doravirine (Rx)

Brand and Other Names:Pifeltro
  • Print

Dosing & Uses

AdultPediatricGeriatric

Dosage Forms & Strengths

tablet

  • 100mg

HIV Infection

Indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection in treatment-naïve adults

1 tablet PO qDay

Also see Administration

Dosage Modifications

Coadministration with rifabutin: Increase doravirine dose to 1 tablet PO BID (~12 hr apart) for the duration of rifabutin treatment

Renal impairment

  • Mild-to-severe: No dosage adjustment necessary
  • End-stage renal disease and dialysis: Not studied

Hepatic impairment

  • Mild-to-moderate (Child-Pugh A to B): No dosage adjustment necessary
  • Severe (Child-Pugh C): Not studied

<18 years: Safety and efficacy not established

Exercise caution in administration in elderly patients, reflecting greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy

Next:

Interactions

Interaction Checker

and doravirine

No Results

     activity indicator 
    No Interactions Found
    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

          Minor

            All Interactions Sort By:
             activity indicator 
            Previous
            Next:

            Adverse Effects

            1-10% (doravirine + 2 NRTIs)

            Nausea (7%)

            Headache (6%)

            Fatigue (6%)

            Diarrhea (5%)

            Abdominal pain (5%)

            Total bilirubin 1.1 to <1.6x ULN (5%)

            AST 2.5 to <5x ULN (4%)

            Lipase 1.5 to <3x ULN (4%)

            Dizziness (3%)

            Creatinine >1.3 to 1.8x ULN (3%)

            ALT 2.5 to <5x ULN (3%)

            Lipase ≥3x ULN (3%)

            Creatine kinase ≥10x ULN (3%)

            Rash (2%)

            Total bilirubin 1.6 to <2.6x ULN (2%)

            Creatinine >1.8x ULN (2%)

            Creatine kinase 6 to <10x ULN (2%)

            Abnormal dreams (1%)

            Insomnia (1%)

            ALT ≥5x ULN (1%)

            <1% (doravirine + 2 NRTIs)

            AST ≥5x ULN

            Alkaline phosphatase 2.5 to <5x ULN

            LDL cholesterol, fasted ≥190 mg/dL

            Triglycerides, fasted >500 mg/dL

            Previous
            Next:

            Warnings

            Contraindications

            Strong CYP3A4 inducers

            • Coadministered with strong CYP3A inducers, as significant decreases in doravirine plasma concentrations may occur, which may decrease the efficacy of doravirine
            • Strong CYP3A inducer examples include carbamazepine, oxcarbazepine, phenobarbital, phenytoin, enzalutamide, rifampin, rifapentine, mitotane, and St. John’s wort

            Cautions

            Immune reconstitution syndrome reported in patients treated with combination antiretroviral therapy; patients may develop an inflammatory response to indolent or residual opportunistic infections (such as Mycobacterium avium infection, cytomegalovirus, Pneumocystis jirovecii pneumonia (PCP), or tuberculosis), which may necessitate further evaluation and treatment

            Autoimmune disorders (eg, Grave disease, polymyositis, Guillain-Barré syndrome) reported to occur in the setting of immune reconstitution; however, time to onset varies and can occur many months after initiation of treatment

            Drug interaction overview

            • Primarily metabolized by CYP3A; drugs that induce or inhibit CYP3A may affect doravirine clearance
            • Coadministration with strong CYP3A inducers may decrease systemic exposure and lead to loss of therapeutic effect and possible HIV resistance (see Contraindications and Dosage Modifications)
            Previous
            Next:

            Pregnancy

            Pregnancy

            Healthcare providers are encouraged to register patients by calling the Antiretroviral Pregnancy Registry (APR) at 1-800-258-4263; pregnancy exposure registry monitors pregnancy outcomes in individuals exposed to doravirine during pregnancy

            Data are not available to establish drug-associated risks to pregnancy outcomes

            Animal data

            • In animal reproduction studies, no adverse developmental effects were observed when doravirine was administered at exposures ≥8 times the exposure in humans at the recommended human dose (RHD)

            Lactation

            The Centers for Disease Control and Prevention do not recommend HIV-infected women breastfeed their infants, owing to potential risk for postnatal transmission of HIV

            Unknown if distributed in human breast milk

            Owing to the potential for HIV transmission (in HIV-negative infants), developing viral resistance (in HIV-positive infants), and adverse reactions in a breastfed infant similar to those seen in adults, instruct women not to breastfeed while taking this medication

            Pregnancy Categories

            A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA:Information not available.

            more...
            Previous
            Next:

            Pharmacology

            Mechanism of Action

            Non-nucleoside reverse transcriptase inhibitor (NNRTI)

            Inhibits HIV-1 replication by noncompetitive inhibition of HIV-1 reverse transcriptase

            Absorption

            Time to steady state: 2 days

            AUC: 16.1 mcg·hr/mL

            Peak plasma concentration: 0.962 mcg/mL

            Peak plasma time: 2 hr

            Absolute bioavailability: 64%

            Effects of food

            • AUC ratio: 1.16
            • Peak plasma concentration ratio: 1.03
            • High fat meal is ~1000 kcal, 50% fat; effect of food is not clinically relevant

            Distribution

            Vd (steady-state): 60.5 L

            Plasma protein binding: 76%

            Metabolism

            Metabolized by CYP3A4

            Elimination

            Half-life: 15 hr

            Clearance: 9.3 mL/min

            Excretion, unchanged: Urine (6%); feces/biliary (minor)

            Previous
            Next:

            Administration

            Oral Administration

            Administer at a regularly scheduled time with or without food

            If a patient misses a dose, take dose right away, unless it is almost time for the next dose; do not to take 2 doses at one time; administer next dose at regularly scheduled time

            Storage

            Store at 20-25°C (68-77°F); excursions permitted to 15-30°C (59-86°F)

            Store in original bottle

            Keep bottle tightly closed to protect from moisture; do not remove desiccants

            Previous
            Next:

            Images

            Previous
            Next:

            Formulary

            FormularyPatient Discounts

            Adding plans allows you to compare formulary status to other drugs in the same class.

            To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.

            Adding plans allows you to:

            • View the formulary and any restrictions for each plan.
            • Manage and view all your plans together – even plans in different states.
            • Compare formulary status to other drugs in the same class.
            • Access your plan list on any device – mobile or desktop.

            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
            QL Quantity Limits
            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
            ST Step Therapy
            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
            OR Other Restrictions
            Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
            Additional Offers
            Email to Patient

            From:

            To:

            The recipient will receive more details and instructions to access this offer.

            By clicking send, you acknowledge that you have permission to email the recipient with this information.

            Email Forms to Patient

            From:

            To:

            The recipient will receive more details and instructions to access this offer.

            By clicking send, you acknowledge that you have permission to email the recipient with this information.

            Previous
            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.