doravirine/lamivudine/tenofovir DF (Rx)

Brand and Other Names:Delstrigo

Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

doravirine/lamivudine/tenofovir DF

tablet

  • 100mg/300mg/300mg

HIV Infection

Indicated as a complete regimen for treatment of HIV-1 infection in patients

  • Without prior antiretroviral therapy (ART) treatment history, OR
  • To replace current ART regimen in those who are virologically suppressed (HIV-1 RNA <50 copies/mL) on a stable ART regimen with no history of treatment failure and no known substitutions associated with resistance to the individual drug components

1 tablet (100 mg doravirine, 300 mg lamivudine, 300 mg tenofovir DF) PO qDay with or without food

Dosage Modifications

Renal impairment

  • Estimated CrCl <50 mL/min: Not recommended (unable to adjust fixed-dose combination)

Hepatic impairment

  • Mild or moderate (Child-Pugh A or B): No dosage adjustment required
  • Severe (Child-Pugh C): Not studied

Coadministration with rifabutin

  • Take 100 mg of doravirine (Pifeltro) ~12 hr after Delstrigo dose for duration of rifabutin coadministration

Dosing Considerations

Monitoring

  • Obtain baseline test for hepatitis B virus (HBV) infection (see Black Box Warnings)
  • Patients with chronic kidney disease: Obtain baseline serum phosphorus and periodically assess during treatment
  • Obtain the following tests at baseline and periodically assess during treatment for all patients
    • Serum creatinine
    • Estimated CrCl
    • Urine glucose
    • Urine protein

Dosage Forms & Strengths

doravirine/lamivudine/tenofovir DF

tablet

  • 100mg/300mg/300mg

HIV Infection

Indicated as a complete regimen for treatment of HIV-1 infection in patients weighing ≥12 years ≥35 kg

  • Without prior antiretroviral therapy (ART) treatment history, OR
  • To replace current ART regimen in those who are virologically suppressed (HIV-1 RNA <50 copies/mL) on a stable ART regimen with no history of treatment failure and no known substitutions associated with resistance to the individual drug components

1 tablet (100 mg doravirine, 300 mg lamivudine, 300 mg tenofovir DF) PO qDay with or without food

Dosage Modifications

Renal impairment

  • Estimated CrCl <50 mL/min: Not recommended (unable to adjust fixed-dose combination)

Hepatic impairment

  • Mild or moderate (Child-Pugh A or B): No dosage adjustment required
  • Severe (Child-Pugh C): Not studied

Coadministration with rifabutin

  • Take 100 mg of doravirine (Pifeltro) ~12 hr after Delstrigo dose for duration of rifabutin coadministration

Dosing Considerations

Monitoring

  • Obtain baseline test for hepatitis B virus (HBV) infection (see Black Box Warnings)
  • Patients with chronic kidney disease: Obtain baseline serum phosphorus and periodically assess during treatment
  • Obtain the following tests at baseline and periodically assess during treatment for all patients
    • Serum creatinine
    • Estimated CrCl
    • Urine glucose
    • Urine protein
Next:

Interactions

Interaction Checker

and doravirine/lamivudine/tenofovir DF

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            Contraindicated (37)

            • amobarbital

              amobarbital will decrease the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of doravirine with a strong CYP3A inducer may decrease doravirine plasma concentrations and/or effects. Potential for loss of virologic response and possible resistance to doravirine.

            • apalutamide

              apalutamide will decrease the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of doravirine with a strong CYP3A inducer may decrease doravirine plasma concentrations and/or effects. Potential for loss of virologic response and possible resistance to doravirine.

            • armodafinil

              armodafinil will decrease the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of doravirine with a CYP3A inducer may decrease doravirine plasma concentrations and/or effects. Potential for loss of virologic response and possible resistance to doravirine.

            • bexarotene

              bexarotene will decrease the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of doravirine with a CYP3A inducer may decrease doravirine plasma concentrations and/or effects. Potential for loss of virologic response and possible resistance to doravirine.

            • bosentan

              bosentan will decrease the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of doravirine with a strong CYP3A inducer may decrease doravirine plasma concentrations and/or effects. Potential for loss of virologic response and possible resistance to doravirine.

            • brigatinib

              brigatinib will decrease the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of doravirine with a CYP3A inducer may decrease doravirine plasma concentrations and/or effects. Potential for loss of virologic response and possible resistance to doravirine.

            • butabarbital

              butabarbital will decrease the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of doravirine with a strong CYP3A inducer may decrease doravirine plasma concentrations and/or effects. Potential for loss of virologic response and possible resistance to doravirine.

            • butalbital

              butalbital will decrease the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of doravirine with a strong CYP3A inducer may decrease doravirine plasma concentrations and/or effects. Potential for loss of virologic response and possible resistance to doravirine.

            • carbamazepine

              carbamazepine will decrease the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of doravirine with a strong CYP3A inducer may decrease doravirine plasma concentrations and/or effects. Potential for loss of virologic response and possible resistance to doravirine.

            • clobazam

              clobazam will decrease the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of doravirine with a CYP3A inducer may decrease doravirine plasma concentrations and/or effects. Potential for loss of virologic response and possible resistance to doravirine.

            • dabrafenib

              dabrafenib will decrease the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of doravirine with a strong CYP3A inducer may decrease doravirine plasma concentrations and/or effects. Potential for loss of virologic response and possible resistance to doravirine.

            • efavirenz

              efavirenz will decrease the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of doravirine with a strong CYP3A inducer may decrease doravirine plasma concentrations and/or effects. Potential for loss of virologic response and possible resistance to doravirine.

            • elvitegravir/cobicistat/emtricitabine/tenofovir DF

              tenofovir DF, elvitegravir/cobicistat/emtricitabine/tenofovir DF. Other (see comment). Contraindicated. Comment: Elvitegravir/cobicistat/emtricitabine/tenofovir is a complete regimen for HIV and should not be administered with other antiretrovirals.

              lamivudine, elvitegravir/cobicistat/emtricitabine/tenofovir DF. Other (see comment). Contraindicated. Comment: Elvitegravir/cobicistat/emtricitabine/tenofovir is a complete regimen for HIV and should not be administered with other antiretrovirals.

            • emtricitabine

              emtricitabine and lamivudine both increase risk of immune reconstitution syndrome. Contraindicated. Coadministration of emtricitabine containing products and lamivudine containing products should be avoided. Combination will result in therapeutic duplication.

              emtricitabine, lamivudine. Other (see comment). Contraindicated. Comment: Coadministration of emtricitabine containing products and lamivudine containing products should be avoided. Combination will result in therapeutic duplication.

            • encorafenib

              encorafenib will decrease the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of doravirine with a CYP3A inducer may decrease doravirine plasma concentrations and/or effects. Potential for loss of virologic response and possible resistance to doravirine.

            • enzalutamide

              enzalutamide will decrease the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of doravirine with a strong CYP3A inducer may decrease doravirine plasma concentrations and/or effects. Potential for loss of virologic response and possible resistance to doravirine.

            • eslicarbazepine acetate

              eslicarbazepine acetate will decrease the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of doravirine with a CYP3A inducer may decrease doravirine plasma concentrations and/or effects. Potential for loss of virologic response and possible resistance to doravirine.

            • etravirine

              etravirine will decrease the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of doravirine with a strong CYP3A inducer may decrease doravirine plasma concentrations and/or effects. Potential for loss of virologic response and possible resistance to doravirine.

            • fezolinetant

              tenofovir DF will increase the level or effect of fezolinetant by affecting hepatic enzyme CYP1A2 metabolism. Contraindicated. Fezolinetant AUC and peak plasma concentration are increased if coadministered with drugs that are weak, moderate, or strong CYP1A2 inhibitors

            • fosphenytoin

              fosphenytoin will decrease the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of doravirine with a strong CYP3A inducer may decrease doravirine plasma concentrations and/or effects. Potential for loss of virologic response and possible resistance to doravirine.

