Pulmosis

Treatment with Pirfenidone should be initiated and supervised by specialist physicians experienced in the diagnosis and treatment of IPF. Upon initiating treatment, the dose should be titrated to the recommended daily dose of nine 267 mg tablets or one 801 mg tablet per day over a 14-days period for adult as follows:

• Days 1 to 7: One 267 mg tablet administered three times a day (801 mg/day)
• Days 8 to 14: One 534 mg tablets administered three times a day (1602 mg/day)
• Day 15 onward: Three 267 mg tablets or one 801 mg tablet administered three times a day (2403 mg/day)

The recommended daily dose of Pirfenidone for patients with IPF is three 267 mg tablets or one 801 mg three times a day with food for a total of 2403 mg/day. Doses above 2403 mg/day are not recommended for any patient. Patients who miss 14 consecutive days or more of Pirfenidone treatment should re-initiate therapy by undergoing the initial 2-week titration regimen up to the recommended daily dose. For treatment interruption of less than 14 consecutive days, the dose can be resumed at the previous recommended daily dose without titration.

Dose adjustments and other considerations for safe use: Gastrointestinal events: In patients who experience intolerance to therapy due to gastrointestinal side effects, patients should be reminded to take the medicinal product with food. If symptoms persist Pirfenidone may be reduced to 1-2 capsules (267 mg-534 mg) 2-3 times/day with food with re-escalation to the recommended daily dose as tolerated. If symptoms continue, patients may be instructed to interrupt treatment for 1 to 2 weeks to allow symptoms to resolve.

Photosensitivity reaction or rash: Patients who experience a mild to moderate photosensitivity reaction or rash should be reminded of the instruction to use a sunblock daily and to avoid sun exposure. The dose of Pirfenidone may be reduced to 3 capsules/day (1 capsule three times a day). If the rash persists after 7 days, Pirfenidone should be discontinued for 15 days, with re-escalation to the recommended daily dose in the same manner as the dose escalation period. Patients who experience severe photosensitivity reaction or rash should be instructed to interrupt the dose and to seek medical advice. Once the rash has resolved, Pirfenidone may be re-introduced and re-escalated up to the recommended daily dose at the discretion of the physician.

Hepatic function: In the event of significant elevation of alanine and/or aspartate aminotransferases (ALT/AST) with or without bilirubin elevation, the dose of Pirfenidone should be adjusted or treatment discontinued according to the guidelines.

The safety of Pirfenidone has been evaluated in clinical studies including 1345 healthy volunteers and patients. The most commonly reported (10%) adverse reactions during clinical study experience with Pirfenidone at a dose of 2403 mg/day compared to placebo, respectively, were nausea (32.8% versus 13.3%), rash (28.7% versus 8.6%), fatigue (22.3% versus 13.3%), diarrhoea (21.7% versus 13.5%), dyspepsia (16.8% versus 5.5%), and photosensitivity reaction (12.2% versus 1.7%). Serious adverse reactions were recorded at similar frequencies among patients treated with 2403 mg/day of Pirfenidone and placebo in clinical studies. The adverse reactions reported at a frequency of 2% in 345 patients receiving Pirfenidone at the recommended dose of 2403 mg/day in two pivotal Phase 3 studies. Adverse reactions from post-marketing experience are also listed. Adverse reactions are listed by System Organ Class (SOC) and within each frequency grouping the adverse reactions are presented in order of decreasing seriousness.

There is limited clinical experience with overdose. Multiple doses of pirfenidone up to a dose of 4806 mg/day were administered as six 267 mg capsules three times daily to healthy adult volunteers over a 12-day dose escalation period. Adverse reactions were mild, transient, and consistent with the most frequently reported adverse reactions for pirfenidone.

Pirfenidone is indicated in adults for the treatment of mild to moderate Idiopathic Pulmonary Fibrosis (IPF).

Pirfenidone is an orally active, small molecule that shows a wide range of biologic activity. In vitro evidence has shown that pirfenidone inhibits collagen synthesis, down-regulates profibrotic cytokines and decreases fibroblast proliferation. Pirfenidone leads to a reduction of TGF-beta2 mRNA levels and of the mature TGF-beta2 protein due to decreased expression and direct inhibition of the TGF-beta pro-protein convertase furin. In addition, pirfenidone reduces the protein levels of the matrix metalloproteinase (MMP)-11, a TGF-beta target gene and furin substrate involved in carcinogenesis.

Immunosuppressant