Truvada

1 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 



2 

1. NAME OF THE MEDICINAL PRODUCT 
 
Truvada 200 mg/245 mg film-coated tablets 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each film-coated tablet contains 200 mg of emtricitabine and 245 mg of tenofovir disoproxil 
(equivalent to 300 mg of tenofovir disoproxil fumarate or 136 mg of tenofovir). 
 
Excipient with known effect 
 
Each tablet contains 96 mg lactose monohydrate. 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Film-coated tablet. 
 
Blue, capsule-shaped, film-coated tablet, of dimensions 19 mm x 8.5 mm, debossed on one side with 
“GILEAD” and on the other side with “701”. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Treatment of HIV-1 infection: 
Truvada is indicated in antiretroviral combination therapy for the treatment of HIV-1 infected adults 
(see section 5.1). 
 
Truvada is also indicated for the treatment of HIV-1 infected adolescents, with NRTI resistance or 
toxicities precluding the use of first line agents (see sections 4.2, 4.4 and 5.1). 
 
Pre-exposure prophylaxis (PrEP): 
Truvada is indicated in combination with safer sex practices for pre-exposure prophylaxis to reduce 
the risk of sexually acquired HIV-1 infection in adults and adolescents at high risk (see sections 4.2, 
4.4 and 5.1). 
 
4.2 Posology and method of administration 
 
Truvada should be initiated by a physician experienced in the management of HIV infection. 
 
Posology 
 
Treatment of HIV in adults and adolescents aged 12 years and older, weighing at least 35 kg: One 
tablet, once daily. 
 
Prevention of HIV in adults and adolescents aged 12 years and older, weighing at least 35 kg: One 
tablet, once daily. 
 
Separate preparations of emtricitabine and tenofovir disoproxil are available for treatment of HIV-1 
infection if it becomes necessary to discontinue or modify the dose of one of the components of 
Truvada.  Please refer to the Summary of Product Characteristics for these medicinal products. 
 



3 

If a dose of Truvada is missed within 12 hours of the time it is usually taken, Truvada should be taken 
as soon as possible and the normal dosing schedule should be resumed.  If a dose of Truvada is missed 
by more than 12 hours and it is almost time for the next dose, the missed dose should not be taken and 
the usual dosing schedule should be resumed. 
 
If vomiting occurs within 1 hour of taking Truvada, another tablet should be taken.  If vomiting occurs 
more than 1 hour after taking Truvada a second dose should not be taken.  
 
Special populations 
 
Elderly: No dose adjustment is required (see section 5.2). 
 
Renal impairment: Emtricitabine and tenofovir are eliminated by renal excretion and the exposure to 
emtricitabine and tenofovir increases in individuals with renal dysfunction (see sections 4.4 and 5.2). 
 
Adults with renal impairment: 
Truvada should only be used in individuals with creatinine clearance (CrCl) < 80 mL/min if the 
potential benefits are considered to outweigh the potential risks.  See Table 1. 
 
Table 1: Dosing recommendations in adults with renal impairment 
 
 Treatment of HIV-1 infection Pre-exposure prophylaxis 
Mild renal impairment  
(CrCl 50-80 mL/min) 

Limited data from clinical studies 
support once daily dosing 
(see section 4.4). 

Limited data from clinical studies 
support once daily dosing in HIV-1 
uninfected individuals with 
CrCl 60-80 mL/min.  Use is not 
recommended in HIV-1 uninfected 
individuals with CrCl < 60 mL/min as 
it has not been studied in this 
population (see sections 4.4 and 5.2). 

Moderate renal impairment 
(CrCl 30-49 mL/min) 

Administration every 48 hours is 
recommended based on modelling 
of single-dose pharmacokinetic 
data for emtricitabine and tenofovir 
disoproxil in non-HIV infected 
subjects with varying degrees of 
renal impairment (see section 4.4). 

Not recommended for use in this 
population. 

Severe renal impairment  
(CrCl < 30 mL/min) and 
haemodialysis patients 

Not recommended because 
appropriate dose reductions cannot 
be achieved with the combination 
tablet. 

Not recommended for use in this 
population. 

 
Paediatrics with renal impairment: 
Not recommended for use in individuals under the age of 18 years with renal impairment (see 
section 4.4). 
 
Hepatic impairment: No dose adjustment is required in patients with hepatic impairment 
(see sections 4.4 and 5.2). 
 
Paediatric population: 
The safety and efficacy of Truvada in children under the age of 12 years have not been established 
(see section 5.2). 
 
Method of administration 
 
Oral administration.  It is preferable that Truvada is taken with food. 
 
The film-coated tablet can be disintegrated in approximately 100 mL of water, orange juice or grape 
juice and taken immediately. 



4 

 
4.3 Contraindications 
 
Hypersensitivity to the active substances or to any of the excipients listed in section 6.1. 
 
Use for pre-exposure prophylaxis in individuals with unknown or positive HIV-1 status. 
 
4.4 Special warnings and precautions for use 
 
Transmission of HIV 
 
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 of HIV by infected individuals should be taken in accordance with national guidelines. 
 
Patients with HIV-1 harbouring mutations 
 
Truvada should be avoided in antiretroviral-experienced patients with HIV-1 harbouring the K65R 
mutation (see section 5.1). 
 
Overall HIV-1 infection prevention strategy 
 
Truvada is not always effective in preventing the acquisition of HIV-1.  The time to onset of 
protection after commencing Truvada is unknown. 
 
Truvada should only be used for pre-exposure prophylaxis as part of an overall HIV-1 infection 
prevention strategy including the use of other HIV-1 prevention measures (e.g. consistent and correct 
condom use, knowledge of HIV-1 status, regular testing for other sexually transmitted infections). 
 
Risk of resistance with undetected HIV-1 infection: 
Truvada should only be used to reduce the risk of acquiring HIV-1 in individuals confirmed to be 
HIV negative (see section 4.3).  Individuals should be re-confirmed to be HIV-negative at frequent 
intervals (e.g. at least every 3 months) using a combined antigen/antibody test while taking Truvada 
for pre-exposure prophylaxis. 
 
Truvada alone does not constitute a complete regimen for the treatment of HIV-1 and 
HIV-1 resistance mutations have emerged in individuals with undetected HIV-1 infection who are 
only taking Truvada.  
 
If clinical symptoms consistent with acute viral infection are present and recent (< 1 month) exposures 
to HIV-1 are suspected, use of Truvada should be delayed for at least one month and HIV-1 status 
reconfirmed before starting Truvada for pre-exposure prophylaxis. 
 
Importance of adherence: 
The effectiveness of Truvada in reducing the risk of acquiring HIV-1 is strongly correlated with 
adherence as demonstrated by measurable drug levels in blood (see section 5.1).  HIV-1 uninfected 
individuals should be counselled at frequent intervals to strictly adhere to the recommended Truvada 
daily dosing schedule.   
 
Patients with hepatitis B or C virus infection 
 
HIV-1 infected patients with chronic hepatitis B or C treated with antiretroviral therapy are at an 
increased risk for severe and potentially fatal hepatic adverse reactions.  Physicians should refer to 
current HIV treatment guidelines for the management of HIV infection in patients co-infected with 
hepatitis B virus (HBV) or hepatitis C virus (HCV). 
 



5 

The safety and efficacy of Truvada for pre-exposure prophylaxis in patients with HBV or HCV 
infection has not been established. 
 
In case of concomitant antiviral therapy for hepatitis B or C, please refer also to the relevant Summary 
of Product Characteristics for these medicinal products.  See also under Use with ledipasvir and 
sofosbuvir or sofosbuvir and velpatasvir below. 
 
Tenofovir disoproxil is indicated for the treatment of HBV and emtricitabine has shown activity 
against HBV in pharmacodynamic studies but the safety and efficacy of Truvada have not been 
specifically established in patients with chronic HBV infection.  
 
Discontinuation of Truvada therapy in patients infected with HBV may be associated with severe 
acute exacerbations of hepatitis.  Patients infected with HBV who discontinue Truvada should be 
closely monitored with both clinical and laboratory follow-up for at least several months after stopping 
treatment.  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 disease 
 
The safety and efficacy of Truvada have not been established in patients with significant underlying 
liver disorders.  The pharmacokinetics of tenofovir has been studied in patients with hepatic 
impairment and no dose adjustment is required.  The pharmacokinetics of emtricitabine has not been 
studied in patients with hepatic impairment.  Based on minimal hepatic metabolism and the renal route 
of elimination for emtricitabine, it is unlikely that a dose adjustment would be required for Truvada in 
patients with hepatic impairment (see sections 4.2 and 5.2). 
 
HIV-1 infected 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. 
 
Renal and bone effects in adults 
 
Renal effects 
Emtricitabine and tenofovir are primarily excreted by the kidneys by a combination of glomerular 
filtration and active tubular secretion.  Renal failure, renal impairment, elevated creatinine, 
hypophosphataemia and proximal tubulopathy (including Fanconi syndrome) have been reported with 
the use of tenofovir disoproxil (see section 4.8). 
 
Renal monitoring 
Prior to initiating Truvada for the treatment of HIV-1 infection or for use in pre-exposure prophylaxis, 
it is recommended that creatinine clearance is calculated in all individuals. 
 
In individuals without risk factors for renal disease, it is recommended that renal function (creatinine 
clearance and serum phosphate) is monitored after two to four weeks of use, after three months of use 
and every three to six months thereafter. 
 
In individuals at risk for renal disease more frequent monitoring of renal function is required. 
 
See also under Co-administration of other medicinal products below. 
 
Renal management in HIV-1 infected patients 
If serum phosphate is < 1.5 mg/dL (0.48 mmol/L) or creatinine clearance is decreased to < 50 mL/min 
in any patient receiving Truvada, renal function should be re-evaluated within one week, including 
measurements of blood glucose, blood potassium and urine glucose concentrations (see section 4.8, 
proximal tubulopathy).  Consideration should be given to interrupting treatment with Truvada in 



6 

patients with creatinine clearance decreased to < 50 mL/min or decreases in serum phosphate 
to < 1.0 mg/dL (0.32 mmol/L).  Interrupting treatment with Truvada should also be considered in case 
of progressive decline of renal function when no other cause has been identified. 
 
Renal safety with Truvada has only been studied to a very limited degree in HIV-1 infected patients 
with impaired renal function (creatinine clearance < 80 mL/min).  Dose interval adjustments are 
recommended for HIV-1 infected patients with creatinine clearance 30-49 mL/min (see section 4.2).  
Limited clinical study data suggest that the prolonged dose interval is not optimal and could result in 
increased toxicity and possibly inadequate response.  Furthermore, in a small clinical study, a 
subgroup of patients with creatinine clearance between 50 and 60 mL/min who received tenofovir 
disoproxil in combination with emtricitabine every 24 hours had a 2-4-fold higher exposure to 
tenofovir and worsening of renal function (see section 5.2).  Therefore, a careful benefit-risk 
assessment is needed when Truvada is used in patients with creatinine clearance < 60 mL/min, and 
renal function should be closely monitored.  In addition, the clinical response to treatment should be 
closely monitored in patients receiving Truvada at a prolonged dosing interval.  The use of Truvada is 
not recommended in patients with severe renal impairment (creatinine clearance < 30 mL/min) and in 
patients who require haemodialysis since appropriate dose reductions cannot be achieved with the 
combination tablet (see sections 4.2 and 5.2). 
 
Renal management in pre-exposure prophylaxis 
Truvada has not been studied in HIV-1 uninfected individuals with creatinine clearance < 60 mL/min 
and is therefore not recommended for use in this population.  If serum phosphate is < 1.5 mg/dL 
(0.48 mmol/L) or creatinine clearance is decreased to < 60 mL/min in any individual receiving 
Truvada for pre-exposure prophylaxis, renal function should be re-evaluated within one week, 
including measurements of blood glucose, blood potassium and urine glucose concentrations (see 
section 4.8, proximal tubulopathy).  Consideration should be given to interrupting use of Truvada in 
individuals with creatinine clearance decreased to < 60 mL/min or decreases in serum phosphate 
to < 1.0 mg/dL (0.32 mmol/L).  Interrupting use of Truvada should also be considered in case of 
progressive decline of renal function when no other cause has been identified. 
 
Bone effects 
Bone abnormalities (infrequently contributing to fractures) may be associated with proximal renal 
tubulopathy (see section 4.8).  If bone abnormalities are suspected then appropriate consultation 
should be obtained. 
 
Treatment of HIV-1 infection 
In a 144-week controlled clinical study that compared tenofovir disoproxil with stavudine in 
combination with lamivudine and efavirenz in antiretroviral-naïve patients, small decreases in bone 
mineral density (BMD) of the hip and spine were observed in both treatment groups.  Decreases in 
BMD of spine and changes in bone biomarkers from baseline were significantly greater in the 
tenofovir disoproxil treatment group at 144 weeks.  Decreases in BMD of hip were significantly 
greater in this group until 96 weeks.  However, there was no increased risk of fractures or evidence for 
clinically relevant bone abnormalities over 144 weeks. 
 
In other studies (prospective and cross-sectional), the most pronounced decreases in BMD were seen 
in patients treated with tenofovir disoproxil as part of a regimen containing a boosted protease 
inhibitor.  Alternative treatment regimens should be considered for patients with osteoporosis that are 
at a high risk for fractures. 
 
Pre-exposure prophylaxis 
In clinical studies of HIV-1 uninfected individuals, small decreases in BMD were observed.  In a study 
of 498 men, the mean changes from baseline to week 24 in BMD ranged from -0.4% to -1.0% across 
hip, spine, femoral neck and trochanter in men who received daily Truvada prophylaxis (n = 247) vs. 
placebo (n = 251).  
 



7 

Renal and bone effects in the paediatric population 
 
There are uncertainties associated with the long-term renal and bone effects of tenofovir disoproxil 
during the treatment of HIV-1 infection in the paediatric population.  There are no data on the 
long-term renal and bone effects of Truvada when used for pre-exposure prophylaxis in uninfected 
adolescents (see section 5.1).  Moreover, the reversibility of renal toxicity after cessation of tenofovir 
disoproxil for treatment of HIV-1 or after cessation of Truvada for pre-exposure prophylaxis cannot be 
fully ascertained. 
 
A multidisciplinary approach is recommended to weigh the benefit/risk balance of the use of Truvada 
for the treatment of HIV-1 infection or for pre-exposure prophylaxis, decide the appropriate 
monitoring during treatment (including decision for treatment withdrawal) and consider the need for 
supplementation on a case by case basis.  
 
