Doravirine

Indications

Doravirine is used for: HIV Infection

Adult Dose

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

Child Dose

<18 years: Safety and efficacy not established

Renal Dose

Administration

Administer at a regularly scheduled time with or without food

Contra Indications

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

Precautions

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

Pregnancy-Lactation

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

Interactions

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

Adverse Effects

Side effects of Doravirine : 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%)

Mechanism of Action

Non-nucleoside reverse transcriptase inhibitor (NNRTI) Inhibits HIV-1 replication by noncompetitive inhibition of HIV-1 reverse transcriptase