Stribild

Name: Stribild

Stribild Overview

Stribild is a prescription medication used to treat human immunodeficiency virus (HIV) in adults who have never taken HIV medications before. Stribild is a single tablet containing four medications which together provide a complete treatment regimen for HIV infection. 

Emtricitabine and tenofovir belong to a group of drugs called nucleoside reverse transcriptase inhibitors (NRTIs). Elvitegravir belongs to a group of drugs called HIV integrase strand transfer inhibitor (HIV-1 INSTI). Elvitegravir, emtricitabine, and tenofovir work by decreasing the amount of HIV in the blood. Cobicistat belongs to a group of drugs called CYP3A inhibitors. Cobicistat helps to keep elvitegravir in the body longer so that the medication will have a greater effect.

This medication comes in tablet form and is taken once daily, with food. Common side effects of Stribild include nausea and diarrhea.

Uses of Stribild

Stribild is a prescription medication that is used without other antiretroviral medicines to treat Human Immunodeficiency Virus-1   (HIV-1) in adults who have never taken HIV-1 medicines before. HIV-1 is the virus that causes AIDS (Acquired Immune Deficiency Syndrome).

Stribild contains the prescription medicines elvitegravir, cobicistat, emtricitabine (Emtriva) and tenofovir (Viread).

It is not known if elvitegravir/cobicistat/emtricitabine/tenofovir is safe and effective in children under 18 years of age.

When used to treat HIV-1 infection, Stribild may:

  • Reduce the amount of HIV-1 in your blood. This is called "viral load".
  • Increase the number of CD4+ (T) cells in your blood that help fight off other infections.
  • Reduce the amount of HIV-1 and increasing the CD4+ (T) cells in your blood may help improve your immune system. This may reduce your risk of death or getting infections that can happen when your immune system is weak (opportunistic infections).

Stribild does not cure HIV-1 infections or AIDS. You must stay on continuous HIV-1 therapy to control HIV-1 infection and decrease HIV-related illnesses.

 

Side Effects of Stribild

Serious side effects have been reported. See "Drug Precautions" section.

The most common side effects of Stribild include:

  • nausea
  • diarrhea

Tell your healthcare provider if you have any side effect that bothers you or that does not go away.

These are not all the possible side effects. For more information, ask your healthcare provider or pharmacist.

Call your healthcare provider for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Stribild Food Interactions

Medicines can interact with certain foods. In some cases, this may be harmful and your doctor may advise you to avoid certain foods. In the case of Stribild there are no specific foods that you must exclude from your diet when receiving this medication.

Stribild Overdose

If you take too much Stribild, call your healthcare provider or go to the nearest hospital emergency room right away.

Commonly used brand name(s)

In the U.S.

  • Stribild

Available Dosage Forms:

  • Tablet

Therapeutic Class: Anti-Infective Agent

Pharmacologic Class: Integrase Inhibitor

Before Using Stribild

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies have not been performed on the relationship of age to the effects of elvitegravir, cobicistat, emtricitabine, and tenofovir combination in children younger than 12 years of age or weighing less than 35 kilograms. Safety and efficacy have not been established.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of elvitegravir, cobicistat, emtricitabine, and tenofovir combination in the elderly. However, elderly patients are more likely to have age-related kidney, liver, or heart problems, which may require caution for patients receiving this medicine.

Pregnancy

Pregnancy Category Explanation
All Trimesters B Animal studies have revealed no evidence of harm to the fetus, however, there are no adequate studies in pregnant women OR animal studies have shown an adverse effect, but adequate studies in pregnant women have failed to demonstrate a risk to the fetus.

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

  • Alfuzosin
  • Carbamazepine
  • Cisapride
  • Colchicine
  • Conivaptan
  • Crizotinib
  • Dihydroergotamine
  • Doxorubicin
  • Doxorubicin Hydrochloride Liposome
  • Dronedarone
  • Eletriptan
  • Eliglustat
  • Eplerenone
  • Ergonovine
  • Ergotamine
  • Fosphenytoin
  • Isavuconazonium Sulfate
  • Ivabradine
  • Lomitapide
  • Lovastatin
  • Lurasidone
  • Maraviroc
  • Methylergonovine
  • Midazolam
  • Naloxegol
  • Pazopanib
  • Phenobarbital
  • Phenytoin
  • Pimozide
  • Primidone
  • Ranolazine
  • Rifampin
  • Riociguat
  • Romidepsin
  • Sildenafil
  • Silodosin
  • Simvastatin
  • St John's Wort
  • Tolvaptan
  • Triazolam
  • Venetoclax

