Vimseltinib
FDA Drug Information • Also known as: Romvimza
- Brand Names
- Romvimza
- Drug Class
- Kinase Inhibitor [EPC]
- Route
- ORAL
- Dosage Form
- CAPSULE
- Product Type
- HUMAN PRESCRIPTION DRUG
Description
11 DESCRIPTION Vimseltinib is a kinase inhibitor. The chemical name of vimseltinib dihydrate is 3-methyl-5-[6-methyl-5-[2-(1-methylpyrazol-4-yl)pyridin-4-yl]oxypyridin-2-yl]-2-(propan-2-ylamino)pyrimidin-4-one, dihydrate. Vimseltinib is a white to off-white crystalline solid. Vimseltinib is a weak base, very slightly soluble in water. The molecular formula for vimseltinib dihydrate is C 23 H 25 N 7 O 2
What Is Vimseltinib Used For?
1 INDICATIONS AND USAGE ROMVIMZA 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. ROMVIMZA is a kinase inhibitor 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. ( 1 )
Dosage and Administration
2 DOSAGE AND ADMINISTRATION Recommended Dosage : 30 mg orally twice weekly, with a minimum of 72 hours between doses as described in the blister package. ( 2.1 ) See full prescribing information for dosage modifications due to hepatotoxicity and drug interactions. ( 2.2 , 2.3 ) 2.1 Recommended Dosage The recommended dosage of ROMVIMZA is 30 mg orally taken twice weekly, with a minimum of 72 hours between doses, as directed on the blister package [ see Clinical Pharmacology ( 12.3 ) ]. Instruct patients to follow the schedule on the blister package and to take ROMVIMZA on the same days each week. ROMVIMZA may be taken with or without food. Swallow ROMVIMZA capsules whole. Do not open, break, or chew the capsules. If a dose is missed by 48 hours or less, take the missed dose as soon as possible and take the next dose on its regularly scheduled day. If a dose is missed by more than 48 hours, skip the missed dose, and take the next dose on its regularly scheduled day. If vomiting occurs within 30 minutes of taking a dose, repeat that dose. Otherwise, take the next dose on its regularly scheduled day. 2.2 Dose Modifications for Adverse Reactions The recommended dose reductions for adverse reactions are provided in Table 1 . Table 1: Recommended Dose Reductions Dose Reduction Twice Weekly Dose First 20 mg Second 14 mg Permanently discontinue ROMVIMZA in patients who are unable to tolerate 14 mg orally twice weekly. The recommended dosage modifications for hepatotoxicity are summarized in Table 2 . Table 2: Recommended Dosage Modifications for Hepatotoxicity Hepatotoxicity Severity ROMVIMZA Dosage Modifications ALT = alanine aminotransferase; ALP = alkaline phosphatase; AST = aspartate aminotransferase; INR = International normalized ratio; ULN = upper limit of normal AST and/or ALT increases >3–5 times ULN and total bilirubin increases up to 2 times ULN Withhold ROMVIMZA until AST and ALT resolve to baseline or ≤3 times ULN, and bilirubin resolves to baseline. Resume at the next lower dose level once Hy's law has been definitively ruled out. Permanently discontinue if adverse reaction does not resolve within 4 weeks. OR Total bilirubin increases up to 2 times ULN AST and/or ALT increases >3–5 times ULN, and total bilirubin increases >2 times ULN or INR >1.5 and ALP <2 times ULN Withhold ROMVIMZA until AST and ALT resolve to baseline or ≤3 times ULN, and bilirubin resolves to baseline. Resume at the next lower dose level once Hy's law has been definitively ruled out. Permanently discontinue if adverse reaction does not resolve within 4 weeks. OR Total bilirubin increases >2 times ULN AST and/or ALT increases >5–8 times ULN, and total bilirubin ≤ULN and without clinical symptoms Withhold ROMVIMZA until AST and ALT resolve to ≤3 times ULN or baseline. Permanently discontinue if adverse reaction does not resolve within 4 weeks. AST and/or ALT increases >5-8 times ULN and total bilirubin increase >ULN, or INR >1.5, or ALP >2 times ULN Permanently...
