the ideal [50:<70 mL/minute. 1 200 Discontinue if estimated Cl cr decreases to> <50 mL/minute during treatment. 1 200 (See Renal Impairment under Cautions.) Pediatric patients: Data insufficient to make dosage recommendations for those with renal impairment. 1 Geriatric Patients Use with caution. 1 (See Geriatric Use under Cautions.) Cautions for Elvitegravir, Cobicistat, Emtricitabine, and tenofovir Disoproxil Fumarate Contraindications Concomitant use with drugs highly dependent on CYP3A for metabolism and for which elevated plasma concentrations are associated with serious and/or life-threatening events (e.g., alfuzosin, cisapride, ergot alkaloids, lovastatin, lurasidone, oral midazolam, pimozide, sildenafil used for treatment of pulmonary arterial hypertension [PAH], simvastatin, triazolam). 1 (See Specific Drugs under Interactions.) Concomitant use with drugs that are potent inducers of CYP3A which may result in decreased elvitegravir and/or cobicistat concentrations resulting in possible decreased antiretroviral efficacy and development of resistance (e.g., carbamazepine, phenobarbital, phenytoin, rifampin, St. John s wort [ Hypericum perforatum ]). 1 (See Specific Drugs under Interactions.) Warnings/Precautions Warnings HIV-infected Individuals Coinfected with HBV Test all HIV-infected patients for presence of HBV before initiating antiretroviral therapy. 1 200 EVG/c/FTC/TDF not indicated for treatment of chronic HBV infection. 1 Safety and efficacy of EVG/c/FTC/TDF not established in patients coinfected with HIV and HBV. 1 Severe acute exacerbations of HBV reported following discontinuance of emtricitabine or tenofovir DF in HIV-infected patients with HBV infection. 1 218 221 HBV exacerbations have been associated with hepatic decompensation and hepatic failure. 1 218 Closely monitor hepatic function (using both clinical and laboratory follow-up) for at least several months after EVG/c/FTC/TDF is discontinued in patients coinfected with HIV and HBV. 1 If appropriate, initiation of HBV treatment may be warranted. 1 Other Warnings/Precautions Renal Toxicity Renal impairment, including acute renal failure and Fanconi syndrome (renal tubular injury with hypophosphatemia), reported with tenofovir DF (a component of EVG/c/FTC/TDF). 1 221 Cobicistat (a component of EVG/c/FTC/TDF) may cause modest increase in S cr and modest decrease in estimated Cl cr due to inhibition of tubular secretion of creatinine; 1 15 glomerular function not affected. 1 15 Determine S cr , estimated Cl cr , serum phosphorus, urine glucose, and urine protein prior to initiation of EVG/c/FTC/TDF and routinely monitor during treatment in all patients. 1 (See Renal Impairment under Cautions.) Do not initiate EVG/c/FTC/TDF in patients with estimated Cl cr> <70 mL/minute; 1 discontinue if estimated Cl cr decreases to> <50 mL/minute during therapy. 1 If a confirmed increase in S cr of >0.4 mg/dL from baseline occurs during EVG/c/FTC/TDF treatment, closely monitor for renal toxicity. 1 Because persistent or worsening bone pain, pain in extremities, fractures, and/or muscular pain or weakness may be manifestations of proximal renal tubulopathy, promptly evaluate renal function in patients at risk for renal dysfunction who present with such symptoms. 1 (See Bone Effects under Cautions.) Avoid EVG/c/FTC/TDF in patients who are receiving or have recently received a nephrotoxic drug (e.g., high-dose or multiple NSAIAs). 1 Acute renal failure reported after initiation of high-dose or multiple NSAIAs in HIV-infected patients at risk for renal dysfunction who appeared stable while receiving tenofovir DF; hospitalization and renal replacement therapy required in some patients. 1 Consider alternatives to NSAIAs in patients at risk for renal dysfunction. 1 Lactic Acidosis and Severe Hepatomegaly with Steatosis Lactic acidosis and severe hepatomegaly with steatosis (sometimes fatal) reported in patients receiving NRTIs, including emtricitabine and tenofovir DF (components of EVG/c/FTC/TDF), in conjunction with other antiretrovirals. 