Frequently asked questions for PIFELTRO® (doravirine)
For answers to questions you may have, select any of the topics below. To see a complete list of Q&As, scroll down.
What is the indication and usage for PIFELTRO?
PIFELTRO is indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection in adult patients:
- with no prior antiretroviral treatment history; OR
- to replace the current antiretroviral regimen in those who are virologically suppressed (HIV-1 RNA less than 50 copies per mL) on a stable antiretroviral regimen with no history of treatment failure and no known substitutions associated with resistance to doravirine.
What is the recommended dosing for PIFELTRO?
Recommended Dosage: One 100-mg tablet once daily with or without food as part of a complete regimen in adult patients with HIV-1.
Dosage Adjustment with Rifabutin
If PIFELTRO is co-administered with rifabutin, increase PIFELTRO dosage to one tablet twice daily (approximately 12 hours apart) for the duration of rifabutin co-administration.
What is the Selected Safety Information for PIFELTRO?
Contraindications
PIFELTRO is contraindicated when coadministered with drugs that are strong cytochrome P450 (CYP)3A enzyme inducers (including the anticonvulsants carbamazepine, oxcarbazepine, phenobarbital, and phenytoin; the androgen receptor inhibitor enzalutamide; the antimycobacterials rifampin and rifapentine; the cytotoxic agent mitotane; and the herbal product St. John’s wort (Hypericum perforatum)), as significant decreases in PIFELTRO plasma concentrations may occur, which may decrease the effectiveness of PIFELTRO.
Immune Reconstitution Syndrome
Immune reconstitution syndrome can occur, including the occurrence of autoimmune disorders with variable time to onset, which may necessitate further evaluation and treatment.
Coadministration of PIFELTRO with efavirenz, etravirine, or nevirapine is not recommended.
If coadministered with rifabutin, increase PIFELTRO dosage to one tablet twice daily (approximately 12 hours apart).
Consult the full Prescribing Information prior to and during treatment for more information on potential drug-drug interactions.
Adverse Reactions
The most common adverse reactions with PIFELTRO (incidence ≥5%, all intensities) were nausea (7%), dizziness (7%), headache (6%), fatigue (6%), diarrhea (6%), abdominal pain (5%), and abnormal dreams (5%).
By week 96 in DRIVE-FORWARD, 2% of adult subjects in the PIFELTRO group and 3% in the DRV+r group had adverse events leading to discontinuation of study medication.
By week 96 in DRIVE-AHEAD, 3% of adult subjects in the doravirine (DOR)/lamivudine (3TC)/tenofovir disoproxil fumarate (TDF) group and 7% in the efavirenz (EFV)/emtricitabine (FTC)/TDF group had adverse events leading to discontinuation of study medication.
In DRIVE-FORWARD, mean changes from baseline at week 48 in LDL-cholesterol (LDL-C) and non-HDL-cholesterol (non-HDL-C) were pre-specified. LDL-C: -4.6 mg/dL in the PIFELTRO group vs 9.5 mg/dL in the DRV+r group. Non-HDL-C: -5.4 mg/dL in the PIFELTRO group vs 13.7 mg/dL in the DRV+r group. The clinical benefits of these findings have not been demonstrated.
In DRIVE-AHEAD, mean changes from baseline at week 48 in LDL-C and non-HDL-C were pre-specified. LDL-C: -2.1 mg/dL in the DELSTRIGO group vs 8.3 mg/dL in the EFV/FTC/TDF group. Non-HDL-C: -4.1 mg/dL in the DELSTRIGO group vs 12.7 mg/dL in the EFV/FTC/TDF group. The clinical benefits of these findings have not been demonstrated.
In DRIVE-SHIFT, mean changes from baseline at week 24 in LDL-C and non-HDL-C were pre-specified. LDL-C: -16.3 mg/dL in the DELSTRIGO group vs -2.6 mg/dL in the PI + ritonavir group. Non-HDL-C: -24.8 mg/dL in the DELSTRIGO group vs -2.1 mg/dL in the PI + ritonavir group. The clinical benefits of these findings have not been demonstrated.
In DRIVE-AHEAD, neuropsychiatric adverse events were reported in the three pre-specified categories of sleep disorders and disturbances, dizziness, and altered sensorium. Twelve percent of adult subjects in the DELSTRIGO group and 26% in the EFV/FTC/TDF group reported neuropsychiatric adverse events of sleep disorders and disturbances; 9% in the DELSTRIGO group and 37% in the EFV/FTC/TDF group reported dizziness; and 4% in the DELSTRIGO group and 8% in the EFV/FTC/TDF group reported altered sensorium.
