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Drug overview for PIFELTRO (doravirine):
Generic name: doravirine (DOR-a-VIR-een)
Drug class: Antiviral-HIV (Antiretroviral) Nonnucleoside RT Inhibitor
Therapeutic class: Anti-Infective Agents
Doravirine, an antiretroviral agent, is a human immunodeficiency virus (HIV) nonnucleoside reverse transcriptase inhibitor (NNRTI).
No enhanced Uses information available for this drug.
Generic name: doravirine (DOR-a-VIR-een)
Drug class: Antiviral-HIV (Antiretroviral) Nonnucleoside RT Inhibitor
Therapeutic class: Anti-Infective Agents
Doravirine, an antiretroviral agent, is a human immunodeficiency virus (HIV) nonnucleoside reverse transcriptase inhibitor (NNRTI).
No enhanced Uses information available for this drug.
DRUG IMAGES
PIFELTRO 100 MG TABLET
The following indications for PIFELTRO (doravirine) have been approved by the FDA:
Indications:
HIV infection
Professional Synonyms:
Human immunodeficiency virus disease
Human immunodeficiency virus infection
Indications:
HIV infection
Professional Synonyms:
Human immunodeficiency virus disease
Human immunodeficiency virus infection
The following dosing information is available for PIFELTRO (doravirine):
No enhanced Dosing information available for this drug.
Doravirine is administered orally once daily without regard to food. Doravirine must be used in conjunction with other antiretrovirals for the treatment of HIV-1 infection. Single-entity doravirine (Pifeltro(R)) is commercially available as tablets.
Doravirine also is commercially available in fixed-combination tablets containing doravirine, lamivudine, and tenofovir disoproxil fumarate (doravirine/lamivudine/tenofovir DF; Delstrigo(R)). Store doravirine tablets in the original bottle at 20-25degreesC (excursions permitted to 15-30degreesC); protect from moisture and do not remove the desiccant.
Doravirine also is commercially available in fixed-combination tablets containing doravirine, lamivudine, and tenofovir disoproxil fumarate (doravirine/lamivudine/tenofovir DF; Delstrigo(R)). Store doravirine tablets in the original bottle at 20-25degreesC (excursions permitted to 15-30degreesC); protect from moisture and do not remove the desiccant.
| DRUG LABEL | DOSING TYPE | DOSING INSTRUCTIONS |
|---|---|---|
| PIFELTRO 100 MG TABLET | Maintenance | Adults take 1 tablet (100 mg) by oral route once daily at the same time each day |
No generic dosing information available.
The following drug interaction information is available for PIFELTRO (doravirine):
There are 1 contraindications.
These drug combinations generally should not be dispensed or administered to the same patient. A manufacturer label warning that indicates the contraindication warrants inclusion of a drug combination in this category, regardless of clinical evidence or lack of clinical evidence to support the contraindication.
| Drug Interaction | Drug Names |
|---|---|
| Doravirine/Strong CYP3A4 Inducers SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient. MECHANISM OF ACTION: Strong inducers of CYP3A4 are expected to increase the metabolism of doravirine.(1) CLINICAL EFFECTS: Concurrent or recent use of strong inducers of CYP3A4 may result in decreased levels and effectiveness of doravirine.(3) PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks. PATIENT MANAGEMENT: Concurrent administration of strong inducers of CYP3A4 with doravirine is contraindicated. A washout period of 4 weeks for the CYP3A4 inducer is recommended prior to initiation of doravirine.(1) DISCUSSION: Doravirine is metabolized by CYP3A4. Strong inducers of CYP3A4 are expected to reduce doravirine levels, which may lead to loss of response.(1) In a study in 10 subjects, rifampin (600 mg daily), a strong inducer of CYP3A4, decreased the area-under-curve (AUC), maximum concentration (Cmax), and 24 hour concentration (C24) of a single dose of doravirine (100 mg) by 88%, 57%, and 97% respectively.(1) Strong inducers of CYP3A4 include apalutamide, barbiturates, carbamazepine, encorafenib, enzalutamide, fosphenytoin, ivosidenib, lumacaftor, mitotane, oxcarbazepine, phenobarbital, phenytoin, primidone, rifampin, rifapentine, and St. John's wort.(1) |
