INLYTA

What it is

INLYTA is axitinib, supplied as red film-coated tablets containing 1 mg or 5 mg of axitinib. Axitinib is a selective tyrosine kinase inhibitor of vascular endothelial growth factor receptors (VEGFR)-1, VEGFR-2, and VEGFR-3.

Approved indications

— Treatment of patients with advanced renal cell carcinoma after failure of one prior systemic therapy.

Dosing overview

The recommended starting oral dose of INLYTA is 5 mg twice daily. Patients who tolerate the starting dose with no adverse reactions >Grade 2 for two consecutive weeks, are normotensive, and are not receiving anti-hypertensive medication, may have their dose increased to 7 mg twice daily, and subsequently to a maximum of 10 mg twice daily using the same criteria. When dose reduction is necessary, the INLYTA dose may be reduced to 3 mg twice daily and further to 2 mg twice daily. A dose decrease is recommended when administering INLYTA to patients with moderate hepatic impairment (Child-Pugh class B), with the starting dose reduced from 5 mg twice daily to 2 mg twice daily.

Key safety warnings

Cardiac failure events were reported in 1.7% of patients receiving INLYTA with Grade 3/4 events in 0.6% and fatal cardiac failure in 0.6%. Monitor for signs or symptoms of cardiac failure periodically throughout treatment with INLYTA, as management may require temporary interruption or permanent discontinuation and/or dose reduction. Hypertension was reported in 40.4% of patients receiving INLYTA with Grade 3 hypertension in 15.3% and Grade 4 in 0.3%. Blood pressure increases have been observed as early as 4 days after starting INLYTA. Blood pressure should be well-controlled prior to initiating INLYTA, and patients should be monitored for hypertension and treated as needed with standard anti-hypertensive therapy. Hypothyroidism was reported in 19.2% of patients receiving INLYTA and hyperthyroidism in 1.1%. Monitor thyroid function before initiation of, and periodically throughout, treatment with INLYTA, with hypothyroidism or hyperthyroidism treated according to standard medical practice. Arterial thromboembolic events were reported in 2.3% of patients in monotherapy studies, and INLYTA should be used with caution in patients who are at risk for or have a history of these events. Venous thromboembolic events were reported in 3.1% of patients with Grade 3/4 events in 2.5%. INLYTA has not been studied in patients who have evidence of untreated brain metastasis or recent active gastrointestinal bleeding and should not be used in those patients. VEGF pathway inhibitors may promote the formation of aneurysms and/or artery dissections, and this risk should be carefully considered in patients with risk factors such as hypertension or history of aneurysm before initiating INLYTA. Monitoring for proteinuria before initiation of and periodically throughout treatment is recommended, and patients who develop moderate to severe proteinuria should have their dose reduced or treatment temporarily interrupted.

Contraindications

Hypersensitivity to axitinib or to any of the excipients.

PBS listing

The 5 mg tablet is listed on the PBS with 2 items, streamlined and authority-required restriction, at an ex-manufacturer price of A$2274.30. The 1 mg tablet is listed on the PBS with 2 items, streamlined and authority-required restriction, at an ex-manufacturer price of A$454.86.

Regulatory history

INLYTA received initial registration on the Australian Register of Therapeutic Goods on 26 July 2012. The AusPAR approval date was 2012-07-19, with axitinib approved for registration for the treatment of patients with advanced renal cell carcinoma after failure of one prior systemic therapy.