Fatigue was more common with pirfenidone (26% versus 19%), however generally benign and reported in the 9 months. It is identified in the PI under Adverse events. Of note, in the EU EMA SPC, dizziness and fatigue are mentioned as potentially influencing ability to drive or operate machinery. Anorexia was more common with pirfenidone (13% versus 5% for likely drug related events). Weight loss was also more frequent in the pirfenidone groups compared to placebo. Other safety issues There is little if any experience with high doses or overdose in the clinical setting. The last part of the trade name is the same as registered product rabeprazole 10 mg or 20 mg trade name, However 267 mg appears unlikely to be associated with a high risk ‘Pariet’. ‘Esbriet’ of errors in transcription, prescribing or dispensing. Evaluator’s overall conclusions on clinical safety Overall the data indicated a well characterised and acceptable safety profile for IPF patients, although monitoring and effective management of adverse events will be required. Dose adjustments may be needed soon after initiation and this is important for the proposed usage. Occurrence of common AEs such as GI and CNS responses may be amenable to measures to improve tolerability, such as dose escalation and dosing with food as recommended in the PI. Dose reduction or interruption might be required to allow recovery and subsequent dose titration. Some AEs require prompt assessment to avoid serious clinical consequences. The onset of an adverse event needs to be recognised as a potential reaction to pirfenidone that might require discontinuation or dose reduction. First round benefit-risk assessment First round assessment of benefits The benefits of pirfenidone in the proposed usage in patients with IPF include: reduction in the decline of percent predicted FVC increased proportion of patients with improved exercise tolerance, (for example 6 MWT) in pooled analyses, suggestion of reduction in mortality. round assessment of risks The risks of pirfenidone in the proposed usage are: Well characterised GI, CNS and hepatic adverse events that can generally be managed in clinical practice drug interactions. First round assessment of benefit-risk balance The benefitrisk balance of pirfenidone, given the proposed usage, is favourable at Round 1.
Fatigue was more common with pirfenidone (26% versus 19%), however generally benign and reported in the 9 months. It is identified in the PI under Adverse events. Of note, in the EU EMA SPC, dizziness and fatigue are mentioned as potentially influencing ability to drive or operate machinery. Anorexia was more common with pirfenidone (13% versus 5% for likely drug related events). Weight loss was also more frequent in the pirfenidone groups compared to placebo. Other safety issues There is little if any experience with high doses or overdose in the clinical setting. The last part of the trade name is the same as registered product rabeprazole 10 mg or 20 mg trade name, ‘Pariet’. However ‘Esbriet’ 267 mg appears unlikely to be associated with a high risk of errors in transcription, prescribing or dispensing. Evaluator’s overall conclusions on clinical safety Overall the data indicated a well characterised and acceptable safety profile for IPF patients, although monitoring and effective management of adverse events will be required. Dose adjustments may be needed soon after initiation and this is important for the proposed usage. Occurrence of common AEs such as GI and CNS responses may be amenable to measures to improve tolerability, such as dose escalation and dosing with food as recommended in the PI. Dose reduction or interruption might be required to allow recovery and subsequent dose titration. Some AEs require prompt assessment to avoid serious clinical consequences. The onset of an adverse event needs to be recognised as a potential reaction to pirfenidone that might require discontinuation or dose reduction. First round benefit-risk assessment First round assessment of benefits The benefits of pirfenidone in the proposed usage in patients with IPF include: reduction in the decline of percent predicted FVC increased proportion of patients with improved exercise tolerance, (for example 6 MWT) in pooled analyses, suggestion of reduction in mortality. round assessment of risks The risks of pirfenidone in the proposed usage are: Well characterised GI, CNS and hepatic adverse events that can generally be managed in clinical practice drug interactions. First round assessment of benefit-risk balance The benefitrisk balance of pirfenidone, given the proposed usage, is favourable at Round 1.