When using Truvada for pre-exposure prophylaxis individuals should be reassessed at each visit to 
ascertain whether they remain at high risk of HIV-1 infection. The risk of HIV-1 infection should be 
balanced against the potential for renal and bone effects with long-term use of Truvada. 
 
Renal effects 
Renal adverse reactions consistent with proximal renal tubulopathy have been reported in HIV-1 
infected paediatric patients aged 2 to < 12 years in clinical study GS-US-104-0352 (see sections 4.8 
and 5.1). 
 
Renal monitoring 
Renal function (creatinine clearance and serum phosphate) should be evaluated prior to initiating 
Truvada for treatment of HIV-1 or for pre-exposure prophylaxis, and should be monitored during use 
as in adults (see above). 
 
Renal management 
If serum phosphate is confirmed to be < 3.0 mg/dL (0.96 mmol/L) in any paediatric patient receiving 
Truvada, renal function should be re-evaluated within one week, including measurements of blood 
glucose, blood potassium and urine glucose concentrations (see section 4.8, proximal tubulopathy). If 
renal abnormalities are suspected or detected then consultation with a nephrologist should be obtained 
to consider interruption of Truvada use. Interrupting use of Truvada should also be considered in case 
of progressive decline of renal function when no other cause has been identified. 
 
Co-administration and risk of renal toxicity 
The same recommendations apply as in adults (see Co-administration of other medicinal products 
below). 
 
Renal impairment 
The use of Truvada is not recommended in individuals under the age of 18 years with renal 
impairment (see section 4.2). Truvada should not be initiated in paediatric patients with renal 
impairment and should be discontinued in paediatric patients who develop renal impairment during 
Truvada use. 
 
Bone effects  
Use of tenofovir disoproxil may cause a reduction in BMD. The effects of tenofovir disoproxil-
associated changes in BMD on long-term bone health and future fracture risk are currently unknown 
(see section 5.1). 
 
If bone abnormalities are detected or suspected during use of Truvada in any paediatric patient, 
consultation with an endocrinologist and/or nephrologist should be obtained. 
 



8 

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 are 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 
 
HIV-1 infected patients receiving Truvada or any other antiretroviral therapy may continue to develop 
opportunistic infections and other complications of HIV infection, and therefore should remain under 
close clinical observation by physicians experienced in the treatment of patients with HIV associated 
diseases. 
 
Osteonecrosis 
 
Although the aetiology is considered to be multifactorial (including corticosteroid use, alcohol 
consumption, severe immunosuppression, higher body mass index), cases of osteonecrosis have been 
reported particularly in patients with advanced HIV-disease and/or long-term exposure to CART.  
Patients should be advised to seek medical advice if they experience joint aches and pain, joint 
stiffness or difficulty in movement. 
 
Co-administration of other medicinal products 
 
Use of Truvada should be avoided with concurrent or recent use of a nephrotoxic medicinal product 
(see section 4.5).  If concomitant use with nephrotoxic agents is unavoidable, renal function should be 
monitored weekly. 



9 

 
Cases of acute renal failure after initiation of high dose or multiple non-steroidal anti-inflammatory 
drugs (NSAIDs) have been reported in HIV-1 infected patients treated with tenofovir disoproxil and 
with risk factors for renal dysfunction.  If Truvada is co-administered with an NSAID, renal function 
should be monitored adequately. 
 
A higher risk of renal impairment has been reported in HIV-1 infected patients receiving tenofovir 
disoproxil in combination with a ritonavir or cobicistat boosted protease inhibitor.  Close monitoring 
of renal function is required in these patients (see section 4.5).  In HIV-1 infected patients with renal 
risk factors, the co-administration of tenofovir disoproxil with a boosted protease inhibitor should be 
carefully evaluated. 
 
Truvada should not be administered concomitantly with other medicinal products containing 
emtricitabine, tenofovir disoproxil, tenofovir alafenamide, or other cytidine analogues, such as 
lamivudine (see section 4.5).  Truvada should not be administered concomitantly with adefovir 
dipivoxil. 
 
Use with ledipasvir and sofosbuvir,  sofosbuvir and velpatasvir or sofosbuvir, velpatasvir and 
voxilaprevir 
Co-administration of tenofovir disoproxil with ledipasvir/sofosbuvir, sofosbuvir/velpatasvir or 
sofosbuvir/velpatasvir/voxilaprevir has been shown to increase plasma concentrations of tenofovir, 
especially when used together with an HIV regimen containing tenofovir disoproxil and a 
pharmacokinetic enhancer (ritonavir or cobicistat). 
 
The safety of tenofovir disoproxil when co-administered with ledipasvir/sofosbuvir, 
sofosbuvir/velpatasvir or sofosbuvir/velpatasvir/voxilaprevir and a pharmacokinetic enhancer has not 
been established.  The potential risks and benefits associated with co-administration should be 
considered, particularly in patients at increased risk of renal dysfunction.  Patients receiving 
ledipasvir/sofosbuvir, sofosbuvir/velpatasvir or sofosbuvir/velpatasvir/voxilaprevir concomitantly with 
tenofovir disoproxil and a boosted HIV protease inhibitor should be monitored for adverse reactions 
related to tenofovir disoproxil. 
 
Co-administration of tenofovir disoproxil and didanosine  
Co-administration is not recommended because it results in a 40-60% increase in systemic exposure to 
didanosine that may increase the risk of didanosine-related adverse reactions (see section 4.5).  Rarely, 
pancreatitis and lactic acidosis, sometimes fatal, have been reported.  Co-administration of tenofovir 
disoproxil and didanosine at a dose of 400 mg daily has been associated with a significant decrease in 
CD4 cell count, possibly due to an intracellular interaction increasing phosphorylated (i.e. active) 
didanosine.  A decreased dosage of 250 mg didanosine co-administered with tenofovir disoproxil 
therapy has been associated with reports of high rates of virological failure within several tested 
combinations. 
 
Triple nucleoside therapy 
 
There have been reports of a high rate of virological failure and of emergence of resistance at an early 
stage in HIV-1 infected patients when tenofovir disoproxil was combined with lamivudine and 
abacavir as well as with lamivudine and didanosine as a once daily regimen.  There is close structural 
similarity between lamivudine and emtricitabine and similarities in the pharmacokinetics and 
pharmacodynamics of these two agents.  Therefore, the same problems may be seen if Truvada is 
administered with a third nucleoside analogue. 
 
Elderly 
 
Truvada has not been studied in individuals over the age of 65 years.  Individuals over the age of 
65 years are more likely to have decreased renal function, therefore caution should be exercised when 
administering Truvada to older people.  
 



10 

Excipients 
 
Truvada contains lactose monohydrate.  Patients with rare hereditary problems of galactose 
intolerance, total lactase deficiency, or glucose-galactose malabsorption should not take this medicinal 
product. 
 
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. 
 
As Truvada contains emtricitabine and tenofovir disoproxil, any interactions that have been identified 
with these agents individually may occur with Truvada.  Interaction studies have only been performed 
in adults. 
 
The steady-state pharmacokinetics of emtricitabine and tenofovir were unaffected when emtricitabine 
and tenofovir disoproxil were administered together versus each medicinal product dosed alone. 
 
In vitro and clinical pharmacokinetic interaction studies have shown the potential for CYP450 
mediated interactions involving emtricitabine and tenofovir disoproxil with other medicinal products 
is low. 
 
Concomitant use not recommended 
 
Truvada should not be administered concomitantly with other medicinal products containing 
emtricitabine, tenofovir disoproxil, tenofovir alafenamide or other cytidine analogues, such as 
lamivudine (see section 4.4).  Truvada should not be administered concomitantly with 
adefovir dipivoxil. 
 
Didanosine: The co-administration of Truvada and didanosine is not recommended (see section 4.4 
and Table 2). 
 
Renally eliminated medicinal products: Since emtricitabine and tenofovir are primarily eliminated by 
the kidneys, co-administration of Truvada with medicinal products that reduce renal function or 
compete for active tubular secretion (e.g. cidofovir) may increase serum concentrations of 
emtricitabine, tenofovir and/or the co-administered medicinal products. 
 
Use of Truvada should be avoided with concurrent or recent use of a nephrotoxic medicinal product.  
Some examples include, but are not limited to, aminoglycosides, amphotericin B, foscarnet, 
ganciclovir, pentamidine, vancomycin, cidofovir or interleukin-2 (see section 4.4). 
 
Other interactions 
 
Interactions between Truvada or its individual component(s) and other medicinal products are listed in 
Table 2 below (increase is indicated as “↑”, decrease as “↓”, no change as “↔”, twice daily as “b.i.d.” 
and once daily as “q.d.”).  If available, 90% confidence intervals are shown in parentheses. 
 



11 

Table 2: Interactions between Truvada or its individual component(s) and other medicinal 
products 
 

Medicinal product by 
therapeutic areas 

Effects on drug levels 
Mean percent change in AUC, 

Cmax, Cmin with 90% confidence 
intervals if available 

(mechanism) 

Recommendation concerning 
co-administration with Truvada 
(emtricitabine 200 mg, tenofovir 

disoproxil 245 mg) 

ANTI-INFECTIVES 
Antiretrovirals 
Protease inhibitors 
Atazanavir/Ritonavir/Tenofovir 
disoproxil  
(300 mg q.d./100 mg q.d./245 mg 
q.d.) 

Atazanavir: 
AUC: ↓ 25% (↓ 42 to ↓ 3) 
Cmax: ↓ 28% (↓ 50 to ↑ 5) 
Cmin: ↓ 26% (↓ 46 to ↑ 10) 
 
Tenofovir: 
AUC: ↑ 37% 
Cmax: ↑ 34% 
Cmin: ↑ 29% 

No dose adjustment is 
recommended.  The increased 
exposure of tenofovir could 
potentiate tenofovir associated 
adverse events, including renal 
disorders.  Renal function should 
be closely monitored (see 
section 4.4). 

Atazanavir/Ritonavir/Emtricitabine Interaction not studied. 
Darunavir/Ritonavir/Tenofovir 
disoproxil 
(300 mg q.d./100 mg q.d./245 mg 
q.d.) 

Darunavir: 
AUC: ↔ 
Cmin: ↔ 
 
Tenofovir: 
AUC: ↑ 22% 
Cmin: ↑ 37% 

No dose adjustment is 
recommended.  The increased 
exposure of tenofovir could 
potentiate tenofovir associated 
adverse events, including renal 
disorders.  Renal function should 
be closely monitored (see 
section 4.4). Darunavir/Ritonavir/Emtricitabine Interaction not studied. 

Lopinavir/Ritonavir/Tenofovir 
disoproxil 
(400 mg b.i.d./100 mg b.i.d/245 mg 
q.d.) 

Lopinavir/Ritonavir: 
AUC: ↔ 
Cmax: ↔ 
Cmin: ↔ 
 
Tenofovir: 
AUC: ↑ 32% (↑ 25 to ↑ 38) 
Cmax: ↔ 
Cmin: ↑ 51% (↑ 37 to ↑ 66) 

No dose adjustment is 
recommended.  The increased 
exposure of tenofovir could 
potentiate tenofovir associated 
adverse events, including renal 
disorders.  Renal function should 
be closely monitored (see 
section 4.4). 

Lopinavir/Ritonavir/Emtricitabine Interaction not studied. 
NRTIs 
Didanosine/Tenofovir disoproxil Co-administration of tenofovir 

disoproxil and didanosine results 
in a 40-60% increase in systemic 
exposure to didanosine that may 
increase the risk for 
didanosine-related adverse 
reactions.  Rarely, pancreatitis 
and lactic acidosis, sometimes 
fatal, have been reported.  
Co-administration of tenofovir 
disoproxil and didanosine at a 
dose of 400 mg daily has been 
associated with a significant 
decrease in CD4 cell count, 
possibly due to an intracellular 
interaction increasing 
phosphorylated (i.e. active) 
didanosine.  A decreased dosage 
of 250 mg didanosine 
co-administered with tenofovir 
disoproxil therapy has been 
associated with reports of high 

Co-administration of Truvada and 
didanosine is not recommended 
(see section 4.4). 



12 

Medicinal product by 
therapeutic areas 

Effects on drug levels 
Mean percent change in AUC, 

Cmax, Cmin with 90% confidence 
intervals if available 

(mechanism) 

Recommendation concerning 
co-administration with Truvada 
(emtricitabine 200 mg, tenofovir 

disoproxil 245 mg) 

rates of virological failure within 
several tested combinations for 
the treatment of HIV-1 infection. 

Didanosine/Emtricitabine Interaction not studied. 
Lamivudine/Tenofovir disoproxil  Lamivudine: 

AUC: ↓ 3% (↓ 8% to ↑ 15) 
Cmax: ↓ 24% (↓ 44 to ↓ 12) 
Cmin: NC 
 
Tenofovir: 
AUC: ↓ 4% (↓ 15 to ↑ 8) 
Cmax: ↑ 102% (↓ 96 to ↑ 108) 
Cmin: NC 

Lamivudine and Truvada should 
not be administered concomitantly 
(see section 4.4). 

Efavirenz/Tenofovir disoproxil  Efavirenz: 
AUC: ↓ 4% (↓ 7 to ↓ 1) 
Cmax: ↓ 4% (↓ 9 to ↑ 2) 
Cmin: NC 
 
Tenofovir: 
AUC: ↓ 1% (↓ 8 to ↑ 6) 
Cmax: ↑ 7% (↓ 6 to ↑ 22) 
Cmin: NC 

No dose adjustment of efavirenz is 
required. 

ANTI-INFECTIVES 
Hepatitis B virus (HBV) antiviral agents 
Adefovir dipivoxil/Tenofovir 
disoproxil 

Adefovir dipivoxil:  
AUC: ↓ 11% (↓ 14 to ↓ 7) 
Cmax: ↓ 7% (↓ 13 to ↓ 0) 
Cmin: NC 

 
Tenofovir: 
AUC: ↓ 2% (↓ 5 to ↑ 0) 
Cmax: ↓ 1% (↓ 7 to ↑ 6) 
Cmin: NC 

Adefovir dipivoxil and Truvada 
should not be administered 
concomitantly (see section 4.4). 

