Erdafitinib (Monograph)

Brand name: Balversa
Drug class: Antineoplastic Agents

Medically reviewed by Drugs.com on Dec 10, 2024. Written by ASHP.

Introduction

Antineoplastic agent; potent of fibroblast growth factor receptors (FGFR)-1, FGFR-2, FGFR-3, and FGFR-4.

Uses for Erdafitinib

Urothelial Carcinoma

Treatment of adults with locally advanced or metastatic urothelial carcinoma with susceptible fibroblast growth factor receptor (FGFR-3) genetic alterations that has progressed during or following at least one prior systemic therapy.

An FDA-approved companion diagnostic test (e.g., Qiagen therascreen FGFR RGQ RT-PCR Kit) is required to confirm the presence of susceptible FGFR-3genetic alterations in tumor specimens prior to initiation of therapy.

Not recommended for treatment of patients who are eligible for and have not received prior programmed cell death (PD)-1 or programmed death-ligand 1 (PD-L1) inhibitor therapy.

The European Society of Medical Oncology (ESMO) updated guideline recommends administration of enfortumab vedotin in combination with pembrolizumab as first-line therapy for treatment-naïve advanced or metastatic urothelial carcinoma, irrespective of platinum eligibility.

If progression occurs on enfortumab vedotin in combination with pembrolizumab, standard platinum-based chemotherapy without maintenance avelumab in unselected patients or erdafitinib in selected FGFR-altered tumors can be recommended.

Erdafitinib Dosage and Administration

General

Pretreatment Screening

Confirm presence of susceptible fibroblast growth factor receptor (FGFR-3) genetic alterations in tumor specimens prior to initiation of erdafitinib therapy.
Because elevated phosphate concentrations occur frequently in patients receiving erdafitinib, phosphate intake should not exceed 600–800 mg daily during therapy.
Assess concomitant therapy, including prescription drugs, OTC drugs, and dietary or herbal supplements, for agents that may alter plasma phosphate concentrations.
Verify pregnancy status in females of reproductive potential prior to initiating therapy.

Patient Monitoring

Monitor serum phosphate concentrations 14–21 days following initiation of erdafitinib therapy and then monthly thereafter or more frequently as clinically indicated.
Perform ophthalmologic examination, including visual acuity assessment, slit lamp examination, fundoscopy, and optical coherence tomography, monthly during the first 4 months of erdafitinib therapy; every 3 months thereafter; and as clinically indicated (e.g., if new or worsening visual disturbances occur).

Premedication and Prophylaxis

To minimize the risk of dry eye, the manufacturer recommends prophylaxis with ophthalmic demulcents (e.g., artificial tears substitutes, hydrating or lubricating ophthalmic gel or ointment). Apply ophthalmic demulcents frequently (i.e., at least every 2 hours) during waking hours.

Administration

Oral Administration

Administer orally once daily without regard to meals. Swallow tablets whole.

If a dose of erdafitinib is missed, take the missed dose as soon as possible on the same day and resume the regular dosing schedule the next day.

If vomiting occurs at any time following administration of erdafitinib, do not administer a replacement dose; take the next dose at the regularly scheduled time.

Dosage

Adults

Urothelial Carcinoma

Oral

Initially, 8 mg once daily; if this initial dosage is tolerated (i.e., serum phosphate concentrations <9 mg/dL, absence of ocular disorders or grade 2 or greater adverse effects) for 14–21 days, increase dosage to a maximum dosage of 9 mg once daily.

If phosphate level ≥9 mg/dL, follow the relevant dose modifications in Table 2.

Continue therapy until disease progression or unacceptable toxicity occurs.

Dosage Modification for Toxicity

Oral

Adverse effects may require temporary interruption, dosage reduction, and/or permanent discontinuance. If dosage modification is required, reduce dosage as described in Table 1.

