Download pdf
CATIE

Pifeltro (doravirine)

Summary

Pifeltro contains one medicine—doravirine. Doravirine belongs to the class of drugs called non-nucleoside reverse transcriptase inhibitors (“non-nukes”). Pifeltro is used as part of combination HIV treatment (ART) and is taken at a dose of one pill once daily with or without food. Overall, Pifeltro was well-tolerated in clinical trials. General side effects were uncommon and included headache and nausea; these were usually mild and temporary.

What is Pifeltro?

Pifeltro contains one medicine—doravirine. Doravirine belongs to the class of drugs called non-nucleoside reverse transcriptase inhibitors (“non-nukes”).

How does Pifeltro work?

Pifeltro works by interfering with an enzyme needed by HIV called reverse transcriptase. Using Pifeltro together with other anti-HIV drugs greatly reduces HIV’s ability to infect cells and make copies of itself.

How do people with HIV use Pifeltro?

Pifeltro is meant to be used as part of combination HIV treatment in people aged 12 years or older who weigh at least 35 kg and who do not have past or current evidence of resistance to doravirine.

For more information about HIV treatment, see CATIE’s Your Guide to HIV Treatment.

For many people with HIV, the use of ART (HIV treatment or antiretroviral therapy) has increased their CD4+ cell counts and decreased the amount of HIV in their blood (viral load). These beneficial effects help to greatly reduce the risk of developing a life-threatening infection or an AIDS-related cancer. Neither Pifeltro nor any other treatment regimen (ART) is a cure for HIV. It is therefore important that you see your doctor for checkups and lab tests on a regular basis.

Evidence shows that HIV-positive people who are on ART, engaged in care, and have an ongoing undetectable viral load are substantially less likely to transmit HIV to others, be it through sex, when sharing equipment to use drugs or during pregnancy and birth. In fact, the evidence for sexual transmission shows that people on ART who maintain an undetectable viral load do not pass HIV to their sexual partners. For further information see the CATIE fact sheet HIV treatment and an undetectable viral load to prevent HIV transmission. However, it is still a good idea to use condoms because they can reduce your risk for getting and passing on other sexually transmitted infections.

Warnings

Special populations

Pregnancy

Doravirine has not been studied in pregnancy and its safety in pregnant people is not known. Pifeltro’s effect on the fetus is not known. If you are pregnant or want to have a baby, let your doctor know.

People who are 65 years or older

According to the manufacturer, Merck, “there are limited data on the use of doravirine in patients aged 65 years and over. There is no evidence that [older patients] require a different dose than younger adult patients.”

People with kidney injury or dysfunction

Merck states: “No dose adjustment of doravirine is required in patients with mild, moderate or severe renal impairment.”

People with liver injury or dysfunction

Merck states: “No dose adjustment of doravirine is required in patients with mild or moderate hepatic impairment.”

Driving and operating machinery

According to Merck, some people who use Pifeltro may experience one or more of the following:

  • tiredness
  • dizziness
  • sleepiness

If you experience any of these, do not drive a vehicle or operate machinery. Wait until these symptoms have cleared.

Side effects

General

In clinical trials, Pifeltro was well tolerated, generally safe and effective. However, as with any treatment, there were side effects but these were uncommon and included the following:

  • nausea
  • lack of energy
  • headache
  • dizziness
  • feeling sleepy during the daytime

If these side effects persist or are bothersome, let your doctor know.

Note that the  people who are typically enrolled in pivotal clinical trials of HIV treatments, including Pifeltro, are generally young and healthy. Once a drug is approved and more widely available, it gets used by populations who are not usually in pivotal clinical trials. These people may be older and may have other health issues—such as cardiovascular disease, liver injury, kidney injury, type 2 diabetes, anxiety, depression, and substance use—that require medications or that cause symptoms. As a result, their experience of side effects may be different from those reported in pivotal clinical trials.

Drug interactions

Some drugs (including prescribed and over-the-counter), herbs and supplements can interfere with the absorption and/or effectiveness of Pifeltro. Such interference is called a drug interaction. Some drugs can reduce the levels of Pifeltro in your blood. This can make Pifeltro less effective and lead to treatment failure, reducing your future treatment options. Other drugs can raise the levels of Pifeltro in your blood, resulting in enhanced side effects or new side effects. Therefore, it is important to disclose to your doctor and pharmacist all the supplements, drugs, and herbs you are taking. Drug interactions can occur with:

  • anti-seizure drugs – carbamazepine, oxcarbazepine, phenobarbital, phenytoin
  • the prostate cancer drug enzalutamide (Xtandi)
  • the anti-cancer drug mitotane (Lysodren)
  • antibiotics – rifampin, rifapentine
  • the herb St. John’s Wort or extracts of this herb including hypericin and hyperforin

Rifabutin

When taking the antibiotic rifabutin, Merck recommends that one tablet of doravirine (100 mg) should be taken twice daily (about 12 hours apart). 

