text: Elvitegravir, Cobicistat, Emtricitabine, and Tenofovir Disoproxil Fumarate: Dosage, Mechanism/Onset of Action, Half-Life - Medicine.com
  Generic name: cobicistat/elvitegravir/emtricitabine/tenofovir systemic
  Brand names: Stribild
  Severe, acute exacerbations of hepatitis B have been reported in patients who are coinfected with HBV and HIV-1 and have discontinued emtricitabine or tenofovir disoproxil fumarate. Hepatic function should be monitored closely, with both clinical and laboratory follow-up for at least several months in patients who are coinfected with HIV-1 and HBV and discontinue this fixed-dose combination. If appropriate, initiation of anti-hepatitis B therapy may be warranted.
  Stribild: Elvitegravir 150 mg, cobicistat 150 mg, emtricitabine 200 mg, and tenofovir disoproxil fumarate 300 mg [contains fd&c blue #2 aluminum lake]
  Integrase strand transfer inhibitor, CYP3A enzyme inhibitor plus nucleoside and nucleotide reverse transcriptase inhibitor combination; the viral cDNA strand produced by reverse transcriptase is processed and inserted into the human genome by the enzyme HIV-1 integrase. Elvitegravir inhibits the catalytic activity of integrase, thus preventing integration of the proviral gene into human DNA. Cobicistat inhibits enzymes of the CYP3A subfamily and enhances systemic exposure to elvitegravir. Emtricitabine is a cytosine analogue and tenofovir disoproxil fumarate (TDF) is an analog of adenosine 5'-monophosphate. Emtricitabine and tenofovir interfere with HIV viral RNA dependent DNA polymerase activities resulting in inhibition of viral replication.
  AUC of elvitegravir and tenofovir increases with food; emtricitabine and cobicistat not significantly affected
  Elvitegravir: CYP3A (major); hepatic glucuronidation mediated by UGT1A1/3 (minor)
  Cobicistat: CYP3A (major); CYP2D6 (minor)
  Emtricitabine and tenofovir: Not significantly metabolized
  Elvitegravir: Feces (94.8%), urine (6.7%); Cobicistat: Feces (86.2%), urine (8.2%); Emtricitabine: Feces (13.7%), urine (70%); Tenofovir: Urine (70% to 80%)
  Plasma: Elvitegravir: 4 hours; Cobicistat: 3 hours; Emtricitabine: 3 hours; Tenofovir: 2 hours
  Elvitegravir: 12.9 hours; Cobicistat: 3.5 hours; Emtricitabine: 10 hours; Tenofovir: 12 to 18 hours
  Elvitegravir: ~99%; Cobicistat: ~98%; Emtricitabine: <4%; Tenofovir: <0.7%
  HIV-1 infection: Treatment of HIV-1 infection in adults and pediatric patients ≥12 years weighing ≥35 kg who are antiretroviral treatment-naïve; as a replacement for the current antiretroviral regimen in patients who are virologically-suppressed (HIV-1 RNA <50 copies/mL) on a stable antiretroviral regimen for ≥6 months with no history of treatment failure and no known substitutions associated with resistance to elvitegravir, cobicistat, emtricitabine, or tenofovir disoproxil fumarate.
  Coadministration with alfuzosin, carbamazepine, cisapride, ergot derivatives (eg, dihydroergotamine, ergotamine, methylergonovine), lomitapide, lovastatin, lurasidone, midazolam (oral), phenobarbital, phenytoin, pimozide, rifampin, sildenafil (for the treatment of pulmonary arterial hypertension), simvastatin, St John's wort, or triazolam
  Canadian labeling: Additional contraindications (not in US labeling): Hypersensitivity to elvitegravir, cobicistat, emtricitabine, tenofovir disoproxil fumarate, or any component of the formulation; coadministration with apixaban, astemizole (not available in Canada), ergonovine, rivaroxaban, salmeterol, or terfenadine (not available in Canada)
  Note: Prior to initiation, patients should be tested for hepatitis B infection, and baseline serum creatinine, estimated creatinine clearance, urine glucose, and urine protein should be assessed in all patients; serum phosphorus should be assessed in patients with chronic kidney disease.
  HIV-1: Oral: One tablet once daily. Note: This combination is a recommended initial regimen for antiretroviral-naive patients with CrCl >70 mL/minute (HHS [adult] 2016).
  Note: Gene mutation and antiretroviral resistance patterns should be evaluated (refer to https://www.iasusa.org/ for more information) when necessary.
  HIV-1 infection, treatment: Children ≥12 years and Adolescents weighing ≥35 kg: Oral: Tablet (elvitegravir 150 mg, cobicistat 150 mg, emtricitabine 200 mg, and tenofovir disoproxil fumarate 300 mg/tablet): One tablet once daily.
  Oral: Administer with food. Manufacturer's labeling does not provide recommendations on tablet crushing or administration via enteral feeding tubes. A single-dose pharmacokinetic study demonstrated that a crushed and suspended tablet combined with enteral nutrition or with food had similar pharmacokinetic parameters compared to a whole tablet administered with food (Jongbloed-de Hoon 2017). In addition, a case report demonstrated sustained virologic response in a patient who was crushing the tablet prior to oral administration (Fulco 2014).
  Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Dispense in original container.
  Gastrointestinal: Nausea (4% to 16%), diarrhea (12%)
  Genitourinary: Proteinuria (52%)
  Renal: Increased serum creatinine (12%)
  Central nervous system: Abnormal dreams (9%), headache (2% to 7%), fatigue (4%), dizziness (3%), insomnia (3%), drowsiness (1%)
  Endocrine & metabolic: Increased amylase (3%)
  Genitourinary: Hematuria (4%)
  Hepatic: Increased serum AST (3%), increased serum ALT (2%)
  Neuromuscular & skeletal: Increased creatine phosphokinase (8%), bone fracture (4%)
  Endocrine & metabolic: Increased serum cholesterol, increased serum triglycerides
  Gastrointestinal: Increased serum lipase
  <1%, postmarketing, and/or case reports: Acute renal failure, Fanconi syndrome, immune reconstitution syndrome, renal failure, renal tubular disease (proximal), scleral icterus, suicidal ideation
  Decreased bone mineral density: Tenofovir disoproxil fumarate has been associated with decreases in bone mineral density and increases in bone metabolism markers in HIV-1 infected adults. Serum parathyroid hormone and 1,25 vitamin D levels were also higher. Decreases in bone mineral density have also been observed in HIV-1 infected pediatric patients. In all pediatric clinical trials, skeletal growth (height) appears unaffected. Consider monitoring of bone density in all patients with a history of pathologic fractures or with other risk factors for bone loss or osteoporosis. Consider calcium and vitamin D supplementation for all patients; effect of supplementation has not been studied but may be beneficial. Long-term bone health and future fracture risk unknown. If abnormalities are suspected, expert assessment is recommended.
  Osteomalacia and renal dysfunction: Tenofovir disoproxil fumarate may cause osteomalacia associated with proximal renal tubulopathy. Bone pain, extremity pain, fractures, arthralgias, weakness, and muscle pain have been reported. In patients at risk for renal impairment, persistent or worsening bone or muscle symptoms should be evaluated for hypophosphatemia and osteomalacia secondary to proximal renal tubulopathy.
  Renal toxicity: Tenofovir disoproxil fumarate may cause renal toxicity, including acute renal failure and Fanconi syndrome; avoid use with concurrent or recent nephrotoxic therapy (including high dose or multiple NSAID use). Acute renal failure (with hospitalization and renal replacement therapy) has occurred in HIV-infected patients with risk factors for renal impairment who were on a stable tenofovir disoproxil fumarate regimen to which a high dose or multiple NSAID therapy was added. Consider alternatives to NSAIDs in patients at risk for renal impairment. Persistent or worsening bone or extremity pain, fractures and/or muscular pain or weakness may be signs of proximal renal tubulopathy; promptly evaluate patients at risk for renal impairment. Calculate estimated CrCl and assess serum creatinine, urine glucose, and urine protein prior to treatment initiation and during therapy in all patients. Assess serum phosphorus in patients with chronic kidney disease. Discontinue if significant decrease in renal function or signs of Fanconi syndrome. Cobicistat inhibits tubular creatinine secretion without affecting glomerular filtration; may cause modest declines in estimated renal function early in therapy which then stabilize; closely monitor patients with >0.4 mg/dL increase of serum creatinine from baseline.
  Chronic hepatitis B: [US Boxed Warning]: Acute, severe exacerbations of hepatitis B have been reported in these patients following discontinuation of emtricitabine or tenofovir disoproxil fumarate. Not indicated for treatment of chronic HBV infection. Closely monitor hepatic function with clinical and laboratory follow-up for at least several months in patients who are coinfected with HIV-1 and HBV and discontinue this fixed-dose combination. If appropriate, initiation of anti-hepatitis B therapy may be warranted, especially in patients with advanced hepatic disease or cirrhosis. All patients with HIV should be tested for HBV prior to initiation of treatment.
  Renal impairment: Initiation of therapy in adults with CrCl <70 mL/minute is not recommended. Continued use is not recommended in adults with CrCl <50 mL/minute.
  CD4 count, HIV RNA plasma levels; serum creatinine, serum phosphorous (in patients with chronic kidney disease), estimated CrCl, urine glucose and urine protein prior to initiation and as clinically indicated during therapy; hepatic function tests; bone density (patients with a history of bone fracture or have risk factors for bone loss); musculoskeletal complaints; patients should be tested for HBV prior to the initiation of antiretroviral therapy; weight. Reevaluation of serum creatinine, BUN, and serum phosphorus in patients with bone pain, extremity pain, fractures, arthralgias, weakness, or muscle pain
  Patients with HIV and HBV coinfection should be monitored for several months following discontinuation of therapy.
  The Health and Human Services perinatal HIV guidelines do not recommend this fixed-dose combination for pregnant females living with HIV who are antiretroviral-naive, who have had antiretroviral therapy (ART) in the past but are restarting, who require a new ART regimen (due to poor tolerance or poor virologic response of current regimen), and who are not yet pregnant but are trying to conceive due to inadequate serum concentrations of elvitegravir and cobicistat observed during pregnancy. For females who become pregnant while taking this combination, consider altering the regimen, or continue with more frequent monitoring if viral suppression is effective and the regimen is well tolerated. Do not administer within 2 hours of iron or calcium containing preparations, including prenatal vitamins (HHS [perinatal] 2019).