elvitegravir/cobicistat/emtricitabine/tenofovir DF (Rx)

Brand and Other Names:Stribild
  • Print

Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

elvitegravir/cobicistat/emtricitabine/tenofovir DF (ie, tenofovir disoproxil fumarate)

tablet

  • 150mg/150mg/200mg/300mg
more...

HIV Infection

Indicated as a complete regimen for treatment of HIV infection in treatment-naive adults and as replacement of current antiretroviral regimen in patients who are virologically-suppressed (HIV-1 RNA <50 copies/mL) on a stable ART 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

1 tablet PO qDay with food

Dosage Modifications

Renal impairment

  • CrCl <70 mL/min: Do not initiate
  • If eCrCl decreases to <50 mL during treatment: Discontinue

Hepatic impairment

  • Mild-to-moderate (Child-Pugh Class A or B): No dosage adjustment required
  • Severe (Child-Pugh Class C): Not recommended

Dosing Considerations

Testing prior to initiating therapy

  • Test for hepatitis B virus infection
  • Assess serum creatinine, serum phosphorous, eCrCl, urine glucose, and urine protein before initiating and during therapy in all patients as clinically appropriate

Dosage Forms & Strengths

elvitegravir/cobicistat/emtricitabine/tenofovir DF (ie, tenofovir disoproxil fumarate)

tablet

  • 150mg/150mg/200mg/300mg
more...

HIV Infection

Indicated as a complete regimen for treatment of HIV infection in treatment-naive pediatric patients aged ≥12 yr and as replacement of the current antiretroviral regimen in patients who are virologically-suppressed (HIV-1 RNA <50 copies/mL) on a stable ART 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

<12 years: Safety and efficacy not established

≥12 years who weigh at least 35 kg: 1 tablet PO qDay with food

Dosage Modifications

Renal impairment: No data are available to make dose recommendations for pediatric patients

Hepatic impairment

  • Mild-to-moderate (Child-Pugh Class A or B): No dosage adjustment required
  • Severe (Child-Pugh Class C): Not recommended

Dosing Considerations

Testing prior to initiating therapy

  • Test for hepatitis B virus infection
  • Assess serum creatinine, serum phosphorous, eCrCl, urine glucose, and urine protein before initiating and during therapy in all patients as clinically appropriate
Next:

Interactions

Interaction Checker

and elvitegravir/cobicistat/emtricitabine/tenofovir DF

No Results

     activity indicator 
    No Interactions Found
    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

          Minor

            All Interactions Sort By:
             activity indicator 
            Previous
            Next:

            Adverse Effects

            >10%

            Proteinuria (39%)

            Nausea (16%)

            Diarrhea (12%)

            1-10%

            Abnormal dreams (9%)

            Headache (7%)

            Serum creatinine increased (7%)

            Fatigue (5%)

            Creatine kinase increased ≥10 x ULN (5%)

            Serum lipids increased (4%); ie, additional patients started on lipid lowering agents while on Stribild

            Rash (3%)

            Dizziness (3%)

            Insomnia (3%)

            Hematuria (3%)

            Flatulence (2%)

            AST increased >5 x ULN (2%)

            Amylase increased >2 x ULN (2%)

            Somnolence (1%)

            Emtricitabine & tenofovir

            • In addition to the adverse drug reactions observed with Stribild, the following adverse drug reactions occurred in at least 5% of patients receiving emtricitabine or tenofovir with other ARTs:
            • Depression, anxiety
            • Abdominal pain, dyspepsia, vomiting, fever
            • Nasopharyngitis, pneumonia, sinusitis, upper respiratory tract infection, increased cough, rhinitis
            • Arthralgia, pain, back pain, myalgia
            • Paresthesia, peripheral neuropathy (including peripheral neuritis and neuropathy
            • Skin discoloration: Higher frequency among emtricitabine-treated patients including hyperpigmentation on the palms and/or soles

            <1%

            Ocular icterus

            Postmarketing Reports

            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

            Severe acute exacerbations of Hepatitis B in patients coinfected with HIV-1 and HBV

            Bone loss and mineralization defects

            Previous
            Next:

            Warnings

            Black Box Warnings

            Post treatment acute exacerbation of hepatitis B

            • Severe acute exacerbations of hepatitis B reported in patients who are coinfected with HIV-1 and HBV and have discontinued products containing emtricitabine and/or tenofovir disoproxil fumarate (TDF), and may occur with discontinuation treatment
            • Closely monitor hepatic function with both clinical and laboratory follow-up for at least several months in patients who are coinfected with HIV-1 and HBV and discontinue treatment
            • If appropriate, antihepatitis B therapy may be warranted

