Pifeltro

Last updated on RxList: 6/21/2021
Pifeltro Side Effects Center

Medical Editor: John P. Cunha, DO, FACOEP

What Is Pifeltro?

Pifeltro (doravirine) is a non-nucleoside reverse transcriptase inhibitor (NNRTI), is indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection in adult patients with no prior antiretroviral treatment history.

What Are Side Effects of Pifeltro?

Common side effects of Pifeltro include:

  • nausea,
  • dizziness,
  • headache,
  • fatigue,
  • diarrhea,
  • abdominal pain,
  • abnormal dreams, and
  • insomnia.

Dosage for Pifeltro

The recommended dosage of Pifeltro is one tablet taken orally once daily with or without food in adult patients.

What Drugs, Substances, or Supplements Interact with Pifeltro?

Pifeltro may interact with enzalutamide, anticonvulsants, antimycobacterials, mitotane, HIV antivirals, and St. John's wort. Tell your doctor all medications and supplements you use.

Pifeltro During Pregnancy or Breastfeeding

Tell your doctor if you are pregnant or plan to become pregnant before using Pifeltro; it is unknown how it would affect a fetus. There is a pregnancy exposure registry that monitors pregnancy outcomes in individuals exposed to Pifeltro during pregnancy. Breastfeeding while using Pifeltro is not recommended due to the potential for to transmit HIV.

Additional Information

Our Pifeltro (doravirine) Tablets, for Oral Use Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

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Pifeltro Consumer Information

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Doravirine affects your immune system, which may cause certain side effects (even weeks or months after you've taken this medicine). Tell your doctor if you have:

  • signs of a new infection--fever, night sweats, swollen glands, cold sores, cough, wheezing, diarrhea, weight loss;
  • trouble speaking or swallowing, problems with balance or eye movement, weakness or prickly feeling; or
  • swelling in your neck or throat (enlarged thyroid), menstrual changes, impotence.

Common side effects may include:

  • nausea, diarrhea, stomach pain;
  • headache, dizziness;
  • tiredness; or
  • strange dreams.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the entire detailed patient monograph for Pifeltro (Doravirine Tablets)

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Pifeltro Professional Information

SIDE EFFECTS

The following adverse reactions are discussed in other sections of the labeling:

  • Immune Reconstitution Syndrome [see WARNINGS AND PRECAUTIONS]

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Adverse Reactions In Adults With No Antiretroviral Treatment History

The safety assessment of PIFELTRO used in combination with other antiretroviral agents is based on Week 96 data from two Phase 3, randomized, international, multicenter, double-blind, active-controlled trials (DRIVE-FORWARD (Protocol 018) and DRIVE-AHEAD (Protocol 021)).

In DRIVE-FORWARD, 766 adult subjects received either PIFELTRO 100 mg (n=383) or darunavir 800 mg + ritonavir 100 mg (DRV+r) (n=383) once daily, each in combination with emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) or abacavir/lamivudine (ABC/3TC). By Week 96, 2% in the PIFELTRO group and 3% in the DRV+r group had adverse events leading to discontinuation of study medication.

In DRIVE-AHEAD, 728 adult subjects received either DELSTRIGO [doravirine (DOR)/3TC/TDF] (n=364) or efavirenz (EFV)/FTC/TDF once daily (n=364). By Week 96, 3% in the DELSTRIGO group and 7% in the EFV/FTC/TDF group had adverse events leading to discontinuation of study medication.

Adverse reactions reported in greater than or equal to 5% of subjects in any treatment group in DRIVEFORWARD and DRIVE-AHEAD are presented in Table 1.

Table 1: Adverse Reactions* (All Grades) Reported in ≥5%† of Subjects in Any Treatment Group in Adults with No Antiretroviral Treatment History in DRIVE-FORWARD and DRIVE-AHEAD (Week 96)