            • ivosidenib

              ivosidenib will decrease the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of doravirine with a strong CYP3A inducer may decrease doravirine plasma concentrations and/or effects. Potential for loss of virologic response and possible resistance to doravirine.

            • lumacaftor/ivacaftor

              lumacaftor/ivacaftor will decrease the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of doravirine with a strong CYP3A inducer may decrease doravirine plasma concentrations and/or effects. Potential for loss of virologic response and possible resistance to doravirine.

            • mitotane

              mitotane will decrease the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of doravirine with a strong CYP3A inducer may decrease doravirine plasma concentrations and/or effects. Potential for loss of virologic response and possible resistance to doravirine.

            • nafcillin

              nafcillin will decrease the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of doravirine with a strong CYP3A inducer may decrease doravirine plasma concentrations and/or effects. Potential for loss of virologic response and possible resistance to doravirine.

            • nevirapine

              nevirapine will decrease the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of doravirine with a strong CYP3A inducer may decrease doravirine plasma concentrations and/or effects. Potential for loss of virologic response and possible resistance to doravirine.

            • oxcarbazepine

              oxcarbazepine will decrease the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of doravirine with a strong CYP3A inducer may decrease doravirine plasma concentrations and/or effects. Potential for loss of virologic response and possible resistance to doravirine.

            • pentobarbital

              pentobarbital will decrease the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of doravirine with a strong CYP3A inducer may decrease doravirine plasma concentrations and/or effects. Potential for loss of virologic response and possible resistance to doravirine.

            • phenobarbital

              phenobarbital will decrease the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of doravirine with a strong CYP3A inducer may decrease doravirine plasma concentrations and/or effects. Potential for loss of virologic response and possible resistance to doravirine.

            • phenytoin

              phenytoin will decrease the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of doravirine with a strong CYP3A inducer may decrease doravirine plasma concentrations and/or effects. Potential for loss of virologic response and possible resistance to doravirine.

            • primidone

              primidone will decrease the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of doravirine with a strong CYP3A inducer may decrease doravirine plasma concentrations and/or effects. Potential for loss of virologic response and possible resistance to doravirine.

            • rifabutin

              rifabutin will decrease the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. If doravirine is coadministered with rifabutin, increase doravirine dose to 100 mg BID (~12 hr apart) for the duration of rifabutin coadministration.

            • rifampin

              rifampin will decrease the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of doravirine with a strong CYP3A inducer may decrease doravirine plasma concentrations and/or effects. Potential for loss of virologic response and possible resistance to doravirine.

            • rifapentine

              rifapentine will decrease the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of doravirine with a strong CYP3A inducer may decrease doravirine plasma concentrations and/or effects. Potential for loss of virologic response and possible resistance to doravirine.

            • secobarbital

              secobarbital will decrease the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of doravirine with a strong CYP3A inducer may decrease doravirine plasma concentrations and/or effects. Potential for loss of virologic response and possible resistance to doravirine.

            • St John's Wort

              St John's Wort will decrease the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of doravirine with a strong CYP3A inducer may decrease doravirine plasma concentrations and/or effects. Potential for loss of virologic response and possible resistance to doravirine.

            • streptozocin

              streptozocin and tenofovir DF both increase nephrotoxicity and/or ototoxicity. Contraindicated. Streptozocin should not be used in combination with or concomitantly with other potential nephrotoxins.

            • telotristat ethyl

              telotristat ethyl will decrease the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of doravirine with a CYP3A inducer may decrease doravirine plasma concentrations and/or effects. Potential for loss of virologic response and possible resistance to doravirine.

            Serious - Use Alternative (21)

            • adefovir

              adefovir, tenofovir DF. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Enhanced nephrotoxicity. Avoid coadministration.

              adefovir increases levels of tenofovir DF by Other (see comment). Avoid or Use Alternate Drug. Comment: Coadministration of tenofovir with drugs that reduce renal function or compete for active tubular secretion may increase serum concentrations of tenofovir. Avoid coadministration.

            • bacitracin

              tenofovir DF and bacitracin both increase nephrotoxicity and/or ototoxicity. Avoid or Use Alternate Drug. Avoid concurrent use of bacitracin with other nephrotoxic drugs

            • betibeglogene autotemcel

              doravirine, betibeglogene autotemcel. Other (see comment). Avoid or Use Alternate Drug. Comment: Do not take antiretroviral medications for at least 1 month before mobilization or expected duration for elimination of the medications, and until all cycles of apheresis are completed. Antiretroviral medications may interfere with manufacturing of apheresed cells.

              tenofovir DF, betibeglogene autotemcel. Other (see comment). Avoid or Use Alternate Drug. Comment: Do not take antiretroviral medications for at least 1 month before mobilization or expected duration for elimination of the medications, and until all cycles of apheresis are completed. Antiretroviral medications may interfere with manufacturing of apheresed cells.

              lamivudine, betibeglogene autotemcel. Other (see comment). Avoid or Use Alternate Drug. Comment: Do not take antiretroviral medications for at least 1 month before mobilization or expected duration for elimination of the medications, and until all cycles of apheresis are completed. Antiretroviral medications may interfere with manufacturing of apheresed cells.

            • cabotegravir

              tenofovir DF, cabotegravir. Other (see comment). Avoid or Use Alternate Drug. Comment: Cabotegravir plus rilpivirine is a complete regimen. Coadministration with other antiretroviral medications for treating HIV-1 infection is not recommended.

              lamivudine, cabotegravir. Other (see comment). Avoid or Use Alternate Drug. Comment: Cabotegravir plus rilpivirine is a complete regimen. Coadministration with other antiretroviral medications for treating HIV-1 infection is not recommended.

              doravirine, cabotegravir. Other (see comment). Avoid or Use Alternate Drug. Comment: Cabotegravir plus rilpivirine is a complete regimen. Coadministration with other antiretroviral medications for treating HIV-1 infection is not recommended.

            • cyclosporine

              cyclosporine and tenofovir DF both increase nephrotoxicity and/or ototoxicity. Avoid or Use Alternate Drug.

            • elivaldogene autotemcel

              elivaldogene autotemcel, doravirine. Either decreases effects of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: Patients should not take antiretroviral medications for at least 1 month before initiating medications for stem cell mobilization, for the duration of the medications? elimination, and until all cycles of apheresis are completed.

            • elivaldogene autotemcel

              elivaldogene autotemcel, lamivudine. Either decreases effects of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: Patients should not take antiretroviral medications for at least 1 month before initiating medications for stem cell mobilization, for the duration of the medications? elimination, and until all cycles of apheresis are completed.

            • dabigatran

              tenofovir DF will decrease the level or effect of dabigatran by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. Avoid coadministration. P-gp inducers reduce systemic exposure of dabigatran

            • edoxaban

              tenofovir DF will decrease the level or effect of edoxaban by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. Avoid coadministration of edoxaban with potent P-gp inducers

            • elivaldogene autotemcel

              elivaldogene autotemcel, tenofovir DF. Either decreases effects of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: Patients should not take antiretroviral medications for at least 1 month before initiating medications for stem cell mobilization, for the duration of the medications? elimination, and until all cycles of apheresis are completed.

            • fexinidazole

              fexinidazole will increase the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Fexinidazole inhibits CYP3A4. Coadministration may increase risk for adverse effects of CYP3A4 substrates.

            • lasmiditan

              lasmiditan increases levels of tenofovir DF by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.

              lasmiditan increases levels of tenofovir DF by Other (see comment). Avoid or Use Alternate Drug. Comment: Lasmiditan inhibits BCRP in vitro. Avoid coadministration of lasmiditan with BCRP substrates.

            • leniolisib

              leniolisib will increase the level or effect of tenofovir DF by Other (see comment). Avoid or Use Alternate Drug. Leniolisib, a BCRP inhibitor, may increase systemic exposure of BCRP substrates

            • letermovir

              tenofovir DF will decrease the level or effect of letermovir by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. Coadministration of letermovir with P-gp inducers is not recommended.

