
(10 mg orally, s.d.) 

Tenofovir alafenamide 
↑ Cmax 1.42 (0.96, 2.09) 
↔ AUC 1.06 (0.84, 1.35) 
 
Tenofovir 
↑ Cmax 2.42 (1.98, 2.95) 
↑ AUC 2.05 (1.54, 2.72) 
 
Darunavir 
↔ Cmax 0.99 (0.91, 1.08) 
↔ AUC 1.01 (0.96, 1.06) 
↔ Cmin 1.13 (0.95, 1.34) 

Co-administration is not recommended. 

Lopinavir/ritonavir 
(800 mg/200 mg orally, 
q.d.) 
 
Tenofovir alafenamidec 
(10 mg orally, s.d.) 

Tenofovir alafenamide 
↑ Cmax 2.19 (1.72, 2.79) 
↑ AUC 1.47 (1.17, 1.85) 
 
Tenofovir 
↑ Cmax 3.75 (3.19, 4.39) 
↑ AUC 4.16 (3.50, 4.96) 
 
Lopinavir 
↔ Cmax 1.00 (0.95, 1.06) 
↔ AUC 1.00 (0.92, 1.09) 
↔ Cmin 0.98 (0.85, 1.12) 

Co-administration is not recommended. 

Tipranavir/ritonavir Interaction not studied. 
Expected: 
↓ Tenofovir alafenamide 

Co-administration is not recommended. 

HIV ANTIRETROVIRAL AGENTS – INTEGRASE INHIBITORS 
Dolutegravir  
(50 mg orally, q.d.) 
 
Tenofovir alafenamidec 
(10 mg orally, s.d.) 

Tenofovir alafenamide 
↑ Cmax 1.24 (0.88, 1.74) 
↑ AUC 1.19 (0.96, 1.48) 
 
Tenofovir 
↔ Cmax 1.10 (0.96, 1.25) 
↑ AUC 1.25 (1.06, 1.47) 
 
Dolutegravir 
↔ Cmax 1.15 (1.04, 1.27) 
↔ AUC 1.02 (0.97, 1.08) 
↔ Cmin 1.05 (0.97, 1.13) 

No dose adjustment of Vemlidy or dolutegravir is 
required. 

Raltegravir Interaction not studied. 
Expected: 
↔ Tenofovir alafenamide 
↔ Raltegravir 

No dose adjustment of Vemlidy or raltegravir is 
required. 

HIV ANTIRETROVIRAL AGENTS – NON-NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS 
Efavirenz  
(600 mg orally, q.d.) 
 
Tenofovir alafenamideh 
(40 mg orally, q.d.) 

Tenofovir alafenamide 
↓ Cmax 0.78 (0.58, 1.05) 
↔ AUC 0.86 (0.72, 1.02) 
 
Tenofovir 
↓ Cmax 0.75 (0.67, 0.86) 
↔ AUC 0.80 (0.73, 0.87) 
↔ Cmin 0.82 (0.75, 0.89) 
 
Expected: 
↔ Efavirenz 

No dose adjustment of Vemlidy or efavirenz is 
required. 



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Medicinal product by 
therapeutic areas 

Effects on drug levels.a,b 
Mean ratio (90% 
confidence interval) for 
AUC, Cmax, Cmin 

Recommendation concerning co-administration 
with Vemlidy 

Nevirapine Interaction not studied. 
Expected: 
↔ Tenofovir alafenamide 
↔ Nevirapine 

No dose adjustment of Vemlidy or nevirapine is 
required. 

Rilpivirine  
(25 mg orally, q.d.) 
 
Tenofovir alafenamide 
(25 mg orally, q.d.) 

Tenofovir alafenamide 
↔ Cmax 1.01 (0.84, 1.22) 
↔ AUC 1.01 (0.94, 1.09) 
 
Tenofovir 
↔ Cmax 1.13 (1.02, 1.23) 
↔ AUC 1.11 (1.07, 1.14) 
↔ Cmin 1.18 (1.13, 1.23) 
 
Rilpivirine 
↔ Cmax 0.93 (0.87, 0.99) 
↔ AUC 1.01 (0.96, 1.06) 
↔ Cmin 1.13 (1.04, 1.23) 

No dose adjustment of Vemlidy or rilpivirine is 
required. 

HIV ANTIRETROVIRAL AGENTS – CCR5 RECEPTOR ANTAGONIST 
Maraviroc Interaction not studied. 

Expected: 
↔ Tenofovir alafenamide 
↔ Maraviroc 

No dose adjustment of Vemlidy or maraviroc is 
required. 

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

Interaction not studied. 
Expected: 
↓ Tenofovir alafenamide 

Co-administration is not recommended. 

ORAL CONTRACEPTIVES 
Norgestimate 
(0.180 mg/0.215 mg/ 
0.250 mg orally, q.d.) 
 
Ethinylestradiol 
(0.025 mg orally, q.d.) 
 
Tenofovir alafenamidec 
(25 mg orally, q.d.) 

Norelgestromin 
↔ Cmax 1.17 (1.07, 1.26) 
↔ AUC 1.12 (1.07, 1.17) 
↔ Cmin 1.16 (1.08, 1.24) 
 
Norgestrel 
↔ Cmax 1.10 (1.02, 1.18) 
↔ AUC 1.09 (1.01, 1.18) 
↔ Cmin 1.11 (1.03, 1.20) 
 
Ethinylestradiol 
↔ Cmax 1.22 (1.15, 1.29) 
↔ AUC 1.11 (1.07, 1.16) 
↔ Cmin 1.02 (0.93, 1.12) 

No dose adjustment of Vemlidy or 
norgestimate/ethinyl estradiol is required. 

a All interaction studies are conducted in healthy volunteers. 
b All No Effect Boundaries are 70%-143%. 
c Study conducted with emtricitabine/tenofovir alafenamide fixed-dose combination tablet. 
d A sensitive CYP3A4 substrate. 
e Study conducted with elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide fixed-dose combination tablet. 
f Study conducted with emtricitabine/rilpivirine/tenofovir alafenamide fixed-dose combination tablet. 
g The predominant circulating nucleoside metabolite of sofosbuvir. 
h Study conducted with tenofovir alafenamide 40 mg and emtricitabine 200 mg. 
i Study conducted with additional voxilaprevir 100 mg to achieve voxilaprevir exposures expected in HCV infected 

patients. 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
 
There are no or limited amount of data (less than 300 pregnancy outcomes) from the use of tenofovir 
alafenamide in pregnant women.  However, a large amount of data on pregnant women (more than 



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1,000 exposed outcomes) indicate no malformative nor feto/neonatal toxicity associated with the use 
of tenofovir disoproxil. 
 
Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity 
(see section 5.3). 
 
The use of tenofovir alafenamide may be considered during pregnancy, if necessary. 
 
Breast-feeding 
 
It is not known whether tenofovir alafenamide is secreted in human milk.  However, in animal studies 
it has been shown that tenofovir is secreted into milk.  There is insufficient information on the effects 
of tenofovir in newborns/infants. 
 
A risk to the breast-fed newborns/infants cannot be excluded; therefore, tenofovir alafenamide should 
not be used during breast-feeding. 
 
