Infigratinib is used to treat cholangiocarcinoma with FGFR2 fusion or rearrangement. Dosing in special populations requires individualized adjustment based on factors such as hepatic and renal function, pregnancy and lactation status, and age.

I. Patients with Hepatic or Renal Impairment

1. Mild to Moderate Renal Impairment

For patients with creatinine clearance of 30 to 89 mL/min, the recommended dose is adjusted to 100 mg once daily.

The dosing schedule remains 21 consecutive days of treatment followed by 7 days off therapy, in 28-day cycles.

2. Severe Renal Impairment

For patients with creatinine clearance below 30 mL/min, the recommended dose has not been established.

The dose is also not established for patients with end-stage renal disease receiving intermittent hemodialysis.

3. Mild to Moderate Hepatic Impairment

For patients with mild hepatic impairment, the recommended dose is 100 mg once daily.

For patients with moderate hepatic impairment, the recommended dose is 75 mg once daily.

The dosing schedule is 21 days of treatment followed by 7 days off therapy.

4. Severe Hepatic Impairment

For patients with total bilirubin greater than 3 times the upper limit of normal, the recommended dose has not been established.

Such patients should avoid use or be treated only after careful risk assessment.

II. Reproductive and Pregnancy-Related Populations

1. Pregnant Women

Based on animal studies and its mechanism of action, infigratinib can cause fetal harm.

Use during pregnancy may cause malformations, fetal growth retardation, and embryo-fetal death.

Women of reproductive potential should have pregnancy status confirmed before treatment and use effective contraception during treatment and for 1 month after the last dose.

2. Lactating Women

There are no data on infigratinib or its metabolites in human milk.

Because of the potential for serious adverse reactions in infants, breastfeeding is not recommended during treatment and for 1 month after the last dose.

3. Males of Reproductive Potential

Male patients with female partners of reproductive potential should use effective contraception during treatment and for 1 month after the last dose.

Animal studies have not shown clear effects on male fertility.

III. Other Special Populations

1. Geriatric Patients

No dose adjustment based on age is required for patients 65 years and older.

Clinical studies have not observed overall differences in safety or effectiveness between older and younger patients.

2. Pediatric Patients

The safety and effectiveness of infigratinib in pediatric patients have not been established.

Animal studies show that juvenile animals may develop bone and tooth toxicity at exposures below the human clinical dose.

3. Smokers and Diet-Related Populations

Grapefruit and grapefruit products should be avoided because they may affect CYP3A4-mediated drug metabolism.

Avoid concomitant use with strong or moderate CYP3A inhibitors or inducers.

Avoid concomitant use with proton pump inhibitors, H2 receptor antagonists, and locally acting antacids; if unavoidable, administer at the required intervals.

4. Patients with Normal Renal Function

For patients with creatinine clearance of at least 90 mL/min, no starting dose adjustment is required.

Renal function and serum phosphate levels should still be monitored during treatment.