ARX-PIRFENIDONE

What it is

ARX-PIRFENIDONE is available as 267 mg and 801 mg film-coated tablets containing pirfenidone.

Approved indications

— Idiopathic pulmonary fibrosis (IPF).

Dosing overview

The recommended daily dose of ARX-PIRFENIDONE for patients with IPF is 801 mg three times a day with food, for a total of 2403 mg/day. Upon initiating treatment, the dose should be titrated to the recommended daily dose of 2403 mg/day over a 14 day period: Days 1 to 7 at 267 mg three times a day (801 mg/day), Days 8 to 14 at 534 mg three times a day (1602 mg/day), and Day 15 onward at 801 mg three times a day (2403 mg/day). Patients who miss 14 consecutive days or more should re-initiate therapy with the initial 2 week titration regimen. For treatment interruption of less than 14 consecutive days, the dose can be resumed at the previous recommended daily dose without titration.

Key safety warnings

Drug-induced liver injury in the form of transient and clinically silent elevations in transaminases has been commonly reported in patients treated with ARX-PIRFENIDONE. Uncommonly, these elevations were associated with concomitant bilirubin increases, and serious clinical consequences including isolated cases with fatal outcome have been reported post-marketing. Patients treated with 2403 mg/day in the three Phase 3 trials had a higher incidence of elevations in ALT or AST ≥3 × ULN than placebo patients (3.7% vs. 0.8%, respectively). Perform liver function tests (ALT, AST, and bilirubin) prior to the initiation of therapy with ARX-PIRFENIDONE in all patients, then monthly for the first 6 months and every 3 months thereafter. Exposure to direct sunlight (including sunlamps) should be avoided or minimized during treatment with ARX-PIRFENIDONE. Patients should be instructed to use an effective sunblock daily, to wear clothing that protects against sun exposure, and to avoid other medicinal products known to cause photosensitivity. The exposure to pirfenidone in smokers was 50% of that observed in non-smokers. Concomitant use of strong inducers of CYP1A2 including smoking should be avoided during ARX-PIRFENIDONE therapy. Patients should be encouraged to discontinue use of strong inducers of CYP1A2 and to stop smoking before and during treatment with pirfenidone. Reports of angioedema (some serious) such as swelling of the face, lips and/or tongue which may be associated with difficulty breathing or wheezing have been received in association with use of ARX-PIRFENIDONE in the post-marketing setting. Reports of anaphylactic reactions have also been received. Patients who develop signs or symptoms of angioedema or severe allergic reactions following administration of ARX-PIRFENIDONE should immediately discontinue treatment. Severe cutaneous adverse reactions (SCAR), including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS), have been reported in association with the use of ARX-PIRFENIDONE in the postmarketing setting. If signs or symptoms of SCAR occur, interrupt ARX-PIRFENIDONE treatment until the aetiology of the reaction has been determined. Consultation with a dermatologist is recommended. If a SCAR is confirmed, permanently discontinue ARX-PIRFENIDONE.

Contraindications

ARX-PIRFENIDONE is contraindicated in patients with hypersensitivity to the active substance or to any of the excipients, concomitant use of fluvoxamine, and history of angioedema with pirfenidone. ARX-PIRFENIDONE is also contraindicated in patients with severe hepatic impairment or end stage liver disease, and in patients with severe renal impairment (CrCl <30 ml/min) or end stage renal disease requiring dialysis.

PBS listing

ARX-PIRFENIDONE 267 mg and 801 mg tablets are listed on the PBS with Authority Required restriction for the treatment of idiopathic pulmonary fibrosis.

Regulatory history

ARX-PIRFENIDONE 267 mg and 801 mg tablets were first listed on the ARTG on 1 December 2023. The product received a PBAC recommendation (new) in March 2018 for idiopathic pulmonary fibrosis with Authority Required benefit for 267 mg and 801 mg tablets.