PIFELTRO

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PIFELTRO

Classes

Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTI)s

Administration

 
NOTE: Must be administered in combination with other antiretroviral medications; never administer as monotherapy.

Oral Administration

Administer orally with or without food.

Adverse Reactions
Severe

suicidal ideation / Delayed / 0-4.0

Moderate

elevated hepatic enzymes / Delayed / 0-5.0
depression / Delayed / 0-4.0
hypercholesterolemia / Delayed / 0-1.0
hypertriglyceridemia / Delayed / 0-1.0
hyperbilirubinemia / Delayed / 0-1.0

Mild

dizziness / Early / 3.0-9.0
nausea / Early / 5.0-7.0
diarrhea / Early / 4.0-6.0
asthenia / Delayed / 4.0-6.0
fatigue / Early / 4.0-6.0
malaise / Early / 4.0-6.0
headache / Early / 4.0-6.0
abdominal pain / Early / 1.0-5.0
nightmares / Early / 1.0-5.0
abnormal dreams / Early / 1.0-5.0
insomnia / Early / 1.0-4.0
rash / Early / 2.0-2.0
maculopapular rash / Early / Incidence not known

Common Brand Names

PIFELTRO

Dea Class

Rx

Description

Non-nucleoside reverse transcriptase inhibitor (NNRTI)
Used in combination with other antiretroviral agents to treat HIV-1 infection in adults and pediatric patients weighing at least 35 kg who are treatment-naive or virologically stable on an antiretroviral regimen without history of treatment failure and no known doravirine resistance-associated substitutions
Contraindicated when co-administered with strong CYP3A inducers which may decrease doravirine effectiveness

Dosage And Indications
For the treatment of human immunodeficiency virus (HIV) infection in combination with other antiretroviral agents in antiretroviral-naive and certain treatment-experienced patients.
NOTE: Use in treatment-experienced patients is limited to those who have been virologically-suppressed (i.e., HIV RNA less than 50 copies/mL) on a stable antiretroviral regimen with no history of treatment failure and who are without known substitutions associated with resistance to doravirine.
Oral dosage Adults

100 mg PO once daily.

Children and Adolescents weighing 35 kg or more

100 mg PO once daily.

Dosing Considerations
Hepatic Impairment

No dosage adjustments are needed for patients with mild to moderate hepatic impairment (Child-Pugh A and B). Treatment has not been evaluated in patients with severe hepatic impairment (Child-Pugh C).

