stribild

Testing: 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, serum phosphorous, estimated serum creatinine clearance, urine glucose, and urine protein in all patients. In patients with chronic kidney disease, also assess serum phosphorus. ( 2.1 ) Recommended dosage: One tablet taken once daily with food. ( 2.2 ) Dosage in renal impairment: Initiation of STRIBILD in patients with estimated creatinine clearance below 70 mL per minute is not recommended. Discontinue in patients with estimated creatinine clearance below 50 mL per minute. ( 2.3 ) 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…

The following adverse reactions are discussed in other sections of the labeling: Severe Acute Exacerbations of Hepatitis B in Patients Coinfected with HIV-1 and HBV [see Warnings and Precautions (5.1) ] . New Onset or Worsening Renal Impairment [see Warnings and Precautions (5.2) ] . Lactic Acidosis/Severe Hepatomegaly with Steatosis [see Warnings and Precautions (5.3) ] . Bone Loss and Mineralization Defects [see Warnings and Precautions (5.5) ] . Immune Reconstitution Syndrome [see Warnings and Precautions (5.6) ] . Most common adverse drug reactions to STRIBILD (incidence greater than or equal to 10%, all grades) are nausea and diarrhea. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Gilead Sciences, Inc. at 1-800-GILEAD-5 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Clinical Trials in HIV-1 Infected Adult Subjects with No Antiretroviral Treatment History The safety assessment of STRIBILD is based on the Week-144 pooled data from 1408 subjects in two randomized, double-blind, active-controlled clinical trials, Study 102 and Study 103, in antiretroviral treatment-naïve…

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 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 adverse events. ( 4 ) Strongly induce CYP3A, which may lead to lower exposure of one or more components and loss of efficacy of STRIBILD and possible resistance. ( 4 )

No data are available on overdose of STRIBILD in patients. If overdose occurs the patient must be monitored for evidence of toxicity. Treatment of overdose with STRIBILD consists of general supportive measures, including monitoring of vital signs as well as observation of the clinical status of the patient. Elvitegravir: Limited clinical experience is available at doses higher than the therapeutic dose of elvitegravir. In one study, boosted elvitegravir equivalent to 2 times the therapeutic dose of 150 mg once daily for 10 days was administered to 42 healthy subjects. No severe adverse reactions were reported. The effects of higher doses are not known. As elvitegravir is highly bound to plasma proteins, it is unlikely that it will be significantly removed by hemodialysis or peritoneal dialysis. Cobicistat: Limited clinical experience is available at doses higher than the therapeutic dose of cobicistat. In two studies, a single dose of cobicistat 400 mg (2.7 times the dose in STRIBILD) was administered to a total of 60 healthy subjects. No severe adverse reactions were reported. The effects of higher doses are not known. As cobicistat is highly bound to plasma proteins, it is unlikely that it will be significantly removed by hemodialysis or peritoneal dialysis. Emtricitabine: Limited clinical experience is available at doses higher than the therapeutic dose of EMTRIVA ® . In…

U.S. Poison Control: call or text 1-800-222-1222 (free, 24/7). In an emergency call 911. From the FDA label; not medical advice.

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. ( 7.1 ) STRIBILD can alter the concentration of drugs metabolized by CYP3A or CYP2D6. Drugs that induce CYP3A can alter the concentrations of one or more components of STRIBILD. Consult the full prescribing information prior to and during treatment for potential drug-drug interactions. ( 4 , 7.2 , 7.3 , 12.3 ) 7.1 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 [see Contraindications (4) , Warnings and Precautions (5.4) and Clinical Pharmacology (12.3) ] . 7.2 Potential for STRIBILD to Affect Other Drugs 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. Coadministration of STRIBILD with drugs that have active metabolite(s) formed by CYP3A may result in reduced plasma concentration of these active metabolite(s) (Table 5). Elvitegravir is a modest inducer of CYP2C9 and may decrease the plasma concentrations of CYP2C9 substrates. 7.3 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). 7.4 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 [see Warnings and Precautions (5.2) ] . 