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

  • Ado-Trastuzumab Emtansine
  • Afatinib
  • Alprazolam
  • Aluminum Carbonate, Basic
  • Aluminum Hydroxide
  • Aluminum Phosphate
  • Amiodarone
  • Amprenavir
  • Apixaban
  • Aprepitant
  • Aripiprazole
  • Atazanavir
  • Avanafil
  • Bedaquiline
  • Betrixaban
  • Boceprevir
  • Bosentan
  • Bosutinib
  • Brigatinib
  • Bromocriptine
  • Budesonide
  • Cabazitaxel
  • Cabozantinib
  • Calcifediol
  • Calcium Carbonate
  • Cariprazine
  • Ceritinib
  • Cilostazol
  • Clarithromycin
  • Cobimetinib
  • Cyclophosphamide
  • Cyclosporine
  • Dabrafenib
  • Daclatasvir
  • Darunavir
  • Dasatinib
  • Deflazacort
  • Delamanid
  • Delavirdine
  • Dexamethasone
  • Diazepam
  • Didanosine
  • Digoxin
  • Dihydroxyaluminum Aminoacetate
  • Dihydroxyaluminum Sodium Carbonate
  • Disopyramide
  • Docetaxel
  • Domperidone
  • Donepezil
  • Erlotinib
  • Erythromycin
  • Eslicarbazepine Acetate
  • Eszopiclone
  • Etravirine
  • Everolimus
  • Fentanyl
  • Flecainide
  • Fluoxetine
  • Fluticasone
  • Fosamprenavir
  • Fosaprepitant
  • Haloperidol
  • Hydrocortisone
  • Ibrutinib
  • Idelalisib
  • Ifosfamide
  • Iloperidone
  • Irinotecan
  • Irinotecan Liposome
  • Itraconazole
  • Ivacaftor
  • Ketoconazole
  • Lapatinib
  • Ledipasvir
  • Levomilnacipran
  • Lidocaine
  • Lopinavir
  • Macitentan
  • Magaldrate
  • Magnesium Carbonate
  • Magnesium Hydroxide
  • Magnesium Oxide
  • Magnesium Trisilicate
  • Manidipine
  • Methadone
  • Mexiletine
  • Midostaurin
  • Mifepristone
  • Morphine
  • Morphine Sulfate Liposome
  • Netupitant
  • Nevirapine
  • Nifedipine
  • Nilotinib
  • Nimodipine
  • Nisoldipine
  • Olaparib
  • Orlistat
  • Oxcarbazepine
  • Oxycodone
  • Palbociclib
  • Panobinostat
  • Pimavanserin
  • Piperaquine
  • Pixantrone
  • Ponatinib
  • Prednisone
  • Propafenone
  • Quetiapine
  • Quinidine
  • Reboxetine
  • Regorafenib
  • Retapamulin
  • Ribociclib
  • Rifabutin
  • Rifapentine
  • Ritonavir
  • Rivaroxaban
  • Rosuvastatin
  • Ruxolitinib
  • Salmeterol
  • Saquinavir
  • Simeprevir
  • Sirolimus
  • Sodium Bicarbonate
  • Sunitinib
  • Suvorexant
  • Tacrolimus
  • Tadalafil
  • Tamoxifen
  • Tamsulosin
  • Telithromycin
  • Temsirolimus
  • Thiotepa
  • Ticagrelor
  • Tipranavir
  • Topotecan
  • Toremifene
  • Trabectedin
  • Tramadol
  • Trazodone
  • Valbenazine
  • Vardenafil
  • Vemurafenib
  • Vilanterol
  • Vilazodone
  • Vinblastine
  • Vincristine
  • Vincristine Sulfate Liposome
  • Vinflunine
  • Vorapaxar
  • Voriconazole
  • Warfarin
  • Zolpidem

Using this medicine with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

  • Aripiprazole Lauroxil
  • Atazanavir
  • Darunavir
  • Indinavir
  • Lopinavir
  • Nelfinavir
  • Ritonavir
  • Tipranavir

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

  • Bone problems (eg, fracture, osteomalacia), history of or
  • Fanconi syndrome (kidney disease), history of or
  • Hepatitis B infection, history of or
  • Kidney failure, history of—Use with caution. May make these conditions worse.
  • Kidney disease, moderate to severe or
  • Liver disease, severe—Use is not recommended in patients with these conditions.