Hepatitis C virus (HCV) antiviral agents 
Ledipasvir/Sofosbuvir 
(90 mg/400 mg q.d.) + 
Atazanavir/Ritonavir 
(300 mg q.d./100 mg q.d.) + 
Emtricitabine/Tenofovir disoproxil  
(200 mg/245 mg q.d.)1 

Ledipasvir: 
AUC: ↑ 96% (↑ 74 to ↑ 121) 
Cmax: ↑ 68% (↑ 54 to ↑ 84) 
Cmin: ↑ 118% (↑ 91 to ↑ 150) 
 
Sofosbuvir: 
AUC: ↔ 
Cmax: ↔ 
 
GS-3310072: 
AUC: ↔ 
Cmax: ↔ 
Cmin: ↑ 42% (↑ 34 to ↑ 49) 
 
Atazanavir: 
AUC: ↔ 
Cmax: ↔ 
Cmin: ↑ 63% (↑ 45 to ↑ 84) 
 
Ritonavir: 
AUC: ↔ 
Cmax: ↔ 
Cmin: ↑ 45% (↑ 27 to ↑ 64) 

Increased plasma concentrations 
of tenofovir resulting from 
co-administration of tenofovir 
disoproxil, ledipasvir/sofosbuvir 
and atazanavir/ritonavir may 
increase adverse reactions related 
to tenofovir disoproxil, including 
renal disorders.  The safety of 
tenofovir disoproxil  when used 
with ledipasvir/sofosbuvir and a 
pharmacokinetic enhancer (e.g. 
ritonavir or cobicistat) has not 
been established. 
 
The combination should be used 
with caution with frequent renal 
monitoring, if other alternatives 
are not available (see section 4.4). 



13 

Medicinal product by 
therapeutic areas 

Effects on drug levels 
Mean percent change in AUC, 

Cmax, Cmin with 90% confidence 
intervals if available 

(mechanism) 

Recommendation concerning 
co-administration with Truvada 
(emtricitabine 200 mg, tenofovir 

disoproxil 245 mg) 

 
Emtricitabine: 
AUC: ↔ 
Cmax: ↔ 
Cmin: ↔ 
 
Tenofovir: 
AUC: ↔ 
Cmax: ↑ 47% (↑ 37 to ↑ 58) 
Cmin: ↑ 47% (↑ 38 to ↑ 57) 

Ledipasvir/Sofosbuvir 
(90 mg/400 mg q.d.) + 
Darunavir/Ritonavir 
(800 mg q.d./100 mg q.d.) + 
Emtricitabine/Tenofovir disoproxil 
(200 mg/245 mg q.d.)1 

Ledipasvir: 
AUC: ↔ 
Cmax: ↔ 
Cmin: ↔ 
 
Sofosbuvir: 
AUC: ↓ 27% (↓ 35 to ↓ 18) 
Cmax: ↓ 37% (↓ 48 to ↓ 25) 
 
GS-3310072: 
AUC: ↔ 
Cmax: ↔ 
Cmin: ↔ 
 
Darunavir: 
AUC: ↔ 
Cmax: ↔ 
Cmin: ↔ 
 
Ritonavir: 
AUC: ↔ 
Cmax: ↔ 
Cmin: ↑ 48% (↑ 34 to ↑ 63) 
 
Emtricitabine: 
AUC: ↔ 
Cmax: ↔ 
Cmin: ↔ 
 
Tenofovir: 
AUC: ↑ 50% (↑ 42 to ↑ 59) 
Cmax: ↑ 64% (↑ 54 to ↑ 74) 
Cmin: ↑ 59% (↑ 49 to ↑ 70) 

Increased plasma concentrations 
of tenofovir resulting from 
co-administration of tenofovir 
disoproxil, ledipasvir/sofosbuvir 
and darunavir/ritonavir may 
increase adverse reactions related 
to tenofovir disoproxil, including 
renal disorders.  The safety of 
tenofovir disoproxil when used 
with ledipasvir/sofosbuvir and a 
pharmacokinetic enhancer (e.g. 
ritonavir or cobicistat) has not 
been established. 
 
The combination should be used 
with caution with frequent renal 
monitoring, if other alternatives 
are not available (see section 4.4). 

Ledipasvir/Sofosbuvir 
(90 mg/400 mg q.d.) + 
Efavirenz/Emtricitabine/Tenofovir 
disoproxil 
(600 mg/200 mg/245 mg q.d.) 

Ledipasvir: 
AUC: ↓ 34% (↓ 41 to ↓ 25) 
Cmax: ↓ 34% (↓ 41 to ↑ 25) 
Cmin: ↓ 34% (↓ 43 to ↑ 24) 
 
Sofosbuvir: 
AUC: ↔ 
Cmax: ↔ 
 
GS-3310072: 
AUC: ↔ 
Cmax: ↔ 
Cmin: ↔ 
 
Efavirenz: 

No dose adjustment is 
recommended.  The increased 
exposure of tenofovir could 
potentiate adverse reactions 
associated with tenofovir 
disoproxil, including renal 
disorders.  Renal function should 
be closely monitored (see 
section 4.4). 



14 

Medicinal product by 
therapeutic areas 

Effects on drug levels 
Mean percent change in AUC, 

Cmax, Cmin with 90% confidence 
intervals if available 

(mechanism) 

Recommendation concerning 
co-administration with Truvada 
(emtricitabine 200 mg, tenofovir 

disoproxil 245 mg) 

AUC: ↔ 
Cmax: ↔ 
Cmin: ↔ 
 
Emtricitabine: 
AUC: ↔ 
Cmax: ↔ 
Cmin: ↔ 
 
Tenofovir: 
AUC: ↑ 98% (↑ 77 to ↑ 123) 
Cmax: ↑ 79% (↑ 56 to ↑ 104) 
Cmin: ↑ 163% (↑ 137 to ↑ 197) 

Ledipasvir/Sofosbuvir 
(90 mg/400 mg q.d.) + 
Emtricitabine/Rilpivirine/ 
Tenofovir disoproxil 
(200 mg/25 mg/245 mg q.d.) 

Ledipasvir: 
AUC: ↔ 
Cmax: ↔ 
Cmin: ↔ 
 
Sofosbuvir: 
AUC: ↔ 
Cmax: ↔ 
 
GS-3310072: 
AUC: ↔ 
Cmax: ↔ 
Cmin: ↔ 
 
Emtricitabine: 
AUC: ↔ 
Cmax: ↔ 
Cmin: ↔ 
 
Rilpivirine: 
AUC: ↔ 
Cmax: ↔ 
Cmin: ↔ 
 
Tenofovir: 
AUC: ↑ 40% (↑ 31 to ↑ 50) 
Cmax: ↔ 
Cmin: ↑ 91% (↑ 74 to ↑ 110) 

No dose adjustment is 
recommended.  The increased 
exposure of tenofovir could 
potentiate adverse reactions 
associated with tenofovir 
disoproxil, including renal 
disorders.  Renal function should 
be closely monitored (see 
section 4.4). 

Ledipasvir/Sofosbuvir 
(90 mg/400 mg q.d.) + 
Dolutegravir (50 mg q.d.) + 
Emtricitabine/Tenofovir disoproxil 
(200 mg/245 mg q.d.) 

Sofosbuvir: 
AUC: ↔ 
Cmax: ↔ 
 
GS-3310072 
AUC: ↔ 
Cmax: ↔ 
Cmin: ↔ 
 
Ledipasvir: 
AUC: ↔ 
Cmax: ↔ 
Cmin: ↔ 
 
Dolutegravir  
AUC: ↔ 
Cmax: ↔ 

No dose adjustment is required.  
The increased exposure of 
tenofovir could potentiate adverse 
reactions associated with tenofovir 
disoproxil, including renal 
disorders.  Renal function should 
be closely monitored (see section 
4.4). 



15 

Medicinal product by 
therapeutic areas 

Effects on drug levels 
Mean percent change in AUC, 

Cmax, Cmin with 90% confidence 
intervals if available 

(mechanism) 

Recommendation concerning 
co-administration with Truvada 
(emtricitabine 200 mg, tenofovir 

disoproxil 245 mg) 

Cmin: ↔ 
 
Emtricitabine: 
AUC: ↔ 
Cmax: ↔ 
Cmin: ↔ 
 
Tenofovir: 
AUC: ↑ 65% (↑ 59 to ↑ 71) 
Cmax: ↑ 61% (↑ 51 to ↑ 72) 
Cmin: ↑ 115% (↑ 105 to ↑ 126) 

Sofosbuvir/Velpatasvir 
(400 mg/100 mg q.d.) + 
Atazanavir/Ritonavir 
(300 mg q.d./100 mg q.d.) + 
Emtricitabine/Tenofovir disoproxil 
(200 mg/245 mg q.d.) 

Sofosbuvir: 
AUC: ↔  
Cmax: ↔  
 
GS-3310072: 
AUC: ↔ 
Cmax: ↔ 
Cmin: ↑ 42% (↑ 37 to ↑ 49) 
 
Velpatasvir: 
AUC: ↑ 142% (↑ 123 to ↑ 164) 
Cmax: ↑ 55% (↑ 41 to ↑ 71) 
Cmin: ↑ 301% (↑ 257 to ↑ 350) 
 
Atazanavir: 
AUC: ↔ 
Cmax: ↔ 
Cmin: ↑ 39% (↑ 20 to ↑ 61) 
 
Ritonavir: 
AUC: ↔ 
Cmax: ↔ 
Cmin: ↑ 29% (↑ 15 to ↑ 44) 
 
Emtricitabine: 
AUC: ↔ 
Cmax: ↔ 
Cmin: ↔ 
 
Tenofovir: 
AUC: ↔ 
Cmax: ↑ 55% (↑ 43 to ↑ 68) 
Cmin: ↑ 39% (↑ 31 to ↑ 48) 

Increased plasma concentrations 
of tenofovir resulting from 
co-administration of tenofovir 
disoproxil, sofosbuvir/velpatasvir 
and atazanavir/ritonavir may 
increase adverse reactions related 
to tenofovir disoproxil, including 
renal disorders.  The safety of 
tenofovir disoproxil when used 
with sofosbuvir/velpatasvir and a 
pharmacokinetic enhancer (e.g. 
ritonavir or cobicistat) has not 
been established. 
 
The combination should be used 
with caution with frequent renal 
monitoring (see section 4.4). 

Sofosbuvir/Velpatasvir 
(400 mg/100 mg q.d.) + 
Darunavir/Ritonavir 
(800 mg q.d./100 mg q.d.) + 
Emtricitabine/Tenofovir disoproxil 
(200 mg/245 mg q.d.) 

Sofosbuvir: 
AUC: ↓ 28% (↓ 34 to ↓ 20) 
Cmax: ↓ 38% (↓ 46 to ↓ 29) 
 
GS-3310072: 
AUC: ↔ 
Cmax: ↔ 
Cmin: ↔ 
 
Velpatasvir: 
AUC: ↔ 
Cmax: ↓ 24% (↓ 35 to ↓ 11) 
Cmin: ↔ 
 

Increased plasma concentrations 
of tenofovir resulting from 
co-administration of tenofovir 
disoproxil, sofosbuvir/velpatasvir 
and darunavir/ritonavir may 
increase adverse reactions related 
to tenofovir disoproxil, including 
renal disorders.  The safety of 
tenofovir disoproxil when used 
with sofosbuvir/velpatasvir and a 
pharmacokinetic enhancer (e.g. 
ritonavir or cobicistat) has not 
been established. 
 



16 

Medicinal product by 
therapeutic areas 

Effects on drug levels 
Mean percent change in AUC, 

Cmax, Cmin with 90% confidence 
intervals if available 

(mechanism) 

Recommendation concerning 
co-administration with Truvada 
(emtricitabine 200 mg, tenofovir 

disoproxil 245 mg) 

Darunavir: 
AUC: ↔ 
Cmax: ↔ 
Cmin: ↔ 
 
Ritonavir: 
AUC: ↔ 
Cmax: ↔ 
Cmin: ↔ 
 
Emtricitabine: 
AUC: ↔ 
Cmax: ↔ 
Cmin: ↔ 
 
Tenofovir: 
AUC: ↑ 39% (↑ 33 to ↑ 44) 
Cmax: ↑ 55% (↑ 45 to ↑ 66) 
Cmin: ↑ 52% (↑ 45 to ↑ 59) 

The combination should be used 
with caution with frequent renal 
monitoring (see section 4.4). 

Sofosbuvir/Velpatasvir 
(400 mg/100 mg q.d.) + 
Lopinavir/Ritonavir 
(800 mg/200 mg q.d.) + 
Emtricitabine/Tenofovir disoproxil 
(200 mg/245 mg q.d.) 

Sofosbuvir: 
AUC: ↓ 29% (↓ 36 to ↓ 22) 
Cmax: ↓ 41% (↓ 51 to ↓ 29) 
 
GS-3310072: 
AUC: ↔ 
Cmax: ↔ 
Cmin: ↔ 
 
Velpatasvir: 
AUC: ↔ 
Cmax: ↓ 30% (↓ 41 to ↓ 17) 
Cmin: ↑ 63% (↑ 43 to ↑ 85) 
 
Lopinavir: 
AUC: ↔ 
Cmax: ↔ 
Cmin: ↔ 
 
Ritonavir: 
AUC: ↔ 
Cmax: ↔ 
Cmin: ↔ 
 
Emtricitabine: 
AUC: ↔ 
Cmax: ↔ 
Cmin: ↔ 
 
Tenofovir: 
AUC: ↔ 
Cmax: ↑ 42% (↑ 27 to ↑ 57) 
Cmin: ↔ 

Increased plasma concentrations 
of tenofovir resulting from 
co-administration of tenofovir 
disoproxil, sofosbuvir/velpatasvir 
and lopinavir/ritonavir may 
increase adverse reactions related 
to tenofovir disoproxil, including 
renal disorders.  The safety of 
tenofovir disoproxil when used 
with sofosbuvir/velpatasvir and a 
pharmacokinetic enhancer (e.g. 
ritonavir or cobicistat) has not 
been established. 
 
The combination should be used 
with caution with frequent renal 
monitoring (see section 4.4). 

Sofosbuvir/Velpatasvir 
(400 mg/100 mg q.d.) + 
Raltegravir 
(400 mg b.i.d) + 
Emtricitabine/Tenofovir disoproxil 
(200 mg/245 mg q.d.) 

