Table 1 Starting doses in myelofibrosis

Polycythaemia vera (PV)

The recommended starting dose of Jakavi in PV is 10 mg twice daily.

Graft versus host disease (GvHD)

The recommended starting dose of Jakavi in acute and chronic GvHD is based on age (see Tables 2 and 3):

Table 3 Starting doses in chronic graft versus host disease

These starting doses in GvHD can be administered using either the tablet for patients who can swallow tablets whole or the oral solution.*

*Oral solution supporting the pediatric patients who cannot swallow tablets whole is not registered in this country.

Jakavi can be added to corticosteroids and/or calcineurin inhibitors (CNIs).

Dose modifications

Doses may be titrated based on efficacy and safety.

Myelofibrosis and polycythaemia vera

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.

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 during treatment as outlined in Table 4, with the goal of avoiding dose interruptions for thrombocytopenia.

Table 5 Dosing recommendations during ruxolitinib therapy for GvHD patients with thrombocytopenia, neutropenia or elevated total bilirubin

Dose adjustment with concomitant strong CYP3A4 inhibitors or dual CYP2C9/3A4 inhibitors

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.

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, PV and GvHD patients 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 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 to 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).

There are no data for GvHD patients with ESRD.

Hepatic impairment

In MF 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. The recommended starting dose is 5 mg twice daily for PV patients. Ruxolitinib dose can be titrated to reduce the risk of cytopenia (see section 4.4).

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.

Elderly patients (≥65 years)

No additional dose adjustments are recommended for elderly patients.

Paediatric population

The safety and efficacy of Jakavi in children and adolescents aged up to 18 years with MF and PV have not been established. No data are available (see section 5.1).

Treatment discontinuation

Treatment of MF and PV may be continued as long as the benefit-risk assessment 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.

In GvHD, 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.

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.

Contraindications: Hypersensitivity to ruxolitinib or to any of the excipients. ♦Pregnancy and lactation.

Warnings and precautions: ♦Decrease in blood cell count: hematologic adverse drug reactions, including thrombocytopenia, anemia, and neutropenia, have been reported with Jakavi treatment. Complete blood counts monitoring recommended. Dose reduction or interruption may be required in patients developing thrombocytopenia, anemia, and neutropenia. ♦Infections: Serious bacterial, mycobacterial, fungal, viral, and other opportunistic infections have occurred in patients treated with Jakavi. Patients should be assessed for the risk of developing serious infections. Physicians should carefully observe patients receiving Jakavi for signs and symptoms of infections and initiate appropriate treatment promptly. Jakavi therapy should not be started until active serious infections have resolved. Tuberculosis cases have been reported. Before starting treatment, patients should be evaluated for active and inactive (“latent”) tuberculosis, as per local recommendations.

Hepatitis B viral load (HBV-DNA titre) increases have been reported in patients with chronic HBV infections. Patients with chronic HBV infection should be treated and monitored according to clinical guidelines. ♦Herpes zoster: Physician to educate patients about early signs and symptoms of herpes zoster, advising for immediate treatment. ♦Progressive multifocal leukencephalopathy (PML) has been reported. Physicians should be alert for neuropsychiatric symptoms suggestive of PML. If PML suspected suspend treatment until PML is excluded. ♦Non-Melanoma Skin Cancer (NMSC): NMSC, including basal cell, squamous cell, and Merkel cell carcinoma, have been reported in Jakavi treated patients.

Periodic skin examination recommended. ♦Lipid Abnormalities/Elevations: Increases in lipid parameters, including total cholesterol, high-density lipoprotein (HDL) cholesterol, low- density lipoprotein (LDL) cholesterol, and triglycerides have been associated with Jakavi.

Monitoring and treatment of dyslipidaemia is recommended. ♦Hepatic and severe renal impairment: Due to increased Jakavi exposure, dose reduction is required. ♦Major adverse cardiac events (MACE) In a large randomised active-controlled study of tofacitinib (another JAK inhibitor) in rheumatoid arthritis patients 50 years of age and older with at least one additional cardiovascular risk factor, a higher rate of MACE, defined as cardiovascular death, non-fatal myocardial infarction (MI) and non-fatal stroke, was observed with tofacitinib compared to tumour necrosis factor (TNF) inhibitors. MACE have been reported in patients receiving Jakavi. Prior to initiating or continuing therapy with Jakavi, the benefits and risks for the individual patient should be considered particularly in patients 65 years of age and older, patients who are current or past long-time smokers, and patients with a history of atherosclerotic cardiovascular disease or other cardiovascular risk factors. ♦Thrombosis In a large randomised active-controlled study of tofacitinib (another JAK inhibitor) in rheumatoid arthritis patients 50 years of age and older with at least one additional cardiovascular risk factor, a dose dependent higher rate of venous thromboembolic events (VTE) including deep venous thrombosis (DVT) and pulmonary embolism (PE) was observed with tofacitinib compared to TNF inhibitors. Events of deep venous thrombosis (DVT) and pulmonary embolism (PE) have been reported in patients receiving Jakavi. In patients with MF and PV treated with Jakavi in clinical studies, the rates of thromboembolic events were similar in Jakavi and control-treated patients. Prior to initiating or continuing therapy with Jakavi, the benefits and risks for the individual patient should be considered, particularly in patients with cardiovascular risk factors.