Fertility 
 
No human data on the effect of tenofovir alafenamide on fertility are available.  Animal studies do not 
indicate harmful effects of tenofovir alafenamide on fertility. 
 
4.7 Effects on ability to drive and use machines 
 
Vemlidy has no or negligible influence on the ability to drive and use machines.  Patients should be 
informed that dizziness has been reported during treatment with tenofovir alafenamide. 
 
4.8 Undesirable effects 
 
Summary of the safety profile 
 
Assessment of adverse reactions is based on pooled safety data from 2 controlled Phase 3 studies 
(GS-US-320-0108 and GS-US-320-0110; “Study 108” and “Study 110”, respectively) in which 
866 HBV infected viremic patients with elevated serum ALT levels received 25 mg tenofovir 
alafenamide once daily in a double-blind fashion through Week 96 (median duration of blinded study 
drug exposure of 104 weeks) and from post-marketing experience. The most frequently reported 
adverse reactions were headache (12%), nausea (6%), and fatigue (6%).  After Week 96, patients 
either remained on their original blinded treatment or received open-label tenofovir alafenamide. 
Changes in lipid laboratory tests were observed in Study 108 and Study 110.  No additional adverse 
reactions to tenofovir alafenamide were identified from Week 96 through Week 144 in the double-
blind phase and in the subset of subjects receiving open-label tenofovir alafenamide treatment (see 
section 5.1). 
 
In an ongoing double-blind, randomized, active-controlled study (GS-US-320-4018; “Study 4018”) in 
virologically suppressed subjects who switched from tenofovir disoproxil to 25 mg tenofovir 
alafenamide (N=243), changes in lipid laboratory tests were observed. No additional adverse reactions 
to tenofovir alafenamide were identified through Week 48.  
 
Tabulated summary of adverse reactions 
 
The following adverse drug reactions have been identified with tenofovir alafenamide in patients with 
chronic hepatitis B (Table 2).  The adverse reactions are listed below by body system organ class and 
frequency based on the Week 96 analysis.  Frequencies are defined as follows: very common (≥ 1/10), 
common (≥ 1/100 to < 1/10) or uncommon (≥ 1/1,000 to < 1/100). 
 



12 

Table 2: Adverse drug reactions identified with tenofovir alafenamide  
 
System organ class 
Frequency Adverse reaction  
Nervous system disorders 
Very common Headache 
Common Dizziness 
Gastrointestinal disorders 
Common Diarrhoea, vomiting, nausea, abdominal pain, abdominal distension, flatulence 
Hepatobiliary disorders 
Common Increased ALT 
Skin and subcutaneous tissue disorders 
Common Rash, pruritus 
Uncommon Angioedema1, urticaria1  
Musculoskeletal and connective tissue disorders 
Common Arthralgia 
General disorders and administration site conditions 
Common Fatigue  
1 Adverse reaction identified through post-marketing surveillance for tenofovir alafenamide-containing products. 
 
Changes in lipid laboratory tests 
In a pooled analysis of Studies 108 and 110, median changes in fasting lipid parameters from baseline 
to Week 96 were observed in both treatment groups. In the tenofovir alafenamide group, decreases in 
median fasting total cholesterol and HDL, and increases in median fasting direct LDL and 
triglycerides were observed, while the tenofovir disoproxil group demonstrated median reductions in 
all parameters (see Table 6). In patients randomised initially to tenofovir alafenamide and switched to 
receive open-label tenofovir alafenamide at Week 96, the median (Q1, Q3) changes from double-blind 
baseline to Week 144 were as follows (mg/dL): total cholesterol was 0 (-16, 18); LDL was 8 (-6, 24); 
HDL was -5 (-12, 2); triglycerides were 11 (-11, 40); total cholesterol to HDL ratio was 0.3 (0.0, 0.7). 
In patients randomised initially to tenofovir disoproxil and switched to open-label tenofovir 
alafenamide at Week 96, the median (Q1, Q3) changes from double-blind baseline to Week 144 were 
as follows (mg/dL): total cholesterol was 1 (-17, 20); LDL was 9 (-5, 26); HDL was -8 (-15, -1); 
triglycerides were 14 (-10, 43); total cholesterol to HDL ratio was 0.4 (0.0, 1.0). 
 
In the open-label phase of Studies 108 and 110, where patients switched to open-label tenofovir 
alafenamide at Week 96, lipid parameters at Week 144 in patients who remained on tenofovir 
alafenamide were similar to those at Week 96, whereas median increases in fasting total cholesterol, 
direct LDL, HDL, and triglycerides were observed in patients who switched from tenofovir disoproxil 
to tenofovir alafenamide at Week 96. In the open label phase, median (Q1, Q3) change from Week 96 
to Week 144 in total cholesterol to HDL ratio was 0.0 (-0.2, 0.4) in patients who remained on 
tenofovir alafenamide and 0.2 (-0.2, 0.6) in patients who switched from tenofovir disoproxil to 
tenofovir alafenamide at Week 96.  
 
In Study 4018, median changes in fasting lipid parameters from baseline to Week 48 were observed in 
both treatment groups. In the group that switched from tenofovir disoproxil to tenofovir alafenamide, 
increases in median fasting total cholesterol, LDL, HDL, and triglycerides were observed, while the 
group continuing treatment with tenofovir disoproxil  demonstrated reductions in median fasting total 
cholesterol, HDL, and triglycerides, and a minimal median increase in LDL (p < 0.001 for the 
difference between treatment groups in all parameters). Median (Q1, Q3) change from baseline at 
Week 48 in total cholesterol to HDL ratio was 0.2 (-0.1, 0.5) in the tenofovir alafenamide group and 
0.0 (-0.3, 0.3) in the tenofovir disoproxil group (p < 0.001 for the difference between treatment 
groups). 
 
 



13 

Metabolic parameters 
Body weight and levels of blood lipids and glucose may increase during therapy. 
 
Reporting of suspected adverse reactions 
 
Reporting suspected adverse reactions after authorisation of the medicinal product is important.  It 
allows continued monitoring of the benefit/risk balance of the medicinal product.  Healthcare 
professionals are asked to report any suspected adverse reactions via the national reporting system 
listed in Appendix V. 
 
4.9 Overdose 
 
If overdose occurs the patient must be monitored for evidence of toxicity (see section 4.8). 
 
Treatment of overdose with tenofovir alafenamide consists of general supportive measures including 
monitoring of vital signs as well as observation of the clinical status of the patient. 
 
Tenofovir is efficiently removed by haemodialysis with an extraction coefficient of 
approximately 54%.  It is not known whether tenofovir can be removed by peritoneal dialysis. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: Antiviral for systemic use, nucleoside and nucleotide reverse 
transcriptase inhibitors; ATC code: J05AF13. 
 