ASA-BUTALB-CAFFEINE-CODEINE, ASCOMP WITH CODEINE, BRAFTOVI, BUTALB-ACETAMINOPH-CAFF-CODEIN, BUTALBITAL, BUTALBITAL-ACETAMINOPHEN, BUTALBITAL-ACETAMINOPHEN-CAFFE, BUTALBITAL-ASPIRIN-CAFFEINE, CARBAMAZEPINE, CARBAMAZEPINE ER, CARBATROL, CEREBYX, DILANTIN, DILANTIN-125, DONNATAL, EPITOL, EQUETRO, ERLEADA, FIORICET, FIORICET WITH CODEINE, FOSPHENYTOIN SODIUM, LYSODREN, MITOTANE, MYSOLINE, ORKAMBI, OXCARBAZEPINE, OXCARBAZEPINE ER, OXTELLAR XR, PENTOBARBITAL SODIUM, PHENOBARBITAL, PHENOBARBITAL SODIUM, PHENOBARBITAL-BELLADONNA, PHENOBARBITAL-HYOSC-ATROP-SCOP, PHENOHYTRO, PHENYTEK, PHENYTOIN, PHENYTOIN SODIUM, PHENYTOIN SODIUM EXTENDED, PRIFTIN, PRIMIDONE, RIFADIN, RIFAMPIN, SEZABY, TEGRETOL, TEGRETOL XR, TENCON, TIBSOVO, TRILEPTAL, XTANDI |
There are 6 severe interactions.
These drug interactions can produce serious consequences in most patients. Actions required for severe interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration scheduling, and providing additional patient monitoring. Review the full interaction monograph for more information.
| Drug Interaction | Drug Names |
|---|---|
| Doravirine/Rifabutin SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Rifabutin, an inducer of CYP3A4, is expected to increase the metabolism of doravirine.(1) CLINICAL EFFECTS: Concurrent or recent use of rifabutin may result in decreased levels and effectiveness of doravirine.(3) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: If concurrent therapy is necessary, increase doravirine dosage to one tablet twice daily for the duration of rifabutin coadministration.(1) DISCUSSION: Doravirine is metabolized by CYP3A4. Moderate inducers of CYP3A4 are expected to reduce doravirine levels, which may lead to loss of response.(1) In a study in 12 subjects, rifabutin (300 mg daily), a moderate inducer of CYP3A4, decreased the area-under-curve (AUC) and 24 hour concentration (C24) of a single dose of doravirine (100 mg) by 50% and 68%, respectively.(1) |
RIFABUTIN, TALICIA |
| Doravirine/Efavirenz;Etravirine;Nevirapine SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Efavirenz, etravirine, and nevirapine may induce the metabolism of doravirine via CYP3A4.(1) CLINICAL EFFECTS: Concurrent use of efavirenz, etravirine, or nevirapine may result in subtherapeutic levels of doravirine.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Coadministration of doravirine with efavirenz, etravirine, or nevirapine is not recommended.(1) DISCUSSION: In a study in 17 healthy subjects, coadministration of efavirenz (600 mg daily) with a single dose of doravirine (100 mg) decreased doravirine's area-under-curve (AUC), maximum concentration (Cmax), and 24 hour concentration (C24) by 62%, 35%, and 85%, respectively.(1) |
EFAVIRENZ, EFAVIRENZ-EMTRIC-TENOFOV DISOP, EFAVIRENZ-LAMIVU-TENOFOV DISOP, ETRAVIRINE, INTELENCE, NEVIRAPINE, NEVIRAPINE ER, SYMFI, SYMFI LO |
| Betibeglogene Autotemcel/Anti-Retrovirals; Hydroxyurea SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Betibeglogene autotemcel is prepared from apheresed cells that are transduced with a replication defective, self-inactivating lentiviral vector. Antiretrovirals may interfere with the manufacturing of apheresed cells. Hydroxyurea may interfere with hematopoietic stem cell (HSC) mobilization of CD34+ cells.(1) CLINICAL EFFECTS: Use of hydroxyurea before mobilization may result in unsuccessful stem cell mobilization. Use of antiretrovirals before mobilization and apheresis may interfere with the production of betibeglogene autotemcel. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Discontinue antiretrovirals and hydroxyurea for at least one month prior to mobilization and until all cycles of apheresis are completed. If a patient requires antiretrovirals for HIV prophylaxis, then confirm a negative HIV test before beginning mobilization and apheresis of CD34+ cells. DISCUSSION: Antiretroviral medications and hydroxyurea may interfere with the manufacturing of betibeglogene autotemcel therapy.(1) |
ZYNTEGLO |