7.5 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 [for magnitude of interaction see Clinical Pharmacology (12.3) ]. The table includes potentially significant interactions but is not all inclusive [see Contraindications (4) and Clinical Pharmacology (12.3) ]. Table 5 Established and Other Potentially Significant This table is not all inclusive. Drug Interactions: Alteration in Dose or Regimen May Be Recommended Based on Drug Interaction Studies or Predicted Interaction Concomitant Drug Class: Drug Name Effect on Concentration ↑=Increase, ↓=Decrease Clinical Comment Alpha 1-adrenoreceptor antagonist: alfuzosin ↑ alfuzosin Coadministration with alfuzosin is contraindicated due to potential for serious and/or life-threatening reactions such as hypotension. Antiarrhythmics: e.g., amiodarone bepridil digoxin Indicates that a drug-drug interaction trial was conducted. disopyramide flecainide systemic lidocaine mexiletine propafenone quinidine ↑ antiarrhythmics ↑ digoxin Therapeutic concentration monitoring, if available, is recommended for antiarrhythmics when coadministered with STRIBILD. Antibacterials: clarithromycin ↑ clarithromycin ↑ cobicistat Patients with CLcr greater than or equal to 60 mL/minute: No dose adjustment of clarithromycin is required. Patients with CLcr between 50 mL/minute and 60 mL/minute: The dose of clarithromycin should be reduced by 50%. Anticoagulants: Direct Oral Anticoagulants (DOACs) apixaban rivaroxaban betrixaban dabigatran edoxaban ↑ apixaban Due to potentially increased bleeding risk, dosing recommendations for coadministration with STRIBILD depends on the apixaban dose. Refer to apixaban dosing instructions for coadministration with strong CYP3A and P-gp inhibitors in apixaban prescribing information. ↑ rivaroxaban Coadministration of rivaroxaban with STRIBILD is not recommended because it may lead to an increased bleeding risk. ↑ betrixaban ↑ dabigatran ↑ edoxaban Due to potentially increased bleeding risk, dosing recommendations for coadministration of betrixaban, dabigatran, or edoxaban with a P-gp inhibitor such as STRIBILD depends on DOAC indication and renal function. Refer to DOAC dosing instructions for coadministration with P-gp inhibitors in DOAC prescribing information. warfarin Effect on warfarin unknown Monitor international normalized ratio (INR) upon coadministration of warfarin with STRIBILD. Anticonvulsants: carbamazepine phenobarbital phenytoin ↓ elvitegravir ↓ cobicistat Coadministration with carbamazepine, phenobarbital, or phenytoin is contraindicated due to potential for loss of elvitegravir therapeutic effect and development of resistance. oxcarbazepine Alternative anticonvulsants should be considered when STRIBILD is coadministered with oxcarbazepine. clonazepam ethosuximide ↑ clonazepam ↑ ethosuximide Clinical monitoring is recommended upon coadministration of clonazepam or ethosuximide with STRIBILD. Antidepressants: Selective Serotonin Reuptake Inhibitors (SSRIs) e.g., paroxetine ↑ SSRIs (except sertraline) ↑ TCAs ↑ trazodone Careful dose titration of the antidepressant and monitoring for antidepressant response are recommended when coadministered with STRIBILD. Tricyclic Antidepressants (TCAs) e.g., amitriptyline desipramine imipramine nortriptyline bupropion trazodone Antifungals: itraconazole ketoconazole voriconazole ↑ elvitegravir ↑ cobicistat ↑ itraconazole ↑ ketoconazole ↑ voriconazole When coadministered with STRIBILD, the maximum daily dose of ketoconazole or itraconazole should not exceed 200 mg per day. An assessment of benefit/risk ratio is recommended to justify use of voriconazole with STRIBILD. Anti-gout: colchicine ↑ colchicine STRIBILD is not recommended to be coadministered with colchicine to patients with renal or hepatic impairment. Treatment of gout-flares – coadministration of colchicine in patients receiving STRIBILD: 0.6 mg (1 tablet) × 1 dose, followed by 0.3 mg (half tablet) 1 hour later. Treatment course to be repeated no earlier than 3 days. Prophylaxis of gout-flares – coadministration of colchicine in patients receiving STRIBILD: If the original regimen was 0.6 mg twice a day, the regimen should be adjusted to 0.3 mg once a day. If the original regimen was 0.6 mg once a day, the regimen should be adjusted to 0.3 mg once every other day. Treatment of familial Mediterranean fever – coadministration of colchicine in patients receiving STRIBILD: Maximum daily dose of 0.6 mg (may be given as 0.3 mg twice a day). Antimycobacterial: rifampin ↓ elvitegravir ↓ cobicistat Coadministration with rifampin is contraindicated due to potential for loss of elvitegravir therapeutic effect and development of resistance . rifabutin rifapentine Coadministration of STRIBILD with rifabutin or rifapentine is not recommended. Antiplatelets: ticagrelor clopidogrel ↑ ticagrelor ↓ clopidogrel active metabolite Coadministration with ticagrelor is not recommended. Coadministration with clopidogrel is not recommended due to potential reduction of the antiplatelet activity of clopidogrel. Antipsychotics: lurasidone ↑ lurasidone Coadministration