VITEKTA

Integrase Strand Transfer Inhibitor (INSTI)s

Not approved for monotherapy. Must be administered with ritonavir, an additional HIV protease inhibitor, and other antiretroviral drug(s).
Administer tablet with food.

suicidal ideation / Delayed / 0-1.0

hyperbilirubinemia / Delayed / 6.0-6.0
hyperamylasemia / Delayed / 6.0-6.0
hematuria / Delayed / 6.0-6.0
hyperglycemia / Delayed / 5.0-5.0
hypertriglyceridemia / Delayed / 5.0-5.0
hypercholesterolemia / Delayed / 5.0-5.0
elevated hepatic enzymes / Delayed / 2.0-3.0
neutropenia / Delayed / 3.0-3.0
depression / Delayed / 0-2.0
lipodystrophy / Delayed / Incidence not known

diarrhea / Early / 7.0-7.0
nausea / Early / 4.0-4.0
headache / Early / 3.0-3.0
vomiting / Early / 0-2.0
abdominal pain / Early / 0-2.0
dyspepsia / Early / 0-2.0
insomnia / Early / 0-2.0
fatigue / Early / 0-2.0
rash / Early / 0-2.0
gynecomastia / Delayed / Incidence not known
breast enlargement / Delayed / Incidence not known
Cushingoid features / Delayed / Incidence not known

VITEKTA

Rx

HIV integrase strand transfer inhibitor (INSTI)
Indicated for the treatment of HIV in antiretroviral-experienced adults
Must be used in combination with ritonavir, an additional HIV protease inhibitor, and other antiretroviral drug(s)

No dosage adjustment is necessary for patients with mild to moderate hepatic impairment (Child-Pugh A or B). Use is not recommended in patients with severe hepatic impairment (Child-Pugh C), as studies have not been conducted in this population.

Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

Acetaminophen; Diphenhydramine: (Moderate) Caution is warranted when elvitegravir is administered with diphenhydramine as there is a potential for decreased diphenhydramine concentrations. Diphenhydramine is a substrate of CYP2C9, while elvitegravir is a CYP2C9 inducer.
Aldesleukin, IL-2: (Moderate) Caution is warranted when elvitegravir is administered with aldesleukin, IL-2 as there is a potential for elevated elvitegravir concentrations. Aldesleukin, IL-2 is a CYP3A4 inhibitor and elvitegravir is a substrate of CYP3A4.
Aliskiren; Valsartan: (Moderate) Caution is warranted when elvitegravir is administered with valsartan as there is a potential for decreased valsartan concentrations. Valsartan is a substrate of CYP2C9; elvitegravir is a CYP2C9 inducer.
Amlodipine; Hydrochlorothiazide, HCTZ; Valsartan: (Moderate) Caution is warranted when elvitegravir is administered with valsartan as there is a potential for decreased valsartan concentrations. Valsartan is a substrate of CYP2C9; elvitegravir is a CYP2C9 inducer.
Amlodipine; Valsartan: (Moderate) Caution is warranted when elvitegravir is administered with valsartan as there is a potential for decreased valsartan concentrations. Valsartan is a substrate of CYP2C9; elvitegravir is a CYP2C9 inducer.
Antacids: (Moderate) Separate administration of elvitegravir and antacids by at least 2 hours. Due to the formation of ionic complexes in the gastrointestinal tract, simultaneous administration results in lower elvitegravir plasma concentrations.
Apalutamide: (Major) Coadministration of elvitegravir with apalutamide is not recommended as there is a potential for decreased elvitegravir concentrations. Decreased antiretroviral concentrations may lead to a reduction of antiretroviral efficacy and the potential development of viral resistance. Elvitegravir is metabolized by CYP3A4 and apalutamide is a strong CYP3A4 inducer.
Aprepitant, Fosaprepitant: (Major) Use caution if elvitegravir and aprepitant, fosaprepitant are used concurrently and monitor for an increase in elvitegravir-related adverse effects for several days after administration of a multi-day aprepitant regimen. Elvitegravir is a CYP3A4 substrate. Aprepitant, when administered as a 3-day oral regimen (125 mg/80 mg/80 mg), is a moderate CYP3A4 inhibitor and inducer and may increase plasma concentrations of elvitegravir. For example, a 5-day oral aprepitant regimen increased the AUC of another CYP3A4 substrate, midazolam (single dose), by 2.3-fold on day 1 and by 3.3-fold on day 5. After a 3-day oral aprepitant regimen, the AUC of midazolam (given on days 1, 4, 8, and 15) increased by 25% on day 4, and then decreased by 19% and 4% on days 8 and 15, respectively. As a single 125 mg or 40 mg oral dose, the inhibitory effect of aprepitant on CYP3A4 is weak, with the AUC of midazolam increased by 1.5-fold and 1.2-fold, respectively. After administration, fosaprepitant is rapidly converted to aprepitant and shares many of the same drug interactions. However, as a single 150 mg intravenous dose, fosaprepitant only weakly inhibits CYP3A4 for a duration of 2 days; there is no evidence of CYP3A4 induction. Fosaprepitant 150 mg IV as a single dose increased the AUC of midazolam (given on days 1 and 4) by approximately 1.8-fold on day 1; there was no effect on day 4. Less than a 2-fold increase in the midazolam AUC is not considered clinically important.
Armodafinil: (Major) Coadministration of with armodafinil is not recommended as there is a potential for decreased elvitegravir concentrations. Decreased antiretroviral concentrations may lead to a reduction of antiretroviral efficacy and the potential development of viral resistance. Armodafinil is a CYP3A4 inducer, while elvitegravir is a substrate of CYP3A4.
Atazanavir: (Moderate) Coadministration of atazanavir boosted with ritonavir and elvitagravir results in significantly elevated plasma concentrations of elvitegravir. The recommended dosing regimen for these drugs used in combination is: elvitegravir 85 mg PO once daily with atazanavir/ritonavir 300/100 mg PO once daily. No data are available for use of other dosage.
Atazanavir; Cobicistat: (Moderate) Coadministration of atazanavir boosted with ritonavir and elvitagravir results in significantly elevated plasma concentrations of elvitegravir. The recommended dosing regimen for these drugs used in combination is: elvitegravir 85 mg PO once daily with atazanavir/ritonavir 300/100 mg PO once daily. No data are available for use of other dosage.
Atropine; Hyoscyamine; Phenobarbital; Scopolamine: (Major) Coadministration may result in significant decreases in the plasma concentrations of elvitegravir, leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Phenobarbital induces the CYP3A4 metabolism of elvitegravir. Consider an alternative anticonvulsant when using elvitegravir. The combination product cobicistat; elvitegravir; emtricitabine; tenofovir is contraindicated in combination with phenobarbital as the concentrations of both elvitegravir and cobicistat may be significantly decreased.
Belladonna Alkaloids; Ergotamine; Phenobarbital: (Major) Coadministration may result in significant decreases in the plasma concentrations of elvitegravir, leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Phenobarbital induces the CYP3A4 metabolism of elvitegravir. Consider an alternative anticonvulsant when using elvitegravir. The combination product cobicistat; elvitegravir; emtricitabine; tenofovir is contraindicated in combination with phenobarbital as the concentrations of both elvitegravir and cobicistat may be significantly decreased.
Bexarotene: (Major) Coadministration of elvitegravir with bexarotene is not recommended as there is a potential for decreased elvitegravir concentrations. Decreased antiretroviral concentrations may lead to a reduction of antiretroviral efficacy and the potential development of viral resistance. Bexarotene is a CYP3A4 inducer, while elvitegravir is a substrate of CYP3A4.
Boceprevir: (Major) Avoid concurrent use of elvitegravir containing antiretroviral regimens with boceprevir. If these drugs are used together, there is a potential for reduced boceprevir concentrations and altered concentrations of the coadministered HIV protease inhibitor. This interaction may result in a reduction of antiretroviral efficacy and the potential development of viral resistance.
Bosentan: (Major) Coadministation of bosentan with elvitegravir may result in elevated bosentan plasma concentrations and reduced elvitegravir concentrations. In patients receiving the antiretroviral for at least 10 days, start bosentan at 62.5 mg daily or every other day (depending on tolerability). When the antiretroviral is initiated in a patients currently receiving bosentan, discontinue bosentan at least 36 hours prior to starting the antiretroviral. After at least 10 days, restart bosentan at 62.5 mg daily or every other day based on tolerability.
Buprenorphine: (Moderate) The plasma concentrations of buprenorphine and its metabolite, norbuprenorphine, are elevated when administered concurrently with elvitegravir. Dose adjustments are not required; however clinical monitoring for adverse effects, such as CNS side effects or respiratory depression, is recommended during coadministration.
Buprenorphine; Naloxone: (Moderate) The plasma concentrations of buprenorphine and its metabolite, norbuprenorphine, are elevated when administered concurrently with elvitegravir. Dose adjustments are not required; however clinical monitoring for adverse effects, such as CNS side effects or respiratory depression, is recommended during coadministration.
Calcium Carbonate: (Moderate) Separate administration of elvitegravir and antacids by at least 2 hours. Due to the formation of ionic complexes in the gastrointestinal tract, simultaneous administration results in lower elvitegravir plasma concentrations.
Calcium Carbonate; Magnesium Hydroxide: (Moderate) Separate administration of elvitegravir and antacids by at least 2 hours. Due to the formation of ionic complexes in the gastrointestinal tract, simultaneous administration results in lower elvitegravir plasma concentrations.
Calcium Carbonate; Risedronate: (Moderate) Separate administration of elvitegravir and antacids by at least 2 hours. Due to the formation of ionic complexes in the gastrointestinal tract, simultaneous administration results in lower elvitegravir plasma concentrations.
Calcium Carbonate; Simethicone: (Moderate) Separate administration of elvitegravir and antacids by at least 2 hours. Due to the formation of ionic complexes in the gastrointestinal tract, simultaneous administration results in lower elvitegravir plasma concentrations.
Carbamazepine: (Major) Coadministration may result in significant decreases in the plasma concentrations of elvitegravir, leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Carbamazepine induces the CYP3A4 metabolism of elvitegravir. Consider an alternative anticonvulsant when using elvitegravir. The combination product cobicistat; elvitegravir; emtricitabine; tenofovir is contraindicated in combination with carbamazepine as the concentrations of both elvitegravir and cobicistat may be significantly decreased.
Carbetapentane; Diphenhydramine; Phenylephrine: (Moderate) Caution is warranted when elvitegravir is administered with diphenhydramine as there is a potential for decreased diphenhydramine concentrations. Diphenhydramine is a substrate of CYP2C9, while elvitegravir is a CYP2C9 inducer.
Celecoxib: (Moderate) The plasma concentrations of celecoxib may be decreased when administered concurrently with elvitegravir. Patients may experience a decreased analgesic effect when these drugs are coadministered. Elvitegravir is a CYP2C9 inducer, while celecoxib is a CYP2C9 substrate.
Ceritinib: (Major) Avoid the use of ceritinib, a time-dependent inhibitor of CYP3A4, with substrates that are primarily metabolized by CYP3A4, such as elvitegravir, as elvitegravir exposure may be increased. If co-administration is unavoidable, consider an elvitegravir dose reduction and monitor for elvitegravir toxicity.
Chloramphenicol: (Moderate) Caution is warranted when elvitegravir is administered with chloramphenicol as there is a potential for elevated elvitegravir concentrations. Chloramphenicol is a CYP3A4 inhibitor and elvitegravir is a substrate of CYP3A4.
Cimetidine: (Moderate) Caution is warranted when elvitegravir is administered with cimetidine as there is a potential for elevated elvitegravir concentrations. Cimetidine is a CYP3A4 and CYP2D6 inhibitor, while elvitegravir is a substrate of CYP3A4.
