Pifeltro
Approved for adults and children who weigh at least 77 pounds (35 kg).
Take missed dose as soon as possible, as long as it is at least 12 hours before your next dose. Do not double up on your next dose. No dosage adjustment necessary for mild, moderate or severe kidney impairment or for mild or moderate liver impairment. Pifeltro has not been studied in people with severe liver impairment.
- See package insert for more complete information on potential side effects and interactions.
pifeltro.com
(800) 672–6372
JO-ANN JOSE, MD, MPH:
Doravirine is part of a combination regimen, Delstrigo. Overall, it’s thought to have a slightly more favorable side effect profile than drugs that are like it. However, there are some drugs that cannot be taken with doravirine, including some seizure and TB medicines, as well as St. John’s wort and some others. There are other drugs that have manageable interactions, but the interaction potential is still there. So it’s important that a discussion about drug interactions occurs if you’re going to start this medicine or a combination regimen that has this medicine in it. You don’t need to take doravirine with food, so that does represent an advantage.
When taken with rifabutin (used for TB and MAC treatment), increase the Pifeltro dose to one 100 mg tablet twice a day, approximately every 12 hours. The following are medications that may lower the blood levels of Pifeltro, and therefore may decrease its effectiveness, and should not be used with Pifeltro: the anticonvulsants carbamazepine, oxcarbazepine, phenobarbital and phenytoin; the androgen receptor inhibitor enzalutamide; the antimycobacterials rifampin and rifapentine; the cytotoxic agent (cancer drug) mitotane and the herbal St. John’s wort. Tell your provider or pharmacist about all medications, herbals and supplements you are taking or thinking of taking, prescribed or not, as there are other drug interactions that are not listed here.
Most common side effects (an incidence of 5% or greater) observed in Pifeltro studies were nausea (7%), headache (6%), fatigue (6%), diarrhea (6%) and abdominal pain (5%). Rash, which is a common side effect of the NNRTI class, was reported in up to 2% of the studied population. Neuropsychiatric events, such as depression, sleep disturbances and dizziness, are another common side effect of NNRTIs. Doravirine did not appear to negatively affect cholesterol in studied populations.
Head-to-head results of doravirine vs. an integrase inhibitor are finally in. A once-daily single-tablet regimen containing doravirine and islatravir (a not yet FDA approved medication) was found to be non-inferior when people switched from Biktarvy, out to one year. “This is the first phase 3 trial to demonstrate that a 2-drug regimen without an integrase inhibitor is non-inferior to BIC/FTC/TAF [Biktarvy],” researchers reported at the CROI 2025 conference. Switching was “generally well tolerated with a comparable safety profile….” Participants were also allowed to add a second pill to their switch, lamivudine. A second switch study from other regimens also found doravirine/islatravir non-inferior out to one year. The lower dose of islatravir used in these studies (.25 mg) avoided earlier problems observed with a higher dose of .75 mg, decreases in lymphocyte and CD4 counts. These are measures of the immune system. FDA approved in 2018, doravirine may be an option for people who have developed drug resistance to other NNRTIs. A single-tablet regimen (STR) containing doravirine was also approved in 2018; see Delstrigo page. Delstrigo, however, contains the older version of tenofovir—tenofovir DF. The standalone Pifeltro allows people to take it with the newer tenofovir alafenamide (TAF), found in Descovy, which has potentially less long-term renal and bone toxicity. On the other hand, TAF is associated with weight gain. Of course, the use of Pifeltro means the necessity for an extra pill, such as Descovy, or maybe more than one extra pill, depending on the regimen being used. Pifeltro was found to be non-inferior to boosted darunavir (Prezista) as well as efavirenz (Sustiva), with data now out to 96 weeks (2 years) in the DRIVE-FORWARD study. Doravirine was superior to boosted darunavir at week 96 in terms of virologic suppression, but it should be noted there was a higher rate of study discontinuation in the boosted darunavir group. Doravirine is a non-nucleoside medication, and it should be noted that this drug class typically has a lower barrier to resistance, as well as extensive cross-resistance. Additionally, the emergence of resistance at the time of virologic failure has been reported with doravirine. Doravirine has tolerability advantages over efavirenz and has relatively favorable lipid effects when compared to both boosted darunavir and efavirenz. It also has fewer potential drug interactions than efavirenz or rilpivirine, and, unlike rilpivirine, virologic efficacy is not known to be compromised among people with high baseline viral loads or low CD4 counts. According to HHS guidelines: “In a cross-trial analysis, DOR was not associated with weight gain compared with [efavirenz] 600 mg or boosted [darunavir].” For individuals with HIV-2, primarily found in West Africa but also present in other countries, an NNRTI would not be recommended as HIV-2 is inherently resistant to NNRTIs. No adequate human data are available yet to establish whether or not Pifeltro poses a risk to pregnancy outcomes. However, it is predicted that blood levels of Pifeltro are lower in pregnancy, which may reduce the effectiveness of the medication. Pregnant individuals can voluntarily enroll in the Antiretroviral Pregnancy Registry through their provider; GO TO apregistry.com.
JUAN MICHAEL PORTER II:
Pifeltro (doravirine) is used in combination with dolutegravir among people with first-generation non-nucleoside drug resistance. It doesn’t need to be taken with food and, despite some interactions with other drugs, can also be taken with antacids. Given its flexibility, it remains a useful drug even today.