Table 1. Dosage Modification for Erdafitinib Toxicity Following Therapy Interruption1
Dose Reduction Level	Current Dosage of 8 mg Daily	Current Dosage of 9 mg Daily
First	Restart at 6 mg daily	Restart at 8 mg daily
Second	Restart at 5 mg daily	Restart at 6 mg daily
Third	Restart at 4 mg daily	Restart at 5 mg daily
Fourth	Discontinue erdafitinib	Restart at 4 mg daily
Fifth		Discontinue erdafitinib

Hyperphosphatemia

Oral

If hyperphosphatemia (≥7 mg/dL) occurs during therapy, temporary interruption, dosage reduction, and/or permanent discontinuance of the drug may be necessary. If serum phosphate with life-threatening consequences occurs and urgent intervention required (e.g., dialysis), permanently discontinue erdafitinib.

Table 2. Dosage Modification for Hyperphosphatemia.1
Serum Phosphate Concentration (mg/dL)	Dosage Modification
7–8.99	Continue therapy at the current dosage; start phosphate binder with food until phosphate level <7 mg/dL Reduce dose if phosphate level remains ≥7 mg/dL for a period of 2 months or if clinically necessary
9 to 10	Withhold therapy with weekly reassessments until phosphate level <7 mg/dL; then restart at the same dose level Start phosphate binder with food until phosphate level <7 mg/dL Reduce dose if phosphate level ≥9 mg/dL for a period of 1 month or if clinically necessary
>10	Withhold therapy with weekly reassessments until phosphate level <7 mg/dL; then restart at the first reduced dose level If hyperphosphatemia (≥10 mg/dL) for >2 weeks, discontinue therapy permanently Utilize medical management of symptoms as clinically relevant

Ocular Effects

Oral

For central serous retinopathy, temporary interruption, dosage reduction, and/or permanent discontinuance may be necessary (see Table 3).

Table 3. Dosage Modification for Central Serous Retinopathy.13
Severity	Dosage Modification
Any grade	Withhold erdafitinib and perform an ophthalmologic evaluation within 2 weeks. If improving within 14 days, restart therapy at the current dose If not improving within 14 days, withhold erdafitinib until improving; once improving, may resume at the next lower dose level Upon restarting erdafitinib, monitor for recurrence every 1 to 2 weeks for a month If recurs or has not improved after 4 weeks of withholding therapy, consider permanent discontinuation

Other Adverse Effects

Oral

For other grade 3 adverse reactions, temporarily interrupt therapy; upon recovery to grade 1 or less or to baseline, resume therapy at a dosage reduced by 1 dose level.

For grade 4 adverse reactions, permanently discontinue drug.

Special Populations

Hepatic Impairment

Mild to moderate hepatic impairment (Child-Pugh class A or B): No dosage adjustment necessary.

Severe hepatic impairment (Child-Pugh class C): Limited data available.

Renal Impairment

Mild to moderate renal impairment (eGFR 30–89 mL/minute per 1.73 m²): No dosage adjustment necessary.

Severe renal impairment: Limited data available.

Geriatric Patients

No special dosage recommendations at this time.

Cautions for Erdafitinib

Contraindications

None.

Warnings/Precautions

Ocular Disorders

Central serous retinopathy and retinal pigment epithelial detachment resulting in visual field defect reported. Dry eye symptoms also reported.

Initiate dry eye prophylaxis with ophthalmic demulcents upon initiation of erdafitinib.

Perform ophthalmologic examinations, including visual acuity assessment, slit lamp examination, fundoscopy, and optical coherence tomography, monthly during the first 4 months of therapy, every 3 months thereafter, and as clinically indicated (e.g., if new or worsening visual disturbances occur); if visual disturbances occur, perform ophthalmologic examinations urgently. If ocular toxicities occur, interrupt therapy or permanently discontinue drug.

Hyperphosphatemia and Soft Tissue Mineralization

Elevated serum phosphate concentration occurs secondary to FGFR inhibition.

Erdafitinib can cause hyperphosphatemia leading to soft tissue mineralization, cutaneous calcinosis, nonuremic calciphylaxis, and vascular calcification.

Phosphate intake should not exceed 600–800 mg daily during therapy, and patients should avoid concurrent use of agents that may increase serum phosphate levels. If hyperphosphatemia (serum phosphate concentrations >7 mg/dL) occurs, consider initiation of an oral phosphate binder until serum phosphate concentrations improve to <7 mg/dL or baseline. Treatment interruption, dosage reduction, or discontinuance of therapy may be necessary.

