What is mechanism of action?

mechanism of action is Non-Nucleoside Reverse Transcriptase Inhibitors [MoA]

Pifeltro (Doravirine)

Check Drug InteractionsCheck known drug interactions.

Dosage & administration

* Recommended dosage: One tablet taken orally once daily with or without food in adults and pediatric patients weighing at least 35 kg. (

2.1 Recommended Dosage

The recommended dosage regimen of PIFELTRO in adults and pediatric patients weighing at least 35 kg is one 100 mg tablet taken orally once daily with or without food

[see Clinical Pharmacology (12.3)]

)
* Dosage adjustment with rifabutin: One tablet taken twice daily (approximately 12 hours apart). (

2.2 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

[see Drug Interactions (7.1)and Clinical Pharmacology (12.3)].

)

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Pifeltro prescribing information

Warnings and Precautions, Severe Skin Reactions (

5.1 Severe Skin Reactions

Severe skin reactions, including Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN), have been reported during the postmarketing experience with doravirine-containing regimens

[see Adverse Reactions (6.2)].

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.

)

11/2024

PIFELTRO^® is indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection in adults and pediatric patients weighing at least 35 kg:

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

[see

14 CLINICAL STUDIES

14.1 Clinical Trial Results in Adults with No Antiretroviral Treatment History

The efficacy of PIFELTRO is based on the analyses of 96-week data from two randomized, multicenter, double-blind, active controlled Phase 3 trials (DRIVE-FORWARD, NCT02275780 and DRIVE-AHEAD, NCT02403674) in participants living with HIV with no antiretroviral treatment history (n=1494).

In DRIVE-FORWARD, 766 participants were randomized and received at least 1 dose of either PIFELTRO once daily or darunavir 800 mg + ritonavir 100 mg (DRV+r) once daily each in combination with emtricitabine/tenofovir DF (FTC/TDF) or abacavir/lamivudine (ABC/3TC) selected by the investigator. At baseline, the median age of participants was 33 years, 16% were female, 27% were Non-White, 4% had hepatitis B and/or C virus co-infection, 10% had a history of AIDS, 20% had HIV-1 RNA greater than 100,000 copies/mL, 86% had CD4+ T-cell count greater than 200 cells/mm³, 13% received ABC/3TC, and 87% received FTC/TDF; these characteristics were similar between treatment groups.

In DRIVE-AHEAD, 728 participants were randomized and received at least 1 dose of either DELSTRIGO (DOR/3TC/TDF) or EFV 600 mg/FTC 200 mg/TDF 300 mg once daily. At baseline, the median age of participants was 31 years, 15% were female, 52% were Non-White, 3% had hepatitis B or C co-infection, 14% had a history of AIDS, 21% had HIV-1 RNA greater than 100,000 copies/mL, and 88% had CD4+ T-cell count greater than 200 cells/mm³; these characteristics were similar between treatment groups.

Week 96 outcomes for DRIVE-FORWARD and DRIVE-AHEAD are provided in Table 10. Side-by-side tabulation is to simplify presentation; direct comparisons across trials should not be made due to differing trial designs.

In DRIVE-FORWARD, the mean CD4+ T-cell counts in the PIFELTRO and DRV+r groups increased from baseline by 224 and 207 cells/mm³, respectively.

In DRIVE-AHEAD, the mean CD4+ T-cell counts in the DELSTRIGO and EFV/FTC/TDF groups increased from baseline by 238 and 223 cells/mm³, respectively.