Adverse Reactions

The following adverse reactions are discussed in other sections of the labeling:

  • Severe Acute Exacerbations of Hepatitis B in Patients Coinfected with HIV-1 and HBV [see Boxed Warning and Warnings and Precautions (5.1)].
  • New Onset or Worsening Renal Impairment [see Warnings and Precautions (5.2)].
  • Lactic Acidosis/Severe Hepatomegaly with Steatosis [see Warnings and Precautions (5.3)].
  • Bone Loss and Mineralization Defects [see Warnings and Precautions (5.5)].
  • Immune Reconstitution Syndrome [see Warnings and Precautions (5.6)].

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Clinical Trials in HIV-1 Infected Adult Subjects with No Antiretroviral Treatment History

The safety assessment of Stribild is based on the Week-144 pooled data from 1408 subjects in two randomized, double-blind, active-controlled clinical trials, Study 102 and Study 103, in antiretroviral treatment-naïve HIV-1 infected adult subjects [see Clinical Studies (14)]. A total of 701 subjects received Stribild once daily in these two studies.

The proportion of subjects who discontinued treatment with Stribild, ATRIPLA, or ATV+RTV+TRUVADA due to adverse events, regardless of severity, was 6.0%, 7.4%, and 8.5%, respectively. Table 2 displays the frequency of adverse reactions greater than or equal to 5% of subjects in any treatment arm.

Table 2 Adverse Reactions* (All Grades) Reported in ≥5% of Adult Subjects in Any Treatment Arm in Studies 102 and 103 (Week-144 Analysis)
Stribild
N=701
ATRIPLA
N=352
ATV+RTV+TRUVADA
N=355
* Frequencies of adverse reactions are based on all treatment-emergent adverse events attributed to study drugs. † Rash event includes dermatitis, drug eruption, eczema, pruritus, pruritus generalized, rash, rash erythematous, rash generalized, rash macular, rash maculo-papular, rash morbilliform, rash papular, rash pruritic, and urticaria.
EYE DISORDERS
  Ocular icterus <1% 0% 13%
GASTROINTESTINAL DISORDERS
  Diarrhea 12% 11% 17%
  Flatulence 2% <1% 8%
  Nausea 16% 9% 14%
GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS
  Fatigue 4% 8% 6%
HEPATOBILIARY DISORDERS
  Jaundice 0% <1% 9%
NERVOUS SYSTEM DISORDERS
  Somnolence 1% 7% 1%
  Headache 7% 4% 6%
  Dizziness 3% 21% 5%
PSYCHIATRIC DISORDERS
  Insomnia 3% 9% 1%
  Abnormal dreams 9% 27% 4%
SKIN AND SUBCUTANEOUS TISSUE DISORDERS
  Rash† 4% 15% 6%

See Warnings and Precautions (5.2) for a discussion of renal adverse reactions from clinical trials experience with Stribild.

Additional adverse reactions observed with Stribild included suicidal ideation and suicide attempt (0.3%), all in subjects with a preexisting history of depression or psychiatric illness.

Clinical Trials in Virologically Suppressed HIV-1 Infected Adult Subjects

No new adverse reactions to Stribild through Week 48 were identified in 584 virologically stably suppressed adult subjects switching to Stribild from a regimen containing a RTV-boosted protease inhibitor (PI) or a non-nucleoside reverse transcriptase inhibitor (NNRTI). In a combined analysis of studies 115 and 121, the frequency of adverse reactions (all grades) was 24% in subjects switching to Stribild compared to 6% of subjects in either group who stayed on their baseline antiretroviral regimen, RTV-boosted PI+TRUVADA or NNRTI+TRUVADA. Common adverse reactions that occurred in greater than or equal to 2% of subjects switching to Stribild were nausea (4%), flatulence (2%), and headache (2%). The proportion of subjects who discontinued treatment with Stribild, the RTV-boosted PI, or the NNRTI due to adverse events was 2%, 3%, and 1%, respectively.

Clinical Trials of the Components of Stribild in Adult Subjects

Emtricitabine and Tenofovir DF: In addition to the adverse reactions observed with Stribild, the following adverse reactions occurred in at least 5% of treatment-experienced or treatment-naïve subjects receiving emtricitabine or tenofovir DF with other antiretroviral agents in other clinical trials: depression, abdominal pain, dyspepsia, vomiting, fever, pain, nasopharyngitis, pneumonia, sinusitis, upper respiratory tract infection, arthralgia, back pain, myalgia, paresthesia, peripheral neuropathy (including peripheral neuritis and neuropathy), anxiety, increased cough, and rhinitis.

