Stribild

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ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 



 

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1. NAME OF THE MEDICINAL PRODUCT 
 
Stribild 150 mg/150 mg/200 mg/245 mg film-coated tablets 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each film-coated tablet contains 150 mg of elvitegravir, 150 mg of cobicistat, 200 mg of emtricitabine 
and 245 mg of tenofovir disoproxil (equivalent to 300 mg of tenofovir disoproxil fumarate or 136 mg 
of tenofovir). 
 
Excipients with known effect 
 
Each tablet contains 10.4 mg lactose (as monohydrate). 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Film-coated tablet (tablet). 
 
Green, capsule-shaped, film-coated tablet of dimensions 20 mm x 10 mm, debossed on one side with 
“GSI” and the number “1” surrounded by a square box on the other side. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Stribild is indicated for the treatment of human immunodeficiency virus-1 (HIV-1) infection in adults 
aged 18 years and over who are antiretroviral treatment-naïve or are infected with HIV-1 without 
known mutations associated with resistance to any of the three antiretroviral agents in Stribild (see 
sections 4.2, 4.4 and 5.1). 
 
Stribild is also indicated for the treatment of HIV-1 infection in adolescents aged 12 to < 18 years 
weighing ≥ 35 kg who are infected with HIV-1 without known mutations associated with resistance to 
any of the three antiretroviral agents in Stribild and who have experienced toxicities which preclude 
the use of other regimens that do not contain tenofovir disoproxil (see sections 4.2, 4.4 and 5.1). 
 
4.2 Posology and method of administration 
 
Therapy should be initiated by a physician experienced in the management of HIV infection. 
 
Posology 
 
Adults and adolescents aged 12 years and older weighing at least 35 kg: One tablet, once daily with 
food. 
 
If the patient misses a dose of Stribild within 18 hours of the time it is usually taken, the patient should 
take Stribild with food as soon as possible and resume the normal dosing schedule.  If a patient misses 
a dose of Stribild by more than 18 hours and it is almost time for the next dose, the patient should not 
take the missed dose and simply resume the usual dosing schedule. 
 
If the patient vomits within 1 hour of taking Stribild another tablet should be taken. 
 



 

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Special populations 
 
Elderly 
No data are available on which to make a dose recommendation for patients over the age of 65 years 
(see sections 4.4 and 5.1).  Stribild should be administered with caution to elderly patients (see 
section 4.4). 
 
Adults with renal impairment 
Stribild should not be initiated in patients with creatinine clearance below 70 mL/min (see sections 4.4 
and 5.2).  See section 4.4 regarding initiation of Stribild in patients with creatinine clearance below 
90 mL/min. 
 
Stribild should be discontinued if creatinine clearance declines below 50 mL/min during treatment 
with Stribild as dose interval adjustment is required for emtricitabine and tenofovir disoproxil and this 
cannot be achieved with the fixed-dose combination tablet (see sections 4.4 and 5.2).  See section 4.4 
regarding patients with creatinine clearance that falls below 70 mL/min while on treatment with 
Stribild. 
 
Paediatric patients with renal impairment 
Use of Stribild is not recommended in paediatric patients under the age of 18 years with renal 
impairment (see section 4.4). 
 
Hepatic impairment 
No dose adjustment of Stribild is required in patients with mild (Child-Pugh Class A) or moderate 
(Child-Pugh Class B) hepatic impairment.  Stribild has not been studied in patients with severe hepatic 
impairment (Child-Pugh Class C).  Therefore, Stribild is not recommended for use in patients with 
severe hepatic impairment (see sections 4.4 and 5.2). 
 
If Stribild is discontinued in patients co-infected with HIV and hepatitis B virus (HBV), these patients 
should be closely monitored for evidence of exacerbation of hepatitis (see section 4.4). 
 
Paediatric population 
The safety and efficacy of Stribild in children under the age of 12 years or weighing < 35 kg have not 
been established (see section 5.2).  
 
Pregnancy 
Treatment with cobicistat and elvitegravir during pregnancy results in lower elvitegravir exposure (see 
sections 4.4 and 5.2).  Therefore, therapy with Stribild should not be initiated during pregnancy, and 
women who become pregnant during therapy with Stribild should be switched to an alternative regimen 
(see sections 4.4 and 4.6). 
 
Method of administration 
 
Stribild should be taken orally, once daily with food (see section 5.2).  The film-coated tablet should 
not be chewed or crushed. 
 
4.3 Contraindications 
 
Hypersensitivity to the active substances or to any of the excipients listed in section 6.1. 
 
Patients who have previously discontinued treatment with tenofovir disoproxil due to renal toxicity, 
with or without reversal of the effects post-discontinuation. 
 



 

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Co-administration is contraindicated with medicinal products that are highly dependent on CYP3A for 
clearance and for which elevated plasma concentrations are associated with serious and/or 
life-threatening events.  Therefore, Stribild should not be co-administered with medicinal products that 
include, but are not limited to, the following (see section 4.5): 
 
• alpha 1-adrenoreceptor antagonists: alfuzosin 
• antiarrhythmics: amiodarone, quinidine 
• ergot derivatives: dihydroergotamine, ergometrine, ergotamine 
• gastrointestinal motility agents: cisapride 
• HMG Co-A reductase inhibitors: lovastatin, simvastatin 
• neuroleptics/antipsychotics: pimozide, lurasidone 
• PDE-5 inhibitors: sildenafil for treatment of pulmonary arterial hypertension 
• sedatives/hypnotics: orally administered midazolam, triazolam 
 
Co-administration is contraindicated with medicinal products that are strong inducers of CYP3A due 
to the potential for loss of virologic response and possible resistance to Stribild.  Therefore, Stribild 
should not be co-administered with medicinal products that include, but are not limited to, the 
following (see section 4.5): 
 
• anticonvulsants: carbamazepine, phenobarbital, phenytoin 
• antimycobacterials: rifampicin 
• herbal products: St. John’s wort (Hypericum perforatum) 
 
Co-administration with dabigatran etexilate, a P-glycoprotein (P-gp) substrate, is contraindicated (see 
section 4.5). 
 
4.4 Special warnings and precautions for use 
 
While effective viral suppression with antiretroviral therapy has been proven to substantially reduce 
the risk of sexual transmission, a residual risk cannot be excluded.  Precautions to prevent 
transmission should be taken in accordance with national guidelines. 
 
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). 
 
There are currently inadequate data to determine whether co-administration of tenofovir disoproxil and 
cobicistat is associated with a greater risk of renal adverse reactions compared with regimens that 
include tenofovir disoproxil without cobicistat. 
 
Patients who have previously discontinued treatment with tenofovir disoproxil due to renal toxicity, 
with or without reversal of the effects post-discontinuation, should not be treated with Stribild (see 
section 4.3). 
 
Renal monitoring 
Before initiating treatment with Stribild 
Creatinine clearance should be calculated and urine glucose and urine protein should be determined in 
all patients.  Stribild should not be initiated in patients with creatinine clearance < 70 mL/min.  It is 
recommended that Stribild is not initiated in patients with creatinine clearance < 90 mL/min unless, 
after review of the available treatment options, it is considered that Stribild is the preferred treatment 
for the individual patient. 
 



 

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During treatment with Stribild 
Creatinine clearance, serum phosphate, urine glucose and urine protein should be monitored every 
four weeks during the first year and then every three months during Stribild therapy.  In patients at risk 
for renal impairment a more frequent monitoring of renal function is required. 
 
Cobicistat inhibits the tubular secretion of creatinine and may cause modest increases in serum 
creatinine and modest declines in creatinine clearance (see section 4.8).  Patients who experience a 
confirmed increase in serum creatinine of greater than 26.5 µmol/L (0.3 mg/dL) from baseline should 
be closely monitored for renal safety. 
 
See also under Co-administration of other medicinal products below. 
 
Renal management 
If serum phosphate is < 0.48 mmol/L (1.5 mg/dL) or creatinine clearance is decreased to < 70 mL/min, 
renal function should be re-evaluated within one week, including measurements of blood glucose, 
blood potassium and urine glucose concentrations (see section 4.8).  It is recommended that Stribild is 
discontinued in patients with creatinine clearance that falls to < 70 mL/min while on treatment unless 
it is considered that the potential benefit of this combination of antiretroviral agents for the individual 
patient outweighs the possible risks of continuing with therapy.  Interrupting treatment with Stribild 
should also be considered in case of progressive decline of renal function when no other cause has 
been identified. 
 
Stribild should be discontinued in patients with confirmed creatinine clearance that falls 
to < 50 mL/min (since the required dose interval adjustments are not possible using this fixed dose 
combination tablet) or with decreases in serum phosphate to < 0.32 mmol/L (1.0 mg/dL) (see 
sections 4.2 and 5.2). 
 
Bone effects 
In the Phase 3 Study GS-US-236-0103, bone mineral density (BMD) was assessed in a non-random 
subset of 120 subjects (Stribild group n = 54; ritonavir-boosted atazanavir (ATV/r) plus emtricitabine 
(FTC)/tenofovir disoproxil group n = 66).  Mean percentage decreases in BMD from baseline to 
Week 144 in the Stribild group were comparable to the ATV/r+FTC/tenofovir disoproxil group at the 
lumbar spine (-1.43% versus -3.68%, respectively) and at the hip (-2.83% versus -3.77%, 
respectively).  In the Phase 3 studies GS-US-236-0102 and GS-US-236-0103, bone fractures occurred 
in 27 subjects (3.9%) in the Stribild group, 8 subjects (2.3%) in the EFV/FTC/tenofovir disoproxil 
group, and 19 subjects (5.4%) in the ATV/r+FTC/tenofovir disoproxil group. 
 
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 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. 
 
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. 
 



 

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Renal and bone effects in the paediatric population 
 
There are uncertainties associated with the long-term effects of tenofovir disoproxil bone and renal 
toxicity.  Moreover, the reversibility of renal toxicity cannot be fully ascertained.  Therefore, a 
multidisciplinary approach is recommended to adequately weigh on a case by case basis the 
benefit/risk balance of treatment, decide the appropriate monitoring during treatment (including 
decision for treatment withdrawal) and consider the need for supplementation. 
 
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 a clinical study of tenofovir disoproxil 
(GS-US-104-0352) (see sections 4.8 and 5.1). 
 
Renal monitoring 
Renal function (creatinine clearance and urine glucose and urine protein) should be evaluated prior to 
treatment initiation, and creatinine clearance, serum phosphate, urine glucose and urine protein should 
be monitored during treatment as in HIV-1 infected adults (see above). 
 
Renal management 
If serum phosphate is confirmed to be < 0.96 mmol/L (3.0 mg/dL)  in any paediatric patient receiving 
Stribild, 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 treatment.  Interrupting treatment with Stribild should also be considered in 
case of progressive decline of renal function when no other cause has been identified.  As in adults, 
adolescents who experience a confirmed increase in serum creatinine of greater than 26.5 µmol/L 
(0.3 mg/dL) from baseline should be closely monitored for renal safety (see above). 
 
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 Stribild is not recommended in paediatric patients with renal impairment (see section 4.2).   
Stribild should not be initiated in paediatric patients with renal impairment and should be discontinued 
in paediatric patients who develop renal impairment during Stribild therapy. 
 
Bone effects 
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). 
 
In a clinical study of HIV-1-infected, treatment-naïve patients aged 12 to < 18 years (N=50), small 
decreases in mean BMD Z-scores were observed following treatment with Stribild (see section 4.8). 
 
If bone abnormalities are detected or suspected in paediatric patients, consultation with an 
endocrinologist and/or nephrologist should be obtained. 
 
Patients with HIV and hepatitis B or C virus co-infection 
 
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 optimal management of 
HIV infection in patients co-infected with hepatitis B virus (HBV). 
 



 

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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.  Stribild should not be administered 
concomitantly with other medicinal products containing tenofovir disoproxil, lamivudine or adefovir 
dipivoxil used for the treatment of hepatitis B virus infection. 
 
Discontinuation of Stribild therapy in patients co-infected with HIV and HBV may be associated with 
severe acute exacerbations of hepatitis.  Patients co-infected with HIV and HBV who discontinue 
Stribild should be closely monitored with both clinical and laboratory follow-up for at least several 
months after stopping treatment.  If appropriate, initiation 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 Stribild have not been established in patients with significant underlying 
liver disorders.  The pharmacokinetics of emtricitabine have not been studied in patients with hepatic 
impairment.  The pharmacokinetics of elvitegravir, cobicistat and tenofovir have been studied in 
patients with moderate hepatic impairment.  Stribild has not been studied in patients with severe 
hepatic impairment (Child-Pugh Class C).  No dose adjustment of Stribild is required in patients with 
mild (Child-Pugh Class A) or moderate (Child-Pugh Class B) hepatic impairment (see sections 4.2 and 
5.2). 
 
Patients with pre-existing liver dysfunction, including chronic active hepatitis, have an increased 
frequency of liver function abnormalities during combination antiretroviral therapy (CART) and 
should be monitored according to standard practice.  If there is evidence of worsening liver disease in 
such patients, interruption or discontinuation of treatment must be considered. 
 
Weight and metabolic parameters 
 
An increase in weight and in levels of blood lipids and glucose may occur during antiretroviral 
therapy.  Such changes may in part be linked to disease control and life style.  For lipids, there is in 
some cases evidence for a treatment effect, while for weight gain there is no strong evidence relating 
this to any particular treatment.  For monitoring of blood lipids and glucose reference is made to 
established HIV treatment guidelines.  Lipid disorders should be managed as clinically appropriate. 
 