Table 10: Virologic Outcome in DRIVE-FORWARD and DRIVE-AHEAD at Week 96 in HIV-1 Adults with No Antiretroviral Treatment History
Outcome	DRIVE-FORWARD		DRIVE-AHEAD
	PIFELTRO + 2 NRTIs Once Daily	DRV+r + 2 NRTIs Once Daily	DELSTRIGO Once Daily	EFV/FTC/TDF Once Daily
	N=383	N=383	N=364	N=364
Note: NRTIs = FTC/TDF or ABC/3TC.
HIV-1 RNA <50 copies/mL	72%	65%	77%	74%
Treatment Differences (95% CI)The 95% CIs for the treatment differences were calculated using stratum-adjusted Mantel-Haenszel method.	7.5% (1.0%, 14.1%)		3.8% (-2.4%, 10.0%)
HIV-1 RNA ≥ 50 copies/mL Includes participants who discontinued study drug or study before Week 96 for lack or loss of efficacy and participants with HIV-1 RNA equal to or above 50 copies/mL in the Week 96 window.	17%	20%	15%	12%
No Virologic Data at Week 96 Window	11%	15%	7%	14%
Discontinued study due to AE or DeathIncludes participants who discontinued because of adverse event (AE) or death if this resulted in no virologic data in the Week 96 window.	2%	4%	3%	8%
Discontinued study for Other ReasonsOther Reasons include: lost to follow-up, non-compliance with study drug, physician decision, pregnancy, protocol deviation, screen failure, withdrawal by participant.	7%	9%	4%	5%
On study but missing data in window	2%	3%	1%	1%
Proportion (%) of Participants With HIV-1 RNA <50 copies/mL at Week 96 by Baseline and Demographic Category
Gender
Male	72% (N = 319)	67% (N = 326)	78% (N = 305)	73% (N = 311)
Female	73% (N = 64)	54% (N = 57)	75% (N = 59)	75% (N = 53)
Race
White	78% (N = 280)	68% (N = 280)	80% (N = 176)	74% (N = 170)
Non-White	58% (N = 103)	57% (N = 102)	76% (N = 188)	74% (N = 194)
EthnicityDoes not include participants whose ethnicity or viral subtypes were unknown.
Hispanic or Latino	76% (N = 93)	63% (N = 86)	81% (N = 126)	77% (N = 119)
Not Hispanic or Latino	71% (N = 284)	66% (N = 290)	76% (N = 238)	72% (N = 239)
NRTI Background Therapy
FTC/TDF	71% (N = 333)	64% (N = 335)	-	-
ABC/3TC	80% (N = 50)	67% (N = 48)	-	-
Baseline HIV-1 RNA (copies/mL)
≤100,000 copies/mL	75% (N = 300)	66% (N = 309)	80% (N = 291)	77% (N = 282)
>100,000 copies/mL	61% (N = 83)	59% (N = 73)	67% (N = 73)	62% (N = 82)
CD4+ T-cell Count (cells/mm³)
≤200 cells/mm³	62% (N = 42)	51% (N = 67)	59% (N = 44)	70% (N = 46)
>200 cells/mm³	74% (N = 341)	68% (N = 316)	80% (N = 320)	74% (N = 318)
Viral Subtype
Subtype B	71% (N = 266)	66% (N = 272)	80% (N = 232)	72% (N = 253)
Subtype Non-B	75% (N = 117)	62% (N = 111)	73% (N = 130)	77% (N = 111)

14.2 Clinical Trial Results in Virologically-Suppressed Adults

The efficacy of switching from a baseline regimen consisting of two NRTIs in combination with a PI plus either ritonavir or cobicistat, or elvitegravir plus cobicistat, or an NNRTI to DELSTRIGO was evaluated in a randomized, open-label trial (DRIVE-SHIFT, NCT02397096), in virologically-suppressed adults living with HIV. Participants must have been virologically-suppressed (HIV-1 RNA < 50 copies/mL) on their baseline regimen for at least 6 months prior to trial entry, with no history of virologic failure. Participants were randomized to either switch to DELSTRIGO at baseline (n = 447, Immediate Switch Group (ISG)), or stay on their baseline regimen until Week 24, at which point they switched to DELSTRIGO (n = 223, Delayed Switch Group (DSG)).

At baseline, the median age of participants was 43 years, 16% were female, and 24% were Non-White, 21% were of Hispanic or Latino ethnicity, 3% had hepatitis B and/or C virus co-infection, 17% had a history of AIDS, 96% had CD4+ T-cell count greater than or equal to 200 cells/mm³, 70% were on a regimen containing a PI plus ritonavir, 24% were on a regimen containing an NNRTI, 6% were on a regimen containing elvitegravir plus cobicistat, and 1% were on a regimen containing a PI plus cobicistat; these characteristics were similar between treatment groups.

Virologic outcome results are shown in Table 11.

