lack of awareness [50:<30 mL/minute: Do not use. 1 (See Renal Impairment under Cautions.) Cautions for Elvitegravir, Cobicistat, Emtricitabine, and Tenofovir Alafenamide 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; these drugs may result in decreased elvitegravir and/or cobicistat concentrations resulting in possible decreased antiretroviral efficacy and development of resistance. 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/TAF not indicated for treatment of chronic HBV infection. 1 Safety and efficacy of EVG/c/FTC/TAF not established in patients coinfected with HIV and HBV. 1 Severe acute exacerbations of HBV reported following discontinuance of preparations containing emtricitabine and/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 Such reactions could occur with EVG/c/FTC/TAF. 1 Closely monitor hepatic function (using both clinical and laboratory follow-up) for at least several months after EVG/c/FTC/TAF 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 prodrugs (e.g., tenofovir DF). 1 221 Cobicistat (a component of EVG/c/FTC/TAF) 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/TAF and routinely monitor during treatment in all patients. 1 (See Renal Impairment under Cautions.) Do not use EVG/c/FTC/TAF in patients with estimated Cl cr> <30 mL/minute. 1 If a confirmed increase in S cr of >0.4 mg/dL from baseline occurs during EVG/c/FTC/TAF treatment, closely monitor for renal toxicity. 1 Discontinue EVG/c/FTC/TAF if clinically important decreases in renal function occur or there is evidence of Fanconi syndrome. 1 Patients receiving a tenofovir prodrug who have impaired renal function or are receiving a nephrotoxic agent (e.g., high-dose or multiple NSAIAs) are at increased risk of developing adverse renal effects. 1 (See Interactions.) Lactic Acidosis and Severe Hepatomegaly with Steatosis Lactic acidosis and severe hepatomegaly with steatosis (sometimes fatal) reported in patients receiving HIV NRTIs, including emtricitabine and tenofovir DF, in conjunction with other antiretrovirals. 1 218 221 Interrupt EVG/c/FTC/TAF 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 Tenofovir prodrugs (tenofovir alafenamide, tenofovir DF) have been associated with decreases in bone mineral density (BMD). 1 200 221 BMD declines reported in adults receiving tenofovir alafenamide have been smaller than those reported in adults receiving tenofovir DF. 1 25 200 In addition, BMD increases reported when some adults were switched from a regimen containing tenofovir DF to a regimen containing tenofovir alafenamide. 1 200 Long-term clinical importance of BMD changes reported with tenofovir prodrugs unknown. 1 25 200 Use of Fixed Combinations Consider cautions, precautions, and contraindications associated with each component of EVG/c/FTC/TAF. 1 218 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 EVG/c/FTC/TAF 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/TAF concomitantly with any preparation that contains any of its components (elvitegravir, cobicistat, emtricitabine, tenofovir alafenamide). 1 In addition, do not use EVG/c/FTC/TAF concomitantly with any preparation containing tenofovir DF, 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-BarrĂ© 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/TAF 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 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/TAF administered separately during organogenesis at elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide exposures up to 23, 3.8, 108, and 53 times higher, respectively, than human exposures at the recommended daily dosage. 1 Experts state data insufficient to recommend routine use of EVG/c/FTC/TAF for initial treatment in pregnant women. 202 Lactation Elvitegravir and cobicistat distributed into milk in rats. 1 Tenofovir distributed into milk in animals following administration of tenofovir DF. 1 Not known whether elvitegravir, cobicistat, or tenofovir alafenamide distributed into human milk. 1 Emtricitabine is distributed into human milk. 1 Not known whether EVG/c/FTC/TAF 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/TAF not established in pediatric patients> <12 years of age or in those weighing> <35 kg. 1 Experts state that EVG/c/FTC/TAF is a preferred antiretroviral regimen in children and adolescents ≥12 years of age weighing ≥35 kg, including those in early puberty (SMR 1 3). 