Clobazam: (Major) Coadministration of elvitegravir with clobazam is not recommended. There is a potential for decreased elvitegravir concentrations. Decreased antiretroviral concentrations may lead to a reduction of antiretroviral efficacy and the potential development of viral resistance. Clobazam is a weak inducer of CYP3A4. Elvitegravir is a substrate of CYP3A4.
Cocaine: (Moderate) Caution is warranted when elvitegravir; is administered with cocaine as there is a potential for elevated concentrations of elvitegravir. Clinical monitoring for adverse effects is recommended during coadministration. Cocaine is an inhibitor of CYP3A4. Elvitegravir is a CYP3A4 substrate.
Dabrafenib: (Major) Coadministration of elvitegravir with dabrafenib is not recommended as there is a potential for decreased elvitegravir concentrations. Decreased antiretroviral concentrations may lead to a reduction of antiretroviral efficacy and the potential development of viral resistance. Elvitegravir is metabolized by CYP3A4; dabrafenib is a moderate CYP3A4 inducer.
Danazol: (Moderate) Caution is warranted when cobicistat is administered with danazol as there is a potential for elevated elvitegravir concentrations. Danazol is a CYP3A4 inhibitor and elvitegravir is a substrate of CYP3A4.
Darunavir: (Moderate) Coadministration of darunavir boosted with cobicistat and elvitegravir is not recommended. Dosing recommendations for such combinations have not been established and coadministration may result in decreased plasma concentrations of the antiretrovirals, resulting in reduction of antiretroviral efficacy and development of viral resistance. However, elvitegravir may be administered with darunavir if boosted with ritonavir. When elvitegravir is administered in combination with darunavir and ritonavir, the recommended dosing is: elvitegravir 150 mg PO once daily with darunavir/ritonavir 600/100 mg PO twice daily. No data are available for use of other dosage for this combination.
Darunavir; Cobicistat: (Moderate) Coadministration of darunavir boosted with cobicistat and elvitegravir is not recommended. Dosing recommendations for such combinations have not been established and coadministration may result in decreased plasma concentrations of the antiretrovirals, resulting in reduction of antiretroviral efficacy and development of viral resistance. However, elvitegravir may be administered with darunavir if boosted with ritonavir. When elvitegravir is administered in combination with darunavir and ritonavir, the recommended dosing is: elvitegravir 150 mg PO once daily with darunavir/ritonavir 600/100 mg PO twice daily. No data are available for use of other dosage for this combination.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Moderate) Coadministration of darunavir boosted with cobicistat and elvitegravir is not recommended. Dosing recommendations for such combinations have not been established and coadministration may result in decreased plasma concentrations of the antiretrovirals, resulting in reduction of antiretroviral efficacy and development of viral resistance. However, elvitegravir may be administered with darunavir if boosted with ritonavir. When elvitegravir is administered in combination with darunavir and ritonavir, the recommended dosing is: elvitegravir 150 mg PO once daily with darunavir/ritonavir 600/100 mg PO twice daily. No data are available for use of other dosage for this combination.
Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: (Moderate) Concurrent administration of elvitegravir with dasabuvir; ombitasvir; paritaprevir; ritonavir may result in elevated elvitegravir plasma concentrations. Elvitegravir is a substrate of uridine glucuronyltransferase (UGT1A1/3) and the hepatic isoenzyme CYP3A4. Ritonavir inhibits the CYP3A4 enzyme, while dasabuvir, ombitasvir, and paritaprevir are UGT1A1 inhibitors. Caution and close monitoring are advised if these drugs are administered together. (Moderate) Concurrent administration of elvitegravir with ritonavir may result in elevated elvitegravir plasma concentrations. Elvitegravir is a substrate of the hepatic isoenzyme CYP3A4. Ritonavir inhibits the CYP3A4 enzyme. Caution and close monitoring are advised if these drugs are administered together.
Dexamethasone: (Major) Avoid concurrent use of dexamethasone with elvitegravir. Coadministration may result in a reduction of antiretroviral efficacy and the potential development of viral resistance to elvitegravir; consider use of an alternative corticosteroid, such as beclomethasone and prednisolone. Dexamethasone induces CYP3A4, and elvitegravir is a substrate of this enzyme.
Dextromethorphan; Diphenhydramine; Phenylephrine: (Moderate) Caution is warranted when elvitegravir is administered with diphenhydramine as there is a potential for decreased diphenhydramine concentrations. Diphenhydramine is a substrate of CYP2C9, while elvitegravir is a CYP2C9 inducer.
Diclofenac: (Moderate) Caution is warranted when elvitegravir is administered with diclofenac as there is a potential for decreased diclofenac concentrations. Diclofenac is a substrate of CYP2C9; elvitegravir is a CYP2C9 inducer.
Diclofenac; Misoprostol: (Moderate) Caution is warranted when elvitegravir is administered with diclofenac as there is a potential for decreased diclofenac concentrations. Diclofenac is a substrate of CYP2C9; elvitegravir is a CYP2C9 inducer.
Didanosine, ddI: (Moderate) Elvitegravir must be taken with food; didanosine, ddI must be taken on an empty stomach. If these drug are administered together, give didanosine on an empty stomach at least 1 hour before or 2 hours after adminstering elvitegravir with food.
Dienogest; Estradiol valerate: (Moderate) Consider the benefits and risk of administering elvitegravir with ethinyl estradiol; norgestimate and other combination oral contraceptives. Concurrent use may result in elevated norgestimate and reduced ethinyl estradiol serum concentrations. Risk associated with these altered concentrations may include increased insulin resistance, dyslipidemia, acne, and venous thrombosis. Consider alternative non-hormonal methods of contraception, such as condoms, to prevent unwanted pregnancy and transmission of HIV/AIDS.
Diphenhydramine: (Moderate) Caution is warranted when elvitegravir is administered with diphenhydramine as there is a potential for decreased diphenhydramine concentrations. Diphenhydramine is a substrate of CYP2C9, while elvitegravir is a CYP2C9 inducer.
Diphenhydramine; Hydrocodone; Phenylephrine: (Moderate) Caution is warranted when elvitegravir is administered with diphenhydramine as there is a potential for decreased diphenhydramine concentrations. Diphenhydramine is a substrate of CYP2C9, while elvitegravir is a CYP2C9 inducer.
Diphenhydramine; Ibuprofen: (Moderate) Caution is warranted when elvitegravir is administered with diphenhydramine as there is a potential for decreased diphenhydramine concentrations. Diphenhydramine is a substrate of CYP2C9, while elvitegravir is a CYP2C9 inducer. (Moderate) The plasma concentrations of ibuprofen may be decreased when administered concurrently with elvitegravir. Patients may experience decreased analgesic or anti-inflammatory effects when these drugs are coadministered. Elvitegravir is a CYP2C9 inducer, while ibuprofen is a CYP2C9 substrate.
Diphenhydramine; Naproxen: (Moderate) Caution is warranted when elvitegravir is administered with diphenhydramine as there is a potential for decreased diphenhydramine concentrations. Diphenhydramine is a substrate of CYP2C9, while elvitegravir is a CYP2C9 inducer. (Moderate) The plasma concentrations of naproxen may be decreased when administered concurrently with elvitegravir. Patients may experience decreased analgesic or anti-inflammatory effects when these drugs are coadministered. Elvitegravir is a CYP2C9 inducer, while naproxen is a CYP2C9 substrate.
Diphenhydramine; Phenylephrine: (Moderate) Caution is warranted when elvitegravir is administered with diphenhydramine as there is a potential for decreased diphenhydramine concentrations. Diphenhydramine is a substrate of CYP2C9, while elvitegravir is a CYP2C9 inducer.
Dronabinol: (Moderate) Use caution if coadministration of dronabinol with elvitegravir is necessary, and monitor for a decrease in the efficacy of dronabinol. Dronabinol is a CYP2C9 and 3A4 substrate; elvitegravir is a moderate inducer of CYP2C9. Concomitant use may result in decreased plasma concentrations of dronabinol.
Drospirenone; Estradiol: (Moderate) Consider the benefits and risk of administering elvitegravir with ethinyl estradiol; norgestimate and other combination oral contraceptives. Concurrent use may result in elevated norgestimate and reduced ethinyl estradiol serum concentrations. Risk associated with these altered concentrations may include increased insulin resistance, dyslipidemia, acne, and venous thrombosis. Consider alternative non-hormonal methods of contraception, such as condoms, to prevent unwanted pregnancy and transmission of HIV/AIDS.
Drospirenone; Ethinyl Estradiol: (Moderate) Consider the benefits and risk of administering elvitegravir with ethinyl estradiol; norgestimate and other combination oral contraceptives. Concurrent use may result in elevated norgestimate and reduced ethinyl estradiol serum concentrations. Risk associated with these altered concentrations may include increased insulin resistance, dyslipidemia, acne, and venous thrombosis. Consider alternative non-hormonal methods of contraception, such as condoms, to prevent unwanted pregnancy and transmission of HIV/AIDS.
Drospirenone; Ethinyl Estradiol; Levomefolate: (Moderate) Consider the benefits and risk of administering elvitegravir with ethinyl estradiol; norgestimate and other combination oral contraceptives. Concurrent use may result in elevated norgestimate and reduced ethinyl estradiol serum concentrations. Risk associated with these altered concentrations may include increased insulin resistance, dyslipidemia, acne, and venous thrombosis. Consider alternative non-hormonal methods of contraception, such as condoms, to prevent unwanted pregnancy and transmission of HIV/AIDS.
Efavirenz: (Major) Avoid coadministration of elvitegravir with efavirenz or efavirenz; emtricitabine; tenofovir, as concurrent use is expected to decrease elvitegravir plasma concentrations. Efavirenz is a substrate and inducer of CYP3A4; elvitegravir is a CYP3A4 substrate. Use of these drugs together may result in loss of antiviral efficacy and potentially the development of viral resistance.
Efavirenz; Emtricitabine; Tenofovir: (Major) Avoid coadministration of elvitegravir with efavirenz or efavirenz; emtricitabine; tenofovir, as concurrent use is expected to decrease elvitegravir plasma concentrations. Efavirenz is a substrate and inducer of CYP3A4; elvitegravir is a CYP3A4 substrate. Use of these drugs together may result in loss of antiviral efficacy and potentially the development of viral resistance.
Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Major) Avoid coadministration of elvitegravir with efavirenz or efavirenz; emtricitabine; tenofovir, as concurrent use is expected to decrease elvitegravir plasma concentrations. Efavirenz is a substrate and inducer of CYP3A4; elvitegravir is a CYP3A4 substrate. Use of these drugs together may result in loss of antiviral efficacy and potentially the development of viral resistance.
Enzalutamide: (Major) Coadministration of elvitegravir with enzalutamide is not recommended as there is a potential for decreased elvitegravir concentrations. Decreased antiretroviral concentrations may lead to a reduction of antiretroviral efficacy and the potential development of viral resistance. Elvitegravir is metabolized by CYP3A4; enzalutamide is a strong CYP3A4 inducer.
Eslicarbazepine: (Major) In vivo studies suggest eslicarbazepine is an inducer of CYP3A4. Coadministration of elvitegravir, may result in significant decreases in the plasma concentrations of the CYP3A4 substrate, elvitegravir, leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Consider use of an alternative anticonvulsant.
Esomeprazole; Naproxen: (Moderate) The plasma concentrations of naproxen may be decreased when administered concurrently with elvitegravir. Patients may experience decreased analgesic or anti-inflammatory effects when these drugs are coadministered. Elvitegravir is a CYP2C9 inducer, while naproxen is a CYP2C9 substrate.
Estradiol; Levonorgestrel: (Moderate) Consider the benefits and risk of administering elvitegravir with ethinyl estradiol; norgestimate and other combination oral contraceptives. Concurrent use may result in elevated norgestimate and reduced ethinyl estradiol serum concentrations. Risk associated with these altered concentrations may include increased insulin resistance, dyslipidemia, acne, and venous thrombosis. Consider alternative non-hormonal methods of contraception, such as condoms, to prevent unwanted pregnancy and transmission of HIV/AIDS.
Estradiol; Norethindrone: (Moderate) Consider the benefits and risk of administering elvitegravir with ethinyl estradiol; norgestimate and other combination oral contraceptives. Concurrent use may result in elevated norgestimate and reduced ethinyl estradiol serum concentrations. Risk associated with these altered concentrations may include increased insulin resistance, dyslipidemia, acne, and venous thrombosis. Consider alternative non-hormonal methods of contraception, such as condoms, to prevent unwanted pregnancy and transmission of HIV/AIDS.
Estradiol; Norgestimate: (Moderate) Consider the benefits and risk of administering elvitegravir with ethinyl estradiol; norgestimate and other combination oral contraceptives. Concurrent use may result in elevated norgestimate and reduced ethinyl estradiol serum concentrations. Risk associated with these altered concentrations may include increased insulin resistance, dyslipidemia, acne, and venous thrombosis. Consider alternative non-hormonal methods of contraception, such as condoms, to prevent unwanted pregnancy and transmission of HIV/AIDS.
Ethinyl Estradiol: (Moderate) Consider the benefits and risk of administering elvitegravir with ethinyl estradiol; norgestimate and other combination oral contraceptives. Concurrent use may result in elevated norgestimate and reduced ethinyl estradiol serum concentrations. Risk associated with these altered concentrations may include increased insulin resistance, dyslipidemia, acne, and venous thrombosis. Consider alternative non-hormonal methods of contraception, such as condoms, to prevent unwanted pregnancy and transmission of HIV/AIDS.
Ethinyl Estradiol; Desogestrel: (Moderate) Consider the benefits and risk of administering elvitegravir with ethinyl estradiol; norgestimate and other combination oral contraceptives. Concurrent use may result in elevated norgestimate and reduced ethinyl estradiol serum concentrations. Risk associated with these altered concentrations may include increased insulin resistance, dyslipidemia, acne, and venous thrombosis. Consider alternative non-hormonal methods of contraception, such as condoms, to prevent unwanted pregnancy and transmission of HIV/AIDS.
Ethinyl Estradiol; Ethynodiol Diacetate: (Moderate) Consider the benefits and risk of administering elvitegravir with ethinyl estradiol; norgestimate and other combination oral contraceptives. Concurrent use may result in elevated norgestimate and reduced ethinyl estradiol serum concentrations. Risk associated with these altered concentrations may include increased insulin resistance, dyslipidemia, acne, and venous thrombosis. Consider alternative non-hormonal methods of contraception, such as condoms, to prevent unwanted pregnancy and transmission of HIV/AIDS.
Ethinyl Estradiol; Etonogestrel: (Moderate) Consider the benefits and risk of administering elvitegravir with ethinyl estradiol; norgestimate and other combination oral contraceptives. Concurrent use may result in elevated norgestimate and reduced ethinyl estradiol serum concentrations. Risk associated with these altered concentrations may include increased insulin resistance, dyslipidemia, acne, and venous thrombosis. Consider alternative non-hormonal methods of contraception, such as condoms, to prevent unwanted pregnancy and transmission of HIV/AIDS.
Ethinyl Estradiol; Levonorgestrel: (Moderate) Consider the benefits and risk of administering elvitegravir with ethinyl estradiol; norgestimate and other combination oral contraceptives. Concurrent use may result in elevated norgestimate and reduced ethinyl estradiol serum concentrations. Risk associated with these altered concentrations may include increased insulin resistance, dyslipidemia, acne, and venous thrombosis. Consider alternative non-hormonal methods of contraception, such as condoms, to prevent unwanted pregnancy and transmission of HIV/AIDS.
Ethinyl Estradiol; Levonorgestrel; Ferrous bisglycinate: (Moderate) Consider the benefits and risk of administering elvitegravir with ethinyl estradiol; norgestimate and other combination oral contraceptives. Concurrent use may result in elevated norgestimate and reduced ethinyl estradiol serum concentrations. Risk associated with these altered concentrations may include increased insulin resistance, dyslipidemia, acne, and venous thrombosis. Consider alternative non-hormonal methods of contraception, such as condoms, to prevent unwanted pregnancy and transmission of HIV/AIDS.
Ethinyl Estradiol; Levonorgestrel; Folic Acid; Levomefolate: (Moderate) Consider the benefits and risk of administering elvitegravir with ethinyl estradiol; norgestimate and other combination oral contraceptives. Concurrent use may result in elevated norgestimate and reduced ethinyl estradiol serum concentrations. Risk associated with these altered concentrations may include increased insulin resistance, dyslipidemia, acne, and venous thrombosis. Consider alternative non-hormonal methods of contraception, such as condoms, to prevent unwanted pregnancy and transmission of HIV/AIDS.
Ethinyl Estradiol; Norelgestromin: (Moderate) Consider the benefits and risk of administering elvitegravir with ethinyl estradiol; norgestimate and other combination oral contraceptives. Concurrent use may result in elevated norgestimate and reduced ethinyl estradiol serum concentrations. Risk associated with these altered concentrations may include increased insulin resistance, dyslipidemia, acne, and venous thrombosis. Consider alternative non-hormonal methods of contraception, such as condoms, to prevent unwanted pregnancy and transmission of HIV/AIDS.
Ethinyl Estradiol; Norethindrone Acetate: (Moderate) Consider the benefits and risk of administering elvitegravir with ethinyl estradiol; norgestimate and other combination oral contraceptives. Concurrent use may result in elevated norgestimate and reduced ethinyl estradiol serum concentrations. Risk associated with these altered concentrations may include increased insulin resistance, dyslipidemia, acne, and venous thrombosis. Consider alternative non-hormonal methods of contraception, such as condoms, to prevent unwanted pregnancy and transmission of HIV/AIDS.
Ethinyl Estradiol; Norethindrone Acetate; Ferrous fumarate: (Moderate) Consider the benefits and risk of administering elvitegravir with ethinyl estradiol; norgestimate and other combination oral contraceptives. Concurrent use may result in elevated norgestimate and reduced ethinyl estradiol serum concentrations. Risk associated with these altered concentrations may include increased insulin resistance, dyslipidemia, acne, and venous thrombosis. Consider alternative non-hormonal methods of contraception, such as condoms, to prevent unwanted pregnancy and transmission of HIV/AIDS.
Ethinyl Estradiol; Norethindrone: (Moderate) Consider the benefits and risk of administering elvitegravir with ethinyl estradiol; norgestimate and other combination oral contraceptives. Concurrent use may result in elevated norgestimate and reduced ethinyl estradiol serum concentrations. Risk associated with these altered concentrations may include increased insulin resistance, dyslipidemia, acne, and venous thrombosis. Consider alternative non-hormonal methods of contraception, such as condoms, to prevent unwanted pregnancy and transmission of HIV/AIDS.
Ethinyl Estradiol; Norethindrone; Ferrous fumarate: (Moderate) Consider the benefits and risk of administering elvitegravir with ethinyl estradiol; norgestimate and other combination oral contraceptives. Concurrent use may result in elevated norgestimate and reduced ethinyl estradiol serum concentrations. Risk associated with these altered concentrations may include increased insulin resistance, dyslipidemia, acne, and venous thrombosis. Consider alternative non-hormonal methods of contraception, such as condoms, to prevent unwanted pregnancy and transmission of HIV/AIDS.
Ethinyl Estradiol; Norgestimate: (Moderate) Consider the benefits and risk of administering elvitegravir with ethinyl estradiol; norgestimate and other combination oral contraceptives. Concurrent use may result in elevated norgestimate and reduced ethinyl estradiol serum concentrations. Risk associated with these altered concentrations may include increased insulin resistance, dyslipidemia, acne, and venous thrombosis. Consider alternative non-hormonal methods of contraception, such as condoms, to prevent unwanted pregnancy and transmission of HIV/AIDS.
