Jakavi

1 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 
 



2 

1. NAME OF THE MEDICINAL PRODUCT 
 

Jakavi 5 mg tablets 

Jakavi 10 mg tablets 

Jakavi 15 mg tablets 

Jakavi 20 mg tablets 

 

 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION 

 

Jakavi 5 mg tablets 

Each tablet contains 5 mg ruxolitinib (as phosphate). 

 

Excipient with known effect 

Each tablet contains 71.45 mg lactose monohydrate. 

 

Jakavi 10 mg tablets 

Each tablet contains 10 mg ruxolitinib (as phosphate). 

 

Excipient with known effect 

Each tablet contains 142.90 mg lactose monohydrate. 

 

Jakavi 15 mg tablets 

Each tablet contains 15 mg ruxolitinib (as phosphate). 

 

Excipient with known effect 

Each tablet contains 214.35 mg lactose monohydrate. 

 

Jakavi 20 mg tablets 

Each tablet contains 20 mg ruxolitinib (as phosphate). 

 

Excipient with known effect 

Each tablet contains 285.80 mg lactose monohydrate. 

 

For the full list of excipients, see section 6.1. 

 

 

3. PHARMACEUTICAL FORM 

 

Tablet. 

 

Jakavi 5 mg tablets 

Round curved white to almost white tablets of approximately 7.5 mm in diameter with “NVR” 

debossed on one side and “L5” debossed on the other side. 

 

Jakavi 10 mg tablets 

Round curved white to almost white tablets of approximately 9.3 mm in diameter with “NVR” 

debossed on one side and “L10” debossed on the other side. 

 

Jakavi 15 mg tablets 

Ovaloid curved white to almost white tablets of approximately 15.0 x 7.0 mm with “NVR” debossed 

on one side and “L15” debossed on the other side. 

 

Jakavi 20 mg tablets 

Elongated curved white to almost white tablets of approximately 16.5 x 7.4 mm with “NVR” debossed 

one one side and “L20” debossed on the other side. 

 



3 

 

4. CLINICAL PARTICULARS 

 

4.1 Therapeutic indications 
 

Myelofibrosis (MF) 

 

Jakavi is indicated for the treatment of disease-related splenomegaly or symptoms in adult patients 

with primary myelofibrosis (also known as chronic idiopathic myelofibrosis), post polycythaemia vera 

myelofibrosis or post essential thrombocythaemia myelofibrosis. 

 

Polycythaemia vera (PV) 

 

Jakavi is indicated for the treatment of adult patients with polycythaemia vera who are resistant to or 

intolerant of hydroxyurea. 

 

4.2 Posology and method of administration 

 

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 

2-4 weeks until Jakavi doses are stabilised, and then as clinically indicated (see section 4.4). 

 

Posology 

 

Starting dose 

The recommended starting dose of ruxolitinib in MF 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 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/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 ruxolitinib is 25 mg twice daily. 



4 

 

Dose adjustment with concomitant strong CYP3A4 inhibitors or fluconazole 

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 section 4.5). Avoid the concomitant use of ruxolitinib with 

fluconazole doses greater than 200 mg daily. 

 

More frequent monitoring (e.g. twice a week) of haematology parameters and of clinical signs and 

symptoms of ruxolitinib-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 ruxolitinib 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 ruxolitinib 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 ruxolitinib and as clinically indicated thereafter once their liver function and blood 

counts have been stabilised. Ruxolitinib dose can be titrated to reduce the risk of cytopenia. 

 

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 have not been 

established. No data are available (see section 5.1). 

  



5 

 

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. 

 

4.3 Contraindications 
 

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 

 

Pregnancy and lactation. 

 

4.4 Special warnings and precautions for use 

 

Myelosuppression 

 

Treatment with Jakavi can cause haematological adverse drug reactions, including thrombocytopenia, 

anaemia and neutropenia. A complete blood count, including a white blood cell count differential, 

must be performed before initiating therapy with Jakavi. Treatment should be discontinued in patients 

with platelet count less than 50,000/mm3 or absoute neutrophil count less than 500/mm3 (see 

section 4.2). 

 

It has been observed that patients with low platelet counts (<200,000/mm3) at the start of therapy are 

more likely to develop thrombocytopenia during treatment. 

 

Thrombocytopenia is generally reversible and is usually managed by reducing the dose or temporarily 

withholding Jakavi (see sections 4.2 and 4.8). However, platelet transfusions may be required as 

clinically indicated. 

 

Patients developing anaemia may require blood transfusions. Dose modifications or interruption for 

patients developing anaemia may also be considered. 

 

Patients with a haemoglobin level below 10.0 g/dl at the beginning of the treatment have a higher risk 

of developing a haemoglobin level below 8.0 g/dl during treatment compared to patients with a higher 

baseline haemoglobin level (79.3% versus 30.1%). More frequent monitoring of haematology 

parameters and of clinical signs and symptoms of Jakavi-related adverse drug reactions is 

recommended for patients with baseline haemoglobin below 10.0 g/dl. 

 

Neutropenia (absolute neutrophil count <500) was generally reversible and was managed by 

temporarily withholding Jakavi (see sections 4.2 and 4.8). 

 

Complete blood counts should be monitored as clinically indicated and dose adjusted as required (see 

sections 4.2 and 4.8). 

 



6 

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. Treatment with Jakavi should not be started until active 

serious infections have resolved. 

 

Tuberculosis has been reported in patients receiving Jakavi. Before starting treatment, patients should 

be evaluated for active and inactive (“latent”) tuberculosis, as per local recommendations. This can 

include medical history, possible previous contact with tuberculosis, and/or appropriate screening such 

as lung x-ray, tuberculin test and/or interferon-gamma release assay, as applicable. Prescribers are 

reminded of the risk of false negative tuberculin skin test results, especially in patients who are 

severely ill or immunocompromised. 

 

Hepatitis B viral load (HBV-DNA titre) increases, with and without associated elevations in alanine 

aminotransferase and aspartate aminotransferase, have been reported in patients with chronic HBV 

infections taking Jakavi. The effect of Jakavi on viral replication in patients with chronic HBV 

infection is unknown. Patients with chronic HBV infection should be treated and monitored according 

to clinical guidelines. 

 

Herpes zoster 

 

Physicians should educate patients about early signs and symptoms of herpes zoster, advising that 

treatment should be sought as early as possible. 

 

Progressive multifocal leukoencephalopathy 

 

Progressive multifocal leukoencephalopathy (PML) has been reported with Jakavi treatment. 

Physicians should be particularly alert to symptoms suggestive of PML that patients may not notice 

(e.g., cognitive, neurological or psychiatric symptoms or signs). Patients should be monitored for any 

of these new or worsening symptoms or signs, and if such symptoms/signs occur, referral to a 

neurologist and appropriate diagnostic measures for PML should be considered. If PML is suspected, 

further dosing must be suspended until PML has been excluded. 

 

Non-melanoma skin cancer 

 

Non-melanoma skin cancers (NMSCs), including basal cell, squamous cell, and Merkel cell 

carcinoma, have been reported in patients treated with ruxolitinib. Most of these patients had histories 

of extended treatment with hydroxyurea and prior NMSC or pre-malignant skin lesions. A causal 

relationship to ruxolitinib has not been established. Periodic skin examination is recommended for 

patients who are at increased risk for skin cancer. 

 

Lipid abnormalities/elevations 

 

Treatment with Jakavi has been associated with increases in lipid parameters including total 

cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, 

and triglycerides. Lipid monitoring and treatment of dyslipidaemia according to clinical guidelines is 

recommended. 

  



7 

 

Special populations 

 

Renal impairment 

The starting dose of Jakavi should be reduced in patients with severe renal impairment. For patients 

with end-stage renal disease on haemodialysis the starting dose for MF patients should be based on 

platelet counts (see section 4.2). Subsequent doses (single dose of 20 mg or two doses of 10 mg given 

12 hours apart in MF patients; single dose of 10 mg or two doses of 5 mg given 12 hours apart in PV 

patients) should be administered only on haemodialysis days following each dialysis session. 

Additional dose modifications should be made with careful monitoring of safety and efficacy (see 

sections 4.2 and 5.2). 

 

Hepatic impairment 

The starting dose of Jakavi should be reduced by approximately 50% in patients with hepatic 

impairment. Further dose modifications should be based on the safety and efficacy of the medicinal 

product (see sections 4.2 and 5.2). 

 

Interactions 

 

If Jakavi is to be co-administered with strong CYP3A4 inhibitors or dual inhibitors of CYP3A4 and 

CYP2C9 enzymes (e.g. fluconazole), the unit dose of Jakavi should be reduced by approximately 

50%, to be administered twice daily (for monitoring frequency see sections 4.2 and 4.5). 

 

The concomitant use of cytoreductive therapies with Jakavi was associated with manageable 

cytopenias (see section 4.2 for dose modifications during cytopenias). 

 

Withdrawal effects 

 

Following interruption or discontinuation of Jakavi, symptoms of MF may return over a period of 

approximately one week. There have been cases of patients discontinuing Jakavi who sustained more 

severe events, particularly in the presence of acute intercurrent illness. It has not been established 

whether abrupt discontinuation of Jakavi contributed to these events. Unless abrupt discontinuation is 

required, gradual tapering of the dose of Jakavi may be considered, although the utility of the tapering 

is unproven. 

 

Excipients 

 

Jakavi contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp 

lactase deficiency or glucose-galactose malabsorption should not take this medicinal product. 

 

4.5 Interaction with other medicinal products and other forms of interaction 
 

Interaction studies have only been performed in adults. 

 

Ruxolitinib is eliminated through metabolism catalysed by CYP3A4 and CYP2C9. Thus, medicinal 

products inhibiting these enzymes can give rise to increased ruxolitinib exposure. 