Mitochondrial dysfunction following exposure in utero 
 
Nucleos(t)ide analogues may impact mitochondrial function to a variable degree, which is most 
pronounced with stavudine, didanosine and zidovudine.  There have been reports of mitochondrial 
dysfunction in HIV negative infants exposed in utero and/or postnatally to nucleoside analogues; these 
have predominantly concerned treatment with regimens containing zidovudine.  The main adverse 
reactions reported are haematological disorders (anaemia, neutropenia) and metabolic disorders 
(hyperlactatemia, hyperlipasemia).  These events have often been transitory.  Late onset neurological 
disorders have been reported rarely (hypertonia, convulsion, abnormal behaviour).  Whether such 
neurological disorders are transient or permanent is currently unknown.  These findings should be 
considered for any child exposed in utero to nucleos(t)ide analogues, who present with severe clinical 
findings of unknown aetiology, particularly neurologic findings.  These findings do not affect current 
national recommendations to use antiretroviral therapy in pregnant women to prevent vertical 
transmission of HIV. 
 
Immune Reactivation Syndrome 
 
In HIV infected patients with severe immune deficiency at the time of institution of CART, an 
inflammatory reaction to asymptomatic or residual opportunistic pathogens may arise and cause 
serious clinical conditions, or aggravation of symptoms.  Typically, such reactions have been observed 
within the first few weeks or months of initiation of CART.  Relevant examples include 
cytomegalovirus retinitis, generalised and/or focal mycobacterial infections, and Pneumocystis 



 

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jirovecii pneumonia.  Any inflammatory symptoms should be evaluated and treatment instituted when 
necessary. 
 
Autoimmune disorders (such as Graves’ disease and autoimmune hepatitis) have also been reported to 
occur in the setting of immune reactivation; however, the reported time to onset is more variable and 
these events can occur many months after initiation of treatment. 
 
Opportunistic infections 
 
Patients receiving Stribild 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 
 
Stribild is indicated for use as a complete regimen for the treatment of HIV-1 infection and must not 
be administered with other antiretroviral products (see section 4.5). 
 
Stribild should not be administered concomitantly with other medicinal products containing tenofovir 
disoproxil, lamivudine or adefovir dipivoxil used for the treatment of hepatitis B virus infection, or 
with other medicinal products containing tenofovir alafenamide. 
 
Concomitant use with nephrotoxic medicinal products 
Use of Stribild should be avoided with concurrent or recent use of a nephrotoxic medicinal product, 
e.g. aminoglycosides, amphotericin B, foscarnet, ganciclovir, pentamidine, vancomycin, cidofovir or 
interleukin 2 (also called aldesleukin) (see section 4.5).  If concomitant use of Stribild and nephrotoxic 
agents is unavoidable, renal function must be monitored weekly. 
 
Cases of acute renal failure after initiation of high dose or multiple non-steroidal anti-inflammatory 
drugs (NSAIDs) have been reported in patients treated with tenofovir disoproxil and with risk factors 
for renal dysfunction.  If Stribild is co-administered with an NSAID, renal function should be 
monitored adequately. 
 
Contraception requirements 
Female patients of childbearing potential should use either a hormonal contraceptive containing at 
least 30 µg ethinyloestradiol and containing drospirenone or norgestimate as the progestogen or should 
use an alternative reliable method of contraception (see sections 4.5 and 4.6).  The use of Stribild with 
oral contraceptives containing other progestogens should be avoided (see section 4.5).  Plasma 
concentrations of drospirenone are expected to be increased following co-administration with Stribild 
and clinical monitoring is recommended due to the potential for hyperkalaemia (see section 4.5). 
 
Use with certain hepatitis C virus antiviral agents 
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 in the setting of 
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 of ledipasvir/sofosbuvir, sofosbuvir/velpatasvir or 



 

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sofosbuvir/velpatasvir/voxilaprevir with Stribild should be considered, particularly in patients at 
increased risk of renal dysfunction.  Patients receiving Stribild concomitantly with 
ledipasvir/sofosbuvir, sofosbuvir/velpatasvir or sofosbuvir/velpatasvir/voxilaprevir should be 
monitored for adverse reactions related to tenofovir disoproxil. 
 
Elderly 
 
Stribild has limited data in patients over the age of 65 years.  Elderly patients are more likely to have 
decreased renal function, therefore caution should be exercised when treating elderly patients with 
Stribild. 
 
Pregnancy 
 
Treatment with cobicistat and elvitegravir during the second and third trimesters of pregnancy has 
been shown to result in lower elvitegravir exposures (see section 5.2).  Cobicistat levels decrease and 
may not provide sufficient boosting.  The substantial reduction in elvitegravir exposure may result in 
virological failure and an increased risk of mother-to-child transmission of HIV infection.  Therefore, 
therapy with Stribild should not be initiated during pregnancy, and women who become pregnant 
during therapy with Stribild should be switched to an alternative regimen (see sections 4.2 and 4.6). 
 
Excipients 
 
Stribild 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 
 
As Stribild contains elvitegravir, cobicistat, emtricitabine and tenofovir disoproxil, any interactions 
that have been identified with these active substances individually may occur with Stribild.  Stribild is 
indicated for use as a complete regimen for the treatment of HIV-1 infection and must not be 
administered with other antiretroviral products.  Therefore, information regarding drug-drug 
interactions with other antiretroviral products (including protease inhibitors and non-nucleoside 
reverse transcriptase inhibitors) is not provided (see section 4.4).  Interaction studies have only been 
performed in adults. 
 
Cobicistat is a strong mechanism-based CYP3A inhibitor and a CYP3A substrate.  Cobicistat is also a 
weak CYP2D6 inhibitor and is metabolised, to a minor extent, by CYP2D6.  The transporters that 
cobicistat inhibits include P-gp, BCRP, OATP1B1 and OATP1B3. 
 
Co-administration of Stribild with medicinal products that are primarily metabolised by CYP3A or 
CYP2D6, or are substrates of P-gp, BCRP, OATP1B1 or OATP1B3 may result in increased plasma 
concentrations of those products, which could increase or prolong their therapeutic effect and adverse 
reactions (see Concomitant use contraindicated and section 4.3).  Co-administration of Stribild with 
medicinal products that have active metabolite(s) formed by CYP3A may result in reduced plasma 
concentrations of these active metabolite(s). 
 
Co-administration of Stribild with medicinal products that inhibit CYP3A may decrease the clearance 
of cobicistat, resulting in increased cobicistat plasma concentrations. 
 
Elvitegravir is a modest inducer and may have the potential to induce CYP2C9 and/or inducible UGT 
enzymes; as such it may decrease the plasma concentration of substrates of these enzymes.  
Elvitegravir is metabolised by CYP3A and, to a minor extent, by UGT1A1.  Medicinal products that 
induce CYP3A activity are expected to increase the clearance of elvitegravir, resulting in decreased 



 

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plasma concentration of elvitegravir which may lead to loss of therapeutic effect of Stribild and 
development of resistance (see Concomitant use contraindicated and section 4.3). 
 
Concomitant use contraindicated 
 
Co-administration of Stribild and some medicinal products that are primarily metabolised by CYP3A 
may result in increased plasma concentrations of these products, which are associated with the 
potential for serious and/or life-threatening reactions such as peripheral vasospasm or ischaemia (e.g., 
dihydroergotamine, ergotamine, ergometrine), or myopathy, including rhabdomyolysis (e.g., 
simvastatin, lovastatin), or prolonged or increased sedation or respiratory depression (e.g., orally 
administered midazolam or triazolam).  Co-administration of Stribild and other medicinal products 
primarily metabolised by CYP3A such as amiodarone, quinidine, cisapride, pimozide, lurasidone, 
alfuzosin and sildenafil for pulmonary arterial hypertension is contraindicated (see section 4.3). 
 
Co-administration of Stribild and some medicinal products that induce CYP3A such as St. John’s wort 
(Hypericum perforatum), rifampicin, carbamazepine, phenobarbital and phenytoin may result in 
significantly decreased cobicistat and elvitegravir plasma concentrations, which may result in loss of 
therapeutic effect and development of resistance (see section 4.3). 
 
Concomitant use not recommended 
 
Renally eliminated medicinal products 
Since emtricitabine and tenofovir are primarily eliminated by the kidneys, co-administration of 
Stribild 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 Stribild should be avoided with concurrent or recent use of nephrotoxic medicinal products.  
Some examples include, but are not limited to, aminoglycosides, amphotericin B, foscarnet, 
ganciclovir, pentamidine, vancomycin, cidofovir or interleukin-2 (also called aldesleukin). 
 
Other interactions 
 
Interactions between the components of Stribild and potential co-administered medicinal products are 
listed in Table 1 below (increase is indicated as “↑”, decrease as “↓”, no change as “↔”).  The 
interactions described are based on studies conducted with the components of Stribild as individual 
agents and/or in combination, or are potential drug interactions that may occur with Stribild. 
 
Table 1: Interactions between the individual components of Stribild and other medicinal 
products 
 

Medicinal product by therapeutic 
areas 

Effects on drug levels 
Mean percent change in AUC, Cmax, 

Cmin1 

Recommendation concerning 
co-administration with Stribild 

ANTI-INFECTIVES 
Antifungals 
Ketoconazole (200 mg twice 
daily)/Elvitegravir (150 mg once 
daily)2 

Elvitegravir: 
AUC: ↑ 48% 
Cmin: ↑ 67% 
Cmax: ↔ 
 
Concentrations of ketoconazole and/or 
cobicistat may increase with 
co-administration of Stribild. 

When administering with Stribild, 
the maximum daily dose of 
ketoconazole should not exceed 
200 mg per day.  Caution is 
warranted and clinical monitoring 
is recommended during the 
co-administration. 



 

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Medicinal product by therapeutic 
areas 

Effects on drug levels 
Mean percent change in AUC, Cmax, 

Cmin1 

Recommendation concerning 
co-administration with Stribild 

Itraconazole3 
Voriconazole3 
Posaconazole3 
Fluconazole 

Interaction not studied with any of the 
components of Stribild. 
 
Concentrations of itraconazole, 
fluconazole and posaconazole may be 
increased when co-administered with 
cobicistat. 
 
Concentrations of voriconazole may 
increase or decrease when 
co-administered with Stribild. 

Clinical monitoring should be made 
upon co-administration with 
Stribild.  When administering with 
Stribild, the maximum daily dose 
of itraconazole should not exceed 
200 mg per day. 
 
An assessment of benefit/risk ratio 
is recommended to justify use of 
voriconazole with Stribild. 

Antimycobacterials 
Rifabutin (150 mg every other 
day)/Elvitegravir (150 mg once 
daily)/Cobicistat (150 mg once 
daily) 

Co-administration of rifabutin, potent 
CYP3A inducer, may significantly 
decrease cobicistat and elvitegravir 
plasma concentrations, which may 
result in loss of therapeutic effect and 
development of resistance. 
 
Rifabutin: 
AUC: ↔ 
Cmin: ↔ 
Cmax: ↔ 
 
25-O-desacetyl-rifabutin 
AUC: ↑ 525% 
Cmin: ↑ 394% 
Cmax: ↑ 384% 
 
Elvitegravir: 
AUC: ↓ 21% 
Cmin: ↓ 67% 
Cmax: ↔ 

Co-administration of Stribild and 
rifabutin is not recommended.  If 
the combination is needed, the 
recommended dose of rifabutin is 
150 mg 3 times per week on set 
days (for example Monday-
Wednesday-Friday). 
Increased monitoring for 
rifabutin-associated adverse 
reactions including neutropenia and 
uveitis is warranted due to an 
expected increase in exposure to 
desacetyl-rifabutin.  Further dose 
reduction of rifabutin has not been 
studied.  It should be kept in mind 
that a twice weekly dose of 150 mg 
may not provide an optimal 
exposure to rifabutin thus leading 
to a risk of rifamycin resistance and 
a treatment failure. 

Hepatitis Cvirus (HCV) antiviral agents 
Ledipasvir/Sofosbuvir Interaction not studied with Stribild. 

 
Co-administration with Stribild may 
lead to increased tenofovir exposure. 

Increased plasma concentrations of 
tenofovir resulting from 
co-administration of Stribild and 
ledipasvir/sofosbuvir may increase 



 

12 

Medicinal product by therapeutic 
areas 

Effects on drug levels 
Mean percent change in AUC, Cmax, 

Cmin1 

Recommendation concerning 
co-administration with Stribild 

Ledipasvir/Sofosbuvir 
(90 mg/400 mg once daily) + 
Elvitegravir/Cobicistat 
(150 mg/150 mg once daily) 

Observed: 
 
Ledipasvir: 
AUC: ↑ 78% 
Cmin: ↑ 91% 
Cmax: ↑ 63% 
 
Sofosbuvir: 
AUC: ↑ 36% 
Cmin: N/A 
Cmax: ↑ 33% 
 
GS-3310075: 
AUC: ↑ 44% 
Cmin: ↑ 53% 
Cmax: ↑ 33% 
 
Elvitegravir: 
AUC: ↔ 
Cmin: ↑ 36% 
Cmax: ↔ 
 
Cobicistat: 
AUC: ↑ 59% 
Cmin: ↑ 325% 
Cmax: ↔ 

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. 
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). 

Sofosbuvir/Velpatasvir 
(400 mg/100 mg once daily) + 
Elvitegravir/Cobicistat/ 
Emtricitabine/Tenofovir Disoproxil 
(150 mg/150 mg/200 mg/245 mg 
once daily) 

Sofosbuvir: 
AUC: ↔ 
Cmax: ↔ 
 
GS-3310075: 
AUC: ↔ 
Cmax: ↔ 
Cmin: ↑ 45% 
 
Velpatasvir: 
AUC: ↔ 
Cmax: ↔ 
Cmin: ↑ 37% 
 
Elvitegravir: 
AUC: ↔ 
Cmax: ↔ 
Cmin: ↔ 
 
Cobicistat: 
AUC: ↔ 
Cmax: ↔ 
Cmin: ↑ 71% 
 
Emtricitabine: 
AUC: ↔ 
Cmax: ↔ 
Cmin: ↔ 
 
Tenofovir: 
AUC: ↔ 
Cmax: ↑ 36% 
Cmin: ↑ 45% 

Increased plasma concentrations of 
tenofovir resulting from 
co-administration of Stribild and 
sofosbuvir/velpatasvir 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. 
cobicistat) has not been established. 
 