Ethinyl Estradiol; Norgestrel: (Moderate) Consider the benefits and risk of administering elvitegravir with ethinyl estradiol; norgestimate and other combination oral contraceptives. Concurrent use may result in elevated norgestimate and reduced ethinyl estradiol serum concentrations. Risk associated with these altered concentrations may include increased insulin resistance, dyslipidemia, acne, and venous thrombosis. Consider alternative non-hormonal methods of contraception, such as condoms, to prevent unwanted pregnancy and transmission of HIV/AIDS.
Famotidine; Ibuprofen: (Moderate) The plasma concentrations of ibuprofen may be decreased when administered concurrently with elvitegravir. Patients may experience decreased analgesic or anti-inflammatory effects when these drugs are coadministered. Elvitegravir is a CYP2C9 inducer, while ibuprofen is a CYP2C9 substrate.
Felbamate: (Major) Coadministration of felbamate with elvitegravir is not recommended. Concurrent use may decrease the plasma concentrations of elvitegravir, leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Felbamate is a CYP3A4 inducer, while elvitegravir is a substrate of CYP3A4.
Fluconazole: (Moderate) Caution is warranted when elvitegravir is administered with fluconazole as there is a potential for elevated elvitegravir concentrations. Fluconazole is a CYP3A4 and CYP2D6 inhibitor, while elvitegravir is a substrate of CYP3A4.
Flurbiprofen: (Moderate) The plasma concentrations of flurbiprofen may be decreased when administered concurrently with elvitegravir. Patients may experience decreased analgesic or anti-inflammatory effects when these drugs are coadministered. Elvitegravir is a CYP2C9 inducer, while flurbiprofen is a CYP2C9 substrate.
Flutamide: (Major) Caution is warranted when elvitegravir is administered with flutamide as there is a potential for decreased concentrations of elvitegravir. Decreased antiretroviral concentrations may lead to a reduction of antiretroviral efficacy and the potential development of viral resistance. Flutamide is a substrate and inducer of CYP3A4. Elvitegravir is a CYP3A4 substrate.
Fluvastatin: (Moderate) The plasma concentrations of fluvastatin may be decreased when administered concurrently with elvitegravir. Patients may experience a decreased antilipemic effect when these drugs are coadministered. Elvitegravir is a CYP2C9 inducer, while fluvastatin is a CYP2C9 substrate.
Fosamprenavir: (Moderate) Coadministration of fosamprenavir boosted with ritonavir and elvitagravir results in an unknown effect on the plasma concentrations of elvitegravir. The recommended dosing regimen for these drugs used in combination is: elvitegravir 150 mg PO once daily with fosamprenavir/ritonavir 700/100 mg PO twice daily. No data are available for use of other doses.
Fosphenytoin: (Major) Coadministration may result in significant decreases in the plasma concentrations of elvitegravir, leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Fosphenytoin induces the CYP3A4 metabolism of elvitegravir. Consider an alternative anticonvulsant when using elvitegravir. The combination product cobicistat; elvitegravir; emtricitabine; tenofovir is contraindicated in combination with fosphenytoin as the concentrations of both elvitegravir and cobicistat may be significantly decreased.
Glimepiride: (Minor) Plasma concentrations of glimepiride may be decreased when administered concurrently with elvitegravir. Patients may experience a decreased hypoglycemic effect when these drugs are coadministered. Elvitegravir is a CYP2C9 inducer, while glimepiride is a CYP2C9 substrate.
Glimepiride; Pioglitazone: (Minor) Plasma concentrations of glimepiride may be decreased when administered concurrently with elvitegravir. Patients may experience a decreased hypoglycemic effect when these drugs are coadministered. Elvitegravir is a CYP2C9 inducer, while glimepiride is a CYP2C9 substrate.
Glimepiride; Rosiglitazone: (Minor) Plasma concentrations of glimepiride may be decreased when administered concurrently with elvitegravir. Patients may experience a decreased hypoglycemic effect when these drugs are coadministered. Elvitegravir is a CYP2C9 inducer, while glimepiride is a CYP2C9 substrate. (Minor) Plasma concentrations of rosiglitazone may be decreased when administered concurrently with elvitegravir. Patients may experience a decreased hypoglycemic effect when these drugs are coadministered. Elvitegravir is a CYP2C9 inducer, while rosiglitazone is a CYP2C9 substrate.
Glipizide: (Minor) Plasma concentrations of glipizide may be decreased when administered concurrently with elvitegravir. Patients may experience a decreased hypoglycemic effect when these drugs are coadministered. Elvitegravir is a CYP2C9 inducer, while glipizide is a CYP2C9 substrate.
Glipizide; Metformin: (Minor) Plasma concentrations of glipizide may be decreased when administered concurrently with elvitegravir. Patients may experience a decreased hypoglycemic effect when these drugs are coadministered. Elvitegravir is a CYP2C9 inducer, while glipizide is a CYP2C9 substrate.
Glyburide: (Minor) Caution is warranted when elvitegravir is administered with glyburide as there is a potential for decreased glyburide concentrations. Patients may experience a decreased hypoglycemic effect during coadministration. Glyburide is a substrate of CYP2C9, while elvitegravir is a CYP2C9 inducer.
Glyburide; Metformin: (Minor) Caution is warranted when elvitegravir is administered with glyburide as there is a potential for decreased glyburide concentrations. Patients may experience a decreased hypoglycemic effect during coadministration. Glyburide is a substrate of CYP2C9, while elvitegravir is a CYP2C9 inducer.
Hydrochlorothiazide, HCTZ; Losartan: (Moderate) Caution is warranted when elvitegravir is administered with losartan as there is a potential for decreased losartan concentrations. Losartan is a substrate of CYP2C9; elvitegravir is a CYP2C9 inducer.
Hydrochlorothiazide, HCTZ; Valsartan: (Moderate) Caution is warranted when elvitegravir is administered with valsartan as there is a potential for decreased valsartan concentrations. Valsartan is a substrate of CYP2C9; elvitegravir is a CYP2C9 inducer.
Hydrocodone; Ibuprofen: (Moderate) The plasma concentrations of ibuprofen may be decreased when administered concurrently with elvitegravir. Patients may experience decreased analgesic or anti-inflammatory effects when these drugs are coadministered. Elvitegravir is a CYP2C9 inducer, while ibuprofen is a CYP2C9 substrate.
Ibuprofen: (Moderate) The plasma concentrations of ibuprofen may be decreased when administered concurrently with elvitegravir. Patients may experience decreased analgesic or anti-inflammatory effects when these drugs are coadministered. Elvitegravir is a CYP2C9 inducer, while ibuprofen is a CYP2C9 substrate.
Ibuprofen; Oxycodone: (Moderate) The plasma concentrations of ibuprofen may be decreased when administered concurrently with elvitegravir. Patients may experience decreased analgesic or anti-inflammatory effects when these drugs are coadministered. Elvitegravir is a CYP2C9 inducer, while ibuprofen is a CYP2C9 substrate.
Ibuprofen; Pseudoephedrine: (Moderate) The plasma concentrations of ibuprofen may be decreased when administered concurrently with elvitegravir. Patients may experience decreased analgesic or anti-inflammatory effects when these drugs are coadministered. Elvitegravir is a CYP2C9 inducer, while ibuprofen is a CYP2C9 substrate.
Indinavir: (Major) Avoid coadministration of indinavir with elvitegravir. No data are available regarding use of these drugs concurrently.
Indomethacin: (Moderate) The plasma concentrations of indomethacin may be decreased when administered concurrently with elvitegravir. Patients may experience decreased analgesic or anti-inflammatory effects when these drugs are coadministered. Elvitegravir is a CYP2C9 inducer, while indomethacin is a CYP2C9 substrate.
Isavuconazonium: (Moderate) Concomitant use of isavuconazonium with elvitegravir may result in increased concentrations of elvitegravir. Isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of the hepatic isoenzyme CYP3A4; elvitegravir is a substrate of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Major) Coadministration of rifampin, a potent CYP3A4 inducer, with elvitegravir, a CYP3A4 substrate, is not recommended. Concurrent use may result in significant decreases in the plasma concentrations of elvitegravir, leading to a reduction of antiretroviral efficacy and the potential development of viral resistance.
Isoniazid, INH; Rifampin: (Major) Coadministration of rifampin, a potent CYP3A4 inducer, with elvitegravir, a CYP3A4 substrate, is not recommended. Concurrent use may result in significant decreases in the plasma concentrations of elvitegravir, leading to a reduction of antiretroviral efficacy and the potential development of viral resistance.
Itraconazole: (Moderate) Monitor for evidence of elvitegravir-related adverse reactions if coadministration is necessary. Itraconazole is a strong CYP3A4 inhibitor; elvitegravir is a CYP3A4 substrate.
Ketoconazole: (Major) Coadministration of ketoconazole with elvitegravir may result in increased plasma concentrations of both drugs. During concurrent use, a maximum ketoconazole dose of 200 mg/day is recommended.
Lansoprazole; Naproxen: (Moderate) The plasma concentrations of naproxen may be decreased when administered concurrently with elvitegravir. Patients may experience decreased analgesic or anti-inflammatory effects when these drugs are coadministered. Elvitegravir is a CYP2C9 inducer, while naproxen is a CYP2C9 substrate.
Lesinurad: (Moderate) Elvitegravir may decrease the systemic exposure and therapeutic effect of lesinurad; monitor for potential reduction in efficacy. Elvitegravir is a mild CYP2C9 inducer, and lesinurad is a CYP2C9 substrate. In addition, lesinurad may decrease the systemic exposure and therapeutic efficacy of elvitegravir; monitor for potential reduction in efficacy. Elvitegravir is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Lesinurad; Allopurinol: (Moderate) Elvitegravir may decrease the systemic exposure and therapeutic effect of lesinurad; monitor for potential reduction in efficacy. Elvitegravir is a mild CYP2C9 inducer, and lesinurad is a CYP2C9 substrate. In addition, lesinurad may decrease the systemic exposure and therapeutic efficacy of elvitegravir; monitor for potential reduction in efficacy. Elvitegravir is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Leuprolide; Norethindrone: (Moderate) Consider the benefits and risk of administering elvitegravir with ethinyl estradiol; norgestimate and other combination oral contraceptives. Concurrent use may result in elevated norgestimate and reduced ethinyl estradiol serum concentrations. Risk associated with these altered concentrations may include increased insulin resistance, dyslipidemia, acne, and venous thrombosis. Consider alternative non-hormonal methods of contraception, such as condoms, to prevent unwanted pregnancy and transmission of HIV/AIDS.
