Erdafitinib – Uses, Dosage, Side Effects, Interactions

Erdafitinib is an oral small molecule inhibitor of fibroblast growth factor receptors (FGFR) 1 to 4 that is used in the therapy of locally advanced, unresectable, or metastatic urothelial carcinoma. Erdafitinib has been associated with a high rate of serum enzyme elevations during therapy but has not been linked to cases of clinically apparent acute liver injury.

Upon administration, it was observed that erdafitinib increased serum phosphate levels as a consequence of FGFR inhibition. Erdafitinib should be increased to the maximum recommended dose to achieve target serum phosphate levels of 5.5– 7.0 mg/dL in early cycles with continuous daily dosing. Subsequently, in afatinib clinical trials, the use of drugs that could increase serum phosphate levels, such as potassium phosphate supplements, vitamin D supplements, antacids, phosphate-containing enemas or laxatives, and medications known to have phosphate as an excipient were prohibited unless no alternatives existed. To manage phosphate elevation, phosphate binders were utilized. Additionally, the concomitant use of agents that can alter serum phosphate levels before the initial afatinib dose increase period based on serum phosphate levels was also avoided. Furthermore, based on the 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.

Use in Cancer

Erdafitinib is approved to treat:

• Urothelial carcinoma (a type of bladder cancer) has spread or cannot be removed by surgery and has specific mutations in the FGFR3 gene or a fusion gene involving the FGFR3 gene or FGFR2 gene. It is used in adults whose cancer worsened during or after treatment with at least one type of platinum chemotherapy.

This use is approved under FDA’s Accelerated Approval Program. As a condition of approval, a confirmatory trial(s) must show that erdafitinib provides a clinical benefit in these patients.

Erdafitinib is also being studied in the treatment of other types of cancer.

Contraindications

The following conditions are contraindicated? with this drug. Check with your physician if you have any of the following:

• high amount of phosphate in the blood
• pregnancy
• a patient who is producing milk and breastfeeding
• detachment of retinal pigment epithelium

Dosage?

Strengths: 3 mg; 4 mg; 5 mg

Urothelial Carcinoma

• 8 mg orally once daily; increase to 9 mg orally once daily based on serum phosphate levels and tolerability at 14 to 21 days until disease progression? or unacceptable toxicity

Dose Adjustments

DOSE REDUCTION SCHEDULE FOR ADVERSE REACTIONS:
9 MG DOSE SCHEDULE:

• First dose reduction: 8 mg
• Second dose reduction: 6 mg
• Third dose reduction: 5 mg
• Fourth dose reduction: 4 mg
• Fifth dose reduction: Stop

8 MG DOSE SCHEDULE:

• First dose reduction: 6 mg
• Second dose reduction: 5 mg
• Third dose reduction: 4 mg
• Fourth dose reduction: Stop

DOSE MODIFICATIONS FOR ADVERSE REACTIONS:
HYPERPHOSPHATEMIA (NOTE: Restrict phosphate intake in all patients to 600 to 800 mg daily; if serum phosphate is above 7 mg/dL consider adding an oral phosphate binder until serum phosphate level returns to less than 5.5 mg/dL):

• Phosphate 5.6 to 6.9 mg/dL (1.8 to 2.3 mmol/L): Continue at current dose
• Phosphate 7 to 9 mg/dL (2.3 to 2.9 mmol/L): Withhold therapy with weekly reassessments until the level returns to less than 5.5 mg/dL (or baseline?); restart at the same dose level; dose may be reduced for hyperphosphatemia lasting longer than 1 week
• Phosphate greater than 9 mg/dL (greater than 2.9 mmol/L): Withhold therapy with weekly reassessments until the level returns to less than 5.5 mg/dL or baseline; restart at 1 dose level lower
• Phosphate greater than 10 mg/dL (greater than 3.2 mmol/L) or significant alteration in baseline renal? function or Grade 3 hypercalcemia: Withhold therapy with weekly reassessments until level returns to less than 5.5 mg/dL or baseline; restart at 2 dose levels lower

