ROMVIMZA

Clinical summary

Indications and usage 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 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 discontinue ROMVIMZA. AST and/or ALT increases >8 times ULN Permanently discontinue ROMVIMZA. 2.3 Dosage Modification for P-glycoprotein (P-gp) Substrates Avoid concomitant use of ROMVIMZA with P-gp substrates. If concomitant use of a P-gp substrate is unavoidable, administer ROMVIMZA at least 4 hours before taking the P-gp substrate unless otherwise recommended in the substrate Prescribing Information [ see Drug Interactions ( 7.1 ) ]. Warnings and cautions 5 WARNINGS 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 [see Clinical Pharmacology ( 12.1 )]. 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 occurre