Vimseltinib dihydrate, a tyrosine kinase inhibitor that inhibits colony-stimulating factor 1 receptor (CSF-1R), is an antineoplastic agent.1, 3
Vimseltinib dihydrate is used for the treatment of adult patients with symptomatic tenosynovial giant cell tumor (TGCT) for which surgical resection will potentially cause worsening functional limitation or severe morbidity.1, 4
Safety and efficacy of vimseltinib are based on results from a double-blind, randomized, placebo-controlled phase 3 study (MOTION) in adults with symptomatic TGCT not amenable to surgery.1, 2 Eligible patients had histologically confirmed TGCT with at least one lesion measuring at least 2 cm in size and were not able to undergo surgery because of the risk of worsening functional limitation or severe morbidity.1, 2 Patients were stratified by tumor location (lower limb versus other location) and region (US versus non-US) and randomized to receive vimseltinib 30 mg orally twice weekly or placebo in 28-day cycles for 24 weeks.1, 2 Previous treatment with either or both non-selective tyrosine kinase inhibitors imatinib or nilotinib was permitted; however, patients who received previous systemic therapy targeting CSF-1 or CSF-1R, including prior administration of vimseltinib, were excluded.2 Patients with metastatic TGCT or active cancer requiring treatment were also excluded from the study.2
A total of 123 patients were randomized.1, 2 Among these patients, the median age was 44 years (range: 20-78 years); 59% were female, 65% white, 74% had previously undergone surgery, 69% were diagnosed with diffuse TGCT, and 23% were previously treated with systemic therapy.1, 2 Disease locations included the knee (67%), ankle (12%), hip (10%), other (5%), foot (3.3%), and wrist (2.4%).1
The primary efficacy outcome measure was overall response rate as assessed by blinded independent radiological review according to Response Evaluation Criteria in Solid Tumor (RECIST v1.1) at week 25.1, 2 Additional efficacy outcome measures included overall response rate assessed at week 25 using tumor volume score (TVS), change from baseline in range of motion of the affected joint at week 25, change from baseline in the Patient-Reported Outcomes Measurement Information System-Physical Function (PROMIS-PF) score for the upper and lower extremities, and BPI-30 response (defined as at least 30% improvement in the mean Brief Pain Inventory [BPI] Worse Pain numeric rating scale [NRS] score without a 30% or greater increase in narcotic analgesic use).1, 2
At week 25, the overall response rate (according to RECIST) was 40 or 0% in patients receiving vimseltinib or placebo, respectively.1, 2 Among patients who had an overall response, duration of response was ≥6 months for 85% of patients and ≥9 months for 58% of patients.1 Complete response occurred in 5% and partial response was achieved in 35% of vimseltinib-treated patients.1, 2 Results of secondary endpoints support the clinical benefit of vimseltinib.5 Overall response rate (according to TVS) was also improved in patients receiving vimseltinib (67%) compared with placebo (0%).1, 2 Active range of motion of the affected joint at week 25 was significantly higher in patients treated with vimseltinib compared with placebo (least squares mean difference of 14.6%).1, 2 Vimseltinib also significantly improved the PROMIS-PF, a measure of physical function, compared with placebo (least squares mean difference of 3.3%).1, 2 BPI worst pain response rate was significantly improved in patients treated with vimseltinib compared with those who received placebo (difference of 26%).1, 2
Following the 24-week, double-blind study period, patients were eligible for continued treatment in an ongoing open-label extension during which all patients received vimseltinib.1, 2 Efficacy outcomes for the extension study have not yet been published.2
Tenosynovial giant cell tumor (TGCT) is a rare, non-malignant tumor which arises from the synovium, bursae, and tendon sheaths of young adults between 20-50 years of age.3, 4, 5 Therapeutic approaches for the management of this disease potentially include observation and symptom management, radiation therapy, surgical interventions, and drug therapy.3 Tumor growth appears to be driven by a mutation involving chromosome 1p13, which induces overexpression of colony stimulating factor-1 (CSF-1) on tumor cells resulting in hyperplasia of synovial cells around joints and tendon sheaths; therefore, systemic therapies targeting CSF-1R have been used in patients with inoperable TGCT and when surgery is associated with a risk of excess morbidity.3