Table 11: Virologic Outcomes in DRIVE-SHIFT in HIV-1 Virologically-Suppressed Participants Who Switched to DELSTRIGO
Outcome	DELSTRIGO Once Daily ISG Week 48 N=447	Baseline Regimen DSG Week 24 N=223
HIV-1 RNA ≥ 50 copies/mL Includes participants who discontinued study drug or study before Week 48 for ISG or before Week 24 for DSG for lack or loss of efficacy and participants with HIV-1 RNA ≥50 copies/mL in the Week 48 window for ISG and in the Week 24 window for DSG.	2%	1%
ISG-DSG, Difference (95% CI)The 95% CI for the treatment difference was calculated using stratum-adjusted Mantel-Haenszel method.^,Assessed using a non-inferiority margin of 4%.	0.7% (-1.3%, 2.6%)
HIV-1 RNA <50 copies/mL	91%	95%
No Virologic Data Within the Time Window	8%	4%
Discontinued study due to AE or DeathIncludes participants who discontinued because of adverse event (AE) or death if this resulted in no virologic data on treatment during the specified window.	3%	<1%
Discontinued study for Other ReasonsOther reasons include: lost to follow-up, non-compliance with study drug, physician decision, protocol deviation, withdrawal by participant.	4%	4%
On study but missing data in window	0	0
Proportion (%) of Participants With HIV-1 RNA <50 copies/mL by Baseline and Demographic Category
Age (years)
< 50	90% (N = 320)	95% (N = 157)
≥ 50	94% (N = 127)	94% (N = 66)
Gender
Male	91% (N = 372)	94% (N = 194)
Female	91% (N = 75)	100% (N = 29)
Race
White	90% (N = 344)	95% (N = 168)
Non-White	93% (N = 103)	93% (N = 55)
Ethnicity
Hispanic or Latino	88% (N = 99)	91% (N = 45)
Not Hispanic or Latino	91% (N = 341)	95% (N = 175)
CD4+ T-cell Count (cells/mm³)
<200 cells/mm³	85% (N = 13)	75% (N = 4)
≥200 cells/mm³	91% (N = 426)	95% (N = 216)
Baseline Regimen Baseline Regimen = PI plus either ritonavir or cobicistat (specifically atazanavir, darunavir, or lopinavir), or elvitegravir plus cobicistat, or NNRTI (specifically efavirenz, nevirapine, or rilpivirine), each administered with two NRTIs.
PI plus either ritonavir or cobicistat	90% (N=316)	94% (N=156)
elvitegravir plus cobicistat or NNRTI	93% (N=131)	96% (N=67)

14.3 Clinical Trial Results in Pediatric Participants

The efficacy of DELSTRIGO (DOR/3TC/TDF) was evaluated in cohort 2 of an open-label, single-arm 2-cohort trial in pediatric participants 12 to less than 18 years of age living with HIV (IMPAACT 2014 (Protocol 027), NCT03332095). In cohort 1, virologically-suppressed participants (n=9) received a single 100 mg dose of PIFELTRO followed by intensive PK sampling. In cohort 2, virologically-suppressed participants (n=43) were switched to DELSTRIGO and treatment-naïve participants (n=2) were started on DELSTRIGO.

In cohort 2, at baseline the median age of participants was 15 years (range: 12 to 17), the median weight was 52 kg (range: 45 to 80), 58% were female, 78% were Asian and 22% were Black, and the median CD4+ T-cell count was 713 cells per mm³(range 84 to 1397). After switching to DELSTRIGO, 95% (41/43) of virologically-suppressed participants remained suppressed (HIV-1 RNA <50 copies/mL) at Week 24. One of the two treatment-naïve participants achieved HIV-1 RNA <50 copies/mL at Week 24. The other treatment-naïve participant met the protocol-defined virologic failure criteria (defined as 2 consecutive plasma HIV-1 RNA test results ≥200 copies/mL at or after Week 24) and was evaluated for the development of resistance; no emergence of genotypic or phenotypic resistance to doravirine, lamivudine, or tenofovir was detected.