Skin discoloration has been reported with higher frequency among emtricitabine-treated subjects; it was manifested by hyperpigmentation on the palms and/or soles and was generally mild and asymptomatic. The mechanism and clinical significance are unknown.

Laboratory Abnormalities:

The frequency of laboratory abnormalities (Grades 3–4) occurring in at least 2% of subjects receiving Stribild in studies 102 and 103 are presented in Table 3.

Table 3 Laboratory Abnormalities (Grades 3–4) Reported in ≥2% of Adult Subjects Receiving Stribild in Studies 102 and 103 (Week-144 Analysis)
Laboratory Parameter Abnormality*,† Stribild
N=701
ATRIPLA
N=352
ATV+RTV+TRUVADA
N=355
* Frequencies are based on treatment-emergent laboratory abnormalities. † For subjects with serum amylase >1.5 × upper limit of normal (ULN), lipase test was also performed. The frequency of increased lipase (Grades 3–4) occurring in Stribild (N=69), ATRIPLA (N=40), and ATV+RTV+TRUVADA (N=38) was 17%, 15%, and 24%, respectively.
AST (>5.0 × ULN) 3% 6% 6%
ALT (>3.0 × ULN) 2% 5% 4%
Amylase* (>2.0 × ULN) 3% 3% 5%
Creatine Kinase (≥10.0 × ULN) 8% 15% 11%
Urine RBC (Hematuria) (>75 RBC/HPF) 4% 2% 4%

In Study 103, BMD was assessed by DEXA in a nonrandom subset of 120 subjects (Stribild group, N=54; ATV+RTV+TRUVADA group, N=66). Mean percentage decreases in BMD from baseline to Week 144 in the Stribild group were comparable to that in the ATV+RTV+TRUVADA group at the lumbar spine (–1.43% versus –3.68%, respectively) and at the hip (–2.83% versus –3.77%, respectively). In studies 102 and 103, bone fractures occurred in 27 subjects (3.9%) in the Stribild group, 8 subjects (2.3%) in the ATRIPLA group, and 19 subjects (5.4%) in the ATV+RTV+TRUVADA group. These findings were consistent with data from an earlier 144-week trial of treatment-naïve subjects receiving tenofovir DF + lamivudine + efavirenz.

Proteinuria (all grades) occurred in 52% of subjects receiving Stribild, 41% of subjects receiving ATRIPLA, and 42% of subjects receiving ATV+RTV+TRUVADA.

The cobicistat component of Stribild has been shown to increase serum creatinine and decrease estimated creatinine clearance due to inhibition of tubular secretion of creatinine without affecting renal glomerular function. In studies 102 and 103, increases in serum creatinine and decreases in estimated creatinine clearance occurred early in treatment with Stribild, after which levels stabilized. Table 4 displays the mean changes in serum creatinine and eGFR levels at Week 144 and the percentage of subjects with elevations in serum creatinine (all grades).

Table 4 Change from Baseline in Serum Creatinine and eGFR and Incidence of Elevated Serum Creatinine (All Grades) in Studies 102 and 103 at Week 144
Stribild
N=701
ATRIPLA
N=352
ATV+RTV+TRUVADA
N=355
* Mean change ± standard deviation
Serum Creatinine (mg/dL)* 0.14 (±0.14) 0.01 (±0.12) 0.09 (±0.15)
eGFR by Cockcroft-Gault (mL/minute)* –14.0 (±16.6) –1.9 (±17.9) –9.8 (±19.4)
Subjects with Elevations in Serum Creatinine (All Grades) (%) 12 2 6

Emtricitabine or Tenofovir DF: In addition to the laboratory abnormalities observed with Stribild, the following laboratory abnormalities have been previously reported in subjects treated with emtricitabine or tenofovir DF with other antiretroviral agents in other clinical trials: Grade 3 or 4 laboratory abnormalities of ALT (M: greater than 215 U per L; F: greater than 170 U per L), alkaline phosphatase (greater than 550 U per L), bilirubin (greater than 2.5 × ULN), serum glucose (less than 40 or greater than 250 mg per dL), glycosuria (greater than or equal to 3+), neutrophils (less than 750 per mm3), fasting cholesterol (greater than 240 mg per dL), and fasting triglycerides (greater than 750 mg per dL).

Serum Lipids: In the clinical trials of Stribild, a similar percentage of subjects receiving Stribild, ATRIPLA, and ATV+RTV+TRUVADA were on lipid-lowering agents at baseline (12%, 12%, and 13%, respectively). While receiving study drug through Week 144, an additional 11% of Stribild subjects were started on lipid-lowering agents, compared to 13% of ATRIPLA and 12% of ATV+RTV+TRUVADA subjects.