The mainstay of treatment for TGCT is surgery when feasible; however, surgery can cause significant joint damage, functional limitation, and morbidity.2, 3, 5 In addition, relapse rates after surgery for patients with the diffuse-type of TGCT have been reported to be as high as 50%.3, 5 Treatment options for patients who cannot undergo surgery are limited.5 Pexidartinib is an oral tyrosine kinase inhibitor approved by FDA for the treatment of TGCT associated with severe morbidity or functional limitations that is not amenable to surgery; however, the drug requires a Risk Evaluation and Mitigation Strategy (REMS) due to serious and potentially fatal hepatotoxicity.5, 6 Systemic therapies including nonselective kinase inhibitors and monoclonal antibodies targeting CSF1R expression also have been used, but are either off-label or investigational therapies.3, 5
While there are no head-to-head comparisons of vimseltinib and pexidartinib in the treatment of TGCT, both drugs produced similar objective response rates in trials (38% in the ENLIVEN phase 3 trial for pexidartinib and 40% in the MOTION phase 3 trial for vimseltinib).1, 6
Vimseltinib is administered orally twice weekly with or without food.1 Doses should be taken at least 72 hours apart on the same days each week; follow the dosing schedule provided by the manufacturer on the blister package.1
Swallow vimseltinib capsules whole; do not open, break, or chew the capsules.1
If a dose of vimseltinib is missed by 48 hours or less, the dose should be taken as soon as possible and the next dose should be taken at the next scheduled time.1 If a dose is missed by more than 48 hours, skip the dose and take the next dose at the regularly scheduled time.1
If vomiting occurs within 30 minutes of taking a dose, repeat the dose.1 If more than 30 minutes have passed, take the next dose at the regularly scheduled time.1
Capsules should be stored at room temperature (20-25°C; with excursions permitted to 15-30°C) in the original blister packs until ready for use.1
Dosage of vimseltinib dihydrate is expressed in terms of vimseltinib.1
For the treatment of symptomatic tenosynovial giant cell tumor (TGCT), the recommended adult dosage of vimseltinib is 30 mg orally twice weekly.1 Continue therapy until disease progression or unacceptable toxicity occurs.1
Dosage Modification for Hepatotoxicity
If hepatotoxicity occurs during vimseltinib therapy, temporary interruption of therapy, dosage reduction, and/or permanent discontinuance of the drug may be necessary.1 If dosage reduction is required, the dosage of vimseltinib should be reduced as described in Table 1.1 Recommended dosage modifications for hepatotoxicity are described in Table 2.1 Permanently discontinue vimseltinib in patients who are unable to tolerate a dosage of 14 mg orally twice weekly.1
Dose Reduction | Twice Weekly Dose |
|---|---|
First | 20 mg |
Second | 14 mg |
Severity | Dosage Modifications |
|---|---|
ALT and/or AST >3-5 times the ULN and total bilirubin increases up to 2 times the ULN OR total bilirubin increases up to 2 times the ULN | Withhold therapy and monitor liver function tests until AST and ALT return to baseline or ≤3 times the ULN and bilirubin returns to baseline. Resume at next lower dose level (see Table 1) if high-risk drug-induced liver injury that can result in acute liver failure (Hy's law) has been ruled out; permanently discontinue vimseltinib if adverse reaction does not resolve within 4 weeks |
ALT and/or AST >3-5 times the ULN and total bilirubin increases >2 times the ULN or the international normalized ratio (INR) is >1.5 and ALP is <2 times the ULN OR total bilirubin >2 times the ULN | Withhold therapy and monitor liver function tests until AST and ALT return to baseline or ≤3 times the ULN and the bilirubin returns to baseline. Resume at next lower dose level (see Table 1) if Hy's law has been ruled out; permanently discontinue vimseltinib if adverse reaction does not resolve within 4 weeks |
AST and/or ALT increases to >5-8 times the ULN, and total bilirubin ≤ULN and without clinical symptoms | Withhold therapy and monitor liver function tests until AST and ALT return to ≤3 times the ULN or to baseline; permanently discontinue vimseltinib if adverse reaction does not resolve within 4 weeks |