 

Interactions resulting in dose reduction of ruxolitinib 

 

CYP3A4 inhibitors 

Strong CYP3A4 inhibitors (such as, but not limited to, boceprevir, clarithromycin, indinavir, 

itraconazole, ketoconazole, lopinavir/ritonavir, ritonavir, mibefradil, nefazodone, nelfinavir, 

posaconazole, saquinavir, telaprevir, telithromycin, voriconazole) 

In healthy subjects co-administration of ruxolitinib (10 mg single dose) with a strong CYP3A4 

inhibitor, ketoconazole, resulted in ruxolitinib Cmax and AUC that were higher by 33% and 91%, 

respectively, than with ruxolitinib alone. The half-life was prolonged from 3.7 to 6.0 hours with 

concurrent ketoconazole administration. 



8 

 

When administering ruxolitinib with strong CYP3A4 inhibitors the unit dose of ruxolitinib should be 

reduced by approximately 50%, to be administered twice daily. Patients should be closely monitored 

(e.g. twice weekly) for cytopenias and dose titrated based on safety and efficacy (see section 4.2). 

 

Dual CYP2C9 and CYP3A4 inhibitors 

In healthy subjects co-administration of ruxolitinib (10 mg single dose) with a dual CYP2C9 and 

CYP3A4 inhibitor, fluconazole, resulted in ruxolitinib Cmax and AUC that were higher by 47% and 

232%, respectively, than with ruxolitinib alone. 

 

50% dose reduction should be considered when using medicinal products which are dual inhibitors of 

CYP2C9 and CYP3A4 enzymes (e.g. fluconazole). Avoid the concomitant use of ruxolitinib with 

fluconazole doses greater than 200 mg daily. 

 

Enzyme inducers 

 

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 (see 

section 4.2). 

 

In healthy subjects given ruxolitinib (50 mg single dose) following the potent CYP3A4 inducer 

rifampicin (600 mg daily dose for 10 days), ruxolitinib AUC was 70% lower than after administration 

of ruxolitinib alone. The exposure of ruxolitinib active metabolites was unchanged. Overall, the 

ruxolitinib pharmacodynamic activity was similar, suggesting the CYP3A4 induction resulted in 

minimal effect on the pharmacodynamics. However, this could be related to the high ruxolitinib dose 

resulting in pharmacodynamic effects near Emax. It is possible that in the individual patient, an increase 

of the ruxolitinib dose is needed when initiating treatment with a strong enzyme inducer. 

 

Other interactions to be considered affecting ruxolitinib 

 

Mild or moderate CYP3A4 inhibitors (such as, but not limited to, ciprofloxacin, erythromycin, 

amprenavir, atazanavir, diltiazem, cimetidine) 

In healthy subjects co-administration of ruxolitinib (10 mg single dose) with erythromycin 500 mg 

twice daily for four days resulted in ruxolitinib Cmax and AUC that were higher by 8% and 27%, 

respectively, than with ruxolitinib alone. 

 

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. 

 

Effects of ruxolitinib on other medicinal products 

 

Substances transported by P-glycoprotein or other transporters 

Ruxolitinib may inhibit P-glycoprotein and breast cancer resistance protein (BCRP) in the intestine. 

This may result in increased sytemic exposure of substrates of these transporters, such as dabigatran 

etexilate, ciclosporin, rosuvastatin and potentially digoxin. Therapeutic drug monitoring (TDM) or 

clinical monitoring of the affected substance is advised. 

 

It is possible that the potential inhibition of P-gp and BCRP in the intestine can be minimised if the 

time between administrations is kept apart as long as possible. 

  



9 

 

A study in healthy subjects indicated that ruxolitinib did not inhibit the metabolism of the oral 

CYP3A4 substrate midazolam. Therefore, no increase in exposure of CYP3A4 substrates is 

anticipated when combining them with ruxolitinib. Another study in healthy subjects indicated that 

ruxolitinib does not affect the pharmacokinetics of an oral contraceptive containing ethinylestradiol 

and levonorgestrel. Therefore, it is not anticipated that the contraceptive efficacy of this combination 

will be compromised by co-administration of ruxolitinib. 

 

4.6 Fertility, pregnancy and lactation 
 

Pregnancy 

 

There are no data from the use of Jakavi in pregnant women. 

 

Animal studies have shown that ruxolitinib is embryotoxic and foetotoxic. Teratogenicity was not 

observed in rats or rabbits. However, the exposure margins compared to the highest clinical dose were 

low and the results are therefore of limited relevance for humans (see section 5.3). The potential risk 

for humans is unknown. As a precautionary measure, the use of Jakavi during pregnancy is 

contraindicated (see section 4.3). 

 

Women of childbearing potential/Contraception 

 

Women of child-bearing potential should use effective contraception during the treatment with Jakavi. 

In case pregnancy should occur during treatment with Jakavi, a risk/benefit evaluation must be carried 

out on an individual basis with careful counselling regarding potential risks to the foetus (see 

section 5.3). 

 

Breast-feeding 

 

Jakavi must not be used during breast-feeding (see section 4.3) 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 (see section 5.3). 

 

Fertility 

 

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

was observed. 

 

4.7 Effects on ability to drive and use machines 
 

Jakavi has no or negligible sedating effect. However, patients who experience dizziness after the 

intake of Jakavi should refrain from driving or using machines. 

 

4.8 Undesirable effects 

 

Summary of the safety profile 

 

Myelofibrosis 

The most frequently reported adverse drug reactions were thrombocytopenia and anaemia. 

 

Haematological adverse drug reactions (any Common Terminology Criteria for Adverse Events 

[CTCAE] grade) included anaemia (83.8%), thrombocytopenia (80.5%) and neutropenia (20.8%). 

 

Anaemia, thrombocytopenia and neutropenia are dose-related effects. 

 



10 

The three most frequent non-haematological adverse drug reactions were bruising (33.3%), other 

bleeding (including epistaxis, post-procedural haemorrhage and haematuria) (24.3%) and dizziness 

(21.9%). 

 

The three most frequent non-haematological laboratory abnormalities were raised alanine 

aminotransferase (40.7%), raised aspartate aminotransferase (31.5%) and hypertriglyceridaemia 

(25.2%). In phase 3 clinical studies in MF, neither CTCAE grade 3 or 4 hypertriglyceridaemia or 

raised aspartate aminotransferase, nor CTCAE grade 4 raised alanine aminotransferase or 

hypercholesterolaemia were observed. 

 

Discontinuation due to adverse events, regardless of causality, was observed in 30.0% of patients. 
 

Polycythaemia vera 

Haematological adverse reactions (any CTCAE grade) included anaemia (61.8%) and 

thrombocytopenia (25.0%). Anaemia and thrombocytopenia CTCAE grade 3 or 4 were reported in 

respectively 2.9% and 2.6%. 

 

The three most frequent non-haematological adverse reactions were weight gain (20.3%), dizziness 

(19.4%) and headache (17.9%). 

 

The three most frequent non-haematological laboratory abnormalities (any CTCAE grade) identified 

as adverse reactions were raised alanine aminotransferase (45.3%), raised aspartate aminotransferase 

(42.6%), and hypercholesterolaemia (34.7%). No CTCAE grade 4 raised alanine aminotransferase or 

hypercholesterolaemia, and one CTCAE grade 4 raised aspartate aminotransferase were observed. 

 

Discontinuation due to adverse events, regardless of causality, was observed in 19.4% of patients. 
 

Tabulated list of adverse drug reactions from clinical studies 

 

Safety in MF patients was evaluated using the long-term follow-up data from two phase 3 studies 

(COMFORT-I and COMFORT-II) including data from patients initially randomised to ruxolitinib 

(n=301) and patients who received ruxolitinib after crossing over from control treatments (n=156). 

The median exposure upon which the ADR frequencies categories for MF patients are based was 

30.5 months (range 0.3 to 68.1 months). 

 

Safety in PV patients was evaluated using the long-term follow-up data from two phase 3 studies 

(RESPONSE, RESPONSE 2) including data from patients initially randomised to ruxolitinib (n=184) 

and patients who received ruxolitinib after crossing over from control treatments (n=156). The median 

exposure upon which the ADR frequencies categories for PV patients are based was 41.7 months 

(range 0.03 to 59.7 months). 
 

In the clinical study programme the severity of adverse drug reactions was assessed based on the 

CTCAE, defining grade 1 = mild, grade 2 = moderate, grade 3 = severe and grade 4=life-threatening. 

 

Adverse drug reactions from clinical studies (Table 1) are listed by MedDRA system organ class. 

Within each system organ class, the adverse drug reactions are ranked by frequency, with the most 

frequent reactions first. In addition, the corresponding frequency category for each adverse drug 

reaction is based on the following convention: very common (≥1/10); common (≥1/100 to <1/10); 

uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000). 

 



11 

Table 1 Frequency category of adverse drug reactions reported in the phase 3 studies 

(COMFORT-I, COMFORT-II, RESPONSE, RESPONSE 2) 

 

Adverse drug reaction Frequency category for MF 

patients 

Frequency category for PV 

patients 

Infections and infestations   

Urinary tract infectionsa,d Very common Very common 

Herpes zostera,d Very common Very common 

Pneumonia Very common Common 

Sepsis Common Uncommon 

Tuberculosise Uncommon Unknownf 

Blood and lymphatic system 

disordersb,d 

  

Anaemiab   

CTCAEc grade 4 

(<6.5g/dl) 

Very common Uncommon 

CTCAEc grade 3 

(<8.0 – 6.5g/dl) 

Very common Common 

Any CTCAEc grade Very common Very common 

Thrombocytopeniab   

CTCAEc grade 4 

(<25,000/mm3) 

Common Uncommon 

CTCAEc grade 3 

(50,000 – 25,000/mm3) 

Very common Common 

Any CTCAEc grade Very common Very common 

Neutropeniab   

CTCAEc grade 4 

(<500/mm3) 

Common Uncommon 

CTCAEc grade 3 

(<1,000 – 500/mm3) 

Common Uncommon 

Any CTCAEc grade Very common Very common 

Bleeding (any bleeding 

including intracranial, and 

gastrointestinal bleeding, 

bruising and other bleeding) 

Very common Very common 

Bruising Very common Very common 

Gastrointestinal bleeding Very common Common 

Intracranial bleeding Common Uncommon 

Other bleeding (including 

epistaxis, post-procedural 

haemorrhage and 

haematuria) 

Very common Very common 

Metabolism and nutrition 

disorders 

  

Hypercholesterolaemiab 

any CTCAEc grade 

Very common Very common 

Hypertriglyceridaemiab 

any CTCAEc grade 

Very common Very common 

Weight gaina Very common Very common 

Nervous system disorders   

Dizzinessa Very common Very common 

Headachea Very common Very common 



12 

Gastrointestinal disorders   

Elevated lipase, any CTCAEc 

grade 
Very common Very common 

Constipationa Very common Very common 

Flatulencea Common Common 

Hepatobiliary disorders   

Raised alanine 

aminotransferaseb 

  

CTCAEc grade 3 

(> 5x – 20 x ULN) 

Common Common 

Any CTCAEc grade Very common Very common 

Raised aspartate 

aminotransferaseb 

  

Any CTCAEc grade Very common Very common 

Vascular disorders   

Hypertensiona Very common Very common 
a Frequency is based on adverse event data. 