201 Clinical trial data indicate safety and efficacy of EVG/c/FTC/TAF in HIV-1-infected, treatment-naive pediatric patients 12 to> <18 years of age is similar to that reported in adults. 1 Geriatric Use No differences in safety or efficacy of EVG/c/FTC/TAF observed between individuals ≥65 years of age and individuals 12 to> <65 years of age. 1 Hepatic Impairment Mild hepatic impairment (Child-Pugh class A): No clinically important effects on pharmacokinetics of tenofovir alafenamide. 1 Moderate hepatic impairment (Child-Pugh class B): No clinically important effects on pharmacokinetics of elvitegravir, cobicistat, or tenofovir alafenamide; 1 not expected to affect pharmacokinetics of emtricitabine. 1 Severe hepatic impairment (Child-Pugh class C): EVG/c/FTC/TAF 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/TAF treatment in all patients. 1 Estimated Cl cr> <30 mL/minute: Do not use EVG/c/FTC/TAF; 1 safety not established. 1 Common Adverse Effects Nausea, diarrhea, fatigue, headache. 1 Interactions for Elvitegravir, Cobicistat, Emtricitabine, and Tenofovir Alafenamide Elvitegravir: Substrate of CYP3A; 1 24 25 weak inducer and weak inhibitor of CYP3A. 24 25 Induces CYP2C9. 1 Does not inhibit CYP1A, 2A6, 2C9, 2C19, 2D6, or 2E1. 24 Inhibits organic anion transport polypeptides (OATP)1B1 and 1B3. 1 24 Cobicistat: Substrate and inhibitor of CYP3A and 2D6. 1 24 25 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 alafenamide: Weak inhibitor of CYP3A in vitro, but does not inhibit or induce CYP3A in vivo. 1 Does not inhibit or induce CYP1A2, 2B6, 2C8, 2C9, 2C19, or 2D6. 1 25 Substrate of P-gp, BCRP, and OATP1B1 and 1B3. 1 25 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/TAF 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, cobicistat, and/or tenofovir alafenamide; 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 concentrations of such substrates. 1 P-gp inhibitors: Potential increased tenofovir alafenamide concentrations. 1 Cobicistat (a P-gp inhibitor) increases tenofovir alafenamide plasma concentrations when the drugs administered as EVG/c/FTC/TAF; 1 further increases not expected if an additional P-gp inhibitor used with EVG/c/FTC/TAF. 1 P-gp inducers: Decreased absorption and decreased plasma concentrations of tenofovir alafenamide expected. 1 Drugs Affected by Breast Cancer Resistance Protein BCRP substrates: Potential increased concentrations of such substrates. 1 BCRP inhibitors: Potential increased tenofovir alafenamide concentrations. 1 Cobicistat (a BCRP inhibitor) increases tenofovir alafenamide plasma concentrations when the drugs administered as EVG/c/FTC/TAF; 1 further increases not expected if an additional BCRP inhibitor used with EVG/c/FTC/TAF. 1 Drugs Affected by Organic Anion Transport Polypeptides OATP1B1 or 1B3 substrates: Potential increased 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 aminoglycoside; 1 may increase risk of adverse effects 1 Antacids, aluminum-, calcium-, and/or magnesium-containing Decreased elvitegravir concentrations and AUC when administered simultaneously 1 200 Give EVG/c/FTC/TAF at least 2 hours before or at least 2 hours after antacids 1 200 Antiarrhythmic agents (e.g., amiodarone, disopyramide, dronedarone, flecainide, lidocaine [systemic], mexiletine, propafenone, quinidine) Amiodarone, disopyramide, dronedarone, flecainide, lidocaine (systemic), mexiletine, propafenone, quinidine: Possible increased antiarrhythmic agent concentrations 1 200 Amiodarone, disopyramide, dronedarone, flecainide, lidocaine (systemic), mexiletine, propafenone, quinidine: Use concomitantly with caution; 1 200 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: Effect on warfarin pharmacokinetics not known, 1 but warfarin concentrations may be affected 200 Apixaban, edoxaban, rivaroxaban: Avoid concomitant use with EVG/c/FTC/TAF 200 Dabigatran: Some experts state dosage adjustments not needed if used with EVG/c/FTC/TAF in patients with Cl cr >50 mL/minute; 200 do not use concomitantly in