AST and/or ALT increases to >5-8 times the ULN and total bilirubin increases to >ULN, or the INR >1.5, or ALP >2 times the ULN | Permanently discontinue |
AST and/or ALT increases to >8 times the ULN | Permanently discontinue |
Dosage Modification for Concomitant Use of P-glycoprotein Substrates
Avoid concomitant use of vimseltinib with P-glycoprotein (P-gp) substrates.1 If concomitant use is unavoidable, administer vimseltinib at least 4 hours before taking the P-gp substrate unless otherwise recommended in the prescribing information for the substrate drug.1
No dosage adjustment is recommended for patients with mild (bilirubin ≤ULN and AST >ULN or bilirubin >1 to 1.5x ULN and any AST) hepatic impairment.1
Vimseltinib has not been studied in patients with moderate (bilirubin >1.5 to 3x ULN and any AST) or severe (bilirubin >3x ULN and any AST) hepatic impairment.1
In patients with mild to moderate renal impairment (estimated glomerular filtration rate [eGFR] ≥30 mL/min), no clinically significant differences in pharmacokinetics were observed for vimseltinib.1
There are no specific dosage recommendations for patients with severe renal impairment (eGFR <30 mL/min).1
There are no specific dosage recommendations for geriatric patients.1
While serious and fatal liver injuries including hepatotoxicity with ductopenia and cholestasis have been reported in patients receiving pexidartinib, another tyrosine kinase inhibitor that targets CSF1R, serious and fatal hepatotoxicity has not been reported with vimseltinib.1 In clinical trials, 2% of 253 vimseltinib-treated patients developed Grade 3 increases in AST and 1% had Grade 3 increases in ALT.1 Dose interruptions were required in 2% of patients and dose reductions occurred in 1% of patients who had experienced elevations in AST and ALT.1 Only one patient discontinued vimseltinib due to Grade 3 elevations in AST.1
Avoid vimseltinib in patients with preexisting elevated AST or ALT concentrations, total bilirubin or direct bilirubin greater than ULN, or active liver or biliary tract disease including increased ALP.1 Monitor liver function tests, including AST, ALT, total bilirubin, direct bilirubin, ALP, and GGT prior to initiation of vimseltinib therapy, twice a month for the first 2 months, and then once every 3 months for the first year of therapy; monitoring should continue as clinically indicated thereafter.1 Based on the severity of hepatotoxicity, temporary interruption of therapy, dosage reduction, or permanent discontinuance of vimseltinib may be necessary.1
Fetal/Neonatal Morbidity and Mortality
Based on animal data and its mechanism of action, vimseltinib may cause fetal harm when administered during pregnancy.1 Available human data do not establish the presence or absence of major birth defects or miscarriage related to the use of vimseltinib; however, structural abnormalities (i.e., skeletal variations, cardiac malformations) have been observed in animal studies at exposures that were 3 times the human exposure at the recommended dosage.1
Verify pregnancy status in females of reproductive potential prior to initiation of therapy.1
Pregnant females should be apprised of the potential risk to a fetus.1 Advise females of reproductive potential to use effective contraception during treatment with vimseltinib and for 1 month after discontinuing treatment.1
Males with female partners of reproductive potential should also use effective contraception during treatment with vimseltinib and for 1 month after discontinuing treatment.1
Allergic Reactions to FD&C Yellow No. 5 (Tartrazine) and No. 6 (Sunset Yellow FCF)
Vimseltinib 20 mg capsules contain FD&C Yellow No. 5 (tartrazine) as a color additive, which may cause allergic reactions (including bronchial asthma) in certain susceptible patients.1
Vimseltinib 14 mg and 20 mg capsules contain FD&C Yellow No. 6 (Sunset Yellow FCF), which may cause allergic reactions.1
Increased Creatinine without Affecting Renal Function
Increases in serum creatinine have been observed that do not affect renal function; use alternative measures that are not based on serum creatinine to assess renal function.1
Vimseltinib may increase serum creatinine by decreasing renal tubular secretion of creatinine by inhibiting renal transporters, organic cation transporter (OCT) 2 and multidrug and toxin extrusion (MATE)1.1
Based on animal data and its mechanism of action, vimseltinib may cause fetal harm when administered during pregnancy.1