Changes from baseline in total cholesterol, HDL-cholesterol, LDL-cholesterol, and triglycerides are presented in Table 5.

Table 5 Lipid Values, Mean Change from Baseline at Week 144 in Adult Subjects Receiving Stribild or Comparator in Studies 102 and 103
Stribild
N=701
ATRIPLA
N=352
ATV+RTV+TRUVADA
N=355
Baseline Week 144 Baseline Week 144 Baseline Week 144
mg/dL Change* mg/dL Change* mg/dL Change*
* The change from baseline is the mean of within-patient changes from baseline for patients with both baseline and Week 144 values.
Total Cholesterol (fasted) 166
[N=675]
+17
[N=535]
161
[N=343]
+22
[N=262]
168
[N=337]
+16
[N=243]
HDL-cholesterol (fasted) 43
[N=675]
+7
[N=535]
43
[N=343]
+9
[N=262]
42
[N=335]
+7
[N=242]
LDL-cholesterol (fasted) 100
[N=675]
+15
[N=535]
97
[N=343]
+19
[N=262]
101
[N=337]
+18
[N=242]
Triglycerides (fasted) 122
[N=675]
+12
[N=535]
121
[N=343]
+5
[N=262]
132
[N=337]
+22
[N=242]

Clinical Trials in Pediatric Subjects

The safety of Stribild in 50 HIV-1 infected, treatment-naïve pediatric subjects aged 12 to less than 18 years and weighing at least 35 kg (77 lbs) was evaluated through 48 weeks in an open-label clinical trial (Study 112) [see Clinical Studies (14.4)]. In this study, the safety profile of Stribild was similar to that in adults. Twenty-two subjects (44%) had treatment-emergent proteinuria (Grades 1–2). One subject met laboratory criteria for proximal renal tubulopathy, evidenced by sustained proteinuria and normoglycemic glycosuria beginning at Week 32. The subject continued to receive Stribild and was ultimately lost to follow-up.

Among the 50 pediatric subjects receiving Stribild for 48 weeks, mean BMD increased from baseline to Week 48, +0.68% at the lumbar spine and +0.77% for total body less head. Mean changes from baseline BMD Z-scores (height-age adjusted) to Week 48 were –0.09 for lumbar spine and –0.12 for total body less head. At Week 48, 7 Stribild subjects had significant (greater than or equal to 4%) lumbar spine BMD loss and 2 had significant total body less head BMD loss.

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of tenofovir DF. Because postmarketing reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. No additional postmarketing adverse reactions specific for emtricitabine have been identified.

Immune System Disorders

allergic reaction, including angioedema

Metabolism and Nutrition Disorders

lactic acidosis, hypokalemia, hypophosphatemia

Respiratory, Thoracic, and Mediastinal Disorders

dyspnea

Gastrointestinal Disorders

pancreatitis, increased amylase, abdominal pain

Hepatobiliary Disorders

hepatic steatosis, hepatitis, increased liver enzymes (most commonly AST, ALT, gamma GT)

Skin and Subcutaneous Tissue Disorders

rash

Musculoskeletal and Connective Tissue Disorders

rhabdomyolysis, osteomalacia (manifested as bone pain and which may contribute to fractures), muscular weakness, myopathy

Renal and Urinary Disorders

acute renal failure, renal failure, acute tubular necrosis, Fanconi syndrome, proximal renal tubulopathy, interstitial nephritis (including acute cases), nephrogenic diabetes insipidus, renal insufficiency, increased creatinine, proteinuria, polyuria

General Disorders and Administration Site Conditions

asthenia

The following adverse reactions, listed under the body system headings above, may occur as a consequence of proximal renal tubulopathy: rhabdomyolysis, osteomalacia, hypokalemia, muscular weakness, myopathy, hypophosphatemia.

Stribild Description

Stribild is a fixed-dose combination tablet containing elvitegravir, cobicistat, emtricitabine, and tenofovir DF for oral administration.

  • Elvitegravir is an HIV-1 integrase strand transfer inhibitor.
  • Cobicistat is a mechanism-based inhibitor of cytochrome P450 (CYP) enzymes of the CYP3A family.
  • Emtricitabine is a synthetic nucleoside analog of cytidine. EMTRIVA is the brand name for emtricitabine.
  • Tenofovir DF is converted in vivo to tenofovir, an acyclic nucleoside phosphonate (nucleotide) analog of adenosine 5'-monophosphate. VIREAD is the brand name for tenofovir DF.