Mechanism of action 
 
Tenofovir alafenamide is a phosphonamidate prodrug of tenofovir (2’-deoxyadenosine 
monophosphate analogue).  Tenofovir alafenamide enters primary hepatocytes by passive diffusion 
and by the hepatic uptake transporters OATP1B1 and OATP1B3.  Tenofovir alafenamide is primarily 
hydrolysed to form tenofovir by carboxylesterase 1 in primary hepatocytes.  Intracellular tenofovir is 
subsequently phosphorylated to the pharmacologically active metabolite tenofovir diphosphate.  
Tenofovir diphosphate inhibits HBV replication through incorporation into viral DNA by the 
HBV reverse transcriptase, which results in DNA chain termination. 
 
Tenofovir has activity that is specific to hepatitis B virus and human immunodeficiency virus (HIV-1 
and HIV-2).  Tenofovir diphosphate is a weak inhibitor of mammalian DNA polymerases that include 
mitochondrial DNA polymerase γ and there is no evidence of mitochondrial toxicity in vitro based on 
several assays including mitochondrial DNA analyses. 
 
Antiviral activity 
 
The antiviral activity of tenofovir alafenamide was assessed in HepG2 cells against a panel of 
HBV clinical isolates representing genotypes A-H.  The EC50 (50% effective concentration) values for 
tenofovir alafenamide ranged from 34.7 to 134.4 nM, with an overall mean EC50 of 86.6 nM.  
The CC50 (50% cytotoxicity concentration) in HepG2 cells was > 44,400 nM. 
 
Resistance 
 
In patients receiving tenofovir alafenamide, sequence analysis was performed on paired baseline and 
on-treatment HBV isolates for patients who either experienced virologic breakthrough (2 consecutive 
visits with HBV DNA ≥ 69 IU/mL after having been < 69 IU/mL, or 1.0 log10 or greater increase in 
HBV DNA from nadir) or patients with HBV DNA ≥ 69 IU/mL at Week 48, or Week 96 or at early 
discontinuation at or after Week 24.   

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


14 

 
In a pooled analysis of patients receiving tenofovir alafenamide in Study 108 and Study 110 at 
Week 48 (N = 20) and Week 96 (N = 72), no amino acid substitutions associated with resistance to 
tenofovir alafenamide were identified in these isolates (genotypic and phenotypic analyses). 
 
In virologically suppressed patients receiving tenofovir alafenamide following switch from tenofovir 
disoproxil  treatment in Study 4018, no patient experienced a virologic blip (one visit with HBV 
DNA ≥ 69 IU/mL), virologic breakthrough or persistent viremia during treatment, and 0 of 243 (0.0%) 
patients qualified for resistance analysis through 48 weeks of tenofovir alafenamide treatment. 
 
Cross-resistance 
The antiviral activity of tenofovir alafenamide was evaluated against a panel of isolates containing 
nucleos(t)ide reverse transcriptase inhibitor mutations in HepG2 cells.  HBV isolates expressing the 
rtV173L, rtL180M, and rtM204V/I substitutions associated with resistance to lamivudine remained 
susceptible to tenofovir alafenamide (< 2-fold change in EC50).  HBV isolates expressing the rtL180M, 
rtM204V plus rtT184G, rtS202G, or rtM250V substitutions associated with resistance to entecavir 
remained susceptible to tenofovir alafenamide.  HBV isolates expressing the rtA181T, rtA181V, or 
rtN236T single substitutions associated with resistance to adefovir remained susceptible to tenofovir 
alafenamide; however, the HBV isolate expressing rtA181V plus rtN236T exhibited reduced 
susceptibility to tenofovir alafenamide (3.7-fold change in EC50).  The clinical relevance of these 
substitutions is not known. 
 
Clinical data 
 
The efficacy and safety of tenofovir alafenamide in patients with chronic hepatitis B are based on 
48- and 96-week data from two randomised, double-blind, active-controlled studies, Study 108 and 
Study 110.  The safety of tenofovir alafenamide is also supported by pooled data from patients in 
Studies 108 and 110 who remained on blinded treatment from Week 96 through Week 144 and 
additionally from patients in the open-label phase of Studies 108 and 110 from Week 96 through 
Week 144 (N = 360 remained on tenofovir alafenamide; N = 180 switched from tenofovir disoproxil 
to tenofovir alafenamide at Week 96). 
 
In Study 108, HBeAg-negative treatment-naïve and treatment-experienced patients with compensated 
liver function were randomised in a 2:1 ratio to receive tenofovir alafenamide (25 mg; N = 285) once 
daily or tenofovir disoproxil (245 mg; N = 140) once daily.  The mean age was 46 years, 61% were 
male, 72% were Asian, 25% were White and 2% (8 subjects) were Black. 24%, 38%, and 31% had 
HBV genotype B, C, and D, respectively.  21% were treatment-experienced (previous treatment with 
oral antivirals, including entecavir (N = 41), lamivudine (N = 42), tenofovir disoproxil (N = 21), or 
other (N = 18)).  At baseline, mean plasma HBV DNA was 5.8 log10 IU/mL, mean serum ALT was 
94 U/L, and 9% of patients had a history of cirrhosis. 
 
In Study 110, HBeAg-positive treatment-naïve and treatment-experienced patients with compensated 
liver function were randomised in a 2:1 ratio to receive tenofovir alafenamide (25 mg; N = 581) once 
daily or tenofovir disoproxil (245 mg; N = 292) once daily.  The mean age was 38 years, 64% were 
male, 82% were Asian, 17% were White and < 1% (5 subjects) were Black.  17%, 52%, and 23% had 
HBV genotype B, C, and D, respectively.  26% were treatment-experienced (previous treatment with 
oral antivirals, including adefovir (N = 42), entecavir (N = 117), lamivudine (N = 84), telbivudine 
(N = 25), tenofovir disoproxil (N = 70), or other (N = 17)).  At baseline, mean plasma HBV DNA was 
7.6 log10 IU/mL, mean serum ALT was 120 U/L, and 7% of patients had a history of cirrhosis. 
 
The primary efficacy endpoint in both studies was the proportion of patients with plasma HBV DNA 
levels below 29 IU/mL at Week 48.  Tenofovir alafenamide met the non-inferiority criteria in 
achieving HBV DNA less than 29 IU/mL when compared to tenofovir disoproxil.  Treatment 
outcomes of Study 108 and Study 110 through Week 48 are presented in Table 3 and Table 4. 
 