The combination should be used 
with caution with frequent renal 
monitoring (see section 4.4). 



 

13 

Medicinal product by therapeutic 
areas 

Effects on drug levels 
Mean percent change in AUC, Cmax, 

Cmin1 

Recommendation concerning 
co-administration with Stribild 

Sofosbuvir/Velpatasvir/ 
Voxilaprevir (400 mg/100 mg/ 
100 mg+100 mg once daily)6 + 
Emtricitabine/Tenofovir disoproxil 
(200 mg/245 mg once daily)7  

Co-administration with Stribild may 
lead to increased tenofovir exposure. 
 
Emtricitabine: 
AUC: ↔ 
Cmax: ↔ 
Cmin: ↔ 
 
Tenofovir: 
AUC: ↑ 39% 
Cmax: ↑ 48% 
Cmin: ↑ 47% 

Increased plasma concentrations of 
tenofovir resulting from 
co-administration of Stribild and 
sofosbuvir/velpatasvir/voxilaprevir 
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. cobicistat) has not been 
established. 
 
The combination should be used 
with caution with frequent renal 
monitoring (see section 4.4). 

Sofosbuvir/Velpatasvir/ 
Voxilaprevir (400 mg/100 mg/ 
100 mg+100 mg once daily)6 + 
Elvitegravir/Cobicistat 
(150 mg/150 mg once daily)8 

Sofosbuvir: 
AUC: ↔ 
Cmax: ↑ 27% 
Cmin: N/A 
 
GS-3310075: 
AUC: ↑ 43% 
Cmax:↔ 
Cmin: N/A 
 
Velpatasvir: 
AUC: ↔ 
Cmax: ↔ 
Cmin: ↑ 46% 
 
Voxilaprevir: 
AUC: ↑ 171% 
Cmax:↑ 92% 
Cmin: ↑ 350% 
 
Elvitegravir: 
AUC: ↔ 
Cmax: ↔ 
Cmin: ↑ 32% 
 
Cobicistat: 
AUC: ↑ 50% 
Cmax: ↔ 
Cmin: ↑ 250% 



 

14 

Medicinal product by therapeutic 
areas 

Effects on drug levels 
Mean percent change in AUC, Cmax, 

Cmin1 

Recommendation concerning 
co-administration with Stribild 

Nucleoside reverse transcriptase inhibitors (NRTIs) 
Didanosine  Co-administration of tenofovir 

disoproxil and didanosine results in a 
40-60% increase in systemic exposure 
to didanosine. 

Co-administration of Stribild and 
didanosine is not recommended. 
 
Increased systemic exposure to 
didanosine may increase 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 rates of virological failure 
within several tested combinations 
for the treatment of 
HIV-1 infection. 
 
However, in case of initiation of 
Stribild in patients previously 
taking didanosine or 
discontinuation of Stribild and 
change to a regimen including 
didanosine there could be a short 
period when measurable plasma 
levels of didanosine and tenofovir 
occur. 

Macrolide antibiotics 
Clarithromycin Interaction not studied with any of the 

components of Stribild. 
 
Concentrations of clarithromycin and/or 
cobicistat may be altered with 
co-administration of Stribild. 

No dose adjustment of 
clarithromycin is required for 
patients with normal renal function 
or mild renal impairment (ClCr 
60-90 mL/min).  Clinical 
monitoring is recommended for 
patients with ClCr < 90 mL/min.  
For patients with ClCr 
< 60 mL/min, alternative 
antibacterials should be considered. 

Telithromycin Interaction not studied with any of the 
components of Stribild. 
 
Concentrations of telithromycin and/or 
cobicistat may be altered with 
co-administration of Stribild. 

Clinical monitoring is 
recommended upon 
co-administration of Stribild. 



 

15 

Medicinal product by therapeutic 
areas 

Effects on drug levels 
Mean percent change in AUC, Cmax, 

Cmin1 

Recommendation concerning 
co-administration with Stribild 

GLUCOCORTICOIDS 
All corticosteroids excluding cutaneous products 
Corticosteroids primarily 
metabolised by CYP3A (including 
betamethasone, budesonide, 
fluticasone, mometasone, 
prednisone, triamcinolone). 

Interaction not studied with any of the 
components of Stribild. 
 
Plasma concentrations of these 
medicinal products may be increased 
when co-administered with Stribild, 
resulting in reduced serum cortisol 
concentrations. 

Concomitant use of Stribild and 
corticosteroids that are metabolised 
by CYP3A (e.g. fluticasone 
propionate or other inhaled or nasal 
corticosteroids) may increase the 
risk of development of systemic 
corticosteroid effects, including 
Cushing’s syndrome and adrenal 
suppression. 
 
Co-administration with 
CYP3A-metabolised 
corticosteroids is not recommended 
unless the potential benefit to the 
patient outweighs the risk, in which 
case patients should be monitored 
for systemic corticosteroid effects. 
Alternative corticosteroids which 
are less dependent on CYP3A 
metabolism e.g. beclomethasone 
for intranasal or inhalational use 
should be considered, particularly 
for long-term use. 

MEDICINAL PRODUCTS or ORAL SUPPLEMENTS CONTAINING POLYVALENT CATIONS (e.g. Mg, Al, 
Ca, Fe, Zn) 
Magnesium/aluminium-containing 
antacid suspension (20 mL single 
dose)/Elvitegravir (50 mg single 
dose)/Ritonavir (100 mg single 
dose) 

Elvitegravir (antacid suspension after ± 
2 hours): 
AUC: ↔ 
Cmin: ↔ 
Cmax: ↔ 
 
Elvitegravir (simultaneous 
administration): 
AUC: ↓ 45% 
Cmin: ↓ 41% 
Cmax: ↓ 47%  
 
Elvitegravir plasma concentrations are 
lower with antacids due to local 
complexation in the gastrointestinal 
tract and not to changes in gastric pH.   

It is recommended to separate 
Stribild and administration of 
antacids, medicinal products or oral 
supplements containing polyvalent 
cations by at least 4 hours. 
 
For information on other acid 
reducing agents (e.g. H2-receptor 
antagonists and proton pump 
inhibitors), see Studies conducted 
with other medicinal products. 

Calcium or iron supplements 
(including multivitamins) 
Other cation-containing antacids 
Cation-containing laxatives 
Sucralfate 
Buffered medicinal products 
 

Interaction not studied with any of the 
components of Stribild. 
 
Elvitegravir plasma concentrations are 
expected to be lower with antacids, 
medicinal products or oral supplements 
containing polyvalent cations, due to 
local complexation in the 
gastrointestinal tract and not to changes 
in gastric pH. 



 

16 

Medicinal product by therapeutic 
areas 

Effects on drug levels 
Mean percent change in AUC, Cmax, 

Cmin1 

Recommendation concerning 
co-administration with Stribild 

ORAL ANTI-DIABETICS 
Metformin Interaction not studied with any of the 

components of Stribild. 
 
Cobicistat reversibly inhibits MATE1, 
and concentrations of metformin may 
be increased when co-administered with 
Stribild. 

Careful patient monitoring and 
dose adjustment of metformin is 
recommended in patients who are 
taking Stribild. 

NARCOTIC ANALGESICS 
Methadone/Elvitegravir/Cobicistat Methadone: 

AUC: ↔ 
Cmin: ↔ 
Cmax: ↔ 
 
Cobicistat: 
AUC: ↔ 
Cmin: ↔ 
Cmax: ↔ 
 
Elvitegravir: 
AUC: ↔ 
Cmin: ↔ 
Cmax: ↔ 

No dose adjustment of methadone 
is required. 

Methadone/Tenofovir disoproxil  Methadone: 
AUC: ↔ 
Cmin: ↔ 
Cmax: ↔ 
 
Tenofovir: 
AUC: ↔ 
Cmin: ↔ 
Cmax: ↔ 

Buprenorphine/Naloxone/ 
Elvitegravir/Cobicistat 

Buprenorphine: 
AUC: ↑ 35% 
Cmin: ↑ 66% 
Cmax: ↔ 12% 
 
Naloxone: 
AUC: ↓ 28% 
Cmax: ↓ 28% 
 
Cobicistat: 
AUC: ↔ 
Cmin: ↔ 
Cmax: ↔ 
 
Elvitegravir: 
AUC: ↔ 
Cmin: ↔ 
Cmax: ↔ 

No dose adjustment of 
buprenorphine/naloxone is 
required. 



 

17 

Medicinal product by therapeutic 
areas 

Effects on drug levels 
Mean percent change in AUC, Cmax, 

Cmin1 

Recommendation concerning 
co-administration with Stribild 

ORAL CONTRACEPTIVES 
Drospirenone/Ethinyloestradiol 
(3 mg/0.02 mg single 
dose)/Cobicistat (150 mg once 
daily) 
 

Interaction not studied with Stribild. 
 
Expected 
Drospirenone: 
AUC: ↑ 

Plasma concentrations of 
drospirenone may be increased 
when co-administered with 
cobicistat-containing products.  
Clinical monitoring is 
recommended due to the potential 
for hyperkalemia. 
 
Caution should be exercised when 
co-administering Stribild and a 
hormonal contraceptive.  The 
hormonal contraceptive should 
contain at least 30 µg 
ethinyloestradiol and contain 
drospirenone or norgestimate as the 
progestogen or patients should use 
an alternative reliable method of 
contraception (see sections 4.4 and 
4.6). 
 
The long-term effects of substantial 
increases in progestogen exposure 
are unknown. 

Norgestimate (0.180/0.215 mg once 
daily)/Ethinyloestradiol (0.025 mg 
once daily)/ 
Elvitegravir (150 mg once 
daily)/Cobicistat (150 mg once 
daily)4 

Norgestimate: 
AUC: ↑ 126% 
Cmin: ↑ 167% 
Cmax: ↑ 108% 
 
Ethinyloestradiol: 
AUC: ↓ 25% 
Cmin: ↓ 44% 
Cmax: ↔ 
 
Elvitegravir: 
AUC: ↔ 
Cmin: ↔ 
Cmax: ↔ 

ANTIARRHYTHMICS 
Digoxin (0.5 mg single 
dose)/Cobicistat (150 mg multiple 
doses) 

Digoxin: 
AUC: ↔ 
Cmax: ↑ 41% 

It is recommended that digoxin 
levels be monitored when digoxin 
is combined with Stribild. 

Disopyramide 
Flecainide 
Systemic lidocaine 
Mexiletine 
Propafenone 

Interaction not studied with any of the 
components of Stribild. 
 
Concentrations of these antiarrhythmic 
drugs may be increased when 
co-administered with cobicistat. 

Caution is warranted and clinical 
monitoring is recommended upon 
co-administration with Stribild. 

ANTI-HYPERTENSIVES 
Metoprolol 
Timolol 

Interaction not studied with any of the 
components of Stribild. 
 
Concentrations of beta-blockers may be 
increased when co-administered with 
cobicistat. 

Clinical monitoring is 
recommended and a dose decrease 
may be necessary when these 
agents are co-administered with 
Stribild. 

Amlodipine 
Diltiazem 
Felodipine 
Nicardipine 
Nifedipine 
Verapamil 

Interaction not studied with any of the 
components of Stribild. 
 
Concentrations of calcium channel 
blockers may be increased when 
co-administered with cobicistat. 

Clinical monitoring of therapeutic 
and adverse effects is 
recommended when these 
medicinal products are 
concomitantly administered with 
Stribild. 

ENDOTHELIN RECEPTOR ANTAGONISTS 
Bosentan Interaction not studied with any of the 

components of Stribild. 
 
Co-administration with Stribild may 
lead to decreased elvitegravir and/or 
cobicistat exposures and loss of 
therapeutic effect and development of 
resistance. 

Alternative endothelin receptor 
antagonists may be considered. 



 

18 

Medicinal product by therapeutic 
areas 

Effects on drug levels 
Mean percent change in AUC, Cmax, 

Cmin1 

Recommendation concerning 
co-administration with Stribild 

ANTICOAGULANTS 
Dabigatran Interaction not studied with any of the 

components of Stribild. 
 
Co-administration with Stribild may 
increase dabigatran plasma 
concentrations with similar effects as 
seen with other strong P-gp inhibitors. 

Co-administration of Stribild with 
dabigatran is contraindicated. 

Apixaban 
Rivaroxaban 
Edoxaban 

Interaction not studied with any of the 
components of Stribild. 
 
Co-administration with Stribild may 
result in increased plasma 
concentrations of the DOAC, which 
may lead to an increased bleeding risk. 

Co-administration of apixaban, 
rivaroxaban or edoxaban is not 
recommended with Stribild. 

Warfarin Interaction not studied with any of the 
components of Stribild. 
 
Concentrations of warfarin may be 
affected upon co-administration with 
Stribild. 

It is recommended that the 
international normalised ratio 
(INR) be monitored upon 
co-administration of Stribild.  INR 
should continue to be monitored 
during the first weeks following 
ceasing treatment with Stribild. 

ANTIPLATELETS 
Clopidogrel 
 

Interaction not studied with any of the 
components of Stribild. 
 
Co-administration of clopidogrel with 
cobicistat is expected to decrease 
clopidogrel active metabolite plasma 
concentrations, which may reduce the 
antiplatelet activity of clopidogrel. 

Co-administration of clopidogrel 
with Stribild is not recommended. 
 

Prasugrel Interaction not studied with any of the 
components of Stribild. 
 
Stribild is not expected to have a 
clinically relevant effect on plasma 
concentrations of the active metabolite 
of prasugrel. 

No dose adjustment of prasugrel is 
required. 



