Ruxolitinib / Jakavi is a selective inhibitor of the Janus Associated Kinases (JAKs) JAK1 and JAK2 (IC 50 values of 3.3 nM and 2.8 nM for JAK1 and JAK2 enzymes, respectively). These mediate the signalling of a number of cytokines and growth factors that are important for haematopoiesis and immune function.

MF and PV are myeloproliferative neoplasms known to be associated with dysregulated JAK1 and JAK2 signalling. The basis for the dysregulation is believed to include high levels of circulating cytokines that activate the JAK-STAT pathway, gain-of-function mutations such as JAK2V617F, and silencing of negative regulatory mechanisms.

MF patients exhibit dysregulated JAK signalling regardless of JAK2V617F mutation status. Activating mutations in JAK2 (V617F or exon 12) are found in >95% of PV patients.

Ruxolitinib / Jakavi inhibits JAK-STAT signalling and cell proliferation of cytokine-dependent cellular models of haematological malignancies, as well as of Ba/F3 cells rendered cytokine-independent by expressing the JAK2V617F mutated protein, with IC 50 ranging from 80-320 nM.

The recommended starting dose of ruxolitinib / Jakavi in MF is 15 mg twice daily for patients with a platelet count between 100,000/mm 3 and 200,000/mm 3 and 20 mg twice daily for patients with a platelet count of >200,000/mm 3 . The recommended starting dose of ruxolitinib in PV is 10 mg given orally twice daily.

There is limited information to recommend a starting dose for patients with platelet counts between 50,000/mm 3 and <100,000/mm 3 . The maximum recommended starting dose in these patients is 5 mg twice daily and the patients should be titrated cautiously.

Contraindicated in pregnancy & lactation. There are no data from the use of ruxolitinib in pregnant women. Animal studies have shown that ruxolitinib is embryotoxic and foetotoxic.

ruxolitinib / Jakavi must not be used during breast-feeding and breast-feeding should therefore be discontinued when treatment is started. It is unknown whether ruxolitinib and/or its metabolites are excreted in human milk.

A risk to the breast-fed child cannot be excluded. Available pharmacodynamic/toxicological data in animals have shown excretion of ruxolitinib and its metabolites in milk

Fertility: There are no human data on the effect of ruxolitinib on fertility. In animal studies, no effect on fertility was observed.

Renal impairment: No specific dose adjustment is needed in patients with mild or moderate renal impairment.

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.

Elderly patients (≥65 years): No additional dose adjustments are recommended for elderly patients.

Paediatric population: The safety and efficacy of Ruxolitinib / Jakavi in children and adolescents aged up to 18 years have not been established. No data are available