15 

Table 3: HBV DNA efficacy parameters at Week 48a 
 
 Study 108 (HBeAg-Negative) Study 110 (HBeAg-Positive) 

 TAF 
(N = 285) 

TDF 
(N = 140) 

TAF 
(N = 581) 

TDF 
(N = 292) 

HBV DNA < 29 IU/mL 94% 93% 64% 67% 
Treatment differenceb 1.8% (95% CI = -3.6% to 7.2%) -3.6% (95% CI = -9.8% to 2.6%) 

HBV DNA ≥ 29 IU/mL 2% 3% 31% 30% 
Baseline HBV DNA 

< 7 log10 IU/mL 
≥ 7 log10 IU/mL 

 
96% (221/230) 
85% (47/55) 

 
92% (107/116) 
96% (23/24) 

N/A N/A 

Baseline HBV DNA 
< 8 log10 IU/mL 
≥ 8 log10 IU/mL 

N/A N/A 
 

82% (254/309) 
43% (117/272) 

 
82% (123/150) 
51% (72/142) 

Nucleoside naïvec 
Nucleoside experienced 

94% (212/225) 
93% (56/60) 

93% (102/110) 
93% (28/30) 

68% (302/444) 
50% (69/137) 

70% (156/223) 
57% (39/69) 

No Virologic data  
at Week 48 4% 4% 5% 3% 

Discontinued study drug 
due to lack of efficacy 0 0 < 1% 0 

Discontinued study drug 
due to AE or death 1% 1% 1% 1% 

Discontinued study drug 
due to other reasonsd 2% 3% 3% 2% 

Missing data during 
window but on study drug < 1% 1% < 1% 0 

N/A = not applicable 
TDF = tenofovir disoproxil  
TAF = tenofovir alafenamide 
a Missing = failure analysis. 
b Adjusted by baseline plasma HBV DNA categories and oral antiviral treatment status strata. 
c Treatment-naïve subjects received < 12 weeks of oral antiviral treatment with any nucleoside or nucleotide analogue 

including tenofovir disoproxil or tenofovir alafenamide. 
d 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. 
 
Table 4: Additional efficacy parameters at Week 48a 
 

 Study 108 (HBeAg-Negative) Study 110 (HBeAg-Positive) 
 TAF 

(N = 285) 
TDF 

(N = 140) 
TAF 

(N = 581) 
TDF 

(N = 292) 
ALT 
Normalised ALT (Central lab)b 83% 75% 72% 67% 
Normalised ALT (AASLD)c 50% 32% 45% 36% 
Serology 
HBeAg loss / seroconversiond N/A N/A 14% / 10% 12% / 8% 
HBsAg loss / seroconversion 0 / 0 0 / 0 1% / 1% < 1% / 0 

N/A = not applicable 
TDF = tenofovir disoproxil  
TAF = tenofovir alafenamide 
a Missing = failure analysis. 
b The population used for analysis of ALT normalisation included only patients with ALT above upper limit of 

normal (ULN) of the central laboratory range at baseline.  Central laboratory ULN for ALT are as follows: ≤ 43 U/L for 
males aged 18 to < 69 years and ≤ 35 U/L for males ≥ 69 years; ≤ 34 U/L for females 18 to < 69 years and ≤ 32 U/L for 
females ≥ 69 years. 

c The population used for analysis of ALT normalisation included only patients with ALT above ULN of the 2016 
American Association of the Study of Liver Diseases (AASLD) criteria (> 30 U/L males and > 19 U/L females) at 
baseline. 

d The population used for serology analysis included only patients with antigen (HBeAg) positive and antibody (HBeAb) 
negative or missing at baseline. 

 



16 

Experience beyond 48 weeks in Study 108 and Study 110 
At Week 96, viral suppression as well as biochemical and serological responses were maintained with 
continued tenofovir alafenamide treatment (see Table 5). 
 
Table 5: HBV DNA and additional efficacy parameters at Week 96a 
 
 Study 108 (HBeAg-Negative) Study 110 (HBeAg-Positive) 

 TAF 
(N = 285) 

TDF 
(N = 140) 

TAF 
(N = 581) 

TDF 
(N = 292) 

HBV DNA < 29 IU/mL 90% 91% 73% 75% 
Baseline HBV DNA 
< 7 log10 IU/mL 
≥ 7 log10 IU/mL 

 
90% (207/230) 
91% (50/55) 

 
91% (105/116) 
92% (22/24) 

N/A N/A 

Baseline HBV DNA 
< 8 log10 IU/mL 
≥ 8 log10 IU/mL 

N/A N/A 
 

84% (260/309) 
60% (163/272) 

 
81% (121/150) 
68% (97/142) 

Nucleoside-naïveb 
Nucleoside-experienced 

90% (203/225) 
90% (54/60) 

92% (101/110) 
87% (26/30) 

75% (331/444) 
67% (92/137) 

75% (168/223) 
72% (50/69) 

ALT 
Normalised ALT (Central lab)c 
Normalised ALT (AASLD)d 

 
81% 
50% 

 
71% 
40% 

 
75% 
52% 

 
68% 
42% 

Serology 
HBeAg loss / seroconversione N/A N/A 22% / 18% 18% / 12% 
HBsAg loss / seroconversion < 1% / < 1%  0 / 0  1% / 1%  1% / 0  

N/A = not applicable 
TDF = tenofovir disoproxil  
TAF = tenofovir alafenamide 
a Missing = failure analysis 
b Treatment-naïve subjects received < 12 weeks of oral antiviral treatment with any nucleoside or nucleotide analogue 

including tenofovir disoproxil  or tenofovir alafenamide. 
c The population used for analysis of ALT normalisation included only patients with ALT above ULN of the central 

laboratory range at baseline.  Central laboratory ULN for ALT are as follows: ≤ 43 U/L for males aged 18 to < 69 years 
and ≤ 35 U/L for males ≥ 69 years; ≤ 34 U/L for females 18 to < 69 years and ≤ 32 U/L for females ≥ 69 years. 

d The population used for analysis of ALT normalisation included only patients with ALT above ULN of the 2016 AASLD 
criteria (> 30 U/L males and > 19 U/L females) at baseline. 

e The population used for serology analysis included only patients with antigen (HBeAg) positive and antibody (HBeAb) 
negative or missing at baseline. 

 
Changes in measures of bone mineral density in Study 108 and Study 110 
In both studies tenofovir alafenamide was associated with smaller mean percentage decreases in bone 
mineral density (BMD; as measured by hip and lumbar spine dual energy X ray absorptiometry 
[DXA] analysis) compared to tenofovir disoproxil after 96 weeks of treatment. 
 
In patients who remained on blinded treatment beyond Week 96, mean percentage change in BMD in 
each group at Week 144 was similar to that at Week 96.  In the open-label phase of both studies, mean 
percentage change in BMD from Week 96 to Week 144 in patients who remained on tenofovir 
alafenamide was +0.4% at the lumbar spine and -0.3% at the total hip, compared to +2.0% at the 
lumbar spine and +0.9% at the total hip in those who switched from tenofovir disoproxil to tenofovir 
alafenamide at Week 96. 
 
Changes in measures of renal function in Study 108 and Study 110 
In both studies tenofovir alafenamide was associated with smaller changes in renal safety parameters 
(smaller median reductions in estimated CrCl by Cockcroft-Gault and smaller median percentage 
increases in urine retinol binding protein to creatinine ratio and urine beta-2-microglobulin to 
creatinine ratio) compared to tenofovir disoproxil after 96 weeks of treatment (see also section 4.4). 
 
In patients who remained on blinded treatment beyond Week 96 in Studies 108 and 110, changes from 
baseline in renal laboratory parameter values in each group at Week 144 were similar to those at 
Week 96.  In the open-label phase of Studies 108 and 110, the mean (SD) change in serum creatinine 



17 

from Week 96 to Week 144 was   +0.002 (0.0924) mg/dL in those who remained on tenofovir 
alafenamide, compared to -0.018 (0.0691) mg/dL in those who switched from tenofovir disoproxil to 
tenofovir alafenamide at Week 96.  In the open-label phase, the median change in eGFR from 
Week 96 to Week 144 was -1.2 mL/min in patients who remained on tenofovir alafenamide, compared 
to +4.2 mL/min in patients who switched from tenofovir disoproxil  to tenofovir alafenamide at 
Week 96.  
 