| Elivaldogene Autotemcel/Anti-Retrovirals SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Elivaldogene autotemcel is prepared from apheresed cells that are transduced with a replication defective, self-inactivating lentiviral vector. Antiretrovirals may interfere with the manufacturing of apheresed cells. CLINICAL EFFECTS: Use of antiretrovirals before mobilization and apheresis may interfere with the production of elivaldogene autotemcel. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Discontinue antiretrovirals for at least one month prior to mobilization and until all cycles of apheresis are completed. If a patient requires antiretrovirals for HIV prophylaxis, then confirm a negative HIV test before beginning mobilization and apheresis of CD34+ cells. DISCUSSION: Antiretroviral medications may interfere with the manufacturing of elivaldogene autotemcel therapy.(1) |
SKYSONA |
| Lovotibeglogene Autotemcel/Anti-Retrovirals SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Lovotibeglogene autotemcel is prepared from apheresed cells that are transduced with a replication defective, self-inactivating lentiviral vector. Antiretrovirals may interfere with the manufacturing of apheresed cells. CLINICAL EFFECTS: Use of antiretrovirals before mobilization and apheresis may interfere with the production of lovotibeglogene autotemcel.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Discontinue antiretrovirals for at least one month prior to mobilization and until all cycles of apheresis are completed.(1) There are some long-acting antiretroviral medications that may require a longer duration of discontinuation for elimination of the medication. If a patient is taking anti-retrovirals for HIV prophylaxis, confirm a negative test for HIV before beginning mobilization and apheresis of CD34+ cells.(1) DISCUSSION: Antiretroviral medications may interfere with the manufacturing of lovotibeglogene autotemcel therapy.(1) |
LYFGENIA |
| Atidarsagene Autotemcel/Anti-Retrovirals SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Atidarsagene autotemcel is prepared from apheresed cells that are transduced with a replication defective, self-inactivating lentiviral vector. Antiretrovirals may interfere with the manufacturing of apheresed cells. CLINICAL EFFECTS: Use of antiretrovirals before mobilization and apheresis may interfere with the production of atidarsagene autotemcel. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Discontinue antiretrovirals for at least one month prior to mobilization (or the expected duration of time needed for elimination of the medication) until all cycles of apheresis are completed. If a patient requires antiretrovirals for HIV prophylaxis, then confirm a negative HIV test before beginning mobilization and apheresis of CD34+ cells. DISCUSSION: Antiretroviral medications may interfere with the manufacturing of atidarsagene autotemcel therapy.(1) |
LENMELDY |
There are 1 moderate interactions.
The clinician should assess the patient’s characteristics and take action as needed. Actions required for moderate interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration.
| Drug Interaction | Drug Names |
|---|---|
| Doravirine/Tecovirimat SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Tecovirimat may induce the metabolism of doravirine via CYP3A4.(1-4) CLINICAL EFFECTS: Concurrent or recent use of tecovirimat may result in decreased levels and effectiveness of doravirine, as well as the development of resistance.(1-4) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Coadministration of doravirine with tecovirimat should be approached with caution. Some experts state that dose adjustment of either drug is not necessary while others suggest the following dosage change: For adult and pediatric patients weighing at least 35 kg, consider increasing doravirine to 100 mg twice daily during treatment with tecovirimat and for approximately 2 weeks after the end of treatment.(1-4) DISCUSSION: In a study in 17 healthy subjects, coadministration of efavirenz (600 mg daily) with a single dose of doravirine (100 mg) decreased doravirine's area-under-curve (AUC), maximum concentration (Cmax), and 24 hour concentration (C24) by 62%, 35%, and 85%, respectively.(1) In a pharmacokinetic study, tecovirimat decreased the Cmax and AUC of midazolam by 39% and 32%, respectively.(2-3) |
TPOXX (NATIONAL STOCKPILE) |
The following contraindication information is available for PIFELTRO (doravirine):
Drug contraindication overview.