            • nintedanib

              tenofovir DF decreases levels of nintedanib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. Avoid coadministration, particularly for P-gp inducers that are also CYP3A4 inducers; nintedanib is a substrate of P-gp and to a less extent CYP3A4.

            • sorbitol

              sorbitol will decrease the level or effect of lamivudine by Other (see comment). Avoid or Use Alternate Drug. Sorbitol-containing solution decreased systemic exposure of lamivudine oral solution in a pediatric study (ARROW trial). Results showed lower rates of virologic suppression, lower plasma lamivudine exposure, and development of viral resistance more frequently than children receiving lamivudine tablets.

            • sotorasib

              sotorasib will decrease the level or effect of tenofovir DF by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. If use is unavoidable, refer to the prescribing information of the P-gp substrate for dosage modifications.

            • tafenoquine

              tafenoquine will increase the level or effect of lamivudine by Other (see comment). Avoid or Use Alternate Drug. Tafenoquine inhibits organic cation transporter-2 (OCT2) and multidrug and toxin extrusion (MATE) transporters in vitro. Avoid coadministration with OCT2 or MATE substrates. If coadministration cannot be avoided, monitor for substrate-related toxicities and consider dosage reduction if needed based on product labeling of the coadministered drug.

            • tepotinib

              tepotinib will increase the level or effect of tenofovir DF by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. If concomitant use unavoidable, reduce the P-gp substrate dosage if recommended in its approved product labeling.

            • trilaciclib

              trilaciclib will decrease the level or effect of lamivudine by Other (see comment). Avoid or Use Alternate Drug. Avoid coadministration of trilaciclib (OCT2, MATE1, and MATE-2K inhibitor) with substrates where minimal increased concentration in kidney or blood may lead to serious or life-threatening toxicities.

            • tucatinib

              tucatinib will increase the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of tucatinib with CYP3A substrates, where minimal concentration changes may lead to serious or life-threatening toxicities. If unavoidable, reduce CYP3A substrate dose according to product labeling.

            Monitor Closely (155)

            • abacavir

              abacavir and lamivudine both increase risk of immune reconstitution syndrome. Use Caution/Monitor.

              abacavir and tenofovir DF both increase risk of immune reconstitution syndrome. Use Caution/Monitor.

            • acalabrutinib

              acalabrutinib increases levels of tenofovir DF by Other (see comment). Use Caution/Monitor. Comment: Acalabrutinib may increase exposure to coadministered BCRP substrates by inhibition of intestinal BCRP.

            • atazanavir

              atazanavir will increase the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of doravirine and CYP3A4 inhibitors may increase plasma concentrations and toxicities of doravirine.

              atazanavir and lamivudine both increase risk of immune reconstitution syndrome. Use Caution/Monitor.

            • acyclovir

              acyclovir and tenofovir DF both increase nephrotoxicity and/or ototoxicity. Use Caution/Monitor.

              acyclovir increases levels of tenofovir DF by Other (see comment). Use Caution/Monitor. Comment: Coadministration of tenofovir with drugs that reduce renal function or compete for active tubular secretion may increase serum concentrations of tenofovir.

            • belzutifan

              belzutifan will decrease the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. If unable to avoid coadministration of belzutifan with sensitive CYP3A4 substrates, consider increasing the sensitive CYP3A4 substrate dose in accordance with its prescribing information.

            • aldesleukin

              aldesleukin, tenofovir DF. Either increases toxicity of the other by nephrotoxicity and/or ototoxicity. Use Caution/Monitor.

              aldesleukin increases levels of tenofovir DF by decreasing renal clearance. Use Caution/Monitor.

            • amikacin

              amikacin and tenofovir DF both increase nephrotoxicity and/or ototoxicity. Use Caution/Monitor.

              amikacin increases levels of tenofovir DF by decreasing elimination. Use Caution/Monitor.

            • amiloride

              tenofovir DF increases levels of amiloride by decreasing renal clearance. Use Caution/Monitor. Potential for increased toxicity. .

            • amphotericin B cholesteryl sulfate

              amphotericin B cholesteryl sulfate and tenofovir DF both increase nephrotoxicity and/or ototoxicity. Use Caution/Monitor. Combination may also increase tenofovir levels.

            • amphotericin B deoxycholate

              amphotericin B deoxycholate and tenofovir DF both increase nephrotoxicity and/or ototoxicity. Use Caution/Monitor. Combination may also increase tenofovir levels.

            • amphotericin B liposomal

              amphotericin B liposomal and tenofovir DF both increase nephrotoxicity and/or ototoxicity. Use Caution/Monitor. Combination may also increase tenofovir levels.

            • amphotericin B phospholipid complex

              amphotericin B phospholipid complex and tenofovir DF both increase nephrotoxicity and/or ototoxicity. Use Caution/Monitor. Combination may also increase tenofovir levels.

            • apalutamide

              apalutamide will decrease the level or effect of tenofovir DF by increasing elimination. Use Caution/Monitor. Apalutamide weakly induces BCRP and may decrease systemic exposure of drugs that are BCRP substrates.

            • atazanavir

              atazanavir and tenofovir DF both increase risk of immune reconstitution syndrome. Use Caution/Monitor.

              tenofovir DF decreases levels of atazanavir by unknown mechanism. Use Caution/Monitor. May result in loss of atazanavir antiviral activity; ritonavir boosting may help to compensate.

            • berotralstat

              berotralstat will increase the level or effect of tenofovir DF by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • bleomycin

              bleomycin increases levels of tenofovir DF by decreasing renal clearance. Use Caution/Monitor. Potential for increased toxicity. .

            • cabozantinib

              lamivudine will increase the level or effect of cabozantinib by Other (see comment). Use Caution/Monitor. MRP2 inhibitors increase cabozantinib toxicity

            • capreomycin

              capreomycin and tenofovir DF both increase nephrotoxicity and/or ototoxicity. Use Caution/Monitor.

            • carboplatin

              carboplatin and tenofovir DF both increase nephrotoxicity and/or ototoxicity. Use Caution/Monitor. Combination may also increase tenofovir levels.

            • celecoxib

              tenofovir DF, celecoxib. Either increases levels of the other by decreasing renal clearance. Modify Therapy/Monitor Closely. Toxicity may result from coadministration of tenofovir DF with other drugs that are also primarily excreted by glomerular filtration and/or active tubular secretion including high-dose or multiple-dose NSAIDs; alternatives to NSAIDs should be considered.

            • cenobamate

              cenobamate will decrease the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Increase dose of CYP3A4 substrate, as needed, when coadministered with cenobamate.

            • ceritinib

              ceritinib will increase the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • chloramphenicol

              chloramphenicol will increase the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of doravirine and CYP3A4 inhibitors may increase plasma concentrations and toxicities of doravirine.

            • cidofovir

              cidofovir and tenofovir DF both increase nephrotoxicity and/or ototoxicity. Use Caution/Monitor.

              cidofovir increases levels of tenofovir DF by Other (see comment). Use Caution/Monitor. Comment: Coadministration of tenofovir with drugs that reduce renal function or compete for active tubular secretion may increase serum concentrations of tenofovir.

            • cimetidine

              cimetidine, tenofovir DF. Either increases levels of the other by decreasing renal clearance. Use Caution/Monitor.

            • cisplatin

              cisplatin and tenofovir DF both increase nephrotoxicity and/or ototoxicity. Use Caution/Monitor.

              cisplatin increases levels of tenofovir DF by decreasing elimination. Use Caution/Monitor.

            • clarithromycin

              clarithromycin will increase the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of doravirine and CYP3A4 inhibitors may increase plasma concentrations and toxicities of doravirine.

            • cobicistat

              cobicistat will increase the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of doravirine and CYP3A4 inhibitors may increase plasma concentrations and toxicities of doravirine.

