VIMSELTINIB Drug Interactions: What You Need to Know

INTERACTIONS P-glycoprotein (P-gp) substrates : Avoid concomitant use of ROMVIMZA with P-gp substrates. If concomitant use cannot be avoided, take ROMVIMZA at least 4 hours prior to P-gp substrates. Concomitant use of vimseltinib with P-gp substrates may increase exposure of these substrates. ( 2.3 , 7.1 )

Breast Cancer Resistance

Protein (BCRP) substrates : Avoid concomitant use of ROMVIMZA with BCRP substrates. Concomitant use of vimseltinib with BCRP substrates may increase exposure of these substrates. ( 7.1 )

Organic Cation Transporter

2 (OCT) substrates : Avoid concomitant use of ROMVIMZA with OCT2 substrates. Concomitant use of vimseltinib with OCT2 substrates may increase exposure of these substrates. ( 7.1 )

7.1 Effects of ROMVIMZA on Other Drugs Table 5 describes drug interactions where concomitant use with ROMVIMZA affects another drug.

Table

5: Effect of ROMVIMZA on Other Drugs P-glycoprotein (P-gp) substrates Prevention or Management Avoid concomitant use with P-gp substrates while taking ROMVIMZA. If concomitant use cannot be avoided, take ROMVIMZA at least 4 hours prior to P-gp substrates [ see Dosage and Administration ( 2.3 ) ] unless otherwise recommended in the substrate Prescribing Information. Mechanism and Clinical Effect(s) This recommendation is based upon a mechanistic understanding of vimseltinib pharmacokinetics and it being a P-gp inhibitor in vitro [ see Clinical Pharmacology ( 12.3 ) ]. Concomitant use of ROMVIMZA with P-gp substrates may increase exposure of these substrates; however, this has not been studied clinically.

Breast Cancer Resistance

Protein (BCRP) substrates Prevention or Management Avoid concomitant use with BCRP substrates while taking ROMVIMZA. Refer to the Prescribing Information of the BCRP substrate for dose modifications if concomitant use cannot be avoided. Mechanism and Clinical Effect(s) This recommendation is based upon a mechanistic understanding of vimseltinib pharmacokinetics and it being a BCRP inhibitor in vitro [ see Clinical Pharmacology ( 12.3 ) ]. Concomitant use of ROMVIMZA with BCRP substrates may increase exposure of these substrates; however, this has not been studied clinically.

Organic Cation Transporter

2 (OCT2) substrates Prevention or Management Avoid concomitant use with OCT2 substrates while taking ROMVIMZA. Refer to the Prescribing Information of the OCT2 substrate for dose modifications if concomitant use cannot be avoided. Mechanism and Clinical Effect(s) This recommendation is based upon a mechanistic understanding of vimseltinib pharmacokinetics and it being an OCT2 inhibitor in vitro [ see Clinical Pharmacology ( 12.3 ) ]. Concomitant use of ROMVIMZA with OCT2 substrates may increase exposure of these substrates; however, this has not been studied clinically.

None. None ( 4 )

AND PRECAUTIONS Hepatotoxicity: Elevated AST and ALT can occur. Evaluate liver tests prior to initiation of treatment and during treatment. ( 2.2 , 5.1 ) Embryo-fetal toxicity: Can cause fetal harm. Advise patients of reproductive potential of the potential risk to a fetus and to use effective contraception. ( 5.2 , 8.1 , 8.3 )

Allergic

Reactions to FD&C Yellow No. 5 (tartrazine) and No. 6 (Sunset Yellow FCF): 14 mg capsule contains FD&C Yellow No. 6 (Sunset Yellow FCF); 20 mg capsule contains FD&C Yellow No.5 (tartrazine) and No. 6 (Sunset Yellow FCF) as color additives, which may cause allergic reactions (including bronchial asthma) in certain susceptible patients. ( 5.3 ) Increased serum creatinine without affecting renal function: Increases in serum creatinine can occur. Use alternative measures that are not based on serum creatinine to assess renal function. ( 5.4 )

5.1 Hepatotoxicity Cases of serious and fatal liver injury have occurred with the use of another kinase inhibitor that targets CSF1R <span class="opacity-50 text-xs">[see Clinical Pharmacology ( 12.1 )]</span>. Serious and fatal liver injury have not been observed with ROMVIMZA. Across clinical trials in 253 patients treated with ROMVIMZA, 2% had Grade 3 increased AST, and 1% had Grade 3 increased ALT. Dose interruptions occurred in 2% of patients and dose reductions occurred in 1% of patients due to AST/ALT increase. One patient discontinued therapy due to Grade 3 AST increased. Avoid ROMVIMZA in patients with pre-existing increased serum transaminases; total bilirubin or direct bilirubin (&gt;ULN); or active liver or biliary tract disease, including ALP. Monitor liver tests, including AST, ALT, total bilirubin, direct bilirubin, ALP and gamma-glutamyl transferase (GGT), prior to initiation of ROMVIMZA, twice a month for the first two months and once every 3 months for the first year of therapy and as clinically indicated thereafter. Withhold and reduce the dose, or permanently discontinue ROMVIMZA based on the severity of the hepatotoxicity [ see Dosage and Administration ( 2.2 ) ].

5.2 Embryo-Fetal Toxicity Based on data from animal studies and its mechanism of action, ROMVIMZA can cause fetal harm when administered to pregnant women. In female rats administered vimseltinib, fetal structural abnormalities occurred at exposures that were at least 3 times the recommended dose based on area under the curve (AUC). Advise pregnant women on the potential risk to the fetus. Advise females of reproductive potential and males with female partners of reproductive potential to use effective contraception during treatment with ROMVIMZA and for 1 month after the last dose [ see Use in Specific Populations ( 8.1 , 8.3 ) ].

5.3 Allergic Reactions to FD&amp;C Yellow No.5 (Tartrazine) and No. 6 (Sunset Yellow FCF) ROMVIMZA 20 mg capsule contains FD&amp;C Yellow No. 5 (tartrazine) which may cause allergic reactions (including bronchial asthma) in certain susceptible patients. Although the overall incidence of FD&amp;C Yellow No. 5 (tartrazine) sensitivity in the general population is low, it is frequently seen in patients who also have aspirin sensitivity. ROMVIMZA 14 mg and 20 mg capsules contain FD&amp;C Yellow No.6 (Sunset Yellow FCF), which may cause allergic reactions.

5.4 Increased Creatinine without Affecting Renal Function In MOTION, serum creatinine increased (mean increase of 19 μmol/L) and reached a maximum mean increase by 10.4 weeks compared to baseline. These increases in serum creatinine may not be associated with changes in renal function. Increases in creatinine reversed upon ROMVIMZA discontinuation. The increases in serum creatinine may be due to inhibition of renal tubular secretion transporters [ see Drug Interactions ( 7.1 ) and Clinical Pharmacology ( 12.3 ) ]. During ROMVIMZA treatment, use alternative measures that are not based on serum creatinine to assess renal function.