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Elvitegravir, Cobicistat, Emtricitabine, and tenofovir Disoproxil Fumarate

Class: HIV Integrase Inhibitors
ATC Class: J05AX08
Chemical Name: 6-[(3-Chloro-2-fluorophenyl)methycypl]-1,4-dihydro-1-[(1S)-1-(hydroxymethyl)-2-methylpropyl]-7-methoxy-4-oxo-3-quinolinecarboxylic acid
Molecular Formula: C23H23ClFNO5C40H53N7O5S2C8H10FN3O3SC9H14N5O4P • H2O
CAS Number: 697761-98-1

Medically reviewed by Drugs.com on Sep 29, 2021. Written by ASHP.

Warning

    HBV Infection
  • Fixed combination of EVG/c/FTC/TDF not indicated for treatment of chronic HBV infection. Safety and efficacy of EVG/c/FTC/TDF not established in HIV-1 infected patients coinfected with HBV.

  • Severe, acute exacerbations of HBV reported following discontinuance of emtricitabine or tenofovir DF in patients coinfected with HIV and HBV. Monitor hepatic function closely with both clinical and laboratory follow-up for at least several months after EVG/c/FTC/TDF discontinued in patients coinfected with HIV and HBV. If appropriate, initiation of HBV treatment may be warranted. (See HIV-infected Individuals Coinfected with HBV under Cautions.)

Introduction

Antiretroviral; fixed combination of elvitegravir, cobicistat, emtricitabine, and tenofovir disoproxil fumarate (tenofovir DF) (EVG/c/FTC/TDF). Elvitegravir (EVG) is an HIV integrase strand transfer inhibitor (INSTI) antiretroviral; cobicistat is a CYP3A inhibitor used as a pharmacokinetic enhancer to decrease metabolism and increase plasma concentrations of EVG; emtricitabine (FTC) and tenofovir DF (TDF) are HIV nucleoside reverse transcriptase inhibitors (NRTIs).

Uses for Elvitegravir, Cobicistat, Emtricitabine, and tenofovir Disoproxil Fumarate

Treatment of HIV Infection

Treatment of HIV-1 infection in antiretroviral-naive (have not previously received antiretroviral therapy) or antiretroviral-experienced (previously treated) adults and pediatric patients ≥12 years of age.

Fixed combination of EVG/c/FTC/TDF used alone as a complete regimen for treatment of HIV-1 infection; do not use with other antiretrovirals.

For initial treatment in antiretroviral-naive adults, experts state EVG/c/FTC/TDF is a recommended INSTI-based regimen.

For initial treatment in HIV-infected pediatric patients, experts state that EVG/c/FTC/TDF is not a preferred or alternative regimen and is recommended only for children and adolescents ≥12 years of age who weigh ≥35 kg and are in late puberty (sexual maturity rating [SMR] 4 or 5).

For antiretroviral-experienced adults and pediatric patients ≥12 years of age, manufacturer states EVG/c/FTC/TDF can be used to replace the current antiretroviral regimen in those with plasma HIV-1 RNA levels <50 copies/mL on a stable antiretroviral regimen for ≥6 months who have no history of treatment failure and are infected with HIV-1 with no known substitutions associated with resistance to the antiretroviral components of the fixed combination (i.e., elvitegravir, emtricitabine, tenofovir).

Postexposure Prophylaxis following Occupational Exposure to HIV

Postexposure prophylaxis of HIV infection following occupational exposure (PEP) in health-care personnel and others exposed via percutaneous injury (e.g., needlestick, cut with sharp object) or mucous membrane or nonintact skin (e.g., chapped, abraded, dermatitis) contact with blood, tissue, or other body fluids that might contain HIV.

USPHS recommends 3-drug regimen of raltegravir and emtricitabine and tenofovir DF as the preferred regimen for PEP following occupational exposures to HIV. EVG/c/FTC/TDF used alone is one of several alternative regimens for PEP.

Management of occupational exposures to HIV is complex and evolving; consult infectious disease specialist, clinician with expertise in administration of antiretrovirals, and/or National Clinicians’ Postexposure Prophylaxis Hotline (PEPline at 888-448-4911) whenever possible. Do not delay initiation of PEP while waiting for expert consultation.

Elvitegravir, Cobicistat, Emtricitabine, and tenofovir Disoproxil Fumarate Dosage and Administration

General

  • Determine Scr, estimated Clcr, serum phosphorus, urine glucose, and urine protein prior to initiation of EVG/c/FTC/TDF and routinely monitor during treatment in all patients. (See Renal Impairment under Cautions.)

  • Test for HBV infection prior to initiation of EVG/c/FTC/TDF. (See HIV-infected Individuals Coinfected with HBV under Cautions.)

Administration

Oral Administration

Administer fixed combination of EVG/c/FTC/TDF orally once daily with food.

Dosage

Each fixed-combination tablet of EVG/c/FTC/TDF contains elvitegravir 150 mg, cobicistat 150 mg, emtricitabine 200 mg, and tenofovir DF 300 mg.

Pediatric Patients

Treatment of HIV Infection
Oral

Pediatric patients ≥12 years of age weighing ≥35kg: 1 tablet of EVG/c/FTC/TDF (elvitegravir 150 mg, cobicistat 150 mg, emtricitabine 200 mg, tenofovir DF 300 mg) once daily.

Adults

Treatment of HIV Infection
Oral

1 tablet of EVG/c/FTC/TDF (elvitegravir 150 mg, cobicistat 150 mg, emtricitabine 200 mg, tenofovir DF 300 mg) once daily.