Renal Impairment

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

Drug Interactions

Adagrasib: (Minor) Coadministration of doravirine and adagrasib may result in increased doravirine plasma concentrations. Doravirine is a CYP3A substrate; adagrasib is a strong inhibitor. In drug interaction studies, concurrent use of strong CYP3A inhibitors increased doravirine exposure by more than 3-fold; however, this increase was not considered clinically significant.
Amoxicillin; Clarithromycin; Omeprazole: (Minor) Coadministration of doravirine and clarithromycin may result in increased doravirine plasma concentrations. Doravirine is a CYP3A4 substrate; clarithromycin is a strong inhibitor. In drug interaction studies, concurrent use of strong CYP3A4 inhibitors increased doravirine exposure by more than 3-fold; however, this increase was not considered clinically significant.
Apalutamide: (Contraindicated) Concurrent administration of doravirine and apalutamide is contraindicated due to decreased doravirine exposure, resulting in potential loss of virologic control. At least a 4-week cessation period is recommended before initiating treatment with doravirine. Doravirine is a CYP3A4 substrate; apalutamide is a strong CYP3A4 inducer.
Armodafinil: (Minor) Concurrent administration of doravirine and armodafinil may result in decreased doravirine exposure, resulting in potential loss of virologic control. Doravirine is a CYP3A4 substrate; armodafinil is a weak CYP3A4 inducer.
Aspirin, ASA; Butalbital; Caffeine: (Moderate) Concurrent administration of doravirine and butalbital may result in decreased doravirine exposure, resulting in potential loss of virologic control. Doravirine is a CYP3A4 substrate; butalbital is a moderate CYP3A4 inducer.
Atazanavir: (Minor) Coadministration of doravirine and atazanavir may result in increased doravirine plasma concentrations. Doravirine is a CYP3A4 substrate; atazanavir is a strong inhibitor. In drug interaction studies, concurrent use of strong CYP3A4 inhibitors increased doravirine exposure by more than 3-fold; however, this increase was not considered clinically significant.
Atazanavir; Cobicistat: (Minor) Coadministration of doravirine and atazanavir may result in increased doravirine plasma concentrations. Doravirine is a CYP3A4 substrate; atazanavir is a strong inhibitor. In drug interaction studies, concurrent use of strong CYP3A4 inhibitors increased doravirine exposure by more than 3-fold; however, this increase was not considered clinically significant. (Minor) Coadministration of doravirine and cobicistat may result in increased doravirine plasma concentrations. Doravirine is a CYP3A4 substrate; cobicistat is a strong inhibitor. In drug interaction studies, concurrent use of strong CYP3A4 inhibitors increased doravirine exposure by more than 3-fold; however, this increase was not considered clinically significant.
Belzutifan: (Moderate) Concurrent administration of doravirine and belzutifan may result in decreased doravirine exposure, resulting in potential loss of virologic control. Doravirine is a CYP3A substrate; belzutifan is a weak CYP3A inducer.
Bexarotene: (Moderate) Concurrent administration of doravirine and bexarotene may result in decreased doravirine exposure, resulting in potential loss of virologic control. Doravirine is a CYP3A4 substrate; bexarotene is a moderate CYP3A4 inducer.
Bosentan: (Moderate) Concurrent administration of doravirine and bosentan may result in decreased doravirine exposure, resulting in potential loss of virologic control. Doravirine is a CYP3A4 substrate; bosentan is a moderate CYP3A4 inducer.
Brigatinib: (Minor) Concurrent administration of doravirine and brigatinib may result in decreased doravirine exposure, resulting in potential loss of virologic control. Doravirine is a CYP3A4 substrate; brigatinib is a weak CYP3A4 inducer.
Butabarbital: (Moderate) Concurrent administration of doravirine and butabarbital may result in decreased doravirine exposure, resulting in potential loss of virologic control. Doravirine is a CYP3A4 substrate; butabarbital is a moderate CYP3A4 inducer.
Butalbital; Acetaminophen: (Moderate) Concurrent administration of doravirine and butalbital may result in decreased doravirine exposure, resulting in potential loss of virologic control. Doravirine is a CYP3A4 substrate; butalbital is a moderate CYP3A4 inducer.
Butalbital; Acetaminophen; Caffeine: (Moderate) Concurrent administration of doravirine and butalbital may result in decreased doravirine exposure, resulting in potential loss of virologic control. Doravirine is a CYP3A4 substrate; butalbital is a moderate CYP3A4 inducer.
Butalbital; Acetaminophen; Caffeine; Codeine: (Moderate) Concurrent administration of doravirine and butalbital may result in decreased doravirine exposure, resulting in potential loss of virologic control. Doravirine is a CYP3A4 substrate; butalbital is a moderate CYP3A4 inducer.
Butalbital; Aspirin; Caffeine; Codeine: (Moderate) Concurrent administration of doravirine and butalbital may result in decreased doravirine exposure, resulting in potential loss of virologic control. Doravirine is a CYP3A4 substrate; butalbital is a moderate CYP3A4 inducer.
Carbamazepine: (Contraindicated) Coadministration of carbamazepine and doravirine is contraindicated due to the potential for loss of virologic response and possible resistance to doravirine or the class of non-nucleoside reverse transcriptase inhibitors (NNRTIs). If doravirine use is necessary, discontinue carbamazepine at least 4-weeks prior to initiation. Doravirine is a CYP3A4 substrate and carbamazepine is a potent CYP3A4 inducer.
Cenobamate: (Moderate) Concurrent administration of doravirine and cenobamate may result in decreased doravirine exposure, resulting in potential loss of virologic control. Doravirine is a CYP3A4 substrate; cenobamate is a moderate CYP3A4 inducer.
Ceritinib: (Minor) Monitor for an increase in doravirine-related adverse reactions if coadministration with ceritinib is necessary; increased doravirine plasma concentrations may occur. Doravirine is a CYP3A4 substrate; ceritinib is a strong inhibitor. In drug interaction studies, concurrent use of strong CYP3A4 inhibitors increased doravirine exposure by more than 3-fold; however, this increase was not considered clinically significant.
Chloramphenicol: (Minor) Coadministration of doravirine and chloramphenicol may result in increased doravirine plasma concentrations. Doravirine is a CYP3A4 substrate; chloramphenicol is a strong inhibitor. In drug interaction studies, concurrent use of strong CYP3A4 inhibitors increased doravirine exposure by more than 3-fold; however, this increase was not considered clinically significant.
Clarithromycin: (Minor) Coadministration of doravirine and clarithromycin may result in increased doravirine plasma concentrations. Doravirine is a CYP3A4 substrate; clarithromycin is a strong inhibitor. In drug interaction studies, concurrent use of strong CYP3A4 inhibitors increased doravirine exposure by more than 3-fold; however, this increase was not considered clinically significant.