Fetal/Neonatal Morbidity and Mortality

May cause fetal harm. Embryofetal toxicity and teratogenicity demonstrated in animals.

Confirmation of pregnancy status is recommended prior to initiating therapy. Avoid pregnancy during therapy. If used during pregnancy, apprise patient of potential fetal hazard.

Specific Populations

Pregnancy

May cause fetal harm.

Lactation

Not known whether erdafitinib is distributed into human milk, affects milk production, or affects nursing infants.

Females should not breast-feed during therapy and for 1 month following the last dose.

Females and Males of Reproductive Potential

Advise females of reproductive potential to use effective contraceptive methods while receiving erdafitinib and for 1 month after discontinuance of the drug.

Advise males with female partners of reproductive potential to use effective methods of contraception while receiving erdafitinib and for 1 month after discontinuance of the drug.

Results of animal studies suggest erdafitinib may impair female fertility.

Pediatric Use

Safety and efficacy not established in pediatric patients.

Chondroid dysplasia or metaplasia in multiple bones and tooth abnormalities (i.e., abnormal or irregular dentin, odontoblast discoloration and degeneration) observed in animals.

Geriatric Use

In clinical trials, 40% of patients were 65 to 74 years of age and 20% were ≥75 years of age; no overall differences in efficacy relative to younger adults. Patients ≥65 years of age experienced higher incidence of adverse reactions requiring treatment discontinuation than younger patients.

Hepatic Impairment

Mild or moderate hepatic impairment (Child-Pugh class A or B) does not substantially affect pharmacokinetics of erdafitinib.

Pharmacokinetics of erdafitinib have not been established in patients with severe hepatic impairment.

Renal Impairment

Mild or moderate renal impairment do not substantially affect pharmacokinetics of erdafitinib.

Pharmacokinetics of erdafitinib have not been established in patients with severe renal impairment or those with renal impairment requiring dialysis.

Pharmacogenomic Considerations

Closely monitor patients who are known or suspected poor CYP2C9 metabolizers carrying the CYP2C9*3/*3 genotype; systemic exposure of erdafitinib may be increased.

Common Adverse Effects

Adverse effects and laboratory abnormalities reported in ≥20% of patients: Increased phosphate, nail disorders, stomatitis, diarrhea, increased creatinine, increased alkaline phosphatase, increased ALT, decreased hemoglobin, decreased sodium, increased AST, fatigue, dry mouth, dry skin, decreased phosphate, decreased appetite, dysgeusia, constipation, increased calcium, dry eye, palmar-plantar erythrodysesthesia syndrome, increased potassium, alopecia, central serous retinopathy.

Drug Interactions

Principally metabolized by CYP2C9 and 3A4.

Time-dependent inhibitor and inducer of CYP3A4, but is not an inhibitor of other major CYP isoenzymes.

In vitro, substrate of P-glycoprotein (P-gp). Inhibitor of P-gp and organic cation transporter (OCT) 2, but is not an inhibitor of breast cancer resistance protein (BCRP), organic anion transporting polypeptide (OATP) 1B or 1B3, organic anion transporter (OAT) 1 or 3, OCT1, and multidrug and toxin extrusion (MATE) 1 or 2K transporters.

Drugs Affecting Hepatic Microsomal Enzymes

Moderate CYP2C9 and/or strong CYP3A4 inhibitors: Possible increased erdafitinib plasma concentrations and increased risk of erdafitinib toxicity. Avoid concomitant use; consider alternative agent with less CYP2C9 and/or 3A4 inhibition potential. If concomitant use cannot be avoided, monitor closely for signs of toxicity; consider dosage modification. When the moderate CYP2C9 or strong CYP3A4 inhibitor is discontinued, resume the erdafitinib dose used before dose modifications in the absence of drug-related toxicity.