1 218 221 Interrupt EVG/c/FTC/TDF treatment if there are clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity (e.g., hepatomegaly and steatosis even in the absence of marked increases in serum aminotransferase concentrations). 1 Bone Effects Decreases in bone mineral density (BMD) from baseline at lumbar spine and hip, increases in several biochemical markers of bone metabolism, and increased serum parathyroid hormone and 1,25 vitamin D levels reported in patients receiving tenofovir DF (a component of EVG/c/FTC/TDF). 1 221 Bone effects reported in pediatric patients are similar to those reported in adults. 1 Effects of tenofovir-associated changes in BMD on long-term bone health and future fracture risk unknown. 1 221 Osteomalacia associated with proximal renal tubulopathy, which may contribute to fractures, reported in patients receiving tenofovir DF. 1 221 Arthralgia and muscle pain or weakness also reported in cases of proximal renal tubulopathy. 1 Consider hypophosphatemia and osteomalacia secondary to proximal renal tubulopathy in patients at risk of renal dysfunction who present with persistent or worsening bone or muscle symptoms while receiving preparations containing tenofovir DF. 1 Consider BMD monitoring in adult and pediatric patients with history of pathologic bone fracture or other risk factors for osteoporosis or bone loss. 1 Effect of calcium and vitamin D supplementation not studied, but may be beneficial for all patients. 1 If bone abnormalities suspected, obtain appropriate consultation. 1 Interactions Concomitant use with certain drugs may result in decreased antiretroviral plasma concentrations leading to loss of therapeutic effect and possible development of resistance; concomitant use with certain other drugs may result in increased antiretroviral plasma concentrations and/or increased plasma concentrations of the concomitant drugs leading to clinically important adverse reactions. 1 (See Contraindications and see Interactions.) Consider potential drug interactions prior to and during therapy. 1 Review drugs used concomitantly with EVG/c/FTC/TDF; 1 monitor patient for adverse reactions associated with these drugs. 1 (See Interactions.) Use of Fixed Combinations Consider cautions, precautions, and contraindications associated with each component of EVG/c/FTC/TDF. 1 218 221 Consider cautionary information applicable to specific populations (e.g., pregnant or nursing women, individuals with hepatic or renal impairment, geriatric patients) for each drug in the fixed combination. 1 218 221 EVG/c/FTC/TDF is used alone as a complete regimen for treatment of HIV-1 infection; 1 200 do not use in conjunction with other antiretrovirals. 1 200 (See Specific Drugs under Interactions.) Do not use EVG/c/FTC/TDF concomitantly with any preparation that contains any of its components (elvitegravir, cobicistat, emtricitabine, tenofovir DF). 1 In addition, do not use EVG/c/FTC/TDF concomitantly with any preparation containing lamivudine, adefovir dipivoxil, or ritonavir. 1 Immune Reconstitution Syndrome During initial treatment, patients who respond to antiretroviral therapy may develop an inflammatory response to indolent or residual opportunistic infections (e.g., Mycobacterium avium complex [MAC], M. tuberculosis , cytomegalovirus [CMV], Pneumocystis jirovecii [formerly P. carinii ]); 1 this may necessitate further evaluation and treatment. 1 Autoimmune disorders (e.g., Graves' disease, polymyositis, Guillain-Barré syndrome) also reported in the setting of immune reconstitution; 1 time to onset is more variable and can occur many months after initiation of antiretroviral therapy. 1 Specific Populations Pregnancy Antiretroviral Pregnancy Registry at 800-258-4263 or . 1 202 Prospective pregnancy data from the Antiretroviral Pregnancy Registry insufficient to date to adequately assess risk of birth defects or miscarriage if EVG/c/FTC/TDF used in pregnant women. 