Clobazam: (Minor) Concurrent administration of doravirine and clobazam may result in decreased doravirine exposure, resulting in potential loss of virologic control. Doravirine is a CYP3A4 substrate; clobazam is a weak CYP3A4 inducer.
Cobicistat: (Minor) Coadministration of doravirine and cobicistat may result in increased doravirine plasma concentrations. Doravirine is a CYP3A4 substrate; cobicistat is a strong inhibitor. In drug interaction studies, concurrent use of strong CYP3A4 inhibitors increased doravirine exposure by more than 3-fold; however, this increase was not considered clinically significant.
Dabrafenib: (Moderate) Concurrent administration of doravirine and dabrafenib may result in decreased doravirine exposure, resulting in potential loss of virologic control. Doravirine is a CYP3A4 substrate; dabrafenib is a moderate CYP3A4 inducer.
Darunavir: (Minor) Coadministration of doravirine and darunavir may result in increased doravirine plasma concentrations. Doravirine is a CYP3A4 substrate; darunavir is a strong inhibitor. In drug interaction studies, concurrent use of strong CYP3A4 inhibitors increased doravirine exposure by more than 3-fold; however, this increase was not considered clinically significant.
Darunavir; Cobicistat: (Minor) Coadministration of doravirine and cobicistat may result in increased doravirine plasma concentrations. Doravirine is a CYP3A4 substrate; cobicistat is a strong inhibitor. In drug interaction studies, concurrent use of strong CYP3A4 inhibitors increased doravirine exposure by more than 3-fold; however, this increase was not considered clinically significant. (Minor) Coadministration of doravirine and darunavir may result in increased doravirine plasma concentrations. Doravirine is a CYP3A4 substrate; darunavir is a strong inhibitor. In drug interaction studies, concurrent use of strong CYP3A4 inhibitors increased doravirine exposure by more than 3-fold; however, this increase was not considered clinically significant.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Minor) Coadministration of doravirine and cobicistat may result in increased doravirine plasma concentrations. Doravirine is a CYP3A4 substrate; cobicistat is a strong inhibitor. In drug interaction studies, concurrent use of strong CYP3A4 inhibitors increased doravirine exposure by more than 3-fold; however, this increase was not considered clinically significant. (Minor) Coadministration of doravirine and darunavir may result in increased doravirine plasma concentrations. Doravirine is a CYP3A4 substrate; darunavir is a strong inhibitor. In drug interaction studies, concurrent use of strong CYP3A4 inhibitors increased doravirine exposure by more than 3-fold; however, this increase was not considered clinically significant.
Deferasirox: (Minor) Concurrent administration of doravirine and deferasirox may result in decreased doravirine exposure, resulting in potential loss of virologic control. Doravirine is a CYP3A4 substrate; deferasirox is a weak CYP3A4 inducer.
Delavirdine: (Minor) Coadministration of doravirine and delavirdine may result in increased doravirine plasma concentrations. Doravirine is a CYP3A4 substrate; delavirdine is a strong inhibitor. In drug interaction studies, concurrent use of strong CYP3A4 inhibitors increased doravirine exposure by more than 3-fold; however, this increase was not considered clinically significant.
Dexamethasone: (Moderate) Monitor for a decrease in doravirine efficacy during concurrent use of doravirine and dexamethasone. If long term coadministration is required, consider using an alternative corticosteroid, such as prednisone or prednisolone. Concomitant use may decrease doravirine exposure leading to potential loss of virologic control. Doravirine is a CYP3A substrate and dexamethasone is a weak CYP3A inducer.
Efavirenz: (Contraindicated) Concurrent treatment with efavirenz and doravirine is not recommended. Both medications are non-nucleoside reverse transcriptase inhibitors (NNRTIs), and using these drugs together would represent duplicate therapy. In addition, taking these drugs together results in decreased doravirine exposure. Doravirine is a CYP3A4 substrate; efavirenz is a CYP3A4 inducer.
Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Contraindicated) Concurrent treatment with efavirenz and doravirine is not recommended. Both medications are non-nucleoside reverse transcriptase inhibitors (NNRTIs), and using these drugs together would represent duplicate therapy. In addition, taking these drugs together results in decreased doravirine exposure. Doravirine is a CYP3A4 substrate; efavirenz is a CYP3A4 inducer.
Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Contraindicated) Concurrent treatment with efavirenz and doravirine is not recommended. Both medications are non-nucleoside reverse transcriptase inhibitors (NNRTIs), and using these drugs together would represent duplicate therapy. In addition, taking these drugs together results in decreased doravirine exposure. Doravirine is a CYP3A4 substrate; efavirenz is a CYP3A4 inducer.
Elagolix: (Moderate) Concurrent administration of doravirine and elagolix may result in decreased doravirine exposure, resulting in potential loss of virologic control. Doravirine is a CYP3A4 substrate; elagolix is a weak to moderate CYP3A4 inducer.
Elagolix; Estradiol; Norethindrone acetate: (Moderate) Concurrent administration of doravirine and elagolix may result in decreased doravirine exposure, resulting in potential loss of virologic control. Doravirine is a CYP3A4 substrate; elagolix is a weak to moderate CYP3A4 inducer.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Minor) Coadministration of doravirine and cobicistat may result in increased doravirine plasma concentrations. Doravirine is a CYP3A4 substrate; cobicistat is a strong inhibitor. In drug interaction studies, concurrent use of strong CYP3A4 inhibitors increased doravirine exposure by more than 3-fold; however, this increase was not considered clinically significant.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Minor) Coadministration of doravirine and cobicistat may result in increased doravirine plasma concentrations. Doravirine is a CYP3A4 substrate; cobicistat is a strong inhibitor. In drug interaction studies, concurrent use of strong CYP3A4 inhibitors increased doravirine exposure by more than 3-fold; however, this increase was not considered clinically significant.
Enzalutamide: (Contraindicated) Concurrent administration of doravirine and enzalutamide is contraindicated due to decreased doravirine exposure, resulting in potential loss of virologic control. At least a 4-week cessation period is recommended before initiating treatment with doravirine. Doravirine is a CYP3A4 substrate; enzalutamide is a strong CYP3A4 inducer.
Eslicarbazepine: (Moderate) Concurrent administration of doravirine and eslicarbazepine may result in decreased doravirine exposure, resulting in potential loss of virologic control. Doravirine is a CYP3A4 substrate; eslicarbazepine is a moderate CYP3A4 inducer.