Postexposure Prophylaxis following Occupational Exposure to HIV†
Oral

1 tablet of EVG/c/FTC/TDF (elvitegravir 150 mg, cobicistat 150 mg, emtricitabine 200 mg, tenofovir DF 300 mg) once daily.

Initiate PEP as soon as possible following occupational exposure to HIV (preferably within hours); continue for 4 weeks, if tolerated.

Special Populations

Hepatic Impairment

Mild or moderate hepatic impairment (Child-Pugh class A or B): Dosage adjustments not needed.

Severe hepatic impairment (Child-Pugh class C): Do not use. (See Hepatic Impairment under Cautions.)

Renal Impairment

Adults: Do not initiate EVG/c/FTC/TDF if estimated Clcr <70 mL/minute. Discontinue if estimated Clcr decreases to <50 mL/minute during treatment. (See Renal Impairment under Cautions.)

Pediatric patients: Data insufficient to make dosage recommendations for those with renal impairment.

Geriatric Patients

Use with caution. (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). (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]). (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.

EVG/c/FTC/TDF not indicated for treatment of chronic HBV infection. Safety and efficacy of EVG/c/FTC/TDF not established in patients coinfected with HIV and HBV.

Severe acute exacerbations of HBV reported following discontinuance of emtricitabine or tenofovir DF in HIV-infected patients with HBV infection. HBV exacerbations have been associated with hepatic decompensation and hepatic failure.

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. If appropriate, initiation of HBV treatment may be warranted.

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).

Cobicistat (a component of EVG/c/FTC/TDF) may cause modest increase in Scr and modest decrease in estimated Clcr due to inhibition of tubular secretion of creatinine; glomerular function not affected.

Determine Scr, estimated Clcr, serum phosphorus, urine glucose, and urine protein prior to initiation of EVG/c/FTC/TDF and routinely monitor during treatment in all patients. (See Renal Impairment under Cautions.)

Do not initiate EVG/c/FTC/TDF in patients with estimated Clcr <70 mL/minute; discontinue if estimated Clcr decreases to <50 mL/minute during therapy.

If a confirmed increase in Scr of >0.4 mg/dL from baseline occurs during EVG/c/FTC/TDF treatment, closely monitor for renal toxicity.

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. (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). 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. Consider alternatives to NSAIAs in patients at risk for renal dysfunction.

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.

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).

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). Bone effects reported in pediatric patients are similar to those reported in adults. Effects of tenofovir-associated changes in BMD on long-term bone health and future fracture risk unknown.

Osteomalacia associated with proximal renal tubulopathy, which may contribute to fractures, reported in patients receiving tenofovir DF. Arthralgia and muscle pain or weakness also reported in cases of proximal renal tubulopathy. 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.

Consider BMD monitoring in adult and pediatric patients with history of pathologic bone fracture or other risk factors for osteoporosis or bone loss. Effect of calcium and vitamin D supplementation not studied, but may be beneficial for all patients. If bone abnormalities suspected, obtain appropriate consultation.

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. (See Contraindications and see Interactions.)

Consider potential drug interactions prior to and during therapy. Review drugs used concomitantly with EVG/c/FTC/TDF; monitor patient for adverse reactions associated with these drugs. (See Interactions.)

Use of Fixed Combinations

Consider cautions, precautions, and contraindications associated with each component of EVG/c/FTC/TDF. 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.

EVG/c/FTC/TDF is used alone as a complete regimen for treatment of HIV-1 infection; do not use in conjunction with other antiretrovirals. (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). In addition, do not use EVG/c/FTC/TDF concomitantly with any preparation containing lamivudine, adefovir dipivoxil, or ritonavir.

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]); this may necessitate further evaluation and treatment.

Autoimmune disorders (e.g., Graves' disease, polymyositis, Guillain-Barré syndrome) also reported in the setting of immune reconstitution; time to onset is more variable and can occur many months after initiation of antiretroviral therapy.

Specific Populations

Pregnancy

Antiretroviral Pregnancy Registry at 800-258-4263 or [Web].

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. 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.

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.

Experts state data insufficient to recommend routine use of EVG/c/FTC/TDF for initial treatment in antiretroviral-naive pregnant women.

Lactation

Elvitegravir and cobicistat distributed into milk in rats; not known whether these drugs distributed into human milk. Emtricitabine and tenofovir DF are distributed into human milk.

Not known whether EVG/c/FTC/TDF affects human milk production or affects the breast-fed infant.

Instruct HIV-infected women not to breast-feed because of risk of HIV transmission and risk of adverse effects in the infant.

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.

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.

Bone effects reported when tenofovir DF is used in pediatric and adolescent patients are similar to those reported in adults. In clinical studies, total body BMD gain in tenofovir DF-treated pediatric patients was less than that reported in control groups; skeletal growth appeared to be unaffected. Effects of tenofovir DF-associated changes in BMD and biochemical markers on long-term bone health and future fracture risk unknown.

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). 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.

Geriatric Use

Insufficient experience in adults ≥65 years of age to determine whether geriatric patients respond differently than younger adults.

Use with caution because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.

Hepatic Impairment

Moderate hepatic impairment (Child-Pugh class B): No clinically important effect on pharmacokinetics of elvitegravir, cobicistat, or tenofovir; not expected to affect emtricitabine pharmacokinetics.

Severe hepatic impairment (Child-Pugh class C): EVG/c/FTC/TDF not recommended; data not available to date regarding pharmacokinetics or safety in such patients.

