Version May 2024
Dosage guidance:
Safety: Restrict phosphate intake to 600 to 800 mg daily. Avoid concomitant use with agents that may alter serum phosphate levels before the initial (days 14 to 21) dose increase period.
Clinical considerations: Patients should receive dry eye prophylaxis with ocular demulcents, as needed.
Urothelial carcinoma, locally advanced or metastatic, FGFR3 mutation positive: Oral: Initial: 8 mg once daily; assess serum phosphate after 14 to 21 days, if serum phosphate is <9 mg/dL (and no ocular disorders or ≥ grade 2 toxicity), increase dose to 9 mg once daily based on tolerability; continue until disease progression or unacceptable toxicity occurs (Loriot 2023; Siefker-Radtke 2022).
Missed or vomited doses: If a dose is missed, administer the missed dose as soon as possible on the same day; return to the normal dosing schedule the following day. If vomiting occurs, administer the next dose the following day. Do not administer extra doses to make up for the missed or vomited dose.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
eGFR ≥30 mL/minute/1.73 m2: There are no dosage adjustments provided in the manufacturer’s labeling; however, there are no clinically meaningful differences in erdafitinib pharmacokinetics.
eGFR <30 mL/minute/1.73 m2: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
End-stage kidney disease requiring dialysis: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Mild to moderate impairment (Child-Turcotte-Pugh class A, B): There are no dosage adjustments provided in the manufacturer’s labeling; however, there are no clinically meaningful differences in erdafitinib pharmacokinetics.
Severe impairment (Child-Turcotte-Pugh class C): There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
|
Original dose |
1st dose reduction |
2nd dose reduction |
3rd dose reduction |
4th dose reduction |
5th dose reduction |
|---|---|---|---|---|---|
|
9 mg once daily. |
8 mg once daily. |
6 mg once daily. |
5 mg once daily. |
4 mg once daily. |
Discontinue erdafitinib. |
|
8 mg once daily. |
6 mg once daily. |
5 mg once daily. |
4 mg once daily. |
Discontinue erdafitinib. |
NA |
|
Adverse reaction |
Severity |
Erdafitinib dosage modification |
|---|---|---|
|
Hyperphosphatemia |
Restrict phosphate intake to 600 to 800 mg daily in all patients; avoid concomitant use of agents that may increase serum phosphate levels. | |
|
<6.99 mg/dL |
Continue erdafitinib at the current dose. | |
|
7 to 8.99 mg/dL |
Start phosphate binder with food until serum phosphate level is <7 mg/dL. Continue erdafitinib at the current dose. If serum phosphate remains ≥7 mg/dL for 2 months or if clinically necessary, reduce the erdafitinib dose. | |
|
9 to 10 mg/dL |
Start phosphate binder with food until serum phosphate level is <7 mg/dL. Withhold erdafitinib; monitor weekly until serum phosphate <7 mg/dL; resume erdafitinib at the same dose level. If serum phosphate remains ≥9 mg/dL for 1 month or if clinically necessary, reduce the erdafitinib dose. | |
|
>10 mg/dL |
Medically manage symptoms as clinically relevant. Withhold erdafitinib; monitor weekly until serum phosphate <7 mg/dL; resume erdafitinib with the dose reduced by one dose level. If serum phosphate remains ≥10 mg/dL for >2 weeks, permanently discontinue erdafitinib. | |
|
Life-threatening consequences; urgent intervention (eg, dialysis) indicated |
Permanently discontinue erdafitinib. | |
|
Ocular toxicity (central serous retinopathy) |
Any |
Withhold erdafitinib and perform ophthalmic evaluation within 2 weeks. Improvement within 14 days: Resume erdafitinib at the current dose. No improvement within 14 days: Withhold erdafitinib until improvement; resume at next lower dose level once improving. Upon resuming erdafitinib, monitor for recurrence every 1 to 2 weeks for a month. Recurrence or no improvement after 4 weeks of interruption: Consider permanent discontinuation. |
|
Other toxicity |
Grade 3 |
Withhold erdafitinib until resolution to grade 1 or baseline; resume at next lower dose level. |
|
Grade 4 |
Permanently discontinue erdafitinib. | |
Refer to adult dosing.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Dermatologic: Alopecia (26%), nail discoloration (11%), nail disease (45%, including onychoclasis, onycholysis, onychomadesis), palmar-plantar erythrodysesthesia (26%), paronychia (17%), xeroderma (34%)
Endocrine & metabolic: Decreased serum albumin (37%), decreased serum magnesium (30%), decreased serum phosphate (24%), decreased serum sodium (40%), hyperphosphatemia (76%), increased serum calcium (22%), increased serum potassium (16%), weight loss (16%)