  DRIVE-FORWARD DRIVE-AHEAD
PIFELTRO +2 NRTIs‡ Once Daily
N=383
DRV+r +2 NRTIs‡ Once Daily
N=383
DELSTRIGO Once Daily
N=364
EFV/FTC/TDF Once Daily
N=364
Nausea 7% 8% 5% 7%
Headache 6% 3% 4% 5%
Fatigue 6% 3% 4% 4%
Diarrhea 6% 13% 4% 6%
Abdominal Pain 5% 2% 1% 2%
Dizziness 3% 2% 7% 32%
Rash 2% 3% 2% 12%
Abnormal Dreams 1% <1% 5% 10%
Insomnia 1% 2% 4% 5%
Somnolence 0% <1% 3% 7%
*Frequencies of adverse reactions are based on all adverse events attributed to trial drugs by the investigator.
†No adverse reactions of Grade 2 or higher (moderate or severe) occurred in ≥ 2% of subjects treated with doravirine.
‡NRTI = nucleoside reverse transcriptase inhibitor.
NRTIs = FTC/TDF or ABC/3TC.
Fatigue: includes fatigue, asthenia, malaise
Abdominal Pain: includes abdominal discomfort, abdominal pain, abdominal pain lower, abdominal pain upper, epigastric discomfort
Rash: includes rash, rash erythematous, rash generalized, rash macular, rash maculo-papular, rash papular, rash pruritic, rash pustular

The majority (77%) of adverse reactions associated with doravirine occurred at severity Grade 1 (mild).

Neuropsychiatric Adverse Events

For DRIVE-AHEAD, the analysis of subjects with neuropsychiatric adverse events by Week 48 is presented in Table 2. The proportion of subjects who reported one or more neuropsychiatric adverse events was 24% and 57% in the DELSTRIGO and EFV/FTC/TDF groups, respectively.

A statistically significantly lower proportion of DELSTRIGO-treated subjects compared to EFV/FTC/TDFtreated subjects reported neuropsychiatric adverse events by Week 48 in the three pre-specified categories of dizziness, sleep disorders and disturbances, and altered sensorium.

Table 2: DRIVE-AHEAD - Analysis of Subjects with Neuropsychiatric Adverse Events* (Week 48)

  DELSTRIGO Once Daily
N=364
EFV/FTC/TDF Once Daily
N=364
Treatment Difference DELSTRIGO - EFV/FTC/TDF Estimate (95% CI)†
Sleep disorders and disturbances‡ 12% 26% -13.5
(-19.1, -7.9)
Dizziness 9% 37% -28.3
(-34.0, -22.5)
Altered sensorium§ 4% 8% -3.8
(-7.6, -0.3)
*All causality and all grade events were included in the analysis.
†The 95% CIs were calculated using Miettinen and Nurminen's method. Categories pre-specified for statistical testing were dizziness (p <0.001), sleep disorders and disturbances (p <0.001), and altered sensorium (p=0.033).
‡Predefined using MedDRA preferred terms, including: abnormal dreams, hyposomnia, initial insomnia, insomnia, nightmare, sleep disorder, somnambulism.
§Predefined using MedDRA preferred terms, including: altered state of consciousness, lethargy, somnolence, syncope.

Neuropsychiatric adverse events in the pre-defined category of depression and suicide/self-injury were reported in 4% and 7% of subjects, in the DELSTRIGO and EFV/FTC/TDF groups, respectively.

In DRIVE-AHEAD through 48 weeks of treatment, the majority of subjects who reported neuropsychiatric adverse events reported events that were mild to moderate in severity (97% [83/86] and 96% [198/207], in the DELSTRIGO and EFV/FTC/TDF groups, respectively) and the majority of subjects reported these events in the first 4 weeks of treatment (72% [62/86] in the DELSTRIGO group and 86% [177/207] in the EFV/FTC/TDF group).

Neuropsychiatric adverse events led to treatment discontinuation in 1% (2/364) and 1% (5/364) of subjects in the DELSTRIGO and EFV/FTC/TDF groups, respectively. The proportion of subjects who reported neuropsychiatric adverse events through Week 4 was 17% (62/364) in the DELSTRIGO group and 49% (177/364) in the EFV/FTC/TDF group. At Week 48, the prevalence of neuropsychiatric adverse events was 12% (44/364) in the DELSTRIGO group and 22% (81/364) in the EFV/FTC/TDF group. At Week 96, the prevalence of neuropsychiatric adverse events was 13% (47/364) in the DELSTRIGO group and 23% (82/364) in the EFV/FTC/TDF group.

Laboratory Abnormalities

The percentages of subjects with selected laboratory abnormalities (that represent a worsening from baseline) who were treated with PIFELTRO or DRV+r in DRIVE-FORWARD, or DELSTRIGO or EFV/FTC/TDF in DRIVE-AHEAD are presented in Table 3.