]

Recommended dosage: One tablet taken orally once daily with or without food in adults and pediatric patients weighing at least 35 kg. (
2.1 Recommended Dosage
The recommended dosage regimen of PIFELTRO in adults and pediatric patients weighing at least 35 kg is one 100 mg tablet taken orally once daily with or without food
[see Clinical Pharmacology (12.3)]
.
)
Dosage adjustment with rifabutin: One tablet taken twice daily (approximately 12 hours apart). (
2.2 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
[see Drug Interactions (7.1)and Clinical Pharmacology (12.3)].
)

Pediatrics: Not recommended for patients weighing less than 35 kg. (
8.4 Pediatric Use
The safety and efficacy of PIFELTRO for the treatment of HIV-1 infection have been established in pediatric patients weighing at least 35 kg
[see Indications and Usage (1)and Dosage and Administration (2.1)].
Use of PIFELTRO in this group is supported by evidence from adequate and well-controlled trials in adults and an open-label trial in virologically-suppressed or treatment-naïve pediatric participants 12 to less than 18 years of age. The safety, efficacy, and exposure of doravirine in these pediatric participants were similar to that in adults
[see Adverse Reactions (6.1), Clinical Pharmacology (12.3), and Clinical Studies (14.3)].
Safety and efficacy of PIFELTRO in pediatric patients weighing less than 35 kg have not been established.
)

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

[see

5.2 Risk of Adverse Reactions or Loss of Virologic Response Due to Drug Interactions

The concomitant use of PIFELTRO and certain other drugs may result in known or potentially significant drug interactions, some of which may lead to loss of therapeutic effect of PIFELTRO and possible development of resistance

[see Dosage and Administration (2.2), Contraindications (4)and Drug Interactions (7.1)].

See Table 6for steps to prevent or manage these possible and known significant drug interactions, including dosing recommendations. Consider the potential for drug interactions prior to and during PIFELTRO therapy, review concomitant medications during PIFELTRO therapy, and monitor for adverse reactions.

7.1 Effect of Other Drugs on PIFELTRO

Co-administration of PIFELTRO with a CYP3A inducer decreases doravirine plasma concentrations, which may reduce PIFELTRO efficacy

[see Contraindications (4), Warnings and Precautions (5.2), and Clinical Pharmacology (12.3)]

. Co-administration of PIFELTRO and drugs that are inhibitors of CYP3A may result in increased plasma concentrations of doravirine.

Table 6 shows significant drug interactions with PIFELTRO.

Table 6: Drug Interactions with PIFELTROThis table is not all inclusive.
Concomitant Drug Class: Drug Name	Effect on Concentration	Clinical Comment
↑ = increase, ↓ = decrease All other drug-drug interactions shown are anticipated based on the known metabolic and elimination pathways.
Androgen Receptors
enzalutamide	↓ doravirine	Co-administration is contraindicated with enzalutamide. At least a 4-week cessation period is recommended prior to initiation of PIFELTRO.
Anticonvulsants
carbamazepine oxcarbazepine phenobarbital phenytoin	↓ doravirine	Co-administration is contraindicated with these anticonvulsants. At least a 4-week cessation period is recommended prior to initiation of PIFELTRO.
Antimycobacterials
rifampinThe interaction between PIFELTRO and the concomitant drug was evaluated in a clinical study. rifapentine	↓ doravirine	Co-administration is contraindicated with rifampin or rifapentine . At least a 4-week cessation period is recommended prior to initiation of PIFELTRO.
rifabutin	↓ doravirine	Increase PIFELTRO dosage to one tablet twice daily when co-administered with rifabutin [see Dosage and Administration (2.2)] .
Cytotoxic Agents
mitotane	↓ doravirine	Co-administration is contraindicated with mitotane. At least a 4-week cessation period is recommended prior to initiation of PIFELTRO.
HIV Antiviral Agents
efavirenz etravirine nevirapine	↓ doravirine	Use with efavirenz, etravirine, or nevirapine is not recommended.
Herbal Products
St. John's wort	↓ doravirine	Co-administration is contraindicated with St. John's wort. At least a 4-week cessation period is recommended prior to initiation of PIFELTRO.

No clinically significant changes in concentration were observed for doravirine when co-administered with the following agents: dolutegravir, TDF, lamivudine, elbasvir and grazoprevir, ledipasvir and sofosbuvir, ritonavir, ketoconazole, aluminum hydroxide/magnesium hydroxide/simethicone containing antacid, pantoprazole, and methadone

[see Clinical Pharmacology (12.3)].