This factsheet is not comprehensive and only lists some of the potential and actual drug interactions with Pifeltro. Speak to your pharmacist to find out more about drug interactions with Pifeltro.

Many HIV-positive people take acid-reducing agents, including over-the-counter preparations such as Tums or Maalox or a class of drugs called PPIs (proton pump inhibitors), including the following:

  • Losec (omeprazole)
  • Nexium (esomeprazole)
  • Pantoloc (pantoprazole)
  • Pariet (rabeprazole)

None of these acid-reducing agents interact with Pifeltro.

Some modest beneficial effects of doravirine

Note that many people who take HIV treatment gain some weight — usually a few kg and this tends to stabilize after a year or two. However, doravirine has modest effects on weight loss. In studies, some people who have used other regimens and then switched to doravirine-based treatment lost a modest amount of weight; a few kg. 

Also, levels of cholesterol in the blood may decrease modestly when people switch to a doravirine-based regimen.

Resistance and cross-resistance

Over time, as new copies of HIV are made in the body, the virus changes its structure. These changes, called mutations, can cause HIV to resist the effects of anti-HIV drugs, which means those drugs will no longer work for you.

To reduce the risk of developing drug resistance, all anti-HIV drugs should be taken every day exactly as prescribed and directed. If doses are delayed, missed or not taken as prescribed, the level of Pifeltro in the blood may fall too low. If this happens, the HIV in your body can become resistant to the medication. If you find you are having problems taking your medications as directed, speak to your doctor, nurse or pharmacist about this. They can find ways to help you.

When HIV becomes resistant to one drug in a class, it sometimes becomes resistant to other drugs in that class. This is called cross-resistance. Feel free to talk with your doctor about your current and future treatment options. To help you decide what these future options might be, at some point your doctor can have a small sample of your blood analyzed to test for resistance.

Dosage

Pifeltro is supplied as white oval-shaped tablets. Each tablet contains 100 mg of doravirine. Pifeltro is taken once daily with or without a meal together with other anti-HIV drugs.

If you forget to take a dose, Merck has this advice:

  • If you miss a dose, take it as soon as you remember. If you do not remember until it is almost time for your next dose, skip the missed dose and take the next dose at your regular time.
  • Do not take two doses of Pifeltro at the same time.
  • If you are not sure what to do, call your doctor or pharmacist.

Availability

Pifeltro is licensed in Canada for the treatment of HIV infection in people aged 12 or more years and who weigh at least 35 kg. Doravirine is used in combination with other anti-HIV drugs. Your doctor or pharmacist can tell you more about the availability and coverage of Pifeltro in your region. CATIE’s online module Federal, Provincial and Territorial Drug Access Programs also contains information about Canadian drug coverage.

References

  1. Merck Canada. Pifeltro (doravirine). Product Monograph. 30 May, 2023.
  2. Orkin C, Molina JM, Cahn P, et al. Safety and efficacy of doravirine as first-line therapy in adults with HIV-1: week 192 results from the open-label extensions of the DRIVE-FORWARD and DRIVE-AHEAD phase 3 trials. Lancet HIV. 2024 Feb;11(2):e75-e85.  
  3. Erlandson KM, Mohaweche R, Morrow M, et al. Energy balance and body composition after switch between integrase strand transfer inhibitors and doravirine among people with HIV. Journal of Antimicrobial Chemotherapy. 2024 Jan 3;79(1):179-185.  
  4. Orkin C, Squires KE, Molina JM, et al. Doravirine/lamivudine/tenofovir disoproxil fumarate is non-inferior to efavirenz/emtricitabine/tenofovir disoproxil fumarate in treatment-naive adults with human immunodeficiency virus-1 infection: week 48 results of the DRIVE-AHEAD trial. Clinical Infectious Diseases.  2021 Jul 1;73(1):33-42.
  5. Kousari AE, Wilson MP, Hawkins KL, et al. Weight change with antiretroviral switch from integrase inhibitor or tenofovir alafenamide-based to Doravirine-Based regimens in people with HIV. HIV Research and Clinical Practice. 2024 Dec;25(1):2339576.  
  6. Calza L, Giglia M, Colangeli V, et al. Improvement in insulin sensitivity after switching from an integrase inhibitor-based regimen to doravirine/tenofovir disoproxil fumarate/lamivudine in people with significant weight gain. HIV Medicine. 2024; in press.
  7. Molina JM, Squires K, Sax PE, et al. Doravirine versus ritonavir-boosted darunavir in antiretroviral-naive adults with HIV-1 (DRIVE-FORWARD): 48-week results of a randomised, double-blind, phase 3, non-inferiority trial. Lancet HIV. 2018 May;5(5):e211-e220.

 

Author(s): Hosein SR

Published: 2024