Each tablet contains 150 mg of elvitegravir, 150 mg of cobicistat, 200 mg of emtricitabine, and 300 mg of tenofovir DF (equivalent to 245 mg of tenofovir disoproxil). The tablets include the following inactive ingredients: lactose monohydrate, microcrystalline cellulose, silicon dioxide, croscarmellose sodium, hydroxypropyl cellulose, sodium lauryl sulfate, and magnesium stearate. The tablets are film coated with a coating material containing indigo carmine (FD&C Blue #2) aluminum lake, polyethylene glycol, polyvinyl alcohol, talc, titanium dioxide, and yellow iron oxide.

Elvitegravir: The chemical name of elvitegravir is 6-(3-Chloro-2-fluorobenzyl)-1-[(2S)-1-hydroxy-3-methylbutan-2-yl]-7-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid.

It has a molecular formula of C23H23ClFNO5 and a molecular weight of 447.9. It has the following structural formula:

Elvitegravir is a white to pale-yellow powder with a solubility of less than 0.3 micrograms per mL in water at 20 °C.

Cobicistat: The chemical name for cobicistat is 1,3-thiazol-5-ylmethyl [(2R,5R)-5-{[(2S)-2-[(methyl{[2-(propan-2-yl)-1,3-thiazol-4-yl]methyl}carbamoyl)amino]-4-(morpholin-4-yl)butanoyl]amino}-1,6-diphenylhexan-2-yl]carbamate.

It has a molecular formula of C40H53N7O5S2 and a molecular weight of 776.0. It has the following structural formula:

Cobicistat is adsorbed onto silicon dioxide. Cobicistat on silicon dioxide is a white to pale-yellow solid with a solubility of 0.1 mg per mL in water at 20 °C.

Emtricitabine: The chemical name of emtricitabine is 5-fluoro-1-[(2R,5S)-2-(hydroxymethyl)-1,3-oxathiolan-5-yl]cytosine. Emtricitabine is the (-)enantiomer of a thio analog of cytidine, which differs from other cytidine analogs in that it has a fluorine in the 5-position.

It has a molecular formula of C8H10FN3O3S and a molecular weight of 247.25. It has the following structural formula:

Emtricitabine is a white to off-white crystalline powder with a solubility of approximately 112 mg per mL in water at 25 °C.

Tenofovir DF: Tenofovir DF is a fumaric acid salt of the bis-isopropoxycarbonyloxymethyl ester derivative of tenofovir. The chemical name of tenofovir DF is 9-[(R)-2-[[bis[[(isopropoxycarbonyl)oxy]-methoxy]phosphinyl]methoxy]propyl]adenine fumarate (1:1). It has a molecular formula of C19H30N5O10P ∙ C4H4O4 and a molecular weight of 635.51. It has the following structural formula:

Tenofovir DF is a white to off-white crystalline powder with a solubility of 13.4 mg per mL in water at 25 °C. All dosages are expressed in terms of tenofovir DF except where otherwise noted.

Clinical Studies

Description of Clinical Trials

The efficacy and safety of Stribild were evaluated in the studies summarized in Table 12.

Table 12 Trials Conducted with Stribild in Subjects with HIV-1 Infection
Trial Population Study Arms (N)* Timepoint (Week)
* Randomized and dosed. † Randomized, double blind, active-controlled trial. ‡ Patients had estimated creatinine clearance greater than or equal to 70 mL/min at screening. § Randomized, open label, active-controlled trial. ¶ HIV-1 RNA less than 50 copies per mL. # Open label trial.
Study 102†,‡ Adults with no antiretroviral treatment history Stribild (348)
ATRIPLA (352)
144
Study 103†,‡ Stribild (353)
TRUVADA+atazanavir+ritonavir (355)
Study 115‡,§
Virologically suppressed adults without a history of virologic failure¶ Stribild (293)
TRUVADA+PI+ritonavir (140)
48
Study 121‡,§ Stribild (291)
TRUVADA+NNRTI (143)
Study 112# Treatment-naïve adolescents between the ages of 12 to less than 18 years Stribild (50) 48

Clinical Trial Results in HIV-1 Infected Adult Subjects with No Antiretroviral Treatment History

In Study 102, subjects were randomized in a 1:1 ratio to receive either Stribild (N=348) once daily or ATRIPLA (N=352) once daily. The mean age was 38 years (range 18–67), 89% were male, 63% were White, 28% were Black, and 2% were Asian. Twenty-four percent of subjects identified as Hispanic/Latino. The mean baseline plasma HIV-1 RNA was 4.8 log10 copies per mL (range 2.6–6.5). The mean baseline CD4+ cell count was 386 cells per mm3 (range 3–1348), and 13% had CD4+ cell counts less than 200 cells per mm3. Thirty-three percent of subjects had baseline viral loads greater than 100,000 copies per mL.