Levonorgestrel: (Moderate) Consider the benefits and risk of administering elvitegravir with ethinyl estradiol; norgestimate and other combination oral contraceptives. Concurrent use may result in elevated norgestimate and reduced ethinyl estradiol serum concentrations. Risk associated with these altered concentrations may include increased insulin resistance, dyslipidemia, acne, and venous thrombosis. Consider alternative non-hormonal methods of contraception, such as condoms, to prevent unwanted pregnancy and transmission of HIV/AIDS.
Lopinavir; Ritonavir: (Moderate) Coadministration of lopinavir; ritonavir and elvitegravir results in significantly elevated plasma concentrations of elvitegravir. The recommended dosing regimen for these drugs used in combination is elvitegravir 85 mg PO once daily with lopinavir; ritonavir 400/100 mg PO twice daily. (Moderate) Concurrent administration of elvitegravir with ritonavir may result in elevated elvitegravir plasma concentrations. Elvitegravir is a substrate of the hepatic isoenzyme CYP3A4. Ritonavir inhibits the CYP3A4 enzyme. Caution and close monitoring are advised if these drugs are administered together.
Lorlatinib: (Moderate) Coadministration may result in significant decreases in the plasma concentrations of elvitegravir, leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Elvitegravir is a CYP3A4 substrate and lorlatinib is a moderate CYP3A4 inducer.
Losartan: (Moderate) Caution is warranted when elvitegravir is administered with losartan as there is a potential for decreased losartan concentrations. Losartan is a substrate of CYP2C9; elvitegravir is a CYP2C9 inducer.
Lumacaftor; Ivacaftor: (Major) Concomitant use of lumacaftor; ivacaftor and elvitegravir is not recommended, as significant decreases in elvitegravir plasma concentrations may occur. This may result in loss of virologic response and possible resistance. Elvitegravir is metabolized by CYP3A, and lumacaftor is a strong CYP3A inducer.
Maraviroc: (Major) Coadministration of maraviroc, a CYP3A substrate, with elvitegravir boosted with ritonavir, a strong CYP3A4 inhibitor, may result in increased maraviroc concentrations. Reduce the dose of maraviroc when coadministered with strong CYP3A inhibitors; coadministration of maraviroc with strong CYP3A inhibitors is contraindicated in patients with CrCl less than 30 mL/min. Adjust the maraviroc dosage as follows when administered with elvitegravir boosted with ritonavir (with or without a concomitant CYP3A inducer): adults and children weighing 40 kg or more: 150 mg PO twice daily; children weighing 30 to 39 kg: 100 mg PO twice daily; children weighing 20 to 29 kg: 75 mg PO twice daily (or 80 mg PO twice daily for solution); children weighing 10 to 19 kg: 50 mg PO twice daily.
Meloxicam: (Moderate) Caution is warranted when elvitegravir is administered with meloxicam as there is a potential for decreased meloxicam concentrations. Meloxicam is primarily metabolized by CYP2C9, while elvitegravir is a CYP2C9 inducer
Mestranol; Norethindrone: (Moderate) Consider the benefits and risk of administering elvitegravir with ethinyl estradiol; norgestimate and other combination oral contraceptives. Concurrent use may result in elevated norgestimate and reduced ethinyl estradiol serum concentrations. Risk associated with these altered concentrations may include increased insulin resistance, dyslipidemia, acne, and venous thrombosis. Consider alternative non-hormonal methods of contraception, such as condoms, to prevent unwanted pregnancy and transmission of HIV/AIDS.
Metformin; Rosiglitazone: (Minor) Plasma concentrations of rosiglitazone may be decreased when administered concurrently with elvitegravir. Patients may experience a decreased hypoglycemic effect when these drugs are coadministered. Elvitegravir is a CYP2C9 inducer, while rosiglitazone is a CYP2C9 substrate.
Methadone: (Moderate) Caution is warranted when elvitegravir is administered with methadone as there is a potential for decreased methadone concentrations and the dosage of methadone may need to be increased. Methadone is partially metabolized by CYP2C9, while elvitegravir is a CYP2C9 inducer.
Mitotane: (Major) Use caution if mitotane and elvitegravir are used concomitantly, due to potential decreased concentrations of elvitegravir leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Mitotane is a strong CYP3A4 inducer and elvitegravir is a CYP3A4 substrate; coadministration may result in decreased plasma concentrations of elvitegravir.
Modafinil: (Major) Coadministration of elvitegravir with modafinil is not recommended as there is a potential for decreased elvitegravir concentrations. Decreased antiretroviral concentrations may lead to a reduction of antiretroviral efficacy and the potential development of viral resistance. Modafinil is a CYP3A4 inducer, while elvitegravir is a substrate of CYP3A4.
Naproxen: (Moderate) The plasma concentrations of naproxen may be decreased when administered concurrently with elvitegravir. Patients may experience decreased analgesic or anti-inflammatory effects when these drugs are coadministered. Elvitegravir is a CYP2C9 inducer, while naproxen is a CYP2C9 substrate.
Naproxen; Pseudoephedrine: (Moderate) The plasma concentrations of naproxen may be decreased when administered concurrently with elvitegravir. Patients may experience decreased analgesic or anti-inflammatory effects when these drugs are coadministered. Elvitegravir is a CYP2C9 inducer, while naproxen is a CYP2C9 substrate.
Naproxen; Sumatriptan: (Moderate) The plasma concentrations of naproxen may be decreased when administered concurrently with elvitegravir. Patients may experience decreased analgesic or anti-inflammatory effects when these drugs are coadministered. Elvitegravir is a CYP2C9 inducer, while naproxen is a CYP2C9 substrate.
Nateglinide: (Minor) Caution is warranted when elvitegravir is administered with nateglinide as there is a potential for decreased nateglinide concentrations. Nateglinide is a primary substrate for CYP2C9 (70%); elvitegravir is a CYP2C9 inducer.
Nebivolol; Valsartan: (Moderate) Caution is warranted when elvitegravir is administered with valsartan as there is a potential for decreased valsartan concentrations. Valsartan is a substrate of CYP2C9; elvitegravir is a CYP2C9 inducer.
Nelfinavir: (Major) Avoid coadministration of nelfinavir with elvitegravir. No data are available regarding use of these drugs concurrently.
Nevirapine: (Major) Avoid coadministration of elvitegravir with nevirapine, as concurrent use is expected to decrease elvitegravir plasma concentrations. Nevirapine is a substrate and inducer of CYP3A4; elvitegravir is a CYP3A4 substrate. Use of these drugs together may result in loss of antiviral efficacy and potentially the development of viral resistance.
Norethindrone: (Moderate) Consider the benefits and risk of administering elvitegravir with ethinyl estradiol; norgestimate and other combination oral contraceptives. Concurrent use may result in elevated norgestimate and reduced ethinyl estradiol serum concentrations. Risk associated with these altered concentrations may include increased insulin resistance, dyslipidemia, acne, and venous thrombosis. Consider alternative non-hormonal methods of contraception, such as condoms, to prevent unwanted pregnancy and transmission of HIV/AIDS.
Norgestrel: (Moderate) Consider the benefits and risk of administering elvitegravir with ethinyl estradiol; norgestimate and other combination oral contraceptives. Concurrent use may result in elevated norgestimate and reduced ethinyl estradiol serum concentrations. Risk associated with these altered concentrations may include increased insulin resistance, dyslipidemia, acne, and venous thrombosis. Consider alternative non-hormonal methods of contraception, such as condoms, to prevent unwanted pregnancy and transmission of HIV/AIDS.
Ombitasvir; Paritaprevir; Ritonavir: (Moderate) Concurrent administration of elvitegravir with dasabuvir; ombitasvir; paritaprevir; ritonavir may result in elevated elvitegravir plasma concentrations. Elvitegravir is a substrate of uridine glucuronyltransferase (UGT1A1/3) and the hepatic isoenzyme CYP3A4. Ritonavir inhibits the CYP3A4 enzyme, while dasabuvir, ombitasvir, and paritaprevir are UGT1A1 inhibitors. Caution and close monitoring are advised if these drugs are administered together. (Moderate) Concurrent administration of elvitegravir with ritonavir may result in elevated elvitegravir plasma concentrations. Elvitegravir is a substrate of the hepatic isoenzyme CYP3A4. Ritonavir inhibits the CYP3A4 enzyme. Caution and close monitoring are advised if these drugs are administered together.
Omeprazole; Sodium Bicarbonate: (Moderate) Separate administration of elvitegravir and antacids by at least 2 hours. Due to the formation of ionic complexes in the gastrointestinal tract, simultaneous administration results in lower elvitegravir plasma concentrations.
Oral Contraceptives: (Moderate) Consider the benefits and risk of administering elvitegravir with ethinyl estradiol; norgestimate and other combination oral contraceptives. Concurrent use may result in elevated norgestimate and reduced ethinyl estradiol serum concentrations. Risk associated with these altered concentrations may include increased insulin resistance, dyslipidemia, acne, and venous thrombosis. Consider alternative non-hormonal methods of contraception, such as condoms, to prevent unwanted pregnancy and transmission of HIV/AIDS.
Oritavancin: (Major) Coadministration of elvitegravir with oritavancin is not recommended. Elvitegravir is metabolized by CYP3A4; oritavancin is a weak CYP3A4 inducer. Plasma concentrations and efficacy of elvitegravir may be reduced if these drugs are administered concurrently.
Oxcarbazepine: (Major) Coadministration may result in significant decreases in the plasma concentrations of elvitegravir, leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Oxcarbazepine induces the CYP3A4 metabolism of elvitegravir. Consider an alternative anticonvulsant when using elvitegravir. The combination product cobicistat; elvitegravir; emtricitabine; tenofovir is contraindicated in combination with oxcarbazepine as the concentrations of both elvitegravir and cobicistat may be significantly decreased.
Pazopanib: (Major) Caution is warranted when elvitegravir is administered with pazopanib as there is a potential for elevated concentrations of both drugs. Both drugs are substrates and inhibitors of CYP3A4.
