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Erdafitinib

Medically reviewed by Drugs.com. Last updated on Jul 26, 2020.

Pronunciation

(er da FI ti nib)

Index Terms

  • Balversa
  • JNJ-42756493
  • Pan-FGFR tyrosine kinase inhibitor JNJ-42756493

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Balversa: 3 mg, 4 mg, 5 mg

Brand Names: U.S.

  • Balversa

Pharmacologic Category

  • Antineoplastic Agent, Fibroblast Growth Factor Receptor (FGFR) Inhibitor
  • Antineoplastic Agent, Tyrosine Kinase Inhibitor

Pharmacology

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.

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 US manufacturer's labeling.

Canadian labeling: Hypersensitivity to erdafitinib or any component of the formulation.

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.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

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

Abametapir: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination

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 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. 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. 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

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

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

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 (High risk with Inhibitors): Erdafitinib may increase the serum concentration of P-glycoprotein/ABCB1 Substrates (High risk with Inhibitors). 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.

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.

Reproductive Considerations

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.

Pregnancy Considerations

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).

Patient Education

What is this drug used for?

• It is used to treat bladder cancer.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• 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

• Joint pain

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Urinary tract infection like blood in the urine, burning or painful urination, passing a lot of urine, fever, lower abdominal pain, or pelvic pain.

• Electrolyte problems like 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

• Infection

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine's uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

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