Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Pifeltro: 100 mg
Pharmacology
Mechanism of Action
Doravirine is a pyridinone non-nucleoside reverse transcriptase inhibitor that inhibits HIV-1 replication by noncompetitive inhibition of HIV-1 reverse transcriptase.
Pharmacokinetics/Pharmacodynamics
Distribution
Vdss: 60.5 L
Metabolism
Primarily metabolized by CYP3A
Excretion
Urine (6% [unchanged drug]); feces (minor [unchanged drug])
Time to Peak
2 hours
Half-Life Elimination
15 hours
Protein Binding
76%
Use: Labeled Indications
HIV-1 infection, treatment: Treatment of HIV-1 infection in combination with other antiretroviral agents 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 <50 copies per mL) on a stable antiretroviral regimen with no history of treatment failure and no known substitutions associated with resistance to doravirine.
Contraindications
Concurrent administration of strong CYP3A inducers, including, but not limited to: Carbamazepine, oxcarbazepine, phenobarbital, phenytoin, enzalutamide, rifampin, rifapentine, mitotane, St John's wort
Canadian labeling: Additional contraindications (not in US labeling): Hypersensitivity to doravirine or any component of the formulation.
Dosage and Administration
Dosing: Adult
HIV-1 infection, treatment: Oral: 100 mg once daily, in combination with other antiretroviral agents
Dosage adjustment for rifabutin coadministration: Increase doravirine to 100 mg twice daily (~12 hours apart) for the duration of rifabutin coadministration.
Dosing: Geriatric
Refer to adult dosing.
Administration
Oral: Administer with or without food
Storage
Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Store in the original bottle; protect from moisture. Do not remove desiccant.
Drug Interactions
Bosentan: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy
CYP3A4 Inducers (Moderate): May decrease the serum concentration of Doravirine. Monitor therapy
CYP3A4 Inducers (Strong): May decrease the serum concentration of Doravirine. Avoid combination
Dabrafenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Consider therapy modification
Deferasirox: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy
Efavirenz: May decrease the serum concentration of Doravirine. Avoid combination
Erdafitinib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy
Ergonovine: Reverse Transcriptase Inhibitors (Non-Nucleoside) may increase the serum concentration of Ergonovine. Specifically, this would be most likely with delavrdine, while other Non-Nucleoside Reverse Transcriptase Inhibitors may be more likely to decrease the concentration of Ergonovine. Avoid combination
Etravirine: May decrease the serum concentration of Doravirine. Avoid combination
Ivosidenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy
Levomethadone: Reverse Transcriptase Inhibitors (Non-Nucleoside) may decrease the serum concentration of Levomethadone. Management: Levomethadone dosage adjustments will likely be required with efavirenz and nevirapine, and may be necessary with rilpivirine as well. Monitor therapy
Lorlatinib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Avoid concurrent use of lorlatinib with any CYP3A4 substrates for which a minimal decrease in serum concentrations of the CYP3A4 substrate could lead to therapeutic failure and serious clinical consequences. Consider therapy modification
Methadone: Reverse Transcriptase Inhibitors (Non-Nucleoside) may increase the metabolism of Methadone. Management: Methadone dosage adjustments will likely be required with efavirenz and nevirapine, and may be necessary with rilpivirine as well. Monitor therapy
Nevirapine: May decrease the serum concentration of Doravirine. Avoid combination
Orlistat: May decrease the serum concentration of Antiretroviral Agents. Monitor therapy
OXcarbazepine: May decrease the serum concentration of Doravirine. Avoid combination
Rifabutin: May decrease the serum concentration of Doravirine. Management: Increase doravirine dose to 1 tablet (100 mg) twice daily when combined with rifabutin. If taking the combination product doravirine/lamivudine/tenofovir, an additional tablet of doravirine (100 mg) should be given 12 hours after the combination product. Consider therapy modification
Rifapentine: May decrease the serum concentration of Doravirine. Avoid combination
Rilpivirine: Reverse Transcriptase Inhibitors (Non-Nucleoside) may increase the serum concentration of Rilpivirine. This mechanism applies to coadministration of delavirdine. Reverse Transcriptase Inhibitors (Non-Nucleoside) may decrease the serum concentration of Rilpivirine. This mechanism applies to coadministration of efavirenz, etravirine, and nevirapine. Avoid combination
Sarilumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy
Siltuximab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy
St John's Wort: May decrease the serum concentration of Doravirine. Avoid combination
Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy
Voriconazole: Reverse Transcriptase Inhibitors (Non-Nucleoside) may decrease the serum concentration of Voriconazole. Voriconazole may increase the serum concentration of Reverse Transcriptase Inhibitors (Non-Nucleoside). Management: Consider avoiding when possible. Use efavirenz with voriconazole only if voriconazole is dosed at 400 mg every 12 hours and efavirenz is dosed at 300 mg daily (adult doses) throughout therapy. Avoid Atripla (efavirenz/emtricitabine/tenofovir). Consider therapy modification
Adverse Reactions
Incidences reflect adverse reactions that occur with combination therapy.