Sofosbuvir: 
AUC: ↔ 
Cmax: ↔ 
 
GS-3310072: 
AUC: ↔ 

No dose adjustment is 
recommended.  The increased 
exposure of tenofovir could 
potentiate adverse reactions 
associated with tenofovir 
disoproxil, including renal 



17 

Medicinal product by 
therapeutic areas 

Effects on drug levels 
Mean percent change in AUC, 

Cmax, Cmin with 90% confidence 
intervals if available 

(mechanism) 

Recommendation concerning 
co-administration with Truvada 
(emtricitabine 200 mg, tenofovir 

disoproxil 245 mg) 

Cmax: ↔ 
Cmin: ↔ 
 
Velpatasvir: 
AUC: ↔ 
Cmax: ↔ 
Cmin: ↔ 
 
Raltegravir: 
AUC: ↔ 
Cmax: ↔ 
Cmin: ↓ 21% (↓ 58 to ↑ 48) 
 
Emtricitabine: 
AUC: ↔ 
Cmax: ↔ 
Cmin: ↔ 
 
Tenofovir: 
AUC: ↑ 40% (↑ 34 to ↑ 45) 
Cmax: ↑ 46% (↑ 39 to ↑ 54) 
Cmin: ↑ 70% (↑ 61 to ↑ 79) 

disorders.  Renal function should 
be closely monitored (see 
section 4.4). 

Sofosbuvir/Velpatasvir 
(400 mg/100 mg q.d.) + 
Efavirenz/Emtricitabine/Tenofovir 
disoproxil 
(600 mg/200 mg/245 mg q.d.) 

Sofosbuvir: 
AUC: ↔ 
Cmax: ↑ 38% (↑ 14 to ↑ 67) 
 
GS-3310072: 
AUC: ↔ 
Cmax: ↔ 
Cmin: ↔ 
 
Velpatasvir: 
AUC: ↓ 53% (↓ 61 to ↓ 43) 
Cmax: ↓ 47% (↓ 57 to ↓ 36) 
Cmin: ↓ 57% (↓ 64 to ↓ 48) 
 
Efavirenz: 
AUC: ↔ 
Cmax: ↔ 
Cmin: ↔ 
 
Emtricitabine: 
AUC: ↔ 
Cmax: ↔ 
Cmin: ↔ 
 
Tenofovir: 
AUC: ↑ 81% (↑ 68 to ↑ 94) 
Cmax: ↑ 77% (↑ 53 to ↑ 104) 
Cmin: ↑ 121% (↑ 100 to ↑ 143) 

Concomitant administration of 
sofosbuvir/velpatasvir and 
efavirenz is expected to decrease 
plasma concentrations of 
velpatasvir.  Co-administration of 
sofosbuvir/velpatasvir with 
efavirenz-containing regimens is 
not recommended. 



18 

Medicinal product by 
therapeutic areas 

Effects on drug levels 
Mean percent change in AUC, 

Cmax, Cmin with 90% confidence 
intervals if available 

(mechanism) 

Recommendation concerning 
co-administration with Truvada 
(emtricitabine 200 mg, tenofovir 

disoproxil 245 mg) 

Sofosbuvir/Velpatasvir 
(400 mg/100 mg q.d.) + 
Emtricitabine/Rilpivirine/Tenofovir 
disoproxil 
(200 mg/25 mg/245 mg q.d.) 

Sofosbuvir: 
AUC: ↔ 
Cmax: ↔ 
 
GS-3310072: 
AUC: ↔ 
Cmax: ↔ 
Cmin: ↔ 
 
Velpatasvir: 
AUC: ↔ 
Cmax: ↔ 
Cmin: ↔ 
 
Emtricitabine: 
AUC: ↔ 
Cmax: ↔ 
Cmin: ↔ 
 
Rilpivirine: 
AUC: ↔ 
Cmax: ↔ 
Cmin: ↔ 
 
Tenofovir: 
AUC: ↑ 40% (↑ 34 to ↑ 46) 
Cmax: ↑ 44% (↑ 33 to ↑ 55) 
Cmin: ↑ 84% (↑ 76 to ↑ 92) 

No dose adjustment is 
recommended.  The increased 
exposure of tenofovir could 
potentiate adverse reactions 
associated with tenofovir 
disoproxil, including renal 
disorders.  Renal function should 
be closely monitored (see 
section 4.4). 

Sofosbuvir/Velpatasvir/ 
Voxilaprevir (400 mg/100 mg/ 
100 mg+100 mg q.d.)3 + Darunavir 
(800 mg q.d.) + Ritonavir (100 mg 
q.d.) + Emtricitabine/Tenofovir 
disoproxil (200 mg/245 mg q.d.) 

Sofosbuvir: 
AUC: ↔ 
Cmax: ↓ 30% 
Cmin: N/A 
 
GS-3310072: 
AUC: ↔ 
Cmax:↔ 
Cmin: N/A 

 
Velpatasvir: 
AUC: ↔ 
Cmax: ↔ 
Cmin: ↔ 
 
Voxilaprevir: 
AUC: ↑ 143% 
Cmax:↑ 72% 
Cmin: ↑ 300% 
 
Darunavir: 
AUC: ↔ 
Cmax: ↔ 
Cmin: ↓ 34% 
 
Ritonavir: 
AUC: ↑ 45% 
Cmax: ↑ 60% 
Cmin: ↔ 
 

Increased plasma concentrations 
of tenofovir resulting from 
co-administration of tenofovir 
disoproxil, 
sofosbuvir/velpatasvir/voxilaprevir 
and darunavir/ritonavir may 
increase adverse reactions related 
to tenofovir disoproxil, including 
renal disorders. The safety of 
tenofovir disoproxil when used 
with 
sofosbuvir/velpatasvir/voxilaprevir 
and a pharmacokinetic enhancer 
(e.g. ritonavir or cobicistat) has 
not been established. 
 
The combination should be used 
with caution with frequent renal 
monitoring (see section 4.4). 



19 

Medicinal product by 
therapeutic areas 

Effects on drug levels 
Mean percent change in AUC, 

Cmax, Cmin with 90% confidence 
intervals if available 

(mechanism) 

Recommendation concerning 
co-administration with Truvada 
(emtricitabine 200 mg, tenofovir 

disoproxil 245 mg) 

Emtricitabine: 
AUC: ↔ 
Cmax: ↔ 
Cmin: ↔ 
 
Tenofovir: 
AUC: ↑ 39% 
Cmax: ↑ 48% 
Cmin: ↑ 47% 

Sofosbuvir 
(400 mg q.d.) + 
Efavirenz/Emtricitabine/Tenofovir 
disoproxil 
(600 mg/200 mg/245 mg q.d.) 

Sofosbuvir: 
AUC: ↔ 
Cmax: ↓ 19% (↓ 40 to ↑ 10) 
 
GS-3310072: 
AUC: ↔ 
Cmax: ↓ 23% (↓ 30 to ↑ 16) 
 
Efavirenz: 
AUC: ↔ 
Cmax: ↔ 
Cmin: ↔ 
 
Emtricitabine: 
AUC: ↔ 
Cmax: ↔ 
Cmin: ↔ 
 
Tenofovir: 
AUC: ↔ 
Cmax: ↑ 25% (↑ 8 to ↑ 45) 
Cmin: ↔ 

No dose adjustment is required. 

Ribavirin/Tenofovir disoproxil Ribavirin: 
AUC: ↑ 26% (↑ 20 to ↑ 32) 
Cmax: ↓ 5% (↓ 11 to ↑ 1) 
Cmin: NC 

No dose adjustment of ribavirin is 
required. 

Herpes virus antiviral agents 
Famciclovir/Emtricitabine Famciclovir: 

AUC: ↓ 9% (↓ 16 to ↓ 1) 
Cmax: ↓ 7% (↓ 22 to ↑ 11) 
Cmin: NC 
 
Emtricitabine: 
AUC: ↓ 7% (↓ 13 to ↓ 1) 
Cmax: ↓ 11% (↓ 20 to ↑ 1) 
Cmin: NC 

No dose adjustment of famciclovir 
is required. 

Antimycobacterials 
Rifampicin/Tenofovir disoproxil Tenofovir: 

AUC: ↓ 12% (↓ 16 to ↓ 8) 
Cmax: ↓ 16% (↓ 22 to ↓ 10) 
Cmin: ↓ 15% (↓ 12 to ↓ 9) 

No dose adjustment is required. 



20 

Medicinal product by 
therapeutic areas 

Effects on drug levels 
Mean percent change in AUC, 

Cmax, Cmin with 90% confidence 
intervals if available 

(mechanism) 

Recommendation concerning 
co-administration with Truvada 
(emtricitabine 200 mg, tenofovir 

disoproxil 245 mg) 

ORAL CONTRACEPTIVES 
Norgestimate/Ethinyl 
oestradiol/Tenofovir disoproxil 

Norgestimate: 
AUC: ↓ 4% (↓ 32 to ↑ 34) 
Cmax: ↓ 5% (↓ 27 to ↑ 24) 
Cmin: NC 
 
Ethinyl oestradiol: 
AUC: ↓ 4% (↓ 9 to ↑ 0) 
Cmax: ↓ 6% (↓ 13 to ↑ 0) 
Cmin: ↓ 2% (↓ 9 to ↑ 6) 

No dose adjustment of 
norgestimate/ethinyl oestradiol is 
required. 

IMMUNOSUPPRESSANTS 
Tacrolimus/Tenofovir 
disoproxil/Emtricitabine 

Tacrolimus: 
AUC: ↑ 4% (↓ 3 to ↑ 11) 
Cmax: ↑ 3% (↓ 3 to ↑ 9) 
Cmin: NC 
Emtricitabine: 
AUC: ↓ 5% (↓ 9 to ↓ 1) 
Cmax: ↓ 11% (↓ 17 to ↓ 5) 
Cmin: NC 
 
Tenofovir: 
AUC: ↑ 6% (↓ 1 to ↑ 13) 
Cmax: ↑13% (↑ 1 to ↑ 27) 
Cmin: NC 

No dose adjustment of tacrolimus 
is required. 

NARCOTIC ANALGESICS 
Methadone/Tenofovir disoproxil  Methadone: 

AUC: ↑ 5% (↓ 2 to ↑ 13) 
Cmax: ↑ 5% (↓ 3 to ↑ 14) 
Cmin: NC 

No dose adjustment of methadone 
is required. 

NC = not calculated. 
N/A = not applicable. 
1 Data generated from simultaneous dosing with ledipasvir/sofosbuvir.  Staggered administration (12 hours apart) provided 
similar results. 
2 The predominant circulating metabolite of sofosbuvir. 
3 Study conducted with additional voxilaprevir 100 mg to achieve voxilaprevir exposures expected in HCV-infected patients. 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
 
A large amount of data on pregnant women (more than 1,000 pregnancy outcomes) indicate no 
malformations or foetal/neonatal toxicity associated with emtricitabine and tenofovir disoproxil.  
Animal studies on emtricitabine and tenofovir disoproxil do not indicate reproductive toxicity (see 
section 5.3).  Therefore the use of Truvada may be considered during pregnancy, if necessary. 
 
Breast-feeding 
 
Emtricitabine and tenofovir have been shown to be excreted in human milk.  There is insufficient 
information on the effects of emtricitabine and tenofovir in newborns/infants.  Therefore Truvada 
should not be used during breast-feeding. 
 
As a general rule, it is recommended that HIV infected women do not breast-feed their infants under 
any circumstances in order to avoid transmission of HIV to the infant. 
 



21 

Fertility 
 
No human data on the effect of Truvada are available.  Animal studies do not indicate harmful effects 
of emtricitabine or tenofovir disoproxil on fertility. 
 
4.7 Effects on ability to drive and use machines 
 
No studies on the effects on the ability to drive and use machines have been performed.  However, 
individuals should be informed that dizziness has been reported during treatment with both 
emtricitabine and tenofovir disoproxil. 
 
4.8 Undesirable effects 
 
Summary of the safety profile 
 
HIV-1 infection: The most frequently reported adverse reactions considered possibly or probably 
related to emtricitabine and/or tenofovir disoproxil were nausea (12%) and diarrhoea (7%) in an 
open-label randomised clinical study in adults (GS-01-934, see section 5.1).  The safety profile of 
emtricitabine and tenofovir disoproxil in this study was consistent with the previous experience with 
these agents when each was administered with other antiretroviral agents. 
 
Pre-exposure prophylaxis: No new adverse reactions to Truvada were identified from two randomised 
placebo-controlled studies (iPrEx, Partners PrEP) in which 2,830 HIV-1 uninfected adults received 
Truvada once daily for pre-exposure prophylaxis.  Patients were followed for a median of 71 weeks 
and 87 weeks, respectively.  The most frequent adverse reaction reported in the Truvada group in the 
iPrEx study was headache (1%). 
 
Tabulated summary of adverse reactions 
 
The adverse reactions considered at least possibly related to treatment with the components of Truvada 
from clinical study and post-marketing experience in HIV-1 infected patients are listed in Table 3, 
below, by body system organ class and frequency.  Within each frequency grouping, undesirable 
effects are presented in order of decreasing seriousness.  Frequencies are defined as very common 
(≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100) or rare (≥ 1/10,000 to 
< 1/1,000). 
 
Table 3: Tabulated summary of adverse reactions associated with the individual components of 
Truvada based on clinical study and post-marketing experience 
 
Frequency Emtricitabine Tenofovir disoproxil  
Blood and lymphatic system disorders: 
Common: neutropenia  
Uncommon: anaemia2  
Immune system disorders: 
Common: allergic reaction  
Metabolism and nutrition disorders: 
Very common:  hypophosphataemia1 
Common: hyperglycaemia, hypertriglyceridaemia  
Uncommon:  hypokalaemia1 
Rare:  lactic acidosis 
Psychiatric disorders: 
Common: insomnia, abnormal dreams   
Nervous system disorders: 
Very common: headache dizziness 
Common: dizziness headache 



22 

Frequency Emtricitabine Tenofovir disoproxil  
Gastrointestinal disorders: 
Very common: diarrhoea, nausea diarrhoea, vomiting, nausea 

Common: 

elevated amylase including elevated 
pancreatic amylase, elevated serum 
lipase, vomiting, abdominal pain, 
dyspepsia  

abdominal pain, abdominal distension, 
flatulence 

Uncommon:  pancreatitis 
Hepatobiliary disorders: 

Common: 

elevated serum aspartate 
aminotransferase (AST) and/or 
elevated serum alanine 
aminotransferase (ALT), 
hyperbilirubinaemia 

increased transaminases 

Rare:  hepatic steatosis, hepatitis 
Skin and subcutaneous tissue disorders: 
Very common:  rash 

Common: 

vesiculobullous rash,  
pustular rash, maculopapular rash, 
rash, pruritus, urticaria, skin 
discolouration (increased 
pigmentation)2 

 

Uncommon: angioedema3  
Rare:  angioedema 
Musculoskeletal and connective tissue disorders: 
Very common: elevated creatine kinase  
Uncommon:  rhabdomyolysis1, muscular weakness1 

Rare: 
 osteomalacia (manifested as bone pain 

and infrequently contributing to 
fractures)1,3, myopathy1 

Renal and urinary disorders: 

Uncommon: 
 increased creatinine, proteinuria, 

proximal renal tubulopathy including 
Fanconi syndrome 

Rare: 

 renal failure (acute and chronic), acute 
tubular necrosis, nephritis (including 
acute interstitial nephritis)3, 
nephrogenic diabetes insipidus 

General disorders and administration site conditions: 
Very common:  asthenia 
Common: pain, asthenia  
1 This adverse reaction may occur as a consequence of proximal renal tubulopathy.  It is not considered to be causally 
associated with tenofovir disoproxil in the absence of this condition. 
2 Anaemia was common and skin discolouration (increased pigmentation) was very common when emtricitabine was 
administered to paediatric patients. 
3 This adverse reaction was identified through post-marketing surveillance but not observed in randomised controlled clinical 
studies in adults or paediatric HIV clinical studies for emtricitabine or in randomised controlled clinical studies or the 
tenofovir disoproxil expanded access program for tenofovir disoproxil.  The frequency category was estimated from a 
statistical calculation based on the total number of patients exposed to emtricitabine in randomised controlled clinical studies 
(n = 1,563) or tenofovir disoproxil in randomised controlled clinical studies and the expanded access program (n = 7,319). 
 