1 Registry data available through January 2016 show no birth defects reported for elvitegravir or cobicistat and no difference in overall risk of major birth defects for emtricitabine or tenofovir DF compared with the background rate of major birth defects in the US. 1 In animal studies, no evidence of adverse developmental effects when components of EVG/c/FTC/TDF administered during the period of organogenesis at elvitegravir, cobicistat, emtricitabine, and tenofovir DF exposures up to 23, 4.3, 120, and 19 times higher, respectively, than human exposures at the recommended daily dosage. 1 Experts state data insufficient to recommend routine use of EVG/c/FTC/TDF for initial treatment in antiretroviral-naive pregnant women. 202 Lactation Elvitegravir and cobicistat distributed into milk in rats; 1 not known whether these drugs distributed into human milk. 1 Emtricitabine and tenofovir DF are distributed into human milk. 1 Not known whether EVG/c/FTC/TDF affects human milk production or affects the breast-fed infant. 1 Instruct HIV-infected women not to breast-feed because of risk of HIV transmission and risk of adverse effects in the infant. 1 202 Pediatric Use Safety and efficacy of EVG/c/FTC/TDF not established in pediatric patients> <12 years of age or in those weighing> <35 kg. 1 Clinical trial data indicate that safety profile of EVG/c/FTC/TDF in HIV-1-infected, treatment-naive pediatric patients 12 to> <18 years of age is similar to that reported in adults. 1 Bone effects reported when tenofovir DF is used in pediatric and adolescent patients are similar to those reported in adults. 1 In clinical studies, total body BMD gain in tenofovir DF-treated pediatric patients was less than that reported in control groups; 1 skeletal growth appeared to be unaffected. 1 Effects of tenofovir DF-associated changes in BMD and biochemical markers on long-term bone health and future fracture risk unknown. 1 Experts state EVG/c/FTC/TDF recommended for initial treatment only in antiretroviral-naive HIV-infected children and adolescents ≥12 years of age weighing ≥35 kg in late puberty (SMR 4 or 5). 201 These experts state that the fixed combination of elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide (EVG/c/FTC/TAF) is preferred in children and adolescents ≥12 years of age weighing ≥35 kg. 201 Geriatric Use Insufficient experience in adults ≥65 years of age to determine whether geriatric patients respond differently than younger adults. 1 Use with caution because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy. 1 Hepatic Impairment Moderate hepatic impairment (Child-Pugh class B): No clinically important effect on pharmacokinetics of elvitegravir, cobicistat, or tenofovir; 1 not expected to affect emtricitabine pharmacokinetics. 1 Severe hepatic impairment (Child-Pugh class C): EVG/c/FTC/TDF not recommended; 1 data not available to date regarding pharmacokinetics or safety in such patients. 1 Renal Impairment Determine S cr , estimated Cl cr , serum phosphorus, urine glucose, and urine protein prior to and routinely monitor during EVG/c/FTC/TDF treatment in all patients. 1 Adults: Do not initiate EVG/c/FTC/TDF in patients with estimated Cl cr> <70 mL/minute. 1 200 Discontinue if estimated Cl cr decreases to> <50 mL/minute during treatment. 1 200 Pediatric patients: Data insufficient to make dosage recommendations for those with renal impairment. 1 Common Adverse Effects Nausea, diarrhea, abnormal dreams, headache. 1 Interactions for Elvitegravir, Cobicistat, Emtricitabine, and tenofovir Disoproxil Fumarate Elvitegravir: Substrate of CYP3A; 1 weak inducer and weak inhibitor of CYP3A. 24 Induces CYP2C9. 1 Does not inhibit CYP1A, 2A6, 2C9, 2C19, 2D6, or 2E1 in vitro. 24 Inhibits organic anion transport polypeptides (OATP) 1B1 and 1B3. 1 24 Cobicistat: Substrate and inhibitor of CYP3A and 2D6; 1 also inhibits CYP3A and 2D6. 1 24 Inhibits p-glycoprotein (P-gp) transport, breast cancer resistance protein (BCRP), and OATP1B1 and 1B3. 1 Emtricitabine: Not a substrate of CYP enzymes; 218 does not inhibit CYP1A2, 2A6, 2B6, 2C9, 2C19, 2D6, or 3A4. 