Concomitant administration of BRAFTOVI with sensitive CYP3A4 substrates may result in increasedtoxicity or decreased efficacy of these agents.

Coadministration of BRAFTOVI with hormonal contraceptives (CYP3A4 substrates) can result in decreasedconcentrations and loss of hormonal contraceptive efficacy. Avoid hormonal contraceptives [see Use in

Specific Populations (8.3)].

7.3 Drugs That Prolong the QT Interval

BRAFTOVI is associated with dose-dependent QTc interval prolongation. Avoid coadministration of

BRAFTOVI with medicinal products with a known potential to prolong QT/QTc interval [see Warnings andPrecautions (5.5), Clinical Pharmacology (12.2)].

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Risk Summary

Based on its mechanism of action, BRAFTOVI can cause fetal harm when administered to a pregnantwoman [see Clinical Pharmacology (12.1)]. There are no available clinical data on the use of BRAFTOVI

during pregnancy. In animal reproduction studies, encorafenib produced embryo-fetal developmentalchanges in rats and rabbits and was an abortifacient in rabbits at doses greater than or equal to those

resulting in exposures approximately 26 (in the rat) and 178 (in the rabbit) times the human exposure at theclinical dose of 450 mg, with no clear findings at lower doses (see Data). Advise pregnant women of the

potential risk to a fetus.

In the U.S. general population, the estimated background risk of major birth defects and miscarriage inclinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

DataAnimal Data

In reproductive toxicity studies, administration of encorafenib to rats during the period of organogenesisresulted in maternal toxicity, decreased fetal weights, and increased incidence of total skeletal variations at a

dose of 20 mg/kg/day (approximately 26 times the human exposure based on area under the concentration-time curve [AUC] at the recommended clinical dose of 450 mg once daily). In pregnant rabbits,

administration of encorafenib during the period of organogenesis resulted in maternal toxicity, decreasedfetal body weights, increased incidence of total skeletal variations and increased post-implantation loss,

including total loss of pregnancy at a dose of 75 mg/kg/day (approximately 178 times the human exposurebased on AUC at the recommended clinical dose of 450 mg once daily). While formal placental transfer

studies have not been performed, encorafenib exposure in the fetal plasma of both rats and rabbits was up to1.7% and 0.8%, respectively, of maternal exposure.

8.2 Lactation

Risk Summary

There are no data on the presence of encorafenib or its metabolites in human milk or the effects ofencorafenib on the breastfed infant, or on milk production. Because of the potential for serious adverse

reactions from BRAFTOVI in breastfed infants, advise women not to breastfeed during treatment withBRAFTOVI and for 2 weeks after the final dose.

8.3 Females and Males of Reproductive Potential

Pregnancy Testing

Verify the pregnancy status of females of reproductive potential prior to initiating BRAFTOVI [see Use inSpecific Populations (8.1)]. 

Contraception

BRAFTOVI can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations(8.1)].

Females