Erdafitinib is a medication used in the treatment of certain types of advanced or metastatic bladder cancer. It belongs to a class of drugs called tyrosine kinase inhibitors (TKIs). Specifically, erdafitinib is a selective inhibitor of the fibroblast growth factor receptor (FGFR) family of kinases.

FGFRs are proteins involved in cell growth and division, and mutations or alterations in these receptors can lead to the development and progression of certain cancers, including bladder cancer. Erdafitinib works by blocking the activity of these abnormal FGFRs, which can help slow down or inhibit the growth of cancer cells.

Erdafitinib was approved by the U.S. Food and Drug Administration (FDA) in April 2019 for the treatment of adults with locally advanced or metastatic bladder cancer that has specific genetic alterations, such as FGFR2 or FGFR3 mutations or gene fusions, and has progressed during or after previous chemotherapy. It is typically used when other treatment options have not been effective.

Erdafitinib (Balversa) is a fibroblast growth factor receptor kinase inhibitor that is indicated for the treatment of patients with locally advanced or metastatic urothelial cancer with susceptibility to FGFR gene mutations.

Erdafitinib Uses:

• Urothelial carcinoma, locally advanced or metastatic:
  • For advanced or metastatic urothelial carcinoma in adults in whom:
    • Susceptibility to FGFR3 or FGFR2 genetic alterations present and
    • The disease spread despite receiving platinum-based therapy including use within 12 months of neoadjuvant or adjuvant platinum-containing chemotherapy

Erdafitinib (Balversa) Dose in Adults

Note:

• This means that if you are taking a medication like erdafitinib, your doctor should check the level of phosphate in your blood 14 to 21 days after you start the treatment.
• To help control your phosphate levels, you should limit the amount of phosphate you get from your diet to somewhere between 600 to 800 milligrams per day.
• This helps ensure that your phosphate levels stay in a healthy range while you're on this medication.

Erdafitinib (Balversa) Dose in the treatment of locally advanced or metastatic urothelial carcinoma (with susceptible FGFR genetic alteration): 

• Initial Dose: You start with 8 milligrams (mg) of erdafitinib once a day.
• After 14 to 21 Days: Your doctor will check your blood phosphate levels. If they are lower than 5.5 milligrams per deciliter (mg/dL), and you haven't experienced severe side effects or eye problems, your doctor may increase your dose to 9 mg once a day. This adjustment depends on how well you tolerate the medication.

You continue taking the medication until your cancer progresses or until you experience severe side effects that you and your doctor decide are unacceptable.

If you miss a dose:

• Take the missed dose as soon as you remember it on the same day.
• Resume your regular dosing schedule the following day.
• Do not take extra doses to make up for the one you missed.

If you vomit after taking a dose:

• Take the next dose on the following day as scheduled.
• Do not take an additional dose to compensate for the one you vomited.

Use in Children:

Not indicated.

Erdafitinib (Balversa) Pregnancy Category: X

• Erdafitinib can potentially harm an unborn baby based on how it works and studies done on animals.
• So, before a woman who can have children starts taking erdafitinib, the doctor should check if she's pregnant or could become pregnant.
• If a woman can have children or if a man is taking erdafitinib and his partner can get pregnant, they should use effective birth control methods while the treatment is ongoing and for one month after they stop taking erdafitinib.
• This is important to prevent pregnancy and protect the potential baby from any harm.

Use of Erdafitinib while breastfeeding

• We don't know if erdafitinib can be found in breast milk.
• Because there's a possibility that it could cause serious problems for a baby who is breastfed, the manufacturer recommends that breastfeeding is not done while a person is taking erdafitinib and for one month after the last dose of the medication.

Erdafitinib (Balversa) Dose in Kidney Disease:

eGFR (estimated glomerular filtration rate) between 30 to 89 mL/minute/1.73 m²:

• The manufacturer's labeling doesn't specify any dosage adjustments for erdafitinib in this range. Furthermore, studies have not shown any significant differences in how the medication behaves in patients with mild or moderate kidney impairment. Therefore, standard dosages can be used in this group.

eGFR less than 30 mL/minute/1.73 m²:

• The manufacturer's labeling also does not provide specific dosage adjustments for erdafitinib in this group.

End-stage renal disease (ESRD) requiring dialysis:

• There are no recommended dosage adjustments for erdafitinib even in individuals with ESRD who require dialysis. This suggests that dialysis is not expected to significantly affect the levels of erdafitinib in the body.

