Erdafixen Tablet

Erdafixen is a kinase inhibitor indicated for the treatment of adult patients with locally advanced or metastatic urothelial carcinoma (mUC) that has-

• Susceptible FGFR3 or FGFR2 genetic alterations and
• Progressed during or following at least one line of prior platinum-containing chemotherapy including within 12 months of neoadjuvant or adjuvant platinum-containing chemotherapy.

Erdafitinib is a kinase inhibitor that binds to and inhibits enzymatic activity of FGFR1, FGFR2, FGFR3 and FGFR4 based on in vitro data. Erdafitinib also binds to RET, CSF1R, PDGFRA, PDGFRB, FLT4, KIT, and VEGFR2. Erdafitinib inhibits FGFR phosphorylation and signaling and decreases cell viability in cell lines expressing FGFR genetic alterations, including point mutations, amplifications, and fusions. Erdafitinib demonstrates antitumor activity in FGFR-expressing cell lines and xenograft models derived from tumor types, including bladder cancer.

The recommended starting dose of Erdafitinib is 8 mg (two 4 mg tablets) orally once daily, with a dose increase to 9 mg (three 3 mg tablets) once daily based on serum phosphate (PO4) levels and tolerability at 14 to 21 days. Treatment should be continued until disease progression or unacceptable toxicity occurs.

If a dose of Erdafitinib is missed, it can be taken as soon as possible on the same day. The regular daily dose schedule for Erdafitinib should be resumed the next day. Extra tablets should not be taken to make up for the missed dose.

Moderate CYP2C9 or strong CYP3A4 inhibitors: Alternative agents should be considered or adverse reactions should be closely monitored.

Strong CYP2C9 or CYP3A4 inducers: Concomitant use with Erdafixen should be avoided.

Moderate CYP2C9 or CYP3A4 inducers: Erdafixen dose should be increased up to 9 mg.

Serum phosphate level-altering agents: Concomitant use with agents that can alter serum phosphate levels before the initial dose modification period should be avoided.

CYP3A4 substrates: Concomitant use with sensitive CYP3A4 substrates with narrow therapeutic indices should be avoided.

OCT2 substrates: Either alternative agents or reduction of the dose of OCT2 substrates based on tolerability should be considered.

P-gp substrates: Erdafixen administration should be separated by at least 6 hours before or after administration of P-gp substrates with narrow therapeutic indices

The most common adverse reactions including laboratory abnormalities (≥20%) are elevated phosphate, stomatitis, fatigue, elevated creatinine, diarrhea, dry mouth, nail disorder, elevated alanine aminotransferase, elevated alkaline phosphatase, decrease in sodium, decrease in appetite, decrease in albumin, dysgeusia, decrease in hemoglobin, dry skin, elevated aspartate aminotransferase, decrease in magnesium, dry eye, alopecia, palmar-plantar erythrodysesthesia syndrome, constipation, decrease in phosphate, abdominal pain, elevated calcium, nausea, and musculoskeletal pain.

Ocular disorders: Erdafixen can cause central serous retinopathy/retinal pigment epithelial detachment (CSR/RPED). Monthly ophthalmological examinations should be performed during the first four months of treatment, every 3 months afterwards, and at any time for visual symptoms. When CSR/RPED occurs, Erdafixen should be withheld and permanently discontinued if it does not resolve within 4 weeks or if Grade 4 in severity.

Hyperphosphatemia: Hyperphosphatemia should be monitored and managed with dose modifications when required.

Embryo-fetal toxicity: Since it can cause fetal harms so patients of the potential risk to the fetus should be advised to use effective contraception.

Pediatric Use: Safety and effectiveness of Erdafixen in pediatric patients have not been established.

Geriatric Use: No overall differences in safety or effectiveness were observed between these patients and younger patients.

Renal Impaired: No dose adjustment is recommended for patients with mild to moderate renal impairment.

Hepatic Impaired: No dose adjustment is recommended for patients with mild (Child-Pugh A) or moderate (Child-Pugh B) hepatic impairment. Limited data are available in patients with severe (Child-Pugh C) hepatic impairment.

CYP2C9 Poor Metabolizers: CYP2C9*3/*3 Genotype: Erdafixen plasma concentrations were predicted to be higher in patients with the CYP2C9*3/*3 genotype. Patients who are known or suspected to have CYP2C9*3/*3 genotype should be monitored for increased adverse reactions.

Cytotoxic Chemotherapy

Store below 30°C, in a cool and dry place. Keep away from light. Keep out of the reach of children.