The safety of DELSTRIGO in virologically-suppressed adults was based on week 48 data from subjects in the DRIVE-SHIFT trial. Overall, the safety profile in virologically-suppressed adult subjects was similar to that in subjects with no ARV treatment history.
Pregnancy/Breastfeeding
There is a pregnancy exposure registry that monitors pregnancy outcomes in individuals exposed to PIFELTRO during pregnancy. Healthcare providers are encouraged to register patients by calling the Antiretroviral Pregnancy Registry (APR) at 1-800-258-4263.
Mothers infected with HIV-1 should be instructed not to breastfeed if they are receiving PIFELTRO due to the potential for HIV-1 transmission.
What is the mechanism of action for PIFELTRO?
Doravirine is a pyridinone non-nucleoside reverse transcriptase inhibitor of HIV-1 and inhibits HIV-1 replication by non-competitive inhibition of HIV-1 reverse transcriptase (RT). The inhibitory concentration at 50% (IC50) of doravirine for RNA-dependent DNA polymerization of recombinant wild-type HIV-1 RT in a biochemical assay was 12.2 ± 2.0 nM (n=3). Doravirine does not inhibit the human cellular DNA polymerases α, β, and mitochondrial DNA polymerase γ.
What drug class does PIFELTRO belong to?
PIFELTRO is a non-nucleoside reverse transcriptase inhibitor (NNRTI).
Is PIFELTRO recommended in the DHHS Guidelines for the Use of Antiretroviral Agents in HIV-1–Infected Adults and Adolescents?
Yes, PIFELTRO is included in the DHHS Guidelines as one of the “Recommended Initial Regimens in Certain Clinical Situations.”
Acronyms
DHHS, Department of Health and Human Services.
What was the study design for the DRIVE-FORWARD trial?
A randomized, multicenter, double-blind, active-controlled, non-inferior, phase 3 trial comparing PIFELTRO 100 mg once daily (n=383) vs darunavir 800 mg + ritonavir 100 mg once daily (n=383), each in combination with 2 NRTIs, FTC/TDF or ABC/3TC selected by the investigator, in treatment-naïve adult participants with HIV-1 RNA ≥1000 copies/mL.1,2
Acronyms
3TC, lamivudine; ABC, abacavir; FTC, emtricitabine; NRTI, nucleoside reverse transcriptase inhibitor; RNA, ribonucleic acid; TDF, tenofovir disoproxil fumarate.
References
- Molina JM, Squires K, Sax PE, et al; for the DRIVE-FORWARD Study Group. 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;5(5):e211-e220. Epub 2018 Mar 25.doi: 10.1016/S2352-3018(18)30021-3.
- Molina JM, Squires K, Sax PE, et al; for the DRIVE-FORWARD Trial Group. Doravirine versus ritonavir-boosted darunavir in antiretroviral-naive adults with HIV-1 (DRIVE-FORWARD): 96-week results of a randomised, double-blind, non-inferiority, phase 3 trial. Lancet HIV. 2020;7(1):e16-e26. Epub 2019 Nov 15. doi: 10.1016/S2352-3018(19)30336-4.
What was the study design for the DRIVE-SHIFT trial?
A randomized, multicenter, active-controlled, non-inferior, open-label phase 3 trial of adult participants with virologically suppressed HIV-1 for ≥6 months on 2 NRTIs with a PI plus either ritonavir or cobicistat, elvitegravir plus cobicistat, or an NNRTI, with no history of virologic failure. Participants were either immediately switched to a doravirine-based FDC (100 mg DOR/300 mg 3TC/300 mg TDF) on day 1 of the 48-week trial (Immediate Switch Group (ISG) [n=447]) or continued their baseline regimen and switched after 24 weeks (Delayed Switch Group (DSG) [n=223]) to a doravirine-based FDC.1,2
Visit resistance profile of PIFELTRO
Acronyms
3TC, lamivudine; DOR, doravirine; FDC, fixed-dose combination; NNRTI, non-nucleoside reverse transcriptase inhibitor; NRTI, nucleoside reverse transcriptase inhibitor; PI, protease inhibitor, and TDF, tenofovir disoproxil fumarate.
References
- Johnson M, Kumar P, Molina JM, et al; for the DRIVE-SHIFT Study Group. Switching to doravirine/lamivudine/tenofovir disoproxil fumarate (DOR/3TC/TDF) maintains HIV-1 virologic suppression through 48 weeks: results of the DRIVE-SHIFT trial. J Acquir Immune Defic Syndr. 2019;81(4):463-472. doi:10.1097/QAI.0000000000002056.
