1. Medicines
  2. Haematology
  3. JAKAVI® (ruxolitinib)
  4. Safety profile

Prescribing information

 

Safety profile

JAKAVI® has a well-characterised safety profile, with manageable AEs1

The safety profile of JAKAVI® has been consistently demonstrated across 5-year follow-up to the COMFORT-I and COMFORT-II trials and in real-world studies – with no newly observed patterns of AEs.1–3 

Table graphic showing adverse events with Jakavi

 

  • Haematological adverse drug reactions (any CTCAE grade) included anaemia (83.8%), thrombocytopenia (80.5%) and neutropenia (20.8%)1
  • Anaemia, thrombocytopenia and neutropenia are dose-related effects1
  • Discontinuation due to adverse events, regardless of causality, was observed in 30.0% of patients1

Anaemia is the most common haematological side-effect of JAKAVI® treatment, but with appropriate monitoring and dose management, your patients can continue treatment with minimal interruptions.1,4,5

JAKAVI®-induced anaemia is transient and manageable2

 

Box with a medicines icon and the text Treatment-related anaemia occurred after 8-12 weeks of therapy and gradually recovers to near-baseline levels by 24 weeks

 

Line graph of mean haemoglobin levels over time from COMFORT-2 with Jakavi vs BAT

 

In the JAKAVI® arm, mean haemoglobin levels decreased over the first 12 weeks of treatment and then recovered to levels similar to those in the BAT arm and remained >10 g/dL from Week 24 onward (>151 weeks).5

One real-world study showed that erythropoietin-stimulating agents (ESAs) are often used first-line to manage treatment-related anaemia if it occurs.7

In a survey of 42 consultant haematologists, 71.4% used ESAs first line.7

The British Committee for Standards in Haematology guidelines recommend the following steps when using ESAs:8

  • Consider trial of EPO <125 units/L
  • Use 10,000 units 3 times a week or darbepoetin 150 μg once a week
  • If no response, double the dose after 2 months and discontinue after 4 months

 

JAKAVI® can be concomitantly prescribed alongside ESAs
to improve or stabilise haemoglobin levels9,10

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. JAKAVI® is also indicated for adult patients with polycythaemia vera who are resistant to or intolerant of hydroxyurea.1

COMFORT-I was a randomised, double-blind, placebo-controlled trial in patients with intermediate-2 or high-risk myelofibrosis. COMFORT-II was a randomised trial comparing JAKAVI® with BAT in patients with primary MF, post-PV MF or post-ET MF. The JAKAVI® treatment group consisted of 155 patients in COMFORT-I and 146 patients in COMFORT-II. The primary endpoint was the proportion of patients with a reduction of ≥35% in spleen volume from baseline to Week 24 and to Week 48, respectively.2,6

* Frequency is based on adverse event data. A subject with multiple occurences of an adverse drug reaction is counted only once in that ADR category. ADRs reported are on treatment or up to 28 days post treatment end date.1
† Frequency is based on all patients exposed to JAKAVI® in clinical studies (N=4755).1
‡ ADR derived from post-marketing experience.
§ 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.1
II CTCAE version 3.0; grade 1 = mild, grade 2 = moderate, grade 3 = severe, grade 4 = life-threatening.1
Pancytopenia is defined as haemoglobin level <100 g/L, platelet count <100x109/L, and neutrophil count <1.5x109/L (or low white blood cell count of grade 2 if neutrophil count is missing), simultaneously in the same lab assessment.1

ADR, adverse drug reaction; AE, adverse event; BAT, best available therapy; BCSH, British Committee for Standards in Haematology; COMFORT, Controlled Myelofibrosis Study with Oral JAK Inhibitor Treatment; CTCAE, common terminology criteria for adverse events; EPO, erythropoietin; ESA, erythropoietin-stimulating agents; ET, essential thrombocythaemia; HBV, hepatitis B; MF, myelofibrosis; PV, polycythaemia vera; SmPC, summary of product characteristics; ULN, upper limit of normal. 

  1. Novartis Pharmaceuticals UK Ltd. JAKAVI® summary of product characteristics.
  2. Harrison C, et al. N Engl J Med. 2012;366:787–798.
  3. Verstovsek S, et al. J Hematol Oncol. 2017;10:55.
  4. Harrison C, et al. Expert Rev Hematol. 2013;6:511–523.
  5. Harrison C, et al. ASH 2015, 5–8 December; Orlando, Florida, USA. Abstract 59.
  6. Verstovsek S, et al. N Engl J Med. 2012;366:799–807.
  7. Harrison C, et al. Br J Haematol. 2020;188:e80–e112.
  8. Reilly JT, et al. Br J Haematol. 2012;158:453–471.
  9. McMullin MF, et al. ASH 2012, 8–11 December; Atlanta, Georgia. Abstract and Poster 2838.
  10. Al-Ali HK, et al. Haematologica. 2016;101:1065–1073.

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UK | May 2021 | 119378
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Adverse events should be reported. Reporting forms and information can be found at www.mhra.gov.uk/yellowcard. Adverse events should also be reported to Novartis via [email protected] or online through the pharmacovigilance intake (PVI) tool at www.report.novartis.com
If you have a question about the product, please contact Medical Information on 01276 698370 or by email at [email protected]