 

19 

Medicinal product by therapeutic 
areas 

Effects on drug levels 
Mean percent change in AUC, Cmax, 

Cmin1 

Recommendation concerning 
co-administration with Stribild 

ANTICONVULSANTS 
Carbamazepine (200 mg twice 
daily)/Elvitegravir (150 mg once 
daily)/Cobicistat (150 mg once 
daily) 

Co-administration of carbamazepine, a 
potent CYP3A inducer, may 
significantly decrease cobicistat and 
elvitegravir plasma concentrations, 
which may result in loss of therapeutic 
effect and development of resistance. 
 
Carbamazepine: 
AUC: ↑ 43% 
Cmin: ↑ 51% 
Cmax: ↑ 40% 
 
Elvitegravir: 
AUC: ↓ 69% 
Cmin: ↓ 97% 
Cmax: ↓ 45% 
 
Cobicistat: 
AUC: ↓ 84% 
Cmin: ↓ 90% 
Cmax: ↓ 72% 
 
Carbamazepine-10,11-epoxide: 
AUC: ↓ 35% 
Cmin: ↓ 41% 
Cmax: ↓ 27% 

Co-administration of Stribild with 
carbamazepine, phenobarbital, or 
phenytoin is contraindicated (see 
section 4.3). 

INHALED BETA AGONIST 
Salmeterol Interaction not studied with any of the 

components of Stribild. 
 
Co-administration with Stribild may 
result in increased plasma 
concentrations of salmeterol, which is 
associated with the potential for serious 
and/or life-threatening reactions. 

Concurrent administration of 
salmeterol and Stribild is not 
recommended. 

HMG CO-A REDUCTASE INHIBITORS 
Rosuvastatin (10 mg single 
dose)/Elvitegravir (150 mg single 
dose)/Cobicistat (150 mg single 
dose) 

Elvitegravir: 
AUC: ↔ 
Cmin: ↔ 
Cmax: ↔ 
 
Rosuvastatin: 
AUC: ↑ 38% 
Cmin: N/A 
Cmax: ↑ 89% 

Concentrations of rosuvastatin are 
transiently increased when 
administered with elvitegravir and 
cobicistat.  Dose modifications are 
not necessary when rosuvastatin is 
administered in combination with 
Stribild. 

Atorvastatin (10 mg single dose)/ 
Elvitegravir (150 mg once daily)/ 
Cobicistat (150 mg once daily)/ 
Emtricitabine (200 mg once daily)/ 
Tenofovir alafenamide (10 mg once 
daily) 
 

Atorvastatin: 
AUC: ↑160% 
Cmin: NC 
Cmax: ↑132%  
 
Elvitegravir: 
AUC: ↔ 
Cmin: ↔ 
Cmax: ↔ 

Concentrations of atorvastatin are 
increased when co-administered 
with elvitegravir and cobicistat.  
Start with the lowest possible dose 
of atorvastatin with careful 
monitoring upon co-administration 
with Stribild. 
 



 

20 

Medicinal product by therapeutic 
areas 

Effects on drug levels 
Mean percent change in AUC, Cmax, 

Cmin1 

Recommendation concerning 
co-administration with Stribild 

Pitavastatin Interaction not studied with any of the 
components of Stribild. 
 
Concentrations of pitavastatin may be 
increased when administered with 
elvitegravir and cobicistat. 

Caution should be exercised when 
co-administering Stribild with 
pitavastatin. 

Pravastatin 
Fluvastatin 

Interaction not studied with any of the 
components of Stribild. 
 
Concentrations of these HMG Co-A 
reductase inhibitors are expected to 
transiently increase when administered 
with elvitegravir and cobicistat. 

Dose modifications are not 
necessary when administered in 
combination with Stribild. 

Lovastatin 
Simvastatin 

Interaction not studied with any of the 
components of Stribild. 

Co-administration of Stribild and 
lovastatin and simvastatin is 
contraindicated (see section 4.3). 

PHOSPHODIESTERASE TYPE 5 (PDE-5) INHIBITORS 
Sildenafil 
Tadalafil 
Vardenafil 

Interaction not studied with any of the 
components of Stribild. 
 
PDE-5 inhibitors are primarily 
metabolised by CYP3A.  
Co-administration with Stribild may 
result in increased plasma 
concentrations of sildenafil and 
tadalafil, which may result in PDE-5 
inhibitor-associated adverse reactions. 

Co-administration of Stribild and 
sildenafil for the treatment of 
pulmonary arterial hypertension is 
contraindicated. 
 
Caution should be exercised, 
including consideration of dose 
reduction, when co-administering 
Stribild with tadalafil for the 
treatment of pulmonary arterial 
hypertension. 
 
For the treatment of erectile 
dysfunction, it is recommended that 
a single dose of sildenafil no more 
than 25 mg in 48 hours, vardenafil 
no more than 2.5 mg in 72 hours, or 
tadalafil no more than 10 mg in 
72 hours be co-administered with 
Stribild. 

ANTIDEPRESSANTS 
Escitalopram 
Trazodone 

Interaction not studied with any of the 
components of Stribild. 
 
Concentrations of trazodone may 
increase upon co-administration with 
cobicistat. 

Careful dose titration of the 
antidepressant and monitoring for 
antidepressant response is 
recommended. 

IMMUNOSUPPRESSANTS 
Ciclosporin 
Sirolimus 
Tacrolimus 

Interaction not studied with any of the 
components of Stribild. 
 
Concentrations of these 
immunosuppressant agents may be 
increased when administered with 
cobicistat. 

Therapeutic monitoring is 
recommended upon 
co-administration with Stribild. 



 

21 

Medicinal product by therapeutic 
areas 

Effects on drug levels 
Mean percent change in AUC, Cmax, 

Cmin1 

Recommendation concerning 
co-administration with Stribild 

SEDATIVES/HYPNOTICS 
Buspirone 
Clorazepate 
Diazepam 
Estazolam 
Flurazepam 
Orally administered midazolam 
Triazolam 
Zolpidem 

Interaction not studied with any of the 
components of Stribild. 
 
Midazolam and triazolam are primarily 
metabolised by CYP3A.  
Co-administration with Stribild may 
result in increased plasma 
concentrations of these drugs, which is 
associated with the potential for serious 
and/or life-threatening reactions. 

Co-administration of Stribild and 
orally administered midazolam and 
triazolam is contraindicated (see 
section 4.3).  With other 
sedatives/hypnotics, dose reduction 
may be necessary and concentration 
monitoring is recommended. 

ANTI-GOUT 
Colchicine Interaction not studied with any of the 

components of Stribild. 
 
Co-administration with Stribild may 
result in increased plasma 
concentrations of this drug. 

Dose reductions of colchicine may 
be required.  Stribild should not be 
co-administered with colchicine to 
patients with renal or hepatic 
impairment. 

N/A = not applicable 
NC = not calculated 
DOAC = direct oral anticoagulant 
1 When data available from drug interaction studies. 
2 Studies performed with ritonavir boosted elvitegravir. 
3 These are drugs within class where similar interactions could be predicted. 
4 Study conducted using Stribild. 
5 The predominant circulating metabolite of sofosbuvir. 
6 Study conducted with additional voxilaprevir 100 mg to achieve voxilaprevir exposures expected in HCV-infected 

patients. 
7 Study conducted with emtricitabine/tenofovir disoproxil + darunavir (800 mg) + ritonavir (100 mg). 
8 Study conducted with elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide fixed dose combination tablet. 
 
Studies conducted with other medicinal products 
 
Based on drug interaction studies conducted with the components of Stribild, no clinically significant 
drug interactions have been either observed or are expected between the components of Stribild and 
the following medicinal products: entecavir, famciclovir, famotidine, omeprazole, ribavirin and 
sertraline. 
 
4.6 Fertility, pregnancy and lactation 
 
Women of childbearing potential / contraception in males and females 
 
The use of Stribild must be accompanied by the use of effective contraception (see section 4.5). 
 
Pregnancy 
 
There are no or limited amount of data (less than 300 pregnancy outcomes) from the use of Stribild in 
pregnant women.  However, a large amount of data in pregnant women (more than1,000 pregnancy 
outcomes) indicate no malformations or foetal/neonatal toxicity associated with emtricitabine and 
tenofovir disoproxil. 
 
Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity 
(see section 5.3). 
 
Treatment with cobicistat and elvitegravir during the second and third trimesters of pregnancy has 
been shown to result in lower elvitegravir exposure (see section 5.2).  Cobicistat levels decrease and 
may not provide sufficient boosting.  The substantial reduction in elvitegravir exposure may result in 
virological failure and an increased risk of mother-to-child transmission of HIV infection.  Therefore, 



 

22 

therapy with Stribild should not be initiated during pregnancy, and women who become pregnant 
during therapy with Stribild should be switched to an alternative regimen (see sections 4.2 and 4.4). 
 
Breast-feeding 
 
It is not known whether elvitegravir or cobicistat are excreted in human milk.  Emtricitabine and 
tenofovir have been shown to be excreted in human milk.  In animal studies it has been shown that 
elvitegravir, cobicistat and tenofovir are excreted in milk.  There is insufficient information on the 
effects of elvitegravir, cobicistat, emtricitabine and tenofovir disoproxil in newborns/infants.  
Therefore Stribild should not be used during breast-feeding. 
 
In order to avoid transmission of HIV to the infant it is recommended that HIV infected women do not 
breast-feed their infants under any circumstances. 
 
Fertility 
 
No human data on the effect of Stribild on fertility are available.  Animal studies do not indicate 
harmful effects of elvitegravir, cobicistat, emtricitabine or tenofovir disoproxil on fertility. 
 
4.7 Effects on ability to drive and use machines 
 
Stribild has no or negligible influence on the ability to drive and use machines.  However, patients 
should be informed that dizziness, fatigue and insomnia have been reported during treatment with 
Stribild. 
 
4.8 Undesirable effects 
 
Summary of the safety profile 
 
The most frequently reported adverse reactions considered possibly or probably related to Stribild in 
clinical studies through 144 weeks in treatment-naïve adult patients were nausea (16%) and diarrhoea 
(12%). 
 
The most frequently reported adverse reactions to Stribild in clinical studies through 48 weeks in 
virologically-suppressed adult patients were nausea (3% to 5%) and fatigue (6%). 
 
In patients receiving tenofovir disoproxil, rare events of renal impairment, renal failure and 
uncommon events of proximal renal tubulopathy (including Fanconi syndrome) sometimes leading to 
bone abnormalities (infrequently contributing to fractures) have been reported.  Monitoring of renal 
function is recommended for patients receiving Stribild (see section 4.4). 
 
Discontinuation of Stribild therapy in patients co-infected with HIV and HBV may be associated with 
severe acute exacerbations of hepatitis (see section 4.4). 
 
Tabulated summary of adverse reactions 
 
Adverse reactions to Stribild from Phase 3 clinical studies GS-US-236-0102 and GS-US-236-0103 and 
adverse reactions to treatment with emtricitabine and tenofovir disoproxil from clinical studies and 
post-marketing experience, when used with other antiretrovirals, are listed in Table 2, below, by body 
system organ class and highest frequency observed.  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). 
 



 

23 

Table 2: Tabulated summary of adverse reactions associated with Stribild based on experience 
from Phase 3 studies GS-US-236-0102 and GS-US-236-0103 and adverse reactions to treatment 
with emtricitabine and tenofovir disoproxil from clinical studies and post-marketing experience, 
when used with other antiretrovirals 
 

Frequency Adverse reaction 
Blood and lymphatic system disorders: 
Common: neutropenia1 
Uncommon: anaemia1,2 
Immune system disorders: 
Common: allergic reaction1 
Metabolism and nutrition disorders: 
Very common: hypophosphataemia1,3 
Common: hyperglycaemia1, hypertriglyceridaemia1, decreased appetite 
Uncommon: hypokalaemia1,3 
Rare: lactic acidosis1 
Psychiatric disorders: 
Common: insomnia, abnormal dreams 

Uncommon: suicidal ideation and suicide attempt (in patients with a pre-existing history of depression or psychiatric illness), depression 
Nervous system disorders: 
Very common: headache, dizziness 
Gastrointestinal disorders: 
Very common: diarrhoea, vomiting, nausea 

Common: 
elevated amylase including elevated pancreatic amylase1, elevated serum 
lipase1, abdominal pain, dyspepsia, constipation, abdominal distension1, 
flatulence 

Uncommon: pancreatitis1 
Hepatobiliary disorders: 
Common: increased transaminases1, hyperbilirubinaemia1 
Rare: hepatic steatosis1, hepatitis1 
Skin and subcutaneous tissue disorders: 
Very common: rash 

Common: vesiculobullous rash
1, pustular rash1, maculopapular rash1, pruritus1, 

urticaria1, skin discolouration (increased pigmentation)1,2 
Uncommon: angioedema1 
Musculoskeletal and connective tissue disorders: 
Very common: elevated creatine kinase1 
Uncommon: rhabdomyolysis1,3, muscular weakness1,3 

Rare: osteomalacia (manifested as bone pain and infrequently contributing to fractures)1,3,5, myopathy1,3 
Renal and urinary disorders: 
Common: increased blood creatinine4 

Uncommon: renal failure
4, proximal renal tubulopathy including Fanconi syndrome 

acquired4, proteinuria 

Rare: acute tubular necrosis
1, nephritis (including acute interstitial nephritis)1,5, 

nephrogenic diabetes insipidus1 



 

24 

Frequency Adverse reaction 
General disorders and administration site conditions: 
Very common: asthenia1 
Common: pain1, fatigue 

1 This adverse reaction was not observed in the Phase 3 clinical studies for Stribild but identified from clinical studies or 
post-marketing experience for emtricitabine or tenofovir disoproxil when used with other antiretrovirals. 

2 Anaemia was common and skin discolouration (increased pigmentation) was very common when emtricitabine was 
administered to paediatric patients. 