- Kumar P, Johnson M, Molina JM, et al; for the DRIVE-SHIFT Study Group. Switching to DOR/3TC/TDF maintains HIV-1 virologic suppression through week 144 in the DRIVE-SHIFT trial. J Acquir Immune Defic Syndr. 2021;87(2):801-805. doi: 10.1097/QAI.0000000000002642.
What was the study design for the DRIVE-AHEAD trial?
A randomized, multicenter, double-blind, active-controlled, non-inferior, phase 3 trial comparing a doravirine-based FDC (100 mg DOR/300 mg 3TC/300 mg TDF) once daily (n=364) vs 600 mg EFV/200 mg FTC/300 mg TDF once daily (n=364) in treatment-naïve adult participants with HIV-1 RNA ≥1000 copies/mL.1,2
Acronyms
3TC, lamivudine; DOR, doravirine; EFV, efavirenz; FDC, fixed-dose combination; FTC, emtricitabine; RNA, ribonucleic acid; TDF, tenofovir disoproxil fumarate.
References
- Orkin C, Squires KE, Molina JM, et al; for the DRIVE-AHEAD Study Group. 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. Clin Infect Dis. 2019;68(4):535-544. doi: 10.1093/cid/ciy540.
- Orkin C, Squires KE, Molina JM, et al. Doravirine/lamivudine/tenofovir disoproxil fumarate (TDF) versus efavirenz/emtricitabine/TDF in treatment-naive adults with human immunodeficiency virus type 1 infection: week 96 results of the randomized, double-blind, phase 3 DRIVE-AHEAD noninferiority trial. Clin Infect Dis. 2021;73(1):33-42. doi: 10.1093/cid/ciaa822.
Does PIFELTRO have any food restrictions?
No. PIFELTRO can be taken with or without food.
What are the most common adverse reactions associated with PIFELTRO?
The most common adverse reactions with PIFELTRO (incidence ≥5%, all intensities) were nausea (7%), headache (6%), fatigue (6%), diarrhea (6%), and abdominal pain (5%).
Does PIFELTRO have any contraindications?
PIFELTRO is contraindicated when co-administered with drugs that are strong cytochrome P450 (CYP)3A enzyme inducers as significant decreases in doravirine plasma concentrations may occur, which may decrease the effectiveness of PIFELTRO. These drugs include, but are not limited to, the following:
- the anticonvulsants carbamazepine, oxcarbazepine, phenobarbital, phenytoin
- the androgen receptor inhibitor enzalutamide
- the antimycobacterials rifampin, rifapentine
- the cytotoxic agent mitotane
- St. John’s wort (Hypericum perforatum)
Can PIFELTRO be taken with a PPI?
Yes, PIFELTRO can be used with a PPI.
PIFELTRO is contraindicated when co-administered with drugs that are strong cytochrome P450 (CYP)3A enzyme inducers (including the anticonvulsants carbamazepine, oxcarbazepine, phenobarbital, and phenytoin; the androgen receptor inhibitor enzalutamide; the antimycobacterials rifampin and rifapentine; the cytotoxic agent mitotane; and the herbal product St. John’s wort (Hypericum perforatum)), as significant decreases in PIFELTRO plasma concentrations may occur, which may decrease the effectiveness of PIFELTRO.
Select Drug Interactions: Use with efavirenz, etravirine, or nevirapine is not recommended. Increase PIFELTRO dosage to one tablet twice daily when co-administered with rifabutin.
Can PIFELTRO be used in combination with an integrase inhibitor?
PIFELTRO was studied in combination therapy with emtricitibine/tenofovir disoproxil fumarate or abacavir/lamivudine. PIFELTRO is indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection in adult patients with no prior antiretroviral treatment history or those who are virologically suppressed (HIV-1 RNA <50 copies/mL) on a stable antiretroviral regimen with no history of treatment failure and no known substitutions associated resistance to doravirine.
Is there a coupon for PIFELTRO?
Yes. Your eligible, privately insured patients may pay as little as $0 in out-of-pocket costs, up to a total program savings of $6,800.
The coupon is not valid for patients who are uninsured or patients with Medicare or other Government Program insurance. Not all patients are eligible and certain restrictions apply. Tell your eligible, privately insured patients to visit Pifeltro.com to review the Terms and Conditions.
Your patients can visit Pifeltro.com to request a coupon, and if eligible, activate and bring to their pharmacy along with their prescription.