            Contraindications

            Coadministration of 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

            • Alfuzosin
            • Carbamazepine, phenobarbital, phenytoin
            • Rifampin
            • Lurasidone, pimozide
            • Dihydroergotamine, ergotamine, methylergonovine
            • Cisapride
            • St. John’s wort (Hypericum perforatum)
            • Lomitapide, lovastatin, simvastatin
            • Sildenafil when administered for pulmonary arterial hypertension
            • Triazolam, orally administered midazolam

            Cautions

            Lactic acidosis and severe hepatomegaly with steatosis reported

            Test patients with HIV-1 for the presence of chronic hepatitis B virus (HBV) before initiating antiretroviral therapy (see Black Box Warnings)

            Fat redistribution and accumulation observed with antiretroviral therapy

            Immune reconstitution syndrome reported, including the occurrence of autoimmune disorders (eg, Graves’ disease, polymyositis, Guillain-Barre syndrome) with variable time to onset

            New onset or worsening renal impairment

            • Estimate CrCl in all patients before initiating and avoid concurrent or recent use of nephrotoxic drugs
            • Cases of acute renal failure and Fanconi syndrome reported with tenofovir and Stribild; assess serum creatinine, serum phosphorus, estimated creatinine clearance, urine glucose, and urine protein before initiating therapy and during therapy in all patients as clinically appropriate
            • Cobicistat may cause modest increases in serum creatinine and modest declines in CrCl without affecting renal glomerular function; serum creatinine >0.4 mg/dL from baseline should be closely monitored for renal safety

            Bone effects of tenofovir

            • Bone mineral density may decrease
            • Osteomalacia associated with proximal renal tubulopathy, manifested as bone pain or pain in extremities and which may contribute to fractures, have been reported

            Drug interactions overview

            • Stribild is a complete regimen for treatment of HIV-1 infection; therefore, do not administer with other antiretroviral medications
            • Cobicistat is a CYP3A and CYP2D6 inhibitor and an inhibitor of the following transporters: P-glycoprotein (P-gp), BCRP, OATP1B1, and OATP1B3
            • Coadministration with drugs that are primarily metabolized by CYP3A or CYP2D6, or are P-gp, BCRP, OATP1B1, or OATP1B3 substrates, may result in increased plasma concentrations of such drugs
            • Elvitegravir is a modest CYP2C9 inducer and may decrease the plasma concentrations of CYP2C9 substrates
            • CYP3A4 inducers 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
            • Coadministration with drugs that reduce renal function or compete for active tubular secretion may increase concentrations of emtricitabine, tenofovir, and other renally eliminated drugs and may increase the risk of adverse reactions
            Previous
            Next:

            Pregnancy & Lactation

            Pregnancy

            An ART pregnancy registry has been established (1-800-258-4263); prospective pregnancy data from the Antiviral Pregnancy Registry (APR) not sufficient to adequately assess risk of birth defects or miscarriage

            Not recommended for use during pregnancy because of substantially lower exposures of cobicistat and elvitegravir during second and third trimesters

            Avoid use in pregnant individuals; an alternative regimen is recommended for individuals who become pregnant during therapy

            Lactation

            The Centers for Disease Control and Prevention do not recommend HIV-infected mothers breastfeed their infants due to potential risk for postnatal transmission of HIV

            Based on limited published data, emtricitabine and tenofovir have been shown to be present in human breast milk; not known whether elvitegravir or cobicistat are present in human breast milk, while elvitegravir and cobicistat have been shown to be present in rat milk

            Owing to potential for HIV transmission (in HIV-negative infants); developing viral resistance (in HIV-positive infants); and adverse reactions in a breastfed infant similar to those seen in adults, instruct mothers not to breastfeed

            Pregnancy Categories

            A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA:Information not available.

            more...
            Previous
            Next:

            Pharmacology

            Mechanism of Action

            Elvitegravir: Integrase inhibitor; inhibits catalytic activity (ie, strand transfer) of HIV-1 integrase, an HIV encoded enzyme required for viral replication; CYP3A4 substrate

            Cobicistat: CYP3A4 inhibitor; mechanism-based pharmaco-enhancer, 1st product to be developed and submitted solely as pharmacokinetic booster for elvitegravir; enhances the systemic exposure of CYP3A substrates, such as elvitegravir, where bioavailability is limited and half-life is shortened by CYP3A-dependent metabolism

