Stribild

STRIBILD- elvitegravir, cobicistat, emtricitabine and tenofovir disoproxil fumarate tablet, film coated
Gilead Sciences, Inc.

WARNING: POSTTREATMENT ACUTE EXACERBATION OF HEPATITIS B

Severe acute exacerbations of hepatitis B have been reported in patients who are coinfected with HIV-1 and HBV and have discontinued EMTRIVA or VIREAD, which are components of STRIBILD. 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 STRIBILD. If appropriate, initiation of anti-hepatitis B therapy may be warranted [see Warnings and Precautions (5.1)] .

1 INDICATIONS AND USAGE

STRIBILD® is indicated as a complete regimen for the treatment of HIV-1 infection in adults and pediatric patients 12 years of age and older weighing at least 35 kg who have no antiretroviral treatment history or to replace the current antiretroviral regimen in those who are virologically suppressed (HIV-1 RNA less than 50 copies/mL) on a stable antiretroviral regimen for at least 6 months with no history of treatment failure and no known substitutions associated with resistance to the individual components of STRIBILD [see Clinical Studies (14)].

2 DOSAGE AND ADMINISTRATION

2.1 Testing Prior to Initiation and During Treatment with STRIBILD

Prior to initiation of STRIBILD, test patients for hepatitis B virus infection [see Warnings and Precautions (5.1)].

Prior to initiation and during use of STRIBILD, on a clinically appropriate schedule, assess serum creatinine, estimated creatinine clearance, urine glucose, and urine protein in all patients. In patients with chronic kidney disease, also assess serum phosphorus [see Warnings and Precautions (5.2)].

2.2 Recommended Dosage

STRIBILD is a four-drug fixed dose combination product containing 150 mg of elvitegravir, 150 mg of cobicistat, 200 mg of emtricitabine, and 300 mg of TDF. The recommended dosage of STRIBILD is one tablet taken orally once daily with food in adults and pediatric patients 12 years of age and older with a body weight at least 35 kg and creatinine clearance greater than or equal to 70 mL per minute [see Clinical Pharmacology (12.3)].

2.3 Dosage Adjustment in Patients with Renal Impairment

Initiation of STRIBILD in patients with estimated creatinine clearance below 70 mL per minute is not recommended. Because STRIBILD is a fixed-dose combination tablet, STRIBILD should be discontinued if estimated creatinine clearance declines below 50 mL per minute during treatment with STRIBILD, as the dose interval adjustment required for emtricitabine and tenofovir disoproxil fumarate (DF) cannot be achieved [see Warnings and Precautions (5.2), Adverse Reactions (6.1), Use in Specific Populations (8.6), Clinical Pharmacology (12.3), and Clinical Studies (14)].

No data are available to make dose recommendations for pediatric patients with renal impairment.

2.4 Not Recommended in Patients with Severe Hepatic Impairment

STRIBILD is not recommended for use in patients with severe hepatic impairment [see Use in Specific Populations (8.7) and Clinical Pharmacology (12.3)].

2.5 Not Recommended During Pregnancy

STRIBILD is not recommended for use during pregnancy because of substantially lower exposures of cobicistat and elvitegravir during the second and third trimesters [see Use in Specific Populations (8.1)].

STRIBILD should not be initiated in pregnant individuals. An alternative regimen is recommended for individuals who become pregnant during therapy with STRIBILD [see Use in Specific Populations (8.1)].

3 DOSAGE FORMS AND STRENGTHS

Each STRIBILD tablet contains 150 mg of elvitegravir, 150 mg of cobicistat, 200 mg of emtricitabine, and 300 mg of TDF (equivalent to 245 mg of tenofovir disoproxil).

The tablets are green, capsule shaped, film coated, and debossed with “GSI” on one side and the number “1” surrounded by a square box ( Figure ) on the other side.

4 CONTRAINDICATIONS

Coadministration of STRIBILD is contraindicated with drugs that are highly dependent on CYP3A for clearance and for which elevated plasma concentrations are associated with serious and/or life-threatening events. These drugs and other contraindicated drugs (which may lead to reduced efficacy of STRIBILD and possible resistance) are listed below [see Drug Interactions (7.5) and Clinical Pharmacology (12.3)].