Etravirine: (Contraindicated) Concurrent treatment with etravirine and doravirine is not recommended. Both medications are non-nucleoside reverse transcriptase inhibitors (NNRTIs), and using these drugs together would represent duplicate therapy. In addition, taking these drugs together may result in decreased doravirine exposure. Doravirine is a CYP3A4 substrate; etravirine is a CYP3A4 inducer.
Fosamprenavir: (Minor) Coadministration of doravirine and fosamprenavir may result in increased doravirine plasma concentrations. Doravirine is a CYP3A4 substrate; fosamprenavir is a strong inhibitor. In drug interaction studies, concurrent use of strong CYP3A4 inhibitors increased doravirine exposure by more than 3-fold; however, this increase was not considered clinically significant.
Fosphenytoin: (Contraindicated) Concurrent administration of doravirine and fosphenytoin is contraindicated due to decreased doravirine exposure, resulting in potential loss of virologic control. At least a 4-week cessation period is recommended before initiating treatment with doravirine. Doravirine is a CYP3A4 substrate; phenytoin (the active metabolite of fosphenytoin) is a strong CYP3A4 inducer.
Glycerol Phenylbutyrate: (Minor) Concurrent administration of doravirine and glycerol phenylbutyrate may result in decreased doravirine exposure, resulting in potential loss of virologic control. Doravirine is a CYP3A substrate; glycerol phenylbutyrate is a weak CYP3A inducer.
Grapefruit juice: (Minor) Instruct patients that consuming grapefruit or grapefruit juice while taking doravirine may result in increased doravirine plasma concentrations. Doravirine is a CYP3A4 substrate; grapefruit is a strong inhibitor. In drug interaction studies, concurrent use of strong CYP3A4 inhibitors increased doravirine exposure by more than 3-fold; however, this increase was not considered clinically significant.
Idelalisib: (Minor) Coadministration of doravirine and idelalisib may result in increased doravirine plasma concentrations. Doravirine is a CYP3A4 substrate; idelalisib is a strong inhibitor. In drug interaction studies, concurrent use of strong CYP3A4 inhibitors increased doravirine exposure by more than 3-fold; however, this increase was not considered clinically significant.
Indinavir: (Minor) Coadministration of doravirine and indinavir may result in increased doravirine plasma concentrations. Doravirine is a CYP3A4 substrate; indinavir is a strong inhibitor. In drug interaction studies, concurrent use of strong CYP3A4 inhibitors increased doravirine exposure by more than 3-fold; however, this increase was not considered clinically significant.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Contraindicated) Concurrent administration of doravirine and rifampin is contraindicated due to decreased doravirine exposure, resulting in potential loss of virologic control. At least a 4-week cessation period is recommended before initiating treatment with doravirine. Doravirine is a CYP3A4 substrate; rifampin is a strong CYP3A4 inducer.
Isoniazid, INH; Rifampin: (Contraindicated) Concurrent administration of doravirine and rifampin is contraindicated due to decreased doravirine exposure, resulting in potential loss of virologic control. At least a 4-week cessation period is recommended before initiating treatment with doravirine. Doravirine is a CYP3A4 substrate; rifampin is a strong CYP3A4 inducer.
Itraconazole: (Minor) Coadministration of doravirine and itraconazole may result in increased doravirine plasma concentrations. Doravirine is a CYP3A4 substrate; itraconazole is a strong inhibitor. In drug interaction studies, concurrent use of strong CYP3A4 inhibitors increased doravirine exposure by more than 3-fold; however, this increase was not considered clinically significant.
Ketoconazole: (Minor) Coadministration of doravirine and ketoconazole may result in increased doravirine plasma concentrations. Doravirine is a CYP3A4 substrate; ketoconazole is a strong inhibitor. In a drug interaction study, concurrent use of ketoconazole increased doravirine exposure by more than 3-fold; however, this increase was not considered clinically significant.
Lansoprazole; Amoxicillin; Clarithromycin: (Minor) Coadministration of doravirine and clarithromycin may result in increased doravirine plasma concentrations. Doravirine is a CYP3A4 substrate; clarithromycin is a strong inhibitor. In drug interaction studies, concurrent use of strong CYP3A4 inhibitors increased doravirine exposure by more than 3-fold; however, this increase was not considered clinically significant.
Lesinurad: (Minor) Concurrent administration of doravirine and lesinurad may result in decreased doravirine exposure, resulting in potential loss of virologic control. Doravirine is a CYP3A4 substrate; lesinurad is a weak CYP3A4 inducer.
Lesinurad; Allopurinol: (Minor) Concurrent administration of doravirine and lesinurad may result in decreased doravirine exposure, resulting in potential loss of virologic control. Doravirine is a CYP3A4 substrate; lesinurad is a weak CYP3A4 inducer.
Levoketoconazole: (Minor) Coadministration of doravirine and ketoconazole may result in increased doravirine plasma concentrations. Doravirine is a CYP3A4 substrate; ketoconazole is a strong inhibitor. In a drug interaction study, concurrent use of ketoconazole increased doravirine exposure by more than 3-fold; however, this increase was not considered clinically significant.
Lonafarnib: (Minor) Coadministration of doravirine and lonafarnib may result in increased doravirine plasma concentrations. Doravirine is a CYP3A4 substrate; lonafarnib is a strong inhibitor. In drug interaction studies, concurrent use of strong CYP3A4 inhibitors increased doravirine exposure by more than 3-fold; however, this increase was not considered clinically significant.
Lopinavir; Ritonavir: (Minor) Coadministration of doravirine and ritonavir may result in increased doravirine plasma concentrations. Doravirine is a CYP3A4 substrate; ritonavir is a strong inhibitor. In a drug interaction study, concurrent use of ritonavir increased doravirine exposure by more than 3-fold; however, this increase was not considered clinically significant.
Lorlatinib: (Moderate) Concurrent administration of doravirine and lorlatinib may result in decreased doravirine exposure, resulting in potential loss of virologic control. Doravirine is a CYP3A4 substrate; lorlatinib is a moderate CYP3A4 inducer.
Lumacaftor; Ivacaftor: (Contraindicated) Concurrent administration of doravirine and lumacaftor; ivacaftor is contraindicated due to decreased doravirine exposure, resulting in potential loss of virologic control. At least a 4-week cessation period is recommended before initiating treatment with doravirine. Doravirine is a CYP3A4 substrate; lumacaftor is a strong CYP3A4 inducer.
Lumacaftor; Ivacaftor: (Contraindicated) Concurrent administration of doravirine and lumacaftor; ivacaftor is contraindicated due to decreased doravirine exposure, resulting in potential loss of virologic control. At least a 4-week cessation period is recommended before initiating treatment with doravirine. Doravirine is a CYP3A4 substrate; lumacaftor is a strong CYP3A4 inducer.