Pregnancy, lactation, females and males of reproductive potential

Pregnancy: Use in pregnancy is contraindicated.

Lactation: Women taking Jakavi should not breast-feed.

Contraception: Sexually active females should use effective contraception during treatment.

Adverse drug reactions:

Myelofibrosis

Very common (≥10%): Urinary tract infections, herpes zoster, pneumonia, anaemia, thrombocytopenia, neutropenia, hypercholesterolaemia, hypertriglyceridaemia, dizziness, headache, constipation, ALT increased, AST increased, hypertension, bruising, Gastrointestinal bleeding, Other bleeding (including epistaxis, post-procedural haemorrhage and haematuria), Elevated lipase, weight gain.

Common (≥1 to <10%): Pancytopenia, flatulence, Intracranial bleeding.

Uncommon (≥0.1 to <1%): Tuberculosis.

Not known (frequency cannot be estimated): HBV reactivation.

Polycythemia vera

Very common (≥10%): Urinary tract infections, herpes zoster, anaemia, thrombocytopenia, bruising, hypercholesterolaemia, hypertriglyceridaemia, weight gain, dizziness, headache, Elevated lipase, constipation, ALT increased, AST increased, hypertension.

Common (≥1 to <10%): Pneumonia, neutropenia, pancytopenia, Gastrointestinal bleeding, Other bleeding (including epistaxis, post-procedural haemorrhage and haematuria), flatulence.

Uncommon (≥0.1 to <1%): Sepsis, Intracranial bleeding. Not known (frequency cannot be estimated): Tuberculosis. Acute Graft versus host disease

Very common (≥10%): CMV infections, sepsis, UTI, thrombocytopenia, anaemia,

neutropenia, pancytopenia, hypercholesterolemia, hypertension, nausea, increased ALT and AST.

Common (≥1 to <10%): headache.

Acute Graft versus host disease (Paediatric pool)

Very common (≥10%): CMV infections, Thrombocytopenia, Anaemia, Neutropenia, Pancytopenia, Hypercholesterolaemia, Hypertension, increased ALT and AST.

Common (≥1 to <10%): Sepsis, Urinary tract infections, Headache, Nausea.

Chronic Graft versus host disease

Very common (≥10%): Thrombocytopenia, Anaemia, Neutropenia, Hypercholesterolaemia, Headache, Hypertension, Increased lipase, Increased amylase, increased ALT and AST, Increased blood creatine phosphokinase, Increased blood creatinine.

Common (≥1 to <10%): CMV infections, Urinary tract infections, BK virus infections, Weight gain, Constipation

Chronic Graft versus host disease (Paediatric pool)

Very common (≥10%): Thrombocytopenia, Anaemia, Neutropenia, Hypercholesterolaemia, Headache, Hypertension, Increased lipase, Increased amylase, increased ALT and AST, Increased blood creatine phosphokinase.

Common (≥1 to <10%): CMV infections, Urinary tract infections, BK virus infections, Weight gain, Constipation, Increased blood creatinine.

Interactions: ♦ Caution with CYP3A4 inhibitors or dual moderate inhibitors of CYP2C9 and CYP3A4 enzymes. Dose reduction recommended when co-administered with strong CYP3A4 inhibitors in MF and PV patients or dual moderate inhibitors of CYP2C9 and CYP3A4 enzymes in MF, PV and GvHD patients. Avoid fluconazole daily doses >200 mg. ♦ CYP3A4 inducers (such as, but not limited to, avasimibe, carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin (rifampicin), St.John’s wort (Hypericum perforatum))

Patients should be closely monitored and the dose titrated based on safety and efficacy.  Mild or moderate CYP3A4 inhibitors (such as, but not limited to, ciprofloxacin, erythromycin, amprenavir, atazanavir, diltiazem, cimetidine) No dose adjustment is recommended when ruxolitinib is co-administered with mild or moderate CYP3A4 inhibitors (e.g. erythromycin). However, patients should be closely monitored for cytopenias when initiating therapy with a moderate CYP3A4 inhibitor

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Leaflet Revision Date: February 2025

Leaflet Presentation Type: R02