Source: European Medicines Agency (EU) Revision Year: 2025 Publisher: Novartis Europharm Limited, Vista Building, Elm Park, Merrion Road, Dublin 4, Ireland
Jakavi 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 (see section 5.1).
Jakavi is indicated for the treatment of adults and paediatric patients aged 6 months and older with chronic graft versus host disease who have inadequate response to corticosteroids or other systemic therapies (see section 5.1).
Jakavi treatment should only be initiated by a physician experienced in the administration of anti- cancer medicinal products.
A complete blood cell count, including a white blood cell count differential, must be performed before initiating therapy with Jakavi.
Complete blood count, including a white blood cell count differential, should be monitored every 2 to 4 weeks until Jakavi doses are stabilised, and then as clinically indicated (see section 4.4).
The recommended starting dose of Jakavi in acute and chronic GvHD is based on age (see Tables 1 and 2):
Table 1. Starting doses in acute graft versus host disease:
| Age group | Starting dose |
|---|---|
| 12 years old and above | 10 mg/2 ml twice daily |
| 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 (see Table 3) |
Table 2. Starting doses in chronic graft versus host disease:
| Age group | Starting dose |
|---|---|
| 12 years old and above | 10 mg/2 ml twice daily |
| 6 years to less than 12 years old | 5 mg/1 ml twice daily |
| 6 months to less than 6 years old | 8 mg/m² twice daily (see Table 3) |
These starting doses in GvHD can be administered using either the tablet for patients who can swallow tablets whole or the oral solution.
The volume of Jakavi to be administered twice daily when using a starting dose of 8 mg/m² in patients less than 6 years old is presented in Table 3.
Table 3. Volume of Jakavi oral solution (5 mg/ml) to be administered twice daily when using a starting dose of 8 mg/m² in patients less than 6 years old:
| Body surface area (BSA) (m²) | Volume (ml) | |
|---|---|---|
| Min | Max | |
| 0.16 | 0.21 | 0.3 |
| 0.22 | 0.28 | 0.4 |
| 0.29 | 0.34 | 0.5 |
| 0.35 | 0.40 | 0.6 |
| 0.41 | 0.46 | 0.7 |
| 0.47 | 0.53 | 0.8 |
| 0.54 | 0.59 | 0.9 |
| 0.60 | 0.65 | 1.0 |
| 0.66 | 0.71 | 1.1 |
| 0.72 | 0.78 | 1.2 |
| 0.79 | 0.84 | 1.3 |
| 0.85 | 0.90 | 1.4 |
| 0.91 | 0.96 | 1.5 |
| 0.97 | 1.03 | 1.6 |
| 1.04 | 1.09 | 1.7 |
| 1.10 | 1.15 | 1.8 |
Jakavi 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 Jakavi at the reduced dose level, treatment should be interrupted. Detailed dosing recommendations are provided in Table 4.
Table 4. 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 Jakavi 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 Jakavi until platelet count ≥20 000/mm³, then resume at one lower dose level. |
| Absolute neutrophil count (ANC) ≥500/mm³ to <750/mm³ | Reduce Jakavi by one dose level. Resume at initial dose level if ANC >1 000/mm³. |
| Absolute neutrophil count <500/mm³ | Hold Jakavi 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 Jakavi at one lower dose level until ≤3.0 x ULN. |
| >5.0 to 10.0 x ULN: Hold Jakavi 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 Jakavi 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 Jakavi at one lower dose level until total bilirubin ≤3.0 x ULN. |
When ruxolitinib is administered with strong CYP3A4 inhibitors or dual inhibitors of CYP2C9 and CYP3A4 enzymes (e.g. fluconazole) the unit dose of ruxolitinib should be reduced by approximately 50%, to be administered twice daily (see sections 4.4 and 4.5). The concomitant use of ruxolitinib with fluconazole doses greater than 200 mg daily should be avoided.
No specific dose adjustment is needed in patients with mild or moderate renal impairment.
The recommended starting dose for GvHD patients with severe renal impairment (creatinine clearance less than 30 ml/min) should be reduced by approximately 50% to be administered twice daily. Patients should be carefully monitored with regard to safety and efficacy during ruxolitinib treatment (see section 4.4).
There are no data for GvHD patients with end-stage renal disease (ESRD).
Ruxolitinib dose can be titrated to reduce the risk of cytopenia.
In patients with mild, moderate or severe hepatic impairment not related to GvHD, the starting dose of ruxolitinib should be reduced by 50% (see section 5.2).
In patients with GvHD liver involvement and an increase of total bilirubin to >3 x ULN, blood counts should be monitored more frequently for toxicity and a dose reduction by one dose level is recommended (see section 4.4).
No additional dose adjustments are recommended for elderly patients.
Tapering of Jakavi may be considered in patients with a response and after having discontinued corticosteroids. A 50% dose reduction of Jakavi every two months is recommended. If signs or symptoms of GvHD reoccur during or after the taper of Jakavi, re-escalation of treatment should be considered.
Jakavi is to be taken orally, with or without food.
It is recommended that a healthcare professional discusses how to administer the prescribed daily dose of the oral solution with the caregiver prior to administration of the first dose.
It is recommended that the dose of Jakavi is taken at a similar time every day, using the re-usable oral syringe provided.
If a dose is missed, the patient should not take an additional dose, but should take the next usual prescribed dose.
The patient can drink water after taking the oral solution to ensure the medicinal product has been completely swallowed. If the patient is unable to swallow and has a nasogastric or gastric tube in situ, the Jakavi oral solution can be administered via a nasogastric or gastric feeding tube of size French 4 (or greater) and not exceeding 125 cm in length. The tube must be flushed with water immediately after delivering the oral solution.
Instructions for preparation are provided in the instructions for use at the end of the leaflet.
There is no known antidote for overdoses with Jakavi. Single doses up to 200 mg have been given with acceptable acute tolerability. Higher than recommended repeat doses are associated with increased myelosuppression including leukopenia, anaemia and thrombocytopenia. Appropriate supportive treatment should be given.
Haemodialysis is not expected to enhance the elimination of ruxolitinib.
2 years.
After opening use within 60 days.
Do not store above 30°C.
Jakavi oral solution is available in 70 ml amber glass bottles with a white polypropylene child-resistant screw cap closure. Packs containing one bottle of 60 ml oral solution, two 1 ml polypropylene oral syringes and one low density polypropylene press-in bottle adapter. The oral syringes are equipped with plunger O-rings and printed with 0.1 ml graduation marks.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
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