            Emtricitabine: Synthetic nucleoside analog of cytidine, is phosphorylated by cellular enzymes to form emtricitabine 5'-triphosphate (active); inhibits the activity of the HIV-1 RT by competing with the natural substrate deoxycytidine 5'-triphosphate and by being incorporated into nascent viral DNA which results in chain termination

            Tenofovir: An acyclic nucleoside phosphonate diester analog of adenosine monophosphate; tenofovir disoproxil fumarate requires initial diester hydrolysis for conversion to tenofovir and subsequent phosphorylations by cellular enzymes to form tenofovir diphosphate; tenofovir diphosphate inhibits HIV-1 RT by competing with the natural substrate deoxyadenosine 5′-triphosphate and, after incorporation into DNA, by DNA chain termination

            Absorption

            Food increases mean systemic exposure of elvitegravir and tenofovir by 34% and 24%, respectively

            A high fat meal (~800 kcal, 50% fat) increases mean systemic exposure of elvitegravir and tenofovir by 87% and 23%, respectively

            Elvitegravir

            • Peak Plasma Time: 4 hr
            • Peak Plasma Concentration: 1.7 mcg/mL
            • Trough Plasma Concentration: 0.45 mcg/mL
            • AUC: 23 mcg•hr/mL

            Cobicistat

            • Peak Plasma Time: 3 hr
            • Peak Plasma Concentration: 1.1 mcg/mL
            • Trough Plasma Concentration: 0.05 mcg/mL
            • AUC: 8.3 mcg•hr/mL

            Emtricitabine

            • Peak Plasma Time: 3 hr
            • Peak Plasma Concentration: 1.9 mcg/mL
            • Trough Plasma Concentration: 0.14 mcg/mL
            • AUC: 12.7 mcg•hr/mL

            Tenofovir

            • Peak Plasma Time: 1 hr (fasting); 2 hr (with food)
            • Peak Plasma Concentration: 0.45 mcg/mL
            • Trough Plasma Concentration: 0.1 mcg/mL
            • AUC: 4.4 mcg•hr/mL

            Distribution

            Elvitegravir

            • Protein Bound: 98-99%

            Cobicistat

            • Protein Bound: 97-98%

            Emtricitabine

            • Protein Bound: <4%

            Tenofovir

            • Protein Bound: <0.7
            • Vd: 1.2-1.3 L/kg

            Metabolism

            Elvitegravir

            • Metabolized by CY3A4
            • Also undergoes glucuronidation via UGT1A1/3 enzymes

            Cobicistat

            • Metabolized by CYP3A4 and CYP2D6 (minor)
            • CYP3A4 inhibitor

            Emtricitabine

            • Not significantly metabolized
            • Metabolized by oxidation

            Tenofovir

            • Not significantly metabolized
            • Converted intracellularly by hydrolysis to tenofovir, then phosphorylated to active tenofovir diphosphate

            Elimination

            Elvitegravir

            • Half-life: 12.9 hr
            • Excretion: 94.8% feces; 6.7% urine

            Cobicistat

            • Half-life: 3.5 hr
            • Excretion: 86.2% feces; 8.2% urine

            Emtricitabine

            • Half-life: 10 hr
            • Dialyzable: 30% removed by hemodialysis
            • Excretion: 86% urine; 14% feces

            Tenofovir

            • Excretion: 70-80% in urine via filtration and active secretion, primarily as unchanged tenofovir
            Previous
            Next:

            Images

            Previous
            Next:

            Formulary

            FormularyPatient Discounts

            Adding plans allows you to compare formulary status to other drugs in the same class.

            To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.

            Adding plans allows you to:

            • View the formulary and any restrictions for each plan.
            • Manage and view all your plans together – even plans in different states.
            • Compare formulary status to other drugs in the same class.
            • Access your plan list on any device – mobile or desktop.

            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
            QL Quantity Limits
            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
            ST Step Therapy
            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
            OR Other Restrictions
            Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
            Additional Offers
            Email to Patient

            From:

            To:

            The recipient will receive more details and instructions to access this offer.

            By clicking send, you acknowledge that you have permission to email the recipient with this information.

            Email Forms to Patient

            From:

            To:

            The recipient will receive more details and instructions to access this offer.

            By clicking send, you acknowledge that you have permission to email the recipient with this information.

            Previous
            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.