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.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Mild, moderate, or severe impairment: No dosage adjustment necessary.
ESRD on hemodialysis: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Mild (Child-Pugh class A) or moderate (Child-Pugh class B) impairment: No dosage adjustment necessary.
Severe impairment: (Child-Pugh class C): There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
(For additional information see "Doravirine: Pediatric drug information")
Note: Gene mutation and antiretroviral (ARV) resistance patterns should be evaluated (refer to https://www.iasusa.org/ for more information) when necessary.
HIV-1 infection, treatment: Note: Use in combination with other ARV agents:
Children and Adolescents weighing ≥35 kg: Oral: 100 mg once daily.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Altered kidney function:
Children and Adolescents weighing ≥35 kg:
Mild, moderate, or severe impairment: No dosage adjustment necessary.
End-stage renal disease (ESRD) on hemodialysis: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Children and Adolescents weighing ≥35 kg:
Mild (Child-Pugh class A) or moderate (Child-Pugh class B) impairment: No dosage adjustment necessary.
Severe impairment: (Child-Pugh class C): There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Refer to adult dosing.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Pifeltro: 100 mg
No
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Pifeltro: 100 mg
Oral: Administer with or without food
Oral: Administer with or without food.
HIV-1 infection, treatment: Treatment of HIV-1 infection in combination with other antiretroviral agents in pediatric patients ≥35 kg and adults 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.
Doravirine may be confused with Dovato
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. 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
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.
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.
Substrate of CYP3A4 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Betibeglogene Autotemcel: Antiretroviral Agents may diminish the therapeutic effect of Betibeglogene Autotemcel. Risk X: Avoid combination
CYP3A4 Inducers (Moderate): May decrease the serum concentration of Doravirine. Risk C: Monitor therapy
CYP3A4 Inducers (Strong): May decrease the serum concentration of Doravirine. Risk X: Avoid combination
Elivaldogene Autotemcel: Antiretroviral Agents may diminish the therapeutic effect of Elivaldogene Autotemcel. Management: Avoid use of antiretroviral medications for at least one month, or for the amount of time required for elimination of the retroviral medication, prior to stem cell mobilization and until the all apheresis cycles are finished Risk X: Avoid combination
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. Risk X: Avoid combination
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. Risk C: Monitor therapy
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. Risk C: Monitor therapy
Orlistat: May decrease the serum concentration of Antiretroviral Agents. Risk C: Monitor therapy
OXcarbazepine: May decrease the serum concentration of Doravirine. Risk X: Avoid combination
Reverse Transcriptase Inhibitors (Non-Nucleoside): May enhance the adverse/toxic effect of other Reverse Transcriptase Inhibitors (Non-Nucleoside). Reverse Transcriptase Inhibitors (Non-Nucleoside) may decrease the serum concentration of other Reverse Transcriptase Inhibitors (Non-Nucleoside). Specifically, efavirenz and nevirapine may decrease the serum concentrations of other non-nucleoside reverse transcriptase inhibitors. Reverse Transcriptase Inhibitors (Non-Nucleoside) may increase the serum concentration of other Reverse Transcriptase Inhibitors (Non-Nucleoside). Specifically, delavirdine may increase the serum concentration of etravirine. Risk X: 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. Risk D: Consider therapy modification
Rifapentine: May decrease the serum concentration of Doravirine. Risk X: Avoid combination
St John's Wort: May decrease the serum concentration of Doravirine. Risk X: Avoid combination
The Health and Human Services (HHS) perinatal HIV guidelines note data are insufficient to recommend doravirine for patients with HIV infection who are not yet pregnant but are trying to conceive.
Viral suppression sustained below the limits of detection with antiretroviral therapy (ART) and modification of therapy (if needed) is recommended in all patients with HIV infection who are planning a pregnancy. Optimization of the health of the person who will become pregnant and a discussion of the potential risks and benefits of ART during pregnancy is also recommended prior to conception. In most cases, recommendations from the HHS perinatal HIV guidelines (based on data obtained from cisgender women) can be applied to transgender and gender diverse people assigned female sex at birth.
Health care providers caring for couples planning a pregnancy when one or both partners are diagnosed with HIV infection may contact the National Perinatal HIV Hotline (1-888-448-8765) for clinical consultation (HHS [perinatal] 2021).
Based on a placental perfusion study, doravirine crosses the placenta.
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 not diagnosed with HIV infection but who were exposed to ART in utero or as a neonate and develop significant organ system abnormalities of unknown etiology (particularly of the CNS or heart) should be evaluated for potential metabolic dysfunction.
The Health and Human Services (HHS) perinatal HIV guidelines note data are insufficient to recommend doravirine for pregnant patients with HIV infection 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), or who become pregnant during therapy. If continued in patients who are virologically suppressed, frequent viral load monitoring (every 1 to 2 months) is recommended.
Pharmacokinetic studies of doravirine are not available to make dosing recommendations for patients who are pregnant.
ART is recommended for all pregnant people with HIV infection to maximize their health, maintain 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. Patients on fully suppressive regimens prior to pregnancy generally may continue the same regimen considering known pregnancy outcomes and pharmacokinetic data. Monitoring of patients who are pregnant is more frequent than in patients who are not pregnant. ART initiated during pregnancy can be modified after delivery. In most cases, recommendations from the HHS perinatal HIV guidelines (based on data obtained from cisgender women) can be applied to transgender and gender diverse people assigned female sex at birth.
Data collection to monitor pregnancy and infant outcomes following exposure to ART is ongoing. Health care providers are encouraged to enroll patients who are pregnant exposed to antiretroviral medications as early in pregnancy as possible in the Antiretroviral Pregnancy Registry (1-800-258-4263 or www.APRegistry.com).
Health care providers caring for pregnant patients with HIV infection and their infants may contact the National Perinatal HIV Hotline (1-888-448-8765) for clinical consultation (HHS [perinatal] 2021).
It is not known if doravirine is present in breast milk.
Maternal or infant antiretroviral therapy does not completely eliminate the risk of postnatal HIV transmission. In addition, multiclass-resistant virus has been detected in breastfeeding infants despite maternal therapy. In the United States, where formula is usually accessible, affordable, safe, and sustainable, and the risk of infant mortality due to diarrhea and respiratory infections is low, the Health and Human Services (HHS) perinatal HIV guidelines do not recommend breastfeeding for patients with HIV infection when safer infant feeding options are available.
Information is available for counseling and managing patients with HIV infection who are considering breastfeeding (1-888-448-8765). In most cases, recommendations from the HHS perinatal HIV guidelines (based on data obtained from cisgender women) can be applied to transgender and gender diverse people assigned female sex at birth (HHS [perinatal] 2021).
Viral load, CD4 count
Doravirine is a pyridinone non-nucleoside reverse transcriptase inhibitor that inhibits HIV-1 replication by noncompetitive inhibition of HIV-1 reverse transcriptase.
Distribution: Vdss: 60.5 L
Protein binding: 76%
Metabolism: Primarily metabolized by CYP3A
Bioavailability: 64%
Half-life elimination: 15 hours
Time to peak: 2 hours
Excretion: Urine (6% [unchanged drug]); feces (minor [unchanged drug])
Pediatric: Overall, exposure in pediatric patients 12 to 18 years of age weighing ≥35 kg was similar to in adults. In the proportion of this population weighing ≥35 to <45 kg, AUC24 was 25% higher and Cmax was 36% higher than adult values; these differences are not considered clinically significant.
Tablets (Pifeltro Oral)
100 mg (per each): $63.89
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