Posology : מינונים

4.2    Posology and method of administration

Rezurock treatment should be initiated and supervised by physicians experienced in the management of chronic GVHD.

Posology

The recommended dose of Rezurock is 200 mg administered orally once daily at approximately the same time with a meal.

Treatment should continue until disease progression or unacceptable toxicity.

A complete blood cell count and liver function test must be performed before initiating therapy with Rezurock.

Dose modification due to adverse reactions

Perform liver function tests at least monthly throughout treatment (see section 4.4).
The recommended Rezurock dose modifications for hepatotoxicity and other adverse reactions are provided in Table 1.

Table 1:     Dose modifications for adverse reactions
Criteria*                                                Rezurock Dosage Modifications Grade 3 ALT or AST (>5 to 20 × ULN) or                   Hold Rezurock until recovery to ≤ Grade 1, then Grade 2 bilirubin (>1.5 to 3 × ULN)                      resume Rezurock at the recommended dose at physician’s discretion.
Grade 4 ALT or AST (>20 × ULN) or                        Permanently discontinue Rezurock.
Grade ≥3 bilirubin (>3 × ULN)
Other Grade 3 adverse reactions                          Hold Rezurock until recovery to ≤ Grade 1, then resume Rezurock at the recommended dose at physician’s discretion.
Other Grade 4 adverse reactions                          Permanently discontinue Rezurock.
ALT = alanine aminotransferase; AST = aspartate aminotransferase; ULN = upper limit of normal.
*Grade 1 is mild, Grade 2 is moderate, Grade 3 is severe, Grade 4 is life-threatening. Toxicity grades are in accordance with National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.3 (NCI-CTCAE v4.3). See section 4.8.

Dose modification due to drug interactions

Strong CYP3A4 inducers and Proton Pump Inhibitors decrease the exposure of belumosudil (see section 4.5).

Strong CYP3A Inducers

Increase the dosage of Rezurock to 200 mg twice daily when co-administered with strong CYP3A inducers.

Proton Pump Inhibitors

Increase the dosage of Rezurock to 200 mg twice daily when co-administered with proton pump inhibitors.

Delayed or missed dose

If a dose is missed or delayed for less than 12 hours after the scheduled dose, the dose should be taken as soon as possible on the same day with a return to the normal schedule the following day.

If a dose is missed or delayed for more than 12 hours after the scheduled dose, the dose should be taken at the usual time the following day.

If a patient vomits following the intake of a dose, the next dose should be taken at the usual time the following day.

Patients should not take extra doses to make up the missed dose.

Special populations
Hepatic impairment

Belumosudil exposure increased in patients with mild (Child-Pugh A) and moderate (Child-Pugh B) hepatic impairment (see section 5.2).

There was no clinically meaningful impact of the increase in exposure; dose modification is not required in patients with mild or moderate hepatic impairment.

No data are available for patients with severe hepatic impairment (Child-Pugh C) (see sections 5.1 and 5.2). Use with caution (see section 4.4).

Renal impairment

No dose modification of Rezurock is required in patients with mild or moderate renal impairment (creatine clearance ≥ 30 mL/min).

No data are available for patients with severe renal impairment (creatine clearance < 30 mL/min) or for patients with end-stage renal disease on dialysis (see sections 5.1 and 5.2). Use with caution.

Elderly patients (≥65 years)

No additional dose adjustments are recommended for elderly patients (see sections 5.1 and 5.2).
Paediatric population

The posology is the same in adults and adolescents aged 12 to 18 years.

The safety and efficacy of Rezurock in children and adolescents aged below 12 years of age have not been established. No data are available (see section 5.1).

Method of administration

For oral use.
Rezurock should be taken at approximately the same time each day with a meal (see section 5.2).

The film-coated tablet should not be broken, crushed or chewed.