Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Balversa: 3 mg, 4 mg, 5 mg
Pharmacology
Mechanism of Action
Erdafitinib is a pan fibroblast growth factor receptor (FGFR) kinase inhibitor that binds to and inhibits FGFR1, FGFR2, FGFR3, and FGFR4 enzyme activity. Erdafitinib also binds to RET, CSF1R, PDGFRA, PDGFRB, FLT4, KIT, and VEGFR2. 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.
Pharmacokinetics/Pharmacodynamics
Distribution
Vd: 29 L
Metabolism
Primarily hepatic by CYP2C9 and CYP3A4
Excretion
Feces: ~69% (19% as unchanged drug); urine: 19% (13% as unchanged drug)
Clearance: 0.362 L/hour
Time to Peak
2.5 hours (range: 2 to 6 hours)
Half-Life Elimination
59 hours
Protein Binding
99.8%, primarily to alpha-1-acid glycoprotein
Use: Labeled Indications
Urothelial carcinoma, locally advanced or metastatic: Treatment of locally advanced or metastatic urothelial carcinoma in adults with susceptible FGFR3 or FGFR2 genetic alterations and who have progressed during or following at least one line of prior platinum-containing chemotherapy, including within 12 months of neoadjuvant or adjuvant platinum-containing chemotherapy
Contraindications
There are no contraindications listed in the manufacturer's labeling.
Dosage and Administration
Dosing: Adult
Note: Assess serum phosphate levels 14 to 21 days after therapy initiation. Restrict phosphate intake to 600 to 800 mg daily.
Urothelial carcinoma, locally advanced or metastatic (with susceptible FGFR genetic alteration): Oral: Initial: 8 mg once daily; after 14 to 21 days, if serum phosphate is <5.5 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.
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.
Dosing: Geriatric
Refer to adult dosing.
Dosing: Adjustment for Toxicity
Recommended dosage reduction levels:
Dose at the time of toxicity: 9 mg once daily.
First dose reduction level: 8 mg once daily.
Second dose reduction level: 6 mg once daily.
Third dose reduction level: 5 mg once daily.
Fourth dose reduction level: 4 mg once daily.
Discontinue if unable to tolerate 4 mg once daily.
Dose at the time of toxicity: 8 mg once daily.
First dose reduction level: 6 mg once daily.
Second dose reduction level: 5 mg once daily.
Third dose reduction level: 4 mg once daily.
Discontinue if unable to tolerate 4 mg once daily.
Hyperphosphatemia: Note: Restrict phosphate intake to 600 to 800 mg daily; if serum phosphate is >7 mg/dL, consider initiating an oral phosphate binder until phosphate level is <5.5 mg/dL.
Phosphate level 5.6 to 6.9 mg/dL: Continue erdafitinib at current dose.
Phosphate level 7 to 9 mg/dL: Interrupt erdafitinib therapy and assess serum phosphate weekly; when level is <5.5 mg/dL (or baseline), reinitiate erdafitinib at the same dose. If hyperphosphatemia persisted for >1 week, consider dose reduction.
Phosphate level >9 mg/dL: Interrupt erdafitinib therapy and assess serum phosphate weekly; when level is <5.5 mg/dL (or baseline), may reinitiate erdafitinib at the next lower dose level.
Phosphate level >10 mg/dL, or significant alteration in baseline renal function, or grade 3 hypercalcemia: Interrupt erdafitinib therapy and assess serum phosphate weekly; when level is <5.5 mg/dL (or baseline), may reinitiate erdafitinib at 2 dose levels lower.
Ocular toxicity (central serous retinopathy/retinal pigment epithelial detachment):
Grade 1 (asymptomatic; clinical or diagnostic observations only): Interrupt erdafitinib therapy until resolution; if resolves within 4 weeks, reinitiate erdafitinib at the next lower dose level. If no recurrence for one month, may consider re-escalating the dose. If central serous retinopathy/retinal pigment epithelial detachment is stable for 2 consecutive eye exams (but not resolved), reinitiate erdafitinib at the next lower dose level.
Grade 2 (visual acuity ≥20/40 or ≤3 lines of decreased vision from baseline): Interrupt erdafitinib therapy until resolution; if resolves within 4 weeks, may reinitiate erdafitinib at the next lower dose level.
Grade 3 (visual acuity <20/40 or >3 lines of decreased vision from baseline): Interrupt erdafitinib therapy until resolution; if resolves within 4 weeks, may reinitiate erdafitinib at 2 dose levels lower. If grade 3 toxicity recurs, consider permanent discontinuation.
