Stribild (elvitegravir, cobicistat, emtricitabine, tenofovir disoproxil fumarate)

Stribild is a prescription medicine that is used without other antiretroviral medicines to treat Human Immunodeficiency Virus-1 (HIV-1) in people 12 years of age and older:

• who have not received anti-HIV-1 medicines in the past, or
• to replace their current anti-HIV-1 medicines:
  • in people who have been on the same anti-HIV-1 medicine regimen for at least 6 months, and
  • who have an amount of HIV-1 in their blood (this is called “viral load”) that is less than 50 copies/mL, and
  • have never failed past HIV-1 treatment.

Stribild may cause the following serious side effects, including:

• New or worse kidney problems, including kidney failure. Your healthcare provider should do blood and urine tests to check your kidneys before you start and while you are taking Stribild. Your healthcare provider may tell you to stop taking Stribild if you develop new or worse kidney problems.
• Too much lactic acid in your blood (lactic acidosis). Too much lactic acid is a serious but rare medical emergency that can lead to death. Tell your healthcare provider right away if you get these symptoms: weakness or being more tired than usual, unusual muscle pain, being short of breath or fast breathing, stomach pain with nausea and vomiting, cold or blue hands and feet, feel dizzy or lightheaded, or a fast or abnormal heartbeat.
• Severe liver problems. In rare cases, severe liver problems can happen that can lead to death. Tell your healthcare provider right away if you get these symptoms: skin or the white part of your eyes turns yellow, dark “tea-colored” urine, light-colored stools, loss of appetite for several days or longer, nausea, or stomach-area pain.
• Bone problems can happen in some people who take Stribild. Bone problems include bone pain, softening, or thinning (which may lead to fractures). Your healthcare provider may need to do tests to check your bones.
• Changes in your immune system (Immune Reconstitution Syndrome) can happen when you start taking HIV-1 medicines. Your immune system may get stronger and begin to fight infections that have been hidden in your body for a long time. Tell your healthcare provider right away if you start having any new symptoms after starting your HIV-1 medicine.

The most common side effects of Stribild include:

• Nausea
• diarrhea

These are not all the possible side effects of Stribild.

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

Testing Prior To Initiation And During Treatment With Stribild

• Prior to initiation of Stribild, test patients for hepatitis B virus infection.
• 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.

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.

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

Not Recommended In Patients With Severe Hepatic Impairment

• Stribild is not recommended for use in patients with severe hepatic impairment.

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.
• Stribild should not be initiated in pregnant individuals.
• An alternative regimen is recommended for individuals who become pregnant during therapy with Stribild.

Not Recommended With Other Antiretroviral Medications

• Stribild is a complete regimen for the treatment of HIV-1 infection; therefore, Stribild should not be administered with other antiretroviral medications for treatment of HIV-1 infection.
• Complete information regarding potential drug-drug interactions with other antiretroviral medications is not provided.

Potential For Stribild To Affect Other Drugs

• The change from baseline is the mean of within-patient changes from baseline for patients with both baseline and Week 144 values.
• Cobicistat, a component of Stribild, is an inhibitor of CYP3A and CYP2D6 and an inhibitor of the following transporters:
  • P-glycoprotein (P-gp),
  • BCRP,
  •  OATP1B1, and
  • OATP1B3.
• Thus, coadministration of Stribild with drugs that are primarily metabolized by CYP3A or CYP2D6, or are substrates of P-gp, BCRP, OATP1B1, or OATP1B3, may result in increased plasma concentrations of such drugs.
• Elvitegravir is a modest inducer of CYP2C9 and may decrease the plasma concentrations of CYP2C9 substrates.

Potential For Other Drugs To Affect One Or More Components Of Stribild

• Elvitegravir and cobicistat, components of Stribild, are metabolized by CYP3A.
• Cobicistat is also metabolized, to a minor extent, by CYP2D6.
• Drugs that induce CYP3A activity are expected to increase the clearance of elvitegravir and cobicistat, resulting in decreased plasma concentration of cobicistat and elvitegravir, which may lead to loss of therapeutic effect of Stribild and development of resistance (Table 5).
• Coadministration of Stribild with other drugs that inhibit CYP3A may decrease the clearance and increase the plasma concentration of cobicistat (Table 5).

Drugs Affecting Renal Function

• Because emtricitabine and tenofovir, components of Stribild, are primarily excreted by the kidneys by a combination of glomerular filtration and active tubular secretion, coadministration of Stribild with drugs that reduce renal function or compete for active tubular secretion may increase concentrations of emtricitabine, tenofovir, and other renally eliminated drugs and this may increase the risk of adverse reactions.
• Some examples of drugs that are eliminated by active tubular secretion include, but are not limited to,
  • acyclovir,
  • cidofovir,
  • ganciclovir,
  • valacyclovir,
  • valganciclovir,
  • aminoglycosides (e.g., gentamicin), and
  • high-dose or multiple NSAIDs.

Established And Other Potentially Significant Interactions

• Table 5 provides a listing of established or potentially clinically significant drug interactions.
• The drug interactions described are based on studies conducted with either Stribild or the components of Stribild (elvitegravir, cobicistat, emtricitabine, and TDF) as individual agents and/or in combination, or are predicted drug interactions that may occur with Stribild.
• The table includes potentially significant interactions but is not all inclusive.

Table 5 : Established and Other Potentially Significant* Drug Interactions: Alteration in Dose or Regimen May Be Recommended Based on Drug Interaction Studies or Predicted Interaction

Drugs Without Clinically Significant Interactions With Stribild

• Based on drug interaction studies conducted with the components of Stribild, no clinically significant drug interactions have been observed when Stribild is combined with the following drugs:
  • famciclovir,
  • famotidine,
  • methadone,
  • omeprazole, and
  • sertraline.

• Stribild is not recommended during pregnancy and to alert their healthcare provider if they become pregnant while taking Stribild.
• There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to Stribild during pregnancy.
• Healthcare providers are encouraged to register patients by calling the Antiretroviral Pregnancy Registry (APR) at 1-800-258-4263.
• Mothers with HIV-1 infection should not breastfeed because HIV-1 can be passed to the baby in breast milM.