            • colistin

              colistin and tenofovir DF both increase nephrotoxicity and/or ototoxicity. Use Caution/Monitor.

            • conivaptan

              conivaptan will increase the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of doravirine and CYP3A4 inhibitors may increase plasma concentrations and toxicities of doravirine.

            • contrast media (iodinated)

              contrast media (iodinated) and tenofovir DF both increase nephrotoxicity and/or ototoxicity. Modify Therapy/Monitor Closely.

            • darolutamide

              darolutamide will increase the level or effect of tenofovir DF by Other (see comment). Modify Therapy/Monitor Closely. Darolutamide is a BCRP inhibitor. Avoid coadministration with BCRP inhibitors. If use is unavoidable, closely monitor for adverse reactions and consider dose reduction of BCRP substrate drug (refer BCRP substrate prescribing information).

            • darunavir

              darunavir will increase the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of doravirine and CYP3A4 inhibitors may increase plasma concentrations and toxicities of doravirine.

            • dichlorphenamide

              dichlorphenamide and tenofovir DF both decrease serum potassium. Use Caution/Monitor.

            • diclofenac

              tenofovir DF, diclofenac. Either increases levels of the other by decreasing renal clearance. Modify Therapy/Monitor Closely. Toxicity may result from coadministration of tenofovir DF with other drugs that are also primarily excreted by glomerular filtration and/or active tubular secretion including high-dose or multiple-dose NSAIDs; alternatives to NSAIDs should be considered.

            • didanosine

              tenofovir DF increases toxicity of didanosine by decreasing elimination. Use Caution/Monitor. May increase risk of pancreatitis; decrease didanosine dose to 250 mg/day if weight >60 kg and decrease to 200 mg/day if weight <60 kg .

            • diflunisal

              tenofovir DF, diflunisal. Either increases levels of the other by decreasing renal clearance. Modify Therapy/Monitor Closely. Toxicity may result from coadministration of tenofovir DF with other drugs that are also primarily excreted by glomerular filtration and/or active tubular secretion including high-dose or multiple-dose NSAIDs; alternatives to NSAIDs should be considered.

            • digoxin

              tenofovir DF increases levels of digoxin by decreasing renal clearance. Use Caution/Monitor. Potential for increased toxicity. .

            • dofetilide

              tenofovir DF increases levels of dofetilide by decreasing renal clearance. Use Caution/Monitor. Potential for increased toxicity. .

            • duvelisib

              tenofovir DF will decrease the level or effect of duvelisib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • efavirenz

              efavirenz and lamivudine both increase risk of immune reconstitution syndrome. Use Caution/Monitor.

              efavirenz and tenofovir DF both increase risk of immune reconstitution syndrome. Use Caution/Monitor.

            • elagolix

              elagolix will increase the level or effect of tenofovir DF by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

              elagolix will decrease the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Elagolix is a weak-to-moderate CYP3A4 inducer. Monitor CYP3A substrates if coadministered. Consider increasing CYP3A substrate dose if needed.

            • enfuvirtide

              enfuvirtide and lamivudine both increase risk of immune reconstitution syndrome. Use Caution/Monitor.

            • fedratinib

              fedratinib will increase the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • emtricitabine

              emtricitabine and tenofovir DF both increase risk of immune reconstitution syndrome. Use Caution/Monitor.

            • encorafenib

              encorafenib will increase the level or effect of tenofovir DF by Other (see comment). Modify Therapy/Monitor Closely. Encorafenib (a BCRP inhibitor) may increase the concentration and toxicities of BCRP substrates. Closely monitor for signs and symptoms of increased exposure and consider adjusting the dose of these substrates.

            • enfuvirtide

              enfuvirtide and tenofovir DF both increase risk of immune reconstitution syndrome. Use Caution/Monitor.

            • entecavir

              tenofovir DF increases levels of entecavir by decreasing renal clearance. Use Caution/Monitor. Potential for increased toxicity. Both drugs are excreted by active tubular secretion.

            • erdafitinib

              lamivudine increases levels of erdafitinib by decreasing renal clearance. Modify Therapy/Monitor Closely. Consider alternatives that are not OCT2 substrates or consider reducing the dose of OCT2 substrates based on tolerability.

            • etodolac

              tenofovir DF, etodolac. Either increases levels of the other by decreasing renal clearance. Modify Therapy/Monitor Closely. Toxicity may result from coadministration of tenofovir DF with other drugs that are also primarily excreted by glomerular filtration and/or active tubular secretion including high-dose or multiple-dose NSAIDs; alternatives to NSAIDs should be considered.

            • famciclovir

              tenofovir DF increases levels of famciclovir by decreasing renal clearance. Use Caution/Monitor. Potential for increased toxicity. .

            • fenofibrate

              fenofibrate increases levels of tenofovir DF by decreasing renal clearance. Use Caution/Monitor. Increased risk of myopathy.

            • fenofibrate micronized

              fenofibrate micronized increases levels of tenofovir DF by decreasing renal clearance. Use Caution/Monitor. Increased risk of myopathy.

            • fenofibric acid

              fenofibric acid increases levels of tenofovir DF by decreasing renal clearance. Use Caution/Monitor. Increased risk of myopathy.

            • fenoprofen

              tenofovir DF, fenoprofen. Either increases levels of the other by decreasing renal clearance. Modify Therapy/Monitor Closely. Toxicity may result from coadministration of tenofovir DF with other drugs that are also primarily excreted by glomerular filtration and/or active tubular secretion including high-dose or multiple-dose NSAIDs; alternatives to NSAIDs should be considered.

            • flucytosine

              flucytosine, tenofovir DF. Either increases toxicity of the other by nephrotoxicity and/or ototoxicity. Use Caution/Monitor.

              flucytosine increases levels of tenofovir DF by decreasing renal clearance. Use Caution/Monitor.

            • flurbiprofen

              tenofovir DF, flurbiprofen. Either increases levels of the other by decreasing renal clearance. Modify Therapy/Monitor Closely. Toxicity may result from coadministration of tenofovir DF with other drugs that are also primarily excreted by glomerular filtration and/or active tubular secretion including high-dose or multiple-dose NSAIDs; alternatives to NSAIDs should be considered.

            • fosamprenavir

              fosamprenavir and lamivudine both increase risk of immune reconstitution syndrome. Use Caution/Monitor.

              fosamprenavir will increase the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of doravirine and CYP3A4 inhibitors may increase plasma concentrations and toxicities of doravirine.

              fosamprenavir and tenofovir DF both increase risk of immune reconstitution syndrome. Use Caution/Monitor.

            • foscarnet

              foscarnet and tenofovir DF both increase nephrotoxicity and/or ototoxicity. Use Caution/Monitor.

            • grapefruit

              grapefruit will increase the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of doravirine and CYP3A4 inhibitors may increase plasma concentrations and toxicities of doravirine.

            • ganciclovir

              ganciclovir, lamivudine. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Increased risk of hematologic toxicity.

            • fostamatinib

              fostamatinib will increase the level or effect of tenofovir DF by decreasing metabolism. Use Caution/Monitor. Concomitant use of fostamatinib may increase concentrations of BCRP substrate drugs. Monitor for toxicities of BCRP substrate drug that may require dosage reduction when given concurrently with fostamatinib.

            • ganciclovir

              ganciclovir increases levels of tenofovir DF by Other (see comment). Use Caution/Monitor. Comment: Coadministration of tenofovir with drugs that reduce renal function or compete for active tubular secretion may increase serum concentrations of tenofovir.

            • gentamicin

              gentamicin and tenofovir DF both increase nephrotoxicity and/or ototoxicity. Use Caution/Monitor.

              gentamicin increases levels of tenofovir DF by decreasing elimination. Use Caution/Monitor.

            • glecaprevir/pibrentasvir

              glecaprevir/pibrentasvir will increase the level or effect of tenofovir DF by decreasing metabolism. Use Caution/Monitor. Glecaprevir/pibrentasvir may increase plasma concentration of BCRP substrates.