Changes in lipid laboratory tests in Study 108 and Study 110 
For patients who switched to open label tenofovir alafenamide at Week 96, changes from double-blind 
baseline for patients randomised initially to tenofovir alafenamide and tenofovir disoproxil at Week 96 
and Week 144 in total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides, and total 
cholesterol to HDL ratio are presented in Table 6. 
 
Table 6: Median changes from double-blind baseline in lipid laboratory tests at Weeks 96 and  
144 for patients who switched to open-label tenofovir alafenamide at Week 96 
 
 TAF-TAF 

(N=360) 
 Double blind baseline Week 96 Week 144 
 Median (Q1, Q3) 

(mg/dL) 
Median change (Q1, Q3) 

(mg/dL) 
Median change (Q1, Q3) 

(mg/dL) 

Total Cholesterol (fasted) 185 (166, 210) 0 (-18, 17) 0 (-16, 18) 
HDL-Cholesterol (fasted) 59 (49, 72) -5 (-12, 1)a -5 (-12,2)b 
LDL-Cholesterol (fasted) 113 (95, 137) 6 (-8, 21)a 8 (-6, 24)b 
Triglycerides (fasted) 87 (67, 122) 8 (-12, 28)a 11 (-11, 40)b 
Total Cholesterol to HDL ratio 3.1 (2.6, 3.9) 0.2 (0.0, 0.6)a 0.3 (0.0, 0.7)b 
 TDF-TAF 

(N=180) 
 Double blind baseline Week 96  Week 144 
 Median (Q1, Q3) 

(mg/dL) 
Median change (Q1, Q3) 

(mg/dL) 
Median change (Q1, Q3) 

(mg/dL) 
Total Cholesterol (fasted) 189 (163, 215) -23 (-40, -1)a 1 (-17, 20) 
HDL-Cholesterol (fasted) 61 (49, 72) -12 (-19, -3)a -8 (-15, -1)b 
LDL-Cholesterol (fasted) 120 (95, 140) -7 (-25, 8)a 9 (-5, 26)b 
Triglycerides (fasted) 89 (69, 114) -11 (-31, 11)a 14 (-10, 43)b 
Total Cholesterol to HDL ratio 3.1 (2.5, 3.7) 0.2 (-0.1, 0.7)a 0.4 (0.0, 1.0)b 
TAF = tenofovir alafenamide 
TDF = tenofovir disoproxil 
a. P-value was calculated for change from double blind baseline at Week 96, from Wilcoxon Signed Rank test and 

was statistically significant (p < 0.001). 
b. P-value was calculated for change from double blind baseline at Week 144, from Wilcoxon Signed Rank test and 

was statistically significant (p < 0.001). 
 
Virologically suppressed adult patients in Study 4018 
The efficacy and safety of tenofovir alafenamide in virologically suppressed adults with chronic 
hepatitis B is based on 48-week data from an ongoing randomized, double-blind, active-controlled 
study, Study 4018. 
 
In Study 4018 virologically suppressed adults with chronic hepatitis B (N=488) were enrolled who had 
been previously maintained on 245 mg tenofovir disoproxil once daily for at least 12 months, with 
HBV DNA < lower limit of quantification (LLOQ) by local laboratory assessment for at least 12 
weeks prior to screening and HBV DNA < 20 IU/mL at screening. Patients were stratified by HBeAg 
status (HBeAg-positive or HBeAg-negative) and age (≥ 50 or < 50 years) and randomized in a 1:1 
ratio to switch to 25 mg tenofovir alafenamide (N=243) or remain on 245 mg tenofovir disoproxil 
once daily (N=245). Mean age was 51 years (22% were ≥ 60 years), 71% were male, 82% were Asian, 
14% were White, and 68% were HBeAg-negative. At baseline, median duration of prior tenofovir 



18 

disoproxil treatment was 220 and 224 weeks in the tenofovir alafenamide and tenofovir disoproxil 
groups, respectively. Previous treatment with antivirals also included interferon (N=63), lamivudine 
(N=191), adefovir dipivoxil (N=185), entecavir (N=99), telbivudine (N=48), or other (N=23).  At 
baseline, mean serum ALT was 27 U/L, median eGFR by Cockcroft-Gault was 90.5 mL/min; 16% of 
patients had a history of cirrhosis. 
 
The primary efficacy endpoint was the proportion of patients with plasma HBV DNA 
levels ≥ 20 IU/mL at Week 48 (as determined by the modified US FDA Snapshot algorithm). 
Additional efficacy endpoints included the proportion of patients with HBV DNA levels < 20 IU/mL, 
ALT normal and ALT normalization, HBsAg loss and seroconversion, and HBeAg loss and 
seroconversion. Tenofovir alafenamide was non-inferior in the proportion of subjects with HBV DNA 
≥ 20 IU/mL at Week 48 when compared to tenofovir disoproxil  as assessed by the modified US FDA 
Snapshot algorithm. Treatment outcomes (HBV DNA < 20 IU/mL by missing=failure) at Week 48 
between treatment groups were similar across subgroups by age, sex, race, baseline HBeAg status, and 
ALT. 
 
Treatment outcomes of Study 4018 at Week 48 are presented in Table 7 and Table 8. 
 
Table 7: HBV DNA efficacy parameters at Week 48a,b  
 

TDF = tenofovir disoproxil  
TAF = tenofovir alafenamide 
a. Week 48 window was between Day 295 and 378 (inclusive).  
b. As determined by the modified US FDA-defined snapshot algorithm.  
c. No patient discontinued treatment due to lack of efficacy.  
d. Adjusted by baseline age groups (< 50, ≥ 50 years) and baseline HBeAg status strata. 
e. Includes patients who discontinued for reasons other than an AE, death or lack of efficacy, e.g., withdrew consent, loss to 
follow-up, etc. 

 
TAF 

(N=243) 
TDF 

(N=245) 

HBV DNA ≥ 20 IU/mLb,c 1 (0.4%) 1 (0.4%) 

 Treatment Differenced 0.0% (95% CI = -1.9% to 2.0%) 

HBV DNA < 20 IU/mL 234 (96.3%) 236 (96.3%) 

Treatment Differenced 0.0% (95% CI = -3.7% to 3.7%) 

No Virologic Data at Week 48  8 (3.3%) 8 (3.3%) 

 Discontinued Study Drug Due to AE or Death 
and Last Available HBV DNA < 20 IU/mL 2 (0.8%) 0 

 Discontinued Study Drug Due to Other Reasonse 
            and Last Available HBV DNA < 20 IU/mL 

6 (2.5%) 8 (3.3%) 

 Missing Data During Window but on Study Drug 0 0 



19 

 
Table 8: Additional efficacy parameters at Week 48a 
 

 
TAF 

(N=243) 
TDF 

(N=245) 