Mavacamten: (Moderate) Concurrent administration of doravirine and mavacamten may result in decreased doravirine exposure, resulting in potential loss of virologic control. Doravirine is a CYP3A substrate; mavacamten is a moderate CYP3A inducer.
Mifepristone: (Minor) Coadministration of doravirine and chronic mifepristone therapy may result in increased doravirine plasma concentrations. Doravirine is a CYP3A4 substrate; mifepristone is a strong inhibitor. In drug interaction studies, concurrent use of strong CYP3A4 inhibitors increased doravirine exposure by more than 3-fold; however, this increase was not considered clinically significant. The clinical significance of CYP450 inhibition with short-term use of mifepristone for termination of pregnancy is unknown.
Mitapivat: (Moderate) Concurrent administration of doravirine and mitapivat may result in decreased doravirine exposure, resulting in potential loss of virologic control. Doravirine is a CYP3A substrate; mitapivat is a weak CYP3A inducer.
Mitotane: (Contraindicated) Concurrent administration of doravirine and mitotane is contraindicated due to decreased doravirine exposure, resulting in potential loss of virologic control. At least a 4-week cessation period is recommended before initiating treatment with doravirine. Doravirine is a CYP3A4 substrate; mitotane is a strong CYP3A4 inducer.
Mobocertinib: (Moderate) Concurrent administration of doravirine and mobocertinib may result in decreased doravirine exposure, resulting in potential loss of virologic control. Doravirine is a CYP3A substrate; mobocertinib is a weak CYP3A inducer.
Modafinil: (Moderate) Concurrent administration of doravirine and modafinil may result in decreased doravirine exposure, resulting in potential loss of virologic control. Doravirine is a CYP3A4 substrate; modafinil is a moderate CYP3A4 inducer.
Nafcillin: (Moderate) Concurrent administration of doravirine and nafcillin may result in decreased doravirine exposure, resulting in potential loss of virologic control. Doravirine is a CYP3A4 substrate; nafcillin is a moderate CYP3A4 inducer.
Nefazodone: (Minor) Coadministration of doravirine and nefazodone may result in increased doravirine plasma concentrations. Doravirine is a CYP3A4 substrate; nefazodone is a strong inhibitor. In drug interaction studies, concurrent use of strong CYP3A4 inhibitors increased doravirine exposure by more than 3-fold; however, this increase was not considered clinically significant.
Nelfinavir: (Minor) Coadministration of doravirine and nelfinavir may result in increased doravirine plasma concentrations. Doravirine is a CYP3A4 substrate; nelfinavir is a strong inhibitor. In drug interaction studies, concurrent use of strong CYP3A4 inhibitors increased doravirine exposure by more than 3-fold; however, this increase was not considered clinically significant.
Nevirapine: (Major) Coadministration of nevirapine and doravirine is not recommended as the combined use of two NNRTIs has not been shown to be beneficial. Concomitant use may also cause a significant decrease in doravirine plasma concentrations and, thus, a loss of therapeutic effect. Doravirine is a CYP3A substrate and nevirapine is a weak CYP3A inducer.
Nirmatrelvir; Ritonavir: (Minor) Coadministration of doravirine and ritonavir may result in increased doravirine plasma concentrations. Doravirine is a CYP3A4 substrate; ritonavir is a strong inhibitor. In a drug interaction study, concurrent use of ritonavir increased doravirine exposure by more than 3-fold; however, this increase was not considered clinically significant.
Odevixibat: (Moderate) Concurrent administration of doravirine and odevixibat may result in decreased doravirine exposure, resulting in potential loss of virologic control. Doravirine is a CYP3A substrate; odevixibat is a weak CYP3A inducer.
Olutasidenib: (Minor) Concurrent administration of doravirine and olutasidenib may result in decreased doravirine exposure, resulting in potential loss of virologic control. Doravirine is a CYP3A substrate; olutasidenib is a weak CYP3A inducer.
Omaveloxolone: (Minor) Concurrent administration of doravirine and omaveloxolone may result in decreased doravirine exposure, resulting in potential loss of virologic control. Doravirine is a CYP3A substrate; omaveloxolone is a weak CYP3A inducer.
Omeprazole; Amoxicillin; Rifabutin: (Major) Increase the doravirine dose to 100 mg PO twice daily (approximately 12 hours apart) if coadministered with rifabutin. Concurrent use decreases doravirine exposure, resulting in potential loss of virologic control. Doravirine is a CYP3A4 substrate and rifabutin is a moderate CYP3A4 inducer.
Oritavancin: (Minor) Concurrent administration of doravirine and oritavancin may result in decreased doravirine exposure, resulting in potential loss of virologic control. Doravirine is a CYP3A4 substrate; oritavancin is a weak CYP3A4 inducer.
Oxcarbazepine: (Contraindicated) Concurrent administration of doravirine and oxcarbazepine is contraindicated due to decreased doravirine exposure, resulting in potential loss of virologic control. At least a 4-week cessation period is recommended before initiating treatment with doravirine. Doravirine is a CYP3A4 substrate; oxcarbazepine is a CYP3A4 inducer.
Pexidartinib: (Moderate) Concurrent administration of doravirine and pexidartinib may result in decreased doravirine exposure, resulting in potential loss of virologic control. Doravirine is a CYP3A4 substrate; pexidartinib is a moderate CYP3A4 inducer.
Phenobarbital: (Contraindicated) Concurrent administration of doravirine and phenobarbital is contraindicated due to decreased doravirine exposure, resulting in potential loss of virologic control. At least a 4-week cessation period is recommended before initiating treatment with doravirine. Doravirine is a CYP3A4 substrate; phenobarbital is a strong CYP3A4 inducer.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Contraindicated) Concurrent administration of doravirine and phenobarbital is contraindicated due to decreased doravirine exposure, resulting in potential loss of virologic control. At least a 4-week cessation period is recommended before initiating treatment with doravirine. Doravirine is a CYP3A4 substrate; phenobarbital is a strong CYP3A4 inducer.
Phentermine; Topiramate: (Minor) Concurrent administration of doravirine and topiramate may result in decreased doravirine exposure, resulting in potential loss of virologic control. Doravirine is a CYP3A4 substrate; topiramate is a weak CYP3A4 inducer.
Phenytoin: (Contraindicated) Concurrent administration of doravirine and phenytoin is contraindicated due to decreased doravirine exposure, resulting in potential loss of virologic control. At least a 4-week cessation period is recommended before initiating treatment with doravirine. Doravirine is a CYP3A4 substrate; phenytoin is a strong CYP3A4 inducer.