Table 3: Selected Laboratory Abnormalities Reported in Adult Subjects with No Antiretroviral Treatment History in DRIVE-FORWARD and DRIVE-AHEAD (Week 96)

Laboratory Parameter Preferred Term (Unit)/Limit DRIVE-FORWARD DRIVE-AHEAD
PIFELTRO +2 NRTIs Once Daily
N=383
DRV+r+ 2 NRTIs Once Daily
N=383
DELSTRIGO Once Daily
N=364
EFV/FTC/TDF Once Daily
N=364
Blood Chemistry
Total bilirubin
1.1 - < 1.6 x ULN 6% 2% 5% 0%
1.6 - <2.6 x ULN 2% <1% 2% 0%
≥2.6 x ULN <1% 0% 1% <1%
Creatinine (mg/dL)
>1.3 - 1.8 x ULN or Increase of >0.3
mg/dL above baseline 4% 6% 3% 2%
>1.8 x ULN or Increase of ≥1.5 x above baseline 4% 4% 3% 2%
Aspartate aminotransferase (IU/L)
2.5 - <5.0 x ULN 5% 4% 3% 3%
≥5.0 x ULN 2% 2% 1% 4%
Alanine aminotransferase (IU/L)
2.5 - <5.0 x ULN 4% 2% 4% 4%
≥5.0 x ULN 2% 3% 1% 3%
Alkaline phosphatase (IU/L)
2.5 - <5.0 x ULN <1% 1% <1% 1%
≥5.0 x ULN 0% <1% 0% <1%
Lipase
1.5 - <3.0 x ULN 7% 6% 6% 4%
≥3.0 x ULN 3% 4% 2% 3%
Creatine kinase (IU/L)
6.0 - <10.0 x ULN 3% 3% 3% 3%
≥10.0 x ULN 5% 6% 4% 6%
Cholesterol, fasted (mg/dL)
≥300 mg/dL 0% 1% 1% <1%
LDL cholesterol, fasted (mg/dL)
≥190 mg/dL <1% 4% <1% 2%
Triglycerides, fasted (mg/dL)
≥500 mg/dL 1% 2% 1% 3%
Each subject is only counted once per parameter at the highest toxicity grade. Only subjects with a baseline value and at least one on-treatment value for a given laboratory parameter are included.
ULN = Upper limit of normal range.
Note: NRTIs = FTC/TDF or ABC/3TC.

Change In Lipids From Baseline

For DRIVE-FORWARD and DRIVE-AHEAD, changes from baseline at Week 48 in LDL-cholesterol, nonHDL-cholesterol, total cholesterol, triglycerides, and HDL-cholesterol are shown in Table 4. Changes from baseline at Week 96 were similar to those seen at Week 48.

The LDL and non-HDL comparisons were pre-specified and are summarized in Table 4. The differences were statistically significant, showing superiority for doravirine for both parameters. The clinical benefit of these findings has not been demonstrated.

Table 4: Mean Change from Baseline in Fasting Lipids in Adult Subjects with No Antiretroviral Treatment History in DRIVE-FORWARD and DRIVE-AHEAD (Week 48)

DRIVE-FORWARD
Laboratory Parameter Preferred Term PIFELTRO +2 NRTIs Once Daily
N=320
DRV+r +2 NRTIs Once Daily
N=311
Difference Estimates (95% CI)
Baseline Change Baseline Change
LDL-Cholesterol (mg/dL)* 91.4 -4.6 92.3 9.5 -14.4
(-18.0, -10.8)
Non-HDL Cholesterol (mg/dL)* 113.6 -5.4 114.5 13.7 -19.4
(-23.4, -15.4)
Total Cholesterol (mg/dL)† 157.2 -1.4 157.8 18.0  
Triglycerides (mg/dL)† 111.0 -3.1 113.7 24.5  
HDL-Cholesterol (mg/dL)† 43.6 4.0 43.3 4.3  
DRIVE-AHEAD
Laboratory Parameter Preferred Term DELSTRIGO Once Daily
N=320
EFV/FTC/TDF Once Daily
N=307
Difference Estimates (95% CI)
Baseline Change Baseline Change
LDL-Cholesterol (mg/dL)* 91.7 -2.1 91.3 8.3 -10.2
(-13.8, -6.7)
Non-HDL Cholesterol (mg/dL)* 114.7 -4.1 115.3 12.7 -16.9
(-20.8, -13.0)
Total Cholesterol (mg/dL)† 156.8 -2.2 156.8 21.1  
Triglycerides (mg/dL)† 118.7 -12.0 122.6 21.6  
HDL-Cholesterol (mg/dL)† 42.1 1.8 41.6 8.4  
Subjects on lipid-lowering agents at baseline were excluded from these analyses (in DRIVE-FORWARD: PIFELTRO n=12 and DRV+r n=14; in DRIVE-AHEAD: DELSTRIGO n=15 and EFV/FTC/TDF n=10). Subjects initiating a lipid-lowering agent post-baseline had their last fasted on-treatment value (prior to starting the agent) carried forward (in DRIVE-FORWARD: PIFELTRO n=6 and DRV+r n=4; in DRIVE-AHEAD: DELSTRIGO n=3 and EFV/FTC/TDF n=8).
*p-values for the pre-specified hypothesis testing for treatment difference were <0.0001 in both DRIVE-FORWARD and DRIVEAHEAD.
†Not pre-specified for hypothesis testing.

