Active Ingredient: Ruxolitinib
Ruxolitinib is indicated for the treatment of adults and paediatric patients aged 28 days and older with acute graft versus host disease who have inadequate response to corticosteroids or other systemic therapies.
For this indication, competent medicine agencies globally authorize below treatments:
For:
Regimen A: Oral, 10 milligrams ruxolitinib, 2 times daily. Afterwards, oral, between 5 milligrams ruxolitinib and 10 milligrams ruxolitinib, 2 times daily.
Regimen B: Oral, 10 milligrams ruxolitinib, 2 times daily. Afterwards, oral, 5 milligrams ruxolitinib, 2 times daily. Afterwards, oral, 5 milligrams ruxolitinib, once daily.
The recommended starting dose of ruxolitinib in in acute GvHD is 10 mg twice daily.
Ruxolitinib can be added to corticosteroids and/or calcineurin inhibitors (CNIs).
Doses may be titrated based on efficacy and safety.
Dose reductions and temporary interruptions of treatment may be needed in GvHD-patients with thrombocytopenia, neutropenia, or elevated total bilirubin after standard supportive therapy including growth-factors, anti-infective therapies and transfusions. One dose level reduction step is recommended (10 mg twice daily to 5 mg twice daily or 5 mg twice daily to 5 mg once daily). In patients who are unable to tolerate ruxolitinib at a dose of 5 mg once daily, treatment should be interrupted. Detailed dosing recommendations are provided in the following table.
Dosing recommendations during ruxolitinib therapy for GvHD patients with thrombocytopenia, neutropenia or elevated total bilirubin:
| Laboratory parameter | Dosing recommendation |
| Platelet count <20 000/mm³ | Reduce ruxolitinib by one dose level. If platelet count ≥20 000/mm³ within seven days, dose may be increased to initial dose level, otherwise maintain reduced dose. |
| Platelet count <15 000/mm³ | Hold ruxolitinib until platelet count ≥20 000/mm³, then resume at one lower dose level. |
| Absolute neutrophil count (ANC) ≥500/mm³ to <750/mm³ | Reduce ruxolitinib by one dose level. Resume at initial dose level if ANC >1 000/mm³. |
| Absolute neutrophil count <500/mm³ | Hold ruxolitinib until ANC >500/mm³, then resume at one lower dose level. If ANC >1 000/mm³, dosing may resume at initial dose level. |
| Total bilirubin elevation not caused by GvHD (no liver GvHD) | >3.0 to 5.0 x upper limit of normal (ULN): Continue ruxolitinib at one lower dose level until ≤3.0 x ULN. |
| >5.0 to 10.0 x ULN: Hold ruxolitinib up to 14 days until total bilirubin ≤3.0 x ULN. If total bilirubin ≤3.0 x ULN dosing may resume at current dose. If not ≤3.0 x ULN after 14 days, resume at one lower dose level. | |
| >10.0 x ULN: Hold ruxolitinib until total bilirubin ≤3.0 x ULN, then resume at one lower dose level. | |
| Total bilirubin elevation caused by GvHD (liver GvHD) | >3.0 x ULN: Continue ruxolitinib at one lower dose level until total bilirubin ≤3.0 x ULN. |
In GvHD, tapering of ruxolitinib may be considered in patients with a response and after having discontinued corticosteroids. A 50% dose reduction of ruxolitinib every two months is recommended. If signs or symptoms of GvHD reoccur during or after the taper of ruxolitinib, re-escalation of treatment should be considered.
It is recommended that the dose of ruxolitinib is taken at a similar time every day.
If a dose is missed, the patient should not take an additional dose, but should take the next usual prescribed dose.
For:
Regimen A: In case that patient age in years is ≥ 6, oral, 5 milligrams ruxolitinib, 2 times daily.
Regimen B: In case that patient age in days is ≥ 28 and patient age in years is < 6, oral, 8 milligrams ruxolitinib per square meter of body surface, 2 times daily.