Strong or moderate 3A4 inducers: Possible decreased erdafitinib plasma concentrations and reduced erdafitinib efficacy. Avoid concomitant use with strong 3A4 inducers. If concomitant use of a moderate 3A4 inducer cannot be avoided upon initiation of erdafitinib, initiate erdafitinib at 9 mg once daily. When the moderate CYP3A4 inducer is discontinued, continue erdafitinib at the same dosage, in the absence of drug-related toxicity.

Drugs Metabolized by Hepatic Microsomal Enzymes

CYP3A4 substrates: Possible altered plasma concentrations of CYP3A4 substrate and either reduced efficacy or increased toxicity of CYP3A4 substrate; effect on sensitive CYP3A4 substrate not established. Avoid concomitant use with sensitive CYP3A4 substrates that have a narrow therapeutic index.

Drugs Affecting or Affected by P-glycoprotein Transport

P-gp inhibitors: Pharmacokinetic interactions unlikely.

P-gp substrates: Possible increased plasma concentrations of P-gp substrate and increased risk of toxicity of P-gp substrate. If concomitant use is necessary, administer erdafitinib ≥6 hours before or after administration of P-gp substrates that have a narrow therapeutic index.

Drugs Affecting Serum Phosphate Concentrations

Concomitant use with drugs affecting serum phosphate concentrations may result in increased or decreased serum phosphate concentrations. Avoid concomitant use prior to initial dosage titration period (i.e., initial 14–21 days of erdafitinib therapy).

Specific Drugs

Drug	Interaction	Comments
Antacids	No clinically meaningful effect on erdafitinib bioavailability	Avoid concomitant use prior to initial serum phosphate concentration-based dosage titration
Antifungals, azoles (e.g., fluconazole, itraconazole)	Strong CYP2C9 and/or CYP3A4 inhibitors: Possible increased erdafitinib plasma concentrations and increased risk of toxicity Fluconazole: Increased peak plasma concentrations and AUC of erdafitinib by 21 and 48%, respectively Itraconazole: Increased peak plasma concentrations and AUC of erdafitinib by 5 and 34%, respectively	Consider alternative antifungal with less CYP2C9 or CYP3A4 inhibition potential; if concomitant use cannot be avoided, monitor closely for toxicity If serious or life-threatening toxicity occurs, interrupt therapy and reduce erdafitinib dosage
Digoxin	Possible increased plasma concentrations of digoxin and increased risk of toxicity	If concomitant use is necessary, administer erdafitinib ≥6 hours before or after administration of digoxin
Histamine H₂-receptor antagonists	No clinically meaningful effect on erdafitinib bioavailability
Midazolam	Possible increased or decreased plasma concentrations of midazolam and reduced efficacy or increased toxicity
Phosphate-containing products (e.g., laxative, enema)	Possible altered serum phosphate concentrations	Avoid concomitant use prior to initial serum phosphate concentration-based dosage titration
Proton-pump inhibitors	No clinically meaningful effect on erdafitinib bioavailability
Potassium phosphate supplements	Possible altered serum phosphate concentrations	Avoid concomitant use prior to initial serum phosphate concentration-based dosage titration
Rifampin	Strong CYP3A inducer: Possible decreased erdafitinib concentrations and reduced efficacy	Avoid concomitant use
Vitamin D supplements	Possible altered serum phosphate concentrations	Avoid concomitant use prior to initial serum phosphate concentration-based dosage titration

Erdafitinib Pharmacokinetics

Absorption

Bioavailability

Pharmacokinetics are dose proportional over dose range of 0.5–12 mg following single or repeated once-daily dosing.

Peak plasma concentrations attained in a median of 2.5 hours.

Steady-state concentrations achieved after 2 weeks of once-daily dosing with approximately 4-fold accumulation.

Food

Administration of single 9-mg dose of erdafitinib with a high-fat, high-calorie meal (800–1000 calories with approximately 50% of calories from fat) did not affect erdafitinib pharmacokinetics in healthy individuals.

Special Populations

Mild hepatic impairment (total bilirubin concentration not exceeding the ULN with AST concentration exceeding the ULN, or total bilirubin concentration above normal but not >1.5 times the ULN with any AST concentration) does not affect pharmacokinetics. Pharmacokinetics not established in patients with moderate or severe hepatic impairment.