  • Alpha 1-adrenoreceptor antagonist: alfuzosin
  • Anticonvulsants: carbamazepine, phenobarbital, phenytoin
  • Antimycobacterial: rifampin
  • Antipsychotics: lurasidone, pimozide
  • Ergot Derivatives: dihydroergotamine, ergotamine, methylergonovine
  • Herbal Products: St. John’s wort (Hypericum perforatum)
  • Lipid-modifying Agents: lomitapide, lovastatin, simvastatin
  • Phosphodiesterase-5 (PDE-5) Inhibitor: sildenafil when administered as Revatio® for the treatment of pulmonary arterial hypertension
  • Sedative/hypnotics: triazolam, orally administered midazolam

5 WARNINGS AND PRECAUTIONS

5.1 Severe Acute Exacerbation of Hepatitis B in Patients Coinfected with HIV-1 and HBV

All patients with HIV-1 should be tested for the presence of hepatitis B virus (HBV) before initiating antiretroviral therapy [see Dosage and Administration (2.1)].

Severe acute exacerbations of hepatitis B (e.g., liver decompensated and liver failure) have been reported in patients who are coinfected with HIV-1 and HBV and have discontinued emtricitabine or TDF, two of the components of STRIBILD. Patients who are coinfected with HIV-1 and HBV should be closely monitored with both clinical and laboratory follow-up for at least several months after stopping treatment with STRIBILD. If appropriate, initiation of anti-hepatitis B therapy may be warranted, especially in patients with advanced liver disease or cirrhosis, since posttreatment exacerbation of hepatitis may lead to hepatic decompensation and liver failure.

5.2 New Onset or Worsening Renal Impairment

Renal impairment, including cases of acute renal failure and Fanconi syndrome (renal tubular injury with severe hypophosphatemia), has been reported with the use of TDF, a component of STRIBILD, and with the use of STRIBILD [see Adverse Reactions (6.2)].

In the clinical trials of STRIBILD over 144 weeks, 13 (1.9%) subjects in the STRIBILD group (N=701), 8 (2.3%) subjects in the atazanavir (ATV) + ritonavir (RTV) + TRUVADA® (emtricitabine 200 mg/TDF 300 mg) group (N=355), and no subjects in the ATRIPLA® (efavirenz 600 mg/emtricitabine 200 mg/TDF 300 mg) group (N=352) discontinued study drug due to a renal adverse reaction. Of these discontinuations, 8 in the STRIBILD group and 1 in the ATV+RTV+TRUVADA group occurred during the first 48 weeks. Four (0.6%) subjects who received STRIBILD developed laboratory findings consistent with proximal renal tubular dysfunction, leading to discontinuation of STRIBILD during the first 48 weeks of treatment. Two of the four subjects had renal impairment (i.e., estimated creatinine clearance less than 70 mL per minute) at baseline. The laboratory findings in these 4 subjects improved but did not completely resolve in all subjects upon discontinuation of STRIBILD. Renal replacement therapy was not required for these subjects. One (0.3%) subject who received ATV+RTV+TRUVADA developed laboratory findings consistent with proximal renal tubular dysfunction, leading to discontinuation of ATV+RTV+TRUVADA after Week 96.

STRIBILD should be avoided with concurrent or recent use of a nephrotoxic agent (e.g., high-dose or multiple nonsteroidal anti-inflammatory drugs [NSAIDs]) [see Drug Interactions (7.4)]. Cases of acute renal failure after initiation of high-dose or multiple NSAIDs have been reported in HIV-infected patients with risk factors for renal dysfunction who appeared stable on TDF. Some patients required hospitalization and renal replacement therapy. Alternatives to NSAIDs should be considered, if needed, in patients at risk for renal dysfunction.

Persistent or worsening bone pain, pain in extremities, fractures, and/or muscular pain or weakness may be manifestations of proximal renal tubulopathy and should prompt an evaluation of renal function in at-risk patients.

Prior to initiation and during use of STRIBILD, on a clinically appropriate schedule, assess serum creatinine, estimated creatinine clearance, urine glucose, and urine protein in all patients. In patients with chronic kidney disease, also assess serum phosphorus. Discontinue STRIBILD in patients who develop clinically significant decreases in renal function or evidence of Fanconi syndrome. Initiation of STRIBILD in patients with estimated creatinine clearance below 70 mL per minute is not recommended [see Dosage and Administration (2.1)].

Although cobicistat (a component of STRIBILD) may cause modest increases in serum creatinine and modest declines in estimated creatinine clearance without affecting renal glomerular function [see Adverse Reactions (6.1)] , patients who experience a confirmed increase in serum creatinine of greater than 0.4 mg per dL from baseline should be closely monitored for renal safety.

The emtricitabine and TDF components of STRIBILD are primarily excreted by the kidney. STRIBILD should be discontinued if estimated creatinine clearance declines below 50 mL per minute as dose interval adjustment required for emtricitabine and TDF cannot be achieved with the fixed-dose combination tablet [see Use in Specific Populations (8.6)].

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