*Concomitant use of doravirine and potent inducers of cytochrome P-450 (CYP) isoenzyme 3A (e.g., carbamazepine, oxcarbazepine, phenobarbital, phenytoin, enzalutamide, rifampin, rifapentine, mitotane, St. John's wort (Hypericum perforatum)) is contraindicated. Concomitant use with such drugs may result in substantially decreased doravirine plasma concentrations and may decrease the effectiveness of doravirine.
*Concomitant use of doravirine and potent inducers of cytochrome P-450 (CYP) isoenzyme 3A (e.g., carbamazepine, oxcarbazepine, phenobarbital, phenytoin, enzalutamide, rifampin, rifapentine, mitotane, St. John's wort (Hypericum perforatum)) is contraindicated. Concomitant use with such drugs may result in substantially decreased doravirine plasma concentrations and may decrease the effectiveness of doravirine.
There are 1 contraindications.
Absolute contraindication.
| Contraindication List |
|---|
| Lactation |
There are 0 severe contraindications.
There are 0 moderate contraindications.
The following adverse reaction information is available for PIFELTRO (doravirine):
Adverse reaction overview.
The most common adverse effects of doravirine (>=5%; all grades) include nausea, dizziness, headache, fatigue, diarrhea, abdominal pain, and abnormal dreams.
The most common adverse effects of doravirine (>=5%; all grades) include nausea, dizziness, headache, fatigue, diarrhea, abdominal pain, and abnormal dreams.
There are 9 severe adverse reactions.
| More Frequent | Less Frequent |
|---|---|
| None. |
Hyperbilirubinemia Increased alanine transaminase Increased aspartate transaminase |
| Rare/Very Rare |
|---|
|
Autoimmune hepatitis Graves' disease Guillain-barre syndrome Polymyositis Stevens-johnson syndrome Toxic epidermal necrolysis |
There are 13 less severe adverse reactions.
| More Frequent | Less Frequent |
|---|---|
|
Acute abdominal pain Diarrhea Dizziness Dream disorder Fatigue Headache disorder Nausea Sleep disorder |
Altered consciousness Drowsy Lethargy Skin rash Syncope |
| Rare/Very Rare |
|---|
| None. |
The following precautions are available for PIFELTRO (doravirine):
Safety and efficacy of doravirine have been established in pediatric patients weighing >=35 kg. The use of doravirine in pediatric patients with HIV infection weighing >=35 kg is supported by well-controlled studies in adults and an additional open-label study in antiretroviral naive and experienced pediatric patients 12 to <18 years of age. The safety, efficacy, and pharmacokinetics of doravirine in this patient population were similar to that in adults.
The safety and efficacy of doravirine have not been established in pediatric patients weighing <35 kg. In pediatric patients weighing at least 35 kg and less than 45 kg receiving doravirine 100 mg daily, AUC and peak plasma concentrations were 25 and 36% higher, respectively, compared to adults; however, these differences are not considered clinically important.
Contraindicated
Severe Precaution
Management or Monitoring Precaution
The safety and efficacy of doravirine have not been established in pediatric patients weighing <35 kg. In pediatric patients weighing at least 35 kg and less than 45 kg receiving doravirine 100 mg daily, AUC and peak plasma concentrations were 25 and 36% higher, respectively, compared to adults; however, these differences are not considered clinically important.
Contraindicated
| None |
Severe Precaution
| None |
Management or Monitoring Precaution
| None |
Antiretroviral Pregnancy Registry at 800-258-4263 or https://www.apregistry.com/.