            • ibuprofen

              tenofovir DF, ibuprofen. Either increases levels of the other by decreasing renal clearance. Modify Therapy/Monitor Closely. Toxicity may result from coadministration of tenofovir DF with other drugs that are also primarily excreted by glomerular filtration and/or active tubular secretion including high-dose or multiple-dose NSAIDs; alternatives to NSAIDs should be considered.

            • ibuprofen IV

              tenofovir DF, ibuprofen IV. Either increases levels of the other by decreasing renal clearance. Modify Therapy/Monitor Closely. Toxicity may result from coadministration of tenofovir DF with other drugs that are also primarily excreted by glomerular filtration and/or active tubular secretion including high-dose or multiple-dose NSAIDs; alternatives to NSAIDs should be considered.

            • idelalisib

              idelalisib will increase the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of doravirine and CYP3A4 inhibitors may increase plasma concentrations and toxicities of doravirine.

            • imatinib

              imatinib will increase the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of doravirine and CYP3A4 inhibitors may increase plasma concentrations and toxicities of doravirine.

            • indinavir

              indinavir will increase the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of doravirine and CYP3A4 inhibitors may increase plasma concentrations and toxicities of doravirine.

              indinavir and lamivudine both increase risk of immune reconstitution syndrome. Use Caution/Monitor.

              indinavir and tenofovir DF both increase risk of immune reconstitution syndrome. Use Caution/Monitor.

            • indomethacin

              tenofovir DF, indomethacin. Either increases levels of the other by decreasing renal clearance. Modify Therapy/Monitor Closely. Toxicity may result from coadministration of tenofovir DF with other drugs that are also primarily excreted by glomerular filtration and/or active tubular secretion including high-dose or multiple-dose NSAIDs; alternatives to NSAIDs should be considered.

            • isoniazid

              isoniazid will increase the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of doravirine and CYP3A4 inhibitors may increase plasma concentrations and toxicities of doravirine.

            • interferon alfa 2b

              interferon alfa 2b, lamivudine. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of liver decompensation.

            • istradefylline

              istradefylline will increase the level or effect of tenofovir DF by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Istradefylline 40 mg/day increased peak levels and AUC of P-gp substrates in clinical trials. Consider dose reduction of sensitive P-gp substrates.

              istradefylline will increase the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Istradefylline 40 mg/day increased peak levels and AUC of CYP3A4 substrates in clinical trials. This effect was not observed with istradefylline 20 mg/day. Consider dose reduction of sensitive CYP3A4 substrates.

            • itraconazole

              itraconazole will increase the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of doravirine and CYP3A4 inhibitors may increase plasma concentrations and toxicities of doravirine.

            • ketoprofen

              tenofovir DF, ketoprofen. Either increases levels of the other by decreasing renal clearance. Modify Therapy/Monitor Closely. Toxicity may result from coadministration of tenofovir DF with other drugs that are also primarily excreted by glomerular filtration and/or active tubular secretion including high-dose or multiple-dose NSAIDs; alternatives to NSAIDs should be considered.

            • ketorolac

              tenofovir DF, ketorolac. Either increases levels of the other by decreasing renal clearance. Modify Therapy/Monitor Closely. Toxicity may result from coadministration of tenofovir DF with other drugs that are also primarily excreted by glomerular filtration and/or active tubular secretion including high-dose or multiple-dose NSAIDs; alternatives to NSAIDs should be considered.

            • lamivudine

              lamivudine and tenofovir DF both increase risk of immune reconstitution syndrome. Use Caution/Monitor.

            • ledipasvir/sofosbuvir

              ledipasvir/sofosbuvir will increase the level or effect of tenofovir DF by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

              ledipasvir/sofosbuvir will increase the level or effect of tenofovir DF by unspecified interaction mechanism. Use Caution/Monitor.

            • lenacapavir

              lenacapavir will increase the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Lencapavir (a moderate CYP3A4 inhibitor) may increase CYP3A4 substrates initiated within 9 months after last SC dose of lenacapavir, which may increase potential risk of adverse reactions of CYP3A4 substrates.

            • lonafarnib

              lonafarnib will increase the level or effect of tenofovir DF by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Lonafarnib is a weak P-gp inhibitor. Monitor for adverse reactions if coadministered with P-gp substrates where minimal concentration changes may lead to serious or life-threatening toxicities. Reduce P-gp substrate dose if needed.

            • lopinavir

              lopinavir will increase the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of doravirine and CYP3A4 inhibitors may increase plasma concentrations and toxicities of doravirine.

            • lorlatinib

              lorlatinib will decrease the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • meclofenamate

              tenofovir DF, meclofenamate. Either increases levels of the other by decreasing renal clearance. Modify Therapy/Monitor Closely. Toxicity may result from coadministration of tenofovir DF with other drugs that are also primarily excreted by glomerular filtration and/or active tubular secretion including high-dose or multiple-dose NSAIDs; alternatives to NSAIDs should be considered.

            • mefenamic acid

              tenofovir DF, mefenamic acid. Either increases levels of the other by decreasing renal clearance. Modify Therapy/Monitor Closely. Toxicity may result from coadministration of tenofovir DF with other drugs that are also primarily excreted by glomerular filtration and/or active tubular secretion including high-dose or multiple-dose NSAIDs; alternatives to NSAIDs should be considered.

            • meloxicam

              tenofovir DF, meloxicam. Either increases levels of the other by decreasing renal clearance. Modify Therapy/Monitor Closely. Toxicity may result from coadministration of tenofovir DF with other drugs that are also primarily excreted by glomerular filtration and/or active tubular secretion including high-dose or multiple-dose NSAIDs; alternatives to NSAIDs should be considered.

            • memantine

              tenofovir DF increases levels of memantine by decreasing renal clearance. Use Caution/Monitor. Potential for increased toxicity. .

            • metformin

              tenofovir DF increases levels of metformin by decreasing renal clearance. Use Caution/Monitor. Increased risk of lactic acidosis.

            • midodrine

              tenofovir DF increases levels of midodrine by decreasing renal clearance. Use Caution/Monitor. Potential for increased toxicity. .

            • mifepristone

              mifepristone will increase the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of doravirine and CYP3A4 inhibitors may increase plasma concentrations and toxicities of doravirine.

            • mitomycin

              mitomycin, tenofovir DF. Either increases toxicity of the other by nephrotoxicity and/or ototoxicity. Use Caution/Monitor.

              mitomycin increases levels of tenofovir DF by decreasing renal clearance. Use Caution/Monitor.

            • morphine

              tenofovir DF increases levels of morphine by decreasing renal clearance. Use Caution/Monitor. Potential for increased toxicity. .

            • nabumetone

              tenofovir DF, nabumetone. Either increases levels of the other by decreasing renal clearance. Modify Therapy/Monitor Closely. Toxicity may result from coadministration of tenofovir DF with other drugs that are also primarily excreted by glomerular filtration and/or active tubular secretion including high-dose or multiple-dose NSAIDs; alternatives to NSAIDs should be considered.

            • naproxen

              tenofovir DF, naproxen. Either increases levels of the other by decreasing renal clearance. Modify Therapy/Monitor Closely. Toxicity may result from coadministration of tenofovir DF with other drugs that are also primarily excreted by glomerular filtration and/or active tubular secretion including high-dose or multiple-dose NSAIDs; alternatives to NSAIDs should be considered.

            • nefazodone

              nefazodone will increase the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of doravirine and CYP3A4 inhibitors may increase plasma concentrations and toxicities of doravirine.

            • nelfinavir

              nelfinavir will increase the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of doravirine and CYP3A4 inhibitors may increase plasma concentrations and toxicities of doravirine.

              nelfinavir and lamivudine both increase risk of immune reconstitution syndrome. Use Caution/Monitor.

              nelfinavir and tenofovir DF both increase risk of immune reconstitution syndrome. Use Caution/Monitor.