Renal Impairment

Determine Scr, estimated Clcr, serum phosphorus, urine glucose, and urine protein prior to and routinely monitor during EVG/c/FTC/TDF treatment in all patients.

Adults: Do not initiate EVG/c/FTC/TDF in patients with estimated Clcr <70 mL/minute. Discontinue if estimated Clcr decreases to <50 mL/minute during treatment.

Pediatric patients: Data insufficient to make dosage recommendations for those with renal impairment.

Common Adverse Effects

Nausea, diarrhea, abnormal dreams, headache.

Interactions for Elvitegravir, Cobicistat, Emtricitabine, and tenofovir Disoproxil Fumarate

Elvitegravir: Substrate of CYP3A; weak inducer and weak inhibitor of CYP3A. Induces CYP2C9. Does not inhibit CYP1A, 2A6, 2C9, 2C19, 2D6, or 2E1 in vitro. Inhibits organic anion transport polypeptides (OATP) 1B1 and 1B3.

Cobicistat: Substrate and inhibitor of CYP3A and 2D6; also inhibits CYP3A and 2D6. Inhibits p-glycoprotein (P-gp) transport, breast cancer resistance protein (BCRP), and OATP1B1 and 1B3.

Emtricitabine: Not a substrate of CYP enzymes; does not inhibit CYP1A2, 2A6, 2B6, 2C9, 2C19, 2D6, or 3A4.

Tenofovir DF and tenofovir: Not substrates of CYP enzymes; tenofovir does not inhibit CYP3A4, 2D6, 2C9, or 2E1, but may have a slight inhibitory effect on CYP1A.

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.

Consider potential interactions associated with each drug in the fixed combination.

Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes

CYP3A or 2D6 substrates: Potential increased plasma concentrations of such substrates.

CYP3A inducers: Potential decreased plasma concentrations of elvitegravir and cobicistat; possible decreased antiretroviral efficacy and development of resistance.

CYP3A inhibitors: Potential increased plasma concentrations of cobicistat.

Drugs Affected by P-glycoprotein Transport

P-gp substrates: Potential increased plasma concentrations of such substrates.

Drugs Affected by Breast Cancer Resistance Protein

BCRP substrates: Potential increased plasma concentrations of such substrates.

Drugs Affected by Organic Anion Transport Polypeptides

OATP1B1 or 1B3 substrates: Potential increased plasma concentrations of such substrates.

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.

Specific Drugs

Drug

Interaction

Comments

Alfuzosin

Possible increased alfuzosin concentrations; may result in hypotension

Concomitant use contraindicated

Aminoglycosides (e.g., gentamicin)

Competition for active tubular secretion may increase concentrations of emtricitabine, tenofovir, and/or the concomitant aminoglycoside; may increase risk of adverse effects

Antacids, aluminum-, calcium-, and/or magnesium-containing

Decreased elvitegravir concentrations and AUC when administered simultaneously

Give EVG/c/FTC/TDF at least 2 hours before or at least 2 hours after antacids

Antiarrhythmic agents (amiodarone, disopyramide, dronedarone, flecainide, lidocaine [systemic], mexiletine, propafenone, quinidine)

Possible increased antiarrhythmic agent concentrations

Use concomitantly with caution; monitor antiarrhythmic agent concentrations if possible

Anticoagulants (apixaban, dabigatran, edoxaban, rivaroxaban, warfarin)

Apixaban, edoxaban, rivaroxaban: Increased anticoagulant concentrations expected

Dabigatran: Possible increased dabigatran concentrations

Warfarin: Possible altered warfarin concentrations

Apixaban, edoxaban, rivaroxaban: Avoid concomitant use with EVG/c/FTC/TDF

Dabigatran: Some experts state dosage adjustments not needed if used with EVG/c/FTC/TDF in patients with Clcr >50 mL/minute; do not use concomitantly in those with Clcr <50 mL/minute

Warfarin: Monitor INR and adjust warfarin dosage accordingly

Anticonvulsants (carbamazepine, ethosuximide, oxcarbazepine, phenobarbital, phenytoin)

Carbamazepine, phenobarbital, phenytoin: Possible increased anticonvulsant concentrations; possible decreased elvitegravir and cobicistat concentrations with possible decreased antiretroviral efficacy and development of resistance

Ethosuximide: Possible increased ethosuximide concentrations

Oxcarbazepine: Possible decreased elvitegravir and cobicistat concentrations

Carbamazepine, phenobarbital, phenytoin: Concomitant use contraindicated

Ethosuximide: If used concomitantly with EVG/c/FTC/TDF, monitor clinically for ethosuximide-associated adverse effects

Oxcarbazepine: Consider alternative anticonvulsant

Antidepressants, tricyclics (amitriptyline, desipramine, doxepin, imipramine, nortriptyline)

Possible increased tricyclic antidepressant concentrations and AUC

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

Antifungals, azoles

Isavuconazonium (prodrug of isavuconazole): Possible increased isavuconazole, elvitegravir, and cobicistat concentrations

Itraconazole: Increased itraconazole concentrations expected; possible increased elvitegravir and cobicistat concentrations

Ketoconazole: Increased ketoconazole, elvitegravir, and cobicistat concentrations

Posaconazole: Possible increased posaconazole, elvitegravir, and cobicistat concentrations

Voriconazole: Possible increased voriconazole, elvitegravir, and cobicistat concentrations

Isavuconazonium: Monitor for virologic efficacy; consider monitoring isavuconazole concentrations