- A subject with multiple occurrence of an adverse drug reaction (ADR) is counted only 
once in that ADR category. 

- ADRs reported are on treatment or up to 28 days post treatment end date. 
b Frequency is based on laboratory values. 

- A subject with multiple occurrences of an ADR is counted only once in that ADR 
category. 

- ADRs reported are on treatment or up to 28 days post treatment end date. 
c Common Terminology Criteria for Adverse Events (CTCAE) version 3.0; grade 1 = mild, 

grade 2 = moderate, grade 3 = severe, grade 4 = life-threatening 
d These ADRs are discussed in the text. 
e Frequency is based on all patients exposed to ruxolitinib in clinical studies (N=4755) 
f ADR derived from post-marketing experience 

 

Upon discontinuation, MF patients may experience a return of MF symptoms such as fatigue, bone 

pain, fever, pruritus, night sweats, symptomatic splenomegaly and weight loss. In clinical studies in 

MF the total symptom score for MF symptoms gradually returned to baseline value within 7 days after 

dose discontinuation (see section 4.4). 

 

Description of selected adverse drug reactions 

 

Anaemia 

In phase 3 clinical studies in MF, median time to onset of first CTCAE grade 2 or higher anaemia was 

1.5 months. One patient (0.3%) discontinued treatment because of anaemia. 

 

In patients receiving ruxolitinib mean decreases in haemoglobin reached a nadir of approximately 
10 g/litre below baseline after 8 to 12 weeks of therapy and then gradually recovered to reach a new 

steady state that was approximately 5 g/litre below baseline. This pattern was observed in patients 

regardless of whether they had received transfusion during therapy. 

 

In the randomised, placebo-controlled study COMFORT-I 60.6% of Jakavi-treated MF patients and 

37.7% of placebo-treated MF patients received red blood cell transfusions during randomised 

treatment. In the COMFORT-II study the rate of packed red blood cell transfusions was 53.4% in the 

Jakavi arm and 41.1% in the best available therapy arm. 

 

In the randomised period of the pivotal studies, anaemia was less frequent in PV patients than in MF 

patients (40.8% versus 82.4%). In the PV population, the CTCAE grade 3 and 4 events were reported 

in 2.7%, while in the MF patients the frequency was 42.56%. 

 



13 

Thrombocytopenia 

In the phase 3 clinical studies in MF, in patients who developed grade 3 or 4 thrombocytopenia, the 
median time to onset was approximately 8 weeks. Thrombocytopenia was generally reversible with 

dose reduction or dose interruption. The median time to recovery of platelet counts above 50,000/mm3 

was 14 days. During the randomised period, platelet transfusions were administered to 4.7% of 

patients receiving ruxolitinib and to 4.0% of patients receiving control regimens. Discontinuation of 

treatment because of thrombocytopenia occurred in 0.7% of patients receiving ruxolitinib and 0.9% 
of patients receiving control regimens. Patients with a platelet count of 100,000/mm3 to 200,000/mm3 

before starting ruxolitinib had a higher frequency of grade 3 or 4 thrombocytopenia compared to 
patients with platelet count >200,000/mm3 (64.2% versus 38.5%). 

 

In the randomised period of the pivotal studies, the rate of patients experiencing thrombocytopenia 

was lower in PV (16.8%) patients compared to MF (69.8%) patients. The frequency of severe (i.e. 

CTCAE grade 3 and 4) thrombocytopenia was lower in PV (2.7%) than in MF (11.6%) patients. 

 

Neutropenia 

In the phase 3 clinical studies in MF, in patients who developed grade 3 or 4 neutropenia, the median 

time to onset was 12 weeks. During the randomised period, dose holding or reductions due to 

neutropenia were reported in 1.0% of patients, and 0.3% of patients discontinued treatment because of 

neutropenia. 

 

In the randomised period of the phase 3 studies in PV patients, neutropenia was reported in 1.6% of 

patients exposed to ruxolitinib compared to 7% in reference treatments. In the ruxolitinib arm one 

patient developed CTCAE grade 4 neutropenia. An extended follow-up of patients treated with 

ruxolitinib showed 2 patients reporting CTCAE grade 4 neutropenia. 

 

Bleeding 

In the phase 3 pivotal studies in MF bleeding events (including intracranial and gastrointestinal, 

bruising and other bleeding events) were reported in 32.6% of patients exposed to ruxolitinib and 
23.2% of patients exposed to the reference treatments (placebo or best available therapy). The 

frequency of grade 3-4 events was similar for patients treated with ruxolitinib or reference treatments 
(4.7% versus 3.1%). Most of the patients with bleeding events during the treatment reported bruising 

(65.3%). Bruising events were more frequently reported in patients taking ruxolitinib compared with 
the reference treatments (21.3% versus 11.6%). Intracranial bleeding was reported in 1% of patients 

exposed to ruxolitinib and 0.9% exposed to reference treatments. Gastrointestinal bleeding was 

reported in 5.0% of patients exposed to ruxolitinib compared to 3.1% exposed to reference 
treatments. Other bleeding events (including events such as epistaxis, post-procedural haemorrhage 

and haematuria) were reported in 13.3% of patients treated with ruxolitinib and 10.3% treated with 
reference treatments. 

 

During the long-term follow-up of phase 3 clinical studies in MF, the cumulative frequency of 

bleeding events increased proportionally to the increase in the follow-up time. Bruising events were 

the most frequently reported bleeding events (33.3%). Intracranial and gastrointestinal bleeding events 

were reported in 1.3% and 10.1% of patients respectively. 

 

  



14 

In the comparative period of phase 3 studies in PV patients, bleeding events (including intracranial and 

gastrointestinal, bruising and other bleeding events) were reported in 16.8% of patients treated with 

ruxolitinib, 15.3% of patients receiving best available therapy in RESPONSE study and 12.0% of 
patients receiving best available therapy in RESPONSE 2 study. Bruising was reported in 10.3% of 

patients treated with ruxolitinib, 8.1% of patients receiving best available therapy in RESPONSE 
study and 2.7% of patients receiving best available therapy in RESPONSE 2 study. No intracranial 

bleeding or gastrointestinal haemorrhage events were reported in patients receiving ruxolitinib. One 

patient treated with ruxolitinib experienced a grade 3 bleeding event (post-procedural bleeding); no 
grade 4 bleeding was reported. Other bleeding events (including events such as epistaxis, 

post-procedural haemorrhage, gingival bleeding) were reported in 8.7% of patients treated with 

ruxolitinib, 6.3% of patients treated with best available therapy in RESPONSE study and 6.7% of 
patients treated with best available therapy in RESPONSE 2 study. 

 

During the long-term follow-up of phase 3 studies in PV, the cumulative frequency of bleeding events 

increased proportionally to the increase in the follow-up time. Bruising events were the most 

frequently reported bleeding events (17.4%). Intracranial and gastrointestinal bleeding events were 

reported in 0.3% and 3.5% of patients respectively. 

 

Infections 

In the phase 3 pivotal studies in MF, grade 3 or 4 urinary tract infection was reported in 1.0% of 

patients, herpes zoster in 4.3% and tuberculosis in 1.0%. In phase 3 clinical studies sepsis was reported 

in 3.0% of patients. An extended follow-up of patients treated with ruxolitinib showed no trends 

towards an increase in the rate of sepsis over time. 

 

In the randomised period of the phase 3 studies in PV patients, one (0.5%) CTCAE grade 3 and no 
grade 4 urinary tract infection was reported. The rate of herpes zoster was similar in PV (4.3%) 

patients and MF (4.0%) patients. There was one report of CTCAE grade 3 post-herpetic neuralgia 
amongst the PV patients. Pneumonia was reported in 0.5% of patients treated with ruxolitinib 

compared to 1.6% of patients in reference treatments. No patients in the ruxolitinib arm reported 

sepsis or tuberculosis. 

 

During long-term follow-up of phase 3 studies in PV, frequently reported infections were urinary tract 

infections (11.8%), herpes zoster (14.7%) and pneumonia (7.1%). Sepsis was reported in 0.6% of 

patients. No patients reported tuberculosis in long-term follow-up. 

 

Elevated lipase 

In the randomised period of the RESPONSE study, the worsening of lipase values was higher in the 

ruxolitinib arm compared to the control arm, mainly due to the differences among grade 1 elevations 

(18.2% vs 8.1%). Grade ≥2 elevations were similar between treatment arms. In RESPONSE 2, the 

frequencies were comparable between the ruxolitinib and the control arm (10.8% vs 8%). During long-

term follow-up of phase 3 PV studies, 7.4% and 0.9% of patients reported grade 3 and grade 4 

elevation of lipase values. No concurrent signs and symptoms of pancreatitis with elevated lipase 

values were reported in these patients. 

