er-da-FI-ti-nib

Therapeutic Classification: antineoplastics

Pharmacologic Classification: kinase inhibitors, fibroblast growth factor receptor inhibitor

• Locally advanced or metastatic urothelial carcinoma that has susceptible fibroblast growth factor receptor (FGFR) 3 or FGFR2 alterations and has progressed during or following 1 line of prior platinum-containing chemotherapy, including within 12 mo of neoadjuvant or adjuvant platinum-containing chemotherapy.

• FGFR kinase inhibitor that binds to and inhibits FGFR1, FGFR2, FGFR3, and FGFR4 enzyme activity which results in decreased FGFR-related signaling and decreased cell viability in cell lines expressing FGFR genetic alterations, including point mutations, amplifications, and fusions.

• Decreased spread of locally advanced or metastatic urothelial carcinoma.

Absorption: Unknown.

Distribution: Widely distributed to tissues.

Protein Binding: >99%.

Metabolism/Excretion: Primarily metabolized in liver by CYP2C9 and CYP3A4 isoenzymes; the CYP2C9 isoenzyme exhibits genetic polymorphism (intermediate or poor metabolizers may have significantly ↑ erdafitinib concentrations and an ↑ risk of adverse reactions).69% excreted in feces (19% as unchanged drug), 19% in urine (13% as unchanged drug).

Half-life: 59 hr.

(plasma concentrations)

Contraindicated in:

• OB: Pregnancy (may cause fetal harm)
• Lactation: Lactation.

Use Cautiously in:

• CYP2C9 poor metabolizers (↑ risk of adverse reactions)
• Rep: Women of reproductive potential and men with female partners of reproductive potential
• Pedi: Safety and effectiveness not established in children.

Derm: alopecia, dry skin, nail detachment, nail discoloration, palmar-plantar erythrodysesthesia syndrome.

EENT: blurred vision, central serous retinopathy/retinal pigment epithelial detachment, conjunctivitis, dry eyes, lacrimation.

Endo: hyperglycemia.

F and E: hypercalcemia, hyperkalemia, hyperphosphatemia, hypomagnesemia, hyponatremia, hypophosphatemia.

GI: abdominal pain, ↓albumin, constipation, diarrhea, dry mouth, ↑liver enzymes, metallic taste, nausea, stomatitis, vomiting.

GU: hematuria, ↑serum creatinine, ↓ fertility (females).

Hemat: anemia, leukopenia, neutropenia, thrombocytopenia.

MS: arthralgia, pain.

Metab: ↓appetite, ↓weight.

Neuro: fatigue.

Resp: dyspnea.

Misc: fever.

Drug-Drug:

• Moderate CYP2C9 inhibitors, including fluconazole, and strong CYP3A4 inhibitors, including itraconazole, may ↑ levels and risk of toxicity; avoid concurrent use, if possible; if must use concurrently, ↓ erdafitinib dose.
• Strong CYP2C9 inducers and strong CYP3A4 inducers, including rifampin, may ↓ levels and effectiveness; avoid concurrent use.
• Moderate CYP2C9 inducers and moderate CYP3A4 inducers may ↓ levels and effectiveness; avoid concurrent use, if possible; if must use concurrently, consider ↑ erdafitinib dose. Serum-phosphate level altering drugs may ↑ or ↓ phosphate levels which can have impact on ability to adjust erdafitinib doses; avoid concurrent use before initial erdafitinib dose increase period.
• May ↑ or ↓ levels of CYP3A4 substrates; avoid concurrent use with CYP3A4 substrates that have a narrow therapeutic index.
• May ↑ levels of organic cation transporter 2 (OCT2) substrates, including metformin; consider alternative therapy or ↓ dose of OCT2 substrate.
• May ↑ levels of P-glycoprotein substrates; avoid concurrent use, if possible; if must use concurrently, separate by 6 hr.

• PO (Adults): 8 mg once daily; may ↑ to 9 mg once daily at 14–21 days if serum phosphate level <5.5 mg/dL, no ocular disorders, and no Grade 2 or higher adverse reactions. Continue therapy until disease progression or unacceptable toxicity.

• Tablets: 3 mg; 4 mg; 5 mg;

• Perform monthly ophthalmological exams including assessment of visual acuity, slit lamp exam, fundoscopy, and optical coherence tomography during first 4 months of therapy and every 3 months afterwards, and urgently for visual symptoms. Monitor for central serous retinopathy/retinal pigment epithelial detachment (CSR/RPED). If Grade 1 CSR/RPED: asymptomatic; clinical or diagnostic observations only, occurs, hold erdafitinib until resolution. If resolves within 4 wk, resume at next lower dose. If no recurrence for 1 mo, consider increasing dose. If stable for 2 consecutive eye exams but not resolved, resume at next lower dose level. If Grade 2: visual acuity 20/40 or better or 3 lines of decreased vision from baseline occurs, hold erdafitinib until resolution. If resolves with in 4 wks, may resume at next lower dose. If Grade 3: visual acuity worse than 20/40 or >3 lines of decreased vision from baseline occurs, hold erdafitinib until resolution. If resolves with in 4 wks, may resume 2 dose levels lower. If recurs, consider permanent discontinuation. If Grade 4: visual acuity 20/200 or worse in affected eye occurs, discontinue erdafitinib permanently.