, and

12.3 Pharmacokinetics

Doravirine pharmacokinetics are similar in healthy participants and participants living with HIV. Doravirine pharmacokinetics are provided in Table 7.

Table 7: Pharmacokinetic Properties of Doravirine
Parameter	Doravirine
Abbreviations: AUC=area under the time concentration curve; C_max=maximum concentration; C₂₄=concentration at 24 hours; T_maxtime to C_max; V_dss= volume of distribution at steady state, t_1/2=elimination half-life; CL/F=apparent clearance; CL_renal=apparent renal clearance
General
Steady State Exposure Doravirine 100 mg once daily to participants living with HIV ^,Presented as geometric mean (%CV: geometric coefficient of variation)
AUC_0-24 (mcg∙h/mL)	16.1 (29)
C_max (mcg/mL)	0.962 (19)
C₂₄ (mcg/mL)	0.396 (63)
Time to Steady State (Days)	2
Accumulation Ratio	1.2 to 1.4
Absorption
Absolute Bioavailability	64%
T_max(h)	2
Effect of FoodGeometric mean ratio [high-fat meal/fasting] and (90% confidence interval) for PK parameters. High fat meal is approximately 1,000 kcal, 50% fat. The effect of food is not clinically relevant.
AUC Ratio	1.16 (1.06, 1.26)
C_maxRatio	1.03 (0.89, 1.19)
C₂₄Ratio	1.36 (1.19, 1.55)
Distribution
V_dss(L)Based on IV dose	60.5
Plasma Protein Binding	76%
Elimination
t_1/2(h)	15
CL/F (mL/min)	106 (35.2)
CL_renal(mL/min)	9.3 (18.6)
Metabolism
Primary Pathway(s)	CYP3A
Excretion
Major Route of Elimination	Metabolism
Urine (unchanged)	6%
Biliary/Fecal (unchanged)	Minor

Specific Populations

In adults, no clinically significant difference on the pharmacokinetics of doravirine were observed based on age (18 to 78 years of age), sex, and race/ethnicity, mild to severe renal impairment (creatinine clearance (CLcr) >15 mL/min, estimated by Cockcroft-Gault), or moderate hepatic impairment (Child-Pugh B). The pharmacokinetics of doravirine in patients with end-stage renal disease or undergoing dialysis, or severe hepatic impairment (Child-Pugh C) is unknown.

Patients with Renal Impairment

In a study comparing 8 participants with severe renal impairment to 8 participants without renal impairment, the single dose exposure of doravirine was 43% higher in participants with severe renal impairment. In a population pharmacokinetic analysis, renal function did not have a clinically relevant effect on doravirine pharmacokinetics. Doravirine has not been studied in patients with end-stage renal disease or in patients undergoing dialysis

[see Use in Specific Populations (8.6)]

Patients with Hepatic Impairment

No clinically significant difference in the pharmacokinetics of doravirine was observed in participants with moderate hepatic impairment (Child-Pugh score B) compared to participants without hepatic impairment. Doravirine has not been studied in participants with severe hepatic impairment (Child-Pugh score C)

[see Use in Specific Populations (8.7)]

Pediatric Patients

Mean doravirine exposures were similar in 54 pediatric participants aged 12 to less than 18 years and weighing at least 35 kg who received doravirine or DELSTRIGO in IMPAACT 2014 (Protocol 027) relative to adults following administration of doravirine or DELSTRIGO (Table 8). For pediatric participants weighing ≥ 35 kg and < 45 kg who received doravirine 100 mg or DELSTRIGO, the population pharmacokinetic model-predicted mean C₂₄of doravirine was comparable to that achieved in adults, whereas mean AUC_0-24and C_maxof doravirine were 25% and 36% higher than adult values, respectively. However, the predicted AUC_0-24and C_maxincreases are not considered clinically significant.