Gastrointestinal: Abdominal pain (23%), constipation (28%), decreased appetite (38%), diarrhea (47%; grades 3/4: 2%), dysgeusia (37%), nausea (21%; grades 3/4: 1%), stomatitis (56%; grades 3/4: 9%), vomiting (13%; grades 3/4: 2%), xerostomia (45%)
Genitourinary: Hematuria (11%), urinary tract infection (17%)
Hematologic & oncologic: Decreased hemoglobin (35%; grades 3/4: 3%), decreased platelet count (19%; grades 3/4: 1%), decreased white blood cell count (17%)
Hepatic: Increased serum alanine aminotransferase (41%), increased serum alkaline phosphatase (41%), increased serum aspartate aminotransferase (30%)
Nervous system: Fatigue (54%; including asthenia)
Neuromuscular & skeletal: Arthralgia (11%), musculoskeletal pain (20%)
Ophthalmic: Blurred vision (17%), conjunctivitis (11%), dry eye syndrome (28%), retinal pigment epithelium detachment (≤25%), retinopathy (central serous: ≤25%)
Renal: Increased serum creatinine (52%)
Respiratory: Oropharyngeal pain (11%)
Miscellaneous: Fever (14%)
1% to 10%:
Endocrine & metabolic: Decreased serum glucose (fasting: 10%)
Hematologic & oncologic: Decreased neutrophils (10%; grades 3/4: 2%)
Ophthalmic: Increased lacrimation (10%)
Respiratory: Dyspnea (10%)
<1%:
Cardiovascular: Vascular calcification
Dermatologic: Cutaneous calcification (including non-uremic calciphylaxis)
There are no contraindications listed in the manufacturer's US labeling.
Canadian labeling: Hypersensitivity to erdafitinib or any component of the formulation.
Concerns related to adverse effects:
• Hyperphosphatemia/soft tissue mineralization: Hyperphosphatemia leading to soft tissue mineralization, cutaneous calcinosis, non-uremic calciphylaxis, and vascular calcification may occur. Hyperphosphatemia has been reported in 73% of patients receiving erdafitinib. The median time to hyperphosphatemia onset was 16 days (range: 8 to 421 days). Almost one-quarter of patients received phosphate binders during erdafitinib treatment. Vascular calcification has been reported in 0.2% of patients.
• Ocular toxicity: Ocular disorders may occur with erdafitinib. Central serous retinopathy/retinal pigment epithelial detachment (CSR/RPED) has been reported in approximately one-quarter of erdafitinib-treated patients, requiring dose modification. The median time to first onset of CSR/RPED was 46 days. Of patients who resumed treatment with erdafitinib following dose modification, two-thirds experienced recurrence and/or worsening of CSR/RPED. CSR/RPED may result in visual field defect. Dry eye symptoms occurred in over one-quarter of patients.
Special populations:
• CYP2C9 poor metabolizers: Systemic exposure of erdafitinib is anticipated to be increased (by ~50%) in patients with the CYP2C9*3/*3 genotype; monitor for increased adverse reactions in patients with known or suspected CYP2C9*3/*3 genotype.
• Older adults: Patients ≥65 years of age experienced a higher incidence of adverse reactions requiring treatment discontinuation compared to patients <65 years of age.
Other warnings/precautions:
• FGFR3 mutation positivity: Erdafitinib is approved for the treatment of locally advanced or metastatic urothelial carcinoma in patients with susceptible FGFR3 genetic alterations in tumor specimens. Information on approved tests may be found at http://www.fda.gov/companiondiagnostics.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Balversa: 3 mg, 4 mg, 5 mg
No
Tablets (Balversa Oral)
3 mg (per each): $403.73
4 mg (per each): $538.30
5 mg (per each): $672.88
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Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Balversa: 3 mg, 4 mg, 5 mg
Oral: Administer with or without food; swallow tablets whole.
This medication is not on the NIOSH (2016) list; however, it may meet the criteria for a hazardous drug. Erdafitinib may cause teratogenicity, reproductive toxicity, and has a structural or toxicity profile similar to existing hazardous agents.
Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2016; USP-NF 2020).
Note: Facilities may perform risk assessment of some hazardous drugs to determine if appropriate for alternative handling and containment strategies (USP-NF 2020). Refer to institution-specific handling policies/procedures.
Urothelial carcinoma, locally advanced or metastatic, FGFR3 mutation positive: Treatment of locally advanced or metastatic urothelial carcinoma in adults with susceptible FGFR3 genetic alterations, as detected by an approved test, and with progression on or after at least 1 prior line of systemic therapy.
Limitations of use: Erdafitinib is not recommended for the treatment of patients who are eligible for and have not received prior PD-1 or PD-L1 inhibitor therapy.