Description of selected adverse reactions 
 
Renal impairment: As Truvada may cause renal damage monitoring of renal function is recommended 
(see section 4.4).  Proximal renal tubulopathy generally resolved or improved after tenofovir 
disoproxil discontinuation.  However, in some HIV-1 infected patients, declines in creatinine 
clearance did not completely resolve despite tenofovir disoproxil discontinuation.  Patients at risk of 
renal impairment (such as patients with baseline renal risk factors, advanced HIV disease, or patients 
receiving concomitant nephrotoxic medications) are at increased risk of experiencing incomplete 
recovery of renal function despite tenofovir disoproxil discontinuation (see section 4.4). 
 



23 

Interaction with didanosine: Co-administration of tenofovir disoproxil and didanosine is not 
recommended as it results in a 40-60% increase in systemic exposure to didanosine that may increase 
the risk of didanosine-related adverse reactions (see section 4.5).  Rarely, pancreatitis and lactic 
acidosis, sometimes fatal, have been reported. 
 
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). 
 
Paediatric population 
 
Assessment of adverse reactions related to emtricitabine is based on experience in three paediatric 
studies (n = 169) where treatment-naïve (n = 123) and treatment-experienced (n = 46) paediatric HIV 
infected patients aged 4 months to 18 years were treated with emtricitabine in combination with other 
antiretroviral agents.  In addition to the adverse reactions reported in adults, anaemia (9.5%) and skin 
discolouration (31.8%) occurred more frequently in clinical trials in paediatric patients than in adults 
(see section 4.8, Tabulated summary of adverse reactions). 
 
Assessment of adverse reactions related to tenofovir disoproxil is based on two randomised trials 
(studies GS-US 104-0321 and GS-US-104-0352) in 184 HIV-1 infected paediatric patients (aged 2 to 
< 18 years) who received treatment with tenofovir disoproxil (n = 93) or placebo/active comparator 
(n = 91) in combination with other antiretroviral agents for 48 weeks (see section 5.1). The adverse 
reactions observed in paediatric patients who received treatment with tenofovir disoproxil were 
consistent with those observed in clinical studies of tenofovir disoproxil in adults (see section 4.8 
Tabulated summary of adverse reactions and 5.1). 
 
Reductions in BMD have been reported in paediatric patients. In HIV-1 infected adolescents (aged 12 
to < 18 years), the BMD Z-scores observed in subjects who received tenofovir disoproxil were lower 
than those observed in subjects who received placebo. In HIV-1 infected children (aged 2 to 15 years), 
the BMD Z-scores observed in subjects who switched to tenofovir disoproxil were lower than those 
observed in subjects who remained on their stavudine- or zidovudine-containing regimen (see 
sections 4.4 and 5.1). 
 
In study GS-US-104-0352, 89 HIV-1 infected paediatric patients with a median age of 7 years (range 
2 to 15 years) were exposed to tenofovir disoproxil for a median of 331 weeks. Eight of the 89 patients 
(9.0%) discontinued study drug due to renal adverse events.  Five subjects (5.6%) had laboratory 
findings clinically consistent with proximal renal tubulopathy, 4 of whom discontinued tenofovir 
disoproxil therapy. Seven patients had estimated glomerular filtration rate (GFR) values between 70 
and 90 mL/min/1.73 m2. Among them, 3 patients experienced a clinically meaningful decline in 
estimated GFR during therapy which improved after discontinuation of tenofovir disoproxil. 
 
Other special populations 
 
Individuals with renal impairment: Since tenofovir disoproxil can cause renal toxicity, close 
monitoring of renal function is recommended in any adults with renal impairment receiving Truvada 
(see sections 4.2, 4.4 and 5.2). The use of Truvada is not recommended in individuals under the age of 
18 years with renal impairment (see sections 4.2 and 4.4). 
 



24 

HIV/HBV or HCV co-infected patients: The adverse reaction profile of emtricitabine and tenofovir 
disoproxil in a limited number of HIV-infected patients in study GS-01-934 who were co-infected 
with HBV (n = 13) or HCV (n = 26) was similar to that observed in patients infected with HIV 
without co-infection.  However, as would be expected in this patient population, elevations in AST 
and ALT occurred more frequently than in the general HIV infected population. 
 
Exacerbations of hepatitis after discontinuation of treatment: In HBV infected patients, clinical and 
laboratory evidence of hepatitis have occurred after discontinuation of treatment (see section 4.4). 
 
Reporting of suspected adverse reactions 
 
Reporting suspected adverse reactions after authorisation of the medicinal product is important.  
It allows continued monitoring of the benefit/risk balance of the medicinal product.  Healthcare 
professionals are asked to report any suspected adverse reactions via the national reporting system 
listed in Appendix V. 
 
4.9 Overdose 
 
If overdose occurs the individual must be monitored for evidence of toxicity (see section 4.8), and 
standard supportive treatment applied as necessary. 
 
Up to 30% of the emtricitabine dose and approximately 10% of the tenofovir dose can be removed by 
haemodialysis.  It is not known whether emtricitabine or tenofovir can be removed by peritoneal 
dialysis. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: Antiviral for systemic use; antivirals for treatment of HIV infections, 
combinations.  ATC code: J05AR03 
 
Mechanism of action  
 
Emtricitabine is a nucleoside analogue of cytidine.  Tenofovir disoproxil is converted in vivo to 
tenofovir, a nucleoside monophosphate (nucleotide) analogue of adenosine monophosphate.  Both 
emtricitabine and tenofovir have activity that is specific to human immunodeficiency virus (HIV-1 and 
HIV-2) and hepatitis B virus. 
 
Emtricitabine and tenofovir are phosphorylated by cellular enzymes to form emtricitabine triphosphate 
and tenofovir diphosphate, respectively.  In vitro studies have shown that both emtricitabine and 
tenofovir can be fully phosphorylated when combined together in cells.  Emtricitabine triphosphate 
and tenofovir diphosphate competitively inhibit HIV-1 reverse transcriptase, resulting in DNA chain 
termination. 
 
Both emtricitabine triphosphate and tenofovir diphosphate are weak inhibitors of mammalian DNA 
polymerases and there was no evidence of toxicity to mitochondria in vitro and in vivo. 
 
Antiviral activity in vitro  
 
Synergistic antiviral activity was observed with the combination of emtricitabine and tenofovir 
in vitro.  Additive to synergistic effects were observed in combination studies with protease inhibitors, 
and with nucleoside and non-nucleoside analogue inhibitors of HIV reverse transcriptase. 
 

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


25 

Resistance 
 
In vitro: Resistance has been seen in vitro and in some HIV-1 infected patients due to the development 
of the M184V/I mutation with emtricitabine or the K65R mutation with tenofovir.  
Emtricitabine-resistant viruses with the M184V/I mutation were cross-resistant to lamivudine, but 
retained sensitivity to didanosine, stavudine, tenofovir and zidovudine.  The K65R mutation can also 
be selected by abacavir or didanosine and results in reduced susceptibility to these agents plus 
lamivudine, emtricitabine and tenofovir.  Tenofovir disoproxil should be avoided in patients with 
HIV-1 harbouring the K65R mutation.  In addition, a K70E substitution in HIV-1 reverse transcriptase 
has been selected by tenofovir and results in low-level reduced susceptibility to abacavir, 
emtricitabine, lamivudine and tenofovir.  HIV-1 expressing three or more thymidine analogue 
associated mutations (TAMs) that included either the M41L or L210W reverse transcriptase mutation 
showed reduced susceptibility to tenofovir disoproxil. 
 
In vivo - treatment of HIV-1: In an open-label randomised clinical study (GS-01-934) in 
antiretroviral-naïve patients, genotyping was performed on plasma HIV-1 isolates from all patients 
with confirmed HIV RNA > 400 copies/mL at weeks 48, 96 or 144 or at the time of early study drug 
discontinuation.  As of week 144: 
 
• The M184V/I mutation developed in 2/19 (10.5%) isolates analysed from patients in the 

emtricitabine/tenofovir disoproxil/efavirenz group and in 10/29 (34.5%) isolates analysed from 
the lamivudine/zidovudine/efavirenz group (p-value < 0.05, Fisher’s Exact test comparing the 
emtricitabine+tenofovir disoproxil group to the lamivudine/zidovudine group among all 
patients).  

• No virus analysed contained the K65R or K70E mutation. 
• Genotypic resistance to efavirenz, predominantly the K103N mutation, developed in virus from 

13/19 (68%) patients in the emtricitabine/tenofovir disoproxil/efavirenz group and in virus from 
21/29 (72%) patients in the comparative group. 

 
In vivo -pre-exposure prophylaxis: Plasma samples from 2 clinical studies of HIV-1 uninfected 
subjects, iPrEx and Partners PrEP, were analysed for 4 HIV-1 variants expressing amino acid 
substitutions (i.e. K65R, K70E, M184V, and M184I) that potentially confer resistance to tenofovir or 
emtricitabine.  In the iPrEx clinical study, no HIV-1 variants expressing K65R, K70E, M184V, or 
M184I were detected at the time of seroconversion among subjects who became infected with HIV-1 
after enrollment in the study.  In 3 of 10 subjects who had acute HIV infection at study enrollment, 
M184I and M184V mutations were detected in the HIV of 2 of 2 subjects in the Truvada group and 1 
of 8 subjects in the placebo group. 
 
In the Partners PrEP clinical study, no HIV-1 variants expressing K65R, K70E, M184V, or M184I 
were detected at the time of seroconversion among subjects who became infected with HIV-1 during 
the study.  In 2 of 14 subjects who had acute HIV infection at study enrollment, the K65R mutation 
was detected in the HIV of 1 of 5 subjects in the tenofovir disoproxil 245 mg group and the M184V 
mutation (associated with resistance to emtricitabine) was detected in the HIV of 1 of 3 subjects in the 
Truvada group. 
 
Clinical data  
 
Treatment of HIV-1 infection: In an open-label randomised clinical study (GS-01-934), 
antiretroviral-naïve HIV-1 infected adult patients received either a once daily regimen of 
emtricitabine, tenofovir disoproxil and efavirenz (n = 255) or a fixed combination of lamivudine and 
zidovudine administered twice daily and efavirenz once daily (n = 254).  Patients in the emtricitabine 
and tenofovir disoproxil group were given Truvada and efavirenz from week 96 to week 144.  At 
baseline the randomised groups had similar median plasma HIV-1 RNA (5.02 and 
5.00 log10 copies/mL) and CD4 counts (233 and 241 cells/mm3).  The primary efficacy endpoint for 
this study was the achievement and maintenance of confirmed HIV-1 RNA concentrations 
< 400 copies/mL over 48 weeks.  Secondary efficacy analyses over 144 weeks included the proportion 



26 

of patients with HIV-1 RNA concentrations < 400 or < 50 copies/mL, and change from baseline in 
CD4 cell count. 
 
The 48-week primary endpoint data showed that the combination of emtricitabine, tenofovir disoproxil 
and efavirenz provided superior antiviral efficacy as compared with the fixed combination of 
lamivudine and zidovudine with efavirenz as shown in Table 4.  The 144 week secondary endpoint 
data are also presented in Table 4. 
 
Table 4: 48- and 144-week efficacy data from study GS-01-934 in which emtricitabine, tenofovir 
disoproxil and efavirenz were administered to antiretroviral-naïve patients with HIV-1 infection 
 

 GS-01-934 
Treatment for 48 weeks 

GS-01-934 
Treatment for 144 weeks 

 Emtricitabine+ 
tenofovir 

disoproxil+efavirenz 

Lamivudine+ 
zidovudine+ 

efavirenz 

Emtricitabine+ 
tenofovir 

disoproxil+efavirenz* 

Lamivudine+ 
zidovudine+ 

efavirenz 
HIV-1 RNA 
< 400 copies/mL (TLOVR) 

84% (206/244) 73% (177/243) 
 

71% (161/227) 58% (133/229) 

p-value 0.002** 0.004** 
% difference (95%CI) 11% (4% to 19%) 13% (4% to 22%) 
HIV-1 RNA 
< 50 copies/mL (TLOVR) 

80% (194/244) 70% (171/243) 
 

64% (146/227) 56% (130/231) 

p-value 0.021** 0.082** 
% difference (95%CI) 9% (2% to 17%) 8% (-1% to 17%) 
Mean change from 
baseline in CD4 cell count 
(cells/mm3) 

+190 +158 +312 +271 

p-value 0.002a 0.089a 
Difference (95%CI) 32 (9 to 55) 41 (4 to 79) 
* Patients receiving emtricitabine, tenofovir disoproxil and efavirenz were given Truvada plus efavirenz from week 96 to 

144. 
** The p-value based on the Cochran-Mantel-Haenszel Test stratified for baseline CD4 cell count 
TLOVR = Time to Loss of Virologic Response 
a: Van Elteren Test 
 
In a randomised clinical study (M02-418), 190 antiretroviral-naïve adults were treated once daily with 
emtricitabine and tenofovir disoproxil in combination with lopinavir/ritonavir given once or twice 
daily.  At 48 weeks, 70% and 64% of patients demonstrated HIV-1 RNA < 50 copies/mL with the 
once and twice daily regimens of lopinavir/ritonavir, respectively.  The mean changes in CD4 cell 
count from baseline were +185 cells/mm3 and +196 cells/mm3, respectively. 
 