 

In phase 3 studies in MF, high lipase values were reported in 18.7% and 19.3% of patients in the 

ruxolitinib arms compared to 16.6% and 14.0% in the control arms in COMFORT-I and 

COMFORT-II studies, respectively. In patients with elevated lipase values, no concurrent signs and 

symptoms of pancreatitis were reported. 

 

Increased systolic blood pressure 

In the phase 3 pivotal clinical studies in MF an increase in systolic blood pressure of 20 mmHg or 

more from baseline was recorded in 31.5% of patients on at least one visit compared with 19.5% of the 

control-treated patients. In COMFORT-I (MF patients) the mean increase from baseline in systolic BP 

was 0-2 mmHg on ruxolitinib versus a decrease of 2-5 mmHg in the placebo arm. In COMFORT-II 
mean values showed little difference between the ruxolitinib-treated and the control-treated MF 

patients. 



15 

 

In the randomised period of the pivotal study in PV patients, the mean systolic blood pressure 

increased by 0.65 mmHg in the ruxolitinib arm versus a decrease of 2 mmHg in the BAT arm. 

 

Reporting of suspected adverse reactions 

 
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 

allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 

professionals are asked to report any suspected adverse reactions via the national reporting system 

listed in Appendix V. 

 

4.9 Overdose 
 

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. 

 

 

5. PHARMACOLOGICAL PROPERTIES 

 

5.1 Pharmacodynamic properties 
 

Pharmacotherapeutic group: Antineoplastic agents, protein kinase inhibitors, ATC code: L01XE18 

 

Mechanism of action 

 

Ruxolitinib is a selective inhibitor of the Janus Associated Kinases (JAKs) JAK1 and JAK2 (IC50 

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 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 IC50 ranging from 80-320 nM. 

 

Pharmacodynamic effects 

 

Ruxolitinib inhibits cytokine-induced STAT3 phosphorylation in whole blood from healthy subjects, 

MF patients and PV patients. Ruxolitinib resulted in maximal inhibition of STAT3 phosphorylation 

2 hours after dosing which returned to near baseline by 8 hours in both healthy subjects and MF 

patients, indicating no accumulation of either parent or active metabolites. 

 

Baseline elevations in inflammatory markers associated with constitutional symptoms such as TNFα, 

IL-6 and CRP in subjects with MF were decreased following treatment with ruxolitinib. MF patients 

did not become refractory to the pharmacodynamic effects of ruxolitinib treatment over time. 

Similarly, patients with PV also presented with baseline elevations in inflammatory markers and these 

markers were decreased following treatment with ruxolitinib. 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


16 

 

In a thorough QT study in healthy subjects, there was no indication of a QT/QTc prolonging effect of 

ruxolitinib in single doses up to a supratherapeutic dose of 200 mg, indicating that ruxolitinib has no 

effect on cardiac repolarisation. 

 

Clinical efficacy and safety 

 

Myelofibrosis 

Two randomised phase 3 studies (COMFORT-I and COMFORT-II) were conducted in patients with 

MF (primary MF, post-polycythaemia vera MF or post-essential thrombocythaemia MF). In both 

studies, patients had palpable splenomegaly at least 5 cm below the costal margin and risk category of 

intermediate-2 or high risk based on the International Working Group (IWG) Consensus Criteria. The 

starting dose of Jakavi was based on platelet count. 

 

COMFORT-I was a double-blind, randomised, placebo-controlled study in 309 patients who were 

refractory to or were not candidates for available therapy. The primary efficacy endpoint was 

proportion of subjects achieving ≥35% reduction from baseline in spleen volume at week 24 as 

measured by Magnetic Resonance Imaging (MRI) or Computed Tomography (CT). 

 

Secondary endpoints included duration of maintenance of a ≥35% reduction from baseline in spleen 

volume, proportion of patients who had ≥50% reduction in total symptom score, changes in total 

symptom scores from baseline to week 24, as measured by the modified MF Symptom Assessment 

Form (MFSAF) v2.0 diary, and overall survival. 

 

COMFORT-II was an open-label, randomised study in 219 patients. Patients were randomised 2:1 to 

ruxolitinib versus best available therapy. In the best available therapy arm, 47% of patients received 

hydroxyurea and 16% of patients received glucocorticoids. The primary efficacy endpoint was 

proportion of patients achieving ≥35% reduction from baseline in spleen volume at week 48 as 

measured by MRI or CT. 

 

Secondary endpoints included proportion of patients achieving a ≥35% reduction of spleen volume 

from baseline at week 24 and duration of maintenance of a ≥35% reduction from baseline spleen 

volume. 

 

In COMFORT-I and COMFORT-II, patient baseline demographics and disease characteristics were 

comparable between the treatment arms. 

 

Table 2 Percentage of patients with ≥35% reduction from baseline in spleen volume at 

week 24 in COMFORT-I and at week 48 in COMFORT-II (ITT) 

 

 COMFORT-I COMFORT-II 

 Jakavi 

(N=155) 

Placebo 

(N=153) 

Jakavi 

(N=144) 

Best available 

therapy 

(N=72) 

Time points Week 24 Week 48 

Number (%) of subjects 

with spleen volume 

reduced by ≥35% 

65 (41.9) 1 (0.7) 41 (28.5) 0 

95% confidence intervals 34.1, 50.1 0, 3.6 21.3, 36.6 0.0, 5.0 

p-value <0.0001 <0.0001 

 

A significantly higher proportion of patients in the Jakavi group achieved ≥35% reduction from 

baseline in spleen volume (Table 2) regardless of the presence or absence of the JAK2V617F mutation 

or the disease subtype (primary MF, post-polycythaemia vera MF, post-essential thrombocythaemia 

MF). 

 

  



17 

Table 3 Percentage of patients with ≥35% reduction from baseline in spleen volume by JAK 

mutation status (safety set) 

 

 COMFORT-I COMFORT-II 

 Jakavi Placebo Jakavi Best available 

therapy 

JAK 

mutation 

status 

Positive 

(N=113) 

n (%) 

Negative 

(N=40) 

n (%) 

Positive 

(N=121) 

n (%) 

Negative 

(N=27) 

n (%) 

Positive 

(N=110) 

n (%) 

Negative 

(N=35) 

n (%) 

Positive 

(N=49) 

n (%) 

Negative 

(N=20) 

n (%) 

Number 

(%) of 

subjects 

with 

spleen 

volume 

reduced by 

≥35% 

54 

(47.8) 

11 

(27.5) 

1 

(0.8) 

0 36 

(32.7) 

5 

(14.3) 

0 0 

Time point After 24 weeks After 48 weeks 

 

The probability of maintaining spleen response (≥35% reduction) on Jakavi for at least 24 weeks was 

89% in COMFORT-I and 87% in COMFORT-II; 52% maintained spleen responses for at least 

48 weeks in COMFORT-II. 

 

In COMFORT-I, 45.9% subjects in the Jakavi group achieved a ≥50% improvement from baseline in 

the week 24 total symptom score (measured using MFSAF diary v2.0), as compared to 5.3% in the 

placebo group (p<0.0001 using chi-square test). The mean change in the global health status at 

week 24, as measured by EORTC QLQ C30 was +12.3 for Jakavi and -3.4 for placebo (p<0.0001). 

 

In COMFORT-I, after a median follow-up of 34.3 months, the death rate in patients randomised to the 

ruxolitinib arm was 27.1% versus 35.1% in patients randomised to placebo; HR 0.687; 95% CI 

0.459-1.029; p=0.0668. 

 

In COMFORT-I, after a median follow–up of 61.7 months, the death rate in patients randomised to the 

ruxolitinib arm was 44.5% (69 of 155 patients) versus 53.2% (82 of 154) in patients randomised to 

placebo. There was a 31% reduction in the risk of death in the ruxolitinib arm as compared to placebo 

(HR 0.69; 95% CI 0.50-0.96; p=0.025). 

 

In COMFORT-II, after a median follow-up of 34.7 months, the death rate in patients randomised to 

ruxolitinib was 19.9% versus 30.1% in patients randomised to best available treatment (BAT); HR 

0.48; 95% CI 0.28-0.85; p=0.009. In both studies, the lower death rates noted in the ruxolitinib arm 

were predominantly driven by the results obtained in the post polycythaemia vera and post essential 

thrombocythaemia subgroups. 

 

In COMFORT-II, after a median follow-up of 55.9 months, the death rate in patients randomised to 

the ruxolitinib arm was 40.4% (59 of 146 patients) versus 47.9% (35 of 73 patients) in patients 

randomized to best available therapy (BAT). There was a 33% reduction in risk of death in the 

ruxolitinib arm compared to the BAT arm (HR 0.67; 95% CI 0.44-1.02; p=0.062). 

 

Polycythaemia vera 

A randomised, open-label, active-controlled phase 3 study (RESPONSE) was conducted in 

222 patients with PV who were resistant to or intolerant of hydroxyurea defined based on the 

European LeukemiaNet (ELN) international working group published criteria. 110 patients were 

randomised to the ruxolitinib arm and 112 patients to the BAT arm. The starting dose of Jakavi was 

10 mg twice daily. Doses were then adjusted in individual patients based on tolerability and efficacy 

with a maximum dose of 25 mg twice daily. BAT was selected by the investigator on a patient-by-

patient basis and included hydroxyurea (59.5%), interferon/pegylated interferon (11.7%), anagrelide 

(7.2%), pipobroman (1.8%) and observation (15.3%). 



18 

 

Baseline demographics and disease characteristics were comparable between the two treatments arms. 

The median age was 60 years (range 33 to 90 years). Patients in the ruxolitinib arm had PV diagnosis 

for a median of 8.2 years and had previously received hydroxyurea for a median of approximately 

3 years. Most patients (>80%) had received at least two phlebotomies in the last 24 weeks prior to 

screening. Comparative data regarding long-term survival and incidence of disease complications is 

missing. 