218 Tenofovir DF and tenofovir: Not substrates of CYP enzymes; 221 tenofovir does not inhibit CYP3A4, 2D6, 2C9, or 2E1, but may have a slight inhibitory effect on CYP1A. 221 The following interactions are based on studies using elvitegravir, elvitegravir administered with cobicistat ( cobicistat-boosted elvitegravir), elvitegravir administered with low-dose ritonavir ( ritonavir-boosted elvitegravir), cobicistat, or EVG/c/FTC/TDF or are predicted to occur. 1 Consider potential interactions associated with each drug in the fixed combination. 1 Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes CYP3A or 2D6 substrates: Potential increased plasma concentrations of such substrates. 1 CYP3A inducers: Potential decreased plasma concentrations of elvitegravir and cobicistat; 1 possible decreased antiretroviral efficacy and development of resistance. 1 CYP3A inhibitors: Potential increased plasma concentrations of cobicistat. 1 Drugs Affected by P-glycoprotein Transport P-gp substrates: Potential increased plasma concentrations of such substrates. 1 Drugs Affected by Breast Cancer Resistance Protein BCRP substrates: Potential increased plasma concentrations of such substrates. 1 Drugs Affected by Organic Anion Transport Polypeptides OATP1B1 or 1B3 substrates: Potential increased plasma concentrations of such substrates. 1 Drugs Affecting Renal Function Drugs that reduce renal function or compete for active tubular secretion: Potential increased concentrations of emtricitabine, tenofovir, and/or concomitant drug. 1 Specific Drugs Drug Interaction Comments Alfuzosin Possible increased alfuzosin concentrations; 1 may result in hypotension 1 Concomitant use contraindicated 1 Aminoglycosides (e.g., gentamicin) Competition for active tubular secretion may increase concentrations of emtricitabine, tenofovir, and/or the concomitant aminoglycoside; 1 may increase risk of adverse effects 1 Antacids, aluminum-, calcium-, and/or magnesium-containing Decreased elvitegravir concentrations and AUC when administered simultaneously 1 9 Give EVG/c/FTC/TDF at least 2 hours before or at least 2 hours after antacids 1 200 Antiarrhythmic agents (amiodarone, disopyramide, dronedarone, flecainide, lidocaine [systemic], mexiletine, propafenone, quinidine) Possible increased antiarrhythmic agent concentrations 1 200 Use concomitantly with caution; 200 monitor antiarrhythmic agent concentrations if possible 1 200 Anticoagulants (apixaban, dabigatran, edoxaban, rivaroxaban, warfarin) Apixaban, edoxaban, rivaroxaban: Increased anticoagulant concentrations expected 200 Dabigatran: Possible increased dabigatran concentrations 200 Warfarin: Possible altered warfarin concentrations 1 200 Apixaban, edoxaban, rivaroxaban: Avoid concomitant use with EVG/c/FTC/TDF 200 Dabigatran: Some experts state dosage adjustments not needed if used with EVG/c/FTC/TDF in patients with Cl cr >50 mL/minute; do not use concomitantly in those with Cl cr> <50 mL/minute 200 Warfarin: Monitor INR and adjust warfarin dosage accordingly 1 200 Anticonvulsants (carbamazepine, ethosuximide, oxcarbazepine, phenobarbital, phenytoin) Carbamazepine, phenobarbital, phenytoin: Possible increased anticonvulsant concentrations; 1 200 possible decreased elvitegravir and cobicistat concentrations with possible decreased antiretroviral efficacy and development of resistance 1 200 Ethosuximide: Possible increased ethosuximide concentrations 1 Oxcarbazepine: Possible decreased elvitegravir and cobicistat concentrations 1 Carbamazepine, phenobarbital, phenytoin: Concomitant use contraindicated 1 200 Ethosuximide: If used concomitantly with EVG/c/FTC/TDF, monitor clinically for ethosuximide-associated adverse effects 1 Oxcarbazepine: Consider alternative anticonvulsant 1 200 Antidepressants, tricyclics (amitriptyline, desipramine, doxepin, imipramine, nortriptyline) Possible increased tricyclic antidepressant concentrations and AUC 1 200 If tricyclic antidepressant initiated in patients receiving EVG/c/FTC/TDF, use lowest initial antidepressant dosage and carefully titrate dosage based on clinical response and/or antidepressant concentrations 1 200 Antifungals, azoles Isavuconazonium (prodrug of isavuconazole): Possible