ALT 

Normal ALT (Central Lab) 89% 85% 

Normal ALT (AASLD) 79% 75% 

Normalized ALT (Central Lab)b,c 50%  37%  

Normalized ALT (AASLD)d,e 50% 26% 

Serology 

HBeAg Loss / Seroconversionf 8% / 3% 6% / 0 

HBsAg Loss / Seroconversion 0 / 0 2% / 0 
TDF = tenofovir disoproxil  
TAF = tenofovir alafenamide 
a. Missing = failure analysis  
b. The population used for analysis of ALT normalization included only patients with ALT above upper limit of normal 
(ULN) of the central laboratory range (> 43 U/L males 18 to < 69 years and > 35 U/L males ≥ 69 years; > 34 U/L females 18 
to < 69 years and > 32 U/L females ≥ 69 years) at baseline.  
c. Proportion of patients at Week 48: TAF, 16/32; TDF, 7/19.  
d. The population used for analysis of ALT normalization included only patients with ALT above ULN of the 2018 American 
Association of the Study of Liver Diseases (AASLD) criteria (35 U/L males and 25 U/L females) at baseline.  
e. Proportion of patients at Week 48: TAF, 26/52; TDF, 14/53.  
f. The population used for serology analysis included only patients with antigen (HBeAg) positive and anti-body (HBeAb) 
negative or missing at baseline. 
 
Changes in bone mineral density in Study 4018 
The mean percentage change in BMD from baseline to Week 48 as assessed by DXA was +1.7% with 
tenofovir alafenamide compared to −0.1% with tenofovir disoproxil at the lumbar spine and +0.7% 
compared to −0.5% at the total hip. BMD declines of greater than 3% at the lumbar spine were 
experienced by 4% of tenofovir alafenamide patients and 17% of tenofovir disoproxil patients at Week 
48. BMD declines of greater than 3% at the total hip were experienced by 2% of tenofovir alafenamide 
patients and 12% of tenofovir disoproxil patients at Week 48. 
 
Changes in renal laboratory tests in Study 4018 
The median change from baseline to Week 48 in eGFR by Cockcroft-Gault method was +0.9 mL per 
minute in the tenofovir alafenamide group and −2.7 mL per minute in those receiving tenofovir 
disoproxil. At Week 48, there was a median increase from baseline in serum creatinine among patients 
randomized to continue treatment with tenofovir disoproxil (0.02 mg/dL) compared with no median 
change from baseline among those who were switched to tenofovir alafenamide (0.00 mg/dL). Further, 
median percentage decreases from baseline were observed in the tenofovir alafenamide group at Week 
48 in urine retinol binding protein to creatinine ratio and urine beta-2-microglobulin to creatinine ratio, 
compared with median percentage increases from baseline for both of these renal parameters in the 
tenofovir disoproxil group. 
 
Changes in lipid laboratory tests in Study 4018 
Changes from baseline to Week 48 in total cholesterol, HDL-cholesterol, LDL-cholesterol, 
triglycerides, and total cholesterol to HDL ratio among subjects treated with tenofovir alafenamide and 
tenofovir disoproxil are presented in Table 9. 



20 

Table 9: Median changes in lipid laboratory tests at Week 48 
 

 TAF 
(N=243) 

TDF  
(N=245) 

 Baseline Week 48 Baseline Week 48 
 (Q1, Q3)  

(mg/dL) 
Median changea 

(Q1, Q3) (mg/dL)  
(Q1, Q3)  
(mg/dL) 

Median changea 
(Q1, Q3) (mg/dL) 

Total Cholesterol (fasted) 166 (147, 189) 19 (6, 33) 169 (147, 188) −4 (−16, 8) 
HDL-Cholesterol (fasted) 48 (41, 56) 3 (−1, 8) 48 (40, 57) −1 (−5, 2) 
LDL-Cholesterol (fasted) 102 (87,123) 16 (5, 27) 103 (87, 120) 1 (−8, 12) 
Triglycerides (fasted) 90 (66, 128) 16 (−3, 44) 89 (68, 126) −2 (−22, 18) 
Total Cholesterol to HDL ratio 3.4 (2.9, 4.2) 0.2 (−0.1, 0.5) 3.4 (2.9, 4.2) 0.0 (−0.3, 0.3) 
TDF = tenofovir disoproxil  
TAF = tenofovir alafenamide 
a. P-value was calculated for the difference between the TAF and TDF groups, from Wilcoxon Rank Sum test and 

was statistically significant (p < 0.001) for median changes (Q1, Q3) from baseline in total cholesterol, 
HDL-cholesterol, LDL-cholesterol, triglycerides and total cholesterol to HDL ratio.  

 
Paediatric population 
 
The European Medicines Agency has deferred the obligation to submit the results of studies with 
Vemlidy in one or more subsets of the paediatric population in the treatment of chronic hepatitis B 
(see sections 4.2 and 5.2 for information on paediatric use). 
 
5.2 Pharmacokinetic properties 
 
Absorption 
 
Following oral administration of tenofovir alafenamide under fasted conditions in adult patients with 
chronic hepatitis B, peak plasma concentrations of tenofovir alafenamide were observed 
approximately 0.48 hours post-dose.  Based on Phase 3 population pharmacokinetic analysis in 
subjects with chronic hepatitis B, mean steady state AUC0-24 for tenofovir alafenamide (N = 698) and 
tenofovir (N = 856) were 0.22 µg•h/mL and 0.32 µg•h/mL, respectively.  Steady state Cmax for 
tenofovir alafenamide and tenofovir were 0.18 and 0.02 µg/mL, respectively.  Relative to fasting 
conditions, the administration of a single dose of tenofovir alafenamide with a high fat meal resulted in 
a 65% increase in tenofovir alafenamide exposure. 
 
Distribution 
 
The binding of tenofovir alafenamide to human plasma proteins in samples collected during clinical 
studies was approximately 80%.  The binding of tenofovir to human plasma proteins is less than 0.7% 
and is independent of concentration over the range of 0.01-25 µg/mL. 
 
Biotransformation 
 
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 carboxylesterase-1 in hepatocytes; and by cathepsin A in peripheral 
blood mononuclear cells (PBMCs) and macrophages.  In vivo, tenofovir alafenamide is hydrolysed 
within cells to form tenofovir (major metabolite), which is phosphorylated to the active metabolite, 
tenofovir diphosphate. 
 
In vitro, tenofovir alafenamide is not metabolised by CYP1A2, CYP2C8, CYP2C9, CYP2C19, or 
CYP2D6.  Tenofovir alafenamide is minimally metabolised by CYP3A4. 
 



21 

Elimination 
 
Renal excretion of intact tenofovir alafenamide is a minor pathway with < 1% of the dose eliminated 
in urine.  Tenofovir alafenamide is mainly eliminated following metabolism to tenofovir.  Tenofovir 
alafenamide and tenofovir have a median plasma half-life of 0.51 and 32.37 hours, respectively.  
Tenofovir is renally eliminated from the body by the kidneys by both glomerular filtration and active 
tubular secretion. 
 
Linearity/non-linearity 
 
Tenofovir alafenamide exposures are dose proportional over the dose range of 8 to 125 mg. 
 
