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Doravirine

Medically reviewed by Drugs.com. Last updated on Aug 18, 2020.

Pronunciation

(DOR a VIR een)

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Pifeltro: 100 mg

Brand Names: U.S.

  • Pifeltro

Pharmacologic Category

  • Antiretroviral, Reverse Transcriptase Inhibitor, Non-nucleoside (Anti-HIV)

Pharmacology

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

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.

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.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

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

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

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

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.

Monitoring Parameters

Viral load, CD4 count

Reproductive Considerations

The Health and Human Services (HHS) perinatal HIV guidelines note data are insufficient to recommend doravirine for females living with HIV who are not yet pregnant but are trying to conceive.

For males and females living with HIV and planning a pregnancy, maximum viral suppression below the limits of detection with antiretroviral therapy (ART), modification of therapy (if needed), optimization of the woman’s health, and a discussion of the potential risks and benefits of ART therapy during pregnancy is recommended prior to conception (HHS [perinatal] 2019).

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), 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

What is this drug used for?

• It is used to treat HIV infection.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Nausea

• Dizziness

• Nightmares

• Trouble sleeping

• Diarrhea

• Abdominal pain

• Headache

• Loss of strength and energy

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Infection

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine's uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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