increased isavuconazole, elvitegravir, and cobicistat concentrations 200 Itraconazole: Increased itraconazole concentrations expected; 1 200 possible increased elvitegravir and cobicistat concentrations 1 200 Ketoconazole: Increased ketoconazole, elvitegravir, and cobicistat concentrations 1 Posaconazole: Possible increased posaconazole, elvitegravir, and cobicistat concentrations 200 Voriconazole: Possible increased voriconazole, elvitegravir, and cobicistat concentrations 1 200 Isavuconazonium: Monitor for virologic efficacy; 200 consider monitoring isavuconazole concentrations 200 Itraconazole: Do not exceed itraconazole dosage of 200 mg daily; 1 experts state use itraconazole dosage >200 mg daily only if itraconazole concentrations monitored 200 Ketoconazole: Do not exceed ketoconazole dosage of 200 mg daily 1 Posaconazole: Monitor posaconazole concentrations 200 Voriconazole: Avoid concomitant use unless benefits outweigh risks; 1 200 if used concomitantly, experts state consider monitoring voriconazole concentrations and adjust voriconazole dosage accordingly 200 Antiplatelet agents (ticagrelor, vorapaxar) Ticagrelor or vorapaxar: Increased antiplatelet concentrations expected 200 Ticagrelor or vorapaxar: Avoid concomitant use 200 Antimycobacterials (rifabutin, rifampin, rifapentine) Rifabutin: Decreased elvitegravir concentrations and AUC and increased rifabutin metabolite concentrations and AUC when used with cobicistat-boosted elvitegravir 1 Rifampin: Possible decreased elvitegravir and cobicistat concentrations with possible decreased antiretroviral efficacy and development of resistance 1 Rifapentine: Possible decreased elvitegravir and cobicistat concentrations with possible decreased antiretroviral efficacy and development of resistance 1 Rifabutin: Concomitant use not recommended 1 200 Rifampin: Concomitant use contraindicated 1 Rifapentine: Concomitant use not recommended 1 200 Antipsychotics (perphenazine, lurasidone, pimozide, risperidone, quetiapine, thioridazine) Lurasidone: Possible serious and/or life-threatening reactions 1 Perphenazine, risperidone, thioridazine: Possible increased antipsychotic agent concentrations 1 Pimozide: Possible increased pimozide concentrations resulting in serious and/or life-threatening reactions (e.g., cardiac arrhythmias) 1 Quetiapine: Increased quetiapine concentrations expected 200 Lurasidone: Concomitant use contraindicated 1 Perphenazine, risperidone, thioridazine: Decreased antipsychotic dosage may be needed; 1 200 if initiated in patients receiving EVG/c/FTC/TDF, use low initial dosage of the antipsychotic 200 Pimozide: Concomitant use contraindicated 1 Quetiapine: Consider alternative antiretroviral; 1 if EVG/c/FTC/TDF necessary in patient receiving stable quetiapine dosage, reduce quetiapine dosage to one-sixth of original dosage and monitor for quetiapine efficacy and adverse effects; 1 200 if quetiapine necessary in patient receiving EVG/c/FTC/TDF, initiate using lowest quetiapine dosage, titrate as needed, and closely monitor for quetiapine efficacy and adverse effects 200 Avanafil Data not available 200 Concomitant use not recommended 200 β-Adrenergic blocking agents (metoprolol, timolol) Metoprolol, timolol: Possible increased β-blocking agent concentrations 1 Metoprolol, timolol: Monitor clinically; 1 reduced β-blocking agent dosage may be needed; 1 200 consider alternative agent not metabolized by CYP isoenzymes (e.g., atenolol, labetalol, nadolol, sotalol) 200 Benzodiazepines (clonazepam, clorazepate, diazepam, estazolam, flurazepam, midazolam, triazolam) Midazolam or triazolam: Increased benzodiazepine concentrations; 1 200 potential for serious and/or life-threatening adverse effects (e.g., prolonged or increased sedation or respiratory depression) 1 200 Clonazepam, clorazepate, diazepam, estazolam, flurazepam: Possible increased benzodiazepine concentrations 1 Oral midazolam or triazolam: Concomitant use contraindicated 1 Parenteral midazolam: Use only in monitored setting where respiratory depression and/or prolonged sedation can be