3 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. 

4 See section 4.8, Description of selected adverse reactions for more details. 
5 This adverse reaction was identified through post-marketing surveillance for emtricitabine or tenofovir disoproxil 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 
Proximal renal tubulopathy generally resolved or improved after tenofovir disoproxil discontinuation.  
However, in some 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). 
 
In the clinical studies of Stribild over 144 weeks, 13 (1.9%) subjects in the Stribild group (n = 701) 
and 8 (2.3%) subjects in the ATV/r+FTC/tenofovir disoproxil group (n = 355) discontinued study drug 
due to a renal adverse reaction.  Of these discontinuations, 7 in the Stribild group and 1 in the 
ATV/r+FTC/tenofovir disoproxil group occurred during the first 48 weeks.  The types of renal adverse 
reactions seen with Stribild were consistent with previous experience with tenofovir disoproxil.  Four 
(0.6%) of the subjects who received Stribild developed laboratory findings consistent with proximal 
tubulopathy leading to discontinuation of Stribild during the first 48 weeks.  No additional proximal 
renal tubular dysfunction cases were reported from Week 48 to Week 144.  Two of the four subjects 
had renal impairment (i.e. estimated creatinine clearance less than 70 mL/min) at baseline.  The 
laboratory findings in these 4 subjects with evidence of proximal tubulopathy improved without 
clinical consequence upon discontinuation of Stribild, but did not completely resolve in all subjects.  
Three (0.8%) subjects who received ATV/r+FTC/tenofovir disoproxil developed laboratory findings 
consistent with proximal renal tubular dysfunction leading to discontinuation of ATV/r+FTC/tenofovir 
disoproxil after Week 96 (see section 4.4). 
 
The cobicistat component of Stribild has been shown to decrease estimated creatinine clearance due to 
inhibition of tubular secretion of creatinine without affecting renal glomerular function.  In studies 
GS-US-236-0102 and GS-US-236-0103, decreases in estimated creatinine clearance occurred early in 
treatment with Stribild, after which they stabilised.  The mean change in estimated glomerular 
filtration rate (eGFR) by Cockcroft-Gault method after 144 weeks of treatment 
was -14.0 ± 16.6 mL/min for Stribild, -1.9 ± 17.9 mL/min for EFV/FTC/tenofovir disoproxil, 
and -9.8 ± 19.4 mL/min for ATV/r+FTC/tenofovir disoproxil. 
 
Lactic acidosis 
Cases of lactic acidosis have been reported with tenofovir disoproxil alone or in combination with 
other antiretrovirals.  Patients with predisposing factors such as patients with decompensated liver 
disease, or patients receiving concomitant medications known to induce lactic acidosis are at increased 
risk of experiencing severe lactic acidosis during tenofovir disoproxil treatment, including fatal 
outcomes. 
 



 

25 

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 
 
Studies with Stribild 
The safety of Stribild in 50 HIV-1-infected, treatment-naïve paediatric patients aged 12 to < 18 years 
was evaluated through 48 weeks in an open-label clinical study (GS-US-236-0112, see section 5.1).  In 
this study, the safety profile of Stribild was similar to that in adults (see section 4.8, Tabulated 
summary of adverse reactions).  Among the 50 paediatric patients receiving Stribild, mean BMD 
increased from baseline to Week 48, +0.68% for lumbar spine and +0.77% for total body less head.  
Mean changes from baseline BMD Z-scores (height-age adjusted) were −0.09 for lumbar spine and 
−0.12 for total body less head at Week 48. 
 
Studies with emtricitabine 
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). 
  
Studies with tenofovir disoproxil  
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 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 



 

26 

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. 
 
Insufficient safety data are available for children below 12 years of age.  Stribild is not recommended 
in this population (see section 4.2). 
 
Other special population(s) 
 
Patients with renal impairment 
Since tenofovir disoproxil can cause renal toxicity, close monitoring of renal function is recommended 
in any adult with renal impairment treated with Stribild (see sections 4.2, 4.4 and 5.2).  The use of 
Stribild is not recommended in paediatric patients with renal impairment (see sections 4.2 and 4.4). 
 
Exacerbations of hepatitis after discontinuation of treatment 
In HIV infected patients co-infected with HBV, 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 patient must be monitored for evidence of toxicity (see section 4.8), and 
standard supportive treatment applied as necessary. 
 
There is no specific antidote for overdose with Stribild.  As elvitegravir and cobicistat are highly 
bound to plasma proteins it is unlikely that elvitegravir and cobicistat will be significantly removed by 
haemodialysis or peritoneal dialysis.  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: Antivirals for systemic use; antivirals for treatment of HIV infections, 
combinations.  ATC code: J05AR09 
 
Mechanism of action and pharmacodynamic effects 
 
Elvitegravir is an HIV-1 integrase strand transfer inhibitor (INSTI).  Integrase is an HIV-1 encoded 
enzyme that is required for viral replication.  Inhibition of integrase prevents the integration of 
HIV-1 DNA into host genomic DNA, blocking the formation of the HIV-1 provirus and propagation 
of the viral infection. 
 
Cobicistat is a selective, mechanism-based inhibitor of cytochromes P450 of the CYP3A subfamily.  
Inhibition of CYP3A-mediated metabolism by cobicistat enhances the systemic exposure of CYP3A 
substrates, such as elvitegravir, where bioavailability is limited and half-life is shortened by 
CYP3A-dependent metabolism. 
 
Emtricitabine is a nucleoside analogue of cytidine.  Tenofovir disoproxil is converted in vivo to 
tenofovir, a nucleoside monophosphate (nucleotide) analogue of adenosine monophosphate.  Both 

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27 

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 
 
The dual-drug combinations and the triple combination of elvitegravir, emtricitabine and tenofovir 
demonstrated synergistic activity in cell culture.  Antiviral synergy was maintained for elvitegravir, 
emtricitabine, and tenofovir when tested in the presence of cobicistat.  No antagonism was observed 
for any of these combinations. 
 
The antiviral activity of elvitegravir against laboratory and clinical isolates of HIV-1 was assessed in 
lymphoblastoid cells, monocyte/macrophage cells, and peripheral blood lymphocytes and the 50% 
effective concentration (EC50) values were in the range of 0.02 to 1.7 nM.  Elvitegravir displayed 
antiviral activity in cell culture against HIV-1 clades A, B, C, D, E, F, G, and O (EC50 values ranged 
from 0.1 to 1.3 nM) and activity against HIV-2 (EC50 of 0.53 nM). 
 
Cobicistat has no detectable anti-HIV activity and does not antagonise or enhance the antiviral effects 
of elvitegravir, emtricitabine, or tenofovir. 
 
The antiviral activity of emtricitabine against laboratory and clinical isolates of HIV-1 was assessed in 
lymphoblastoid cell lines, the MAGI-CCR5 cell line, and peripheral blood mononuclear cells.  The 
EC50 values for emtricitabine were in the range of 0.0013 to 0.64 µM.  Emtricitabine displayed 
antiviral activity in cell culture against HIV-1 clades A, B, C, D, E, F, and G (EC50 values ranged from 
0.007 to 0.075 µM) and showed strain specific activity against HIV-2 (EC50 values ranged from 0.007 
to 1.5 µM). 
 
The antiviral activity of tenofovir against laboratory and clinical isolates of HIV-1 was assessed in 
lymphoblastoid cell lines, primary monocyte/macrophage cells and peripheral blood lymphocytes.  
The EC50 values for tenofovir were in the range of 0.04 to 8.5 µM.  Tenofovir displayed antiviral 
activity in cell culture against HIV-1 clades A, B, C, D, E, F, G, and O (EC50 values ranged from 0.5 
to 2.2 µM) and strain specific activity against HIV-2 (EC50 values ranged from 1.6 to 5.5 µM). 
 
Resistance 
 
In cell culture 
Resistance to emtricitabine or tenofovir has been seen in vitro and in the HIV-1 from some patients 
due to the development of the M184V or M184I emtricitabine resistance substitution in reverse 
transcriptase or the K65R tenofovir resistance substitution in reverse transcriptase.  In addition, a 
K70E substitution in HIV-1 reverse transcriptase has been selected clinically by tenofovir disoproxil 
and results in low-level reduced susceptibility to abacavir, emtricitabine, tenofovir, and lamivudine. 
 
Emtricitabine-resistant viruses with the M184V/I substitution were cross-resistant to lamivudine, but 
retained sensitivity to didanosine, stavudine, tenofovir and zidovudine.  The K65R substitution can 
also be selected by abacavir, stavudine 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 substitution. 
 



 

28 

In patients, 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. 
 
HIV-1 isolates with reduced susceptibility to elvitegravir have been selected in cell culture.  Reduced 
susceptibility to elvitegravir was most commonly associated with the integrase substitutions T66I, 
E92Q and Q148R.  Additional integrase substitutions observed in cell culture selection included 
H51Y, F121Y, S147G, S153Y, E157Q, and R263K.  HIV-1 with the raltegravir-selected substitutions 
T66A/K, Q148H/K, and N155H showed cross-resistance to elvitegravir.  Primary mutations for 
raltegravir/elvitegravir do not affect the in vitro susceptibility of dolutegravir as single mutations, and 
the additional presence of secondary mutations (except Q148) also does not result in relevant fold 
changes in experiments with site directed mutants. 
 
No development of resistance to cobicistat can be demonstrated in HIV-1 in vitro due to its lack of 
antiviral activity. 
 
Substantial cross-resistance was observed between most elvitegravir-resistant HIV-1 isolates and 
raltegravir, and between emtricitabine-resistant isolates and lamivudine.  Patients who failed treatment 
with Stribild and who had HIV-1 with emergent Stribild resistance substitutions harboured virus that 
remained susceptible to all PIs, NNRTIs, and most other NRTIs. 
 
In treatment-naïve patients 
In a pooled analysis of antiretroviral-naïve patients receiving Stribild in Phase 3 studies 
GS-US-236-0102 and GS-US-236-0103 through Week 144, genotyping was performed on plasma 
HIV-1 isolates from all patients with confirmed virologic failure or who had HIV-1 RNA 
> 400 copies/mL at virologic failure, at Week 48, at Week 96, at Week 144 or at the time of early 
study drug discontinuation.  As of Week 144, the development of one or more primary elvitegravir, 
emtricitabine, or tenofovir resistance-associated substitutions was observed in 18 of the 42 patients 
with evaluable genotypic data from paired baseline and Stribild treatment-failure isolates (2.6%, 
18/701 patients).  Of the 18 patients with viral resistance development, 13 occurred through Week 48, 
3 occurred between Week 48 to Week 96, and 2 occurred between Week 96 to Week 144 of treatment.  
The substitutions that emerged were M184V/I (n = 17) and K65R (n = 5) in reverse transcriptase and 
E92Q (n = 9), N155H (n = 5), Q148R (n = 3), T66I (n = 2), and T97A (n = 1) in integrase.  Other 
substitutions in integrase that occurred in addition to a primary INSTI resistance substitution each in 
single cases were H51Y, L68V, G140C, S153A, E157Q, and G163R.  Most patients who developed 
resistance substitutions to elvitegravir developed resistance substitutions to both emtricitabine and 
elvitegravir.  In phenotypic analyses of isolates from patients in the resistance analysis population, 
13 patients (31%) had HIV-1 isolates with reduced susceptibility to elvitegravir, 17 patients (40%) had 
reduced susceptibility to emtricitabine, and 2 patients (5%) had reduced susceptibility to tenofovir. 
 
In Study GS-US-236-0103, 27 patients treated with Stribild had HIV-1 with the NNRTI-associated 
K103N substitution in reverse transcriptase at baseline and had virologic success (82% at Week 144) 
similar to the overall population (78%), and no emergent resistance to elvitegravir, emtricitabine, or 
tenofovir in their HIV-1. 
 
In virologically-suppressed patients 
No emergent resistance to Stribild was identified in clinical studies of virologically-suppressed 
patients who switched from a regimen containing a ritonavir-boosted protease inhibitor (PI+RTV) 
(Study GS-US-236-0115), an NNRTI (Study GS-US-236-0121) or raltegravir (RAL) (Study 
GS-US-236-0123). 
 
Twenty patients from these studies who switched to Stribild had the NNRTI-associated K103N 
substitution in their historical genotype prior to starting initial antiretroviral therapy.  Eighteen of these 
20 patients maintained virologic suppression through 48 weeks.  Due to protocol violation, two 
patients with historical K103N substitutions discontinued early with HIV-1 RNA < 50 copies/mL. 
 



 

29 

Clinical experience 
 
The efficacy of Stribild in HIV-1 infected treatment-naïve adult patients is based on the analyses of 
144-week data from 2 randomised, double-blinded, active-controlled, Phase 3 studies, 
GS-US-236-0102 and GS-US-236-0103 (n = 1,408).  The efficacy of Stribild in HIV-1 infected 
virologically-suppressed adult patients is based on the analyses of 48-week data from two randomised, 
open-label studies (Studies GS-US-236-0115 and GS-US-236-0121) and a single group open-label 
study (Study GS-US-236-0123) (n = 910; 628 receiving Stribild). 
 
Treatment-naïve HIV-1 infected adult patients 
In Study GS-US-236-0102 HIV-1 infected antiretroviral treatment-naïve adult patients received once-
daily treatment of Stribild or once-daily treatment of fixed-dose combination of EFV/FTC/tenofovir 
disoproxil.  In Study GS-US-236-0103 HIV-1 infected antiretroviral treatment-naïve adult patients 
received once daily treatment of Stribild or ritonavir-boosted atazanavir (ATV/r) plus fixed-dose 
combination of emtricitabine (FTC)/tenofovir disoproxil.  For both studies at 48 weeks, the virologic 
response rate was evaluated in both treatment arms.  Virologic response was defined as achieving an 
undetectable viral load (< 50 HIV-1 RNA copies/mL, snapshot analysis). 
 