1% to 10%:
Cardiovascular: Increased serum creatine kinase (3% to 5%)
Central nervous system: Fatigue (6%), headache (6%), dizziness (3%), abnormal dreams (1%), insomnia (1%)
Dermatologic: Skin rash (2%)
Endocrine & metabolic: Increased serum triglycerides (1%)
Gastrointestinal: Nausea (7%), increased serum lipase (3% to 7%), diarrhea (6%), abdominal pain (5%)
Hepatic: Increased serum bilirubin (≤6%), increased serum aspartate aminotransferase (2% to 5%), increased serum alanine aminotransferase (2% to 4%)
Renal: Increased serum creatinine (4%)
<1%, postmarketing, and/or case reports: Increased LDL cholesterol, increased serum alkaline phosphatase
Warnings/Precautions
Concerns related to adverse effects:
- Immune reconstitution syndrome: Patients may develop immune reconstitution syndrome resulting in the occurrence of an inflammatory response to an indolent or residual opportunistic infection during initial HIV treatment or activation of autoimmune disorders (eg, Graves disease, polymyositis, Guillain-Barré syndrome, autoimmune hepatitis) later in therapy; further evaluation and treatment may be required.
Concurrent drug therapy issues:
- Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
Monitoring Parameters
Viral load, CD4 count
Pregnancy
Pregnancy Considerations
Data collected by the antiretroviral registry related to the use of doravirine in pregnancy are insufficient to evaluate teratogenicity.
Maternal antiretroviral therapy (ART) may be associated with adverse pregnancy outcomes including preterm delivery, stillbirth, low birth weight, and small for gestational age infants. Actual risks may be influenced by maternal factors, such as disease severity, gestational age at initiation of therapy, and specific ART regimen, therefore close fetal monitoring is recommended. Because there is clear benefit to appropriate treatment, maternal ART should not be withheld due to concerns for adverse neonatal outcomes. Long-term follow-up is recommended for all infants exposed to antiretroviral medications; children without HIV but who were exposed to ART in utero and develop significant organ system abnormalities of unknown etiology (particularly of the CNS or heart) should be evaluated for potential mitochondrial dysfunction. Hypersensitivity reactions (including hepatic toxicity and rash) are more common in women on NNRTI therapy; it is not known if pregnancy increases this risk.
The Health and Human Services (HHS) perinatal HIV guidelines note data are insufficient to recommend doravirine for pregnant females living with HIV who are antiretroviral naive, who have had ART therapy in the past but are restarting, who require a new ART regimen (due to poor tolerance or poor virologic response of current regimen), who are not yet pregnant but are trying to conceive, or who become pregnant during therapy. Pharmacokinetic studies of doravirine are not available to make dosing recommendations for pregnant females.
In general, ART is recommended for all pregnant females living with HIV to keep the viral load below the limit of detection and reduce the risk of perinatal transmission. Therapy should be individualized following a discussion of the potential risks and benefits of treatment during pregnancy. Monitoring of pregnant females is more frequent than in nonpregnant adults. ART should be continued postpartum for all females living with HIV and can be modified after delivery.
Health care providers are encouraged to enroll pregnant females exposed to antiretroviral medications as early in pregnancy as possible in the Antiretroviral Pregnancy Registry (1-800-258-4263 or http://www.APRegistry.com). Health care providers caring for pregnant females living with HIV and their infants may contact the National Perinatal HIV Hotline (1-888-448-8765) for clinical consultation (HHS [perinatal] 2019).
Patient Education
- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Patient may experience nausea, dizziness, nightmares, trouble sleeping, diarrhea, abdominal pain, headache, or loss of strength and energy. Have patient report immediately to prescriber signs of infection (HCAHPS).
- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.