Available human data do not establish the presence or absence of major birth defects or miscarriage related to the use of vimseltinib.1
Verify pregnancy status in females of reproductive potential prior to the initiation of vimseltinib.1
It is not known whether vimseltinib or its metabolites are distributed into human milk.1
The effects of the drug on breast-fed infants or on the production of milk are also unknown.1 Because of the potential for serious adverse reactions to vimseltinib in breast-fed infants, females should be advised not to breast-feed while receiving the drug and for at least 1 month after the last dose.1
Females and Males of Reproductive Potential
Verify pregnancy status in females of reproductive potential prior to the initiation of vimseltinib.1
Advise females of reproductive potential to use effective contraception during treatment with vimseltinib and for 1 month after the final dose.1 Advise male patients with female partners of reproductive potential to use effective contraception during treatment with vimseltinib and for 1 month after the final dose.1
Results of animal studies suggest that vimseltinib may impair male and female fertility.1
Safety and efficacy of vimseltinib have not been established in pediatric patients.1
Experience with vimseltinib in patients ≥65 years of age is insufficient to determine whether geriatric patients respond differently than younger individuals.1
Vimseltinib has not been studied in patients with moderate to severe hepatic impairment (total bilirubin >1.5 times the ULN with any AST).1
There are no clinically significant differences in the pharmacokinetics of vimseltinib in patients with mild to moderate renal impairment (estimated glomerular filtration rate [eGFR] ≥30 mL/min).1
Vimseltinib has not been studied in patients with severe renal impairment (eGFR <30 mL/min).1
Vimseltinib may increase serum creatinine concentrations by decreasing renal tubular secretion of creatinine, but may not affect renal function.1 During treatment with vimseltinib, use alternative methods that do not depend on serum creatinine to assess renal function.1
The most common adverse effects of vimseltinib occurring in ≥20% of patients in clinical studies were increased AST concentrations, increased ALT concentrations, periorbital edema, fatigue, rash, increased cholesterol, peripheral edema, facial edema, decreased neutrophils, decreased leukocytes, and pruritus.1
Cytochrome P-450 (CYP) isoenzymes do not appear to play a major role in the metabolism of vimseltinib.1 In vitro studies indicate that vimseltinib is not a substrate of CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, or CYP3A4.1 Vimseltinib does not inhibit CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, or CYP3A4.1 Vimseltinib does not induce CYP1A2, CYP2B5, or CYP3A4.1
Vimseltinib is an inhibitor of P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), bile salt exchange pump (BSEP), organic anion transporter protein (OATP) 1B1, OATP1B3, organic cation transporter (OCT) 2, multidrug and toxin extrusion protein (MATE) 1, and MATE2-K.1 In vitro studies indicate that vimseltinib does not inhibit organic anion transport (OAT)1 and OAT3.1 In vitro studies also indicate that vimseltinib is a substrate of P-gp, but not BCRP, BSEP, OATP1B1, OATP1B3, OAT1, OAT3, OCT2, MATE1, or MATE2-K.1
Drugs Affecting or Affected by Transport Systems
P-gp substrates: Concomitant use of vimseltinib with P-gp substrates may increase systemic exposure of the substrate drug.1 Avoid concomitant use of vimseltinib with P-gp substrates.1 If concomitant use cannot be avoided, administer vimseltinib at least 4 hours prior to taking the P-gp substrate unless otherwise recommended in the prescribing information for the substrate drug.1
P-gp inhibitors: No clinically significant differences in vimseltinib pharmacokinetics were observed when used concomitantly with itraconazole, a P-gp inhibitor.1
BCRP substrates: Concomitant use of vimseltinib with BCRP substrates may increase systemic exposure of the substrate drug.1 Avoid concomitant use of vimseltinib with BCRP substrates.1 If concomitant use cannot be avoided, refer to the prescribing information for the BCRP substrate for dose modifications.1
OCT2 substrates: Concomitant use of vimseltinib with OCT2 substrates may increase systemic exposure of the substrate drug.1 Avoid concomitant use of vimseltinib with OCT2 substrates.1 If concomitant use cannot be avoided, refer to the prescribing information for the OCT2 substrate for dose modifications.1