• Verify negative pregnancy test before starting therapy.
  • Patient selection is based on presence of susceptible FGFR genetic alterations in tumor specimens as detected by an FDA-approved companion diagnostic. Information on FDA-approved tests for the detection of FGFR genetic alterations in urothelial cancer is available at: www.fda.gov/CompanionDiagnostics.
  • Assess serum phosphate levels 14–21 days after starting therapy. Increase dose to 9 mg once daily if serum phosphate <5.5 mg/dL and no ocular disorders or Grade 2 adverse reactions. Monitor phosphate levels monthly for hyperphosphatemia. If serum phosphate 5.6-6.9 mg/dL (1.8-2.3 mmol/L), continue erdafitinib at same dose. If serum phosphate 7.0-9.0 mg/dL (2.3-2.9 mmol/L), hold erdafitinib with weekly reassessments until level <5.5 mg/dL (or baseline). Then restart at same dose level. Dose reduction may be used for hyperphosphatemia lasting >1 wk. If serum phosphate >9.0 mg/dL (> 2.9 mmol/L), hold erdafitinib and monitor weekly until level <5.5 mg/dL (or baseline). Resume at 1 dose level lower. If serum phosphate >10.0 mg/dL (> 3.2 mmol/L) or significant change in baseline renal function or Grade 3 hypercalcemia occurs, hold erdafitinib and monitor weekly until level <5.5 mg/dL (or baseline). Resume at 2 dose levels lower.

• Limit phosphate intake to 600–800 mg daily. If serum phosphate >7.0 mg/dL, may add oral phosphate binder until serum phosphate levels <5.5 mg/dL.
• Recommended Dose Modifications : If 9 mg dose,1st dose reduction: to 8 mg, 2nd dose reduction: to 6 mg, 3rd reduction: to 5 mg, 4th reduction: to 4 mg, 5th dose reduction discontinue therapy. If 8 mg dose, 1st dose reduction: to 6 mg, 2nd reduction: to 5 mg, 3rd reduction: to 4 mg, 4th reduction discontinue therapy.
• PO: Administer once daily without regard to food. DNC: Swallow tablets whole; do not crush, break, or chew.

• Instruct patient to take erdafitinib as directed. If vomiting occurs any time after taking, take next dose the next day as scheduled. Take missed doses as soon as remembered on the same day. Resume regular schedule next day; do not double doses. Advise patient to read Patient Information before starting and with Rx refill in case of changes.
• Advise patient to notify health care professional immediately if eye problems (dry or inflamed eyes, blurred vision, loss of vision or other visual changes). Instruct patient to use artificial tear substitutes, hydrating or lubricating eye gels or ointments at least every 2 hr during waking hours to help prevent dry eyes.
• Advise patient to notify health care professional promptly if nail or skin problems (nails separating from nail bed, nail pain, nail bleeding, breaking of nails, color or texture changes in nails, infected skin around nail, itchy skin rash, dry skin, cracks in skin) occur.
• Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications.
• Rep: May cause fetal harm. Advise females of reproductive potential and males with female partners of reproductive potential to use effective contraception and avoid breastfeeding during and for 1 mo after last dose. May impair fertility in females of reproductive potential.
• Emphasize the importance of routine lab tests and eye exams.

• Decreased spread of locally advanced or metastatic urothelial carcinoma.

Balversa

• Deficient knowledge, Relate med (Patient/Family Teaching).

NDC Code^*

• 59676- Janssen Products LP
  • 59676-030- BALVERSA
    • 59676-030-56- 1 BOTTLE in 1 CARTON (59676-030-56) > 56 TABLET, FILM COATED in 1 BOTTLE

• 59676- Janssen Products LP
  • 59676-030- BALVERSA
    • 59676-030-84- 1 BOTTLE in 1 CARTON (59676-030-84) > 84 TABLET, FILM COATED in 1 BOTTLE

• 59676- Janssen Products LP
  • 59676-040- BALVERSA
    • 59676-040-28- 1 BOTTLE in 1 CARTON (59676-040-28) > 28 TABLET, FILM COATED in 1 BOTTLE

• 59676- Janssen Products LP
  • 59676-040- BALVERSA
    • 59676-040-56- 1 BOTTLE in 1 CARTON (59676-040-56) > 56 TABLET, FILM COATED in 1 BOTTLE

• 59676- Janssen Products LP
  • 59676-050- BALVERSA
    • 59676-050-28- 1 BOTTLE in 1 CARTON (59676-050-28) > 28 TABLET, FILM COATED in 1 BOTTLE