NEXAVAR

What it is

Nexavar is a film-coated tablet containing 274 mg sorafenib tosilate, equivalent to 200 mg of sorafenib. Sorafenib is a multikinase inhibitor that targets various receptor tyrosine kinases and RAF kinases (serine/threonine kinases) associated with tumour growth.

Approved indications

— Advanced hepatocellular carcinoma. — Advanced renal cell carcinoma. — Locally advanced or metastatic, progressive, differentiated thyroid carcinoma refractory to radioactive iodine.

Dosing overview

The recommended daily dose of Nexavar is 400 mg (2 × 200 mg tablets) taken twice a day, either without food or together with a moderate fat meal. Treatment should be continued until the patient is no longer clinically benefiting from therapy or until unacceptable toxicity occurs. When dose reduction is necessary during the treatment of hepatocellular carcinoma and advanced renal cell carcinoma, the Nexavar dose should be reduced to two tablets of 200 mg once daily. When dose reduction is necessary during the treatment of differentiated thyroid carcinoma, the Nexavar dose should be reduced to 600 mg daily in divided doses (two tablets of 200 mg and one tablet of 200 mg twelve hours apart).

Key safety warnings

Hand foot skin reaction (palmar plantar erythrodysaesthesia) and rash represent the most common adverse drug reactions with Nexavar and are usually Grade 1 and 2, generally appearing during the first six weeks of treatment. An increased incidence of hypertension was observed in Nexavar-treated patients, usually mild to moderate, occurring early in the course of treatment, and amenable to management with standard antihypertensive therapy. An increase in the risk of bleeding may occur following Nexavar administration, although the incidence of severe bleeding events is uncommon. Infrequent bleeding events or elevations in the International Normalized Ratio (INR) have been reported in some patients taking warfarin while on Nexavar therapy, and patients taking warfarin concomitantly should be monitored regularly for changes in prothrombin time, INR and for clinical bleeding episodes. Nexavar has been shown to prolong the QT/QTc interval, which may lead to an increased risk for ventricular arrhythmias, and should be used with caution in patients who have, or may develop prolongation of QTc, such as patients with a congenital long QT syndrome, patients treated with a high cumulative dose of anthracycline therapy, patients taking certain anti-arrhythmic medicines or other medicinal products that lead to QT prolongation, and those with electrolyte disturbances such as hypokalemia, hypocalcaemia, or hypomagnesemia. Women should avoid becoming pregnant while on therapy, and women of childbearing potential must be apprised of the potential hazard to the fetus, which includes severe malformation (teratogenicity), failure to thrive and fetal death (embryotoxicity). Breastfeeding should be discontinued during Nexavar therapy.

Contraindications

Nexavar is contraindicated in patients with known severe hypersensitivity to sorafenib or any of the excipients in the tablet.

Regulatory history

Nexavar (sorafenib as tosilate) 200 mg tablet was first registered on the Australian Register of Therapeutic Goods on 27 September 2006. The TGA approved Nexavar for the extension of indication to treat patients with locally advanced or metastatic, progressive, differentiated thyroid carcinoma refractory to radioactive iodine on 22 April 2014, following a comprehensive evaluation of the submitted clinical data.