Erdafitinib (Balversa) Dose in Liver disease:

Mild hepatic impairment:

• If a person has mild liver impairment, which is characterized by total bilirubin levels at or below the upper limit of normal (ULN) and elevated AST levels (liver enzyme), or total bilirubin levels between greater than 1 to 1.5 times ULN with any AST level, there are no specific dosage adjustments recommended in the manufacturer's labeling.
• Studies have shown that there were no significant differences in how erdafitinib behaves in patients with mild hepatic impairment compared to those with normal liver function.
• Therefore, standard dosages can be used in this group.

Moderate or severe hepatic impairment:

• The manufacturer's labeling also does not provide specific dosage adjustments for erdafitinib in individuals with moderate or severe liver impairment.
• This suggests that erdafitinib may not be significantly affected by moderate or severe liver impairment.

Common Side Effects of Erdafitinib (Balversa):

• Central Nervous System:
  • Fatigue
• Dermatologic:
  • Onycholysis
  • Xeroderma
  • Alopecia
  • Palmar-Plantar Erythrodysesthesia
  • Paronychia
  • Nail Discoloration
• Endocrine & Metabolic:
  • Hyperphosphatemia
  • Decreased Serum Sodium
  • Decreased Serum Albumin
  • Decreased Serum Magnesium
  • Decreased Serum Phosphate
  • Increased Serum Calcium
  • Increased Serum Potassium
  • Weight Loss
• Gastrointestinal:
  • Stomatitis
  • Diarrhea
  • Xerostomia
  • Decreased Appetite
  • Dysgeusia
  • Constipation
  • Abdominal Pain
  • Nausea
  • Vomiting
• Genitourinary:
  • Urinary Tract Infection
  • Hematuria
• Hematologic & Oncologic:
  • Decreased Hemoglobin
  • Decreased Platelet Count
  • Decreased White Blood Cell Count
• Hepatic:
  • Increased Serum Alanine Aminotransferase
  • Increased Serum Alkaline Phosphatase
  • Increased Serum Aspartate Aminotransferase
• Neuromuscular & Skeletal:
  • Musculoskeletal Pain
  • Arthralgia
• Ophthalmic:
  • Dry Eye Syndrome
  • Retinal Pigment Epithelium Detachment
  • Retinopathy
  • Blurred Vision
  • Conjunctivitis
• Renal:
  • Increased Serum Creatinine
• Respiratory:
  • Oropharyngeal Pain
• Miscellaneous:
  • Fever

Less Common Side Effects of Erdafitinib (Balversa):

• Hematologic & oncologic:
  • Increase in fasting plasma glucose
  • Decreased neutrophils
• Ophthalmic:
  • Increased lacrimation
• Respiratory:
  • Dyspnea

• Neuromuscular & skeletal:
  • Asthenia

Contraindication to Erdafitinib (Balversa):

• According to the manufacturer's labeling, there are no specific contraindications (conditions or situations in which the medication should not be used) listed for erdafitinib.
• However, this doesn't mean that the medication is necessarily safe or suitable for everyone.

Warnings and precautions

Hyperphosphatemia

• More than 75% of patients who take erdafitinib have experienced high phosphate levels (hyperphosphatemia).
• It usually happens about 20 days after starting the treatment, but it can occur anywhere from 8 to 116 days in some cases.
• Some patients need to take phosphate binders while on erdafitinib.
• To manage this, doctors should check your phosphate levels before and during the treatment.
• You should try to limit the amount of phosphate you get from your diet to between 600 and 800 milligrams each day.
• Also, avoid taking other medicines or supplements that might increase your phosphate levels during the first 14 to 21 days of treatment.
• If your phosphate levels become too high, your doctor may need to adjust your treatment or even temporarily stop it. They might also prescribe phosphate binders to help lower the phosphate levels.

