Vimseltinib (Monograph)

Brand name: Romvimza
Drug class: Antineoplastic Agents

Introduction

Vimseltinib, a kinase inhibitor that inhibits colony-stimulating factor 1 receptor (CSF1R), is an antineoplastic agent.

Uses for Vimseltinib

Vimseltinib has the following uses:

Vimseltinib is indicated for treatment of adult patients with symptomatic tenosynovial giant cell tumor (TGCT) for which surgical resection will potentially cause worsening functional limitation or severe morbidity.

Vimseltinib Dosage and Administration

General

Vimseltinib dihydrate is available in the following dosage form(s) and strength(s):

Capsules: 14 mg, 20 mg, and 30 mg of vimseltinib.

Dosage

It is essential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:

Adults

Dosage and Administration

• Recommended Dosage: 30 mg orally twice weekly, with a minimum of 72 hours between doses as described in the blister package.

• See full prescribing information for dosage modifications due to hepatotoxicity and drug interactions.

Cautions for Vimseltinib

Contraindications

None

Warnings/Precautions

Hepatotoxicity

Cases of serious and fatal liver injury have occurred with the use of another kinase inhibitor that targets CSF1R. Serious and fatal liver injury have not been observed with vimseltinib.

Across clinical trials in 253 patients treated with vimseltinib, 2% had increased Grade 3 AST, and 1% had increased Grade 3 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 increased Grade 3 AST.

Avoid vimseltinib in patients with pre-existing increased serum transaminases; total bilirubin or direct bilirubin (>ULN); or active liver or biliary tract disease, including alkaline phosphatase (ALP). Monitor liver tests, including AST, ALT, total bilirubin, direct bilirubin, ALP and gamma-glutamyl transferase (GGT), prior to initiation of vimseltinib, 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 vimseltinib based on the severity of the hepatotoxicity.

Embryo-fetal Toxicity

Based on data from animal studies and its mechanism of action, vimseltinib 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 vimseltinib and for 1 month after the last dose.

Allergic Reactions to FD&C Yellow No.5 (Tartrazine) and No. 6 (Sunset Yellow FCF)

Vimseltinib 20 mg capsule contains FD&C Yellow No. 5 (tartrazine) which may cause allergic reactions (including bronchial asthma) in certain susceptible patients. Although the overall incidence of FD&C Yellow No. 5 (tartrazine) sensitivity in the general population is low, it is frequently seen in patients who also have aspirin sensitivity.

Vimseltinib 14 mg and 20 mg capsules contain FD&C Yellow No.6 (Sunset Yellow FCF), which may cause allergic reactions.

Increased Creatinine without Affecting Renal Function

In the MOTION study, 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 vimseltinib discontinuation. The increases in serum creatinine may be due to inhibition of renal tubular secretion transporters. During vimseltinib treatment, use alternative measures that are not based on serum creatinine to assess renal function.

Specific Populations

Pregnancy

Based on data from animal studies and its mechanism of action, vimseltinib can cause fetal harm when administered to a pregnant woman. There are no available data on vimseltinib use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. In female rats administered vimseltinib during the period of organogenesis, fetal structural abnormalities occurred at exposures that were at least 3 times the recommended dose based on AUC. Advise pregnant women of the potential risk to a fetus.

The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

Lactation

There are no data on the presence of vimseltinib or its metabolites in either human or animal milk or its effects on a breastfed child or on milk production. Because of the potential for serious adverse reactions in the breastfed child, advise women not to breastfeed during treatment with vimseltinib and for 1 month after the last dose.

Females and Males of Reproductive Potential

Vimseltinib can cause fetal harm when administered to a pregnant woman.

Verify pregnancy status in females of reproductive potential prior to the initiation of vimseltinib.

Advise females of reproductive potential to use effective contraception during treatment with vimseltinib and for 1 month after the last dose.

Advise males that are partnered with females of reproductive potential to use effective contraception during treatment with vimseltinib and for 1 month after the last dose.

Based on findings from animal studies, vimseltinib may impair fertility.

Pediatric Use

The safety and effectiveness of vimseltinib in pediatric patients have not been established.

In a 26-week repeat-dose toxicology study, rats administered vimseltinib at ≥2.5 mg/kg/day had physeal thickening and decay of the incisors and molars. Bone and tooth toxicities occurred at exposures at least 8 times the recommended dose based on AUC.

Geriatric Use

Clinical studies of vimseltinib did not include a sufficient number of patients 65 years of age and older to determine whether they respond differently from younger patients.

Hepatic Impairment

No dose adjustment is recommended for patients with mild (bilirubin ≤upper limit of normal [ULN] and AST >ULN or bilirubin >1x to 1.5x ULN and any AST) hepatic impairment. Vimseltinib has not been studied in patients with moderate (bilirubin >1.5x to 3x ULN and any AST) or severe (bilirubin >3x ULN and any AST) hepatic impairment.

Common Adverse Effects

Most common adverse reactions (incidence ≥20%), including laboratory abnormalities are increased AST, periorbital edema, fatigue, rash, increased cholesterol, peripheral edema, face edema, decreased neutrophils, decreased leukocytes, pruritus, and increased ALT.

Drug Interactions

Specific Drugs

It is essential that the manufacturer's labeling be consulted for more detailed information on interactions with this drug, including possible dosage adjustments. Interaction highlights:

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

• Breast Cancer Resistance Protein (BCRP) substrates: Avoid concomitant use of vimseltinib with BCRP substrates. Concomitant use of vimseltinib with BCRP substrates may increase exposure of these substrates.

• Organic Cation Transporter 2 (OCT) substrates: Avoid concomitant use of vimseltinib with OCT2 substrates. Concomitant use of vimseltinib with OCT2 substrates may increase exposure of these substrates.

Actions

Mechanism of Action

Vimseltinib is a kinase inhibitor that inhibits colony-stimulating factor 1 receptor (CSF1R). In vitro, vimseltinib inhibited CSF1R autophosphorylation, signaling induced by CSF1 ligand binding, and proliferation of cells expressing CSF1R.

Advice to Patients

• Advise patients to read the FDA approved patient labeling (Medication Guide).

• Advise patients there may be a potential risk of hepatotoxicity and that they will need to undergo laboratory tests to monitor liver function and to immediately report any signs or symptoms of severe liver injury to their healthcare provider.

• Advise pregnant women and females of reproductive potential of the potential risk to the fetus. Advise females of reproductive potential to inform their healthcare provider of a known or suspected pregnancy.

• Advise females of reproductive potential to avoid pregnancy and to use effective contraception during treatment with vimseltinib and for 1 month after the last dose.

• Advise males with female partners of reproductive potential to use effective contraception during treatment and for 1 month after the last dose of vimseltinib.

• Advise females not to breastfeed during treatment with vimseltinib and for 1 month after the final dose.

• Advise patients that vimseltinib may impair fertility.

• Advise patients that vimseltinib 20 mg contains FD&C Yellow No. 5 (tartrazine), which may cause allergic-type reactions (including bronchial asthma) in certain susceptible persons or in patients who also have aspirin hypersensitivity.

• Instruct patients that doses should be taken twice weekly at least 72 hours apart.

• Instruct patients to swallow capsules whole (do not open, break, or chew).

• Advise patients to inform their healthcare providers of all concomitant products, including over-the-counter products and supplements.

Additional Information

AHFSfirstRelease^™. For additional information until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual uses, dosage and administration, cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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