managed; 1 200 consider reduced midazolam dosage, particularly if >1 dose will be used 1 200 Clonazepam, clorazepate, diazepam, estazolam, flurazepam: Monitor clinically; 1 reduced benzodiazepine dosage may be needed; 1 if initiated in patient receiving EVG/c/FTC/TDF, use low initial dosage 200 Diazepam: Consider alternative benzodiazepine (e.g., lorazepam, oxazepam, temazepam) 200 Bosentan Possible increased bosentan concentrations 1 In patient already receiving EVG/c/FTC/TDF for ≥10 days, initiate bosentan using dosage of 62.5 mg once daily or every other day based on individual tolerability 1 200 In patient already receiving bosentan, discontinue bosentan for at least 36 hours prior to initiating EVG/c/FTC/TDF; 1 200 after ≥10 days of EVG/c/FTC/TDF, resume bosentan using dosage of 62.5 mg once daily or every other day based on individual tolerability 1 200 Buprenorphine/naloxone Increased buprenorphine and norbuprenorphine concentrations and AUCs; 1 200 decreased naloxone concentrations and AUC Monitor closely for sedation and adverse cognitive effects; 1 200 dosage adjustments not needed 200 If patient receiving EVG/c/FTC/TDF is switched from transmucosal buprenorphine to subdermal implant, monitor to ensure buprenorphine effect is adequate and not excessive 200 Bupropion Possible increased or decreased bupropion concentrations 1 200 Carefully titrate antidepressant dosage based on clinical response 1 200 Buspirone Possible increased buspirone concentrations 1 Monitor clinically; 1 reduced buspirone dosage may be needed; 1 200 if initiated in patient receiving EVG/c/FTC/TDF, use low initial dosage 200 Calcium-channel blocking agents (amlodipine, diltiazem, felodipine, nicardipine, nifedipine, verapamil) Possible increased calcium-channel blocking agent concentrations 1 Use concomitantly with caution; 1 200 titrate dosage of calcium-channel blocking agent; 200 monitor for efficacy and adverse effects 1 200 Calcium supplements Possible decreased elvitegravir concentrations 200 Give EVG/c/FTC/TDF at least 2 hours before or at least 6 hours after oral calcium supplements; 200 monitor for antiretroviral efficacy 200 Cisapride Possible increased cisapride concentrations; 1 potential for serious and/or life-threatening reactions (e.g., cardiac arrhythmias) 1 Concomitant use contraindicated 1 Cobicistat Increased elvitegravir concentrations and AUC as the result of cobicistat inhibition of CYP3A; 1 200 acts as a pharmacokinetic enhancer ( cobicistat-boosted elvitegravir); 1 8 9 200 used to therapeutic advantage in fixed combination EVG/c/FTC/TDF 1 8 9 200 Slightly increased emtricitabine concentrations and AUC and slightly increased tenofovir concentrations; 8 not considered clinically important 8 Does not antagonize antiretroviral effects of elvitegravir, tenofovir, or emtricitabine 1 Component of fixed combination EVG/c/FTC/TDF 1 Colchicine Increased colchicine concentrations expected 1 200 Patients with renal or hepatic impairment: Concomitant use not recommended 1 200 Colchicine for treatment of gout flares: In those receiving EVG/c/FTC/TDF, use initial colchicine dose of 0.6 mg followed by 0.3 mg 1 hour later and repeat dose no earlier than 3 days later 1 200 Colchicine for prophylaxis of gout flares: In those receiving EVG/c/FTC/TDF, decrease colchicine dosage to 0.3 mg once daily in those originally receiving 0.6 mg twice daily or decrease dosage to 0.3 mg once every other day in those originally receiving 0.6 mg once daily 1 200 Colchicine for treatment of familial Mediterranean fever (FMF): In those receiving EVG/c/FTC/TDF, use maximum colchicine dosage of 0.6 mg daily (may be given as 0.3 mg twice daily) 1 200 Corticosteroids (beclomethasone, betamethasone, budesonide, ciclesonide, dexamethasone, fluticasone, methylprednisolone, mometasone, prednisolone, prednisone, triamcinolone) Fluticasone (orally inhaled, intranasal) or other orally inhaled or intranasal corticosteroids whose exposures are substantially affected by potent CYP3A inhibitors (e.g., ciclesonide, mometasone): Increased corticosteroid