Posaconazole: (Minor) Coadministration of doravirine and posaconazole may result in increased doravirine plasma concentrations. Doravirine is a CYP3A4 substrate; posaconazole is a strong inhibitor. In drug interaction studies, concurrent use of strong CYP3A4 inhibitors increased doravirine exposure by more than 3-fold; however, this increase was not considered clinically significant.
Primidone: (Contraindicated) Concurrent administration of doravirine and primidone is contraindicated due to decreased doravirine exposure, resulting in potential loss of virologic control. At least a 4-week cessation period is recommended before initiating treatment with doravirine. Doravirine is a CYP3A4 substrate; primidone is a strong CYP3A4 inducer.
Ribociclib: (Minor) Coadministration of doravirine and ribociclib may result in increased doravirine plasma concentrations. Doravirine is a CYP3A4 substrate; ribociclib is a strong inhibitor. In drug interaction studies, concurrent use of strong CYP3A4 inhibitors increased doravirine exposure by more than 3-fold; however, this increase was not considered clinically significant.
Ribociclib; Letrozole: (Minor) Coadministration of doravirine and ribociclib may result in increased doravirine plasma concentrations. Doravirine is a CYP3A4 substrate; ribociclib is a strong inhibitor. In drug interaction studies, concurrent use of strong CYP3A4 inhibitors increased doravirine exposure by more than 3-fold; however, this increase was not considered clinically significant.
Rifabutin: (Major) Increase the doravirine dose to 100 mg PO twice daily (approximately 12 hours apart) if coadministered with rifabutin. Concurrent use decreases doravirine exposure, resulting in potential loss of virologic control. Doravirine is a CYP3A4 substrate and rifabutin is a moderate CYP3A4 inducer.
Rifampin: (Contraindicated) Concurrent administration of doravirine and rifampin is contraindicated due to decreased doravirine exposure, resulting in potential loss of virologic control. At least a 4-week cessation period is recommended before initiating treatment with doravirine. Doravirine is a CYP3A4 substrate; rifampin is a strong CYP3A4 inducer.
Rifapentine: (Contraindicated) Concurrent administration of doravirine and rifapentine is contraindicated due to decreased doravirine exposure, resulting in potential loss of virologic control. At least a 4-week cessation period is recommended before initiating treatment with doravirine. Doravirine is a CYP3A4 substrate; rifapentine is a strong CYP3A4 inducer.
Ritonavir: (Minor) Coadministration of doravirine and ritonavir may result in increased doravirine plasma concentrations. Doravirine is a CYP3A4 substrate; ritonavir is a strong inhibitor. In a drug interaction study, concurrent use of ritonavir increased doravirine exposure by more than 3-fold; however, this increase was not considered clinically significant.
Saquinavir: (Minor) Coadministration of doravirine and saquinavir may result in increased doravirine plasma concentrations. Doravirine is a CYP3A4 substrate; saquinavir is a strong inhibitor. In drug interaction studies, concurrent use of strong CYP3A4 inhibitors increased doravirine exposure by more than 3-fold; however, this increase was not considered clinically significant.Coadministration may increase doravirine exposure. Concurrent use of strong inhibitors like saquinavir increased doravirine exposure by more than 3-fold; however, this increase was not considered clinically significant.
Secobarbital: (Moderate) Concurrent administration of doravirine and secobarbital may result in decreased doravirine exposure, resulting in potential loss of virologic control. Doravirine is a CYP3A4 substrate; secobarbital is a moderate CYP3A4 inducer.
Sodium Phenylbutyrate; Taurursodiol: (Minor) Concurrent administration of doravirine and taurursodiol may result in decreased doravirine exposure, resulting in potential loss of virologic control. Doravirine is a CYP3A substrate; taurursodiol is a weak CYP3A inducer.
Sotorasib: (Moderate) Concurrent administration of doravirine and sotorasib may result in decreased doravirine exposure, resulting in potential loss of virologic control. Doravirine is a CYP3A4 substrate; sotorasib is a moderate CYP3A4 inducer.
St. John's Wort, Hypericum perforatum: (Contraindicated) Concurrent administration of doravirine and St. John's Wort is contraindicated due to decreased doravirine exposure, resulting in potential loss of virologic control. At least a 4-week cessation period is recommended before initiating treatment with doravirine. Doravirine is a CYP3A4 substrate; St. John's Wort is a strong CYP3A4 inducer.
Tazemetostat: (Minor) Concurrent administration of doravirine and tazemetostat may result in decreased doravirine exposure, resulting in potential loss of virologic control. Doravirine is a CYP3A4 substrate; tazemetostat is a weak CYP3A4 inducer.
Tecovirimat: (Minor) Concurrent administration of doravirine and tecovirimat may result in decreased doravirine exposure, resulting in potential loss of virologic control. Doravirine is a CYP3A4 substrate; tecovirimat is a weak CYP3A4 inducer.
Telotristat Ethyl: (Minor) Concurrent administration of doravirine and telotristat may result in decreased doravirine exposure, resulting in potential loss of virologic control. Doravirine is a CYP3A4 substrate; telotristat is a weak CYP3A4 inducer.
Tipranavir: (Minor) Coadministration of doravirine and tipranavir may result in increased doravirine plasma concentrations. Doravirine is a CYP3A4 substrate; tipranavir is a strong inhibitor. In drug interaction studies, concurrent use of strong CYP3A4 inhibitors increased doravirine exposure by more than 3-fold; however, this increase was not considered clinically significant.
Topiramate: (Minor) Concurrent administration of doravirine and topiramate may result in decreased doravirine exposure, resulting in potential loss of virologic control. Doravirine is a CYP3A4 substrate; topiramate is a weak CYP3A4 inducer.
Tucatinib: (Minor) Coadministration of doravirine and tucatinib may result in increased doravirine plasma concentrations. Doravirine is a CYP3A4 substrate; tucatinib is a strong inhibitor. In drug interaction studies, concurrent use of strong CYP3A4 inhibitors increased doravirine exposure by more than 3-fold; however, this increase was not considered clinically significant.
Vonoprazan; Amoxicillin; Clarithromycin: (Minor) Coadministration of doravirine and clarithromycin may result in increased doravirine plasma concentrations. Doravirine is a CYP3A4 substrate; clarithromycin is a strong inhibitor. In drug interaction studies, concurrent use of strong CYP3A4 inhibitors increased doravirine exposure by more than 3-fold; however, this increase was not considered clinically significant.
Voriconazole: (Minor) Coadministration of doravirine and voriconazole may result in increased doravirine plasma concentrations. Doravirine is a CYP3A4 substrate; voriconazole is a strong inhibitor. In drug interaction studies, concurrent use of strong CYP3A4 inhibitors increased doravirine exposure by more than 3-fold; however, this increase was not considered clinically significant.