Baseline characteristics and treatment outcomes for both Studies GS-US-236-0102 and 
GS-US-236-0103 are presented in Tables 3 and 4, respectively. 
 
Table 3: Demographic and baseline characteristics of antiretroviral treatment-naïve HIV-1 
infected adult subjects in studies GS-US-236-0102 and GS-US-236-0103 
 

 Study GS-US-236-0102 Study GS-US-236-0103 
 Stribild 

 
n = 348 

EFV/FTC/ 
tenofovir 
disoproxil 

n = 352 

Stribild 
 

n = 353 

ATV/r + FTC/ 
tenofovir 
disoproxil 

n = 355 
Demographic characteristics 

Mean age, years (range) 38.0 
(18-67) 

38.0 
(19-72) 

Sex   
 Male 89% 90% 
 Female 11% 10% 
Ethnicity   
 White 63% 74% 
 Black/African American 28% 17% 
 Asian 2% 5% 
 Other 7% 4% 

Baseline disease characteristicsa 
Mean baseline plasma 
HIV-1 RNA (range) 
log10 copies/mL 

4.8 
(2.6-6.5) 

4.8 
(1.7-6.6) 

Percentage of subjects with 
viral load 
> 100,000 copies/mL 

33 40 

Mean baseline CD4+ cell 
count (range), x 106 cells/L 

386 
(3-1,348) 

370 
(5-1,132) 

Percentage of subjects with 
CD4+ cell counts 
≤ 200 cells/mm3 

13 13 

a Patients were stratified by baseline HIV-1 RNA in both studies. 
 



 

30 

Table 4: Virologic outcome of randomised treatment of studies GS-US-236-0102 and 
GS-US-236-0103 at Week 48 (snapshot analysis)a and Week 144b 
 

 Week 48 Week 144 
 Study 

GS-US-236-0102 
Study 

GS-US-236-0103 
Study 

GS-US-236-0102 
Study 

GS-US-236-0103 
  

Stribild 
n = 348 

EFV/ 
FTC/ 

tenofovir 
disoproxil 

n = 352 

 
Stribild 
n = 353 

ATV/r + 
FTC/ 

tenofovir 
disoproxil 

n = 355 

 
Stribild 
n = 348 

EFV/ 
FTC/ 

tenofovir 
disoproxil 
n = 352 

 
Stribild 
n = 353 

ATV/r + 
FTC/ 

tenofovir 
disoproxil 

n = 355 
Virologic success 
HIV-1 RNA 
< 50 copies/mL 

88% 84% 90% 87% 80% 75% 78% 75% 

Treatment 
difference 

3.6% (95% CI 
= -1.6%, 8.8%) 

3.0% (95% CI 
= -1.9%, 7.8%) 

4.9% (95% CI 
= -1.3%, 11.1%) 

3.1% (95% CI 
= -3.2%, 9.4%) 

Virologic failurec 7% 7% 5% 5% 7% 10% 8% 7% 
No virologic data 
at Week 48 or 
144 window 

        

Discontinued 
study drug due 
to AE or deathd 

3% 5% 3% 5% 6% 8% 6% 8% 

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

2% 3% 2% 3% 5% 7% 8% 9% 

Missing data 
during window 
but on study drug 

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

a Week 48 window is between Day 309 and 378 (inclusive). 
b Week 144 window is between Day 967 and 1,050 (inclusive). 
c Includes subjects who had ≥ 50 copies/mL in the Week 48 or Week 144 window, subjects who discontinued early due to 

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

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

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

 
Stribild met the non-inferiority criteria in achieving HIV-1 RNA < 50 copies/mL when compared to 
efavirenz/emtricitabine/tenofovir disoproxil and when compared to atazanavir/ritonavir + 
emtricitabine/tenofovir disoproxil. 
 
In Study GS-US-236-0102, the mean increase from baseline in CD4+ cell count at Week 48 was 
239 cells/mm3 in the Stribild-treated patients and 206 cells/mm3 in the EFV/FTC/tenofovir disoproxil-
treated patients.  At Week 144, the mean increase from baseline in CD4+ cell count was 321 cells/mm3 
in the Stribild-treated patients and 300 cells/mm3 in the EFV/FTC/tenofovir disoproxil-treated 
patients.  In Study GS-US-236-0103, the mean increase from baseline in CD4+ cell count at Week 48 
was 207 cells/mm3 in the Stribild-treated patients and 211 cells/mm3 in the ATV/r+FTC/tenofovir 
disoproxil-treated patients.  At Week 144, the mean increase from baseline in CD4+ cell count was 
280 cells/mm3 in the Stribild-treated patients and 293 cells/mm3 in the ATV/r+FTC/tenofovir 
disoproxil-treated patients. 
 
Virologically-suppressed HIV-1 infected patients 
In Study GS-US-236-0115 and Study GS-US-236-0121, patients had to be on either their first or 
second antiretroviral regimen with no history of virologic failure, have no current or past history of 
resistance to the antiretroviral components of Stribild and must have been suppressed on a PI+RTV or 



 

31 

an NNRTI in combination with FTC/tenofovir disoproxil (HIV-1 RNA < 50 copies/mL) for at least six 
months prior to screening.  Patients were randomised in a 2:1 ratio to either switch to Stribild or stay 
on their baseline antiretroviral regimen (SBR) for 48 weeks.  In Study GS-US-236-0115, virologic 
success rates were: Stribild 93.8% (272 of 290 patients); SBR 87.1% (121 of 139 patients).  The mean 
increase from baseline in CD4+ cell count at Week 48 was 40 cells/mm3 in the Stribild-treated patients 
and 32 cells/mm3 in the PI+RTV+FTC/tenofovir disoproxil-treated patients.  In Study 
GS-US-236-0121, virologic success rates were: Stribild 93.4% (271 of 290 patients) and SBR 88.1% 
(126 of 143 patients).  The mean increase from baseline in CD4+ cell count at Week 48 was 
56 cells/mm3 in the Stribild-treated patients and 58 cells/mm3 in the NNRTI+FTC/tenofovir 
disoproxil-treated patients. 
 
In Study GS-US-236-0123, patients had to have previously only received RAL in combination with 
FTC/tenofovir disoproxil as their first antiretroviral regimen for at least six months.  Patients had to be 
stably suppressed for at least six months prior to study entry, have no current or past history of 
resistance to the antiretroviral components of Stribild, and have HIV-1 RNA < 50 copies/mL at 
screening.  All 48 patients who received at least one dose of Stribild remained suppressed 
(HIV-1 RNA < 50 copies/mL) through Week 48.  The mean increase from baseline in CD4+ cell count 
at Week 48 was 23 cells/mm3. 
 
Paediatric population 
 
Studies with Stribild 
The efficacy and safety of Stribild  in HIV-1-infected, treatment-naïve paediatric patients aged 12 to 
less than 18 years is based on the analyses of 48-week data from the single-group, open-label study 
GS-US-236-0112 (N=50).  Mean age was 15 years (range, 12−17), 70% were male, 68% black, 28% 
Asian.  At baseline, mean plasma HIV-1 RNA was 4.60 log10 copies/mL, mean CD4+ cell count 
399 cells/mm3 (range, 133-734), and mean CD4+% 20.9% (range, 4.5%-41.1%).  Twenty percent had 
baseline plasma HIV-1 RNA >100,000 copies/mL. 
 
At Week 48, 44 of 50 (88%) adolescent patients treated with Stribild achieved 
HIV-1 RNA <50 copies/mL and 4 achieved HIV-1 RNA ≥50 copies/mL; 1 patient discontinued study 
drug, and 1 had no virologic data at Week 48.  The mean decrease in HIV-1 RNA was −3.16 log10 
copies/mL, and the mean increase in CD4+ cell count was 229 cells/mm3.  No emergent resistance to 
Stribild was detected through Week 48. 
 
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.  
 
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. 
 



 

32 

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). 
 
The safety and efficacy of Stribild in children under the age of 12 years have not been established (see 
section 4.2 for information on paediatric use). 
 
5.2 Pharmacokinetic properties 
 
Absorption 
 
Following oral administration of Stribild with food in HIV-1 infected subjects, peak plasma 
concentrations were observed 4 hours post-dose for elvitegravir, 3 hours post-dose for cobicistat, 
3 hours post-dose for emtricitabine, and 2 hours for tenofovir following the rapid conversion of 
tenofovir disoproxil.  The steady-state mean Cmax, AUCtau, and Ctrough (mean ± SD) following multiple 
doses of Stribild in HIV-1 infected subjects, respectively, were 1.7 ± 0.39 µg/mL, 23 ± 7.5 µg•h/mL, 
and 0.45 ± 0.26 µg/mL for elvitegravir, which provides inhibitory quotient of ~ 10 (ratio of Ctrough: 
protein binding-adjusted IC95 for wild-type HIV-1 virus).  Corresponding steady-state mean Cmax, 
AUCtau, and Ctrough (mean ± SD) were 1.1 ± 0.40 µg/mL, 8.3 ± 3.8 µg•h/mL, and 0.05 ± 0.13 µg/mL 
for cobicistat, 1.9 ± 0.5 µg/mL, 13 ± 4.5 µg•h/mL, and 0.14 ± 0.25 µg/mL for emtricitabine, and 
0.45 ± 0.16 µg/mL, 4.4 ± 2.2 µg•h/mL, and 0.1 ± 0.08 µg/mL for tenofovir. 
 



 

33 

Relative to fasting conditions, the administration of Stribild with a light meal (~373 kcal, 20% fat) or 
high-fat meal (~800 kcal, 50% fat) resulted in increased exposures of elvitegravir and tenofovir.  For 
elvitegravir, Cmax and AUC increased 22% and 36% with a light meal, while increasing 56% and 91% 
with a high-fat meal, respectively.  The Cmax and AUC of tenofovir increased 20% and 25% 
respectively with a light meal, while the Cmax was unaffected and AUC increased 25% with a high fat 
meal.  Cobicistat exposures were unaffected by a light meal and although there was a modest decrease 
of 24% and 18% in Cmax and AUC respectively with a high-fat meal, no difference was observed in its 
pharmacoenhancing effect on elvitegravir.  Emtricitabine exposures were unaffected with light or 
high-fat meal. 
 
Distribution 
 
Elvitegravir is 98-99% bound to human plasma proteins and binding is independent of drug 
concentration over the range of 1 ng/mL to 1,600 ng/mL.  The mean plasma to blood drug 
concentration ratio was 1.37.  Cobicistat is 97-98% bound to human plasma proteins and the mean 
plasma to blood drug concentration ratio was 2. 
 
Following intravenous administration the volume of distribution of emtricitabine and tenofovir was 
approximately 1,400 mL/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.  At peak plasma concentration, the mean plasma to 
blood drug concentration ratio was ~ 1.0 and the mean semen to plasma drug concentration ratio was 
~ 4.0.  In vitro 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 
 
Elvitegravir undergoes oxidative metabolism by CYP3A (major route), and glucuronidation by 
UGT1A1/3 enzymes (minor route).  Following oral administration of boosted [14C]elvitegravir, 
elvitegravir was the predominant species in plasma, representing ~94% of the circulating radioactivity.  
Aromatic and aliphatic hydroxylation or glucuronidation metabolites are present in very low levels, 
display considerably lower anti-HIV activity and do not contribute to the overall antiviral activity of 
elvitegravir. 
 
Cobicistat is metabolised via CYP3A and/or CYP2D6-mediated oxidation and does not undergo 
glucuronidation.  Following oral administration of [14C]cobicistat, 99% of circulating radioactivity in 
plasma was unchanged cobicistat. 
 
In vitro studies indicate that emtricitabine is not an inhibitor of human CYP450 enzymes.  Following 
administration of [14C]emtricitabine, complete recovery of the emtricitabine dose was achieved in 
urine (~ 86%) and faeces (~ 14%).  Thirteen percent of the dose was recovered in the urine as three 
putative metabolites.  The biotransformation of emtricitabine includes oxidation of the thiol moiety to 
form the 3’-sulfoxide diastereomers (~ 9% of dose) and conjugation with glucuronic acid to form 
2’-O-glucuronide (~ 4% of dose).  No other metabolites were identifiable. 
 
In vitro studies have determined that neither tenofovir disoproxil nor tenofovir are substrates for the 
CYP450 enzymes.  Moreover, at concentrations substantially higher (approximately 300-fold) than 
those observed in vivo, tenofovir did not inhibit in vitro drug metabolism mediated by any of the major 
human CYP450 isoforms involved in drug biotransformation (CYP3A4, CYP2D6, CYP2C9, 
CYP2E1, or CYP1A1/2).  Tenofovir disoproxil had no effect on any of the CYP450 isoforms, except 
CYP1A1/2, where a small (6%) but statistically significant reduction in metabolism of a CYP1A1/2 
substrate was observed. 
 



 

34 

Elimination 
 
Following oral administration of [14C]elvitegravir/ritonavir, 94.8% of the dose was recovered in 
faeces, consistent with the hepatobiliary elimination of elvitegravir; 6.7% of the administered dose 
was recovered in urine.  The median terminal plasma half-life of elvitegravir following administration 
of Stribild is approximately 12.9 hours. 
 
Following oral administration of [14C]cobicistat, 86% and 8.2% of the dose were recovered in faeces 
and urine, respectively.  The median terminal plasma half-life of cobicistat following administration of 
Stribild is approximately 3.5 hours and the associated cobicistat exposures provide elvitegravir Ctrough 
approximately 10-fold above the protein-binding adjusted IC95 for wild-type HIV-1 virus. 
 
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 
(human organic anion transporter [hOAT1]) 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. 
 
Elderly 
 
Pharmacokinetics of elvitegravir, cobicistat, emtricitabine and tenofovir have not been evaluated in the 
elderly (over 65 years). 
 
