Jakavi 5 mg tablets: Each tablet contains 5 mg ruxolitinib (as phosphate).
Jakavi 10 mg tablets: Each tablet contains 10 mg ruxolitinib (as phosphate).
Jakavi 15 mg tablets: Each tablet contains 15 mg ruxolitinib (as phosphate).
Jakavi 20 mg tablets : Each tablet contains 20 mg ruxolitinib (as phosphate).
Excipient with known effect:
Jakavi 5 mg tablets: Each tablet contains 71.45 mg lactose monohydrate.
Jakavi 10 mg tablets: Each tablet contains 142.90 mg lactose monohydrate.
Jakavi 15 mg tablets: Each tablet contains 214.35 mg lactose monohydrate.
Jakavi 20 mg tablets : Each tablet contains 285.80 mg lactose monohydrate.
For the full list of excipients, see section 6.1.
Jakavi treatment should only be initiated by a physician experienced in the administration of anti-cancer agents.
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 2-4 weeks until Jakavi doses are stabilised, and then as clinically indicated (see section 4.4).
Posology
Starting dose
The recommended starting dose of Jakavi in myelofibrosis is 15 mg twice daily for patients with a platelet count between 100,000/mm3 and 200,000/mm3 and 20 mg twice daily for patients with a platelet count of >200,000/mm3. The recommended starting dose of Jakavi in polycythaemia vera is 10 mg given orally twice daily.
There is limited information to recommend a starting dose for patients with platelet counts between 50,000/mm3 and <100,000/mm3. The maximum recommended starting dose in these patients is 5 mg twice daily and the patients should be titrated cautiously.
Dose modifications
Doses may be titrated based on safety and efficacy. Treatment should be discontinued for platelet counts less than 50,000/mm3 or absolute neutrophil counts less than 500/mm3. In PV, treatment should also be interrupted when haemoglobin is below 8 g/dl. After recovery of blood counts above these levels, dosing may be re-started at 5 mg twice daily and gradually increased based on careful monitoring of complete blood cell count, including a white blood cell count differential.
Dose reductions should be considered if the platelet count decreases below 100,000/mm3, with the goal of avoiding dose interruptions for thrombocytopenia. In PV, dose reductions should also be considered if haemoglobin decreases below 12 g/dl and is recommended if it decreases below 10 g/dl.
If efficacy is considered insufficient and blood counts are adequate, doses may be increased by a maximum of 5 mg twice daily, up to the maximum dose of 25 mg twice daily.
The starting dose should not be increased within the first four weeks of treatment and thereafter no more frequently than at 2-week intervals.
The maximum dose of Jakavi is 25 mg twice daily.
Dose adjustment with concomitant strong CYP3A4 inhibitors or fluconazole
When Jakavi is administered with strong CYP3A4 inhibitors or dual inhibitors of CYP2C9 and CYP3A4 enzymes (e.g. fluconazole) the unit dose of Jakavi should be reduced by approximately 50%, to be administered twice daily (see section 4.5).
More frequent monitoring (e.g. twice a week) of haematology parameters and of clinical signs and symptoms of Jakavi-related adverse drug reactions is recommended while on strong CYP3A4 inhibitors or dual inhibitors of CYP2C9 and CYP3A4 enzymes.
Special populations
Renal impairment
No specific dose adjustment is needed in patients with mild or moderate renal impairment.
In patients with severe renal impairment (creatinine clearance less than 30 ml/min) the recommended starting dose based on platelet count for MF patients should be reduced by approximately 50% to be administered twice daily. The recommended starting dose for PV patients with severe renal impairment is 5 mg twice daily. Patients should be carefully monitored with regard to safety and efficacy during Jakavi treatment.
There are limited data to determine the best dosing options for patients with end-stage renal disease (ESRD) on haemodialysis. Pharmacokinetic/pharmacodynamic simulations based on available data in this population suggest that the starting dose for MF patients with ESRD on haemodialysis is a single dose of 15-20 mg or two doses of 10 mg given 12 hours apart, to be administered post-dialysis and only on the day of haemodialysis. A single dose of 15 mg is recommended for MF patients with platelet count between 100,000/mm3 and 200,000/mm3. A single dose of 20 mg or two doses of 10 mg given 12 hours apart is recommended for MF patients with platelet count of >200,000/mm3. Subsequent doses (single administration or two doses of 10 mg given 12 hours apart) should be administered only on haemodialysis days following each dialysis session.
The recommended starting dose for PV patients with ESRD on haemodialysis is a single dose of 10 mg or two doses of 5 mg given 12 hours apart, to be administered post-dialysis and only on the day of haemodialysis. These dose recommendations are based on simulations and any dose modification in ESRD should be followed by careful monitoring of safety and efficacy in individual patients. No data is available for dosing patients who are undergoing peritoneal dialysis or continuous venovenous haemofiltration (see section 5.2).
Hepatic impairment
In patients with any hepatic impairment the recommended starting dose based on platelet count should be reduced by approximately 50% to be administered twice daily. Subsequent doses should be adjusted based on careful monitoring of safety and efficacy. Patients diagnosed with hepatic impairment while receiving Jakavi should have complete blood counts, including a white blood cell count differential, monitored at least every one to two weeks for the first 6 weeks after initiation of therapy with Jakavi and as clinically indicated thereafter once their liver function and blood counts have been stabilised. Jakavi dose can be titrated to reduce the risk of cytopenia.
Older people (≥65 years)
No additional dose adjustments are recommended for older people.
Paediatric population
The safety and efficacy of Jakavi in children aged up to 18 years have not been established. No data are available (see section 5.1).
Treatment discontinuation
Treatment may be continued as long as the benefit-risk remains positive. However the treatment should be discontinued after 6 months if there has been no reduction in spleen size or improvement in symptoms since initiation of therapy.
It is recommended that, for patients who have demonstrated some degree of clinical improvement, ruxolitinib therapy be discontinued if they sustain an increase in their spleen length of 40% compared with baseline size (roughly equivalent to a 25% increase in spleen volume) and no longer have tangible improvement in disease-related symptoms.
Method of administration
Jakavi is to be taken orally, with or without food.
If a dose is missed, the patient should not take an additional dose, but should take the next usual prescribed dose.