 

The primary composite endpoint was the proportion of patients achieving both an absence of 

phlebotomy eligibility (HCT control) and a ≥35% reduction in spleen volume from baseline at 

week 32. Phlebotomy eligibility was defined as a confirmed HCT of >45%, i.e. at least 3 percentage 

points higher than the HCT obtained at baseline or a confirmed HCT of >48%, depending on which 

was lower. Key secondary endpoints included the proportion of patients who achieved the primary 

endpoint and remained free from progression at week 48, as well as the proportion of patients 

achieving complete haematological remission at week 32. 

 

The study met its primary objective and a higher proportion of patients in the Jakavi group achieved 

the primary composite endpoint and each of its individual components. Significantly more patients 

treated with Jakavi (23%) achieved a primary response (p<0.0001) compared to BAT (0.9%). 

Haematocrit control was achieved in 60% of patients in the Jakavi arm compared to 18.8% in the BAT 

arm and a ≥35% reduction in spleen volume was achieved in 40% of patients in the Jakavi arm 

compared to 0.9% in the BAT arm (Figure 1). 

 

Both key secondary endpoints were also met. The proportion of patients achieving a complete 

haematological remission was 23.6% on Jakavi compared to 8.0% on BAT (p=0.0013) and the 

proportion of patients achieving a durable primary response at week 48 was 20% on Jakavi and 0.9% 

on BAT (p<0.0001). 

 

Figure 1 Patients achieving the primary endpoint and components of the primary endpoint at 

week 32 

 
 

Symptom burden was assessed using the MPN-SAF total symptom score (TSS) electronic patient 

diary, which consisted of 14 questions. At week 32, 49% and 64% of patients treated with ruxolitinib 

achieved a ≥50% reduction in TSS-14 and TSS-5, respectively, compared to only 5% and 11% of 

patients on BAT. 

 

  

23

40

60

1 1

19

0

10

20

30

40

50

60

70

Primary composite endpoint at
week 32

≥35% reduction in spleen 
volume

Haematocrit control without
phlebotomy

P
er

ce
n

ta
ge

 e
 o

f 
p

at
ie

n
ts

.RUX

.BAT

P value: < .0001
Odds ratio (ruxolitinib/BAT) 

and 95% CI: 
32.67 (5.04, 1337)

Individual components of primary 
response at week 32



19 

Treatment benefit perception was measured by the Patient Global Impression of Change (PGIC) 

questionnaire. 66% of patients treated with ruxolitinib compared to 19% treated with BAT reported an 

improvement as early as four weeks after beginning treatment. Improvement in perception of 

treatment benefit was also higher in patients treated with ruxolitinib at week 32 (78% versus 33%). 

 

Additional analyses from the RESPONSE study to assess durability of response were conducted at 

week 80 and week 256 following randomisation. Out of 25 patients who had achieved primary 

response at week 32, 3 patients had progressed by week 80 and 6 patients by week 256. The 

probability to have maintained a response from week 32 up to week 80 and week 256 was 92% and 

74%, respectively (see Table 4). 

 

Table 4 Durability of primary response in the RESPONSE study 

 

 Week 32 Week 80 Week 256 

Primary response 

achieved at week 32* 

n/N (%) 

25/110 (23%) n/a n/a 

Patients maintaining 

primary response 

n/a 22/25 19/25 

Probability of 

maintaining primary 

response 

n/a 92% 74% 

* According to the primary response composite endpoint criteria: absence of 

phlebotomy eligibility (HCT control) and a ≥35% reduction in spleen volume 

from baseline. 

n/a: not applicable 

 

A second randomised, open label, active-controlled phase 3b study (RESPONSE 2) was conducted in 

149 PV patients who were resistant to, or intolerant of, hydroxyurea but without palpable 

splenomegaly. The primary endpoint defined as the proportion of patients achieving HCT control 

(absence of phlebotomy eligibility) at week 28 was met (62.2% in the Jakavi arm versus 18.7% in the 

BAT arm). The key secondary endpoint defined as the proportion of patients achieving complete 

haematological remission at week 28 was also met (23.0% in the Jakavi arm versus 5.3% in the BAT 

arm). 

 

Paediatric population 

 

The European Medicines Agency has waived the obligation to submit the results of studies with Jakavi 

in all subsets of the paediatric population for the treatment of MF and PV (see section 4.2 for 

information on paediatric use). 

 

5.2 Pharmacokinetic properties 

 

Absorption 

 

Ruxolitinib is a Biopharmaceutical Classification System (BCS) class 1 compound, with high 

permeability, high solubility and rapid dissolution characteristics. In clinical studies, ruxolitinib is 

rapidly absorbed after oral administration with maximal plasma concentration (Cmax) achieved 

approximately 1 hour post-dose. Based on a human mass balance study, oral absorption of ruxolitinib, 

as ruxolitinib or metabolites formed under first-pass, is 95% or greater. Mean ruxolitinib Cmax and total 

exposure (AUC) increased proportionally over a single dose range of 5-200 mg. There was no 

clinically relevant change in the pharmacokinetics of ruxolitinib upon administration with a high-fat 

meal. The mean Cmax was moderately decreased (24%) while the mean AUC was nearly unchanged 

(4% increase) on dosing with a high-fat meal. 

 



20 

Distribution 

 

The mean volume of distribution at steady state is approximately 75 litres in MF and PV patients. At 

clinically relevant concentrations of ruxolitinib, binding to plasma proteins in vitro is approximately 

97%, mostly to albumin. A whole body autoradiography study in rats has shown that ruxolitinib does 

not penetrate the blood-brain barrier. 

 

Biotransformation 

 

Ruxolitinib is mainly metabolised by CYP3A4 (>50%), with additional contribution from CYP2C9. 

Parent compound is the predominant entity in human plasma, representing approximately 60% of the 

drug-related material in circulation. Two major and active metabolites are present in plasma 

representing 25% and 11% of parent AUC. These metabolites have one half to one fifth of the parent 

JAK-related pharmacological activity. The sum total of all active metabolites contributes to 18% of 

the overall pharmacodynamics of ruxolitinib. At clinically relevant concentrations, ruxolitinib does not 

inhibit CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6 or CYP3A4 and is not a potent 

inducer of CYP1A2, CYP2B6 or CYP3A4 based on in vitro studies. In vitro data indicate that 

ruxolitinib may inhibit P-gp and BCRP. 

 

Elimination 

 

Ruxolitinib is mainly eliminated through metabolism. The mean elimination half-life of ruxolitinib is 

approximately 3 hours. Following a single oral dose of [14C]-labelled ruxolitinib in healthy adult 

subjects, elimination was predominately through metabolism, with 74% of radioactivity excreted in 

urine and 22% via faeces. Unchanged parent substance accounted for less than 1% of the excreted 

total radioactivity. 

 

Linearity/non-linearity 

 

Dose proportionality was demonstrated in the single and multiple dose studies. 

 

Special populations 

 

Effects of age, gender or race 

Based on studies in healthy subjects, no relevant differences in ruxolitinib pharmacokinetics were 

observed with regard to gender and race. In a population pharmacokinetic evaluation in MF patients, 

no relationship was apparent between oral clearance and patient age or race. The predicted oral 

clearance was 17.7 l/h in women and 22.1 l/h in men, with 39% inter-subject variability in MF 

patients. Clearance was 12.7 l/h in PV patients, with a 42% inter-subject variability and no relationship 

was apparent between oral clearance and gender, patient age or race, based on a population 

pharmacokinetic evaluation in PV patients. 

 

Paediatric population 

The safety and effectiveness of Jakavi in paediatric patients have not been established (see section 5.1, 

“Paediatric population”). 

 

Renal impairment 

Renal function was determined using both Modification of Diet in Renal Disease (MDRD) and urinary 

creatinine. Following a single ruxolitinib dose of 25 mg, the exposure of ruxolitinib was similar in 

subjects with various degrees of renal impairment and in those with normal renal function. However, 

plasma AUC values of ruxolitinib metabolites tended to increase with increasing severity of renal 

impairment, and were most markedly increased in the subjects with severe renal impairment. It is 

unknown whether the increased metabolite exposure is of safety concern. A dose modification is 

recommended in patients with severe renal impairment and end-stage renal disease (see section 4.2). 

Dosing only on dialysis days reduces the metabolite exposure, but also the pharmacodynamic effect, 

especially on the days between dialysis. 

 



21 

Hepatic impairment 

Following a single ruxolitinib dose of 25 mg in patients with varying degrees of hepatic impairment, 

the mean AUC for ruxolitinib was increased in patients with mild, moderate and severe hepatic 

impairment by 87%, 28% and 65%, respectively, compared to patients with normal hepatic function. 

There was no clear relationship between AUC and the degree of hepatic impairment based on 

Child-Pugh scores. The terminal elimination half-life was prolonged in patients with hepatic 

impairment compared to healthy controls (4.1-5.0 hours versus 2.8 hours). A dose reduction of 

approximately 50% is recommended for patients with hepatic impairment (see section 4.2). 

 

5.3 Preclinical safety data 

 

Ruxolitinib has been evaluated in safety pharmacology, repeated dose toxicity, genotoxicity and 

reproductive toxicity studies and in a carcinogenicity study. Target organs associated with the 

pharmacological action of ruxolitinib in repeated dose studies include bone marrow, peripheral blood 

and lymphoid tissues. Infections generally associated with immunosuppression were noted in dogs. 

Adverse decreases in blood pressure along with increases in heart rate were noted in a dog telemetry 

study, and an adverse decrease in minute volume was noted in a respiratory study in rats. The margins 

(based on unbound Cmax) at the non-adverse level in the dog and rat studies were 15.7-fold and 

10.4-fold greater, respectively, than the maximum human recommended dose of 25 mg twice daily. 

No effects were noted in an evaluation of the neuropharmacological effects of ruxolitinib. 

 

In juvenile rat studies, administration of ruxolitinib resulted in effects on growth and bone measures. 

