Binimetinib Special Population Precautions
1. Pregnancy
May cause fetal harm.
2. Lactation
It is unknown whether binimetinib or its metabolites are excreted in human milk. The effects on the breastfed infant and on milk production are also unknown. Breastfeeding should be discontinued during treatment and for 3 days after the last dose.
3. Females and Males of Reproductive Potential
Verify pregnancy status in females of reproductive potential before initiating treatment.
Advise females of reproductive potential to use effective contraception during treatment and for at least 30 days after the last dose.
4. Pediatric Use
Safety and effectiveness have not been established.
5. Geriatric Use
No overall differences in safety and effectiveness of binimetinib in combination with encorafenib were observed between elderly patients and younger adults.
6. Hepatic Impairment
Mild hepatic impairment has no substantial effect on the systemic exposure of binimetinib; no dose adjustment is required. Systemic exposure is increased in patients with moderate or severe hepatic impairment; dose reduction is recommended.
7. Renal Impairment
Severe renal impairment has no substantial effect on the systemic exposure of binimetinib.
Binimetinib Common Adverse Reactions
1. The most common adverse reactions (≥25%) with binimetinib in combination with encorafenib for the treatment of melanoma include: fatigue, nausea, diarrhea, vomiting, abdominal pain.
2. The most common adverse reactions (≥25%) with binimetinib in combination with encorafenib for the treatment of NSCLC include: fatigue, nausea, diarrhea, musculoskeletal pain, vomiting, abdominal pain, visual disturbance, constipation, dyspnea, rash, cough.
Binimetinib Drug Interactions
1. Binimetinib is primarily metabolized by uridine diphosphate glucuronosyltransferase (UGT) 1A1, and to a lesser extent by CYP1A2 and CYP2C19, forming a minor active metabolite (M3).
2. It does not cause time-dependent inhibition of CYP isoenzymes 1A2, 2C9, 2D6, and 3A, and has little or no induction effect on CYP2C9.
3. In vitro studies show that binimetinib is a weak inhibitor of UGT1A and organic cation transporter (OCT) 2, but not an inhibitor of OCT1.
4. Binimetinib is a substrate of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP), but not a substrate of OCT1 or organic anion transporting polypeptides (OATP) 1B1, OATP1B3, and OATP2B1.