Side Effects (Adverse Reactions)
6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Hepatotoxicity [ see Warnings and Precautions ( 5.1 ) ] 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. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Deciphera Pharmaceuticals, LLC at 1-888-724-3274 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The pooled safety population described in the Warnings and Precautions reflects exposure to ROMVIMZA in 83 patients with TGCT enrolled in the double-blind portion and in 35 patients with TGCT in the open-label portion who crossed over to ROMVIMZA in MOTION, and in 135 patients with TGCT or solid tumors in other clinical trials. The safety of ROMVIMZA was evaluated in 83 adult patients with TGCT in MOTION [ see Clinical Studies ( 14 ) ]. MOTION excluded patients with bilirubin, AST, or ALT >ULN. All patients received ROMVIMZA twice weekly until disease progression or unacceptable toxicity. Among these patients, 82% were exposed for 6 months or longer and 30% were exposed for greater than one year. Serious adverse reactions occurred in 2.4% of patients who received ROMVIMZA. Serious adverse reactions in ≥1% included subcutaneous abscess (1.2%) and cellulitis (1.2%). Permanent discontinuation due to an adverse reaction occurred in 4.8% of patients who received ROMVIMZA. Adverse reactions leading to permanent discontinuation in one patient each included periorbital edema, neuropathy, rash, and hypertension. Dose reductions due to an adverse reaction or laboratory abnormality occurred in 39% of patients who received ROMVIMZA. Adverse reactions leading to dose reductions in ≥2% of patients receiving ROMVIMZA were rash, periorbital edema, peripheral edema, fatigue, pruritus, face edema, increased CPK, neuropathy, and hypertension. Dose interruptions due to an adverse reaction or laboratory abnormality occurred in 40% of patients who received ROMVIMZA. Adverse reactions leading to interruptions in ≥2% of patients included rash, fatigue, peripheral edema, increased CPK, periorbital edema, face edema, pruritus, neuropathy, and hypertension. The most common (≥20%) adverse reactions, including laboratory abnormalities that occurred in patients receiving ROMVIMZA were increased AST, periorbital edema, fatigue, rash, increased cholesterol, peripheral edema, face edema, decreased neutrophils, decreased leukocytes, pruritus, and increased ALT. Table 3 and Table 4 summarize the adverse reactions and laboratory abnormalities in MOTION during the randomized phase through Week 25. Table 3: Adverse Reactions Occurring in ≥10% of Patients Receiving ROMVIMZA with a Difference Between Arms of >5% Compared to Placebo Through Week 25 in MOTION Adverse Reaction* ROMVIMZA N=83 Placebo N=39 All Grades (%) Grade 3 or 4 (%) All Grades (%) Grade 3 or 4 (%) *The severity of adverse reactions was assessed using CTCAE v5.0. 1 Includes multiple related terms Eye disorders Periorbital edema 1 60 3.6 21 0 Lacrimation increased 12 0 0 0 Dry eye 1 10 0 0 0 General disorders and administration site conditions Fatigue 1 59 1.2 38 2.6 Peripheral edema 1 33 1.2 8 0 Face edema 31 1.2 8 0 Skin and subcutaneous tissue disorders Rash 1 47 3.6 5 0 Pruritus 29 2.4 8 0 Vascular disorders Hypertension 17 4.8 10 2.6 Nervous system disorders Neuropathy 1 12 1.2 2.6 0 Other clinically significant adverse reactions occurring in <10% of patients treated with ROMVIMZA include blurred vision (6%). Table 4: Laboratory...
Drug Interactions
7 DRUG 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.
Contraindications
4 CONTRAINDICATIONS None. None ( 4 )
Pregnancy and Breastfeeding
8.1 Pregnancy Risk Summary Based on data from animal studies and its mechanism of action, ROMVIMZA 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 ( see Data ) . 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. Data Animal Data In a rat embryo-fetal development study, pregnant female rats were dosed once daily during the period of organogenesis (gestational days 6 to 17) at doses of 2.5, 5, or 15 mg/kg/day. Structural abnormalities (skeletal variations) occurred at ≥2.5 mg/kg/day (approximately 3 times the exposure at the recommended dose based on AUC). Additional structural abnormalities (cardiac malformations) were observed at the highest dose of 15 mg/kg/day (approximately 23 times the exposure at the recommended dose based on AUC).
How Supplied
16 HOW SUPPLIED/STORAGE AND HANDLING Table 7: ROMVIMZA 14 mg, 20 mg, and 30 mg Capsules Strength Description Package Size and Type NDC Number 14 mg Size 4 hard gelatin capsule with white body and orange cap with black print “DCV14”, packed in oPA-film/ aluminum foil /PVC-film blisters with push-through aluminum foil lidding. Each carton contains one child-resistant blister pack containing 8 capsules (four-week supply) 73207-302-40 20 mg Size 2 hard gelatin capsule with white body and yellow cap with black print “DCV20”, packed in oPA-film/ aluminum foil /PVC-film blisters with push-through aluminum foil lidding. Each carton contains one child-resistant blister pack containing 8 capsules (four-week supply) 73207-303-40 30 mg Size 1 hard gelatin capsule with white body and light blue cap with black print “DCV30”, packed in oPA-film/ aluminum foil /PVC-film blisters with push-through aluminum foil lidding. Each carton contains one child-resistant blister pack containing 8 capsules (four-week supply) 73207-304-40 Store at controlled room temperature 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [See USP Controlled Room Temperature]. Store capsules in their original blister packs until ready to be taken. Do not store ROMVIMZA in another container.
About This Information
This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.
What are side effects?
Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.
What are drug interactions?
Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.