Table 8: Steady State Pharmacokinetics for Doravirine Following Administration of Doravirine or DELSTRIGO in Pediatric Participants Living with HIV Aged 12 to Less than 18 Years and Weighing at Least 35 kg
ParameterPresented as geometric mean (%CV: geometric coefficient of variation)	DoravirineFrom population PK analysis (n=53 weighing ≥45 kg, n=1 weighing ≥35 kg to <45 kg)
Abbreviations: AUC=area under the time concentration curve; C_max=maximum concentration; C₂₄=concentration at 24 hours
AUC_0-24 (mcg∙h/mL)	16.4 (24)
C_max (mcg/mL)	1.03 (16)
C₂₄ (mcg/mL)	0.379 (42)

Drug Interaction Studies

Doravirine is primarily metabolized by CYP3A, and drugs that induce or inhibit CYP3A may affect the clearance of doravirine. Co-administration of doravirine and drugs that induce CYP3A may result in decreased plasma concentrations of doravirine. Co-administration of doravirine and drugs that inhibit CYP3A may result in increased plasma concentrations of doravirine.

Doravirine is not likely to have a clinically relevant effect on the exposure of medicinal products metabolized by CYP enzymes. Doravirine did not inhibit major drug metabolizing enzymes

in vitro

, including CYPs 1A2, 2B6, 2C8, 2C9, 2C19, 2D6, 3A4, and UGT1A1 and is not likely to be an inducer of CYP1A2, 2B6, or 3A4. Based on

in vitro

assays, doravirine is not likely to be an inhibitor of OATP1B1, OATP1B3, P-glycoprotein, BSEP, OAT1, OAT3, OCT2, MATE1, and MATE2K. Drug interaction studies were performed with doravirine and other drugs likely to be co-administered or commonly used as probes for pharmacokinetic interactions. The effects of co-administration with other drugs on the exposure (C_max, AUC, and C₂₄) of doravirine are summarized in Table 9. A single doravirine 100 mg dose was administered in these studies unless otherwise noted.

Table 9: Drug Interactions: Changes in Pharmacokinetic Parameter Values of Doravirine in the Presence of Co-administered Drug
Co-administered Drug	Regimen of Co-administered Drug	N	Geometric Mean Ratio (90% CI) of Doravirine Pharmacokinetics with/without Co-administered Drug (No Effect=1.00)
Co-administered Drug	Regimen of Co-administered Drug	N	AUCAUC_0-∞for single-dose, AUC_0-24for once daily.	C_max	C₂₄
CI = confidence interval; QD = once daily; BID = twice daily
Azole Antifungal Agents
ketoconazoleChanges in doravirine pharmacokinetic values are not clinically relevant.	400 mg QD	10	3.06 (2.85, 3.29)	1.25 (1.05, 1.49)	2.75 (2.54, 2.98)
Antimycobacterials
rifampin	600 mg QD	10	0.12 (0.10, 0.15)	0.43 (0.35, 0.52)	0.03 (0.02, 0.04)
rifabutin	300 mg QD	12	0.50 (0.45, 0.55)	0.99 (0.85, 1.15)	0.32 (0.28, 0.35)
rifabutin	300 mg QDDoravirine 100 mg BID resulted in similar pharmacokinetic values when compared to 100 mg QD without rifabutin.	15	1.03 (0.94, 1.14)	0.97 (0.87, 1.08)	0.98 (0.88, 1.10)
HIV Antiviral Agents
ritonavir ^,A single doravirine 50 mg dose (0.5 times the recommended approved dose) was administered.	100 mg BID	8	3.54 (3.04, 4.11)	1.31 (1.17, 1.46)	2.91 (2.33, 3.62)
efavirenz	600 mg QDThe first day following the cessation of efavirenz therapy and initiation of doravirine 100 mg QD.	17	0.38 (0.33, 0.45)	0.65 (0.58, 0.73)	0.15 (0.10, 0.23)
efavirenz	600 mg QD14 days following the cessation of efavirenz therapy and initiation of doravirine 100 mg QD.	17	0.68 (0.58, 0.80)	0.86 (0.77, 0.97)	0.50 (0.39, 0.64)

Based on drug interaction studies conducted with doravirine, no clinically significant drug interactions have been observed following the co-administration of doravirine and the following drugs: dolutegravir, ritonavir, TDF, lamivudine, elbasvir and grazoprevir, ledipasvir and sofosbuvir, ketoconazole, aluminum hydroxide/magnesium hydroxide/simethicone containing antacid, pantoprazole, atorvastatin, an oral contraceptive containing ethinyl estradiol and levonorgestrel, metformin, methadone, and midazolam.

]

. 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)

Pifeltro (Doravirine)

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