CENTRAL SEROUS RETINOPATHY/RETINAL PIGMENT EPITHELIAL DETACHMENT (CSR/RPED):

• Grade 1 (asymptomatic?; clinical or diagnostic observations only): Withhold therapy until resolution; if resolves within 4 weeks, resume at the next lower dose level; then, if no recurrence? for a month, consider re-escalation; if stable for 2 consecutive eye exams but not resolved, resume at the next lower dose level
• Grade 2: Visual acuity? 20/40 or better or less than or equal to 3 lines of decreased vision from baseline: Withhold therapy until resolution; if resolves within 4 weeks resume at the next lower dose level
• Grade 3: Visual acuity worse than 20/40 or greater than 3 lines of decreased vision from baseline: Withhold therapy until resolution; if resolves within 4 weeks resume 2 dose levels lower; if recurs, consider permanent discontinuation of therapy
• Grade 4: (visual acuity 20/200 or worse in the affected eye): Permanently discontinue therapy.

OTHER ADVERSE REACTIONS:

• Grade 3: Withhold therapy until resolves to Grade 1 or baseline; resume 1 dose level lower
• Grade 4: Permanently discontinue therapy.

Side Effects

The Most Common

• nausea?
• diarrhea?
• vomiting?
• constipation?
• sores on lips, mouth, or throat?
• dry mouth
• changes in taste
• abdominal pain
• decreased appetite
• weight loss
• unusual hair thinning or hair loss
• fever
• muscle or joint pain
• burning during urination
• fatigue or tiredness
• shortness of breath
• blurred vision, loss of vision, or other visual changes
• nail problems or changes
• itchy, dry, painful, or cracked skin
• rash
• swelling, pain, redness, or peeling of skin on the palms and soles of the feet
• muscle cramps, numbness, or tingling around the mouth

More Common

• changed sense of taste
• constipation
• decreased appetite
• diarrhea
• discolored nails
• dry eyes
• dry mouth, nose, skin
• fatigue
• hair loss
• infected skin around the nail
• itchy skin rash
• muscle pain
• nausea
• sore throat
• stomach pain
• vaginal dryness
• vomiting
• watery eyes
• weakness
• weight loss
• vision problems, vision loss;
• eye pain or redness;
• painful or irritated eyelids;
• feeling like something is in your eye;
• watery eyes, your eyes may be more sensitive to light; or
• problems with your fingernails or toenails–pain, bleeding, separation of the nails from the skin (nail bed), unusual breakage, changes in nail color or texture, cracks or infection in your cuticles.

Rare

• blood in the urine
• dry eyes
• fever
• mouth sores
• signs of anemia (low red blood cells; e.g., dizziness, pale skin, unusual tiredness or weakness, shortness of breath)
• skin or nail problems (e.g., nail pain, cracked skin, very dry skin, bleeding under the nail, nail separation from the bed)
• skin rash
• swelling or peeling skin of the hands and feet
• symptoms of a urinary tract infection (e.g., pain when urinating, urinating more often than usual, low back or flank pain)
• vision problems (e.g., blurred vision, vision loss, cloudy vision)

Drug Interaction

Pregnancy Category

Pregnancy category X 

Pregnancy

This medication should not be taken during pregnancy. Erdafitinib may cause severe harm to a developing baby if it is taken by the mother while she is pregnant. Female partners of men taking this medication should not become pregnant. Both females and males must use a reliable method of birth control (e.g., condoms, birth control pill) during treatment and for at least 3 months after treatment is finished. If you become pregnant while taking this medication, contact your doctor immediately.

Breast-feeding

This medication may pass into breast milk. If you are a breast-feeding mother and are taking erdafitinib, it may affect your baby. Due to the potential for serious harm to a baby, if they are exposed to this medication, breastfeeding mothers are advised not to use this medication.

References