Limited clinical experience in patients co-infected with HIV and HBV suggests that treatment with 
emtricitabine or tenofovir disoproxil in antiretroviral combination therapy to control HIV infection 
results in a reduction in HBV DNA (3 log10 reduction or 4 to 5 log10 reduction, respectively) (see 
section 4.4). 
 
Pre-exposure prophylaxis: The iPrEx study (CO-US-104-0288) evaluated Truvada or placebo in 
2,499 HIV-uninfected men (or transgender women) who have sex with men and who were considered 
at high risk for HIV infection.  Subjects were followed for 4,237 person-years.  Baseline 
characteristics are summarised in Table 5. 
 



27 

Table 5: Study population from study CO-US-104-0288 (iPrEx) 
 

 Placebo 
(n = 1248) 

Truvada 
(n = 1251) 

Age (Yrs), Mean (SD)   27 (8.5) 27 (8.6) 
Race, N (%) 

Black/African American 97 (8) 117 (9) 
White 208 (17) 223 (18) 
Mixed/Other 878 (70) 849 (68) 
Asian 65 (5) 62 (5) 

Hispanic/Latino Ethnicity, N (%) 906 (73) 900 (72) 
Sexual Risk Factors at Screening 

Number of Partners Previous 12 Weeks, Mean (SD)   18 (43) 18 (35) 
URAI Previous 12 Weeks, N (%) 753 (60) 732 (59) 
URAI with HIV+ (or unknown status) Partner Previous 6 Mos, N (%) 1009 (81) 992 (79) 
Involved in Transactional Sex Last 6 Month, N (%)   510 (41) 517 (41) 
Known HIV+ Partner Last 6 Months, N (%) 32 (3) 23 (2) 
Syphilis Seroreactivity, N (%) 162/1239 (13) 164/1240 (13) 
Serum Herpes Simplex Virus Type 2 Infection, N (%) 430/1243 (35) 458/1241 (37) 
Urine Leukocyte Esterase Positive, N (%)  22 (2) 23 (2) 

URAI = unprotected receptive anal intercourse 
 
The incidences of HIV seroconversion overall and in the subset reporting unprotected receptive anal 
intercourse are shown in Table 6.  Efficacy was strongly correlated with adherence as assessed by 
detection of plasma or intracellular drug levels in a case-control study (Table 7).   
 
Table 6: Efficacy in study CO-US-104-0288 (iPrEx) 
 

 Placebo Truvada P-valuea, b 
mITT Analysis 
Seroconversions / N  83 / 1217 48 / 1224 0.002 Relative Risk Reduction (95% CI)b 42% (18%, 60%) 
URAI Within 12 Weeks Prior to Screening, mITT Analysis 
Seroconversions / N  72 / 753 34 / 732 0.0349 Relative Risk Reduction (95% CI)b 52% (28%, 68%) 
a P-values by logrank test.  P-values for URAI refer to the null hypothesis that efficacy differed between subgroup strata 
(URAI, no URAI). 
b Relative risk reduction calculated for mITT based on incident seroconversion, ie, occurring post-baseline through first 
post-treatment visit (approximately 1 month after last study drug dispensation). 
 
Table 7: Efficacy and adherence in study CO-US-104-0288 (iPrEx, matched case-control 
analysis)  
 

Cohort 
Drug 

Detected 
Drug Not 
Detected 

Relative Risk Reduction 
(2-sided 95% CI)a 

HIV-Positive Subjects  4 (8%) 44 (92%) 94% (78%, 99%) 
HIV-Negative Matched Control Subjects 63 (44%) 81 (56%) — 
a Relative risk reduction calculated on incident (post-baseline) seroconversion from the double-blind treatment period and 
through the 8-week follow-up period.  Only samples from subjects randomized to Truvada were evaluated for detectable 
plasma or intracellular tenofovir disoproxil-DP levels. 
 
The Partners PrEP clinical study (CO-US-104-0380) evaluated Truvada, tenofovir disoproxil 245 mg, 
or placebo in 4,758 HIV-uninfected subjects from Kenya or Uganda in serodiscordant heterosexual 
couples.  Subjects were followed for 7,830 person-years.  Baseline characteristics are summarised in 
Table 8. 
 



28 

Table 8: Study population from study CO-US-104-0380 (Partners PrEP) 
 
 

Placebo 
(n = 1584) 

Tenofovir 
disoproxil 

245 mg  
(n = 1584) 

Truvada 
(n = 1579) 

Age (Yrs), Median (Q1, Q3)   34 (28, 40) 33 (28, 39) 33 (28, 40) 
Gender, N (%) 

Male 963 (61) 986 (62) 1013 (64) 
Female 621 (39) 598 (38) 566 (36) 

Key Couple Characteristics, N (%) or Median (Q1, Q3)  
Married to study partner  1552 (98) 1543 (97) 1540 (98) 
Years living with study partner 7.1 (3.0, 14.0) 7.0 (3.0, 13.5) 7.1 (3.0, 14.0) 
Years aware of discordant status 0.4 (0.1, 2.0) 0.5 (0.1, 2.0) 0.4 (0.1, 2.0) 

 
The incidence of HIV seroconversion is shown in Table 9.  The rate of HIV-1 seroconversion in males 
was 0.24/100 person-years of Truvada exposure and the rate of HIV-1 seroconversion in females was 
0.95/100 person-years of Truvada exposure.  Efficacy was strongly correlated with adherence as 
assessed by detection of plasma or intracellular drug levels and was higher among substudy 
participants who received active adherence counselling and as show in Table 10. 
 
Table 9: Efficacy in study CO-US-104-0380 (Partners PrEP) 
 

 Placebo 
Tenofovir disoproxil 

245 mg  Truvada 
Seroconversions / Na 52 / 1578 17 / 1579 13 / 1576 
Incidence per 100 person-years (95% CI) 1.99 (1.49, 2.62) 0.65 (0.38, 1.05) 0.50 (0.27, 0.85) 

Relative Risk Reduction (95% CI) — 67% (44%, 81%) 75% (55%, 87%)  
a Relative risk reduction calculated for mITT cohort based on incident (post-baseline) seroconversion.  Comparisons for 
active study groups are made versus placebo. 

 
Table 10: Efficacy and adherence in study CO-US-104-0380 (Partners PrEP) 
 

Study Drug 
Quantification 

Number with Tenofovir Detected/Total 
Samples (%) 

Risk Estimate for HIV-1 Protection:  
Detection Versus No Detection 

of Tenofovir 

Case Cohort 
Relative Risk 

Reduction (95% CI) p-value 
FTC/tenofovir 
disoproxil Groupa 3 / 12 (25%) 375 / 465 (81%) 90% (56%, 98%) 0.002 

Tenofovir disoproxil 
Groupa 6 / 17 (35%) 363 / 437 (83%) 86% (67%, 95%) < 0.001 

Adherence Substudy 

Adherence Substudy Participantsb   

Placebo 
Tenofovir disoproxil 

245 mg+Truvada 
Relative Risk 

Reduction (95% CI) p-value 

Seroconversions / Nb 14 / 404 (3.5%) 0 / 745 (0%) 100% (87%, 100%) < 0.001 
a ‘Case’ = HIV seroconverter; ‘Cohort’ = 100 randomly selected subjects from each of the tenofovir disoproxil 245 mg and 
Truvada groups.  Only Case or Cohort samples from subjects randomised to either tenofovir disoproxil 245 mg or Truvada 
were evaluated for detectable plasma tenofovir levels. 
b Substudy participants received active adherence monitoring, e.g. unannounced home visits and pill counts, and counselling 
to improve compliance with study drug. 
 
Paediatric population 
 
The safety and efficacy of Truvada in children under the age of 12 years have not been established.  
 
Treatment of HIV-1 infection in the paediatric population 
There are no clinical studies conducted with Truvada in the paediatric population with HIV-1 
infection.  



29 

 
Clinical efficacy and safety of Truvada was established from studies conducted with emtricitabine and 
tenofovir disoproxil when given as single agents. 
 
Studies with emtricitabine 
In infants and children older than 4 months, the majority of patients taking emtricitabine achieved or 
maintained complete suppression of plasma HIV-1 RNA through 48 weeks (89% achieved ≤ 400 
copies/mL and 77% achieved ≤ 50 copies/mL).  
 
Studies with tenofovir disoproxil  
In study GS-US-104-0321, 87 HIV-1 infected treatment-experienced patients 12 to < 18 years of age 
were treated with tenofovir disoproxil (n = 45) or placebo (n = 42) in combination with an optimised 
background regimen (OBR) for 48 weeks. Due to limitations of the study, a benefit of tenofovir 
disoproxil over placebo was not demonstrated based on plasma HIV-1 RNA levels at week 24. 
However, a benefit is expected for the adolescent population based on extrapolation of adult data and 
comparative pharmacokinetic data (see section 5.2). 
 
In patients who received treatment with tenofovir disoproxil or placebo, mean lumbar spine BMD 
Z-score was -1.004 and -0.809, and mean total body BMD Z-score was -0.866 and -0.584, 
respectively, at baseline. Mean changes at week 48 (end of double-blind phase) were -0.215 and -
0.165 in lumbar spine BMD Z-score, and -0.254 and -0.179 in total body BMD Z-score for the 
tenofovir disoproxil and placebo groups, respectively. The mean rate of BMD gain was less in the 
tenofovir disoproxil group compared to the placebo group. At week 48, six adolescents in the 
tenofovir disoproxil group and one adolescent in the placebo group had significant lumbar spine BMD 
loss (defined as > 4% loss). Among 28 patients receiving 96 weeks of treatment with tenofovir 
disoproxil, BMD Z-scores declined by -0.341 for lumbar spine and -0.458 for total body. 
 
In study GS-US-104-0352, 97 treatment-experienced patients 2 to < 12 years of age with stable, 
virologic suppression on stavudine- or zidovudine-containing regimens were randomised to either 
replace stavudine or zidovudine with tenofovir disoproxil (n = 48) or continue on their original 
regimen (n = 49) for 48 weeks. At week 48, 83% of patients in the tenofovir disoproxil treatment 
group and 92% of patients in the stavudine or zidovudine treatment group had HIV-1 RNA 
concentrations < 400 copies/mL. The difference in the proportion of patients who maintained 
< 400 copies/mL at week 48 was mainly influenced by the higher number of discontinuations in the 
tenofovir disoproxil treatment group. When missing data were excluded, 91% of patients in the 
tenofovir disoproxil treatment group and 94% of patients in the stavudine or zidovudine treatment 
group had HIV-1 RNA concentrations < 400 copies/mL at week 48.  
 
Reductions in BMD have been reported in paediatric patients. In patients who received treatment with 
tenofovir disoproxil, or stavudine or zidovudine, mean lumbar spine BMD Z-score was -1.034 and 
-0.498, and mean total body BMD Z-score was -0.471 and -0.386, respectively, at baseline. Mean 
changes at week 48 (end of randomised phase) were 0.032 and 0.087 in lumbar spine BMD Z-score, 
and -0.184 and -0.027 in total body BMD Z-score for the tenofovir disoproxil and stavudine or 
zidovudine groups, respectively. The mean rate of lumbar spine bone gain at week 48 was similar 
between the tenofovir disoproxil treatment group and the stavudine or zidovudine treatment group. 
Total body bone gain was less in the tenofovir disoproxil treatment group compared to the stavudine 
or zidovudine treatment group. One tenofovir disoproxil treated subject and no stavudine or 
zidovudine treated subjects experienced significant (> 4%) lumbar spine BMD loss at week 48. BMD 
Z-scores declined by -0.012 for lumbar spine and by -0.338 for total body in the 64 subjects who were 
treated with tenofovir disoproxil for 96 weeks. BMD Z-scores were not adjusted for height and 
weight.  
 
In study GS-US-104-0352, 8 out of 89 paediatric patients (9.0%) exposed to tenofovir disoproxil 
discontinued study drug due to renal adverse events.  Five subjects (5.6%) had laboratory findings 
clinically consistent with proximal renal tubulopathy, 4 of whom discontinued tenofovir disoproxil 
therapy (median tenofovir disoproxil exposure 331 weeks). 
 



30 

Pre-exposure prophylaxis in the paediatric population 
The efficacy and safety of Truvada for pre-exposure prophylaxis in adolescents who adhere to daily 
dosing is expected to be similar to that in adults at the same level of adherence.  The potential renal 
and bone effects with long-term use of Truvada for pre-exposure prophylaxis in adolescents are 
unknown (see section 4.4). 
 
5.2 Pharmacokinetic properties 
 
Absorption 
 
The bioequivalence of one Truvada film-coated tablet with one emtricitabine 200 mg hard capsule and 
one tenofovir disoproxil245 mg film-coated tablet was established following single dose 
administration to fasting healthy subjects.  Following oral administration of Truvada to healthy 
subjects, emtricitabine and tenofovir disoproxil are rapidly absorbed and tenofovir disoproxil is 
converted to tenofovir.  Maximum emtricitabine and tenofovir concentrations are observed in serum 
within 0.5 to 3.0 h of dosing in the fasted state.  Administration of Truvada with food resulted in a 
delay of approximately three quarters of an hour in reaching maximum tenofovir concentrations and 
increases in tenofovir AUC and Cmax of approximately 35% and 15%, respectively, when administered 
with a high fat or light meal, compared to administration in the fasted state.  In order to optimise the 
absorption of tenofovir, it is recommended that Truvada should preferably be taken with food. 
 
Distribution 
 
Following intravenous administration the volume of distribution of emtricitabine and tenofovir was 
approximately 1.4  L/kg and 800 mL/kg, respectively.  After oral administration of emtricitabine or 
tenofovir disoproxil, emtricitabine and tenofovir are widely distributed throughout the body.  In vitro 
binding of emtricitabine to human plasma proteins was < 4% and independent of concentration over 
the range of 0.02 to 200 µg/mL.  In vitro protein binding of tenofovir to plasma or serum protein was 
less than 0.7 and 7.2%, respectively, over the tenofovir concentration range 0.01 to 25 µg/mL. 
 
Biotransformation 
 
There is limited metabolism of emtricitabine.  The biotransformation of emtricitabine includes 
oxidation of the thiol moiety to form the 3'-sulphoxide diastereomers (approximately 9% of dose) and 
conjugation with glucuronic acid to form 2'-O-glucuronide (approximately 4% of dose).  In vitro 
studies have determined that neither tenofovir disoproxil nor tenofovir are substrates for the CYP450 
enzymes.  Neither emtricitabine nor tenofovir inhibited in vitro drug metabolism mediated by any of 
the major human CYP450 isoforms involved in drug biotransformation.  Also, emtricitabine did not 
inhibit uridine-5'-diphosphoglucuronyl transferase, the enzyme responsible for glucuronidation. 
 