those with Cl cr> <50 mL/minute 200 Warfarin: Monitor INR 1 Anticonvulsants (carbamazepine, ethosuximide, oxcarbazepine, phenobarbital, phenytoin) Carbamazepine, phenobarbital, phenytoin: Possible decreased elvitegravir, cobicistat, and tenofovir alafenamide concentrations with possible decreased antiretroviral efficacy and development of resistance 1 Ethosuximide: Possible increased ethosuximide concentrations; 1 possible decreased elvitegravir, cobicistat, and tenofovir alafenamide concentrations 1 Oxcarbazepine: Possible decreased elvitegravir, cobicistat, and tenofovir alafenamide concentrations 1 Carbamazepine, phenobarbital, phenytoin: Concomitant use contraindicated 1 Ethosuximide: Clinical monitoring recommended 1 Oxcarbazepine: Consider alternative anticonvulsant 1 Antidepressants, tricyclics (amitriptyline, desipramine, doxepin, imipramine, nortriptyline) Possible increased tricyclic antidepressant concentrations and AUC 1 200 Desipramine: Increased desipramine concentrations when used concomitantly with cobicistat 1 Initiate tricyclic antidepressant using lowest initial dosage and carefully titrate dosage according to clinical response 1 Antifungals, azoles Isavuconazonium (prodrug of isavuconazole): Possible increased isavuconazole, elvitegravir, and cobicistat concentrations 200 Itraconazole: Possible increased itraconazole, elvitegravir, and cobicistat concentrations 1 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 Isavuconazonium: Monitor for virologic efficacy; 200 consider monitoring isavuconazole concentrations 200 Itraconazole: Do not exceed itraconazole dosage of 200 mg daily 1 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 Antimycobacterials (rifabutin, rifampin, rifapentine) Rifabutin: Decreased elvitegravir concentrations and AUC and increased rifabutin metabolite concentrations and AUC when used with cobicistat-boosted elvitegravir; 1 possible decreased tenofovir alafenamide concentrations; 1 possible decreased antiretroviral efficacy and development of resistance 1 Rifampin: Possible decreased elvitegravir, cobicistat, and tenofovir alafenamide concentrations with possible decreased antiretroviral efficacy and development of resistance 1 Rifapentine: Possible decreased elvitegravir, cobicistat, and tenofovir alafenamide concentrations with possible decreased antiretroviral efficacy and development of resistance 1 Rifabutin: Concomitant use not recommended 1 Rifampin: Concomitant use contraindicated 1 Rifapentine: Concomitant use not recommended 1 Antiplatelet agents (ticagrelor, vorapaxar) Ticagrelor or vorapaxar: Increased antiplatelet agent concentrations expected 200 Ticagrelor or vorapaxar: Avoid concomitant use 200 Antipsychotics (e.g., lurasidone, perphenazine, pimozide, quetiapine, risperidone, thioridazine) Lurasidone: Possible serious and/or life-threatening reactions 1 Perphenazine, risperidone, thioridazine: Possible increased antipsychotic 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 1 Lurasidone: Concomitant use contraindicated 1 Perphenazine, risperidone, thioridazine: Decreased antipsychotic dosage may be needed 1 Pimozide: Concomitant use contraindicated 1 Quetiapine: Consider alternative antiretroviral; 1 if EVG/c/FTC/TAF necessary in patient receiving stable quetiapine dosage, reduce quetiapine dosage to one-sixth of original dosage and monitor for quetiapine-associated adverse effects 1 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-blocker dosage may be needed 1 Benzodiazepines (e.g., clonazepam, clorazepate, diazepam, estazolam, flurazepam, lorazepam, midazolam, triazolam) Diazepam: Possible increased diazepam concentrations 1 Lorazepam: Clinically important effects on lorazepam concentrations not expected 1 Midazolam or triazolam: Increased benzodiazepine concentrations; 1 potential for serious and/or life-threatening adverse effects (e.g., prolonged or increased sedation or respiratory depression) 1 Clonazepam, clorazepate, estazolam, flurazepam: Possible increased benzodiazepine concentrations 1 200 Diazepam: Use concomitantly only in monitored setting where respiratory depression and/or prolonged sedation can be managed; 1 experts state consider alternatives to