Pharmacokinetics in special populations 
 
Age, gender and ethnicity 
No clinically relevant differences in pharmacokinetics according to age or ethnicity have been 
identified.  Differences in pharmacokinetics according to gender were not considered to be clinically 
relevant. 
 
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. 
 
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 but 
< 30 mL/min) in studies of tenofovir alafenamide. 
 
Paediatric population 
The pharmacokinetics of tenofovir alafenamide and tenofovir were evaluated in HIV-1 infected, 
treatment-naïve adolescents who received tenofovir alafenamide (10 mg) given with elvitegravir, 
cobicistat and emtricitabine as a fixed-dose combination tablet (E/C/F/TAF; Genvoya).  No clinically 
relevant differences in tenofovir alafenamide or tenofovir pharmacokinetics were observed between 
adolescent and adult HIV-1 infected subjects.  
 
5.3 Preclinical safety data 
 
Non-clinical studies in rats and dogs revealed bone and kidney as the primary target organs of toxicity.  
Bone toxicity was observed as reduced BMD in rats and dogs at tenofovir exposures at least four times 
greater than those expected after administration of tenofovir alafenamide.  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 
tenofovir alafenamide. 
 
Tenofovir alafenamide was not mutagenic or clastogenic in conventional genotoxic assays. 
 
Because there is a lower tenofovir exposure in rats and mice after tenofovir alafenamide 
administration compared to tenofovir disoproxil, carcinogenicity studies and a rat peri-postnatal study 
were conducted only with tenofovir disoproxil.  No special hazard for humans was revealed in 
conventional studies of carcinogenic potential with tenofovir disoproxil (as fumarate) and toxicity to 
reproduction and development with tenofovir disoproxil (as fumarate) or tenofovir alafenamide.  
Reproductive toxicity studies in rats and rabbits showed no effects on mating, fertility, pregnancy or 
foetal parameters.  However, tenofovir disoproxil reduced the viability index and weight of pups in a 
peri-postnatal toxicity study at maternally toxic doses.  A long-term oral carcinogenicity study in mice 
showed a low incidence of duodenal tumours, considered likely related to high local concentrations in 



22 

the gastrointestinal tract at the high dose of 600 mg/kg/day.  The mechanism of tumour formation in 
mice and potential relevance for humans is uncertain. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Tablet core 
 
Lactose monohydrate 
Microcrystalline cellulose (E460(i)) 
Croscarmellose sodium (E468) 
Magnesium stearate (E470b) 
 
Film-coating 
 
Polyvinyl alcohol (E1203) 
Titanium dioxide (E171) 
Macrogol (E1521) 
Talc (E553b) 
Iron oxide yellow (E172) 
 
6.2 Incompatibilities 
 
Not applicable. 
 
6.3 Shelf life 
 
4 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 
 
Vemlidy tablets are packaged in high density polyethylene (HDPE) bottles and enclosed with a 
polypropylene continuous-thread, child-resistant cap, lined with an induction-activated aluminium foil 
liner.  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. 
 
 



23 

7. MARKETING AUTHORISATION HOLDER

Gilead Sciences Ireland UC 
Carrigtohill 
County Cork, T45 DP77 
Ireland 

8. MARKETING AUTHORISATION NUMBER(S)

EU/1/16/1154/001 
EU/1/16/1154/002 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation: 09 January 2017 

10. DATE OF REVISION OF THE TEXT

Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu. 

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


24 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX II 
 

A. MANUFACTURER(S) RESPONSIBLE FOR BATCH 
RELEASE 

 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY 

AND USE 
 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE 

MARKETING AUTHORISATION 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO 

THE SAFE AND EFFECTIVE USE OF THE MEDICINAL 
PRODUCT 

 



25 

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

AUTHORISATION 
 
• Periodic Safety Update reports 
 
The requirements for submission of periodic safety update reports for this medicinal product are set 
out in the list of Union reference dates (EURD list) provided for under Article 107c(7) of 
Directive 2001/83/EC and any subsequent updates published on the European medicines web-portal. 
 
The marketing authorisation holder shall submit the first periodic safety update report for this product 
within 6 months following authorisation.  
 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

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

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

 



26 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 



27 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 
 



28 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING AND THE IMMEDIATE 
PACKAGING 
 
BOTTLE AND CARTON LABELLING 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Vemlidy 25 mg film-coated tablets  
tenofovir alafenamide 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each film-coated tablet contains tenofovir alafenamide fumarate (equivalent to 25 mg of tenofovir 
alafenamide). 
 
 
3. LIST OF EXCIPIENTS 
 
Contains lactose 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. 
 
Do not swallow desiccant. 
 
 
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 
 
 



29 

9. SPECIAL STORAGE CONDITIONS 
 
Store in the original package in order to protect from moisture.  Keep the bottle tightly closed. 
 
 
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/1/16/1154/001 30 film-coated tablets 
EU/1/16/1154/002 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 
 
Vemlidy [Outer packaging only] 
 
 
17. UNIQUE IDENTIFIER - 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
PC: {number} 
SN: {number} 
NN: {number} 
 



30 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 



31 

Package leaflet: Information for the patient 
 

Vemlidy 25 mg film-coated tablets 
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 Vemlidy is and what it is used for 
2. What you need to know before you take Vemlidy 
3. How to take Vemlidy 
4. Possible side effects 
5. How to store Vemlidy 
6. Contents of the pack and other information 
 
 
1. What Vemlidy is and what it is used for 
 
Vemlidy contains the active substance tenofovir alafenamide.  This is an antiviral medicine, known as 
a nucleotide reverse transcriptase inhibitor (NtRTI). 
 
Vemlidy is used to treat chronic (long-term) hepatitis B in adults and adolescents 12 years of age 
and older, who weigh at least 35 kg.  Hepatitis B is an infection affecting the liver, caused by the 
hepatitis B virus.  In patients with hepatitis B, Vemlidy controls the infection by stopping the virus 
from multiplying. 
 
 
2. What you need to know before you take Vemlidy 
 
Do not take Vemlidy 
 
• if you are allergic to tenofovir alafenamide or any of the other ingredients of this medicine 

(listed in section 6). 
 
 If this applies to you, do not take Vemlidy and tell your doctor immediately. 
 
Warnings and precautions 
 
• Take care not to pass on your hepatitis B to other people.  You can still infect others when 

taking this medicine.  Vemlidy does not reduce the risk of passing on hepatitis B to others 
through sexual contact or blood contamination.  You must continue to take precautions to avoid 
this.  Discuss with your doctor the precautions needed to avoid infecting others.   

 
• Tell your doctor if you have a history of liver disease.  Patients with liver disease, who are 

treated for hepatitis B with antiviral medicines, have a higher risk of severe and potentially fatal 



32 

liver complications.  Your doctor may need to carry out blood tests to monitor your liver 
function. 

 
• Talk to your doctor or pharmacist if you have had kidney disease or if tests have shown 

problems with your kidneys.  Before starting treatment and during treatment, your doctor may 
order blood tests to monitor how your kidneys work. 

 
• Talk to your doctor if you also have hepatitis C or D.  Vemlidy has not been tested on 

patients who have hepatitis C or D as well as hepatitis B. 
 
