INREBIC

What it is

INREBIC is a hard capsule containing 100 mg fedratinib (equivalent to 117.30 mg fedratinib dihydrochloride monohydrate). Fedratinib is an oral kinase inhibitor with activity against wild type and mutationally activated Janus Associated Kinase 2 (JAK2) and FMS-like tyrosine kinase 3 (FLT3), and is a JAK2-selective inhibitor with higher inhibitory activity for JAK2 over family members JAK1, JAK3, and TYK2. This medicinal product is subject to additional monitoring in Australia.

Approved indications

— Treatment of disease-related splenomegaly or symptoms in adult patients with primary myelofibrosis, post polycythaemia vera myelofibrosis or post essential thrombocythaemia myelofibrosis who are Janus Associated Kinase (JAK) inhibitor naïve or have been treated with ruxolitinib.

Dosing overview

The recommended dose of INREBIC is 400 mg taken orally once daily for patients with a baseline platelet count of ≥ 50 × 10⁹/L. INREBIC may be taken with or without food, and administration with a high fat meal may reduce the incidence of nausea and vomiting. While on treatment, all patients should receive prophylaxis with daily 100 mg oral thiamine and should have thiamine levels assessed periodically as clinically indicated.

Key safety warnings

Serious and fatal encephalopathy, including Wernicke's, has occurred in patients treated with INREBIC. Wernicke's encephalopathy is a neurologic emergency. The risk of Wernicke's encephalopathy is reduced via thiamine monitoring and prophylaxis with daily oral thiamine. Signs and symptoms of Wernicke's encephalopathy may include ataxia, mental status changes, and ophthalmoplegia (for example, nystagmus, diplopia). Treatment with INREBIC may cause anaemia, thrombocytopenia and neutropenia. Complete blood counts should be obtained at baseline, periodically during treatment, and as clinically indicated. Anaemia generally occurs within the first 3 months of treatment. Patients with a haemoglobin level below 10.0 g/dL at the start of therapy are more likely to develop anaemia of Grade 3 or above during treatment and should be carefully monitored as clinically indicated. Thrombocytopenia generally occurs within the first 3 months of treatment. Patients with low platelet counts (<100 × 10⁹/L) at the start of therapy are more likely to develop thrombocytopenia of Grade 3 or above during treatment and should be carefully monitored as clinically indicated. Nausea, vomiting, and diarrhoea are among the most frequent adverse reactions in INREBIC-treated patients. Consider providing appropriate prophylactic anti-emetic therapy (for example, 5-HT3 receptor antagonists) during INREBIC treatment. Treat diarrhoea with anti-diarrhoeal medications promptly at the first onset of symptoms. Elevations of ALT and AST have been reported with INREBIC treatment. Monitor hepatic function at baseline, periodically during treatment, and as clinically indicated. Uveitis has been observed in post-marketing clinical trials. Advise patients on the risks of developing uveitis before starting fedratinib therapy. Certain ethnic groups (such as Asians) may be at higher risk of developing uveitis.

Contraindications

Hypersensitivity to the active substance or to any of the excipients.

PBS listing

Capsule 100 mg (as hydrochloride) is listed on the PBS with streamlined and authority required restrictions, with an ex-manufacturer price of A$5637.78.

Regulatory history

INREBIC fedratinib 100 mg capsule was first listed on the ARTG on 13 February 2025. The AusPAR (Australian Public Assessment Report) was approved on 12 February 2025. In May 2025, the PBAC did not recommend INREBIC for treatment of patients with intermediate-2/high-risk myelofibrosis and post-polycythaemia vera or post-essential thrombocythaemia myelofibrosis who have had prior ruxolitinib treatment.