Itraconazole: Do not exceed itraconazole dosage of 200 mg daily; experts state use itraconazole dosage >200 mg daily only if itraconazole concentrations monitored

Ketoconazole: Do not exceed ketoconazole dosage of 200 mg daily

Posaconazole: Monitor posaconazole concentrations

Voriconazole: Avoid concomitant use unless benefits outweigh risks; if used concomitantly, experts state consider monitoring voriconazole concentrations and adjust voriconazole dosage accordingly

Antiplatelet agents (ticagrelor, vorapaxar)

Ticagrelor or vorapaxar: Increased antiplatelet concentrations expected

Ticagrelor or vorapaxar: Avoid concomitant use

Antimycobacterials (rifabutin, rifampin, rifapentine)

Rifabutin: Decreased elvitegravir concentrations and AUC and increased rifabutin metabolite concentrations and AUC when used with cobicistat-boosted elvitegravir

Rifampin: Possible decreased elvitegravir and cobicistat concentrations with possible decreased antiretroviral efficacy and development of resistance

Rifapentine: Possible decreased elvitegravir and cobicistat concentrations with possible decreased antiretroviral efficacy and development of resistance

Rifabutin: Concomitant use not recommended

Rifampin: Concomitant use contraindicated

Rifapentine: Concomitant use not recommended

Antipsychotics (perphenazine, lurasidone, pimozide, risperidone, quetiapine, thioridazine)

Lurasidone: Possible serious and/or life-threatening reactions

Perphenazine, risperidone, thioridazine: Possible increased antipsychotic agent concentrations

Pimozide: Possible increased pimozide concentrations resulting in serious and/or life-threatening reactions (e.g., cardiac arrhythmias)

Quetiapine: Increased quetiapine concentrations expected

Lurasidone: Concomitant use contraindicated

Perphenazine, risperidone, thioridazine: Decreased antipsychotic dosage may be needed; if initiated in patients receiving EVG/c/FTC/TDF, use low initial dosage of the antipsychotic

Pimozide: Concomitant use contraindicated

Quetiapine: Consider alternative antiretroviral; 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; 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

Avanafil

Data not available

Concomitant use not recommended

β-Adrenergic blocking agents (metoprolol, timolol)

Metoprolol, timolol: Possible increased β-blocking agent concentrations

Metoprolol, timolol: Monitor clinically; reduced β-blocking agent dosage may be needed; consider alternative agent not metabolized by CYP isoenzymes (e.g., atenolol, labetalol, nadolol, sotalol)

Benzodiazepines (clonazepam, clorazepate, diazepam, estazolam, flurazepam, midazolam, triazolam)

Midazolam or triazolam: Increased benzodiazepine concentrations; potential for serious and/or life-threatening adverse effects (e.g., prolonged or increased sedation or respiratory depression)

Clonazepam, clorazepate, diazepam, estazolam, flurazepam: Possible increased benzodiazepine concentrations

Oral midazolam or triazolam: Concomitant use contraindicated

Parenteral midazolam: Use only in monitored setting where respiratory depression and/or prolonged sedation can be managed; consider reduced midazolam dosage, particularly if >1 dose will be used

Clonazepam, clorazepate, diazepam, estazolam, flurazepam: Monitor clinically; reduced benzodiazepine dosage may be needed; if initiated in patient receiving EVG/c/FTC/TDF, use low initial dosage

Diazepam: Consider alternative benzodiazepine (e.g., lorazepam, oxazepam, temazepam)

Bosentan

Possible increased bosentan concentrations

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

In patient already receiving bosentan, discontinue bosentan for at least 36 hours prior to initiating EVG/c/FTC/TDF; 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

Buprenorphine/naloxone

Increased buprenorphine and norbuprenorphine concentrations and AUCs; decreased naloxone concentrations and AUC

Monitor closely for sedation and adverse cognitive effects; dosage adjustments not needed

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

Bupropion

Possible increased or decreased bupropion concentrations

Carefully titrate antidepressant dosage based on clinical response

Buspirone

Possible increased buspirone concentrations

Monitor clinically; reduced buspirone dosage may be needed; if initiated in patient receiving EVG/c/FTC/TDF, use low initial dosage

Calcium-channel blocking agents (amlodipine, diltiazem, felodipine, nicardipine, nifedipine, verapamil)

Possible increased calcium-channel blocking agent concentrations

Use concomitantly with caution; titrate dosage of calcium-channel blocking agent; monitor for efficacy and adverse effects

Calcium supplements

Possible decreased elvitegravir concentrations

Give EVG/c/FTC/TDF at least 2 hours before or at least 6 hours after oral calcium supplements; monitor for antiretroviral efficacy

Cisapride

Possible increased cisapride concentrations; potential for serious and/or life-threatening reactions (e.g., cardiac arrhythmias)

Concomitant use contraindicated

Cobicistat

Increased elvitegravir concentrations and AUC as the result of cobicistat inhibition of CYP3A; acts as a pharmacokinetic enhancer (cobicistat-boosted elvitegravir); used to therapeutic advantage in fixed combination EVG/c/FTC/TDF

Slightly increased emtricitabine concentrations and AUC and slightly increased tenofovir concentrations; not considered clinically important

Does not antagonize antiretroviral effects of elvitegravir, tenofovir, or emtricitabine

Component of fixed combination EVG/c/FTC/TDF

Colchicine

Increased colchicine concentrations expected

Patients with renal or hepatic impairment: Concomitant use not recommended

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

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

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)