In Study 103, subjects were randomized in a 1:1 ratio to receive either Stribild (N=353) once daily or ATV 300 mg + RTV 100 mg + TRUVADA (N=355) once daily. The mean age was 38 years (range 19–72), 90% were male, 74% were White, 17% were Black, and 5% were Asian. Sixteen percent of subjects identified as Hispanic/Latino. The mean baseline plasma HIV-1 RNA was 4.8 log10 copies per mL (range 1.7–6.6). The mean baseline CD4+ cell count was 370 cells per mm3 (range 5–1132), and 13% had CD4+ cell count less than 200 cells per mm3. Forty-one percent of subjects had baseline viral loads greater than 100,000 copies per mL.

In both studies, subjects were stratified by baseline HIV-1 RNA (less than or equal to 100,000 copies per mL or greater than 100,000 copies per mL).

Treatment outcomes of Study 102 and Study 103 through 144 weeks are presented in Table 13.

Table 13 Virologic Outcome of Randomized Treatment of Study 102 and Study 103 at Week 144*
Study 102 Study 103
Stribild
N=348
ATRIPLA
N=352
Stribild
N=353
ATV+RTV+ TRUVADA
N=355
* Week-144 window is between Day 967 and 1050 (inclusive). † Includes subjects who had ≥50 copies/mL in the 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. ‡ Includes patients who discontinued due to an 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. § 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.
Virologic Success
HIV-1 RNA <50 copies/mL
80% 75% 78% 75%
  Treatment Difference 4.9% (95% CI = –1.3%, 11.1%) 3.1% (95% CI = –3.2%, 9.4%)
Virologic Failure† 7% 10% 8% 7%
No Virologic Data in Week 144 Window
  Discontinued Study Drug Due to AE or Death‡ 6% 8% 6% 8%
  Discontinued Study Drug Due to Other Reasons and Last Available HIV-1 RNA <50 copies/mL§ 5% 7% 8% 9%
  Missing Data During Window but on Study Drug 1% 0% 1% 1%

In Study 102, the mean increase from baseline in CD4+ cell count at Week 144 was 298 cells per mm3 in the Stribild-treated subjects and 272 cells per mm3 in the ATRIPLA -treated subjects. In Study 103, the mean increase from baseline in CD4+ cell count at Week 144 was 261 cells per mm3 in the Stribild-treated subjects and 269 cells per mm3 in the ATV+RTV+TRUVADA-treated subjects.

Clinical Trial Results in Virologically Suppressed HIV-1 Infected Adult Subjects with No History of Virologic Failure

In Study 115, subjects had to be on either their first or second antiretroviral regimen with no history of virologic failure, with no current or past history of resistance to the antiretroviral components of Stribild, and must have been suppressed (HIV-1 RNA <50 copies/mL) on a ritonavir-boosted PI in combination with TRUVADA for at least 6 months prior to screening. Subjects were randomized in a 2:1 ratio to either switch to Stribild (Stribild arm, N=293; randomized and dosed) or stay on their baseline antiretroviral regimen for 48 weeks (PI+RTV+TRUVADA arm, N=140; randomized and dosed). Subjects had a mean age of 41 years (range 21–76), 86% were male, 80% were White, and 15% were Black. The mean baseline CD4+ cell count was 610 cells per mm3 (range 74–1919). At screening subjects were receiving atazanavir (40%), darunavir (40%), lopinavir (17%), fosamprenavir (3%), or saquinavir (<1%) as the PI in their regimen.

In Study 121, subjects had to be on either their first or second antiretroviral regimen with no history of virologic failure, with no current or past history of resistance to the antiretroviral components of Stribild, and must have been suppressed (HIV-1 RNA <50 copies/mL) on a NNRTI in combination with TRUVADA for at least 6 months prior to screening. Subjects were randomized in a 2:1 ratio to either switch to Stribild (Stribild arm, N=291; randomized and dosed) or stay on their baseline antiretroviral regimen for 48 weeks (NNRTI+TRUVADA arm, N=143; randomized and dosed). Subjects had a mean age of 41 years (range 20–72); 93% were male, 78% were White, and 17% were Black. The mean baseline CD4+ cell count was 588 cells per mm3 (range 100–1614). Randomization was stratified by use of efavirenz in the baseline regimen. At screening subjects were receiving efavirenz (78%) (predominantly as ATRIPLA [74%]), nevirapine (17%), rilpivirine (4%) (as COMPLERA [4%]), or etravirine (1%) as the NNRTI in their regimen.

