GIOTRIF

What it is

GIOTRIF is a film-coated tablet containing afatinib (as afatinib dimaleate), available in strengths of 20 mg, 30 mg, 40 mg and 50 mg. Afatinib is an irreversible ErbB family blocker that covalently binds to and irreversibly blocks signalling from homo- and heterodimers formed by EGFR, HER2, ErbB3 and ErbB4.

Approved indications —

Locally advanced or metastatic non-squamous non-small cell carcinoma of the lung with activating EGFR mutations, either as first line therapy or after failure of cytotoxic chemotherapy. — Locally advanced or metastatic squamous non-small cell carcinoma of the lung progressing on or after platinum-based chemotherapy.

Dosing overview

The recommended dose of GIOTRIF is 40 mg orally once daily. Dose escalation to a maximum of 50 mg per day may be considered in patients who tolerate the 40 mg starting dose (absence of diarrhoea, skin rash, stomatitis and other drug-related events of CTCAE Grade >1) in the first cycle of treatment. For patients with severe renal impairment, the starting dose should be 30 mg once daily; no adjustments are necessary for patients with mild or moderate renal impairment. GIOTRIF should be taken without food, with food not consumed for at least 3 hours before and at least 1 hour after taking GIOTRIF.

Key safety warnings

Diarrhoea, including severe diarrhoea, has been reported during treatment with GIOTRIF and may result in electrolyte abnormalities and dehydration, which in rare cases has resulted in fatal outcomes. Diarrhoea usually occurs within the first 2 weeks of treatment, with Grade 3 diarrhoea most frequently occurring within the first 6 weeks; proactive management including adequate hydration combined with antidiarrhoeal agents is important. Rash or acne has been reported in patients treated with GIOTRIF, generally manifesting as mild or moderate erythematous and acneiform rash, which may occur or worsen in sun-exposed areas. Bullous, blistering and exfoliative skin conditions including rare cases suggestive of Stevens-Johnson syndrome and toxic epidermal necrolysis have been reported; GIOTRIF should be interrupted or discontinued if severe bullous, blistering or exfoliating conditions develop. There have been reports of interstitial lung disease (ILD) or ILD-like events, including fatalities, in patients receiving GIOTRIF, with drug-related ILD-like events reported in 0.7% of patients treated across all clinical trials. Careful assessment of all patients with acute onset and unexplained worsening of pulmonary symptoms should be performed to exclude ILD; GIOTRIF should be interrupted pending investigation, and if ILD is diagnosed, GIOTRIF should be permanently discontinued. Gastrointestinal perforation, including fatalities, has been reported during treatment with GIOTRIF in 0.2% of patients across all randomised controlled clinical trials, with most cases associated with concomitant medications such as corticosteroids or NSAIDs, or underlying risk factors.

Contraindications

GIOTRIF is contraindicated in patients with known hypersensitivity to afatinib or to any of the excipients.

PBS listing

PBS listing information is not provided in the available documents.

Regulatory history

GIOTRIF afatinib 20 mg, 30 mg, 40 mg and 50 mg film-coated tablets were first listed on the ARTG on 2013-11-07. The TGA approved the submission for afatinib (GIOTRIF) on 2013-11-01 as a new chemical entity.