Adverse Reactions In Virologically-Suppressed Adults

The safety of DELSTRIGO in virologically-suppressed adults was based on Week 48 data from 670 subjects in the DRIVE-SHIFT trial (Protocol 024), a randomized, international, multicenter, open-label trial in which virologically-suppressed subjects were switched from a baseline regimen consisting of two NRTIs in combination with a protease inhibitor (PI) plus either ritonavir or cobicistat, or elvitegravir plus cobicistat, or a non-nucleoside reverse transcriptase inhibitor (NNRTI) to DELSTRIGO. Overall, the safety profile in virologically-suppressed adult subjects was similar to that in subjects with no antiretroviral treatment history.

Laboratory Abnormalities

Serum ALT And AST Elevations

In the DRIVE-SHIFT trial, 22% and 16% of subjects in the immediate switch group experienced ALT and AST elevations greater than 1.25 X ULN, respectively, through 48 weeks on DELSTRIGO. For these ALT and AST elevations, no apparent patterns with regard to time to onset relative to switch were observed. One percent of subjects had ALT or AST elevations greater than 5 X ULN through 48 weeks on DELSTRIGO. The ALT and AST elevations were generally asymptomatic and not associated with bilirubin elevations. In comparison, 4% and 4% of subjects in the delayed switch group experienced ALT and AST elevations of greater than 1.25 X ULN through 24 weeks on their baseline regimen.

Change In Lipids From Baseline

Changes from baseline at Week 24 in LDL-cholesterol, non-HDL-cholesterol, total cholesterol, triglycerides, and HDL-cholesterol in subjects on a PI plus ritonavir-based regimen at baseline are shown in Table 5. The LDL and non-HDL comparisons were pre-specified, and the differences were statistically significant, showing superiority for an immediate switch to DELSTRIGO for both parameters. The clinical benefit of these findings has not been demonstrated.

Table 5: Mean Change from Baseline in Fasting Lipids in Adult Virologically-Suppressed Subjects on a PI plus Ritonavir-based Regimen at Baseline in DRIVE-SHIFT (Week 24)

Laboratory Parameter Preferred Term DELSTRIGO (Week 0-24) Once Daily
N=244
PI+ritonavir (Week 0-24) Once Daily
N=124
Difference Estimates
Baseline Change Baseline Change Difference (95% CI)
LDL-Cholesterol (mg/dL)* 108.7 -16.3 110.5 -2.6 -14.5
(-18.9, -10.1)
Non-HDL Cholesterol (mg/dL)* 138.6 -24.8 138.8 -2.1 -22.8
(-27.9, -17.7)
Total Cholesterol (mg/dL)† 188.5 -26.1 187.4 -0.2  
Triglycerides (mg/dL)† 153.1 -44.4 151.4 -0.4  
HDL-Cholesterol (mg/dL)† 50.0 -1.3 48.5 1.9  
Subjects on lipid-lowering agents at baseline were excluded from these analyses (DELSTRIGO n=26 and PI+ritonavir n=13). Subjects initiating a lipid-lowering agent post-baseline had their last fasted on-treatment value (prior to starting the agent) carried forward (DELSTRIGO n=4 and PI+ritonavir n=2).
*P-value for the pre-specified hypothesis testing for treatment difference was <0.0001.
†Not pre-specified for hypothesis testing.

Read the entire FDA prescribing information for Pifeltro (Doravirine Tablets)

© Pifeltro Patient Information is supplied by Cerner Multum, Inc. and Pifeltro Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.

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