The recommended starting dose of ruxolitinib in acute GvHD is based on age:
Table 1. Starting doses in acute graft versus host disease:
| Age group | Starting dose |
|---|---|
| 6 years to less than 12 years old | 5 mg/1 ml twice daily |
| 28 days to less than 6 years old | 8 mg/m² twice daily |
Ruxolitinib can be added to corticosteroids and/or calcineurin inhibitors (CNIs).
Doses may be titrated based on efficacy and safety.
Dose reductions and temporary interruptions of treatment may be needed in GvHD-patients with thrombocytopenia, neutropenia, or elevated total bilirubin after standard supportive therapy including growth-factors, anti-infective therapies and transfusions. The recommended starting dose for GvHD patients should be reduced by approximately 50% to be administered twice daily. In patients who are unable to tolerate ruxolitinib at the reduced dose level, treatment should be interrupted. Detailed dosing recommendations are provided in Table 2.
Table 2. Dosing recommendations during ruxolitinib therapy for GvHD patients with thrombocytopenia, neutropenia or elevated total bilirubin:
| Laboratory parameter | Dosing recommendation |
|---|---|
| Platelet count <20 000/mm³ | Reduce ruxolitinib by one dose level. If platelet count ≥20 000/mm³ within seven days, dose may be increased to initial dose level, otherwise maintain reduced dose. |
| Platelet count <15 000/mm³ | Hold ruxolitinib until platelet count ≥20 000/mm³, then resume at one lower dose level. |
| Absolute neutrophil count (ANC) ≥500/mm³ to <750/mm³ | Reduce ruxolitinib by one dose level. Resume at initial dose level if ANC >1 000/mm³. |
| Absolute neutrophil count <500/mm³ | Hold ruxolitinib until ANC >500/mm³, then resume at one lower dose level. If ANC >1 000/mm³, dosing may resume at initial dose level. |
| Total bilirubin elevation not caused by GvHD (no liver GvHD) | >3.0 to 5.0 x upper limit of normal (ULN): Continue ruxolitinib at one lower dose level until ≤3.0 x ULN. |
| >5.0 to 10.0 x ULN: Hold ruxolitinib up to 14 days until total bilirubin ≤3.0 x ULN. If total bilirubin ≤3.0 x ULN dosing may resume at current dose. If not ≤3.0 x ULN after 14 days, resume at one lower dose level. | |
| >10.0 x ULN: Hold ruxolitinib until total bilirubin ≤3.0 x ULN, then resume at one lower dose level. | |
| Total bilirubin elevation caused by GvHD (liver GvHD) | >3.0 x ULN: Continue ruxolitinib at one lower dose level until total bilirubin ≤3.0 x ULN. |
Tapering of ruxolitinib may be considered in patients with a response and after having discontinued corticosteroids. A 50% dose reduction of ruxolitinib every two months is recommended. If signs or symptoms of GvHD reoccur during or after the taper of ruxolitinib, re-escalation of treatment should be considered.
It is recommended that the dose of ruxolitinib is taken at a similar time every day.
If a dose is missed, the patient should not take an additional dose, but should take the next usual prescribed dose.
Liability Disclaimer : RxReasoner has utilized reasonable care in providing content and services that are accurate, complete and up to date. However, RxReasoner does not accept any responsibility or liability about it. The content and services of RxReasoner are for informational purposes only and they are not intended to be a substitute for the knowledge, expertise, skill, and judgment of physicians, pharmacists, nurses, or other healthcare professionals involved in patient care. RxReasoner offers no medical advice. Users are responsible for the use of the provided content. A shown indication or treatment should not be construed to indicate that the medication is safe, appropriate, or effective in any given patient or under any particular circumstances. The absence of an indication or treatment should not roule out the existence of other appropriate medications. Always seek the advice of a physician or other qualified health provider with any questions you may have regarding a medical condition or medicament. RxReasoner is not liable for any damages allegedly sustained arising out of the use of its content and services.