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

Methylprednisolone, prednisolone, triamcinolone (intra-articular, epidural, intraorbital, other local injections): Increased corticosteroid concentrations; may result in adrenal insufficiency or Cushing's syndrome

Dexamethasone or other corticosteroids that induce CYP3A (systemic): Possible decreased elvitegravir and cobicistat concentrations with possible decreased antiretroviral efficacy and development of resistance

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

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

Methylprednisolone, prednisolone, triamcinolone (intra-articular, epidural, intraorbital, other local injections): Do not use concomitantly

Dexamethasone (systemic): Consider alternative corticosteroid; if used concomitantly, use caution and monitor virologic response

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

Daclatasvir

Possible increased daclatasvir concentrations

If used concomitantly with EVG/c/FTC/TDF, use daclatasvir dosage of 30 mg once daily

Dasabuvir

Fixed combination of dasabuvir, ombitasvir, paritaprevir, and ritonavir (dasabuvir/ombitasvir/paritaprevir/ritonavir): Data not available regarding concomitant use with EVG/c/FTC/TDF

Dasabuvir/ombitasvir/paritaprevir/ritonavir: Concomitant use with EVG/c/FTC/TDF not recommended

Digoxin

Possible increased digoxin concentrations

Use concomitantly with caution; monitor digoxin concentrations if possible

Elbasvir and grazoprevir

Fixed combination of elbasvir and grazoprevir (elbasvir/grazoprevir): Possible increased elbasvir and grazoprevir concentrations

Elbasvir/grazoprevir: Concomitant use with EVG/c/FTC/TDF not recommended

Eplerenone

Increased eplerenone concentrations expected

Some experts state concomitant use contraindicated

Ergot alkaloids (dihydroergotamine, ergotamine, methylergonovine)

Potential for serious and/or life-threatening adverse effects (e.g., peripheral vasospasm, ischemia of extremities)

Concomitant use contraindicated

Estrogens/progestins

Oral contraceptives containing ethinyl estradiol and norgestimate: Decreased ethinyl estradiol concentrations and AUC and increased norgestimate concentrations and AUC; possible effects of increased norgestimate unknown but may include increased risk of insulin resistance, dyslipidemia, acne, venous thrombosis

Oral contraceptives containing progestin other than norgestimate: Not studied

Other hormonal contraceptives (e.g., patch, vaginal ring, injections): Not studied

Oral contraceptives containing ethinyl estradiol and norgestimate: Consider risks/benefits of concomitant use, particularly in women at risk of norgestimate-associated adverse effects

Oral contraceptives containing progestins other than norgestimate: Consider alternative nonhormonal methods of contraception

Other hormonal contraceptives (e.g., patch, vaginal ring, injections): Consider alternative nonhormonal methods of contraception

Flibanserin

Increased flibanserin concentrations expected

Some experts state concomitant use contraindicated

Histamine H2-receptor antagonists (e.g., famotidine)

Famotidine: No clinically important effect on elvitegravir concentrations or AUC

Histamine H2-receptor antagonists: Clinically important interactions with EVG/c/FTC/TDF not expected

Dosage adjustment not needed if EVG/c/FTC/TDF used concomitantly with a histamine H2-receptor antagonist

HIV entry and fusion inhibitors (maraviroc)

Maraviroc: Increased maraviroc concentrations and AUC

Do not use concomitantly with EVG/c/FTC/TDF

HIV integrase inhibitors (INSTIs)

Dolutegravir, elvitegravir, raltegravir: Do not use concomitantly with EVG/c/FTC/TDF

HIV nonnucleoside reverse transcriptase inhibitor antiretrovirals (NNRTIs)

Efavirenz, etravirine, nevirapine, rilpivirine: Possible altered elvitegravir, cobicistat, and/or NNRTI concentrations

Efavirenz, etravirine, nevirapine, rilpivirine: Do not use concomitantly with EVG/c/FTC/TDF

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

Other NRTIs (including lamivudine): Do not use concomitantly with EVG/c/FTC/TDF

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

Ritonavir: Has an effect on CYP3A similar to that reported with cobicistat

HIV PIs (with or without low-dose ritonavir or cobicistat): Do not use concomitantly with EVG/c/FTC/TDF

Ritonavir: Do not use ritonavir or any ritonavir-containing preparation concomitantly with EVG/c/FTC/TDF

HMG-CoA reductase inhibitors (statins)

Atorvastatin, lovastatin, simvastatin: Increased concentrations of the antilipemic agent; increased risk of statin-associated adverse effects, including myopathy and rhabdomyolysis

Pitavastatin, pravastatin: Data not available regarding concomitant use with EVG/c/FTC/TDF

Rosuvastatin: Increased rosuvastatin concentrations and AUC; no clinically important effect on elvitegravir pharmacokinetics

Atorvastatin: Initiate using lowest atorvastatin dosage and titrate slowly; monitor for atorvastatin-associated adverse effects

Lovastatin: Concomitant use contraindicated

Rosuvastatin: Some experts recommend slowly titrating rosuvastatin dosage; use lowest possible rosuvastatin dose

Simvastatin: Concomitant use contraindicated

Immunosuppressive agents (cyclosporine, everolimus, sirolimus, tacrolimus)

Cyclosporine, everolimus, sirolimus, tacrolimus: Possible increased immunosuppressive agent concentrations

Cyclosporine, sirolimus, tacrolimus: Monitor immunosuppressive agent concentrations and associated toxicities