Reduced bone growth was observed at doses ≥5 mg/kg/day when treatment started on postnatal day 7 

(comparable to human newborn) and at ≥15 mg/kg/day when treatment started on postnatal days 14 or 

21 (comparable to human infant, 1–3 years). Fractures and early termination of rats were observed at 

doses ≥30 mg/kg/day when treatment was started on postnatal day 7. Based on unbound AUC, the 

exposure at the NOAEL (no observed adverse effect level) in juvenile rats treated as early as postnatal 

day 7 was 0.3-fold that of adult patients at 25 mg twice daily, while reduced bone growth and fractures 

occurred at exposures that were 1.5- and 13-fold that of adult patients at 25 mg twice daily, 

respectively. The effects were generally more severe when administration was initiated earlier in the 

postnatal period. Other than bone development, the effects of ruxolitinib in juvenile rats were similar 

to those in adult rats. Juvenile rats are more sensitive than adult rats to ruxolitinib toxicity. 

 

Ruxolitinib decreased foetal weight and increased post-implantation loss in animal studies. There was 

no evidence of a teratogenic effect in rats and rabbits. However, the exposure margins compared to the 

highest clinical dose were low and the results are therefore of limited relevance for humans. No effects 

were noted on fertility. In a pre- and post-natal development study, a slightly prolonged gestation 

period, reduced number of implantation sites, and reduced number of pups delivered were observed. In 

the pups, decreased mean initial body weights and short period of decreased mean body weight gain 

were observed. In lactating rats, ruxolitinib and/or its metabolites were excreted into the milk with a 

concentration that was 13-fold higher than the maternal plasma concentration. Ruxolitinib was not 

mutagenic or clastogenic. Ruxolitinib was not carcinogenic in the Tg.rasH2 transgenic mouse model. 

 

  



22 

 

6. PHARMACEUTICAL PARTICULARS 

 

6.1 List of excipients 

 

Cellulose, microcrystalline 

Magnesium stearate 

Silica, colloidal anhydrous 

Sodium starch glycolate (Type A) 

Povidone K30 

Hydroxypropylcellulose 300 to 600 cps 

Lactose monohydrate 

 

6.2 Incompatibilities 

 

Not applicable. 

 

6.3 Shelf life 

 

3 years 

 

6.4 Special precautions for storage 

 

Do not store above 30°C. 

 

6.5 Nature and contents of container 

 

PVC/PCTFE/Aluminium blister packs containing 14 or 56 tablets or multipacks containing 168 

(3 packs of 56) tablets. 

 

Not all pack sizes or types may be marketed. 

 

6.6 Special precautions for disposal 
 

No special requirements. 

 

 

7. MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

  



23 

 

8. MARKETING AUTHORISATION NUMBER(S) 

 

Jakavi 5 mg tablets 

EU/1/12/773/004-006 

 

Jakavi 10 mg tablets 

EU/1/12/773/014-016 

 

Jakavi 15 mg tablets 

EU/1/12/773/007-009 

 

Jakavi 20 mg tablets 

EU/1/12/773/010-012 

 

 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 

 

Date of first authorisation: 23 August 2012 

Date of latest renewal: 24 April 2017 

 

 

10. DATE OF REVISION OF THE TEXT 

 

 

Detailed information on this medicinal product is available on the website of the European Medicines 

Agency http://www.ema.europa.eu 

  



24 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX II 

 

A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE 

 

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY 

AND USE 

 

C. OTHER CONDITIONS AND REQUIREMENTS OF THE 

MARKETING AUTHORISATION 

 

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO 

THE SAFE AND EFFECTIVE USE OF THE MEDICINAL 

PRODUCT 

 



25 

A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE 

 

Name and address of the manufacturer responsible for batch release 

Novartis Pharma GmbH 

Roonstrasse 25 

D-90429 Nuremberg 

Germany 

 

Novartis Farmacéutica S.A. 

Ronda de Santa Maria 158 

08210 Barberà del Vallès, Barcelona 

Spain 

 

The printed package leaflet of the medicinal product must state the name and address of the 

manufacturer responsible for the release of the concerned batch. 
 

 

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 

 

Medicinal product subject to restricted medical prescription (see Annex I: Summary of Product 

Characteristics, section 4.2). 

 

 

C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 

 

 Periodic Safety Update Reports 

 
The requirements for submission of periodic safety update reports for this medicinal product are set 

out in the list of Union reference dates (EURD list) provided for under Article 107c(7) of Directive 

2001/83/EC and any subsequent updates published on the European medicines web-portal. 

 

 

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 

 

 Risk Management Plan (RMP) 

 

The MAH shall perform the required pharmacovigilance activities and interventions detailed in 

the agreed RMP presented in Module 1.8.2 of the Marketing Authorisation and any agreed 

subsequent updates of the RMP. 

 
An updated RMP should be submitted: 

 At the request of the European Medicines Agency; 

 Whenever the risk management system is modified, especially as the result of new information 
being received that may lead to a significant change to the benefit/risk profile or as the result of 

an important (pharmacovigilance or risk minimisation) milestone being reached. 

 

  



26 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX III 

 

LABELLING AND PACKAGE LEAFLET 

  



27 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

A. LABELLING 
 

  



28 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

CARTON OF UNIT PACK 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Jakavi 5 mg tablets 

ruxolitinib 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each tablet contains 5 mg ruxolitinib (as phosphate). 

 

 

3. LIST OF EXCIPIENTS 

 

Contains lactose. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Tablets 

 

14 tablets 

56 tablets 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Oral use. 

Read the package leaflet before use. 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

Do not store above 30°C. 

 

 



29 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/12/773/004 14 tablets 

EU/1/12/773/005 56 tablets 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Jakavi 5 mg 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC: 

SN: 
NN: 

 

  



30 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

OUTER CARTON OF MULTIPACK 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Jakavi 5 mg tablets 

ruxolitinib 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each tablet contains 5 mg ruxolitinib (as phosphate). 

 

 

3. LIST OF EXCIPIENTS 

 

Contains lactose. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Tablets 

 

Multipack: 168 (3 packs of 56) tablets. 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Oral use 

Read the package leaflet before use. 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

Do not store above 30°C. 

 

 



31 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/12/773/006 168 tablets (3x56) 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Jakavi 5 mg 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC: 

SN: 

NN: 

 

  



32 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

INTERMEDIATE CARTON OF MULTIPACK 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Jakavi 5 mg tablets 

ruxolitinib 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each tablet contains 5 mg ruxolitinib (as phosphate). 

 

 

3. LIST OF EXCIPIENTS 

 

Contains lactose. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Tablets 

 

56 tablets. Component of a multipack. Not to be sold separately. 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Oral use. 

Read the package leaflet before use. 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

Do not store above 30°C. 

 

 



33 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/12/773/006 168 tablets (3x56) 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Jakavi 5 mg 

  



34 

 

MINIMUM PARTICULARS TO APPEAR ON BLISTER OR STRIPS 

 

BLISTERS 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Jakavi 5 mg tablets 

ruxolitinib 

 

 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

Lot 

 

 

5. OTHER 

 

Monday 

Tuesday 

Wednesday 

Thursday 

Friday 

Saturday 

Sunday 

 

 

 
  



35 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

CARTON OF UNIT PACK 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Jakavi 10 mg tablets 

ruxolitinib 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each tablet contains 10 mg ruxolitinib (as phosphate). 

 

 

3. LIST OF EXCIPIENTS 

 

Contains lactose. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Tablets 

 

14 tablets 

56 tablets 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Oral use. 

Read the package leaflet before use. 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

Do not store above 30°C. 

 

 



36 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/12/773/014 14 tablets 

EU/1/12/773/015 56 tablets 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Jakavi 10 mg 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC: 

SN: 
NN: 

 

  



37 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

OUTER CARTON OF MULTIPACK 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Jakavi 10 mg tablets 

ruxolitinib 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each tablet contains 10 mg ruxolitinib (as phosphate). 

 

 

3. LIST OF EXCIPIENTS 

 

Contains lactose. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Tablets 

 

Multipack: 168 (3 packs of 56) tablets. 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Oral use 

Read the package leaflet before use. 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

Do not store above 30°C. 

 

 



38 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/12/773/016 168 tablets (3x56) 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Jakavi 10 mg 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC: 

SN: 

NN: 

 

  



39 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

INTERMEDIATE CARTON OF MULTIPACK 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Jakavi 10 mg tablets 

ruxolitinib 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each tablet contains 10 mg ruxolitinib (as phosphate). 

 

 

3. LIST OF EXCIPIENTS 

 

Contains lactose. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Tablets 

 

56 tablets. Component of a multipack. Not to be sold separately. 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Oral use. 

Read the package leaflet before use. 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

Do not store above 30°C. 

 

 



40 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/12/773/016 168 tablets (3x56) 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Jakavi 10 mg 

  



41 

 

MINIMUM PARTICULARS TO APPEAR ON BLISTER OR STRIPS 

 

BLISTERS 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Jakavi 10 mg tablets 

ruxolitinib 

 

 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

Lot 

 

 

5. OTHER 

 

Monday 

Tuesday 

Wednesday 

Thursday 

Friday 

Saturday 

Sunday 

 

 

 
  



42 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

CARTON OF UNIT PACK 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Jakavi 15 mg tablets 

ruxolitinib 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each tablet contains 15 mg ruxolitinib (as phosphate). 

 

 

3. LIST OF EXCIPIENTS 

 

Contains lactose. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Tablets 

 

14 tablets 

56 tablets 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Oral use. 

Read the package leaflet before use. 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

Do not store above 30°C. 

 

 



43 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/12/773/007 14 tablets 

EU/1/12/773/008 56 tablets 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Jakavi 15 mg 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC: 

SN: 
NN: 

 

  



44 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

OUTER CARTON OF MULTIPACK 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Jakavi 15 mg tablets 

ruxolitinib 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each tablet contains 15 mg ruxolitinib (as phosphate). 

 

 

3. LIST OF EXCIPIENTS 

 

Contains lactose. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Tablets 

 

Multipack: 168 (3 packs of 56) tablets. 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Oral use 

Read the package leaflet before use. 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

Do not store above 30°C. 

