Chemical formula: C₂₃H₂₅N₇O₂ Molecular mass: 431.207 g/mol PubChem compound: 86267612
Vimseltinib interacts in the following cases:
Vimseltinib is an inhibitor of OCT2 in vitro. Concomitant use of vimseltinib with OCT2 substrates (e.g. metformin) may increase the concentrations of OCT2 substrates and increase the risk of adverse reactions related to these substrates. Clinical studies with OCT2 substrates have not been conducted. The concomitant use of OCT2 substrates should be avoided. Refer to the Summary of Product Characteristics of the OCT2 substrate for dose modifications if concomitant use cannot be avoided.
Vimseltinib is an inhibitor of BCRP in vitro. Concomitant use of vimseltinib with BCRP substrates (e.g. rosuvastatin) may increase the concentrations of BCRP substrates and increase the risk of adverse reactions related to these substrates. Clinical studies with BCRP substrates have not been conducted.
The concomitant use of BCRP substrates should be avoided. Refer to the Summary of Product Characteristics of the BCRP substrate for dose modifications if concomitant use cannot be avoided.
No dose adjustment is recommended in patients with mild hepatic impairment (Child-Pugh A). Dose reductions to 14 mg twice weekly for patients with mild hepatic impairment have not been used and efficacy has not been established. No clinical data are available in patients with moderate and severe hepatic impairment. Therefore, vimseltinib should not be used in these patients.
Vimseltinib is an inhibitor of P-gp in vitro. Concomitant use of vimseltinib with P-gp substrates (e.g. digoxin, dabigatran) may increase the concentrations of P-gp substrates and increase the risk of adverse reactions related to these substrates. Clinical studies with P-gp substrates have not been conducted.
The concomitant use of P-gp substrates should be avoided. Refer to the Summary of Product Characteristics of the P-gp substrate for dose modifications if concomitant use cannot be avoided.
No clinical data are available in patients with severe renal impairment. Therefore, vimseltinib should not be used in these patients.
It is unknown whether vimseltinib may reduce the effectiveness of systemically acting hormonal contraceptives, and therefore women using systemically acting hormonal contraceptives should add a barrier method.
Based on findings from animal studies, vimseltinib may impair fertility in males.
There are no available data from the use of vimseltinib in pregnant women. Based on findings from animal studies, vimseltinib may cause foetal harm when administered to pregnant women. Studies in animals have shown reproductive toxicity (foetal structural abnormalities and cardiac malformations). Vimseltinib is contraindicated in pregnant women.
It is unknown whether vimseltinib is excreted in human milk. A risk to the breast-fed child cannot be excluded. Women should not breast-feed during treatment with vimseltinib.
Women of childbearing potential must use effective contraception during treatment with vimseltinib and for 30 days after the final dose. The pregnancy status of women of childbearing potential must be verified prior to initiating vimseltinib and during treatment.
Effects of vimseltinib on hormonal contraceptive have not been studied. Therefore, a barrier method should be added if hormonal contraceptives are used.
Based on findings from animal studies, vimseltinib may impair fertility in males.
Vimseltinib has minor influence on the ability to drive and use machines. Fatigue or blurred vision may occur following administration of vimseltinib.
The safety of vimseltinib is based on pooled data from 184 patients with TGCT who received vimseltinib at a dose of 30 mg twice weekly in 2 clinical studies. The MOTION study, a phase 3, double-blind, multicentre, randomised (2:1), placebo-controlled study, included 122 adult patients who received vimseltinib (n=83) or placebo (n=39) in the double-blind period; 35 patients crossed over from placebo and received vimseltinib in the open-label period. The phase ½ study DCC-3014-01-001 included a total of 66 patients with TGCT who received vimseltinib at a dose of 30 mg twice weekly.
The median duration of treatment in the pooled safety population was 13 months. The median age of patients who received vimseltinib was 44 years (range from 20 to 78 years) and the population was 60% female and 72% White.
The most frequently observed adverse reactions were increased aspartate aminotransferase (AST) (92%), periorbital oedema (63%), increased cholesterol (53%), rash (51%), increased creatinine (43%), decreased neutrophils (36%), fatigue (30%), face oedema (28%), increased alanine aminotransferase (ALT) (27%), pruritus (27%), peripheral oedema (22%) and hypertension (21%).
Grade ¾ adverse reactions were hypertension (9%), rash (3%), pruritus (3%), decreased neutrophils (3%), periorbital oedema (2%), fatigue (2%), increased cholesterol (1%), neuropathy (0.5%), face oedema (0.5%), generalised oedema (0.5%), and increased AST (0.5%). Serious adverse reactions were peripheral oedema (0.5%) and increased creatine phosphokinase (CPK) (0.5%).
Permanent discontinuation due to an adverse reaction occurred in 7% of patients. The most frequently observed adverse reactions leading to permanent discontinuation were rash (3%), periorbital oedema (2%), neuropathy (1%) and pruritus (1%).
Dose reductions or interruptions due to an adverse reaction occurred in 59% of patients. The most frequently observed adverse reactions leading to dose reductions or interruptions were rash (21%), periorbital oedema (18%), increased creatine phosphokinase (CPK) (17%), pruritus (10%), face oedema (7%), generalised oedema (7%), fatigue (6%) and peripheral oedema (5%).
The adverse reactions are listed below by system organ class and frequency categories, defined as: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1 000 to <1/100), rare (≥1/10 000 to <1/1 000), very rare (<1/10 000), not known (cannot be estimated from the available data). Within each frequency category, adverse reactions are presented in order of decreasing seriousness.
Adverse reactions observed in MOTION and DCC-3014-01-001 studies:
| System organ class | Frequency category | Adverse reaction |
|---|---|---|
| Nervous system disorders | Very common | Neuropathy1 |
| Eye disorders | Very common | Periorbital oedema2, lacrimation increased |
| Common | Dry eye, vision blurred | |
| Vascular disorders | Very common | Hypertension |
| Skin and subcutaneous tissue disorders | Very common | Rash3, pruritus, dry skin |
| General disorders and administration site conditions | Very common | Peripheral oedema, fatigue, face oedema, generalised oedema |
| Investigations4 | Very common | Blood creatine phosphokinase increased5, aspartate aminotransferase increased, blood cholesterol increased, blood creatinine increased, neutrophil count decreased, alanine aminotransferase increased, alkaline phosphatase increased |
1 Neuropathy comprises peripheral neuropathy, paraesthesia, hypoaesthesia, peripheral sensory neuropathy.
2 Periorbital oedema comprises eye oedema, eyelid oedema, swelling of eyelid, periorbital oedema, periorbital swelling.
3 Rash comprises rash, rash erythematous, rash macular, rash maculo-papular, rash papular, rash pruritic, dermatitis acneiform, erythema.
4 Terms based on laboratory parameters.
5 Frequency category for blood creatine phosphokinase increased is based on laboratory data from DCC-3014-01-001 only.
Consistent with the mechanism of action, increased CPK was reported during the MOTION study in vimseltinib-treated patients. The frequency of increased CPK cannot be determined from the MOTION study because CPK was not assessed at baseline. In the phase ½ study conducted in 66 patients receiving vimseltinib 30 mg twice weekly, increased CPK was observed in all patients.
No overall differences in safety were observed between patients ≥65 years of age and patients <65 years of age.
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