Cyclosporine, everolimus, sirolimus, tacrolimus: Some experts recommend initiating immunosuppressive agent using a reduced dosage and monitoring for toxicities; consultation with specialist may be needed

Iron preparations

Possible decreased elvitegravir concentrations

Give EVG/c/FTC/TDF at least 2 hours before or at least 6 hours after iron preparations; monitor for antiretroviral efficacy

Ivabradine

Increased ivabradine concentrations expected

Some experts state concomitant use contraindicated

Laxatives containing polyvalent cations

Possible decreased elvitegravir concentrations

Give EVG/c/FTC/TDF at least 2 hours before or at least 6 hours after laxatives containing polyvalent cations; monitor for antiretroviral efficacy

Ledipasvir and sofosbuvir

Fixed combination of ledipasvir and sofosbuvir (ledipasvir/sofosbuvir): Increased ledipasvir concentrations and increased tenofovir concentrations expected; safety of increased tenofovir concentrations in patients receiving ledipasvir/sofosbuvir and EVG/c/FTC/TDF not established

Ledipasvir/sofosbuvir: Do not use concomitantly with EVG/c/FTC/TDF

Macrolides (clarithromycin)

Clarithromycin: Possible increased clarithromycin and/or cobicistat concentrations

Clarithromycin: Dosage modification not needed in patients with Clcr ≥60 mL/minute; reduce clarithromycin dosage by 50% in those with Clcr 50–60 mL/minute; do not use concomitantly with EVG/c/FTC/TDF if Clcr <50 mL/minute

Methadone

Clinically important pharmacokinetic interactions not expected

Dosage adjustments not needed

Multivitamins or other preparations containing calcium, iron, aluminum magnesium, or zinc

Possible decreased elvitegravir concentrations

Give EVG/c/FTC/TDF at least 2 hours before or at least 6 hours after multivitamins; monitor for antiretroviral efficacy

NSAIAs

High-dose or multiple NSAIAs: Competition for active tubular secretion may increase concentrations of emtricitabine, tenofovir, and/or the concomitant NSAIA; may increase risk of adverse effects

In patients at risk for renal dysfunction, consider alternatives to NSAIAs

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; may increase risk of adverse effects

Entecavir, famciclovir: Clinically important interaction not expected

Ribavirin: Clinically important interaction not expected

Adefovir: Do not use concomitantly with EVG/c/FTC/TDF

Ombitasvir

Dasabuvir/ombitasvir/paritaprevir/ritonavir: Data not available regarding concomitant use with EVG/c/FTC/TDF

Dasabuvir/ombitasvir/paritaprevir/ritonavir: Concomitant use with EVG/c/FTC/TDF not recommended

Paritaprevir

Dasabuvir/ombitasvir/paritaprevir/ritonavir: Data not available regarding concomitant use with EVG/c/FTC/TDF

Dasabuvir/ombitasvir/paritaprevir/ritonavir: Concomitant use with EVG/c/FTC/TDF not recommended

Proton-pump inhibitors (e.g., omeprazole)

Omeprazole: No clinically important effect on elvitegravir concentrations or AUC

Proton-pump inhibitors: Clinically important interactions with EVG/c/FTC/TDF not expected

Dosage adjustments not needed if EVG/c/FTC/TDF used concomitantly with a proton-pump inhibitor

Ranolazine

Experts state do not use concomitantly

Salmeterol

Possible increased salmeterol concentrations; may increase risk of QT prolongation, palpitations, or sinus tachycardia

Concomitant use with EVG/c/FTC/TDF not recommended

Selective serotonin-reuptake inhibitors (SSRIs)

Citalopram, escitalopram, fluoxetine, paroxetine, sertraline: Possible increased SSRI concentrations

Fluvoxamine: Possible increased or decreased elvitegravir concentrations

Citalopram, escitalopram, fluoxetine, paroxetine, sertraline: Initiate SSRI using lowest dose and carefully titrate dosage based on antidepressant response

Fluvoxamine: Some experts state consider alternative to fluvoxamine or alternative to EVG/c/FTC/TDF

Sildenafil

Increased sildenafil concentrations and increased risk of sildenafil-associated adverse effects (e.g., hypotension, syncope, visual disturbances, prolonged erection)

Sildenafil for treatment of PAH: Concomitant use with EVG/c/FTC/TDF contraindicated

Sildenafil for treatment of erectile dysfunction: Do not exceed sildenafil dosage of 25 mg once every 48 hours; closely monitor for sildenafil-related adverse effects

Simeprevir

Increased simeprevir concentrations expected

Concomitant use not recommended

Sofosbuvir

Clinically important pharmacokinetic interactions not expected

May be used concomitantly without dosage adjustments

Sofosbuvir and velpatasvir

Fixed combination of sofosbuvir and velpatasvir (sofosbuvir/velpatasvir): Increased tenofovir exposures

Sofosbuvir/velpatasvir: Monitor for tenofovir-associated adverse effects

St. John’s wort (Hypericum perforatum)

Possible decreased elvitegravir and cobicistat concentrations with possible decreased antiretroviral efficacy and development of resistance

Concomitant use contraindicated

Sucralfate

Possible decreased elvitegravir concentrations

Give EVG/c/FTC/TDF at least 2 hours before or at least 6 hours after sucralfate; monitor for antiretroviral efficacy

Suvorexant

Increased suvorexant concentrations expected

Concomitant use with EVG/c/FTC/TDF not recommended

Tadalafil

Increased tadalafil concentrations and increased risk of tadalafil-associated adverse effects (e.g., hypotension, syncope, visual disturbances, prolonged erection)