How Supplied

PIFELTRO Oral Tab: 100mg

Maximum Dosage
Adults

100 mg/day PO.

Geriatric

100 mg/day PO.

Adolescents

weight 35 kg or more: 100 mg/day PO.
weight less than 35 kg: Safety and efficacy have not been established.

Children

weight 35 kg or more: 100 mg/day PO.
weight less than 35 kg: Safety and efficacy have not been established.

Infants

Safety and efficacy have not been established.

Neonates

Safety and efficacy have not been established.

Mechanism Of Action

Doravirine inhibits HIV-1 reverse transcriptase. Unlike nucleoside reverse transcriptase inhibitors (NRTIs), it does not compete for binding nor does it require phosphorylation to be active. Doravirine binds directly to a site on reverse transcriptase that is distinct from where NRTIs bind. This binding causes disruption of the enzyme's active site thereby blocking RNA-dependent and DNA-dependent DNA polymerase activities. The 50% maximal inhibitory concentrations (EC50) for wild-type laboratory-adapted strains of HIV-1 is approximately 12 nM. Human cellular DNA polymerase alpha, beta, and mitochondrial gamma are not inhibited by doravirine.[63484]
Doravirine-resistant strains have been selected in cell cultures, with observed emergent RT amino acid substitutions being V106A, V106I, V106M, V108I, H221Y, F227C, F227I, F227L, F227V, M230I, L234I, P236L, and Y318F. In clinical trials, 13 of the 36 subjects (36%) in the resistance analysis subset showed doravirine-associated resistance substitutions in RT; which included 1 or more of the following: V90G/I, A98G, V106A, V106I, V106M/T, V108I, E138G, Y188L, H221Y, P225H, P225L, P225P/S, F227C, F227C/R, Y318Y/F, and Y318Y/S. Also, 10 of the 36 subjects (28%) developed genotypic and/or phenotypic resistance to other antiretrovirals (e.g., abacavir, lamivudine, emtricitabine, tenofovir). Cross-resistance to efavirenz, etravirine, rilpivirine, and nevirapine is likely after the development of treatment-emergent doravirine resistance.[63484]
Avoid the use of doravirine in patients with HIV-2, as HIV-2 is intrinsically resistant to NNRTIs. To identify the HIV strain, The Centers for Disease Control and Prevention guidelines for HIV diagnostic testing recommend initial HIV testing using an HIV-1/HIV-2 antigen/antibody combination immunoassay and subsequent testing using an HIV-1/HIV-2 antibody differentiation immunoassay.[46638]