Virologic outcomes of Study 115 and Study 121 are presented in Table 14. Five treated subjects were excluded from the efficacy analysis: in Study 115, three Stribild subjects had protocol-prohibited documented resistance and one PI+RTV+TRUVADA subject was not on a protease inhibitor-based regimen at screening; in Study 121, one Stribild subject had protocol-prohibited documented resistance.

Table 14 Virologic Outcomes of Randomized Treatment in Study 115 and Study 121 at Week 48
Study GS-US-236-0115* Study GS-US-236-0121*
Stribild
N=290
PI+RTV+TRUVADA
N=139
Stribild
N=290
NNRTI+TRUVADA
N=143
* Week-48 window is between Day 295 and 378 (inclusive). † Includes subjects who had ≥50 copies/mL in the Week-48 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. ‡ Includes subjects who discontinued due to an 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. § 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.
Virologic Success
HIV-1 RNA <50 copies/mL
94% 87% 93% 88%
Virologic Failure† 1% 1% 1% 1%
No Virologic Data in Week 48 Window 6% 12% 6% 11%
  Discontinued Study Drug Due to AE or Death‡ 2% 1% 2% 1%
  Discontinued Study Drug Due to Other Reasons and Last Available HIV-1 RNA <50 copies/mL§ 4% 10% 4% 9%
  Missing Data During Window but on Study Drug 0% 0% 0% 1%

Clinical Trial Results in HIV-1Treatment-Naïve Adolescent Subjects Aged 12 to Less than 18 Years

In Study 112, the efficacy, safety, and pharmacokinetics of Stribild were evaluated in a single group, open-label trial in HIV-1 infected treatment-naïve adolescents aged 12 to less than 18 years of age and weighing at least 35 kg (77 lbs) (N=50). Mean age was 15 years (range 12–17); 70% were male, 68% black, and 28% Asian. At baseline, mean plasma HIV-1 RNA was 4.60 log10 copies per mL (range 3.18–5.73), mean CD4+ cell count was 399 cells per mm3 (range 133–734), and mean CD4+ percentage was 20.9% (range 4.5%–41.1%). Twenty percent had baseline plasma HIV-1 RNA >100,000 copies per mL.

At Week 48, 44 of 50 (88%) adolescent patients treated with Stribild achieved HIV-1 RNA <50 copies per mL and 4 had HIV-1 RNA ≥50 copies per mL; 1 patient discontinued study drug; 1 had no virologic data at Week 48. The mean decrease from baseline in HIV-1 RNA was –3.16 log10 copies per mL; mean increase from baseline in CD4+ cell count was 229 cells per mm3. No emergent resistance to Stribild was detected through Week 48.

Stribild side effects

Get emergency medical help if you have signs of an allergic reaction to Stribild: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Early symptoms of lactic acidosis may get worse over time and this condition can be fatal. Get emergency medical help if you have even mild symptoms: muscle pain or weakness, numb or cold feeling in your arms and legs, trouble breathing, stomach pain, nausea with vomiting, fast or uneven heart rate, dizziness, or feeling very weak or tired.

Call your doctor at once if you have:

  • kidney problems - little or no urination; painful or difficult urination; swelling in your feet or ankles; feeling tired or short of breath; or

  • liver problems - nausea, swelling around your midsection, upper stomach pain, unusual tiredness, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes).

Stribild may increase your risk of certain infections or autoimmune disorders by changing the way your immune system works. Symptoms may occur weeks or months after you start treatment. Tell your doctor if you have:

  • signs of a new infection - fever, night sweats, swollen glands, mouth sores, diarrhea, stomach pain, weight loss;

  • chest pain (especially when you breathe), dry cough, wheezing, feeling short of breath;

  • cold sores, sores on your genital or anal area;

  • rapid heart rate, feeling anxious or irritable, weakness or prickly feeling, problems with balance or eye movement;

  • trouble speaking or swallowing, severe lower back pain, loss of bladder or bowel control; or

  • swelling in your neck or throat (enlarged thyroid), menstrual changes, impotence, loss of interest in sex.

Common Stribild side effects may include:

  • diarrhea;

  • nausea; or

  • changes in the shape or location of body fat (especially in your arms, legs, face, neck, breasts, and waist).

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

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