Erdafitinib may be confused with enasidenib, encorafenib, Entadfi, entrectinib, eribulin, erlotinib, futibatinib, gefitinib, infigratinib, pemigatinib
Balversa may be confused with Balziva
This medication is in a class the Institute for Safe Medication Practices (ISMP) includes among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.
Substrate of CYP2C9 (major), CYP3A4 (major), P-glycoprotein/ABCB1 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
CYP2C9 Inhibitors (Moderate): May increase the serum concentration of Erdafitinib. Management: Avoid concomitant use of erdafitinib and moderate CYP2C9 inhibitors when possible. If combined, monitor closely for erdafitinib adverse reactions and consider dose modifications accordingly. Risk D: Consider therapy modification
CYP3A4 Inducers (Moderate): May decrease the serum concentration of Erdafitinib. Management: Dose modifications of erdafitinib may be required. See full monograph for details. Risk D: Consider therapy modification
CYP3A4 Inducers (Strong): May decrease the serum concentration of Erdafitinib. Risk X: Avoid combination
CYP3A4 Inhibitors (Strong): May increase the serum concentration of Erdafitinib. Management: Avoid concomitant use of erdafitinib and strong CYP3A4 inhibitors when possible. If combined, monitor closely for erdafitinib adverse reactions and consider dose modifications accordingly. Risk D: Consider therapy modification
CYP3A4 Substrates (Narrow Therapeutic Index/Sensitive with Inducers): Erdafitinib may decrease the serum concentration of CYP3A4 Substrates (Narrow Therapeutic Index/Sensitive with Inducers). Risk X: Avoid combination
CYP3A4 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors): Erdafitinib may increase the serum concentration of CYP3A4 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk X: Avoid combination
Fexinidazole: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
OCT2 Substrates (Clinically Relevant with Inhibitors): Erdafitinib may increase the serum concentration of OCT2 Substrates (Clinically Relevant with Inhibitors). Management: Consider alternatives to this combination when possible. If combined, monitor for increased effects/toxicities of OCT2 substrates and consider OCT2 substrate dose reductions when appropriate. Risk D: Consider therapy modification
P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors): Erdafitinib may increase the serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Management: If coadministration with these narrow therapeutic index/sensitive P-gp substrates is unavoidable, separate erdafitinib administration by at least 6 hours before or after administration of these P-gp substrates. Risk D: Consider therapy modification
Serum Phosphate Level-Altering Agents: May diminish the therapeutic effect of Erdafitinib. Management: Avoid coadministration of serum phosphate level-altering agents with erdafitinib before initial dose increase period based on serum phosphate levels (Days 14 to 21). Risk D: Consider therapy modification
Evaluate pregnancy status prior to use in patients who could become pregnant. Patients who could become pregnant and patients with partners who could become pregnant should use effective contraception during treatment and for 1 month after the last erdafitinib dose.
Based on the mechanism of action, and data from animal reproduction studies, in utero exposure to erdafitinib may cause fetal harm.
A pregnancy registry is available for all cancers diagnosed during pregnancy at Cooper Health (1-877-635-4499).
It is not known if erdafitinib is present in breast milk.
Due to the potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended by the manufacturer during treatment and for 1 month after the last erdafitinib dose.
Restrict phosphate intake to 600 to 800 mg daily.
Assess for susceptible FGFR3 genetic alteration (in tumor specimens). Monitor serum phosphate level at baseline, at 14 to 21 days after therapy initiation, and then monthly or as clinically necessary; monitor weekly if hyperphosphatemia occurs. Evaluate pregnancy status prior to use (in patients who could become pregnant). Perform ophthalmological exams at baseline and then monthly for the first 4 months of erdafitinib therapy, then every 3 months thereafter, and as clinically necessary (monitor every 1 to 2 weeks for 1 month for recurrence if central serous retinopathy occurs); exam should include visual acuity assessment, slit lamp examination, fundoscopy, and optical coherence tomography. Monitor for increased adverse reactions (in patients with known or suspected CYP2C9*3/*3 genotype). Monitor adherence.
The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.
Erdafitinib is a pan fibroblast growth factor receptor (FGFR) kinase inhibitor that binds to and inhibits FGFR1, FGFR2, FGFR3, and FGFR4 enzyme activity. FGFR inhibition results in decreased FGFR-related signaling and decreased cell viability in cell lines expressing FGFR genetic alterations, including point mutations, amplifications, and fusions.
Distribution: Vd: 29 L
Protein binding: 99.7%, primarily to alpha-1-acid glycoprotein
Metabolism: Primarily hepatic by CYP2C9 and CYP3A4
Half-life elimination: 59 hours
Time to peak: 2.5 hours (range: 2 to 6 hours)
Excretion: Feces: ~69% (19% as unchanged drug); urine: 19% (13% as unchanged drug)
Clearance: 0.362 L/hour
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