with lurasidone is contraindicated due to potential for serious and/or life-threatening reactions. pimozide ↑ pimozide Coadministration with pimozide is contraindicated due to potential for serious and/or life-threatening reactions such as cardiac arrhythmias. quetiapine ↑ quetiapine Initiation of STRIBILD in patients taking quetiapine: Consider alternative antiretroviral therapy to avoid increases in quetiapine exposure. If coadministration is necessary, reduce the quetiapine dose to 1/6 of the current dose and monitor for quetiapine-associated adverse reactions. Refer to the quetiapine prescribing information for recommendations on adverse reaction monitoring. Initiation of quetiapine in patients taking STRIBILD : Refer to the quetiapine prescribing information for initial dosing and titration of quetiapine. Other antipsychotics e.g., perphenazine risperidone thioridazine ↑ antipsychotic A decrease in the dose of antipsychotics that are metabolized by CYP3A4 or CYP2D6 may be needed when coadministered with STRIBILD. Beta-Blockers: e.g., metoprolol timolol ↑ beta-blockers Clinical monitoring is recommended and a dose decrease of the beta-blocker may be necessary when these agents are coadministered with STRIBILD. Calcium Channel Blockers: e.g., amlodipine diltiazem felodipine nicardipine nifedipine verapamil ↑ calcium channel blockers Clinical monitoring is recommended upon coadministration of calcium channel blockers with STRIBILD. Corticosteroids: e.g., betamethasone budesonide ciclesonide dexamethasone fluticasone methylprednisolone mometasone triamcinolone ↓ elvitegravir ↓ cobicistat ↑ corticosteroids Coadministration with oral dexamethasone or other systemic corticosteroids that induce CYP3A may result in loss of therapeutic effect and development of resistance to elvitegravir. Consider alternative corticosteroids. Coadministration with corticosteroids (all routes of administration) whose exposures are significantly increased by strong CYP3A inhibitors can increase the risk for Cushing's syndrome and adrenal suppression. Alternative corticosteroids including beclomethasone, prednisone, and prednisolone (whose PK and/or PD are less affected by strong CYP3A inhibitors relative to other studied steroids) should be considered, particularly for long-term use. Endothelin Receptor Antagonists: bosentan ↑ bosentan Coadministration of bosentan in patients on STRIBILD: In patients who have been receiving STRIBILD for at least 10 days, start bosentan at 62.5 mg once daily or every other day based upon individual tolerability. Coadministration of STRIBILD in patients on bosentan: Discontinue use of bosentan at least 36 hours prior to initiation of STRIBILD. After at least 10 days following the initiation of STRIBILD, resume bosentan at 62.5 mg once daily or every other day based upon individual tolerability. Ergot Derivatives: dihydroergotamine, ergotamine, methylergonovine ↑ ergot derivatives Coadministration is contraindicated due to potential for serious and/or life-threatening reactions such as acute ergot toxicity characterized by peripheral vasospasm and ischemia of the extremities and other tissues. Hepatitis C Antiviral Agents: ledipasvir/sofosbuvir sofosbuvir/velpatasvir sofosbuvir/velpatasvir/voxilaprevir ↑ tenofovir The safety of increased tenofovir concentrations in the setting of HARVONI ® (ledipasvir/sofosbuvir) and STRIBILD has not been established. Coadministration is not recommended. Patients receiving STRIBILD concomitantly with EPCLUSA ® (sofosbuvir/velpatasvir) or VOSEVI ® (sofosbuvir/velpatasvir/voxilaprevir) should be monitored for adverse reactions associated with tenofovir disoproxil fumarate. Herbal Products: St. John's wort (Hypericum perforatum) ↓ elvitegravir ↓ cobicistat Coadministration is contraindicated due to potential for loss of elvitegravir therapeutic effect and development of resistance. Hormonal Contraceptives: drospirenone/ethinyl estradiol levonorgestrel norgestimate/ethinyl estradiol ↑ drospirenone ↑ levonorgestrel ↑ norgestimate ↓ ethinyl estradiol Additional or alternative non-hormonal forms of contraception should be considered when estrogen based contraceptives are coadministered with STRIBILD. Plasma concentrations of drospirenone may be increased when coadministered with cobicistat- containing products. Clinical monitoring is recommended due to the potential for hyperkalemia. The effects of increases in the concentration of the progestational component norgestimate are not fully known and can include increased risk of insulin resistance, dyslipidemia, acne, and venous thrombosis. The potential risks and benefits associated with coadministration of norgestimate/ethinyl estradiol with STRIBILD should be considered, particularly in women who have risk factors for these events. Coadministration of STRIBILD with