 

 



45 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/12/773/009 168 tablets (3x56) 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Jakavi 15 mg 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC: 

SN: 

NN: 

 

  



46 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

INTERMEDIATE CARTON OF MULTIPACK 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Jakavi 15 mg tablets 

ruxolitinib 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each tablet contains 15 mg ruxolitinib (as phosphate). 

 

 

3. LIST OF EXCIPIENTS 

 

Contains lactose. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Tablets 

 

56 tablets. Component of a multipack. Not to be sold separately. 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Oral use. 

Read the package leaflet before use. 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

Do not store above 30°C. 

 

 



47 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/12/773/009 168 tablets (3x56) 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Jakavi 15 mg 

  



48 

 

MINIMUM PARTICULARS TO APPEAR ON BLISTER OR STRIPS 

 

BLISTERS 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Jakavi 15 mg tablets 

ruxolitinib 

 

 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

Lot 

 

 

5. OTHER 

 

Monday 

Tuesday 

Wednesday 

Thursday 

Friday 

Saturday 

Sunday 

 

 

 
  



49 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

CARTON OF UNIT PACK 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Jakavi 20 mg tablets 

ruxolitinib 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each tablet contains 20 mg ruxolitinib (as phosphate). 

 

 

3. LIST OF EXCIPIENTS 

 

Contains lactose. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Tablets 

 

14 tablets 

56 tablets 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Oral use. 

Read the package leaflet before use. 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

Do not store above 30°C. 

 

 



50 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/12/773/010 14 tablets 

EU/1/12/773/011 56 tablets 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Jakavi 20 mg 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC: 

SN: 
NN: 

 

  



51 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

OUTER CARTON OF MULTIPACK 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Jakavi 20 mg tablets 

ruxolitinib 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each tablet contains 20 mg ruxolitinib (as phosphate). 

 

 

3. LIST OF EXCIPIENTS 

 

Contains lactose. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Tablets 

 

Multipack: 168 (3 packs of 56) tablets. 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Oral use 

Read the package leaflet before use. 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

Do not store above 30°C. 

 

 



52 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/12/773/012 168 tablets (3x56) 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Jakavi 20 mg 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC: 

SN: 

NN: 

 

  



53 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

INTERMEDIATE CARTON OF MULTIPACK 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Jakavi 20 mg tablets 

ruxolitinib 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each tablet contains 20 mg ruxolitinib (as phosphate). 

 

 

3. LIST OF EXCIPIENTS 

 

Contains lactose. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Tablets 

 

56 tablets. Component of a multipack. Not to be sold separately. 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Oral use. 

Read the package leaflet before use. 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

Do not store above 30°C. 

 

 



54 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/12/773/012 168 tablets (3x56) 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Jakavi 20 mg 

 

  



55 

 

MINIMUM PARTICULARS TO APPEAR ON BLISTER OR STRIPS 

 

BLISTERS 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Jakavi 20 mg tablets 

ruxolitinib 

 

 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

Lot 

 

 

5. OTHER 

 

Monday 

Tuesday 

Wednesday 

Thursday 

Friday 

Saturday 

Sunday 

 

 

 
  



56 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

B. PACKAGE LEAFLET 



57 

Package leaflet: Information for the patient 

 

Jakavi 5 mg tablets 

Jakavi 10 mg tablets 

Jakavi 15 mg tablets 

Jakavi 20 mg tablets 

ruxolitinib 

 

Read all of this leaflet carefully before you start taking this medicine because it contains 

important information for you. 

- Keep this leaflet. You may need to read it again. 
- If you have any further questions, ask your doctor or pharmacist. 
- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours. 

- If you get any side effects, talk to your doctor or pharmacist. This includes any possible side 
effects not listed in this leaflet. See section 4. 

 

What is in this leaflet 

 

1. What Jakavi is and what it is used for 

2. What you need to know before you take Jakavi 

3. How to take Jakavi 

4. Possible side effects 

5. How to store Jakavi 

6. Contents of the pack and other information 

 

 

1. What Jakavi is and what it is used for 

 

Jakavi contains the active substance ruxolitinib. 

 

Jakavi is used to treat adult patients with an enlarged spleen or with symptoms related to 

myelofibrosis, a rare form of blood cancer. 

 

Jakavi is also used to treat patients with polycythaemia vera who are resistant to or intolerant of 

hydroxyurea. 

 

How Jakavi works 

Enlargement of the spleen is one of the characteristics of myelofibrosis. Myelofibrosis is a disorder of 

the bone marrow, in which the marrow is replaced by scar tissue. The abnormal marrow can no longer 

produce enough normal blood cells and as a result the spleen becomes significantly enlarged. By 

blocking the action of certain enzymes (called Janus Associated Kinases), Jakavi can reduce the size 

of the spleen in patients with myelofibrosis and relieve symptoms such as fever, night sweats, bone 

pain and weight loss in patients with myelofibrosis. Jakavi can help reduce the risk of serious blood or 

vascular complications. 

 

Polycythaemia vera is a disorder of the bone marrow, in which the marrow produce too many red 

blood cells. The blood becomes thicker as a result of the increased red blood cells. Jakavi can relieve 

the symptoms, reduce spleen size and the volume of red blood cells produced in patients with 

polycythaemia vera by selectively blocking enzymes called Janus Associated Kinases (JAK1 and 

JAK2), thus potentially reducing the risk of serious blood or vascular complications. 

 

If you have any questions about how Jakavi works or why this medicine has been prescribed for you, 

ask your doctor. 

 

 



58 

2. What you need to know before you take Jakavi 

 

Follow all the doctor’s instructions carefully. They may differ from the general information contained 

in this leaflet. 

 

Do not take Jakavi 
- if you are allergic to ruxolitinib or any of the other ingredients of this medicine (listed in 

section 6). 

- if you are pregnant or breast-feeding. 

If either of the above applies to you, tell your doctor who will then decide whether you should start 

treatment with Jakavi. 

 

Warnings and precautions 

Talk to your doctor or pharmacist before taking Jakavi 

- if you have any infections. It may be necessary to treat your infection before starting Jakavi. It is 
important that you tell your doctor if you have ever had tuberculosis or if you have been in close 

contact with someone who has or has had tuberculosis. Your doctor may perform tests to see if 

you have tuberculosis or any other infections. It is important that you tell your doctor if you 

have ever had hepatitis B. 

- if you have any kidney problems. Your doctor may need to prescribe a different dose of Jakavi. 
- if you have or have ever had any liver problems. Your doctor may need to prescribe a different 

dose of Jakavi. 

- if you are taking other medicines (see section “Other medicines and Jakavi”). 
- if you have ever had tuberculosis. 
- if you have ever had skin cancer. 
 

Talk to your doctor or pharmacist during your treatment with Jakavi 
- if you experience unexpected bruising and/or bleeding, unusual tiredness, shortness of breath 

during exercise or at rest, unusually pale skin, or frequent infections (these are signs of blood 

disorders). 

- if you experience fever, chills or other symptoms of infections. 
- if you experience chronic coughing with blood-tinged sputum, fever, night sweats and weight 

loss (these can be signs of tuberculosis). 

- if you have any of the following symptoms or if anyone close to you notices that you have any 
of these symptoms: confusion or difficulty thinking, loss of balance or difficulty walking, 

clumsiness, difficulty speaking, decreased strength or weakness on one side of your body, 

blurred and/or loss of vision. These may be signs of a serious brain infection and your doctor 

may suggest further testing and follow-up. 

- if you develop painful skin rash with blisters (these are signs of shingles). 
- if you notice skin changes. This may require further observation, as certain types of skin cancer 

(non-melanoma) have been reported. 

 

Blood tests 

Before you start treatment with Jakavi, your doctor will perform blood tests to determine the best 

starting dose for you. You will need to have further blood tests during treatment so that your doctor 

can monitor the amount of blood cells (white cells, red cells and platelets) in your body and assess 

how you are responding to the treatment and whether Jakavi is having an unwanted effect on these 

cells. Your doctor may need to adjust the dose or stop treatment. Your doctor will carefully check if 

you have any signs or symptoms of infection before starting and during your treatment with Jakavi. 

Your doctor will also regularly check the level of lipids (fat) in your blood. 

 

Stopping Jakavi 

When you stop taking Jakavi, the myelofibrosis symptoms may come back. Your doctor may want to 

gradually reduce the amount of Jakavi taken each day, before stopping it completely. 

  



59 

 

Children and adolescents 

This medicine is not intended for use by children or adolescents aged below 18 years because it has 

not been studied in this age group. 

 

Other medicines and Jakavi 

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 

medicines. 

 

It is particularly important that you mention any of the following medicines containing any of the 

following active substances, as your doctor may need to adjust the Jakavi dose for you. 

 

The following may increase the risk of side effects with Jakavi: 

- Some medicines used to treat infections. These include medicines used to treat fungal diseases 
(such as ketoconazole, itraconazole, posaconazole, fluconazole and voriconazole), medicines 

used to treat certain types of bacterial infections (antibiotics such as clarithromycin, 

telithromycin, ciprofloxacin, or erythromycin), medicines to treat viral infections, including 

HIV infection/AIDS (such as amprenavir, atazanavir, indinavir, lopinavir/ritonavir, nelfinavir, 

ritonavir, saquinavir), medicines to treat hepatitis C (boceprevir, telaprevir). 

- Nefazodone, a medicine to treat depression. 
- Mibefradil or diltiazem, medicines to treat hypertension and chronic angina pectoris. 
- Cimetidine, a medicine to treat heartburn. 
 

The following may reduce the effectiveness of Jakavi: 

- Avasimibe, a medicine to treat heart disease. 
- Phenytoin, carbamazepine or phenobarbital and other anti-epileptics used to stop seizures or 

fits. 

- Rifabutin or rifampicin, medicines used to treat tuberculosis (TB). 
- St. John’s wort (Hypericum perforatum), a herbal product used to treat depression. 
 

While you are taking Jakavi you should never start a new medicine without checking first with the 

doctor who prescribed Jakavi. This includes prescription medicines, non-prescription medicines and 

herbal or alternative medicines. 