diazepam (e.g., lorazepam, oxazepam, temazepam) 200 Oral midazolam or triazolam: Concomitant use contraindicated 1 Parenteral midazolam: Use concomitantly only in monitored setting where respiratory depression and/or prolonged sedation can be managed; 1 consider reduced midazolam dosage, particularly if >1 dose will be used 1 Clonazepam, clorazepate, estazolam, flurazepam: Experts recommend low initial benzodiazepine dosage with close monitoring 200 Bosentan Possible increased bosentan concentrations 1 In patient already receiving EVG/c/FTC/TAF for ≥10 days, initiate bosentan using dosage of 62.5 mg once daily or every other day based on individual tolerability 1 In patient already receiving bosentan, discontinue bosentan for at least 36 hours prior to initiating EVG/c/FTC/TAF; 1 after ≥10 days of EVG/c/FTC/TAF, resume bosentan using dosage of 62.5 mg once daily or every other day based on individual tolerability 1 Buprenorphine/naloxone Increased buprenorphine and norbuprenorphine concentrations and AUCs; 1 decreased naloxone concentrations and AUC 1 Monitor closely for sedation and adverse cognitive effects; 1 dosage adjustments not needed 1 If patient receiving EVG/c/FTC/TAF is switched from transmucosal buprenorphine to subdermal implant, monitor to ensure buprenorphine effect is adequate and not excessive 200 Bupropion Possible increased bupropion concentrations 1 Carefully titrate antidepressant dosage based on clinical response 1 Buspirone Possible increased buspirone concentrations 1 Monitor clinically; 1 reduced buspirone dosage may be needed 1 Calcium-channel blocking agents (amlodipine, diltiazem, felodipine, nicardipine, nifedipine, verapamil) Possible increased calcium-channel blocking agent concentrations 1 Use concomitantly with caution 1 ; monitor clinically 1 Calcium supplements Possible decreased elvitegravir concentrations 200 Give EVG/c/FTC/TAF 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 acts as a pharmacokinetic enhancer ( cobicistat-boosted elvitegravir); 1 used to therapeutic advantage in fixed-combination EVG/c/FTC/TAF 1 Increased tenofovir alafenamide concentrations and AUC as the result of cobicistat inhibition of P-gp, BCRP, and OATP1B1 and 1B3 1 25 Does not antagonize antiretroviral effects of elvitegravir, tenofovir, or emtricitabine 1 Component of fixed-combination EVG/c/FTC/TAF 1 Colchicine Increased colchicine concentrations expected 1 Patients with renal or hepatic impairment: Concomitant use not recommended 1 Colchicine for treatment of gout flares: In those receiving EVG/c/FTC/TAF, 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 Colchicine for prophylaxis of gout flares: In those receiving EVG/c/FTC/TAF, 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 Colchicine for treatment of familial Mediterranean fever (FMF): In those receiving EVG/c/FTC/TAF, use maximum colchicine dosage of 0.6 mg daily (may be given as 0.3 mg twice daily) 1 Corticosteroids (dexamethasone, fluticasone) Dexamethasone (systemic): Possible decreased elvitegravir and cobicistat concentrations 1 Fluticasone (orally inhaled, intranasal): Possible increased fluticasone concentrations 1 Methylprednisolone, prednisolone, or triamcinolone (intra-articular or other local injections): Increased corticosteroid concentrations; 200 may result in adrenal insufficiency or Cushing's syndrome 200 Dexamethasone (systemic): Consider alternative corticosteroid 1 Fluticasone (orally inhaled, intranasal): Consider alternative corticosteroid, particularly for long-term use 1 Methylprednisolone, prednisolone, or triamcinolone (intra-articular or other local injections): Do not use concomitantly with EVG/c/FTC/TAF 200 Daclatasvir Possible increased daclatasvir concentrations 178 200 If used concomitantly with EVG/c/FTC/TAF, 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/TAF 200 Dasabuvir/ombitasvir/paritaprevir/ritonavir: Concomitant use with EVG/c/FTC/TAF not recommended 200 Digoxin Increased digoxin concentrations 1 Use concomitantly with caution; monitor digoxin concentrations 1 Elbasvir and grazoprevir Fixed combination of elbasvir and grazoprevir (elbasvir/grazoprevir): Possible increased elbasvir and grazoprevir concentrations 