concentrations; may result in adrenal insufficiency or Cushing's syndrome 1 200 Methylprednisolone, prednisolone, triamcinolone (intra-articular, epidural, intraorbital, other local injections): Increased corticosteroid concentrations; 1 200 may result in adrenal insufficiency or Cushing's syndrome 1 200 Dexamethasone or other corticosteroids that induce CYP3A (systemic): Possible decreased elvitegravir and cobicistat concentrations with possible decreased antiretroviral efficacy and development of resistance 1 200 Corticosteroids whose exposures substantially affected by potent CYP3A inhibitors (systemic) (e.g., betamethasone, prednisone): Increased corticosteroid concentrations; may result in adrenal insufficiency or Cushing's syndrome 1 Fluticasone (orally inhaled, intranasal) or other corticosteroids whose exposures are substantially affected by potent CYP3A inhibitors (e.g., ciclesonide, mometasone): Consider alternative corticosteroid (e.g., beclomethasone), particularly for long-term use 1 200 Methylprednisolone, prednisolone, triamcinolone (intra-articular, epidural, intraorbital, other local injections): Do not use concomitantly 200 Dexamethasone (systemic): Consider alternative corticosteroid; 1 200 if used concomitantly, use caution and monitor virologic response 200 Other systemic corticosteroids whose exposures substantially affected by potent CYP3A inhibitors (e.g., betamethasone, budesonide, prednisone): Consider alternative corticosteroids (e.g., prednisolone), particularly for long-term use 1 Daclatasvir Possible increased daclatasvir concentrations 178 200 If used concomitantly with EVG/c/FTC/TDF, use daclatasvir dosage of 30 mg once daily 178 200 Dasabuvir Fixed combination of dasabuvir, ombitasvir, paritaprevir, and ritonavir (dasabuvir/ombitasvir/paritaprevir/ritonavir): Data not available regarding concomitant use with EVG/c/FTC/TDF 200 Dasabuvir/ombitasvir/paritaprevir/ritonavir: Concomitant use with EVG/c/FTC/TDF not recommended 200 Digoxin Possible increased digoxin concentrations Use concomitantly with caution; 200 monitor digoxin concentrations if possible 1 200 Elbasvir and grazoprevir Fixed combination of elbasvir and grazoprevir (elbasvir/grazoprevir): Possible increased elbasvir and grazoprevir concentrations 177 200 Elbasvir/grazoprevir: Concomitant use with EVG/c/FTC/TDF not recommended 177 200 Eplerenone Increased eplerenone concentrations expected 200 Some experts state concomitant use contraindicated 200 Ergot alkaloids (dihydroergotamine, ergotamine, methylergonovine) Potential for serious and/or life-threatening adverse effects (e.g., peripheral vasospasm, ischemia of extremities) 1 Concomitant use contraindicated 1 Estrogens/progestins Oral contraceptives containing ethinyl estradiol and norgestimate: Decreased ethinyl estradiol concentrations and AUC and increased norgestimate concentrations and AUC; 1 7 200 possible effects of increased norgestimate unknown but may include increased risk of insulin resistance, dyslipidemia, acne, venous thrombosis 1 200 Oral contraceptives containing progestin other than norgestimate: Not studied 1 Other hormonal contraceptives (e.g., patch, vaginal ring, injections): Not studied 1 Oral contraceptives containing ethinyl estradiol and norgestimate: Consider risks/benefits of concomitant use, particularly in women at risk of norgestimate-associated adverse effects 1 200 Oral contraceptives containing progestins other than norgestimate: Consider alternative nonhormonal methods of contraception 1 200 Other hormonal contraceptives (e.g., patch, vaginal ring, injections): Consider alternative nonhormonal methods of contraception 1 200 Flibanserin Increased flibanserin concentrations expected 200 Some experts state concomitant use contraindicated 200 Histamine H 2 -receptor antagonists (e.g., famotidine) Famotidine: No clinically important effect on elvitegravir concentrations or AUC 1 Histamine H 2 -receptor antagonists: Clinically important interactions with EVG/c/FTC/TDF not expected 1 200 Dosage adjustment not needed if EVG/c/FTC/TDF used