 

Pregnancy and breast-feeding 

Do not take Jakavi during pregnancy. Talk to your doctor about how to take appropriate measures to 

avoid becoming pregnant during your treatment with Jakavi. 

 

Do not breast-feed while taking Jakavi. Tell your doctor if you are breast-feeding. 

 

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 

your doctor or pharmacist for advice before taking this medicine. 

 

Driving and using machines 

If you experience dizziness after taking Jakavi, do not drive or use machines. 

 

Jakavi contains lactose 

Jakavi contains lactose (milk sugar). If you have been told by your doctor that you have an intolerance 

to some sugars, contact your doctor before taking this medicine. 

  



60 

 

 

3. How to take Jakavi 

 

Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor 

or pharmacist if you are not sure. 

 

The dose of Jakavi depends on the patient’s blood cell count. Your doctor will measure the amount of 

blood cells in your body and find the best dose for you, particularly if you have liver or kidney 

problems. 

- The recommended starting dose in myelofibrosis is 15 mg twice daily or 20 mg twice daily, 
depending on your blood cell count. 

- The recommended starting dose in polycythaemia vera is 10 mg twice daily. 
- The maximum dose is 25 mg twice daily. 
 

Your doctor will always tell you exactly how many Jakavi tablets to take. 

 

During the treatment your doctor may recommend a lower or higher dose to you if the results of blood 

tests show that this is necessary, if you have problems with your liver or kidneys, or if you also need 

treatment with certain other medicines. 

 

If you receive dialysis, take either one single dose or two separate doses of Jakavi only on dialysis 

days, after the dialysis has been completed. Your doctor will tell you if you should take one or two 

doses and how many tablets to take for each dose. 

 

You should take Jakavi every day at the same time, either with or without food. 

 

You should continue taking Jakavi for as long as your doctor tells you to. This is a long-term 

treatment. 

 

Your doctor will regularly monitor your condition to make sure that the treatment is having the desired 

effect. 

 

If you have questions about how long to take Jakavi, talk to your doctor or pharmacist. 

 

If you experience certain side effects (e.g. blood disorders), your doctor might need to change the 

amount of Jakavi you have to take or tell you to stop taking Jakavi for a while. 

 

If you take more Jakavi than you should 

If you accidentally take more Jakavi than your doctor prescribed, contact your doctor or pharmacist 

immediately. 

 

If you forget to take Jakavi 

If you forgot to take Jakavi simply take your next dose at the scheduled time. Do not take a double 

dose to make up for a forgotten dose. 

 

If you stop taking Jakavi 

If you interrupt your treatment with Jakavi your myelofibrosis-related symptoms may come back. 

Therefore, you should not stop taking Jakavi without discussing it with your doctor. 

 

If you have any further questions on the use of this medicine, ask your doctor or pharmacist. 

  



61 

 

 

4. Possible side effects 
 

Like all medicines, this medicine can cause side effects, although not everybody gets them. 

 

Most of the side effects of Jakavi are mild to moderate and will generally disappear after a few days to 

a few weeks of treatment. 

 

Tell your doctor immediately if you experience any of the following side effects. Some are very 

common (may affect more than 1 in 10 people), some are common (may affect up to 1 in 10 people): 

- any sign of bleeding in the brain, such as sudden altered level of consciousness, persistent 
headache, numbness, tingling, weakness or paralysis (common) 

- any sign of bleeding in the stomach or intestine, such as passing black or bloodstained stools, or 
vomiting blood (very common) 

- unexpected bruising and/or bleeding, unusual tiredness, shortness of breath during exercise or at 
rest, unusually pale skin, or frequent infections (possible symptoms of blood disorders) (very 

common) 

- painful skin rash with blisters (possible symptoms of shingles (herpes zoster)) (very common) 
- fever, chills or other symptoms of infections (very common) 
- low level of red blood cells (anaemia), low level of white blood cells (neutropenia) or low level 

of platelets (thrombocytopenia) (very common) 

 

Other side effects with Jakavi 

Very common (may affect more than 1 in 10 people): 

- high level of cholesterol or fat in the blood (hypertriglyceridaemia) 
- abnormal liver function test results 
- dizziness 
- headache 
- urinary tract infections 
- weight gain 
- fever, cough, difficult or painful breathing, wheezing, pain in chest when breathing (possible 

symptoms of pneumonia) 

- high blood pressure (hypertension), which may also be the cause of dizziness and headaches 
- constipation 
- high level of lipase in the blood 
 

Common (may affect up to 1 in 10 people): 

- frequently passing wind (flatulence) 
 

Uncommon (may affect up to 1 in 100 people): 

- tuberculosis 
 

Reporting of side effects 

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects 

not listed in this leaflet. You can also report side effects directly via the national reporting system 

listed in Appendix V. By reporting side effects you can help provide more information on the safety of 

this medicine. 

  

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


62 

 

 

5. How to store Jakavi 
 

Keep this medicine out of the sight and reach of children. 

 

Do not use this medicine after the expiry date which is stated on the carton or blister after “EXP”. 

 

Do not store above 30°C. 

 

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 

throw away medicines you no longer use. These measures will help protect the environment. 

 

 

6. Contents of the pack and other information 

 

What Jakavi contains 

- The active substance of Jakavi is ruxolitinib. 
- Each 5 mg Jakavi tablet contains 5 mg of ruxolitinib. 
- Each 10 mg Jakavi tablet contains 10 mg of ruxolitinib. 
- Each 15 mg Jakavi tablet contains 15 mg of ruxolitinib. 
- Each 20 mg Jakavi tablet contains 20 mg of ruxolitinib. 
- The other ingredients are: microcrystalline cellulose, magnesium stearate, colloidal anhydrous 

silica, sodium starch glycolate, povidone, hydroxypropylcellulose, lactose monohydrate. 

 

What Jakavi looks like and contents of the pack 

Jakavi 5 mg tablets are white to almost white round tablets with “NVR” debossed on one side and 

“L5” debossed on the other side. 

Jakavi 10 mg tablets are white to almost white round tablets with “NVR” debossed on one side and 

“L10” debossed on the other side. 

Jakavi 15 mg tablets are white to almost white oval tablets with “NVR” debossed on one side and 

“L15” debossed on the other side. 

Jakavi 20 mg tablets are white to almost white elongated tablets with “NVR” debossed on one side 

and “L20” debossed on the other side. 

 

Jakavi tablets are supplied in blister packs containing 14 or 56 tablets or multipacks containing 168 

(3 packs of 56) tablets 

 

Not all packs may be marketed in your country. 

  



63 

 

Marketing Authorisation Holder 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

Manufacturer 
Novartis Pharma GmbH 

Roonstrasse 25 

90429 Nuremberg 

Germany 

 

Novartis Farmacéutica S.A. 

Ronda de Santa Maria 158 

08210 Barberà del Vallès, Barcelona 

Spain 

 

For any information about this medicine, please contact the local representative of the Marketing 

Authorisation Holder: 

 

België/Belgique/Belgien 
Novartis Pharma N.V. 

Tél/Tel: +32 2 246 16 11 

 

Lietuva 
SIA Novartis Baltics Lietuvos filialas 

Tel: +370 5 269 16 50 

 

България 

Novartis Bulgaria EOOD 

Тел.: +359 2 489 98 28 

 

Luxembourg/Luxemburg 
Novartis Pharma N.V. 

Tél/Tel: +32 2 246 16 11 

 

Česká republika 
Novartis s.r.o. 

Tel: +420 225 775 111 

 

Magyarország 

Novartis Hungária Kft. 

Tel.: +36 1 457 65 00 

Danmark 
Novartis Healthcare A/S 

Tlf: +45 39 16 84 00 

 

Malta 

Novartis Pharma Services Inc. 

Tel: +356 2122 2872 

Deutschland 
Novartis Pharma GmbH 

Tel: +49 911 273 0 

 

Nederland 
Novartis Pharma B.V. 

Tel: +31 88 04 52 111 

Eesti 

SIA Novartis Baltics Eesti filiaal 

Tel: +372 66 30 810 

 

Norge 
Novartis Norge AS 

Tlf: +47 23 05 20 00 

Ελλάδα 
Novartis (Hellas) A.E.B.E. 

Τηλ: +30 210 281 17 12 

 

Österreich 
Novartis Pharma GmbH 

Tel: +43 1 86 6570 

España 

Novartis Farmacéutica, S.A. 

Tel: +34 93 306 42 00 

 

Polska 

Novartis Poland Sp. z o.o. 

Tel.: +48 22 375 4888 



64 

France 

Novartis Pharma S.A.S. 

Tél: +33 1 55 47 66 00 

 

Portugal 
Novartis Farma - Produtos Farmacêuticos, S.A. 

Tel: +351 21 000 8600 

Hrvatska 

Novartis Hrvatska d.o.o. 

Tel. +385 1 6274 220 

 

România 

Novartis Pharma Services Romania SRL 

Tel: +40 21 31299 01 

Ireland 
Novartis Ireland Limited 

Tel: +353 1 260 12 55 

 

Slovenija 
Novartis Pharma Services Inc. 

Tel: +386 1 300 75 50 

Ísland 

Vistor hf. 

Sími: +354 535 7000 

 

Slovenská republika 

Novartis Slovakia s.r.o. 

Tel: +421 2 5542 5439 

 

Italia 
Novartis Farma S.p.A. 

Tel: +39 02 96 54 1 

Suomi/Finland 
Novartis Finland Oy 

Puh/Tel: +358 (0)10 6133 200 

 

Κύπρος 

Novartis Pharma Services Inc. 

Τηλ: +357 22 690 690 

 

Sverige 

Novartis Sverige AB 

Tel: +46 8 732 32 00 

 

Latvija 

SIA Novartis Baltics 

Tel: +371 67 887 070 

 

United Kingdom 

Novartis Pharmaceuticals UK Ltd. 

Tel: +44 1276 698370 

 

 

 

This leaflet was last revised in 
 

Other sources of information 

Detailed information on this medicine is available on the European Medicines Agency website: 

http://www.ema.europa.eu 

 


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET