Stribild by Gilead Sciences, Inc

Stribild (elvitegravir, cobicistat, emtricitabine, tenofovir disoproxil fumarate) is approved for treatment of HIV-1 infection.


In 2012, the FDA approved Stribild (elvitegravir, cobicistat, emtricitabine, tenofovir disoproxil fumarate) tablets for treatment of HIV-1 infection in treatment-naïve adult patients, and patients switching from long-term use (ie, >6 months) of an alternative antiretroviral regimen. Patients switching from an alternative regimen must have low HIV-1 RNA levels (ie, <50 copies/mL) and no history of treatment failure or resistance to any of the medications in Stribild.1,2

Use of Stribild is contraindicated in patients using medications that depend on drugs with a narrow therapeutic index that rely on CYP3A-mediated clearance and strong CYP3A inducers that may lower exposure to the medications in Stribild. Exposure to subtherapeutic levels of the medications in Stribild may increase the risk of treatment failure and may lead to drug resistance mutations.

Importantly, this medication carries a black box warning for lactic acidosis, severe hepatomegaly with steatosis, and acute exacerbations of hepatitis B after initiation of treatment.2

Mechanism of Action
Stribild is a combination of 4 medications: the integrase strand transfer inhibitor elvitegravir, which prevents HIV-1 from incorporating into human DNA; the CYP3A inhibitor cobicistat, which enhances exposure to elvitegravir; and the nucleoside analogs emtricitabine and tenofovir disoproxil fumarate, which stop viral replication by terminating growing strands of viral DNA.2

Pharmacology and Pharmacokinetics
Because tenofovir disoproxil fumarate is primarily excreted renally, Stribild therapy should not be initiated in patients with an initial creatinine clearance less than 70 mL/min and should not be continued if a patient’s creatinine clearance declines to a level less than 50 mL/min while on therapy. Although Stribild may be used in patients with mild-to-moderate hepatic impairment, due to a lack of safety data, use of Stribild in patients with severe hepatic impairment is not recommended.2

Dosage and Administration
Each tablet of Stribild contains 150 mg of elvitegravir, 150 mg of cobicistat, 200 mg of emtricitabine, and 300 mg of tenofovir disoproxil fumarate. Instruct patients to take 1 tablet daily with food.2

Clinical Studies
Researchers investigated clinical results with Stribild versus an active control in patients with and without antiviral treatment history in a series of 4 large randomized clinical trials: 2 double-blind trials in antiretroviral-naïve individuals and 2 open-label trials in patients with low viral load transitioning from previous therapy. In all trials, patients were assessed on the primary outcome of virologic success, defined by an HIV-1 RNA level <50 copies/mL.2

In 700 treatment-naïve patients receiving therapy for 144 weeks and randomized to treatment arms in a 1:1 ratio, 80% of patients attained virologic success with Stribild versus 75% of patients receiving Atripla (efavirenz/emtricitabine/tenofovir disoproxil fumarate). Similarly, in 708 treatment-naïve patients receiving therapy for 144 weeks and randomized to treatment arms in a 1:1 ratio, 78% of patients receiving Stribild attained virologic success versus 75% of patients receiving atazanavir/ritonavir plus Truvada (emtricitabine/tenofovir disoproxil fumarate).

In both studies, results were not significantly different between treatment groups, proving noninferiority.2-4 In treatment-experienced patients, over 48 weeks, 429 patients were randomized in a 2:1 ratio to receive Stribild or Truvada with a protease inhibitor and ritonavir, with virologic success occurring in 94% of patients and 87% of patients, respectively.

In a similar 48-week study of 433 treatment-experienced patients randomized 2:1 to Stribild or Truvada with a nonnucleoside reverse transcriptase inhibitor, virologic success occurred in 93% of patients and 88% of patients, respectively.2,5,6

Warnings and Precautions
In addition to the aforementioned warnings, use of Stribild has been associated with fat redistribution, immune reconstitution syndrome, and autoimmune disorders. However, these adverse events are rare.

The most common adverse events in clinical trial were nausea (16% of patients) and diarrhea (12% of patients).2 Patients taking Stribild should not take other medications that duplicate the active ingredients in Stribild.

Other antiretroviral components that should not be used concomitantly include lamivudine, adefovir dipivoxil, and ritonavir.2 Inorganic antacids may reduce exposure to the elvitegravir component of Stribild.

To avoid this interaction, instruct patients to separate doses of Stribild and inorganic antacids by at least 2 hours. Doses of the antifungal ketoconazole or itraconazole should not exceed 200 mg daily, and doses of bosentan, phosphodiesterase 5 inhibitors, and colchicine should be reduced.2

Patients may require dose reductions of narcotics, sedative/hypnotics, neuroleptics, antidepressants, immunosupressants, beta-blockers, and antiarrhythmic drugs, as use of Stribild may increase levels of medications in these classes. SPT

References
  1. FDA approves new combination pill for HIV treatment for some patients [press release]. Silver Spring, MD: FDA; August 27, 2012. www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm317004.htm. Accessed September 2015.
  2. Stribild (elvitegravir, cobicistat, emtricitabine and tenofovir disoproxil fumarate) [package insert]. Foster City, CA: Gilead Sciences, Inc; 2015.
  3. Sax PE, DeJesus E, Mills A, et al; GS-US-236-0102 study team. Co-formulated elvitegravir, cobicistat, emtricitabine, and tenofovir versus co-formulated efavirenz, emtricitabine, and tenofovir for initial treatment of HIV-1 infection: a randomised, double-blind, phase 3 trial, analysis of results after 48 weeks. Lancet. 2012;379(9835):2439-2448. doi: 10.1016/S0140-6736(12)60917-9.
  4. DeJesus E, Rockstroh JK, Henry K, et al; GS-US-236-0102 study team. Co-formulated elvitegravir, cobicistat, emtricitabine, and tenofovir disoproxil fumarate versus ritonavir-boosted atazanavir plus co-formulated emtricitabine and tenofovir disoproxil fumarate for initial treatment of HIV-1 infection: a randomised, double-blind, phase 3, non-inferiority trial. Lancet. 2012;379(9835):2429-2438. doi: 10.1016/S0140-6736(12)60918-0.
  5. Arribas JR, Pialoux G, Gathe J, et al. Simplification to coformulated elvitegravir, cobicistat, emtricitabine, and tenofovir versus continuation of ritonavir-boosted protease inhibitor with emtricitabine and tenofovir in adults with virologically suppressed HIV (STRATEGY-PI): 48 week results of a randomised, open-label, phase 3b, non-inferiority trial. Lancet Infect Dis. 2014;14(7):581-589. doi: 10.1016/S1473-3099(14)70782-0.
  6. Pozniak A, Markowitz M, Mills A, et al. Switching to coformulated elvitegravir, cobicistat, emtricitabine, and tenofovir versus continuation of non-nucleoside reverse transcriptase inhibitor with emtricitabine and tenofovir in virologically suppressed adults with HIV (STRATEGY-NNRTI): 48 week results of a randomised, open-label, phase 3b non-inferiority trial. Lancet Infect Dis. 2014;14(7):590-599. doi: 10.1016/S1473-3099(14)70796-0.



About the Author
Michael R. Page, PharmD, RPh, earned his PharmD from the Ernest Mario School of Pharmacy at Rutgers University. He has worked as a community pharmacist at CVS Pharmacy and is currently clinical editor in clinical and scientific affairs at Pharmacy Times.




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