Drug information of Erdafitinib
Erdafitinib is a small molecule inhibitor of FGFR approved for treatment of cancer and marketed under the name Balversa. FGFRs are a subset of tyrosine kinases which are unregulated in some tumors and influence tumor cell differentiation, proliferation, angiogenesis, and cell survival.
Mechanism of effect
In vitro, erdafitinib inhibits FGFR phosphorylation and signaling and decreases cell viability in cell lines expressing FGFR genetic alterations, including point mutations, amplifications, and fusions.
Cardiac Electrophysiology: Based on evaluation of QTc interval in an open-label, dose escalation and dose expansion study in 187 patients with cancer, erdafitinib had no large effect (i.e., > 20 ms) on the QTc interval.
Serum Phosphate: Erdafitinib increased serum phosphate level as a consequence of FGFR inhibition.
Absorption: Median time to achieve peak plasma concentration (tmax) was 2.5 hours (range: 2 to 6 hours).
Distribution: The mean apparent volume of distribution of erdafitinib was 29 L in patients.
Erdafitinib protein binding was 99.8% in patients, primarily to alpha-1-acid glycoprotein.
Elimination: The mean total apparent clearance (CL/F) of erdafitinib was 0.362 L/h in patients. The mean effective half-life of erdafitinib was 59 hours in patients.
Metabolism: Erdafitinib is primarily metabolized by CYP2C9 and CYP3A4. The contribution of CYP2C9 and CYP3A4 in the total clearance of erdafitinib is estimated to be 39% and 20% respectively. Unchanged erdafitinib was the major drug-related moiety in plasma, there were no circulating metabolites.
Excretion: Following a single oral dose of radiolabeled erdafitinib, approximately 69% of the dose was recovered in feces (19% as unchanged) and 19% in urine (13% as unchanged).
treatment of adult patients with locally advanced or metastatic urothelial carcinoma which has:
• susceptible FGFR3 or FGFR2 genetic alterations and
• progressed during or following at least one line of prior platinum-containing chemotherapy including within 12 months of neoadjuvant or adjuvant platinum-containing chemotherapy.
Recommended initial dosage: 8 mg orally once daily with a dose increase to 9 mg daily if criteria are met.
Side effectsDiarrhea , nausea , dry mouth , Hypomagnesemia , Creatinine increased , dry eyes , hypercalcemia , dry skin , Hypophosphatemia , tiredness , Abdominal pain
The most common adverse reactions including laboratory abnormalities (≥20%) were phosphate increased, stomatitis, fatigue, creatinine increased, diarrhea, dry mouth, onycholysis, alanine aminotransferase increased, alkaline phosphatase increased, sodium decreased, decreased appetite, albumin decreased, dysgeusia, hemoglobin decreased, dry skin, aspartate aminotransferase increased, magnesium decreased, dry eye, alopecia, palmar-plantar erythrodysesthesia syndrome, constipation, phosphate decreased, abdominal pain, calcium increased, nausea, and musculoskeletal pain.
InteractionsQuinine , Nintedanib , aluminum hydroxide/magnesium carbonate , Aliskiren , Itraconazole , Bosentan , Gemfibrozil , Dexamethasone , Ketoconazole , Clarithromycin , Calcitriol , Amprenavir , Aluminium hydroxide , Efavirenz , Paliperidone , Pazopanib , Butabarbital , Doravirine , Desloratadine , trametinib , Potassium Phosphate , Clorazepate
Ocular disorders: BALVERSA can cause central serous retinopathy/retinal pigment epithelial detachment (CSR/RPED). Perform monthly ophthalmological examinations during the first four months of treatment, every 3 months afterwards, and at any time for visual symptoms. Withhold BALVERSA when CSR/RPED occurs and permanently discontinue if it does not resolve within 4 weeks or if Grade 4 in severity.
Hyperphosphatemia: Increases in phosphate levels are a pharmacodynamic effect of BALVERSA. Monitor for hyperphosphatemia and manage with dose modifications when required.
Embryo-fetal toxicity: Can cause fetal harm. Advise patients of the potential risk to the fetus and to use effective contraception
Points of recommendation
Advise patients to contact their healthcare provider if they experience any visual changes.
Advise patients to contact their healthcare provider if they experience progressive or intolerable skin, mucous or nail disorders.
Advise patients to inform their healthcare providers of all concomitant medications, including prescription medicines, over-the-counter drugs, and herbal products.
If a dose is missed, advise patients to take the missed as soon as possible. Resume the regular daily dose schedule for BALVERSA the next day. Extra tablets should not be taken to make up for the missed dose.