REZUROCK

/ Sanofi

The recommended dose of belumosudil 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.
See prescribing information for full details.

Treatment of patients aged 12 years and older with chronic graft-versus-host disease (chronic GVHD) who have received at least two prior lines of systemic therapy.

* Pregnancy
* Hypersensitivity to the active substance or to any of the excipients

Women of childbearing potential
Women of childbearing potential should be advised to avoid becoming pregnant while taking belumosudil and of the potential risk to a foetus, and to have a pregnancy test prior to starting treatment with belumosudil.
Women of childbearing potential must use a highly effective method of contraception during treatment with belumosudil and for at least one week after the last dose of belumosudil.
Male patients
Male patients with female partners of childbearing potential should be advised that their female partners should avoid becoming pregnant while taking belumosudil and of the potential risk to a foetus.
Males with female partners of childbearing potential must use a highly effective method of contraception during treatment with belumosudil and for at least a week after the last dose of belumosudil.
Breast-feeding
Breast-feeding is not recommended during treatment with belumosudil and for at least one week after the last dose
Hepatotoxicity
Increases in liver function tests were observed in clinical studies with belumosudil and generally occurred early during treatment with the incidence decreasing thereafter. Liver function tests should be performed prior to the initiation of treatment with belumosudil and monitored at least monthly during treatment with belumosudil and the dose should be adjusted for ≥ Grade 2 toxicities.

The most common adverse reactions (≥5%) were asthenia (21.0%), nausea (12.4%), liver function test abnormalities of elevation of AST (7.5%), elevation of ALT (7.0%) and elevation of GGT (4.8%), headache (8.6%), diarrhoea (7.0%) and musculoskeletal pain (5.9%).
See prescribing information for full details.

Effect of CYP3A inducers on belumosudil
The co-administration of multiple doses of rifampin (a strong CYP3A4 inducer) decreased belumosudil Cmax by 59% and AUC by 72%. The co-administration of strong CYP3A4 inducers with belumosudil may decrease belumosudil exposure. Increase the dose of belumosudil to 200 mg twice daily. The co-administration of moderate CYP3A4 inducers e.g., efavirenz is predicted to have a reduced effect on belumosudil as compared to strong CYP3A4 inducers. The co-administration of moderate CYP3A4 inducers with belumosudil may decrease belumosudil exposure. No dose adjustment is recommended.
Effect of proton pump inhibitors on belumosudil
The co-administration of multiple doses of rabeprazole decreased belumosudil Cmax by 87% and AUC by 80%. The co-administration of multiple doses of omeprazole decreased belumosudil Cmax by 68% and AUC by 47%. The co-administration of proton pump inhibitors with belumosudil may decrease belumosudil exposure. Increase the dose of belumosudil to 200 mg twice daily.
Effect of other gastric acid reducing agents on belumosudil
The co-administration of belumosudil with gastric acid reducing agents other than proton pump inhibitors may decrease belumosudil exposure. No dose adjustment is recommended, however belumosudil and the gastric acid reducing agent should be taken 12 hours apart.
See prescribing information for full details.

Women of childbearing potential/Contraception in males and females
Women of childbearing potential must have their pregnancy status verified prior to initiating treatment with belumosudil, and must use a reliable and highly effective method of contraception during treatment with belumosudil and for at least one week after the last dose of belumosudil. In case pregnancy should occur during treatment with belumosudil, a risk/benefit evaluation must be carried out on an individual basis with careful counselling regarding potential risks to the foetus.
Male patients with female partners of childbearing potential should be advised that their female partners should avoid becoming pregnant while taking belumosudil and of the potential risks to a foetus.
Male patients with female partners of childbearing potential must use a highly effective method of contraception during treatment and for at least one week after the last dose of belumosudil.
Pregnancy: There are no data on the use of belumosudil in pregnant women.
Lactation: It is unknown whether belumosudil or its metabolites are excreted in human milk. A risk to the infant cannot be excluded. Because of the potential for serious adverse reactions in a breast-fed child, breast-feeding should be discontinued during treatment with belumosudil and for at least one week after the last dose.

There is no specific experience in the management of belumosudil overdose in patients. There is no known antidote for overdoses with belumosudil. Appropriate supportive treatment should be given.