Mild or moderate renal impairment (eGFR 30–89 mL/min per 1.73 m²) does not affect pharmacokinetics. Pharmacokinetics not established in patients with severe renal impairment or those with renal impairment requiring dialysis.

Poor CYP2C9 metabolizers (those with CYP2C9*3/*3 genotype): Systemic exposure increased by 50% compared with individuals with the CYP2C9*1/*1 wild-type genotype.

Distribution

Extent

Not known whether erdafitinib is distributed into human milk.

Plasma Protein Binding

99.8% (mainly α₁-acid glycoprotein).

Elimination

Metabolism

Principally metabolized by CYP2C9 and 3A4.

Elimination Route

Eliminated in feces (69% of the recovered dose [19% as unchanged drug]) and urine (19% [13% as unchanged drug]).

Half-life

59 hours.

Special Populations

Age, sex, race, or body weight does not have meaningful effects on clearance of erdafitinib.

Stability

Storage

Oral

Tablets

20–25°C (excursions permitted between 15–30°C).

Actions

A potent and reversible inhibitor of FGFR-1, FGFR-2, FGFR-3, and FGFR-4.
FGFR signaling pathway involved in proliferation and processes critical to cell survival and tumor progression (e.g., angiogenesis, metastasis, inhibition of apoptosis); aberrant expression of FGFR signaling implicated in pathogenesis of various solid tumors. Inhibition of FGFR reduces cell viability in cell lines with aberrant FGFR expression.
Serum phosphate concentration is a marker of FGFR inhibition.
Demonstrates antitumor activity in FGFR-expressing cell lines and xenograft models of tumor types such as bladder cancer.
Also binds to ret proto-oncogene (RET), colony stimulating factor receptor type 1 (CSF-1R), platelet-derived growth factor receptors (PDGFR)-α and PDGFR-β, fms-like tyrosine kinase-4 (Flt-4), stem cell factor receptor (c-Kit), and vascular endothelial growth factor receptor (VEGFR)-2.

Advice to Patients

Instruct patients to read the manufacturer’s patient information.
Advise patients to take erdafitinib tablets once daily without regard to meals. Advise patients to swallow erdafitinib tablets whole. If a dose is vomited, stress the importance of taking the next dose at the regularly scheduled time; an additional dose should not be administered to make up for the vomited dose.
If a dose is missed, stress the importance of taking the missed dose as soon as possible on the same day and taking the next dose at the regularly scheduled time on the following day. An additional dose should not be taken to make up for a missed dose.
Risk of ocular disorders. Stress the importance of patients immediately informing their clinician if any visual changes (e.g., blurry or loss of vision) occur. Stress the importance of preventing or treating dry eyes with artificial tears substitutes or hydrating or lubricating eye gels or ointments at least every 2 hours while awake.
Risk of dermatologic effects. Stress the importance of informing clinician if progressive or intolerable skin, mucous, or nail disorders occur.
Risk of hyperphosphatemia and soft tissue mineralization. Advise patients that phosphate intake should not exceed 600–800 mg daily during therapy. Advise patients to avoid drugs that may alter serum phosphate concentrations during the first 14–21 days of erdafitinib therapy. Stress the importance of patients immediately informing their clinician if painful skin lesions or any symptoms related to acute change in phosphate levels such as muscle cramps, numbness, or tingling around the mouth occur.
Risk of fetal harm. Advise females of reproductive potential and males who are partners of such females that they should use effective methods of contraception while receiving the drug and for 1 month after discontinuance of therapy. Stress the importance of females informing clinicians if they are or plan to become pregnant. If pregnancy occurs, advise pregnant females of potential risk to the fetus.
Advise females to avoid breast-feeding while receiving the drug and for 1 month after discontinuance of therapy.
Stress the importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs (e.g., potassium phosphate supplements, vitamin D supplements, antacids, phosphate-containing medications), as well as any concomitant illnesses.
Inform patients of other important precautionary information.

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care. For further information on the handling of antineoplastic agents, see the ASHP Guidelines on Handling Hazardous Drugs at [Web].

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Erdafitinib is available only from a designated specialty pharmacy. Contact the manufacturer for additional information.