Tadalafil for treatment of PAH in patients who have been receiving EVG/c/FTC/TDF for ≥1 week: Use initial tadalafil dosage of 20 mg once daily; if tolerated, increase dosage to 40 mg once daily

EVG/c/FTC/TDF in patients receiving tadalafil for PAH: Discontinue tadalafil for at least 24 hours prior to initiating EVG/c/FTC/TDF; 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

Tadalafil for treatment of erectile dysfunction: Do not exceed tadalafil dosage of 10 mg once every 72 hours; closely monitor for tadalafil-related adverse effects; some experts recommend initiating tadalafil at a dose of 5 mg

Trazodone

Possible increased trazodone concentrations

If trazodone initiated in patients receiving EVG/c/FTC/TDF, use lowest initial trazodone dosage and carefully titrate dosage based on response

Vardenafil

Possible increased vardenafil concentrations and increased risk of vardenafil-associated adverse effects (e.g., hypotension, syncope, visual disturbances, prolonged erection)

Vardenafil for treatment of erectile dysfunction: Do not exceed vardenafil dosage of 2.5 mg once every 72 hours; closely monitor for vardenafil-related adverse effects

Zolpidem

Increased zolpidem concentrations expected

Monitor clinically; reduced zolpidem dosage may be needed; if initiated in patients receiving EVG/c/FTC/TDF, use low initial zolpidem dosage

Elvitegravir, Cobicistat, Emtricitabine, and tenofovir Disoproxil Fumarate Pharmacokinetics

Absorption

Bioavailability

Following an oral dose of EVG/c/FTC/TDF with food, peak plasma concentrations of elvitegravir and cobicistat occur at 4 and 3 hours, respectively, and peak plasma concentrations of emtricitabine and tenofovir occur at 3 and 2 hours, respectively.

Cobicistat component of EVG/c/FTC/TDF increases plasma concentrations of elvitegravir; cobicistat does not have clinically important effect on pharmacokinetics of emtricitabine or tenofovir DF.

Food

Relative to fasting, administration of EVG/c/FTC/TDF with high-fat meal (approximately 800 kcal, 50% fat) increases mean systemic exposures of elvitegravir and tenofovir by 87 and 23%, respectively, and decreases mean systemic exposures of cobicistat and emtricitabine by 17 and 4%, respectively.

Distribution

Extent

Elvitegravir and cobicistat: Distributed into milk in rats; not known whether distributed into human milk.

Emtricitabine and tenofovir: Distributed into human milk.

Plasma Protein Binding

Elvitegravir: Approximately 99%.

Cobicistat: Approximately 98%.

Emtricitabine: <4%.

Tenofovir: <0.7%.

Elimination

Metabolism

Elvitegravir: Metabolized principally by CYP3A to produce inactive M1 metabolite, also undergoes glucuronidation via UGT1A1/3 to produce inactive M4 metabolite. Cobicistat, a CYP3A inhibitor, is included in fixed combination of EVG/c/FTC/TDF to inhibit metabolism of and increase plasma concentrations of elvitegravir.

Cobicistat: Metabolized principally by CYP3A and, to a lesser extent, by CYP2D6. Does not undergo glucuronidation.

Emtricitabine: Undergoes oxidation and conjugation with glucuronic acid. Phosphorylated intracellularly and converted by cellular enzymes to the active emtricitabine 5′-triphosphate.

Tenofovir DF: Prodrug of tenofovir; undergoes initial diester hydrolysis for conversion to tenofovir and subsequent phosphorylation by cellular enzymes to form the active tenofovir diphosphate.

Elimination Route

Elvitegravir: 94.8% in feces, 6.7% in urine. Unlikely to be removed by hemodialysis or peritoneal dialysis.

Cobicistat: 86.2% in feces, 8.2% in urine. Unlikely to be removed by hemodialysis or peritoneal dialysis.

Emtricitabine: 70% in urine (glomerular filtration and active tubular secretion), 13.7% in feces. Removed by hemodialysis; not known whether removed by peritoneal dialysis.

Tenofovir: 70–80% in urine (glomerular filtration and active tubular secretion). Removed by hemodialysis.

Half-life

Elvitegravir: 12.9 hours.

Cobicistat: 3.5 hours.

Emtricitabine: 10 hours.

Tenofovir: 12–18 hours.

Special Populations

Children and adolescents 12 to <18 years of age: Following oral administration of EVG/c/FTC/TDF, elvitegravir and tenofovir exposures 30 and 37% higher, respectively, than those observed in adults; difference not considered clinically important based on exposure-response relationships. Cobicistat and emtricitabine exposures similar to those observed in adults.

Mild or moderate hepatic impairment (Child-Pugh class A or B): No clinically important effect on pharmacokinetics of elvitegravir or cobicistat. Pharmacokinetics of emtricitabine and tenofovir unlikely to be affected.

Severe hepatic impairment (Child-Pugh class C): Pharmacokinetics of EVG/c/FTC/TDF not studied.

Renal impairment: No clinically important effects on pharmacokinetics of elvitegravir or cobicistat. Pharmacokinetics of emtricitabine and tenofovir altered (decreased clearance resulting in increased plasma concentrations and AUC).

Stability

Storage

Oral

Tablets

25°C (may be exposed to 15–30°C).

Store in original container; keep tightly closed.

Actions and Spectrum

  • EVG/c/FTC/TDF is a fixed-combination antiretroviral containing elvitegravir, cobicistat, emtricitabine, and tenofovir DF.

