Pifeltro

•    See package insert for more complete information on potential side effects and interactions. 

Most common side effects (at least 5% of people taking it) observed with Pifeltro in studies were nausea (7%), dizziness (7%), headache (6%), fatigue (6%), diarrhea (5%), abdominal pain (5%), abnormal dreams (1%), and increased bilirubin (5%). Rash, which is a common side effect of the NNRTIs, was reported in up to 2% of the studied population. In one study (DRIVE-AHEAD), an in-depth analysis was conducted of the incidence of neuropsychiatric adverse events associated with a doravirine-containing regimen (Delstrigo) compared to Atripla. Neuropsychiatric events, such as depression, sleep disturbances, and dizziness, are another common side effect of the NNRTI class. Doravirine did not appear to negatively affect cholesterol in studied populations.

New interactions continue to be discovered after drug approval. When using with the antibiotic drug rifabutin (used for TB and MAC treatment), increase the Pifeltro dose to one tablet twice a day, approximately every 12 hours. The following are among the 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 which are not listed here.

Received FDA approval in 2018. Doravirine may be an option for patients who have developed drug resistance to other NNRTIs. A single-tablet regimen (STR) containing doravirine was also approved last year; see Delstrigo page. Delstrigo, however, contains the older version of tenofovir, tenofovir DF. The stand-alone Pifeltro allows people to take it with the newer and less toxic tenofovir alafenamide, or TAF (found in Descovy). On the other hand, of course, the use of Pifeltro means the necessity for an extra pill of Descovy, or maybe more than one extra pill, depending on the regimen being used. Merck has applied to the FDA for a switch indication, so that people with undetectable viral load on their current treatment can switch to a Pifeltro-based regimen. Pifeltro was found to be non-inferior to boosted darunavir (Prezista) as well as efavirenz (Sustiva) at 48 weeks. 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 class of drugs typically has a lower barrier to resistance as well as have extensive cross-resistance. Additionally, the emergence of resistance at the time of virologic failure has been reported with doravirine. Despite the side effects listed above, doravirine has tolerability advantages over efavirenz and has relatively favorable lipid effects when compared with both boosted darunavir and efavirenz. It also has fewer potential drug interactions than efavirenz or rilpivirine, and, unlike rilpivirine, virologic efficacy is not compromised in those with high baseline viral loads or low CD4 counts. Doravirine has not been directly compared to integrase inhibitor-based regimens in clinical trials yet. Because there were significantly fewer people who received doravirine + Epzicom compared to those who received Truvada, the guidelines consider Pifeltro plus Epzicom to be an option for initial therapy but the guidelines panel has less confidence in this regimen than in the other doravirine-containing regimens. There is no data on the safety of doravirine use in pregnancy. In the DRIVE-FORWARD study, comparing doravirine to darunavir, the treatment-naïve individuals in the study were 80% (darunavir group) and 84% (doravirine group) undetectable (less than 50 copies viral load). That’s a lower success rate than is expected in HIV treatment today, but was thought to be affected by the number of people who quickly dropped out of the study when they saw how many pills they had to take. Those drop-outs were counted as virologic failures. Only 1 of 364 doravirine-treated patients developed drug resistance, a low number for an NNRTI; there was no resistance noted in the boosted darunavir group. See more data online. Pifeltro now has a switch indication, so that people with undetectable viral load on a stable HIV treatment can switch to a regimen that includes Pifeltro if they have no drug resistance to it and no history of treatment failure.

Pifeltro was FDA approved in August 2018 and is also considered to be a “second generation” NNRTI due to its enhanced resistance profile compared to Sustiva and other older “first generation” NNRTIs. In fact, lab studies predict that it may be effective after a first generation NNRTI has failed and left HIV resistance mutations. To date, data from two large clinical trials comparing doravirine to Sustiva and to Prezista/Norvir have shown that Pilfeltro has similar anti-HIV potency as those two known potent medications and fewer side effects. Pifeltro is also approved (August 2018) as an STR combining it with generic tenofovir DF and lamivudine (see Delstrigo).

Pifeltro is the new Merck once-a-day stand-alone non-nucleoside reverse transcriptase inhibitor used to treat HIV in combination with other HIV medicines. Pifeltro is contained in the single-tablet regimen Delstrigo. This treatment is contraindicated with medications that are metabolized by the P450 enzyme inducer. This enzyme causes a significant decrease in doravirine plasma levels and low plasma levels decrease its effectiveness.