Human data are not adequate to establish whether or not doravirine poses a risk to pregnancy outcomes. In animal reproduction studies, no adverse developmental effects were observed when doravirine was administered to rabbits or rats at exposures that were 8 or 9 times higher, respectively, than human exposures at the recommended human dosage. In rabbits and rats, doravirine crossed the placenta resulting in fetal plasma concentrations up to 40 and 52%, respectively, of maternal concentrations observed on gestation day 20.
Human data are not adequate to establish whether or not doravirine poses a risk to pregnancy outcomes. In animal reproduction studies, no adverse developmental effects were observed when doravirine was administered to rabbits or rats at exposures that were 8 or 9 times higher, respectively, than human exposures at the recommended human dosage. In rabbits and rats, doravirine crossed the placenta resulting in fetal plasma concentrations up to 40 and 52%, respectively, of maternal concentrations observed on gestation day 20.
It is not known whether doravirine is distributed into human milk, affects human milk production, or affects the breast-fed infant. Doravirine was distributed into the milk of lactating rats following oral administration (milk concentrations were approximately 1.5 times higher than maternal plasma concentrations at 2 hours after a dose on lactation day 14). The HHS perinatal HIV transmission guideline provides updated recommendations on infant feeding.
The guideline states that patients with HIV should receive evidence-based, patient-centered counseling to support shared decision making about infant feeding. During counseling, patients should be informed that feeding with appropriate formula or pasteurized donor human milk from a milk bank eliminates the risk of postnatal HIV transmission to the infant. Additionally, achieving and maintaining viral suppression with antiretroviral therapy during pregnancy and postpartum reduces the risk of breastfeeding HIV transmission to <1%, but does not completely eliminate the risk. Replacement feeding with formula or banked pasteurized donor milk is recommended when patients with HIV are not on antiretroviral therapy and/or do not have a suppressed viral load during pregnancy (at a minimum throughout the third trimester), as well as at delivery.
The guideline states that patients with HIV should receive evidence-based, patient-centered counseling to support shared decision making about infant feeding. During counseling, patients should be informed that feeding with appropriate formula or pasteurized donor human milk from a milk bank eliminates the risk of postnatal HIV transmission to the infant. Additionally, achieving and maintaining viral suppression with antiretroviral therapy during pregnancy and postpartum reduces the risk of breastfeeding HIV transmission to <1%, but does not completely eliminate the risk. Replacement feeding with formula or banked pasteurized donor milk is recommended when patients with HIV are not on antiretroviral therapy and/or do not have a suppressed viral load during pregnancy (at a minimum throughout the third trimester), as well as at delivery.
Experience in patients 65 years of age and older is insufficient to determine whether they respond differently to doravirine than younger adults. Doravirine should be used with caution in geriatric patients because of age-related decreases in hepatic, renal, and/or cardiac function and potential for concomitant disease and drug therapy. The pharmacokinetics of doravirine in adults are not substantially affected by age in those 18-78 years of age.
The following prioritized warning is available for PIFELTRO (doravirine):
No warning message for this drug.
No warning message for this drug.
The following icd codes are available for PIFELTRO (doravirine)'s list of indications:
| HIV infection | |
| B20 | Human immunodeficiency virus [HIv] disease |
| B97.35 | Human immunodeficiency virus, type 2 [HIV 2] as the cause of diseases classified elsewhere |
| O98.7 | Human immunodeficiency virus [HIv] disease complicating pregnancy, childbirth and the puerperium |
| O98.71 | Human immunodeficiency virus [HIv] disease complicating pregnancy |
| O98.711 | Human immunodeficiency virus [HIv] disease complicating pregnancy, first trimester |
| O98.712 | Human immunodeficiency virus [HIv] disease complicating pregnancy, second trimester |
| O98.713 | Human immunodeficiency virus [HIv] disease complicating pregnancy, third trimester |
| O98.719 | Human immunodeficiency virus [HIv] disease complicating pregnancy, unspecified trimester |
| O98.72 | Human immunodeficiency virus [HIv] disease complicating childbirth |
| O98.73 | Human immunodeficiency virus [HIv] disease complicating the puerperium |
| Z21 | Asymptomatic human immunodeficiency virus [HIv] infection status |
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