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Expert Medical Perspective: PIFELTRO Video Series

Dr. David Wohl Discusses the Resistance Profile of a Treatment Option for Certain PLWH: Watch Now.

Efficacy and Safety of an HIV-1 Treatment Option

Review Efficacy and Safety Data for an HIV-1 Treatment Option for Certain PLWH

Efficacy and Safety of an HIV-1 Treatment Option

Resistance Profile of an HIV-1 Treatment Option

Review Clinical Trial Data on an ARV Treatment Option for Certain PLWH

Resistance Profile of an HIV-1 Treatment Option

Abbreviations

ARV, antiretroviral; PLWH, persons living with HIV-1

Selected Indication

PIFELTRO® (doravirine) is indicated in combination with other antiretroviral (ARV) agents for the treatment of HIV-1 infection in adult patients with no prior ARV treatment history or to replace the current ARV regimen in those who are virologically suppressed (HIV-1 RNA less than 50 copies per mL) on a stable ARV regimen with no history of treatment failure and no known substitutions associated with resistance to doravirine.

Selected Safety Information

  • 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.
  • Severe skin reactions, including Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN), have been reported during the postmarketing experience with doravirine-containing regimens. Discontinue PIFELTRO, and other medications known to be associated with severe skin reactions, immediately if a painful rash with mucosal involvement or a progressive severe rash develops. Clinical status should be closely monitored, and appropriate therapy should be initiated.
  • 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.
  • 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 participants in the PIFELTRO group and 3% in the darunavir+ritonavir (DRV+r) group had adverse events leading to discontinuation of study medication.
  • By week 96 in DRIVE-AHEAD, 3% of adult participants 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 DOR/3TC/TDF group vs 8.3 mg/dL in the EFV/FTC/TDF group. Non-HDL-C: -4.1 mg/dL in the DOR/3TC/TDF 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 DOR/3TC/TDF group vs -2.6 mg/dL in the PI + ritonavir group. Non-HDL-C: -24.8 mg/dL in the DOR/3TC/TDF 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 participants in the DOR/3TC/TDF group and 26% in the EFV/FTC/TDF group reported neuropsychiatric adverse events of sleep disorders and disturbances; 9% in the DOR/3TC/TDF group and 37% in the EFV/FTC/TDF group reported dizziness; and 4% in the DOR/3TC/TDF group and 8% in the EFV/FTC/TDF group reported altered sensorium.
  • The safety of DOR/3TC/TDF in virologically-suppressed adults was based on week 48 data from participants in the DRIVE-SHIFT trial. Overall, the safety profile in virologically-suppressed adult participants was similar to that in participants with no ARV treatment history.
  • 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.
  • Inform individuals with HIV-1 infection of the potential risks of breastfeeding, including: (1) HIV-1 transmission (in HIV-1–negative infants), (2) developing viral resistance (in HIV-1–positive infants), and (3) serious adverse reactions in a breastfed infant similar to those seen in adults.
  • No dosage adjustment is necessary with patients with mild, moderate, or severe renal impairment. PIFELTRO has not been adequately studied in patients with end-stage renal disease and has not been studied in dialysis patients.

 

Before prescribing PIFELTRO® (doravirine), please read the accompanying Prescribing Information. The Patient Information also is available.

Selected Indication
Selected Safety Information

PIFELTRO® (doravirine) is indicated in combination with other antiretroviral (ARV) agents for the treatment of HIV-1 infection in adult patients with no prior ARV treatment history or to replace the current ARV regimen in those who are virologically suppressed (HIV-1 RNA less than 50 copies per mL) on a stable ARV regimen with no history of treatment failure and no known substitutions associated with resistance to doravirine.

Selected Safety Information

  • 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.
  • Severe skin reactions, including Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN), have been reported during the postmarketing experience with doravirine-containing regimens. Discontinue PIFELTRO, and other medications known to be associated with severe skin reactions, immediately if a painful rash with mucosal involvement or a progressive severe rash develops. Clinical status should be closely monitored, and appropriate therapy should be initiated.
  • 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.
  • 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 participants in the PIFELTRO group and 3% in the darunavir+ritonavir (DRV+r) group had adverse events leading to discontinuation of study medication.
  • By week 96 in DRIVE-AHEAD, 3% of adult participants 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 DOR/3TC/TDF group vs 8.3 mg/dL in the EFV/FTC/TDF group. Non-HDL-C: -4.1 mg/dL in the DOR/3TC/TDF 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 DOR/3TC/TDF group vs -2.6 mg/dL in the PI + ritonavir group. Non-HDL-C: -24.8 mg/dL in the DOR/3TC/TDF 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 participants in the DOR/3TC/TDF group and 26% in the EFV/FTC/TDF group reported neuropsychiatric adverse events of sleep disorders and disturbances; 9% in the DOR/3TC/TDF group and 37% in the EFV/FTC/TDF group reported dizziness; and 4% in the DOR/3TC/TDF group and 8% in the EFV/FTC/TDF group reported altered sensorium.
  • The safety of DOR/3TC/TDF in virologically-suppressed adults was based on week 48 data from participants in the DRIVE-SHIFT trial. Overall, the safety profile in virologically-suppressed adult participants was similar to that in participants with no ARV treatment history.
  • 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.
  • Inform individuals with HIV-1 infection of the potential risks of breastfeeding, including: (1) HIV-1 transmission (in HIV-1–negative infants), (2) developing viral resistance (in HIV-1–positive infants), and (3) serious adverse reactions in a breastfed infant similar to those seen in adults.
  • No dosage adjustment is necessary with patients with mild, moderate, or severe renal impairment. PIFELTRO has not been adequately studied in patients with end-stage renal disease and has not been studied in dialysis patients.

 

Before prescribing PIFELTRO® (doravirine), please read the accompanying Prescribing Information. The Patient Information also is available.