Perampanel: (Major) Caution is warranted when elvitegravir is administered with perampanel as there is a potential for decreased concentrations of elvitegravir. Decreased antiretroviral concentrations may lead to a reduction of antiretroviral efficacy and the potential development of viral resistance. Perampanel is an inducer of CYP3A4. Elvitegravir is a CYP3A4 substrate.
Phenobarbital: (Major) Coadministration may result in significant decreases in the plasma concentrations of elvitegravir, leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Phenobarbital induces the CYP3A4 metabolism of elvitegravir. Consider an alternative anticonvulsant when using elvitegravir. The combination product cobicistat; elvitegravir; emtricitabine; tenofovir is contraindicated in combination with phenobarbital as the concentrations of both elvitegravir and cobicistat may be significantly decreased.
Phentermine; Topiramate: (Moderate) Caution is warranted when elvitegravir is administered with topiramate as there is a potential for decreased elvitegravir concentrations. Decreased antiretroviral concentrations may lead to a reduction of antiretroviral efficacy and the potential development of viral resistance. Topiramate is not extensively metabolized, but is a mild CYP3A4 inducer. Elvitegravir is a CYP3A4 substrate.
Phenytoin: (Major) Coadministration may result in significant decreases in the plasma concentrations of elvitegravir, leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Phenytoin induces the CYP3A4 metabolism of elvitegravir. Consider an alternative anticonvulsant when using elvitegravir. The combination product cobicistat; elvitegravir; emtricitabine; tenofovir is contraindicated in combination with phenytoin as the concentrations of both elvitegravir and cobicistat may be significantly decreased.
Primidone: (Major) Coadministration may result in significant decreases in the plasma concentrations of elvitegravir, leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Primodine is converted to phenobarbital. Phenobarbital induces the CYP3A4 metabolism of elvitegravir. Consider an alternative anticonvulsant when using elvitegravir. The combination product cobicistat; elvitegravir; emtricitabine; tenofovir is contraindicated in combination with primidone as the concentrations of both elvitegravir and cobicistat may be significantly decreased.
Quinine: (Major) Coadministration of elvitegravir with quinine is not recommended as there is a potential for altered elvitegravir concentrations and reduced quinine concentrations. Changes antiretroviral concentrations may lead to a reduction of antiretroviral efficacy and the potential development of viral resistance. Elvitegravir is a substrate of CYP3A4, and quinine may induce or inhibit CYP3A4. Elvitegravir also induces CYP2C9, and quinine is partially metabolized by CYP2C9.
Regorafenib: (Moderate) Use caution if coadministration of regorafenib with elvitegravir is necessary, and monitor for an increase in elvitegravir-related adverse reactions. Elvitegravir is a substrate of UGT1A1 and 1A3. Regorafenib, M-2, and M-5 all competitively inhibit UGT1A9 and 1A1 in vitro.
Rifabutin: (Major) Coadministration of rifabutin with elvitegravir may result in reduced elvitegravir concentrations and elevated rifabutin concentrations. If these drugs must be used concurrently, reduce the dose of rifabutin by at least 75% of the usual 300 mg/day dose (e.g., 150 mg every other day or 3x/week). If the rifabutin dose is reduced, no dose adjustment is required for elvitegravir. Monitor closely for rifabutin-associated adverse events.
Rifampin: (Major) Coadministration of rifampin, a potent CYP3A4 inducer, with elvitegravir, a CYP3A4 substrate, is not recommended. Concurrent use may result in significant decreases in the plasma concentrations of elvitegravir, leading to a reduction of antiretroviral efficacy and the potential development of viral resistance.
Rifapentine: (Major) Coadministration of rifapentine, a potent CYP3A4 inducer, with elvitegravir, a CYP3A4 substrate, is not recommended. Concurrent use may result in significant decreases in the plasma concentrations of elvitegravir, leading to a reduction of antiretroviral efficacy and the potential development of viral resistance.
Ritonavir: (Moderate) Concurrent administration of elvitegravir with ritonavir may result in elevated elvitegravir plasma concentrations. Elvitegravir is a substrate of the hepatic isoenzyme CYP3A4. Ritonavir inhibits the CYP3A4 enzyme. Caution and close monitoring are advised if these drugs are administered together.
Rosiglitazone: (Minor) Plasma concentrations of rosiglitazone may be decreased when administered concurrently with elvitegravir. Patients may experience a decreased hypoglycemic effect when these drugs are coadministered. Elvitegravir is a CYP2C9 inducer, while rosiglitazone is a CYP2C9 substrate.
Rosuvastatin: (Moderate) Caution is warranted when elvitegravir is administered with rosuvastatin as there is a potential for decreased rosuvastatin concentrations. Alternatively, when elvitegravir is boosted with cobicistat, the concentration of rosuvastatin may be increased due to inhibition of OATP by cobicistat. In one pharmacokinetic study, the Cmax and AUC of rosuvastatin were increased by 89% and 38%, respectively, when given concurrently with cobicistat and elvitegravir. Patients may experience a decreased antilipemic effect elvitegravir and rosuvastatin are coadministered. If elvitegravir is boosted with cobicistat, patients may be at increased risk for side effects of rosuvastatin. Rosuvastatin is a substrate of CYP2C9, while elvitegravir is a CYP2C9 inducer.
Sacubitril; Valsartan: (Moderate) Caution is warranted when elvitegravir is administered with valsartan as there is a potential for decreased valsartan concentrations. Valsartan is a substrate of CYP2C9; elvitegravir is a CYP2C9 inducer.
Saquinavir: (Major) Avoid coadministration of saquinavir with elvitegravir. No data are available regarding use of these drugs concurrently.
Selegiline: (Moderate) Caution is warranted when elvitegravir is administered with selegiline as there is a potential for decreased selegiline concentrations. Selegiline is a substrate of CYP2C9, while elvitegravir is a CYP2C9 inducer.
Sodium Bicarbonate: (Moderate) Separate administration of elvitegravir and antacids by at least 2 hours. Due to the formation of ionic complexes in the gastrointestinal tract, simultaneous administration results in lower elvitegravir plasma concentrations.
St. John's Wort, Hypericum perforatum: (Major) Coadministration of St. John's Wort, Hypericum perforatum with elvitegravir is not recommended. St. John's Wort induces C YP3A4; elvitegravir is a substrate of this enzyme. Concurrent use may result in significant decreases in the plasma concentrations of elvitegravir, leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. St. John's Wort in all forms, including teas, should be avoided.
Streptogramins: (Moderate) Caution is warranted when elvitegravir is administered with dalfopristin; quinupristin as there is a potential for elevated elvitegravir concentrations. Quinupristin is a CYP3A4 inhibitor and elvitegravir is a substrate of CYP3A4.
Sulfamethoxazole; Trimethoprim, SMX-TMP, Cotrimoxazole: (Moderate) Caution is warranted when elvitegravir is administered with sulfamethoxazole; trimethoprim, SMX-TMP as there is a potential for decreased sulfamethoxazole concentrations. Sulfamethoxazole is a substrate of CYP2C9, while elvitegravir is a CYP2C9 inducer.
Telaprevir: (Major) Avoid concurrent use of elvitegravir containing antiretroviral regimens with telaprevir. If these drugs are used together, there is a potential for reduced telaprevir concentrations and altered concentrations of the coadministered HIV protease inhibitor. This interaction may result in a reduction of antiretroviral efficacy and the potential development of viral resistance.
Telotristat Ethyl: (Moderate) Use caution if coadministration of telotristat ethyl and elvitegravir is necessary, as the systemic exposure of elvitegravir may be decreased resulting in reduced efficacy. If these drugs are used together, monitor patients for suboptimal efficacy of elvitegravir; consider increasing the dose of elvitegravir if necessary. Elvitegravir is a CYP3A4 substrate. The mean Cmax and AUC of another sensitive CYP3A4 substrate was decreased by 25% and 48%, respectively, when coadministered with telotristat ethyl; the mechanism of this interaction appears to be that telotristat ethyl increases the glucuronidation of the CYP3A4 substrate.
Terbinafine: (Moderate) Caution is advised when administering terbinafine with elvitegravir. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may lower the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP2C9. Elvitegravir is an inducer of CYP2C9. Monitor patients for breakthrough fungal infections if these drugs are coadministered.
Tipranavir: (Moderate) Coadministration of tipranavir boosted with ritonavir and elvitagravir results in an unknown effect on the plasma concentrations of elvitegravir. The recommended dosing regimen for these drugs used in combination is: elvitegravir 150 mg PO once daily with tipranavir/ritonavir 500/200 mg PO twice daily. No data are available for use of other dosage.
Topiramate: (Moderate) Caution is warranted when elvitegravir is administered with topiramate as there is a potential for decreased elvitegravir concentrations. Decreased antiretroviral concentrations may lead to a reduction of antiretroviral efficacy and the potential development of viral resistance. Topiramate is not extensively metabolized, but is a mild CYP3A4 inducer. Elvitegravir is a CYP3A4 substrate.
Valsartan: (Moderate) Caution is warranted when elvitegravir is administered with valsartan as there is a potential for decreased valsartan concentrations. Valsartan is a substrate of CYP2C9; elvitegravir is a CYP2C9 inducer.
Vemurafenib: (Major) Coadministration of with vemurafenib is not recommended as there is a potential for decreased elvitegravir concentrations. Decreased antiretroviral concentrations may lead to a reduction of antiretroviral efficacy and the potential development of viral resistance. Vemurafenib is a CYP3A4 inducer, while elvitegravir is a substrate of CYP3A4.
Warfarin: (Moderate) Close monitoring of the international normalized ration (INR) is advised when administering warfarin concurrently with elvitegravir. Serum concentrations of warfarin may be altered during coadministration. Elvitegravir is an inducer of CYP2C9; an isoenzymes partially responsible for the metabolism of warfarin. These drugs used in combination may result in decreased warfarin plasma concentrations.