            • neomycin PO

              neomycin PO and tenofovir DF both increase nephrotoxicity and/or ototoxicity. Use Caution/Monitor.

              neomycin PO increases levels of tenofovir DF by decreasing elimination. Use Caution/Monitor.

            • posaconazole

              posaconazole will increase the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of doravirine and CYP3A4 inhibitors may increase plasma concentrations and toxicities of doravirine.

            • nevirapine

              lamivudine and nevirapine both increase risk of immune reconstitution syndrome. Use Caution/Monitor.

            • nevirapine

              nevirapine and tenofovir DF both increase risk of immune reconstitution syndrome. Use Caution/Monitor.

            • orlistat

              orlistat will decrease the level or effect of tenofovir DF by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Loss of virological control reported in HIV-infected patients taking orlistat concomitantly. Exact mechanism is unclear, but may include a drug-drug interaction that inhibits systemic absorption of the antiretroviral drug. Monitor HIV RNA levels frequently and if increased HIV viral load confirmed, discontinue orlistat.

              orlistat will decrease the level or effect of lamivudine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Loss of virological control reported in HIV-infected patients taking orlistat concomitantly. Exact mechanism is unclear, but may include a drug-drug interaction that inhibits systemic absorption of the antiretroviral drug. Monitor HIV RNA levels frequently and if increased HIV viral load confirmed, discontinue orlistat.

            • oteseconazole

              oteseconazole will increase the level or effect of tenofovir DF by Other (see comment). Modify Therapy/Monitor Closely. Otesezonale, a BCRP inhibitor, may increase the effects and risk of toxicities of BCRP substrates. Use lowest starting dose of BCRP substrate, or consider reducing BCRP substrate dose.

            • peginterferon alfa 2a

              peginterferon alfa 2a, lamivudine. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of liver decompensation.

            • oxaliplatin

              oxaliplatin and tenofovir DF both increase nephrotoxicity and/or ototoxicity. Use Caution/Monitor. Combination may also increase tenofovir levels.

            • oxaprozin

              tenofovir DF, oxaprozin. Either increases levels of the other by decreasing renal clearance. Modify Therapy/Monitor Closely. Toxicity may result from coadministration of tenofovir DF with other drugs that are also primarily excreted by glomerular filtration and/or active tubular secretion including high-dose or multiple-dose NSAIDs; alternatives to NSAIDs should be considered.

            • pamidronate

              pamidronate increases levels of tenofovir DF by decreasing renal clearance. Use Caution/Monitor. Combination may increase risk of nephrotoxicity.

            • peginterferon alfa 2b

              peginterferon alfa 2b, lamivudine. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of liver decompensation.

            • pemetrexed

              pemetrexed, tenofovir DF. Either increases levels of the other by decreasing renal clearance. Use Caution/Monitor.

              pemetrexed, tenofovir DF. Either increases toxicity of the other by nephrotoxicity and/or ototoxicity. Use Caution/Monitor.

            • penicillamine

              penicillamine, tenofovir DF. Either increases toxicity of the other by nephrotoxicity and/or ototoxicity. Use Caution/Monitor.

              penicillamine increases levels of tenofovir DF by decreasing renal clearance. Use Caution/Monitor.

            • pentamidine

              pentamidine and tenofovir DF both increase nephrotoxicity and/or ototoxicity. Use Caution/Monitor. Combination may also increase tenofovir levels.

            • peramivir

              tenofovir DF increases levels of peramivir by decreasing renal clearance. Use Caution/Monitor. Caution when peramivir coadministered with nephrotoxic drugs.

            • piroxicam

              tenofovir DF, piroxicam. Either increases levels of the other by decreasing renal clearance. Modify Therapy/Monitor Closely. Toxicity may result from coadministration of tenofovir DF with other drugs that are also primarily excreted by glomerular filtration and/or active tubular secretion including high-dose or multiple-dose NSAIDs; alternatives to NSAIDs should be considered.

            • pramipexole

              tenofovir DF increases levels of pramipexole by decreasing renal clearance. Use Caution/Monitor. Potential for increased toxicity. .

            • probenecid

              probenecid increases levels of tenofovir DF by decreasing renal clearance. Use Caution/Monitor. Potential for increased toxicity. .

            • procainamide

              tenofovir DF increases levels of procainamide by decreasing renal clearance. Use Caution/Monitor. Potential for increased toxicity. .

            • quinidine

              tenofovir DF, quinidine. Either increases levels of the other by decreasing renal clearance. Use Caution/Monitor.

            • regorafenib

              regorafenib will increase the level or effect of tenofovir DF by Other (see comment). Modify Therapy/Monitor Closely. Regorafenib likely inhibits BCRP (ABCG2) transport. Coadministration with a BCRP substrate may increase systemic exposure to the substrate and related toxicity.

            • ribavirin

              ribavirin increases toxicity of lamivudine by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Use alternatives if available. Increased risk of lactic acidosis.

            • ritonavir

              ritonavir will increase the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of doravirine and CYP3A4 inhibitors may increase plasma concentrations and toxicities of doravirine.

              ritonavir and lamivudine both increase risk of immune reconstitution syndrome. Use Caution/Monitor.

              ritonavir and tenofovir DF both increase risk of immune reconstitution syndrome. Use Caution/Monitor.

              ritonavir increases levels of tenofovir DF by decreasing elimination. Use Caution/Monitor.

            • rucaparib

              rucaparib will increase the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust dosage of CYP3A4 substrates, if clinically indicated.

            • safinamide

              safinamide will increase the level or effect of tenofovir DF by Other (see comment). Use Caution/Monitor. Safinamide and its major metabolite may inhibit intestinal BCRP. Monitor BCRP substrates for increased pharmacologic or adverse effects.

            • saquinavir

              saquinavir and lamivudine both increase risk of immune reconstitution syndrome. Use Caution/Monitor.

              saquinavir will increase the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of doravirine and CYP3A4 inhibitors may increase plasma concentrations and toxicities of doravirine.

            • saquinavir

              saquinavir and tenofovir DF both increase risk of immune reconstitution syndrome. Use Caution/Monitor.

            • stiripentol

              stiripentol will increase the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of doravirine and CYP3A4 inhibitors may increase plasma concentrations and toxicities of doravirine.

            • sarecycline

              sarecycline will increase the level or effect of tenofovir DF by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor for toxicities of P-gp substrates that may require dosage reduction when coadministered with P-gp inhibitors.

            • sirolimus

              sirolimus, tenofovir DF. Either increases toxicity of the other by nephrotoxicity and/or ototoxicity. Use Caution/Monitor.

              sirolimus increases levels of tenofovir DF by decreasing renal clearance. Use Caution/Monitor.

            • sitagliptin

              tenofovir DF, sitagliptin. Either increases levels of the other by decreasing renal clearance. Use Caution/Monitor.

            • sofosbuvir

              sofosbuvir will increase the level or effect of tenofovir DF by unspecified interaction mechanism. Use Caution/Monitor.

            • sofosbuvir/velpatasvir

              sofosbuvir/velpatasvir will increase the level or effect of tenofovir DF by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor for tenofovir-associated adverse reactions in patients receiving EPCLUSA concomitantly with a regimen containing tenofovir DF

            • stavudine

              stavudine and tenofovir DF both increase risk of immune reconstitution syndrome. Use Caution/Monitor.

              lamivudine and stavudine both increase risk of immune reconstitution syndrome. Use Caution/Monitor.

            • stiripentol

              stiripentol will increase the level or effect of tenofovir DF by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Consider reducing the dose of P-glycoprotein (P-gp) substrates, if adverse reactions are experienced when administered concomitantly with stiripentol.

              stiripentol will increase the level or effect of tenofovir DF by Other (see comment). Use Caution/Monitor. Stiripentol is a BCRP transport inhibitor. Consider dosage reduction for BCRP substrates if adverse effects are experienced when coadministered.