  • Elvitegravir (EVG) is an HIV integrase strand transfer inhibitor antiretroviral. Inhibits activity of HIV-1 integrase, an enzyme that integrates HIV DNA into the host cell genome. Active against HIV-1 and also has some in vitro activity against HIV type 2 (HIV-2); inactive against HBV and HCV.

  • Cobicistat is a mechanism-based CYP3A inhibitor and is included in EVG/c/FTC/TDF as a pharmacokinetic enhancer to decrease elvitegravir metabolism and increase plasma concentrations of the drug, resulting in trough concentrations of elvitegravir sufficient to allow for once-daily dosing (cobicistat-boosted elvitegravir). Has no antiretroviral or antiviral activity and is not active against HIV-1, HBV, or HCV. Does not antagonize the antiretroviral activity of elvitegravir, emtricitabine, or tenofovir.

  • Emtricitabine (FTC) is an HIV NRTI. Prodrug that is inactive until converted intracellularly to an active 5′-triphosphate metabolite. Active against HIV-1 and also has some in vitro activity against HIV-2.

  • Tenofovir DF (TDF) is a nucleotide reverse transcriptase inhibitor antiretroviral classified as an HIV NRTI. Prodrug that is inactive until it undergoes diester hydrolysis in vivo to tenofovir and is subsequently metabolized to the active metabolite (tenofovir diphosphate). Active against HIV-1 and also has some in vitro activity against HIV-2; also active against HBV.

  • HIV-1 resistant to elvitegravir, emtricitabine, and tenofovir have been produced in vitro and have emerged during EVG/c/FTC/TDF therapy. One or more primary mutations associated with resistance to elvitegravir, emtricitabine, and/or tenofovir have been identified in HIV-1 isolates from patients who received EVG/c/FTC/TDF and were considered to be virologic treatment failures.

  • Cross-resistance between elvitegravir and other HIV integrase inhibitors (e.g., dolutegravir, raltegravir) reported. Cross-resistance also occurs among the HIV NRTIs.

Advice to Patients

  • Critical nature of compliance with HIV therapy and importance of remaining under the care of a clinician. Importance of taking as prescribed; do not alter or discontinue antiretroviral regimen without consulting clinician.

  • Antiretroviral therapy is not a cure for HIV infection; opportunistic infections and other complications associated with HIV disease may still occur.

  • Advise patients that sustained decreases in plasma HIV RNA have been associated with reduced risk of progression to acquired immunodeficiency syndrome (AIDS) and death.

  • Advise patients that effective antiretroviral regimens can decrease HIV concentrations in blood and genital secretions and strict adherence to such regimens in conjunction with risk-reduction measures may decrease, but cannot absolutely eliminate, the risk of secondary transmission of HIV to others. Importance of continuing to practice safer sex (e.g., using latex or polyurethane condoms to minimize sexual contact with body fluids), never sharing personal items that can have blood or body fluids on them (e.g., toothbrushes, razor blades), and never reusing or sharing needles.

  • Importance of reading patient information provided by the manufacturer.

  • Advise patients that the fixed combination of elvitegravir, cobicistat, emtricitabine, and tenofovir DF (EVG/c/FTC/TDF) is a complete regimen for treatment of HIV-1 infection and should not be used in conjunction with other antiretroviral agents.

  • Importance of taking EVG/c/FTC/TDF with food.

  • If a dose is missed, take the dose as soon as it is remembered and take next dose at regularly scheduled time. If a dose is skipped, do not take a double dose to make up for the missed dose.

  • Inform patients that testing for HBV infection recommended before antiretroviral therapy initiated. Also advise patients that severe acute exacerbations of HBV infection have been reported following discontinuance of emtricitabine or tenofovir DF in HIV-infected patients coinfected with HBV.

  • Advise patients that renal impairment, including cases of acute renal failure or Fanconi syndrome, has occurred. Importance of not using EVG/c/FTC/TDF concomitantly with or shortly after nephrotoxic agents (e.g., high-dose or multiple NSAIAs).

  • Advise patients that lactic acidosis and severe hepatomegaly with steatosis, including fatalities, have occurred with emtricitabine and tenofovir DF (components of EVG/c/FTC/TDF). Importance of contacting clinician if symptoms suggestive of lactic acidosis or hepatotoxicity (e.g., nausea, vomiting, unusual/unexpected stomach discomfort, weakness) occur.

  • Advise patients that decreased bone mineral density (BMD) has occurred and that assessment of BMD should be considered in those with a history of pathologic bone fracture or other risk factors for osteoporosis or bone loss.

  • Advise patients that signs and symptoms of inflammation from previous infections may occur soon after initiation of antiretroviral therapy in some individuals with advanced HIV infection (AIDS). These symptoms may be due to an improvement in immune response, enabling the body to fight infections that may have been present with no obvious symptoms. Importance of immediately informing a healthcare provider if any symptoms of infection occur.

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and herbal products (e.g., St. John's wort), as well as any concomitant illnesses.

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed. Advise HIV-infected women not to breast-feed.

  • Importance of advising patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Elvitegravir, Cobicistat, Emtricitabine, and Tenofovir Disoproxil Fumarate

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets, film-coated

Elvitegravir 150 mg, Cobicistat 150 mg, Emtricitabine 200 mg, and Tenofovir Disoproxil Fumarate 300 mg

Stribild

Gilead

AHFS DI Essentials™. © Copyright 2022, Selected Revisions October 9, 2017. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

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