150 mg/day PO.

150 mg/day PO.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

Elvitegravir inhibits the activity of HIV integrase, which is one of three HIV encoded enzymes required for viral replication. Inhibition of integrase by elvitegravir prevents the insertion, or integration, of unintegrated linear HIV DNA into the host cell genome, thereby preventing the formation of HIV provirus and propagation of the viral infection. Elvitegravir is active against HIV-1, but does not inhibit human topoisomerases I or II, nor does it inhibit replication of hepatitis B or C virus.
 
The major HIV integrase substitutions associated with reduced susceptibility to elvitegravir are T66A/I/K, E92G/Q, T97A, S147G, Q148H/K/R and N155H. Cross-resistance occurs among integrase strand transfer inhibitors; however, the degree of cross-resistance depends on the type and number of HIV integrase substitutions.

Elvitegravir is administered orally. Following systemic absorption, the drug is 98—99% plasma protein bound, with binding being independent of plasma concentration. The mean blood to plasma ratio is 1.37. Elvitegravir is primarily metabolized via CYP3A enzymes and, to a lesser extent, undergoes glucuronidation by UGT1A1/3 enzymes. Elvitegravir is excreted in the feces (94.8%) and urine (6.7%) with a median terminal plasma half-life of approximately 8.7 hours.
 
Affected cytochrome P450 isoenzymes: CYP2C9, CYP3A4, UGT1A1/3
Elvitegravir is a significant substrate of CYP3A, and undergoes glucuronidation via the UGT1A1/3 enzymes. The drug also is a modest inducer of CYP2C9. Concomitant administration with CYP3A4 inducers may lead to a loss of virologic efficacy and possible resistance. Coadministration with a potent CYP3A4 inhibitor (ketoconazole) does not require dosage adjustments.

Antiretroviral therapy should be provided to all women during pregnancy, regardless of HIV RNA concentrations or CD4 cell count. Using highly active antiretroviral combination therapy (HAART) to maximally suppress viral replication is the most effective strategy to prevent the development of resistance and to minimize the risk of perinatal transmission. In treatment-naive women, begin HAART as soon as pregnancy is recognized or HIV is diagnosed, without waiting for the results of resistance testing; subsequent modifications to the treatment regimen should be made once the test results are available. Women who are currently receiving antiretroviral treatment when pregnancy is recognized should continue their treatment regimen if it is currently effective in suppressing viral replication; consider resistance testing if HIV RNA concentrations more than 500 copies/mL. For women not currently receiving HAART, but who have previously received treatment, obtain a complete and accurate history of all prior antiretroviral regimens used and results of prior resistance testing, and perform resistance testing if HIV RNA concentrations more than 500 copies/mL; treatment should be initiated prior to receiving resistance test results. Elvitegravir is classified as FDA pregnancy risk category B; however, guidelines recommend against use of elvitegravir-containing regimens in pregnant women as inadequate drug concentrations and viral breakthroughs have been reported during the 2nd and 3rd trimesters. Consider use of more effective antiretroviral regimens. If an elvitegravir-containing regimen must be used during pregnancy, frequently monitor viral loads and elvitegravir concentrations. No adequate and well-controlled studies in pregnant women have been conducted, and data involving first trimester exposures are insufficient to drawl conclusions regarding the potential for birth defects. In animal studies involving rats and rabbits, no evidence of teratogenicity or adverse reproductive effects were observed. Nucleoside reverse transcriptase inhibitors (NRTIs) are known to induce mitochondrial dysfunction. An association of mitochondrial dysfunction in infants and in-utero antiretroviral exposure has been suggested, but not established. While the development of severe or fatal mitochondrial disease in exposed infants appears to be extremely rare, more intensive monitoring of hematologic and electrolyte parameters during the first few weeks of life is advised. Nucleoside analogs have been associated with the development of lactic acidosis, especially during pregnancy. It is unclear if pregnancy augments the incidence of lactic acidosis/hepatic steatosis in patients receiving nucleoside analogs. However, because pregnancy itself can mimic some of the early symptoms of the lactic acid/hepatic steatosis syndrome or be associated with other significant disorders of liver metabolism, clinicians need to be alert for early diagnosis of this syndrome. Pregnant women receiving nucleoside analogs should have LFTs and serum electrolytes assessed more frequently during the last trimester of pregnancy and any new symptoms should be evaluated thoroughly. Regular laboratory monitoring is recommended to determine antiretroviral efficacy. Monitor CD4 counts at the initial visit and at least every 3 months during pregnancy; consideration may be given to monitoring every 6 months in patients on HAART with consistently suppressed viral loads and a CD4 count well above the opportunistic infection threshold. Monitor plasma HIV RNA at the initial visit, 2 to 4 weeks after initiating or changing therapy, monthly until undetectable, then at least every 3 months during pregnancy, and at 34 to 36 weeks gestation. Perform antiretroviral resistance assay (genotypic testing) at baseline in all women with HIV RNA concentrations more than 500 copies/mL, unless they have already been tested for resistance. First trimester ultrasound is recommended to confirm gestational age and provide accurate estimation of gestational age at deliver. A second trimester ultrasound can be used for both anatomical survey and determination of gestational age in those patients not seen until later in gestation. Perform standard glucose screening in women receiving antiretroviral therapy at 24 to 28 weeks gestation, although it should be noted that some experts would perform earlier screening with ongoing chronic protease inhibitor-based therapy initiated prior to pregnancy, similar to recommendations for women with high-risk factors for glucose intolerance. All pregnant women should be counseled about the importance of adherence to their antiretroviral regimen to reduce the potential for development of resistance and perinatal transmission. It is strongly recommended that antiretroviral therapy, once initiated, not be discontinued. If a woman decides to discontinue therapy, a consultation with a HIV specialist is recommended. It is strongly recommended that health care providers report cases of antenatal antiretroviral drug exposure to the Antiretroviral Pregnancy Registry; telephone 800-258-4263; the Antiretroviral Pregnancy Registry is also accessible via the Internet.

To reduce the risk of postnatal transmission, HIV-infected mothers within the United States are advised by the Centers for Disease Control and Prevention to avoid breast-feeding. This recommendation applies to both untreated women and women who are receiving antiretroviral therapy, including elvitegravir. It is unknown if elvitegravir is present in human milk. Antiretroviral drugs whose passage into human breast milk have been evaluated include tenofovir, emtricitabine, nevirapine, zidovudine, lamivudine, and nelfinavir.