Product information and disease description Product description Product information Drug/Drug, drug/disease interactions

Effects of Tovorafenib on other drugs

5 evidence topics · 3 sources

CYP3A substrates and hormonal contraceptives: US prescribing information

“Hormonal Contraceptives : Avoid coadministration of hormonal contraceptives with OJEMDA. If coadministration is unavoidable, use an additional effective nonhormonal contraceptive method during coadministration and for 28 days after discontinuation of OJEMDA.” (opens the source at this quote in a new tab)
“Other CYP3A Substrates: Avoid coadministration of OJEMDA with certain CYP3A substrates where minimal concentration changes may lead to serious therapeutic failures. If coadministration is unavoidable, monitor patients for loss of efficacy unless otherwise recommended in the Prescribing Information for CYP3A substrates.” (opens the source at this quote in a new tab)
“Coadministration with hormonal contraceptives (CYP3A substrate) may decrease progestin-x and ethinyl estradiol exposure, which may lead to contraceptive failure and/or an increase in breakthrough bleeding” (opens the source at this quote in a new tab)

Model-predicted effect on midazolam and in vitro enzyme and transporter effects

“CYP3A Substrates: Midazolam (CYP3A4 substrate) steady-state C max and AUC are predicted to decrease by at least 20% following coadministration with tovorafenib.” (opens the source at this quote in a new tab)
“CYP450 Enzymes : Tovorafenib inhibits CYP2C8, CYP2C9, CYP2C19 and CYP3A, but does not inhibit CYP1A2, CYP2B6, and CYP2D6 at clinically relevant concentrations.” (opens the source at this quote in a new tab)
“Tovorafenib induces CYP3A, CYP2C8, CYP1A2, CYP2B6, CYP2C9 and CYP2C19 at clinically relevant concentrations.” (opens the source at this quote in a new tab)

Narrow therapeutic index CYP3A substrates, other CYP substrates, and transporter substrates: EU product information

“Coadministration of tovorafenib with certain CYP3A substrates (e.g. tacrolimus) where minimal concentration changes may lead to serious therapeutic failures should be avoided.” (opens the source at this quote in a new tab)
“In vitro data indicated that tovorafenib may have the potential to induce CYP1A2 and CYP2B6 and to inhibit CYP2C8, CYP2C9. The clinical relevance of these findings is unknown.” (opens the source at this quote in a new tab)
“In vitro data indicated that tovorafenib may have the potential to inhibit BCRP, OATP1B1, OATP1B3 and MATE1, the clinical relevance of these findings is unknown.” (opens the source at this quote in a new tab)

Ongoing clinical probe-substrate study

“The MAH commits to submit the results of the study DAY101-104 to assess the effects of tovorafenib on the pharmacokinetics of probe substrates caffeine (CYP1A2), repaglinide (CYP2C8), flurbiprofen (CYP2C9), omeprazole (CYP2C19), midazolam (CYP3A4), bupropion (CYP2B6), and rosuvastatin (BCRP) in healthy participants.” (opens the source at this quote in a new tab)

QT-prolonging agents

“Tovorafenib presents a potential risk for QT prolongation, especially in case of association with other QT-prolonging agents.” (opens the source at this quote in a new tab)