JAKAVI

What it is

Jakavi contains ruxolitinib as the phosphate salt, available in tablet strengths of 5 mg, 10 mg, 15 mg and 20 mg. Ruxolitinib is an inhibitor of the Janus Associated Kinases (JAKs) JAK1 and JAK2 with nanomolar potency. This medicinal product is subject to additional monitoring in Australia to allow quick identification of new safety information.

Approved indications

— Treatment of disease-related splenomegaly or symptoms in patients with primary myelofibrosis, post-polycythemia vera myelofibrosis or post-essential thrombocythemia myelofibrosis. — Treatment of adult patients with polycythemia vera who are resistant to or intolerant of hydroxyurea. — Treatment of patients aged 12 years and older with acute graft-versus-host disease who have inadequate response to corticosteroids. — Treatment of patients aged 12 years and older with chronic graft-versus-host disease who have inadequate response to corticosteroids.

Dosing overview Doses should be individualised based on safety and efficacy.

If efficacy is considered insufficient and blood counts are adequate, doses may be increased in 5 mg twice daily increments to a maximum dose of 25 mg twice daily. Complete blood counts should be monitored every 2 to 4 weeks until doses are stabilised, and then as clinically indicated.

Key safety warnings

Treatment with Jakavi can cause haematological adverse reactions, including thrombocytopenia, anaemia and neutropenia. Myelofibrosis patients with low platelet counts (<200 × 10⁹/L) at the start of therapy are more likely to develop thrombocytopenia during treatment, which was generally reversible and usually managed by reducing the dose or temporarily withholding Jakavi. Bleeding, including bruising and other bleeding events, and rarely gastrointestinal, intracranial, or fatal haemorrhage, has been reported in patients treated with Jakavi. Serious bacterial, mycobacterial, fungal, viral and other opportunistic infections have occurred in patients treated with Jakavi, and physicians should carefully observe patients for signs and symptoms of infections. Tuberculosis has been reported in patients receiving Jakavi, and before starting treatment, patients should be evaluated for active and inactive tuberculosis. Hepatitis B viral load increases, with and without associated elevations in alanine aminotransferase and aspartate aminotransferase, have been reported in patients with chronic HBV infections taking Jakavi. Progressive Multifocal Leukoencephalopathy has been reported with ruxolitinib treatment, and physicians should be alert for neuropsychiatric symptoms suggestive of PML. Treatment with Jakavi has been associated with increases in lipid parameters including total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides, and lipid monitoring and treatment of dyslipidaemia according to clinical guidelines is recommended. Cases of diverticulitis and gastrointestinal perforations have been reported with JAK inhibitors, and Jakavi should be used with caution in patients with diverticular disease and in patients chronically treated with nonsteroidal anti-inflammatory drugs, corticosteroids and opioids.

Contraindications

Hypersensitivity to the active substance or any of the excipients.

PBS listing

Jakavi tablets are listed on the PBS in strengths of 5 mg, 10 mg, 15 mg and 20 mg with authority required and streamlined restrictions, at an ex-manufacturer price of A$2256.25 for 5 mg tablets and A$4512.50 for other strengths.

Regulatory history

Jakavi was first registered on the ARTG on 3 July 2013, initially in strengths of 5 mg, 15 mg and 20 mg, with the 10 mg strength added on 16 December 2015. In July 2016, the PBAC recommended a new PBS listing for myelofibrosis under Section 85 Authority Required conditions. In November 2017, the PBAC recommended a new indication for treatment of polycythaemia vera. An AusPAR was published on 27 January 2022 approving Jakavi for the extended indications of acute and chronic graft-versus-host disease in patients aged 12 years and older who have an inadequate response to corticosteroids. In November 2022, the PBAC recommended listing for moderate to severe chronic graft-versus-host disease refractory to, dependent on or intolerant of corticosteroids in patients aged 12 years and older.