Patients in different physiological and pathological states have differences in drug metabolism and tolerance. Adjusting doses and enhancing monitoring for special populations is a key step to ensure treatment safety and efficacy.
I. Patients with Hepatic Impairment
Rizabrutinib is primarily metabolized in the liver.
1. Mild (Child-Pugh A) or Moderate (Child-Pugh B) Hepatic Impairment:
No起始 dose adjustment is needed, but regular monitoring of liver function indicators (e.g., ALT, AST, total bilirubin) during treatment is recommended to watch for worsening hepatic impairment.
2. Severe (Child-Pugh C) Hepatic Impairment:
(1) The recommended dose is adjusted to 80 mg twice daily (standard regimen is 160 mg twice daily or 320 mg once daily).
(2) Data on safety and efficacy in this population are limited; closely monitor for bleeding, infection, and liver-related adverse reactions during treatment.
II. Patients with Renal Impairment
1. Mild to Moderate Renal Impairment (creatinine clearance ≥30 ml/min):
No dose adjustment needed.
2. Severe Renal Impairment (creatinine clearance<30 ml/min) or on Dialysis:
Although population pharmacokinetic models show similar exposure to patients with normal renal function, routine dose reduction is not mandatory. Close monitoring for bleeding, infection, and changes in blood counts is recommended during treatment.
III. Women of Childbearing Potential, Pregnancy, and Lactation
1. Pregnancy:
(1) Animal studies showed cardiac malformations (2- or 3-chamber heart) and eye developmental abnormalities in rat fetuses at blood concentrations equivalent to 5 times the human therapeutic dose.
(2) Therefore, the drug is contraindicated during pregnancy.
(3) If pregnancy occurs while on treatment, immediately inform the physician.
2. Contraception Requirements:
(1) Women of childbearing potential must use highly effective contraceptive measures during treatment and for at least 1 month after the last dose.
(2) As the effect of this drug on hormonal contraceptives is unknown, barrier contraception (e.g., condom) is recommended in addition.
3. Lactation:
(1) It is unknown whether this drug is excreted in human milk.
(2) Due to the potential for serious adverse reactions in the nursing infant, it is recommended to suspend breastfeeding during treatment and for at least 1 week after the last dose.
IV. Elderly Patients
1. No specific dose adjustment is required for elderly patients, but this population has more underlying diseases (e.g., hypertension, heart disease) and higher risks of bleeding and atrial fibrillation.
2. Enhanced monitoring of ECG, blood pressure, and signs of bleeding is recommended.
V. Children
The safety and efficacy in children and adolescents under 18 years have not been established. No relevant study data are available, therefore use is not recommended.
