Pirfenidone Viatris

Treatment with Pirfenidone Viatris should be initiated and supervised by specialist physicians experienced in the diagnosis and treatment of IPF. 3 Posology Adults Upon initiating treatment, the dose should be titrated to the recommended daily dose of 2 403 mg/day over a 14-day period as follows:  Days 1 to 7: a dose of 267 mg administered three times a day (801 mg/day)  Days 8 to 14: a dose of 534 mg administered three times a day (1 602 mg/day)  Day 15 onward: a dose of 801 mg administered three times a day (2 403 mg/day) The recommended maintenance daily dose of Pirfenidone Viatris is 801 mg three times a day with food for a totalof 2 403 mg/day.

9). Patients who miss 14 consecutive days or more of Pirfenidone Viatris 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 undesirable effects, patients should be reminded to take the medicinal product with food.

If symptoms persist, the dose of pirfenidone may be reduced to 267 mg – 534 mg two to three 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 one to two weeks to allow symptoms to resolve.

4). The dose of pirfenidone may be reduced to 801 mg each day (267 mg three times a day). If the rash persists after 7 days, Pirfenidone Viatris should be discontinued for 15 days, with re-escalation to the recommended daily dose in the same manner as the dose escalation period.

4). Once the rash has resolved, Pirfenidone Viatris 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 listed in section

1%). More than 170 patients have been investigated in open studies for more than five years and some forup to 10 years. Table 1 shows the adverse reactions reported at a frequency of ≥ 2% in 623 patients receiving pirfenidoneat the recommended dose of 2 403 mg/day in three pooled pivotal Phase 3 studies.

Adverse reactionsfrom post-marketing experience are also listed in Table 1. Adverse reactions are listed by SystemOrgan Class (SOC) and within each frequency grouping [Very common (≥ 1/10), common (≥ 1/100 to< 1/10), uncommon (≥ 1/1 000 to < 1/100), rare (≥ 1/10 000 to < 1/1 000), not known (cannot beestimated from the available data)] the adverse reactions are presented in order of decreasing seriousness.

4). Exposure-adjusted analyses of pooled clinical trials in IPF confirmed that the safety and tolerability profile of pirfenidone in IPF patients with advanced disease (n=366) is consistent with that established in IPF patients with non-advanced disease (n=942).

Description of selected adverse reactions Decreased appetite During the pivotal clinical trials, cases of decreased appetite were readily manageable and generally not associated with significant sequelae. Uncommonly, cases of decreased appetite were associated with significant weight loss and required medical intervention.

Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.

4. 2). e. Child-Pugh Class A and B). However, since plasma levels of pirfenidone may be increased in some individuals 4 with mild to moderate hepatic impairment, caution should be used with Pirfenidone Viatris treatment in this population.

2). Renal impairment No dose adjustment is necessary in patients with mild renal impairment. Pirfenidone Viatris should be used with caution in patients with moderate (CrCl 30-50 ml/min) renal impairment. 2). Paediatric population There is no relevant use of Pirfenidone Viatris in the paediatric population for the indication of IPF.

Method of administration Pirfenidone Viatris is for oral use. 2). 1. 4). 5). 4). 2). 4 Special warnings and precautions for use Hepatic function Elevated transaminases have been commonly reported in patients treated with pirfenidone. 8). If a patient exhibits an aminotransferase elevation > 3 to <5 x ULN without bilirubin elevation and without symptoms or signs of drug-induced liver injury after starting Pirfenidone Viatris therapy, other causes should be excluded, and the patient monitored closely.

Discontinuation of other medicines associated with liver toxicity should be considered. If clinically appropriate, the dose of Pirfenidone Viatris should be reduced or interrupted. Once liver function tests are within normal limits Pirfenidone Viatris may be re-escalated to the recommended daily dose if tolerated.

Drug-induced liver injury Uncommonly, elevations in AST and ALT were associated with concomitant bilirubin increases. 8). In addition to the recommended regular monitoring of liver function tests, prompt clinical evaluation and measurement of liver function tests should be performed in patients who report symptoms that may indicate liver injury, including fatigue, anorexia, right upper abdominal discomfort, dark urine, or jaundice.

5 If a patient exhibits an aminotransferase elevation > 3 to <5 x ULN accompanied by hyperbilirubinaemia or clinical signs or symptoms indicative of liver injury, Pirfenidone Viatris should be permanently discontinued and the patient should not be rechallenged.

1. 4). 5). 4). 2).