• Talk to your doctor if you also have HIV.  If you are not sure whether you have HIV, your 

doctor should offer you HIV testing before you start taking Vemlidy for hepatitis B. 
 
 If any of these apply to you, talk to your doctor before taking Vemlidy. 
 
Children and adolescents 
 
Do not give this medicine to children who are under 12 years old or weigh less than 35 kg.  
Vemlidy has not been tested in children aged less than 12 years old or weighing less than 35 kg. 
 
Other medicines and Vemlidy 
 
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 
medicines.  Vemlidy may interact with other medicines.  As a result, the amounts of Vemlidy or other 
medicines in your blood may change.  This may stop your medicines from working properly, or may 
make any side effects worse. 
 
Medicines used in treating hepatitis B infection 
Do not take Vemlidy with other medicines containing: 
• tenofovir alafenamide 
• tenofovir disoproxil  
• adefovir dipivoxil 
 
Other types of medicines 
Talk to your doctor if you are taking: 
• antibiotics used to treat bacterial infections including tuberculosis, containing: 

- rifabutin, rifampicin or rifapentine 
• antiviral medicines used to treat HIV, such as: 

- ritonavir or cobicistat boosted darunavir, lopinavir or atazanavir 
• anticonvulsants used to treat epilepsy, such as: 

- carbamazepine, oxcarbazepine, phenobarbital or phenytoin 
• herbal remedies used to treat depression and anxiety, containing: 

- St. John’s wort (Hypericum perforatum) 
• antifungal medicines used to treat fungal infections, containing: 

- ketoconazole or itraconazole 
 
 Tell your doctor if you are taking these or any other medicines. 
 
Pregnancy and breast-feeding 
 
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 
your doctor or pharmacist for advice before taking this medicine. 
 
• Tell your doctor immediately if you become pregnant. 
 



33 

• Do not breast-feed during treatment with Vemlidy.  It is recommended that you do not 
breast-feed to avoid passing tenofovir alafenamide or tenofovir to the baby through breast milk. 

 
Driving and using machines 
 
Vemlidy can cause dizziness.  If you feel dizzy when taking Vemlidy, do not drive and do not use any 
tools or machines. 
 
Vemlidy contains lactose 
 
If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor 
before taking this medicine. 
 
Vemlidy contains sodium 
 
This medicine contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially 
‘sodium-free’. 
 
 
3. How to take Vemlidy 
 
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 one tablet once a day with food.  Treatment should continue for as long as 
your doctor tells you.  Usually this is for at least 6 to 12 months and may be for many years. 
 
If you take more Vemlidy than you should 
 
If you accidentally take more than the recommended dose of Vemlidy 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 the tablet bottle 
with you so that you can easily describe what you have taken. 
 
If you forget to take Vemlidy 
 
It is important not to miss a dose of Vemlidy.  If you do miss a dose, work out how long since you 
should have taken it. 
 
• If it is less than 18 hours after you usually take Vemlidy, take it as soon as you can, and then 

take your next dose at its regular time. 
 
• If it is more than 18 hours after you usually take Vemlidy, then do not take the missed dose.  

Wait and take the next dose at the regular time.  Do not take a double dose to make up for a 
forgotten tablet. 

 
If you are sick (vomit) less than 1 hour after taking Vemlidy, take another tablet.  You do not need 
to take another tablet if you are sick (vomit) more than 1 hour after taking Vemlidy. 
 
If you stop taking Vemlidy 
 
Do not stop taking Vemlidy without your doctor’s advice.  Stopping treatment with Vemlidy may 
cause your hepatitis B to get worse.  In some patients with advanced liver disease or cirrhosis, this 
could be life-threatening.  If you stop taking Vemlidy, you will need regular health checks and blood 
tests for several months to check your hepatitis B infection. 
 



34 

• Talk to your doctor before you stop taking Vemlidy for any reason, particularly if you are 
experiencing any side effects or you have another illness. 

 
• Tell your doctor immediately about new or unusual symptoms after you stop treatment, 

particularly symptoms you associate with hepatitis B infection. 
 
• Talk to your doctor before you restart taking Vemlidy tablets. 
 
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. 
 
Very common side effects 
(may affect more than 1 in 10 people) 
• Headache 
 
Common side effects 
(may affect up to 1 in 10 people) 
• Diarrhoea 
• Being sick (vomiting) 
• Feeling sick (nausea) 
• Dizziness 
• Stomach pain 
• Joint pain (arthralgia) 
• Rash 
• Itchiness 
• Feeling bloated 
• Wind (flatulence) 
• Feeling tired 
 
Uncommon side effects 
(may affect up to 1 in 100 people) 
• Swelling of the face, lips, tongue or throat (angioedema) 
• Hives (urticaria) 
 
Tests may also show: 
• Increased level of a liver enzyme (ALT) in the blood 
 
 If any of these side effects get serious tell your doctor. 
 
During HBV therapy there may be an increase in weight,  fasting levels of blood lipids and/or glucose. 
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. 
 
 

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


35 

5. How to store Vemlidy 
 
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 bottle and carton after {EXP}.  
The expiry date refers to the last day of that month. 
 
Store in the original package in order to protect from moisture.  Keep the bottle tightly closed. 
 
Do not throw away any medicines via wastewater or household waste.  Ask your pharmacist how to 
throw away medicines you no longer use.  These measures will help protect the environment. 
 
 
6. Contents of the pack and other information 
 
What Vemlidy contains 
 
The active substance is tenofovir alafenamide.  Each Vemlidy film-coated tablet contains tenofovir 
alafenamide fumarate, equivalent to 25 mg of tenofovir alafenamide. 
 
The other ingredients are 
Tablet core: 
Lactose monohydrate, microcrystalline cellulose (E460(i)), croscarmellose sodium (E468), 
magnesium stearate (E470b). 
 
Film-coating: 
Polyvinyl alcohol (E1203), titanium dioxide (E171), macrogol (E1521), talc (E553b), iron 
oxide yellow (E172). 
 
What Vemlidy looks like and contents of the pack 
 
Vemlidy film-coated tablets are yellow, round, printed (or marked) with “GSI” on one side of the 
tablet and “25” on the other side of the tablet.  Vemlidy comes in bottles of 30 tablets (with a silica gel 
desiccant that must be kept in the bottle to help protect your tablets).  The silica gel desiccant is 
contained in a separate sachet or canister and should not be swallowed. 
 
The following pack sizes are available: outer cartons containing 1 bottle of 30 film-coated tablets and 
outer cartons containing 90 (3 bottles of 30) film-coated tablets.  Not all pack sizes may be marketed. 
 
Marketing Authorisation Holder 
Gilead Sciences Ireland UC 
Carrigtohill 
County Cork, T45 DP77 
Ireland 
 
Manufacturer 
Gilead Sciences Ireland UC 
IDA Business & Technology Park 
Carrigtohill 
County Cork 
Ireland 
 



36 

For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien 
Gilead Sciences Belgium SPRL-BVBA 
Tél/Tel: + 32 (0) 24 01 35 50 
 

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

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

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

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

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

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

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

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

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

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



37 

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 (0) 22 262 8702 
 

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

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


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