Concomitant use of vimseltinib and dabigatran, a P-gp substrate, is expected to increase systemic exposure and peak plasma concentrations of dabigatran by 2- to 3-fold.1 When dabigatran is administered 4 hours after vimseltinib, systemic exposure and peak plasma concentrations of dabigatran are predicted to increase up to 1.3-fold.1 Avoid concomitant use of vimseltinib and dabigatran; if concomitant use cannot be avoided, administer vimseltinib at least 4 hours prior to taking dabigatran unless otherwise recommended in the prescribing information for dabigatran.1
No clinically significant differences in vimseltinib pharmacokinetics were observed when the drug was used concomitantly with rabeprazole, a proton pump inhibitor.1
Vimseltinib is a tyrosine kinase inhibitor that is highly selective for colony-stimulating factor 1 receptor (CSF-1R).1, 3 Overexpression of CSF-1R ligand promotes cell proliferation and accumulation in the synovium.1, 3 Vimseltinib inhibits CSF1R autophosphorylation, signaling induced by CSF1 ligand binding, and proliferation of cells expressing CSF1R.1 In preclinical studies, vimseltinib was shown to decrease infiltrating tumor-associated macrophages (TAMs) and CD16+ monocytes.3
Vimseltinib pharmacokinetics are dose proportional.1 No clinically significant differences in vimseltinib pharmacokinetics were observed following the administration of a high-fat meal (800 to 1000 kcal, 50% fat), compared to fasted conditions.1 Following oral administration, peak plasma concentrations of vimseltinib are achieved in a median of 1 hour (0.5 to 4 hours) and are not affected by a high-fat diet or fasting state.1 Vimseltinib is 96.5% bound to human serum albumin.1 Vimseltinib principally undergoes oxidation, N-demethylation, and N-dealkylation with secondary biotransformation pathways including N-demethylation, dehydrogenation, and oxidation.1 Following oral administration of a single radiolabeled dose of vimseltinib, approximately 43% of the radioactivity was recovered in feces (9.1% as unchanged drug) and 38% was recovered in urine (5.1% unchanged).1 The mean elimination half-life of vimseltinib is approximately 6 days.1 No clinically significant differences in the pharmacokinetics of vimseltinib have been observed based on race (Asian, Black, or Arican American, White) or sex.1
Additional Information
The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer's labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care. For further information on the handling of antineoplastic agents, see the ASHP Guidelines on Handling Hazardous Drugs at [Web]
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.
Vimseltinib is only available through select specialty pharmacies. For more information, visit: [Web].
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Oral | Capsules | 14 mg (of vimseltinib) | Romvimza® | Deciphera Pharmaceuticals |
20 mg (of vimseltinib) | Romvimza® | Deciphera Pharmaceuticals | ||
30 mg (of vimseltinib) | Romvimza® | Deciphera Pharmaceuticals |
AHFS® Drug Information. © Copyright, 1959-2025, Selected Revisions August 10, 2025. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, MD 20814.
Only references cited for selected revisions after 1984 are available electronically.
1. Deciphera Pharmaceuticals, LLC. ROMVIMZA (Vimseltinib) capsules prescribing information. Waltham, MA; 2025 Feb.
2. Gelderblom H, Bhadri V, Stacchiotti S, et al; MOTION investigators. Vimseltinib versus placebo for tenosynovial giant cell tumour (MOTION): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2024 Jun 22;403(10445):2709-2719. doi: 10.1016/S0140-6736(24)00885-7. Epub 2024 Jun 3. PMID: 38843860; PMCID: PMC11740396.
3. Chan AS, Katiyar V, Dy P, Singh V. Updates on the Treatment of Tenosynovial Giant Cell Tumor. Hematol Oncol Stem Cell Ther. 2023 May 23;16(4):307-315. doi: 10.56875/2589-0646.1032. PMID: 37363972. [Web]
4. Palmerini E, Trent JC, Hornicek FJ Jr. Medical Management of Tenosynovial Giant Cell Tumor. Curr Oncol Rep. 2025 May 20. doi: 10.1007/s11912-025-01679-x. Epub ahead of print. PMID: 40392406. [Web]
5. US Food and Drug Administration. Center for Drug Evaluations and Research Application Number: 219304Orig1s000 Multi-Discipline Review. From FDA website. Accessed 2025 Apr 30. [Web]
6. Daiichi Sankyo Inc. Turalio® (pexidartinib) capsules prescribing information. Basking Ridge, NJ; 2023 Nov.