other hormonal contraceptives (e.g., contraceptive patch, contraceptive vaginal ring, or injectable contraceptives) or oral contraceptives containing progestogens other than drospirenone, levonorgestrel, or norgestimate has not been studied; therefore, alternative (non-hormonal) methods of contraception can be considered. Immuno-suppressants: e.g., cyclosporine sirolimus tacrolimus ↑ immuno-suppressants Therapeutic monitoring of the immunosuppressive agents is recommended upon coadministration with STRIBILD. Lipid-modifying Agents: HMG-CoA Reductase Inhibitors: lovastatin simvastatin ↑ lovastatin ↑ simvastatin Coadministration with lovastatin or simvastatin is contraindicated due to potential for serious reactions such as myopathy including rhabdomyolysis. atorvastatin ↑ atorvastatin Initiate atorvastatin with the lowest starting dose of atorvastatin and titrate carefully while monitoring for safety (e.g., myopathy). Do not exceed a dosage of atorvastatin 20 mg daily. Other Lipid-modifying Agents: lomitapide ↑ lomitapide Coadministration with lomitapide is contraindicated due to potential for markedly increased transaminases. Narcotic Analgesics: buprenorphine/naloxone ↑ buprenorphine ↑ norbuprenorphine ↓ naloxone Patients should be closely monitored for sedation and cognitive effects. fentanyl ↑ fentanyl Careful monitoring of therapeutic and adverse effects of fentanyl (including potentially fatal respiratory depression) is recommended with coadministration. tramadol ↑ tramadol A dose decrease may be needed for tramadol with concomitant use. Inhaled Beta Agonist: salmeterol ↑ salmeterol Coadministration of salmeterol and STRIBILD is not recommended because it may result in increased risk of cardiovascular adverse events associated with salmeterol, including QT prolongation, palpitations, and sinus tachycardia. Medications or Oral Supplements Containing Polyvalent Cations (e.g., Mg, Al, Ca, Fe, Zn): calcium or iron supplements, including multivitamins cation-containing antacids or laxatives sucralfate buffered medications ↓ elvitegravir Separate STRIBILD and administration of medications, antacids, or oral supplements containing polyvalent cations by at least 2 hours. Phosphodiesterase-5 (PDE-5) Inhibitors: sildenafil tadalafil vardenafil ↑ PDE-5 inhibitors Coadministration of sildenafil with STRIBILD is contraindicated when used for treatment of pulmonary arterial hypertension (PAH), due to potential for PDE-5 inhibitor associated adverse reactions, including hypotension, syncope, visual disturbances, and priapism. Use of tadalafil for PAH: Coadministration of tadalafil in patients on STRIBILD: In patients receiving STRIBILD for at least 1 week, start tadalafil at 20 mg once daily. Increase tadalafil dose to 40 mg once daily based upon individual tolerability. Coadministration of STRIBILD in patients on tadalafil: Avoid use of tadalafil during the initiation of STRIBILD. Stop tadalafil at least 24 hours prior to starting STRIBILD. After at least one week following initiation of STRIBILD, resume tadalafil at 20 mg once daily. Increase tadalafil dose to 40 mg once daily based upon individual tolerability. Use of PDE-5 inhibitors for erectile dysfunction: The below PDE-5 inhibitors can be used along with increased monitoring for PDE-5-inhibitor associated adverse events: Sildenafil at a single dose not exceeding 25 mg in 48 hours, or Tadalafil at a single dose not exceeding 10 mg in 72 hours, or Vardenafil at a single dose not exceeding 2.5 mg in 72 hours Sedative/hypnotics: midazolam (oral), triazolam ↑ midazolam ↑ triazolam Coadministration with triazolam or orally administered midazolam is contraindicated due to potential for serious and/or life-threatening reactions such as prolonged or increased sedation or respiratory depression. Triazolam and orally administered midazolam are extensively metabolized by CYP3A. Coadministration of triazolam or orally administered midazolam with STRIBILD may cause large increases in the concentrations of these benzodiazepines. Other benzodiazepines: e.g., parenterally administered midazolam clorazepate diazepam estazolam flurazepam buspirone zolpidem ↑ sedatives/hypnotics Coadministration of parenteral midazolam with STRIBILD should be done in a setting that ensures close clinical monitoring and appropriate medical management in case of respiratory depression and/or prolonged sedation. Dosage reduction for midazolam should be considered, especially if more than a single dose of midazolam is administered. With other sedative/hypnotics, dose reduction may be necessary and clinical monitoring is recommended. 7.6 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 or are expected when STRIBILD is combined with the following drugs: famciclovir, famotidine, methadone, omeprazole, prasugrel (active metabolite), and sertraline.