            • tazemetostat

              tazemetostat will decrease the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

            • tenofovir DF

              lamivudine and tenofovir DF both increase risk of immune reconstitution syndrome. Use Caution/Monitor.

            • streptomycin

              streptomycin and tenofovir DF both increase nephrotoxicity and/or ototoxicity. Use Caution/Monitor.

              streptomycin increases levels of tenofovir DF by decreasing elimination. Use Caution/Monitor.

            • sulindac

              tenofovir DF, sulindac. Either increases levels of the other by decreasing renal clearance. Modify Therapy/Monitor Closely. Toxicity may result from coadministration of tenofovir DF with other drugs that are also primarily excreted by glomerular filtration and/or active tubular secretion including high-dose or multiple-dose NSAIDs; alternatives to NSAIDs should be considered.

            • tacrolimus

              tacrolimus and tenofovir DF both increase nephrotoxicity and/or ototoxicity. Modify Therapy/Monitor Closely.

            • tafamidis

              tafamidis will increase the level or effect of tenofovir DF by Other (see comment). Use Caution/Monitor. Tafamidis inhibits breast cancer resistant protein (BCRP) in vitro and may increase exposure of BCRP substrates following tafamidis or tafamidis meglumine administration. Dosage adjustment of these BCRP substrates may be necessary.

            • tafamidis meglumine

              tafamidis meglumine will increase the level or effect of tenofovir DF by Other (see comment). Use Caution/Monitor. Tafamidis inhibits breast cancer resistant protein (BCRP) in vitro and may increase exposure of BCRP substrates following tafamidis or tafamidis meglumine administration. Dosage adjustment of these BCRP substrates may be necessary.

            • telavancin

              telavancin, tenofovir DF. Either increases toxicity of the other by nephrotoxicity and/or ototoxicity. Use Caution/Monitor.

              telavancin increases levels of tenofovir DF by decreasing renal clearance. Use Caution/Monitor.

            • tipranavir

              tipranavir and lamivudine both increase risk of immune reconstitution syndrome. Use Caution/Monitor.

              tipranavir will increase the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of doravirine and CYP3A4 inhibitors may increase plasma concentrations and toxicities of doravirine.

              tipranavir and tenofovir DF both increase risk of immune reconstitution syndrome. Use Caution/Monitor.

            • tobramycin

              tenofovir DF and tobramycin both increase nephrotoxicity and/or ototoxicity. Use Caution/Monitor.

              tobramycin increases levels of tenofovir DF by decreasing elimination. Use Caution/Monitor.

            • ublituximab

              ublituximab decreases effects of doravirine by immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely.

            • trimethoprim

              trimethoprim increases effects of lamivudine by basic (cationic) drug competition for renal tubular clearance. Use Caution/Monitor. Potential for increased toxicity.

            • tolmetin

              tenofovir DF, tolmetin. Either increases levels of the other by decreasing renal clearance. Modify Therapy/Monitor Closely. Toxicity may result from coadministration of tenofovir DF with other drugs that are also primarily excreted by glomerular filtration and/or active tubular secretion including high-dose or multiple-dose NSAIDs; alternatives to NSAIDs should be considered.

            • trospium chloride

              tenofovir DF, trospium chloride. Either increases levels of the other by decreasing renal clearance. Use Caution/Monitor.

            • tucatinib

              tucatinib will increase the level or effect of tenofovir DF by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Consider reducing the dosage of P-gp substrates, where minimal concentration changes may lead to serious or life-threatening toxicities.

            • ublituximab

              ublituximab decreases effects of tenofovir DF by immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely.

              ublituximab decreases effects of lamivudine by immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely.

            • valacyclovir

              valacyclovir increases levels of tenofovir DF by Other (see comment). Use Caution/Monitor. Comment: Coadministration of tenofovir with drugs that reduce renal function or compete for active tubular secretion may increase serum concentrations of tenofovir.

            • valganciclovir

              valganciclovir, lamivudine. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Use alternatives if available. Increased risk of hematologic toxicity.

            • valganciclovir

              valganciclovir increases levels of tenofovir DF by Other (see comment). Use Caution/Monitor. Comment: Coadministration of tenofovir with drugs that reduce renal function or compete for active tubular secretion may increase serum concentrations of tenofovir.

            • vancomycin

              tenofovir DF and vancomycin both increase nephrotoxicity and/or ototoxicity. Use Caution/Monitor.

            • verapamil

              tenofovir DF increases levels of verapamil by decreasing renal clearance. Use Caution/Monitor. Potential for increased toxicity. .

            • voclosporin

              voclosporin, tenofovir DF. Either increases toxicity of the other by nephrotoxicity and/or ototoxicity. Modify Therapy/Monitor Closely. Coadministration with drugs associated with nephrotoxicity may increase the risk for acute and/or chronic nephrotoxicity.

            • voriconazole

              voriconazole will increase the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of doravirine and CYP3A4 inhibitors may increase plasma concentrations and toxicities of doravirine.

            • zidovudine

              lamivudine and zidovudine both increase risk of immune reconstitution syndrome. Use Caution/Monitor.

              tenofovir DF and zidovudine both increase risk of immune reconstitution syndrome. Use Caution/Monitor.

            Minor (11)

            • acetazolamide

              acetazolamide will increase the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • anastrozole

              anastrozole will increase the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • black cohosh

              black cohosh, tenofovir DF. Either increases toxicity of the other by pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of hepatoxicity.

            • cyclophosphamide

              cyclophosphamide will increase the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • isavuconazonium sulfate

              isavuconazonium sulfate will increase the level or effect of lamivudine by Other (see comment). Minor/Significance Unknown. Isavuconazonium sulfate, an OCT2 inhibitor, may increase the effects or levels of OCT2 substrates.

            • ketoconazole

              ketoconazole will increase the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown. Coadministration of doravirine and CYP3A4 inhibitors may increase plasma concentrations and toxicities of doravirine.

            • larotrectinib

              larotrectinib will increase the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • levoketoconazole

              levoketoconazole will increase the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown. Coadministration of doravirine and CYP3A4 inhibitors may increase plasma concentrations and toxicities of doravirine.

            • paromomycin

              paromomycin and tenofovir DF both increase nephrotoxicity and/or ototoxicity. Minor/Significance Unknown.

              paromomycin increases levels of tenofovir DF by decreasing elimination. Minor/Significance Unknown.

            • ribociclib

              ribociclib will increase the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • sulfamethoxazole

              sulfamethoxazole increases levels of lamivudine by decreasing renal clearance. Minor/Significance Unknown.

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            Adverse Effects

            >10%

            Sleep disorders and disturbances (12%)

            1-10%

            Dizziness (9%)

            Nausea (7%)

            Headache (6%)

            Fatigue (6%)

            Diarrhea (5%)

            Abdominal pain (5%)

            Total bilirubin 1.1 to <1.6x ULN (5%)

            Altered sensorium (4%)

            AST 2.5 to <5x ULN (4%)

            Lipase 1.5 to <3x ULN (4%)

            Creatinine >1.3 to 1.8x ULN (3%)

            ALT 2.5 to <5x ULN (3%)

            Lipase ≥3x ULN (3%)

            Creatine kinase ≥10x ULN (3%)

            Rash (2%)

            Total bilirubin 1.6 to <2.6x ULN (2%)

            Creatinine >1.8x ULN (2%)

            Creatine kinase 6 to <10x ULN (2%)

            Abnormal dreams (1%)

            Insomnia (1%)

            ALT ≥5x ULN (1%)

            <1%

            AST ≥5x ULN

            Alkaline phosphatase 2.5 to <5x ULN

            LDL cholesterol, fasted ≥190 mg/dL

            Triglycerides, fasted >500 mg/dL

            Postmarketing Reports

            Lamivudine

            • Body as a whole: Redistribution/accumulation of body fat
            • Endocrine and metabolic: Hyperglycemia
            • General: Weakness
            • Hemic and lymphatic: Anemia (eg, pure red cell aplasia and severe anemias progressing on therapy)
            • Hepatic and pancreatic: Lactic acidosis and hepatic steatosis, posttreatment exacerbations of hepatitis B
            • Hypersensitivity: Anaphylaxis, urticaria
            • Musculoskeletal: Muscle weakness, CPK elevation, rhabdomyolysis
            • Skin: Alopecia, pruritus