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. 
 
Tenofovir is primarily excreted by the kidney by both filtration and an active tubular transport system 
with approximately 70-80% of the dose excreted unchanged in urine following intravenous 
administration.  The apparent clearance of tenofovir averaged approximately 307 mL/min.  Renal 
clearance has been estimated to be approximately 210 mL/min, which is in excess of the glomerular 
filtration rate.  This indicates that active tubular secretion is an important part of the elimination of 
tenofovir.  Following oral administration, the elimination half-life of tenofovir is approximately 12 to 
18 hours. 
 



31 

Elderly 
 
Pharmacokinetic studies have not been performed with emtricitabine or tenofovir (administered as 
tenofovir disoproxil) in the elderly (over 65 years of age). 
 
Gender 
 
Emtricitabine and tenofovir pharmacokinetics are similar in male and female patients. 
 
Ethnicity 
 
No clinically important pharmacokinetic difference due to ethnicity has been identified for 
emtricitabine.  The pharmacokinetics of tenofovir (administered as tenofovir disoproxil) have not been 
specifically studied in different ethnic groups. 
 
Paediatric population 
 
Pharmacokinetic studies have not been performed with Truvada in children and adolescents (under 
18 years of age).  Steady-state pharmacokinetics of tenofovir were evaluated in 8 HIV-1 infected 
adolescent patients (aged 12 to < 18 years) with body weight ≥ 35 kg and in 23 HIV-1 infected 
children aged 2 to < 12 years.  Tenofovir exposure achieved in these paediatric patients receiving oral 
daily doses of tenofovir disoproxil 245 mg or 6.5 mg/kg body weight tenofovir disoproxil up to a 
maximum dose of 245 mg was similar to exposures achieved in adults receiving once-daily doses of 
tenofovir disoproxil 245 mg.  Pharmacokinetic studies have not been performed with tenofovir 
disoproxil in children under 2 years.  In general, the pharmacokinetics of emtricitabine in infants, 
children and adolescents (aged 4 months up to 18 years) are similar to those seen in adults. 
 
The pharmacokinetics of emtricitabine and tenofovir (administered as tenofovir disoproxil) are 
expected to be similar in HIV-1 infected and uninfected adolescents based on the similar exposures of 
emtricitabine and tenofovir in HIV-1 infected adolescents and adults, and the similar exposures of 
emtricitabine and tenofovir in HIV-1 infected and uninfected adults. 
 
Renal impairment 
 
Limited pharmacokinetic data are available for emtricitabine and tenofovir after co-administration of 
separate preparations or as Truvada in patients with renal impairment.  Pharmacokinetic parameters 
were mainly determined following administration of single doses of emtricitabine 200 mg or tenofovir 
disoproxil 245 mg to non-HIV infected subjects with varying degrees of renal impairment.  The degree 
of renal impairment was defined according to baseline creatinine clearance (CrCl) (normal renal 
function when CrCl > 80 mL/min; mild impairment with CrCl = 50-79 mL/min; moderate impairment 
with CrCl = 30-49 mL/min and severe impairment with CrCl = 10-29 mL/min). 
 
The mean (%CV) emtricitabine drug exposure increased from 12 (25%) µg•h/mL in subjects with 
normal renal function, to 20 (6%) µg•h/mL, 25 (23%) µg•h/mL and 34 (6%) µg•h/mL, in subjects with 
mild, moderate and severe renal impairment, respectively.  The mean (%CV) tenofovir drug exposure 
increased from 2,185 (12%) ng•h/mL in subjects with normal renal function, to 3,064 (30%) ng•h/mL, 
6,009 (42%) ng•h/mL and 15,985 (45%) ng•h/mL, in subjects with mild, moderate and severe renal 
impairment, respectively. 
 
The increased dose interval for Truvada in HIV-1 infected patients with moderate renal impairment is 
expected to result in higher peak plasma concentrations and lower Cmin levels as compared to patients 
with normal renal function.  In subjects with end-stage renal disease (ESRD) requiring haemodialysis, 
between dialysis drug exposures substantially increased over 72 hours to 53 (19%) µg•h/mL of 
emtricitabine, and over 48 hours to 42,857 (29%) ng•h/mL of tenofovir. 
 
A small clinical study was conducted to evaluate the safety, antiviral activity and pharmacokinetics of 
tenofovir disoproxil in combination with emtricitabine in HIV infected patients with renal impairment.  



32 

A subgroup of patients with baseline creatinine clearance between 50 and 60 mL/min, receiving once 
daily dosing, had a 2-4-fold increase in tenofovir exposure and worsening renal function. 
 
The pharmacokinetics of emtricitabine and tenofovir (administered as tenofovir disoproxil) in 
paediatric patients with renal impairment have not been studied.  No data are available to make dose 
recommendations (see sections 4.2 and 4.4). 
 
Hepatic impairment 
 
The pharmacokinetics of Truvada have not been studied in subjects with hepatic impairment. 
 
The pharmacokinetics of emtricitabine have not been studied in non-HBV infected subjects with 
varying degrees of hepatic insufficiency.  In general, emtricitabine pharmacokinetics in HBV infected 
subjects were similar to those in healthy subjects and in HIV infected patients. 
 
A single 245 mg dose of tenofovir disoproxil was administered to non-HIV infected subjects with 
varying degrees of hepatic impairment defined according to Child-Pugh-Turcotte (CPT) classification.  
Tenofovir pharmacokinetics were not substantially altered in subjects with hepatic impairment 
suggesting that no dose adjustment is required in these subjects.  The mean (%CV) tenofovir Cmax and 
AUC0-∞ values were 223 (34.8%) ng/mL and 2,050 (50.8%) ng•h/mL, respectively, in normal subjects 
compared with 289 (46.0%) ng/mL and 2,310 (43.5%) ng•h/mL in subjects with moderate hepatic 
impairment, and 305 (24.8%) ng/mL and 2,740 (44.0%) ng•h/mL in subjects with severe hepatic 
impairment. 
 
5.3 Preclinical safety data 
 
Emtricitabine: Non-clinical data on emtricitabine reveal no special hazard for humans based on 
conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity, carcinogenic 
potential and toxicity to reproduction and development. 
 
Tenofovir disoproxil: Non-clinical safety pharmacology studies on tenofovir disoproxil reveal no 
special hazard for humans.  Repeated dose toxicity studies in rats, dogs and monkeys at exposure 
levels greater than or equal to clinical exposure levels and with possible relevance to clinical use 
include renal and bone toxicity and a decrease in serum phosphate concentration.  Bone toxicity was 
diagnosed as osteomalacia (monkeys) and reduced BMD (rats and dogs).  The bone toxicity in young 
adult rats and dogs occurred at exposures ≥ 5-fold the exposure in paediatric or adult patients; bone 
toxicity occurred in juvenile infected monkeys at very high exposures following subcutaneous dosing 
(≥ 40-fold the exposure in patients).  Findings in the rat and monkey studies indicated that there was a 
substance-related decrease in intestinal absorption of phosphate with potential secondary reduction in 
BMD. 
 
Genotoxicity studies revealed positive results in the in vitro mouse lymphoma assay, equivocal results 
in one of the strains used in the Ames test, and weakly positive results in an UDS test in primary rat 
hepatocytes.  However, it was negative in an in vivo mouse bone marrow micronucleus assay. 
 
Oral carcinogenicity studies in rats and mice only revealed a low incidence of duodenal tumours at an 
extremely high dose in mice.  These tumours are unlikely to be of relevance to humans. 
 
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 
periand postnatal toxicity study at maternally toxic doses. 
 
Combination of emtricitabine and tenofovir disoproxil: Genotoxicity and repeated dose toxicity 
studies of one month or less with the combination of these two components found no exacerbation of 
toxicological effects compared to studies with the separate components. 
 
 



33 

6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Tablet core: 
Croscarmellose sodium 
Lactose monohydrate 
Magnesium stearate (E572) 
Microcrystalline cellulose (E460) 
Pregelatinised starch (gluten free) 
 
Film-coating: 
Glycerol triacetate (E1518) 
Hypromellose (E464) 
Indigo carmine aluminium lake (E132) 
Lactose monohydrate 
Titanium dioxide (E171) 
 
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 
 
High density polyethylene (HDPE) bottle with a polypropylene child-resistant closure containing 
30 film-coated tablets and a silica gel desiccant. 
 
The following pack sizes are available: outer cartons containing 1 bottle of 30 film-coated tablets and 
outer cartons containing 60 (2 bottles of 30) and 90 (3 bottles of 30) film-coated tablets.  Not all pack 
sizes may be marketed. 
 
6.6 Special precautions for disposal 
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Gilead Sciences Ireland UC 
Carrigtohill 
County Cork, T45 DP77 
Ireland 
 
 



34 

8. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/04/305/001 
EU/1/04/305/002 
EU/1/04/305/003 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 21 February 2005 
Date of latest renewal: 20 January 2010 
 
 
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. 



35 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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 

 



36 

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

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

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

• Additional risk minimisation measures 
 
The marketing authorisation holder (MAH) shall ensure that all physicians who are expected to 
prescribe/use Truvada in either adolescent patients for the treatment of HIV-1 infection or in adults 
and adolescents for PrEP are provided with a physician educational pack containing the Summary of 
Product Characteristics and an appropriate educational brochure, as detailed below: 
 
• HIV pediatric renal educational brochure 
• PrEP educational brochure for prescribers entitled ‘Important Safety Information for Prescribers 

About Truvada for a Pre-exposure Prophylaxis (PrEP) Indication’  
• PrEP Checklist for prescribers 



37 

• PrEP educational brochure for the individual at risk entitled ‘Important Information About 
Truvada to Reduce the Risk of getting Human Immunodeficiency Virus (HIV) Infection’ 

• PrEP reminder card 
 
HIV paediatric renal educational brochure: 
 
The HIV paediatric renal educational brochure should contain the following key messages: 
 
• That a multidisciplinary approach is recommended for the management of paediatric patients 
• That there is an increased risk of renal disease in HIV infected patients associated with tenofovir 

disoproxil fumarate-containing products such as Truvada 
• That Truvada is not recommended for use in paediatric patients with renal impairment 
• That use of Truvada should be avoided with concomitant or recent use of nephrotoxic medicinal 

products. If Truvada is used with nephrotoxic medicinal products, renal function should be 
closely monitored according to the recommended schedule 

• That paediatric patients should have their baseline renal function assessed prior to initiating 
Truvada therapy 

• The importance of regular monitoring of renal function during Truvada therapy 
• Recommended schedule for monitoring renal function considering the presence or absence of 

additional risk factors for renal impairment 
• That if serum phosphate is confirmed to be < 3.0 mg/dL (0.96 mmol/L) in any paediatric patient 

receiving tenofovir disoproxil fumarate, renal function should be re-evaluated within one week. 
If renal abnormalities are detected or suspected then consultation with a nephrologist should be 
obtained to consider interruption of Truvada treatment 

• That Truvada may cause a reduction in BMD and the effects of Truvada associated changes in 
BMD on long-term bone health and future fracture risk are currently unknown in paediatric 
patients 

• That if bone abnormalities are detected or suspected then consultation with an endocrinologist 
and/or nephrologist should be obtained 

 
PrEP educational brochure for prescribers: 
 
• Reminder of the key safety information regarding the use of Truvada for PrEP in adults and 

adolescents  
• Reminder of factors to help identify individuals at high risk of acquiring HIV-1 
• Reminder on the risk of development of HIV-1 drug resistance in undiagnosed HIV-1–Infected 

individuals 
• Provides safety information on adherence, HIV testing, renal, bone and HBV status. 
 
PrEP Checklist for prescribers: 
 
• Reminders for evaluations/counselling at the initial visit and follow-up. 

 
PrEP educational brochure for the individual at risk (to be provided by healthcare provider 
[HCP]): 
 
• Reminders on what the individual should know before and while taking Truvada to reduce the 

risk of getting HIV infection 
• Reminder on the importance of strict adherence to the recommended dosing regimen 
• Provides information on how to take Truvada 
• Provides information on the possible side effects 
• Provides information on how to store Truvada. 
 



38 

PrEP reminder card for the individual at risk (to be provided by HCP): 
 
• Reminders to adhere to the dosing schedule 
• Reminder to attend scheduled clinic visits. 

 



39 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 



40 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 
 



41 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING AND THE IMMEDIATE 
PACKAGING 
 
BOTTLE AND CARTON LABELLING 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Truvada 200 mg/245 mg film-coated tablets 
emtricitabine/tenofovir disoproxil 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each film-coated tablet contains 200 mg of emtricitabine and 245 mg of tenofovir disoproxil 
(equivalent to 300 mg of tenofovir disoproxil fumarate or 136 mg of tenofovir). 
 
 
3. LIST OF EXCIPIENTS 
 
Contains lactose monohydrate, see leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
30 film-coated tablets. 
60 (2 bottles of 30) film-coated tablets. 
90 (3 bottles of 30) film-coated tablets. 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Oral use. 
 
Read the package leaflet before 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. 
 



42 

 
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/1/04/305/001 30 film-coated tablets 
EU/1/04/305/003 60 (2 x 30) film-coated tablets 
EU/1/04/305/002 90 (3 x 30) film-coated tablets 
 
 
13. BATCH NUMBER 
 
Lot  
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Truvada [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] 
 



43 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 



44 

Package leaflet: Information for the user 
 

Truvada 200 mg/245 mg film-coated tablets 
emtricitabine/tenofovir disoproxil 

 
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 Truvada is and what it is used for 
2. What you need to know before you take Truvada 
3. How to take Truvada 
4. Possible side effects 
5. How to store Truvada 
6. Contents of the pack and other information 
 
 
1. What Truvada is and what it is used for 
 
Truvada contains two active substances, emtricitabine and tenofovir disoproxil.  Both of these 
active substances are antiretroviral medicines which are used to treat HIV infection.  Emtricitabine is 
a nucleoside reverse transcriptase inhibitor and tenofovir is a nucleotide reverse transcriptase 
inhibitor.  However, both are generally known as NRTIs and they work by interfering with the normal 
working of an enzyme (reverse transcriptase) that is essential for the virus to reproduce itself. 
 
• Truvada is used to treat Human Immunodeficiency Virus 1 (HIV-1) infection in adults  
• It is also used to treat HIV in adolescents aged 12 to less than 18 years who weigh at least 

35 kg, and who have already been treated with other HIV medicines that are no longer effective 
or have caused side effects. 
 