Gender 
 
No clinically relevant pharmacokinetic differences due to gender have been identified for 
cobicistat-boosted elvitegravir, emtricitabine and tenofovir disoproxil. 
 
Ethnicity 
 
No clinically relevant pharmacokinetic differences due to ethnicity have been identified for 
cobicistat-boosted elvitegravir, emtricitabine and tenofovir disoproxil. 
 
Paediatric population 
 
Exposures of elvitegravir and tenofovir in paediatric patients aged 12 to <18 years who received 
Stribild in GS-US-236-0112 were increased by 30% and 37% respectively, when compared with 
historical adult controls.  Tenofovir exposures were in the range of those observed in tenofovir 
disoproxil-containing boosted-protease inhibitor regimens.  Exposures of cobicistat and emtricitabine 
in paediatric patients aged 12 to <18 years were similar to exposures achieved in adults.  
The pharmacokinetics of elvitegravir or cobicistat in paediatric subjects <12 years of age have not 
been fully established. 
 
Renal impairment 
 
A study of pharmacokinetics of cobicistat-boosted elvitegravir was performed in non-HIV-1 infected 
subjects with severe renal impairment (creatinine clearance below 30 mL/min).  No clinically relevant 
differences in elvitegravir or cobicistat pharmacokinetics were observed between subjects with severe 
renal impairment and healthy subjects.  No dose adjustment of elvitegravir or cobicistat is necessary 



 

35 

for patients with renal impairment.  The pharmacokinetics of emtricitabine and tenofovir are altered in 
subjects with renal impairment.  In subjects with creatinine clearance below 50 mL/min or with end 
stage renal disease requiring dialysis, Cmax, and AUC of emtricitabine and tenofovir were increased 
(see section 4.4). 
 
Hepatic impairment 
 
Both elvitegravir and cobicistat are primarily metabolised and eliminated by the liver.  A study of 
pharmacokinetics of cobicistat-boosted elvitegravir was performed in non-HIV-1 infected subjects 
with moderate hepatic impairment.  No clinically relevant differences in elvitegravir or cobicistat 
pharmacokinetics were observed between subjects with moderate impairment and healthy subjects.  
No dose adjustment of elvitegravir or cobicistat is necessary for patients with mild to moderate hepatic 
impairment.  The effect of severe hepatic impairment on the pharmacokinetics of elvitegravir or 
cobicistat has not been studied.  The pharmacokinetics of emtricitabine have not been studied in 
subjects with hepatic impairment; however, emtricitabine is not significantly metabolised by liver 
enzymes, so the impact of liver impairment should be limited.  Clinically relevant changes in tenofovir 
pharmacokinetics in patients with hepatic impairment were not observed.  Therefore, no tenofovir 
disoproxil dose adjustment is required in patients with hepatic impairment. 
 
Hepatitis B and/or hepatitis C virus co-infection 
 
Pharmacokinetics of emtricitabine and tenofovir disoproxil have not been fully evaluated in 
hepatitis B and/or C virus co-infected patients.  Limited data from population pharmacokinetic 
analysis (n = 24) indicated that hepatitis B and/or C virus infection had no clinically relevant effect on 
the exposure of boosted elvitegravir. 
 
Pregnancy and postpartum 
 
The results reported from a prospective study (IMPAACT P1026s) showed that treatment with 
cobicistat and elvitegravir-containing regimens during pregnancy results in lower elvitegravir and 
cobicistat exposures (Table 5).  
 
Table 5: Changes in pharmacokinetic parameters from the IMPAACT P1026s study for 
elvitegravir and cobicistat in women receiving cobicistat and elvitegravir-containing regimens 
during the second and third trimesters of pregnancy compared to paired postpartum data  
 

Comparison to paired 
postpartum data, n 

Mean % change of elvitegravir 
pharmacokinetic parametersa 

Mean % change of cobicistat 
pharmacokinetic parametersa 

AUC24 Cmax C24 AUC24 Cmax C24 
2T/PP, n = 14 ↓ 24%b ↓ 8% ↓ 81%b ↓ 44%b ↓ 28%b ↓ 60%b 
3T/PP, n = 24 ↓ 44%b ↓ 28%b ↓ 89%b ↓ 59%b ↓ 38%b ↓ 76%b 

2T = second trimester; 3T = third trimester; PP =postpartum 
a paired comparisons 
b P<0.10 compared with postpartum 
 
5.3 Preclinical safety data 
 
Elvitegravir was negative in an in vitro bacterial mutagenicity test (Ames test) and negative in an 
in vivo rat micronucleus assay at doses up to 2,000 mg/kg.  In an in vitro chromosomal aberration test, 
elvitegravir was negative with metabolic activation; however, an equivocal response was observed 
without activation. 
 
Cobicistat was not mutagenic or clastogenic in conventional genotoxicity assays.  Ex vivo rabbit 
studies and in vivo dog studies suggest that cobicistat has a low potential for QT prolongation, and 
may slightly prolong the PR interval and decrease left ventricular function at concentrations at least 
11-fold higher than the human exposure at the recommended 150 mg daily dose.  In a human clinical 
study of 35 healthy subjects, echocardiograms performed at baseline and after receiving 150 mg 



 

36 

cobicistat once daily for at least 15 days indicated no clinically significant change in left ventricular 
function. 
 
Reproductive toxicity studies in rats and rabbits with cobicistat showed no effects on mating, fertility, 
pregnancy or foetal parameters.  However increased postimplantation loss and decreased foetal 
weights were observed in rats associated with significant decreases in maternal body weights at 
125 mg/kg/day. 
 
Long term oral carcinogenicity studies with elvitegravir and cobicistat did not show any carcinogenic 
potential in mice and rats. 
 
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. 
 
Non-clinical data on tenofovir disoproxil reveal no special hazard for humans based on conventional 
studies of safety pharmacology, genotoxicity, carcinogenic potential, and toxicity to reproduction and 
development.  Findings in repeat-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 included 
kidney and bone changes and a decrease in serum phosphate concentration.  Bone toxicity was 
diagnosed as osteomalacia (monkeys) and reduced bone mineral density (rats and dogs).  Reproductive 
toxicity studies in rats and rabbits showed no effects on mating, fertility, pregnancy or foetal 
parameters.  However, tenofovir disoproxil reduced the viability index and weight of pups in a peri-
postnatal toxicity study at maternally toxic doses. 
 
The active substances elvitegravir, cobicistat and tenofovir disoproxil are persistent in the 
environment. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Tablet core 
Croscarmellose sodium 
Hydroxypropyl cellulose 
Lactose (as monohydrate) 
Magnesium stearate 
Microcrystalline cellulose 
Silicon dioxide 
Sodium lauryl sulfate 
 
Film-coating 
Indigo carmine aluminium lake (E132) 
Macrogol  3350 (E1521) 
Polyvinyl alcohol (partially hydrolysed) (E1203) 
Talc (E553B) 
Titanium dioxide (E171) 
Yellow iron oxide (E172) 
 
6.2 Incompatibilities 
 
Not applicable. 
 
6.3 Shelf life 
 
3 years. 



 

37 

 
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 90 (3 bottles of 30) film-coated tablets. 
 
Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal 
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Gilead Sciences Ireland UC 
Carrigtohill 
County Cork, T45 DP77 
Ireland 
 
 
8. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/13/830/001 
EU/1/13/830/002 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 24 May 2013 
Date of latest renewal: 19 April 2018 
 
 
10. DATE OF REVISION OF THE TEXT 
 
 
{MM/YYYY} 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu. 
  



 

38 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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 

 
 



 

39 

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

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

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

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

 
• Additional risk minimisation measures 
 
The Marketing Authorisation Holder (MAH) shall ensure that all physicians who are expected to 
prescribe/use Stribild in adolescent patients are provided with a physician educational pack containing 
the following: 
 
I. The Summary of Product Characteristics 
II. Stribild renal educational brochure for prescribers of adolescent patients. 
 
The MAH must agree the content and format of the medical educational pack with the national 
competent authority in each Member State prior to its distribution in their territory. 
 



 

40 

The Stribild renal educational brochure for prescribers of adolescent patients shall contain the 
following key safety messages: 
 
1. That there is an increased risk of renal disease in HIV infected patients associated with tenofovir 

disoproxil fumarate-containing products such as Stribild. 
2. That patients who have previously discontinued treatment with tenofovir disoproxil due to renal 

toxicity should not be treated with Stribild. 
3. That patients should have creatinine clearance calculated and urine glucose and urine protein 

determined prior to initiating Stribild therapy. 
4. The importance of regular monitoring of creatinine clearance, serum phosphate, urine glucose 

and urine protein during Stribild therapy. 
5. The recommended schedule for monitoring renal function considering the presence or absence 

of additional risk factors for renal impairment. 
6. That cobicistat inhibits the tubular secretion of creatinine and may cause modest increases in 

serum creatinine and modest declines in creatinine clearance without affecting renal glomerular 
function. 

7. That patients who experience a confirmed increase in serum creatinine of greater than 
26.5 µmol/L (0.3 mg/dL) from baseline should be closely monitored for renal safety. 

8. That use of Stribild should be avoided with concomitant or recent use of nephrotoxic medicinal 
products.  If Stribild is used with nephrotoxic medicinal products, renal function should be 
closely monitored according to the recommended schedule. 

9. That a multidisciplinary approach is recommended for the management of adolescent patients. 
10. That Stribild is not recommended for use in adolescent patients with renal impairment. 
11. That if serum phosphate is confirmed to be < 3.0 mg/dl (0.96 mmol/l) in any adolescent patient 

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

12.  That tenofovir disoproxil fumarate may cause a reduction in BMD and the effects of tenofovir 
disoproxil fumarate associated changes in BMD on long term bone health and future fracture 
risk are currently unknown in adolescent patients. 

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

 
 
  



 

41 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 
 

 
  



 

42 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 



 

43 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING AND THE IMMEDIATE 
PACKAGING 
 
BOTTLE AND CARTON LABELLING 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Stribild 150 mg/150 mg/200 mg/245 mg film-coated tablets 
elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each film-coated tablet contains 150 mg of elvitegravir, 150 mg of cobicistat, 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, see leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
30 film-coated tablets. 
30 tablets. 
 
90 (3 bottles of 30) film-coated tablets. 
90 (3 bottles of 30) tablets. 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
 
Oral use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 



 

44 

9. SPECIAL STORAGE CONDITIONS 
 
Store in the original package in order to protect from moisture.  Keep the bottle tightly closed. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Gilead Sciences Ireland UC 
Carrigtohill 
County Cork, T45 DP77 
Ireland 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/13/830/001 30 film-coated tablets 
EU/1/13/830/002 90 (3 bottles of 30) film-coated tablets 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Stribild [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]  



 

45 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 



 

46 

Package leaflet: Information for the user 
 

Stribild 150 mg/150 mg/200 mg/245 mg film-coated tablets 
elvitegravir/cobicistat/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 Stribild is and what it is used for 
2. What you need to know before you take Stribild 
3. How to take Stribild 
4. Possible side effects 
5. How to store Stribild 
6. Contents of the pack and other information 
 
 
1. What Stribild is and what it is used for 
 
Stribild contains four active substances: 
 
• elvitegravir, an antiretroviral medicine known as an integrase inhibitor 
• cobicistat, a booster (pharmacokinetic enhancer) of the effects of elvitegravir 
• emtricitabine, an antiretroviral medicine known as a nucleoside reverse transcriptase inhibitor 

(NRTI) 
• tenofovir disoproxil, an antiretroviral medicine known as a nucleotide reverse transcriptase 

inhibitor (NtRTI) 
 
Stribild is a single tablet regimen for the treatment of human immunodeficiency virus (HIV) infection 
in adults. 
 
Stribild is also used to treat HIV-1 infected 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 have caused side effects. 
 
Stribild reduces the amount of HIV in your body.  This will improve your immune system and 
reduce the risk of developing illnesses linked to HIV infection. 
 
 
2. What you need to know before you take Stribild 
 
Do not take Stribild 
 
• If you are allergic to elvitegravir, cobicistat, emtricitabine, tenofovir, tenofovir disoproxil, 

or any of the other ingredients of this medicine (listed in section 6 of this leaflet). 
• If you stopped treatment with any medicine containing tenofovir disoproxil on the advice of 

your doctor following problems with your kidney function. 
• If you are taking one of these medicines: 

- alfuzosin (used to treat an enlarged prostate gland) 
- amiodarone, quinidine (used to correct irregular heartbeats) 



 

47 

- dabigatran (used to prevent and treat blood clots) 
- carbamazepine, phenobarbital, phenytoin (used to prevent seizures) 
- rifampicin (used to prevent and treat tuberculosis and other infections) 
- dihydroergotamine, ergotamine, ergometrine (used to treat migraine headache) 
- cisapride (used to relieve certain stomach problems) 
- St. John’s wort (Hypericum perforatum, a herbal remedy used for depression and 

anxiety) or products that contain it 
- lovastatin, simvastatin (used to lower blood cholesterol) 
- pimozide, lurasidone (used to treat abnormal thoughts or feelings) 
- sildenafil (used to treat pulmonary arterial hypertension – a lung disease that makes 

breathing difficult) 
- orally administered midazolam, triazolam (used to help you sleep and/or relieve 

anxiety) 
 
 If any of these applies to you, you should not take Stribild and you should tell your doctor 

immediately. 
 
Warnings and precautions 
 
You must remain under the care of your doctor while taking Stribild. 
 
You can still pass on HIV when taking this medicine, although the risk is lowered by effective 
antiretroviral therapy.  Discuss with your doctor the precautions needed to avoid infecting other 
people.  This medicine is not a cure for HIV infection.  While taking Stribild you may still develop 
infections or other illnesses associated with HIV infection. 
 
Talk to your doctor before taking Stribild: 
• If you have kidney problems, or have had kidney problems, or if tests have shown problems 

with your kidneys.  Your doctor will carefully consider whether to treat you with Stribild. 
 