            Tenofovir DF

            • Immune system disorders: Allergic reaction, including angioedema
            • Metabolism and nutrition disorders: Lactic acidosis, hypokalemia, hypophosphatemia
            • Respiratory, thoracic, and mediastinal disorders: Dyspnea
            • Gastrointestinal disorders: Pancreatitis, increased amylase, abdominal pain
            • Hepatobiliary disorders: Hepatic steatosis, hepatitis, increased liver enzymes (most commonly AST, ALT gamma GT)
            • Skin and SC tissue disorders: Rash
            • Musculoskeletal and connective tissue disorders: Rhabdomyolysis, osteomalacia (manifested as bone pain and which may contribute to fractures), muscular weakness, myopathy
            • Renal and urinary disorders: Acute renal failure, renal failure, acute tubular necrosis, Fanconi syndrome, proximal renal tubulopathy, interstitial nephritis (including acute cases), nephrogenic diabetes insipidus, renal insufficiency, increased creatinine, proteinuria, polyuria
            • General disorders and administration site conditions: Asthenia
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            Warnings

            Black Box Warnings

            Test all patients for HBV before initiating ARTs

            Severe acute hepatitis B exacerbations reported in patients coinfected with HIV-1 and HBV who have discontinued lamivudine or tenofovir DF

            Monitor both clinical and laboratory values for several months after discontinuing Delstrigo in patients who are coinfected with HIV-1 and HBV

            If appropriate, initiate antihepatitis B therapy

            Contraindications

            Hypersensitivity to lamivudine

            Strong CYP3A inducers

            • Doravirine is contraindicated with strong CYP3A inducers, which may decrease effectiveness
            • Strong CYP3A inducer examples
              • Anticonvulsants (eg, carbamazepine, oxcarbazepine, phenobarbital, phenytoin)
              • Antimycobacterials (eg, rifampin, rifapentine)
              • Enzalutamide
              • Mitotane
              • St. John’s wort (Hypericum perforatum)

            Cautions

            Severe acute exacerbations of hepatitis B (eg, liver decompensated, liver failure) reported in patients coinfected with HIV-1 and HBV and who have discontinued products containing lamivudine and/or tenofovir DF

            Renal impairment, including cases of acute renal failure and Fanconi syndrome (renal tubular injury with severe hypophosphatemia), reported with tenofovir DF; avoid with concurrent or recent use of nephrotoxic agents (eg, high-dose or multiple NSAIDs)

            Discontinue if CrCl declines below 50 mL/min

            Tenofovir DF associated with decreased bone mineral density (BMD) and increased biochemical markers of bone metabolism; consider assessing BMD in patients at risk

            Immune reconstitution syndrome reported with combination ART

            Autoimmune disorders (eg, Grave disease, polymyositis, Guillain-Barré syndrome, autoimmune hepatitis) reported to occur in the setting of immune reconstitution; however, time to onset varies and can occur many months after initiation of treatment

            Drug interaction overview

            • Coadministration of doravirine with strong CYP3A inducers may decrease systemic exposure and lead to loss of therapeutic effect and possible HIV resistance
            • Since Delstrigo is a complete regimen for HIV-1 infection, coadministration with other antiretroviral medications for HIV-1 infection not recommended; information regarding potential drug-drug interactions with other antiretroviral medications is not provided
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            Pregnancy

            Pregnancy

            Healthcare providers are encouraged to register patients by calling the Antiretroviral Pregnancy Registry (APR) at 1-800-258-4263; pregnancy exposure registry monitors pregnancy outcomes in individuals exposed during pregnancy

            Data are not available to establish drug-associated risks to pregnancy outcomes

            Doravirine has not been evaluated in pregnancy; however, lamivudine and tenofovir DF use during pregnancy has been evaluated in a limited number of individuals reported to the APR; available data from the APR show no difference in the overall risk of major birth defects for lamivudine and TDF compared with the background rate for major birth defects of 2.7% in the US reference population

            Lactation

            The Centers for Disease Control and Prevention do not recommend HIV-infected women breastfeed their infants, owing to potential risk for postnatal transmission of HIV

            Pregnancy Categories

            A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA: Information not available.

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            Pharmacology

            Mechanism of Action

            Doravirine: Non-nucleoside reverse transcriptase inhibitor (NNRTI); inhibits HIV-1 replication by noncompetitive inhibition of HIV-1 reverse transcriptase

            Lamivudine: Nucleoside reverse transcriptase inhibitor (NRTI); following phosphorylation to active metabolite, inhibits HIV reverse transcriptase via DNA chain termination after incorporation

            Tenofovir DF: NRTI; following hydrolysis and subsequent phosphorylation, inhibits HIV-1 reverse transcriptase by competing with the natural substrate deoxyadenosine 5′-triphosphate (ATP) and, after incorporation into DNA, by DNA chain termination

            Absorption

            Bioavailability

            • Doravirine: 64%
            • Lamivudine: 86%
            • Tenofovir AF: 25%

            Peak plasma time

            • Doravirine: 2 hr
            • Tenofovir AF: 1 hr

            Peak plasma concentration

            • Doravirine: 0.962 mcg/mL
            • Lamivudine: 2.04 mcg/mL
            • Tenofovir AF: 0.3 mcg/mL

            AUC

            • Doravirine: 16.1 mcg·h/mL
            • Lamivudine: 8.87 mcg·h/mL
            • Tenofovir AF: 2.29 mcg·h/mL

            Distribution

            Protein bound

            • Doravirine: 76%
            • Lamivudine: <36%
            • Tenofovir AF: <0.7%

            Vd

            • Doravirine: 60.5 L
            • Lamivudine: 1.3 L/kg
            • Tenofovir AF: 1.3 L/kg

            Metabolism

            Doravirine: CYP3A (primary)

            Lamivudine: CYP3A (minor)

            Tenofovir AF: No CYP metabolism

            Elimination

            Half-life

            • Doravirine: 15 hr
            • Lamivudine: 5-7 hr
            • Tenofovir AF: 17 hr

            Renal clearance

            • Doravirine: 9.3 mL/min
            • Lamivudine: 199.7 mL/min
            • Tenofovir AF: 243.5 mL/min

            Total clearance

            • Doravirine: 106 mL/min
            • Lamivudine: 398.5 mL/min
            • Tenofovir AF: 1043.7 mL/min

            Excretion

            • Major elimination route
              • Doravirine: Metabolism
              • Lamivudine and tenofovir AF: Glomerular filtration and active tubular secretion
            • Urine (unchanged)
              • Doravirine: 6%
              • Lamivudine: 71%
              • Tenofovir AF: 70-80%
            • Biliary/fecal (unchanged)
              • Doravirine: Minor
              • Lamivudine and tenofovir AF: Not applicable
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            Administration

            Oral Administration

            Complete regimen for HIV in adults without prior ART treatment history; do not prescribe with other ARTs

            Instruct patient to take at a regularly scheduled time of the day

            May take with or without food

            Missed dose

            • If patient forgets dose, instruct them to take the missed dose right away, unless it is almost time for the next dose
            • If time nearer to next dose, advise not to take 2 doses at once and to take the next dose at the regularly scheduled time

            Storage

            Store at 20-25°C (68-77°F); excursions permitted to 15-30°C (59-86°F)

            Store in original bottle

            Keep bottle tightly closed to protect from moisture; do not remove desiccants

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            Images

            No images available for this drug.
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            Patient Handout

            A Patient Handout is not currently available for this monograph.
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            Formulary

            FormularyPatient Discounts

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            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
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            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.