Grade 4 (visual acuity ≤20/200 in affected eye): Permanently discontinue erdafitinib.
Dry eye symptoms: Administer dry eye prophylaxis (with ocular demulcents) as needed.
Other toxicity:
Grade 3: Interrupt erdafitinib therapy until improvement to grade 1 or baseline, then may reinitiate at the next lower dose level.
Grade 4: Permanently discontinue erdafitinib.
Administration
Oral: Administer with or without food; swallow tablets whole.
Dietary Considerations
Restrict phosphate intake to 600 to 800 mg daily.
Storage
Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C (59°F and 86°F)
Drug Interactions
Alpelisib: May decrease the serum concentration of CYP2C9 Substrates (High risk with Inducers). Monitor therapy
Aprepitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy
Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy
Conivaptan: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination
CYP2C9 Inhibitors (Moderate): May decrease the metabolism of CYP2C9 Substrates (High risk with Inhibitors). Monitor therapy
CYP3A4 Inducers (Moderate): May decrease the serum concentration of Erdafitinib. Management: Dose modifications of erdafitinib may be required. See full monograph for details. Consider therapy modification
CYP3A4 Inducers (Strong): May decrease the serum concentration of Erdafitinib. Avoid combination
CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy
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. Consider therapy modification
CYP3A4 Substrates (High risk with Inducers): Erdafitinib may decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy
CYP3A4 Substrates (High risk with Inhibitors): Erdafitinib may increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy
Dabrafenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Consider therapy modification
Dabrafenib: May decrease the serum concentration of CYP2C9 Substrates (High risk with Inducers). Management: Seek alternatives to the CYP2C9 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Consider therapy modification
Deferasirox: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy
Duvelisib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy
Fluconazole: May increase the serum concentration of Erdafitinib. Management: Avoid concomitant use of erdafitinib and fluconazole when possible. If combined, monitor closely for erdafitinib adverse reactions and consider dose modifications accordingly. Consider therapy modification
Fosaprepitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy
Fosnetupitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy
Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination
Idelalisib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination
Ivosidenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy
Larotrectinib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy
Lorlatinib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Avoid concurrent use of lorlatinib with any CYP3A4 substrates for which a minimal decrease in serum concentrations of the CYP3A4 substrate could lead to therapeutic failure and serious clinical consequences. Consider therapy modification
MiFEPRIStone: May increase the serum concentration of CYP2C9 Substrates (High risk with Inhibitors). Management: Use CYP2C9 substrates at the lowest recommended dose, and monitor closely for adverse effects, during and in the 2 weeks following mifepristone treatment. Consider therapy modification
MiFEPRIStone: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Minimize doses of CYP3A4 substrates, and monitor for increased concentrations/toxicity, during and 2 weeks following treatment with mifepristone. Avoid cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, and tacrolimus. Consider therapy modification
Netupitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy
OCT2 Substrates: Erdafitinib may increase the serum concentration of OCT2 Substrates. Monitor therapy
Palbociclib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy
P-glycoprotein/ABCB1 Substrates: Erdafitinib may increase the serum concentration of P-glycoprotein/ABCB1 Substrates. Monitor therapy
Sarilumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy
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). Exceptions: Calcipotriene; Calcitriol (Topical); Potassium Bicarbonate; Sodium Bicarbonate. Consider therapy modification
Siltuximab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy
Simeprevir: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy
Stiripentol: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Use of stiripentol with CYP3A4 substrates that are considered to have a narrow therapeutic index should be avoided due to the increased risk for adverse effects and toxicity. Any CYP3A4 substrate used with stiripentol requires closer monitoring. Consider therapy modification
Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy
Adverse Reactions
>10%:
Central nervous system: Fatigue (54%)
Dermatologic: Onycholysis (41%), xeroderma (34%), alopecia (26%), palmar-plantar erythrodysesthesia (26%), paronychia (17%), nail discoloration (11%)
Endocrine & metabolic: Hyperphosphatemia (76%), decreased serum sodium (40%), decreased serum albumin (37%), decreased serum magnesium (30%), decreased serum phosphate (24%), increased serum calcium (22%), increased serum potassium (16%), weight loss (16%)