Pharmacokinetics

Doravirine is administered orally. Following systemic absorption, doravirine has a volume of distribution of 60.5 liters and is 76% bound to plasma proteins. The drug undergoes extensive metabolism in the liver by CYP3A enzymes. Metabolites account for the majority of the drug elimination, with only 6% of the dose being excreted in the urine as unchanged drug. Biliary/fecal excretion is a minor elimination pathway. The elimination half-life is 15 hours.[63484]
 
Affected cytochrome P450 isoenzymes: CYP3A
Doravirine is primarily metabolized CYP3A4. The drug is neither an inducer nor an inhibitor of CYP450 isoenzymes or drug transporters.[63484]

Oral Route

The absolute oral bioavailability of doravirine is 64%, and the time to reach maximum plasma concentrations (Tmax) is 2 hours. Steady-state concentrations are achieved by treatment day 2, and the drug has an accumulation ratio of 1.2 to 1.4. Although doravirine may be administered with or without food, administration with a high-fat meal (i.e., 1,000 kcal, 50% fat) increases the exposure ratio by 1.16 (1.06, 1.26) and the 24-hour drug concentration by 1.36 (1.19, 1.55).

Pregnancy And Lactation
Pregnancy

Antiretroviral therapy should be provided to all patients 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. Begin HAART as soon as pregnancy is recognized, or HIV is diagnosed. There are insufficient data to recommend the use of doravirine-containing regimens in pregnant patients or patients who are trying to become pregnant. However, for virologically suppressed patients who become pregnant while receiving doravirine, consider whether to change to an alternative treatment option or continue the same regimen. If the decision is made with the patient to continue, viral loads should be monitored more frequently (i.e., every 1 to 2 months). The Antiretroviral Pregnancy Registry (APR) has prospectively monitored 8 patients treated with doravirine during the first trimester and 2 patients treated during the second and third trimesters. One infant with first trimester exposure was noted to have a birth defect. This information is insufficient to make conclusions regarding the safety of doravirine during pregnancy. Regular laboratory monitoring is recommended to determine antiretroviral efficacy. Monitor CD4 counts at the initial visit. Patients who have been on HAART for at least 2 years and have consistent viral suppression and CD4 counts consistently greater than 300 cells/mm3 do not need CD4 counts monitored after the initial visit during the pregnancy. However, CD4 counts should be monitored every 3 months during pregnancy for patients on HAART less than 2 years, patients with CD4 count less than 300 cells/mm3, or patients with inconsistent adherence or detectable viral loads. Monitor plasma HIV RNA at the initial visit (with review of prior levels), 2 to 4 weeks after initiating or changing therapy, monthly until undetectable, and then at least every 3 months during pregnancy. Viral load should also be assessed at approximately 36 weeks gestation, or within 4 weeks of delivery, to inform decisions regarding mode of delivery and optimal treatment for newborns. Patients whose HIV RNA levels are above the threshold for resistance testing (usually greater than 500 copies/mL but may be possible for levels greater than 200 copies/mL in some laboratories) should undergo antiretroviral resistance testing (genotypic testing, and if indicated, phenotypic testing). Resistance testing should be conducted before starting therapy in treatment-naive patients who have not been previously tested, starting therapy in treatment-experienced patients (including those who have received pre-exposure prophylaxis), modifying therapy in patients who become pregnant while receiving treatment, or modifying therapy in patients who have suboptimal virologic response to treatment that was started during pregnancy. DO NOT delay initiation of antiretroviral therapy while waiting on the results of resistance testing; treatment regimens can be modified, if necessary, once the testing results are known. First trimester ultrasound is recommended to confirm gestational age and provide an accurate estimation of gestational age at delivery. 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 patients 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 patients with high-risk factors for glucose intolerance. Liver function testing is recommended within 2 to 4 weeks after initiating or changing antiretroviral therapy, and approximately every 3 months thereafter during pregnancy (or as needed). All pregnant patients 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 patient decides to discontinue therapy, a consultation with an HIV specialist is recommended. There is a pregnancy exposure registry that monitors outcomes in pregnant patients exposed to doravirine; information about the registry can be obtained at www.apregistry/com or by calling 1-800-258-4263.

HIV treatment guidelines recommend clinicians provide mothers with evidence-based, patient-centered counseling to support shared decision-making regarding infant feeding. Inform patients that use of replacement feeding (i.e., formula or banked pasteurized donor human milk) eliminates the risk of HIV transmission; thus, replacement feeding is recommended for use when mothers with HIV are not on antiretroviral therapy (ART) or do not have suppressed viral load during pregnancy, as well as at delivery. For patients on ART who have achieved and maintained viral suppression during pregnancy (at minimum throughout the third trimester) and postpartum, the transmission risk from breast-feeding is less than 1%, but not zero. Virologically suppressed mothers who choose to breast-feed should be supported in this decision. If breast-feeding is chosen, counsel the patient about the importance of adherence to therapy and recommend that the infant be exclusively breast-fed for up to 6 months of age, as exclusive breast-feeding has been associated with a lower rate of HIV transmission as compared to mixed feeding (i.e., breast milk and formula). Promptly identify and treat mastitis, thrush, and cracked or bleeding nipples, as these conditions may increase the risk of HIV transmission through breast-feeding. Breast-fed infants should undergo immediate diagnostic and virologic HIV testing. Testing should continue throughout breast-feeding and up to 6 months after cessation of breast-feeding. For expert consultation, healthcare workers may contact the Perinatal HIV Hotline (888-448-8765). It is unknown if doravirine is present in human milk, affects human milk production, or has an effect on the breastfed infant.[46675]