− Truvada should always be used combined with other medicines to treat HIV infection. 
− Truvada can be administered in place of emtricitabine and tenofovir disoproxil used 

separately at the same doses. 
 

People who are HIV positive 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 Truvada you may still develop 
infections or other illnesses associated with HIV infection. 
 
• Truvada is also used to reduce the risk of getting HIV-1 infection in adults, and 

adolescents aged 12 years to less than 18 years who weigh at least 35 kg, when taken daily, 
together with safer sex practices: 
See section 2 for a list of precautions to take against HIV infection. 

 
 



45 

2. What you need to know before you take Truvada 
 
Do not take Truvada to treat HIV or to reduce the risk of getting HIV if you are allergic to 
emtricitabine, tenofovir, tenofovir disoproxil, or any of the other ingredients of this medicine (listed in 
section 6). 
 

 If this applies to you, tell your doctor immediately. 
 
Before taking Truvada to reduce the risk of getting HIV: 
 
Truvada can only help reduce your risk of getting HIV before you are infected. 
 
• You must be HIV negative before you start to take Truvada to reduce the risk of getting 

HIV.  You must get tested to make sure that you do not already have HIV infection. Do not take 
Truvada to reduce your risk unless you are confirmed to be HIV negative.  People who do have 
HIV must take Truvada in combination with other drugs.  

 
• Many HIV tests can miss a recent infection.  If you get a flu-like illness, it could mean you 

have recently been infected with HIV. 
These may be signs of HIV infection: 
• tiredness 
• fever 
• joint or muscle aches 
• headache 
• vomiting or diarrhoea 
• rash 
• night sweats 
• enlarged lymph nodes in the neck or groin 
 Tell your doctor about any flu-like illness – either in the month before starting 

Truvada, or at any time while taking Truvada. 
 
Warnings and precautions 
 
While taking Truvada to reduce the risk of getting HIV: 
 
• Take Truvada every day to reduce your risk, not just when you think you have been at risk 

of HIV infection.  Do not miss any doses of Truvada, or stop taking it.  Missing doses may 
increase your risk of getting HIV infection. 

 
• Get tested for HIV regularly. 
 
• If you think you were infected with HIV, tell your doctor straight away.  They may want to do 

more tests to make sure you are still HIV negative. 
 
• Just taking Truvada may not stop you getting HIV. 

o Always practice safer sex.  Use condoms to reduce contact with semen, vaginal fluids, 
or blood. 

o Do not share personal items that can have blood or body fluids on them, such as 
toothbrushes and razor blades. 

o Do not share or re-use needles or other injection or drug equipment.  
o Get tested for other sexually transmitted infections such as syphilis and gonorrhoea.  These 

infections make it easier for HIV to infect you. 
 
Ask your doctor if you have any more questions about how to prevent getting HIV or spreading HIV 
to other people. 
 



46 

While taking Truvada to treat HIV or to reduce the risk of getting HIV: 
 
• Truvada may affect your kidneys.  Before and during treatment, your doctor may order blood 

tests to measure kidney function.  Tell your doctor if you have had kidney disease, or if tests 
have shown kidney problems. Truvada should not be given to adolescents with existing kidney 
problems. If you have kidney problems, your doctor may advise you to stop taking Truvada or, 
if you already have HIV, to take Truvada less frequently.  Truvada is not recommended if you 
have severe kidney disease or are on dialysis. 

 
Bone problems (sometimes resulting in fractures) may also occur due to damage to kidney 
tubule cells (see section 4, Possible side effects). 

 
• Talk to your doctor if you have a history of liver disease, including hepatitis.  Patients 

infected with HIV who also have 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 or C, your doctor will carefully consider the best treatment regimen 
for you. 

 
• Know your hepatitis B virus (HBV) infection status before starting Truvada.  If you have 

HBV, there is a serious risk of liver problems when you stop taking Truvada, whether or not 
you also have HIV.  It is important not to stop taking Truvada without talking to your doctor: 
see section 3, Do not stop taking Truvada. 

 
• Talk to your doctor if you are over 65.  Truvada has not been studied in patients over 65 years 

of age.  
 
• Talk to your doctor if you are intolerant to lactose (see Truvada contains lactose later in this 

section). 
 
Children and adolescents 
 
Truvada is not for use in children under 12 years of age. 
 
Other medicines and Truvada 
 
Do not take Truvada if you are already taking other medicines that contain the components of 
Truvada (emtricitabine and tenofovir disoproxil) or any other antiviral medicines that contain 
tenofovir alafenamide, lamivudine or adefovir dipivoxil. 
 
Taking Truvada with other medicines that can damage your kidneys: it is especially important to 
tell your doctor if you are taking any of these medicines, including 

• aminoglycosides (for bacterial infection) 
• amphotericin B (for fungal infection) 
• foscarnet (for viral infection) 
• ganciclovir (for viral infection) 
• pentamidine (for infections) 
• vancomycin (for bacterial infection) 
• interleukin-2 (to treat cancer) 
• cidofovir (for viral infection) 
• non-steroidal anti-inflammatory drugs (NSAIDs, to relieve bone or muscle pains) 

 
If you are taking another antiviral medicine called a protease inhibitor to treat HIV, your doctor may 
order blood tests to closely monitor your kidney function. 
 
It is also important to tell your doctor if you are taking ledipasvir/sofosbuvir, sofosbuvir/velpatasvir 
or sofosbuvir/velpatasvir/voxilaprevir to treat hepatitis C infection. 



47 

 
Taking Truvada with other medicines containing didanosine (for treatment of HIV infection): 
Taking Truvada with other antiviral medicines that contain didanosine can raise the levels of 
didanosine in your blood and may reduce CD4 cell counts.  Rarely, inflammation of the pancreas and 
lactic acidosis (excess lactic acid in the blood), which sometimes causes death, have been reported 
when medicines containing tenofovir disoproxil and didanosine were taken together.  Your doctor will 
carefully consider whether to treat you with combinations of tenofovir and didanosine. 
 
 Tell your doctor if you are taking any of these medicines.  Tell your doctor or pharmacist if 

you are taking, have recently taken or might take any other medicines.  
 
Truvada with food and drink 
 
• Whenever possible, Truvada should be taken with food. 
 
Pregnancy and breast-feeding 
 
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a 
baby, ask your doctor or pharmacist for advice before taking this medicine. 
 
If you have taken Truvada during your pregnancy, your doctor may request regular blood tests and 
other diagnostic tests to monitor the development of your child.  In children whose mothers took 
NRTIs during pregnancy, the benefit from the protection against HIV outweighed the risk of 
side effects. 
 
• Do not breast-feed during treatment with Truvada.  This is because the active substances in 

this medicine pass into human breast milk. 
 
• If you are a woman with HIV it is recommended that you do not breast-feed, to avoid passing 

the virus to the baby in breast milk. 
 
Driving and using machines 
 
Truvada can cause dizziness.  If you feel dizzy while taking Truvada, do not drive and do not use any 
tools or machines. 
 
Truvada 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. 
 
Truvada 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 Truvada 
 
• 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 of Truvada to treat HIV is: 
 
• Adults: one tablet each day, where possible, with food. 
 
• Adolescents aged 12 to less than 18 years who weigh at least 35 kg: one tablet each day, 

whenever possible with food.   



48 

 
The recommended dose of Truvada to reduce the risk of getting HIV is:  
 
• Adults: one tablet each day, whenever possible with food. 
• Adolescents aged 12 to less than 18 years who weigh at least 35 kg: one tablet each day, 

whenever possible with food. 
 

If you have difficulty swallowing, you can use the tip of a spoon to crush the tablet.  Then mix 
the powder with about 100 mL (half a glass) of water, orange juice or grape juice, and drink 
immediately. 

 
• Always take the dose recommended by your doctor.  This is to make sure that your medicine 

is fully effective, and to reduce the risk of developing resistance to the treatment.  Do not 
change the dose unless your doctor tells you to. 

 
• If you are being treated for HIV infection your doctor will prescribe Truvada with other 

antiretroviral medicines.  Please refer to the patient information leaflets of the other 
antiretrovirals for guidance on how to take those medicines. 

 
• If you are taking Truvada to reduce the risk of getting HIV, take Truvada every day, not just 

when you think you have been at risk of HIV infection. 
 
Ask your doctor if you have any questions about how to prevent getting HIV or prevent spreading HIV 
to other people. 
 
If you take more Truvada than you should 
 
If you accidentally take more than the recommended dose of Truvada, contact your doctor or nearest 
emergency department for advice.  Keep the tablet bottle with you so that you can easily describe what 
you have taken. 
 
If you miss a dose 
 
It is important not to miss a dose of Truvada. 
 
• If you notice within 12 hours of the time you usually take Truvada, take the tablet preferably 

with food as soon as possible.  Then take the next dose at your usual time. 
• If you notice 12 hours or more after the time you usually take Truvada, forget about the missed 

dose.  Wait and take the next dose, preferably with food, at your usual time. 
 
If you vomit less than 1 hour after taking Truvada, take another tablet.  You do not need to take 
another tablet if you were sick more than 1 hour after taking Truvada. 
 
Do not stop taking Truvada 
 
• If you take Truvada for treatment of HIV infection, stopping tablets may reduce the 

effectiveness of the anti-HIV therapy recommended by your doctor.  
 

• If you are taking Truvada to reduce the risk of getting HIV, do not stop taking Truvada or 
miss any doses. Stopping use of Truvada, or missing doses, may increase your risk of getting 
HIV infection. 

 
 Do not stop taking Truvada without contacting your doctor.  
 



49 

• If you have hepatitis B, it is especially important not to stop your Truvada 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. 
 
Possible serious side effects:  
 
• Lactic acidosis (excess lactic acid in the blood) is a rare but potentially life-threatening side 

effect.  Lactic acidosis occurs more often in women, particularly if they are overweight, and in 
people with liver disease.  The following may be signs of lactic acidosis: 
• deep rapid breathing 
• drowsiness 
• feeling sick (nausea), being sick (vomiting)  
• stomach pain 

 
 If you think you may have lactic acidosis, get medical help 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 anti-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 to treat 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, get medical help 

immediately. 
 
Possible side effects: 
 
Very common side effects  
(may affect more than 1 in 10 people) 
• diarrhoea, being sick (vomiting), feeling sick (nausea) 
• dizziness, headache 
• rash 
• feeling weak 
 
Tests may also show: 
• decreases in phosphate in the blood 



50 

• increased creatine kinase 
 
Common side effects 
(may affect up to 1 in 10 people) 
• pain, stomach pain 
• difficulty sleeping, abnormal dreams 
• problems with digestion resulting in discomfort after meals, feeling bloated, flatulence 
• rashes (including red spots or blotches sometimes with blistering and swelling of the skin), 

which may be allergic reactions, itching, changes in skin colour including darkening of the skin 
in patches 

• other allergic reactions, such as wheezing, swelling or feeling light-headed 
 
Tests may also show: 
• low white blood cell count (a reduced white blood cell count can make you more prone to 

infection) 
• increased triglycerides (fatty acids), bile or sugar in the blood 
• liver and pancreas problems 
 
Uncommon side effects 
(may affect up to 1 in 100 people) 
• pain in the abdomen (tummy) caused by inflammation of the pancreas 
• swelling of the face, lips, tongue or throat 
• anaemia (low red blood cell count) 
• breakdown of muscle, muscle pain or weakness which may occur due to damage to the kidney 

tubule cells 
 
Tests may also show: 
• decreases in potassium in the blood 
• increased creatinine in your blood 
• changes to your urine 
 
Rare side effects 
(may affect up to 1 in 1,000 people) 
• Lactic acidosis (see Possible serious side effects) 
• fatty liver 
• yellow skin or eyes, itching, or pain in the abdomen (tummy) caused by inflammation of 

the liver 
• inflammation of the kidney, passing a lot of urine and feeling thirsty, kidney failure, damage to 

kidney tubule cells 
• softening of the bones (with bone pain and sometimes resulting in fractures) 
• back pain caused by kidney problems 
 
Damage to kidney tubule cells may be associated with breakdown of muscle, softening of the bones 
(with bone pain and sometimes resulting in fractures), muscle pain, muscle weakness and decreases in 
potassium or phosphate in the blood. 
 
 If you notice any of the side effects listed above or if any of the side effects get serious, talk 

to your doctor or pharmacist. 
 
The frequency of the following side effects is not known.  
• Bone problems.  Some patients taking combination antiretroviral medicines such as Truvada 

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 



51 

• 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 treatment for HIV 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. 
 
Other effects in children  

• Children given emtricitabine very commonly experienced changes in skin colour including  
• darkening of the skin in patches 

• Children commonly experienced low red blood cell count (anaemia). 
• this may cause the child to be tired or breathless  

  If you notice any of these symptoms tell your doctor. 
 
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 Truvada 
 
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 Truvada contains 
 
• The active substances are emtricitabine and tenofovir disoproxil.  Each Truvada film-coated 

tablet contains 200 mg of emtricitabine and 245 mg of tenofovir disoproxil (equivalent to 
300 mg of tenofovir disoproxil fumarate or 136 mg of tenofovir). 

 
• The other ingredients are croscarmellose sodium, glycerol triacetate (E1518), hypromellose 

(E464), indigo carmine aluminium lake (E132), lactose monohydrate, magnesium stearate 
(E572), microcrystalline cellulose (E460), pregelatinised starch (gluten free) and titanium 
dioxide (E171). 

 
What Truvada looks like and contents of the pack 
 
Truvada film-coated tablets are blue, capsule-shaped tablets, engraved on one side with the word 
“GILEAD” and on the other side with the number “701”.  Truvada comes in bottles of 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. 
 
The following pack sizes are available: outer cartons containing 1 bottle of 30 film-coated tablets and 
60 (2 bottles of 30) and 90 (3 bottles of 30) film-coated tablets.  Not all pack sizes may be marketed. 

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


52 

 
Marketing Authorisation Holder: 
Gilead Sciences Ireland UC 
Carrigtohill 
County Cork, T45 DP77 
Ireland 
 
Manufacturer: 
Gilead Sciences Ireland UC 
IDA Business & Technology Park 
Carrigtohill 
County Cork 
Ireland 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien 
Gilead Sciences Belgium SPRL-BVBA 
Tél/Tel: + 32 (0) 24 01 35 50 
 

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

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

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

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

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

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

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

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

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

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

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

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

Österreich 
Gilead Sciences GesmbH 
Tel: + 43 1 260 830 
 

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

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

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

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

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

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



53 

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. 
 
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