Ocular toxicities:

• About one-quarter of patients in a clinical trial experienced a condition called Central Serous Retinopathy (CSR) or Retinal Pigment Epithelial Detachment (RPED). Some of these cases were severe (grade 3).
• CSR/RPED typically showed up around 50 days after starting erdafitinib. In some cases, it resolved on its own in 13% of patients, but for another 13%, it persisted.
• CSR/RPED can affect your vision, especially the central part.
• If you develop CSR/RPED, your doctor may temporarily stop your erdafitinib treatment. If the problem doesn't get better within four weeks or if it's very severe (grade 4), they might stop the treatment permanently.
• Dry eye symptoms were also seen in over one-quarter of patients, including some severe cases (grade 3). Your doctor may give you eye lubricants or other treatments as needed.
• You should have eye check-ups when you start erdafitinib (baseline) and then monthly for the first four months of treatment. After that, you'll have them every three months and more often if you have urgent eye problems.
• These eye exams will include checking your vision, looking at your eyes with a special light (slit lamp examination), checking the back of your eyes (fundoscopy), and using a special imaging technique called optical coherence tomography.
• If you experience eye problems, your doctor may need to pause your treatment, change the dosage, or even stop it altogether.

Erdafitinib: Drug Interaction

Note: Drug Interaction Categories:

• Risk Factor C: Monitor When Using Combination
• Risk Factor D: Consider Treatment Modification
• Risk Factor X: Avoid Concomitant Use

Monitoring parameters:

Before Starting Erdafitinib:

• Check if the patient has the specific genetic changes (FGFR genetic alteration) that make them eligible for erdafitinib treatment.
• Measure the phosphate level in the patient's blood before starting treatment.
• If the patient is a woman who can become pregnant, confirm her pregnancy status before beginning erdafitinib.

During Erdafitinib Treatment:

• Continuously monitor the phosphate levels in the patient's blood:
  • At the beginning of treatment.
  • 14 to 21 days after starting treatment.
  • Then, every month or as needed based on the patient's condition.
• If the patient is a woman of reproductive potential, make sure she uses effective contraception during treatment and for one month after the last erdafitinib dose.
• Conduct regular eye exams:
  • At the start of erdafitinib therapy (baseline).
  • Monthly for the first four months of treatment.
  • Then, every three months thereafter and as needed if there are urgent eye issues.
• For patients with a known or suspected CYP2C9*3/*3 genotype, monitor them closely for an increased risk of adverse reactions.
• Keep an eye on patient adherence to the treatment plan, ensuring they take the medication as prescribed.

How to administer Erdafitinib (Balversa)?

• You can take it with or without food, so it's flexible.
• Just swallow the tablets whole, don't crush or break them.

Mechanism of action of Erdafitinib (Balversa):

• Erdafitinib is a medication that falls into a class of drugs called kinase inhibitors.
• It works by targeting and inhibiting the activity of specific enzymes called fibroblast growth factor receptors (FGFRs).
• Erdafitinib can block several types of FGFRs, including FGFR1, FGFR2, FGFR3, and FGFR4.
• Additionally, it can also affect other enzymes and receptors like RET, CSF1R, PDGFRA, PDGFRB, FLT4, KIT, and VEGFR2.
• When erdafitinib inhibits FGFRs, it interferes with the signaling processes that these receptors are involved in.
• This interference leads to reduced cell viability, which means that it can slow down or inhibit the growth of cancer cells, especially in cases where FGFR genetic alterations are present.
• These alterations can include mutations, gene amplifications, or gene fusions related to FGFRs.

Distribution:

• Volume of distribution (V) is approximately 29 liters (indicating how the drug is distributed throughout the body).

Protein Binding:

• Erdafitinib is highly bound to proteins in the blood, primarily to a protein called alpha-1-acid glycoprotein.
• About 99.8% of the drug is bound to this protein.

Metabolism:

• Erdafitinib is mainly metabolized in the liver by enzymes known as CYP2C9 and CYP3A4.
• These enzymes help break down the drug.

Half-life Elimination:

• The half-life of elimination for erdafitinib is approximately 59 hours. This is the time it takes for half of the drug to be removed from the body.

Time to Peak:

• Erdafitinib reaches its peak concentration in the bloodstream about 2.5 hours after it's taken. This can vary a bit, with a range of 2 to 6 hours.

Excretion:

• The majority of erdafitinib and its metabolites are excreted through the feces (about 69%), with approximately 19% of the drug being eliminated in the urine. In both cases, a portion of the drug is excreted unchanged.

Clearance:

• The clearance of erdafitinib from the body is approximately 0.362 liters per hour. This value represents how quickly the drug is removed from the bloodstream by the body's processes.

International Brand Names of Erdafitinib:

• Balversa

Erdafitinib Brand Names in Pakistan:

Not available.