Gastrointestinal: Stomatitis (56%; grade 3/4: 9%), diarrhea (47%), xerostomia (45%), decreased appetite (38%), dysgeusia (37%), constipation (28%), abdominal pain (23%), nausea (21%), vomiting (13%)
Genitourinary: Urinary tract infection (17%), hematuria (11%)
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%)
Neuromuscular & skeletal: Musculoskeletal pain (20%), arthralgia (11%)
Ophthalmic: Dry eye syndrome (28%), retinal pigment epithelium detachment (≤25%), retinopathy (central serous: ≤25%), blurred vision (17%), conjunctivitis (11%)
Renal: Increased serum creatinine (52%)
Respiratory: Oropharyngeal pain (11%)
Miscellaneous: Fever (14%)
1% to 10%:
Hematologic & oncologic: Increase in fasting plasma glucose (10%), decreased neutrophils (10%; grades 3/4: 2%)
Ophthalmic: Increased lacrimation (10%)
Respiratory: Dyspnea (10%)
Frequency not defined: Neuromuscular & skeletal: Asthenia
Warnings/Precautions
Concerns related to adverse effects:
- Hyperphosphatemia: Hyperphosphatemia has been reported in over 75% of patients receiving erdafitinib. The median time to hyperphosphatemia onset (any grade) was 20 days (range: 8 to 116 days). Almost one-third of patients received phosphate binders during erdafitinib treatment. Monitor phosphate levels at baseline and during therapy; restrict phosphate intake to 600 to 800 mg daily. Avoid concomitant use with agents which may increase serum phosphate levels (eg, potassium phosphate or vitamin D supplements, antacids, phosphate-containing enemas or laxatives, and other medications with phosphate excipients) before the initial (days 14 to 21) dose increase period (based on serum phosphate levels). Hyperphosphatemia may require treatment interruption, dosage adjustment, and/or the use of phosphate binders.
- Ocular toxicity: Central serous retinopathy/retinal pigment epithelial detachment (CSR/RPED) has been reported in one-quarter of patients in a clinical trial, including grade 3 events. The median time to first onset of CSR/RPED was 50 days, with resolution in 13% of patients; persistent CSR/RPED was reported in another 13% of patients. CSR/RPED may result in visual field defect, including central field of vision. Temporarily interrupt erdafitinib if CSR/RPED develops; permanently discontinue if toxicity does not resolve within 4 weeks or for grade 4 toxicity. Dry eye symptoms occurred in over one-quarter of patients, including grade 3 events; administer dry eye prophylaxis (with ocular demulcents) as needed. Perform ophthalmological examinations at baseline and monthly for the first 4 months of erdafitinib therapy, then every 3 months thereafter, and as clinically needed for urgent visual symptoms. Exam should include visual acuity assessment, slit lamp examination, fundoscopy, and optical coherence tomography. Ocular toxicity may require therapy interruption, dosage adjustment, and/or therapy discontinuation.
Concurrent drug therapy issues:
- Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
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.
Other warnings/precautions:
- FGFR alteration positivity: Erdafitinib is approved for the treatment of locally advanced or metastatic urothelial carcinoma in patients with susceptible FGFR genetic alterations. Information on approved tests may be found at http://www.fda.gov/companiondiagnostics.
Monitoring Parameters
Assess for susceptible FGFR genetic alteration; serum phosphate level at baseline, at 14 to 21 days after therapy initiation, and then monthly or as clinically necessary; evaluate pregnancy status prior to use in females of reproductive potential; 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 for increased adverse reactions (in patients with known or suspected CYP2C9*3/*3 genotype). Monitor adherence.
Pregnancy
Pregnancy Considerations
Based on the mechanism of action, and data from animal reproduction studies, in utero exposure to erdafitinib may cause fetal harm.
Evaluate pregnancy status prior to use in females of reproductive potential. Females of reproductive potential and males with female partners of reproductive potential should use effective contraception during treatment and for 1 month after the last erdafitinib dose.
A pregnancy registry is available for all cancers diagnosed during pregnancy at Cooper Health (1-877-635-4499).
Patient Education
- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Patient may experience dry eyes, hair loss, nausea, vomiting, abdominal pain, diarrhea, constipation, mouth irritation, mouth sores, lack of appetite, weight loss, loss of strength and energy, dry skin, dry mouth, change in taste, muscle pain, or joint pain. Have patient report immediately to prescriber signs of a urinary tract infection (blood in the urine, burning or painful urination, passing a lot of urine, fever, lower abdominal pain, or pelvic pain), signs of electrolyte problems (mood changes, confusion, muscle pain or weakness, abnormal heartbeat, seizures, lack of appetite, or severe nausea or vomiting), vision changes, eye pain, severe eye irritation, nail changes, skin changes, redness or irritation of palms or soles of feet, chest pain, shortness of breath, difficult urination, change in amount of urine passed, dark urine, yellow skin, or signs of infection (HCAHPS).
- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.