Stribild may affect your kidneys.  Before starting treatment, your doctor will order blood tests to 
assess your kidney function.  Your doctor will also order blood tests during treatment to monitor 
your kidneys. 

 
Stribild is not usually taken with other medicines that can damage your kidneys (see Other 
medicines and Stribild).  If this is unavoidable, your doctor will monitor your kidney function 
more frequently. 
 

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

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

 
• If you are over 65.  Stribild has not been studied in patients over 65 years of age.  If you are 

older than this and are prescribed Stribild, your doctor will monitor you carefully. 
 
 If any of these applies to you, talk to your doctor before taking Stribild. 
 



 

48 

While you are taking Stribild 
 
Once you start taking Stribild, look out for: 
 
• any signs of inflammation or infection 
• bone problems 
 
 If you notice any of these symptoms, tell your doctor immediately. 
 
Children and adolescents 
 
Do not give this medicine to children under 12 years of age.  The use of Stribild in children below 
12 years of age and who weigh less than 35kg has not been studied. 
 
Other medicines and Stribild 
 
There are some medicines that should never be taken with Stribild. 
These are mentioned above under the heading “Do not take Stribild - If you are taking one of these 
medicines”. 
 
Tell your doctor or pharmacist if you are taking any other medicines or have recently taken any.  
Stribild may interact with other medicines.  As a result, the amounts of Stribild or other medicines in 
your blood may be affected.  This may stop your medicines from working properly, or may make any 
side effects worse.  In some cases, your doctor may need to adjust your dose or check your blood 
levels. 
 
It is especially important to talk to your doctor if you are taking any of the following: 
 
• any other medicines containing: 

- tenofovir disoproxil  
- tenofovir alafenamide 
- lamivudine 
- adefovir dipivoxil 

 
• medicines that may damage your kidneys, examples include: 

- aminoglycosides (such as streptomycin, neomycin and gentamicin), vancomycin (for 
bacterial infections) 

- foscarnet, ganciclovir, cidofovir (for viral infections) 
- amphotericin B, pentamidine (for fungal infections) 
- interleukin-2, also called aldesleukin (to treat cancer) 
- non-steroidal anti-inflammatory drugs (NSAIDs, to relieve bone or muscle pains) 

 
It is also important to tell your doctor if you are taking any of the following types of medicines: 
 
• antifungals, used to treat fungal infections, such as: 

- ketoconazole, itraconazole, voriconazole, fluconazole and posaconazole 
• antivirals, used to treat hepatitis C infection: 

- ledipasvir/sofosbuvir, sofosbuvir/velpatasvir and sofosbuvir/velpatasvir/voxilaprevir 
• antibiotics, used to treat bacterial infections including tuberculosis, containing: 

- rifabutin, clarithromycin or telithromycin 
• antidepressants, used to treat depression: 

- medicines containing trazodone or escitalopram 
• sedatives and hypnotics, used to treat anxiety: 

- buspirone, clorazepate, diazepam, estazolam, flurazepam and zolpidem 
• immunosuppressants, used to control your body’s immune response after a transplant, such as: 

- ciclosporin, sirolimus and tacrolimus 



 

49 

• corticosteroids including: 
- betamethasone, budesonide, fluticasone, mometasone, prednisone, triamcinolone. 
These medicines are used to treat allergies, asthma, inflammatory bowel diseases, inflammatory 
conditions of the eyes, joints and muscles and other inflammatory conditions. If alternatives 
cannot be used, its use should only take place after medical evaluation and under close 
monitoring by your doctor for corticosteroid side effects. 

• medicines used to treat diabetes: 
- metformin 

• contraceptive pill, used to prevent pregnancy 
• erectile dysfunction medicines, used to treat impotence, such as: 

- sildenafil, tadalafil and vardenafil 
• heart medicines, such as: 

- digoxin, disopyramide, flecainide, lidocaine, mexiletine, propafenone, metoprolol, 
timolol, amlodipine, diltiazem, felodipine, nicardipine, nifedipine and verapamil 

• medicines used to treat pulmonary arterial hypertension: 
- bosentan 

• anticoagulants, used to prevent and treat blood clots, such as: 
- warfarin, edoxaban, apixaban and rivaroxaban 

• bronchodilators, used to treat asthma and other lung-related problems: 
- salmeterol 

• cholesterol lowering medicines, such as: 
- rosuvastatin, atorvastatin, pravastatin, fluvastatin and pitavastatin 

• medicines used to treat gout: 
- colchicine 

• antiplatelets, used to reduce the risk of blood clots such as: 
- clopidogrel  

• medicines or oral supplements containing minerals (such as magnesium, aluminium, 
calcium, iron, zinc), such as: 
- mineral supplements, vitamins (including multivitamins), antacids and laxatives  
 If you are taking medicines, oral supplements, antacids or laxatives containing minerals 

(such as magnesium, aluminium, calcium, iron, zinc), take them at least 4 hours before or 
at least 4 hours after Stribild. 

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

without contacting your doctor. 
 
Pregnancy and breast-feeding 
 
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 
your doctor or pharmacist for advice before taking this medicine. 
 
• Tell your doctor immediately if you become pregnant, think you may be pregnant or are 

planning to have a baby.  Pregnant women should not take Stribild.  The amount of this 
medicine in your blood may decrease during pregnancy which may stop it from working 
properly. 

• Use effective contraception while taking Stribild. 
 
Do not breast-feed during treatment with Stribild.  This is because some of 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 
 
Stribild can cause dizziness, tiredness or insomnia.  If you are affected while taking Stribild, do not 
drive and do not use any tools or machines. 
 



 

50 

Stribild 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. 
 
Stribild 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 Stribild 
 
Always take this medicine exactly as your doctor has told you.  Check with your doctor or pharmacist 
if you are not sure. 
 
Recommended dose for adults and adolescents aged 12 to less than 18 years who weigh at least 
35 kg: 
 
• One tablet each day by mouth, with food.  Do not chew, crush or split the tablet. 
 
Always take the dose recommended by your doctor.  This is to make sure that your medicine is 
fully effective, and to reduce the risk of developing resistance to the treatment.  Do not change the 
dose unless your doctor tells you to. 
 
If you are taking medicines, oral supplements, antacids or laxatives containing minerals (such as 
magnesium, aluminium, calcium, iron, zinc), take them at least 4 hours before or at least 4 hours after 
Stribild. 
 
If you take more Stribild than you should 
 
If you accidentally take more than the recommended dose of Stribild you may be at increased risk of 
experiencing possible side effects with this medicine (see section 4, Possible side effects). 
 
Contact your doctor or nearest emergency department immediately for advice.  Keep the tablet bottle 
with you so that you can easily describe what you have taken. 
 
If you forget to take Stribild 
 
It is important not to miss a dose of Stribild. 
 
If you do miss a dose: 
• and you notice within 18 hours of the time you usually take Stribild, you must take the tablet 

as soon as possible.  Always take the tablet with food.  Then take the next dose as usual. 
• and you notice 18 hours or more after the time you usually take Stribild, then do not take the 

missed dose.  Wait and take the next dose, with food, at your usual time. 
 
If you vomit less than 1 hour after taking Stribild, take another tablet with food. 
 
Do not stop taking Stribild 
 
Do not stop taking Stribild without talking to your doctor.  Stopping Stribild can seriously affect 
your response to future treatment.  If Stribild is stopped for any reason, speak to your doctor before 
you restart taking Stribild tablets. 
 



 

51 

When your supply of Stribild starts to run low, get more from your doctor or pharmacist.  This is 
very important because the amount of virus may start to increase if the medicine is stopped for even a 
short time.  The disease may then become harder to treat. 
 
If you have HIV infection and hepatitis B, it is especially important not to stop your Stribild 
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 (such as yellowing of your skin or 
the white part of your eyes, dark “tea-coloured” urine, light-coloured stools, loss of appetite for 
several days or longer, feeling or being sick, or stomach-area pain). 

 
If you have any further questions on the use of this medicine, ask your doctor or pharmacist. 
 
 
4. Possible side effects 
 
During HIV therapy there may be an increase in weight and in levels of blood lipids and glucose.  This 
is partly linked to restored health and life style, and in the case of blood lipids sometimes to the HIV 
medicines themselves.  Your doctor will test for these changes. 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them.  When 
treating HIV infection, it is not always possible to tell whether some of the unwanted effects are 
caused by Stribild or by other medicines that you are taking at the same time, or by the HIV disease 
itself. 
 
Possible serious side effects: tell a doctor immediately 
 
• Lactic acidosis (excess lactic acid in the blood) is a rare but potentially life-threatening side 

effect of some HIV medicines.  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 
- tiredness or drowsiness 
- feeling sick (nausea), being sick (vomiting) 
- stomach pain 

 If you think you may have lactic acidosis, tell your doctor immediately. 
 
• Any signs of inflammation or infection.  In some patients with advanced HIV infection 

(AIDS) and a history of opportunistic infections (infections that occur in people with a weak 
immune system), signs and symptoms of inflammation from previous infections may occur soon 
after 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.  In addition to the opportunistic infections, autoimmune 
disorders (a condition that occurs when the immune system attacks healthy body tissue) may 
also occur after you start taking medicines for the treatment of your HIV infection.  
Autoimmune disorders may occur many months after the start of treatment.  If you notice 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, please inform your doctor immediately to seek necessary treatment. 

 If you notice any symptoms of inflammation or infection, tell your doctor immediately. 
 
Very common side effects 
(may affect at least 1 in every 10 patients treated) 
• diarrhoea 



 

52 

• vomiting 
• feeling sick (nausea) 
• weakness 
• headache, dizziness 
• rash 
 
Tests may also show: 
• decreased phosphate in your blood 
• increased levels of creatine kinase in the blood that may result in muscle pain and weakness 
 
Common side effects 
(may affect 1 to 10 in every 100 patients treated) 
• decreased appetite 
• difficulty sleeping (insomnia), abnormal dreams 
• pain, stomach pain 
• problems with digestion resulting in discomfort after meals (dyspepsia) 
• feeling bloated 
• constipation, wind (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 
• tiredness 
 
Tests may also show: 
• low white blood cell count (which can make you more prone to infection) 
• increased sugar, fatty acids (triglycerides), bilirubin in your blood 
• liver and pancreas problems 
• increased levels of creatinine in your blood 
 
Uncommon side effects 
(may affect up to 1 in every 100 patients treated) 
• suicidal ideation and suicide attempt (in patients who have had depression or mental health 

problems before), depression 
• back pain caused by kidney problems, including kidney failure.  Your doctor may do blood tests 

to see if your kidneys are working properly 
• damage to kidney tubule cells 
• swelling of the face, lips, tongue or throat 
• pain in the abdomen (tummy) caused by inflammation of the pancreas (pancreatitis) 
• breakdown of muscle, muscle pain or weakness 
 
Tests may also show: 
• anaemia (low red blood cell count) 
• decreased levels of potassium in the blood 
• changes to your urine 
 
Rare side effects 
(may affect up to 1 in every 1,000 patients treated) 
• lactic acidosis (see Possible serious side effects: tell a doctor immediately) 
• yellow skin or eyes, itching, or pain in the abdomen (tummy) caused by inflammation of the 

liver (hepatitis) 
• fatty liver 
• inflammation of the kidney (nephritis) 
• passing a lot of urine and feeling thirsty (nephrogenic diabetes insipidus) 
• softening of the bones (with bone pain and sometimes resulting in fractures) 



 

53 

 
The 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 may 
occur due to damage to kidney tubule cells. 
 
 If any of the side effects get serious tell your doctor. 
 
Other effects that may be seen during HIV treatment 
 
The frequency of the following side effects is not known (frequency cannot be estimated from the 
available data). 
 
• Bone problems.  Some patients taking combination antiretroviral medicines such as Stribild 

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

 
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. 
 
 If you get any side effects, talk to your doctor or pharmacist.  This includes any possible side 

effects not listed in this leaflet. 
 
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 Stribild 
 
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. 
 
 

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


 

54 

6. Contents of the pack and other information 
 
What Stribild contains 
 
The active substances are elvitegravir, cobicistat, emtricitabine and tenofovir disoproxil.  Each 
Stribild film-coated tablet contains 150 mg of elvitegravir, 150 mg of cobicistat, 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 
 
Tablet core: 
Croscarmellose sodium, hydroxypropyl cellulose, lactose monohydrate, magnesium stearate, 
microcrystalline cellulose, silicon dioxide, sodium lauryl sulfate. 
 
Film-coating: 
Indigo carmine aluminium lake (E132), macrogol  3350 (E1521), polyvinyl alcohol (partially 
hydrolysed) (E1203), talc (E553B), titanium dioxide (E171), yellow iron oxide (E172). 
 
What Stribild looks like and contents of the pack 
 
Stribild film-coated tablets are green, capsule-shaped tablets, debossed on one side with “GSI” and the 
number “1” surrounded by a square box on the other side of the tablet.  Stribild comes in bottles of 
30 tablets (with a silica gel desiccant that must be kept in the bottle to help protect your tablets).  The 
silica gel desiccant is contained in a separate sachet or canister and should not be swallowed. 
 
The following pack sizes are available: outer cartons containing 1 bottle of 30 film-coated tablets and 
90 (3 bottles of 30) film-coated tablets.  Not all pack sizes may be marketed. 
 
Marketing Authorisation Holder 
Gilead Sciences Ireland UC 
Carrigtohill 
County Cork, T45 DP77 
Ireland 
 
Manufacturer 
Gilead Sciences Ireland UC 
IDA Business & Technology Park 
Carrigtohill 
County Cork 
Ireland 
 
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 
 



 

55 

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

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

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

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

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

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

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

Österreich 
Gilead Sciences GesmbH 
Tel: + 43 1 260 830 
 

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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
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