177 200 Elbasvir/grazoprevir: Concomitant use 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 possible effects of increased norgestimate unknown but may include increased risk of insulin resistance, dyslipidemia, acne, venous thrombosis 1 Oral contraceptives containing progestin other than norgestimate: Not studied 1 Other hormonal contraceptives (e.g., transdermal systems, 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 Oral contraceptives containing progestins other than norgestimate: Consider alternative nonhormonal methods of contraception 1 Other hormonal contraceptives (e.g., transdermal systems, vaginal ring, injections): Consider alternative nonhormonal methods of contraception 1 Flibanserin Increased flibanserin concentrations expected 200 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/TAF not expected 1 HIV INSTIs Elvitegravir: Component of fixed-combination EVG/c/FTC/TAF; do not use concomitantly 1 HIV NRTIs Emtricitabine, tenofovir alafenamide: Components of EVG/c/FTC/TAF; 1 do not use any preparation containing emtricitabine or tenofovir alafenamide concomitantly with EVG/c/FTC/TAF 1 Tenofovir DF: Do not use any preparation containing tenofovir DF concomitantly with EVG/c/FTC/TAF 1 Other HIV NRTIs (including lamivudine): Do not use concomitantly with EVG/c/FTC/TAF 1 HIV protease inhibitors (PIs) Ritonavir: Do not use ritonavir or any ritonavir-containing preparation concomitantly with EVG/c/FTC/TAF 1 HMG-CoA reductase inhibitors (statins) Atorvastatin: Possible increased atorvastatin concentrations 1 Lovastatin, simvastatin: Possible increased statin concentrations may lead to serious adverse effects, including myopathy and rhabdomyolysis 1 200 Rosuvastatin: Increased rosuvastatin concentrations and AUC; 1 no clinically important effect on elvitegravir pharmacokinetics 1 Atorvastatin: Initiate using lowest atorvastatin dosage and titrate carefully; monitor for atorvastatin-associated adverse effects 1 Lovastatin, simvastatin: Concomitant use contraindicated 1 Immunosuppressive agents (everolimus, cyclosporine, sirolimus, tacrolimus) Cyclosporine: Possible increased cyclosporine, elvitegravir, and cobicistat concentrations 1 Everolimus, sirolimus, tacrolimus: Possible increased immunosuppressive agent concentrations 1 200 Cyclosporine: Monitor cyclosporine concentrations; 1 monitor for EVG/c/FTC/TAF-associated adverse effects; some experts state initiate immunosuppressive agent using decreased dosage and monitor for toxicities; 200 consultation with a specialist may be necessary 200 Everolimus, sirolimus, tacrolimus: Monitor immunosuppressive agent concentrations; 1 200 some experts state initiate immunosuppressive agent using decreased dosage and monitor for toxicities; 200 consultation with a specialist may be necessary 200 Iron preparations Possible decreased elvitegravir concentrations 200 Give EVG/c/FTC/TAF 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/TAF 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): Clinically important pharmacokinetic interactions not expected 1 200 Ledipasvir/sofosbuvir: Dosage adjustments not needed 200 Macrolides (clarithromycin) Clarithromycin: Possible increased macrolide and/or cobicistat concentrations 1 Clarithromycin: Dosage modification not needed in patients with Cl cr ≥60 mL/minute; 1 reduce clarithromycin dosage by 50% in those with Cl cr 50 60 mL/minute 1 Methadone Clinically important pharmacokinetic interactions not expected 1 Multivitamins or other preparations containing calcium, iron, aluminum, magnesium, or zinc Possible decreased elvitegravir concentrations 200 Give EVG/c/FTC/TAF at least 2 hours before or at least 6 hours after multivitamins; 200 monitor for antiretroviral efficacy 200 NSAIAs High-dose or multiple NSAIAs: Competition for active tubular secretion may increase concentrations of emtricitabine, tenofovir, and/or the concomitant NSAIA; 1 may increase risk of adverse effects 1 Avoid EVG/c/FTC/TAF in patients who are receiving or have recently received a nephrotoxic drug (e.g., high-dose or multiple NSAIAs) 1 Nucleoside and nucleotide antivirals (acyclovir, adefovir, cidofovir, entecavir, famciclovir, ganciclovir, ribavirin, valacyclovir, valganciclovir) Acyclovir, cidofovir, ganciclovir, valacyclovir, valganciclovir: Competition for active tubular secretion may increase concentrations of emtricitabine, tenofovir, and/or the concomitant antiviral; 1 may increase risk of adverse effects 1 Entecavir, famciclovir: Clinically important interaction not expected 1 Ribavirin: Clinically important interaction not expected 1 Adefovir: Do not use concomitantly with EVG/c/FTC/TAF 1 Ombitasvir Dasabuvir/ombitasvir/paritaprevir/ritonavir: Data not available regarding concomitant use with EVG/c/FTC/TAF 200 Dasabuvir/ombitasvir/paritaprevir/ritonavir: Concomitant use with EVG/c/FTC/TAF not recommended 200 Paritaprevir Dasabuvir/ombitasvir/paritaprevir/ritonavir: Data not available regarding concomitant use with EVG/c/FTC/TAF 200 Dasabuvir/ombitasvir/paritaprevir/ritonavir: Concomitant use with EVG/c/FTC/TAF not recommended 200 Proton-pump inhibitors (e.g., omeprazole) Omeprazole: No clinically important effect on elvitegravir concentrations or AUC 1 Proton-pump inhibitors: Clinically important interactions with EVG/c/FTC/TAF not expected 1 Ranolazine Experts state do not use concomitantly 200 Salmeterol Possible increased salmeterol concentrations; 1 may increase risk of QT prolongation, palpitations, or sinus tachycardia 1 Concomitant use with EVG/c/FTC/TAF not recommended 1 Selective serotonin-reuptake inhibitors (SSRIs) SSRIs: Possible increased SSRI concentrations 1 Sertraline: Clinically important interactions not expected 1 SSRIs: Carefully titrate SSRI dosage and monitor antidepressant response 1 Sildenafil Increased sildenafil concentrations and increased risk of sildenafil-associated adverse effects (e.g., hypotension, syncope, visual disturbances, prolonged erection) 1 Sildenafil for treatment of PAH: Concomitant use with EVG/c/FTC/TAF contraindicated 1 Sildenafil for treatment of erectile dysfunction: Do not exceed sildenafil dosage of 25 mg once every 48 hours; 1 closely monitor for sildenafil-related adverse effects 1 Simeprevir Increased simeprevir concentrations expected 200 Concomitant use not recommended 200 Sofosbuvir Clinically important pharmacokinetic interactions not expected 1 Dosage adjustments not needed 200 Sofosbuvir and velpatasvir Fixed combination of sofosbuvir and velpatasvir (sofosbuvir/velpatasvir): No clinically important pharmacokinetic interactions 1 St. John s wort ( Hypericum perforatum ) Possible decreased elvitegravir, cobicistat, and tenofovir alafenamide concentrations with possible decreased antiretroviral efficacy and development of resistance 1 Concomitant use contraindicated 1 Sucralfate Possible decreased elvitegravir concentrations 200 Give EVG/c/FTC/TAF at least 2 hours before or at least 6 hours after sucralfate; 200 monitor for antiretroviral efficacy 200 Suvorexant Increased suvorexant concentrations expected 200 Experts state concomitant use not recommended 200 Tadalafil Increased tadalafil concentrations and increased risk of tadalafil-associated adverse effects (e.g., hypotension, syncope, visual disturbances, prolonged erection) 1 Tadalafil for treatment of PAH in patients who have been receiving EVG/c/FTC/TAF for ≥1 week: Use initial tadalafil dosage of 20 mg once daily; 1 if tolerated, increase dosage to 40 mg once daily 1 EVG/c/FTC/TAF in patients receiving tadalafil for PAH: Discontinue tadalafil for at least 24 hours prior to initiating EVG/c/FTC/TAF; 1 after ≥1 week of the antiretroviral agent, may resume tadalafil at a dosage of 20 mg once daily, and, if tolerated, may increase dosage to 40 mg once daily 1 Tadalafil for treatment of erectile dysfunction: Do not exceed tadalafil dosage of 10 mg once every 72 hours; 1 closely monitor for tadalafil-related adverse effects 1 Trazodone Possible increased trazodone concentrations 1 Carefully titrate trazodone dosage and monitor antidepressant response 1 Vardenafil Possible increased vardenafil concentrations and increased risk of vardenafil-associated adverse effects (e.g., hypotension, syncope, visual disturbances, prolonged erectio rewarding
weak spot Elvitegravir, Cobicistat, Emtricitabine, and Tenofovir Alafenamide before
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