concomitantly with a histamine H 2 -receptor antagonist 200 HIV entry and fusion inhibitors (maraviroc) Maraviroc: Increased maraviroc concentrations and AUC 10 Do not use concomitantly with EVG/c/FTC/TDF 200 HIV integrase inhibitors (INSTIs) Dolutegravir, elvitegravir, raltegravir: Do not use concomitantly with EVG/c/FTC/TDF 1 200 HIV nonnucleoside reverse transcriptase inhibitor antiretrovirals (NNRTIs) Efavirenz, etravirine, nevirapine, rilpivirine: Possible altered elvitegravir, cobicistat, and/or NNRTI concentrations 200 Efavirenz, etravirine, nevirapine, rilpivirine: Do not use concomitantly with EVG/c/FTC/TDF 1 200 HIV nucleoside and nucleotide reverse transcriptase inhibitor antiretrovirals (NRTIs) Emtricitabine and tenofovir DF: Components of EVG/c/FTC/TDF; do not use any preparation containing emtricitabine or tenofovir DF concomitantly with EVG/c/FTC/TDF 1 200 Other NRTIs (including lamivudine): Do not use concomitantly with EVG/c/FTC/TDF 1 200 HIV protease inhibitors (PIs) (atazanavir, darunavir, fosamprenavir, lopinavir, ritonavir, saquinavir, tipranavir) HIV PIs (with or without low-dose ritonavir or cobicistat): Possible altered concentrations of elvitegravir, cobicistat, and/or the HIV protease inhibitor 200 Ritonavir: Has an effect on CYP3A similar to that reported with cobicistat 1 200 HIV PIs (with or without low-dose ritonavir or cobicistat): Do not use concomitantly with EVG/c/FTC/TDF 1 200 Ritonavir: Do not use ritonavir or any ritonavir-containing preparation concomitantly with EVG/c/FTC/TDF 1 HMG-CoA reductase inhibitors (statins) Atorvastatin, lovastatin, simvastatin: Increased concentrations of the antilipemic agent; 1 200 increased risk of statin-associated adverse effects, including myopathy and rhabdomyolysis 1 200 Pitavastatin, pravastatin: Data not available regarding concomitant use with EVG/c/FTC/TDF 200 Rosuvastatin: Increased rosuvastatin concentrations and AUC; 1 no clinically important effect on elvitegravir pharmacokinetics 1 Atorvastatin: Initiate using lowest atorvastatin dosage and titrate slowly; monitor for atorvastatin-associated adverse effects 1 200 Lovastatin: Concomitant use contraindicated 1 Rosuvastatin: Some experts recommend slowly titrating rosuvastatin dosage; 200 use lowest possible rosuvastatin dose 200 Simvastatin: Concomitant use contraindicated 1 Immunosuppressive agents (cyclosporine, everolimus, sirolimus, tacrolimus) Cyclosporine, everolimus, sirolimus, tacrolimus: Possible increased immunosuppressive agent concentrations 1 200 Cyclosporine, sirolimus, tacrolimus: Monitor immunosuppressive agent concentrations and associated toxicities 1 Cyclosporine, everolimus, sirolimus, tacrolimus: Some experts recommend initiating immunosuppressive agent using a reduced dosage and monitoring for toxicities; 200 consultation with specialist may be needed 200 Iron preparations Possible decreased elvitegravir concentrations 200 Give EVG/c/FTC/TDF at least 2 hours before or at least 6 hours after iron preparations; 200 monitor for antiretroviral efficacy 200 Ivabradine Increased ivabradine concentrations expected 200 Some experts state concomitant use contraindicated 200 Laxatives containing polyvalent cations Possible decreased elvitegravir concentrations 200 Give EVG/c/FTC/TDF at least 2 hours before or at least 6 hours after laxatives containing polyvalent cations; 200 monitor for antiretroviral efficacy 200 Ledipasvir and sofosbuvir Fixed combination of ledipasvir and sofosbuvir (ledipasvir/sofosbuvir): Increased ledipasvir concentrations and increased tenofovir concentrations expected; 1 200 safety of increased tenofovir concentrations in patients receiving ledipasvir/sofosbuvir and EVG/c/FTC/TDF not established 1 Ledipasvir/sofosbuvir: Do not use concomitantly with EVG/c/FTC/TDF 1 200 Macrolides (clarithromycin) Clarithromycin: Possible increased clarithromycin and/or cobicistat concentrations 1 Clarithromycin: Dosage modification a variety of
prescribed drugs Elvitegravir, Cobicistat, Emtricitabine, and tenofovir Disoproxil Fumarate generally
EmoticonEmoticon