PIRFENIDONE TAB,ORAL
Clinical Criteria Summary
Indication & Diagnostic Requirements
- Diagnosis of idiopathic pulmonary fibrosis (IPF)
- Must meet ATS/ERS/JRS/ALAT diagnostic requirements
- Confirmed through formal interdisciplinary discussion (Interstitial Lung Disease Consensus Committee or similar)
- Requires exclusion of other known causes of interstitial lung disease (e.g., environmental exposures, connective tissue disease, drug toxicity)
- Requires pattern of usual interstitial pneumonia on high-resolution computed tomography (HRCT) and/or specific combinations of HRCT and surgical lung biopsy patterns
Patient Selection & Exclusion Criteria
- Patient should NOT receive pirfenidone if: IPF diagnosis unconfirmed; current smoker; severe hepatic impairment (Child Pugh Class C); end-stage renal disease requiring dialysis; currently receiving nintedanib; taking combination of moderate/strong CYP1A2 inhibitors with other CYP inhibitors that cannot be altered/discontinued; or documented ongoing nonadherence
- Treatment must be initiated and followed by a VA Pulmonologist experienced in ILD diagnosis and management
Dosage & Administration
- Recommended dosage: 801 mg three times daily with food (total 2403 mg/day)
- Doses should be taken at the same time each day
- Titration schedule for initiation or resumption after ≥14-day lapse over 14 days: Days 1–7: one 267mg capsule three times daily; Days 8–14: two 267mg capsules three times daily; Day 15 onward: one 801mg tablet three times daily
- Dose modifications may be required for side effects, liver function abnormalities, or drug interactions
Monitoring & Laboratory Requirements
- Pulmonary specialty follow-up including pulmonary function testing at least biannually to assess drug response
- Adherence monitoring required for maximal benefit
- Liver chemistries (AST, ALT, total bilirubin): obtain at baseline, monthly for 6 months, then every 3 months thereafter
- FVC and DLCO measurements: routine monitoring at 3–6 month intervals; more frequent testing if progressive dyspnea or rapidly progressive course present
- Advise patients to avoid/minimize sunlight/UV exposure and use SPF≥50 sunblock and occlusive clothing/hats due to photosensitivity/rash risk
Management of Adverse Reactions & Liver Abnormalities
- AST/ALT >3 to ≤5x ULN without symptoms/hyperbilirubinemia: discontinue confounding medications, exclude other causes, monitor closely, repeat tests as indicated; maintain full dose if appropriate or reduce/interrupt until normal, then re-titrate
- AST/ALT >3 to ≤5x ULN with symptoms/hyperbilirubinemia: permanently discontinue and do not rechallenge
- AST/ALT >5x ULN: permanently discontinue and do not rechallenge
- Strong CYP1A2 inhibitors: Co-administration of pirfenidone with strong CYP1A1 inhibitors (ex: fluvoxamine, enoxacin) is not recommended; if unavoidable, reduce dose of pirfenidone to 267mg three times daily
- Moderate CYP1A2 inhibitors: Reduce dose of pirfenidone to 534mg three times daily in combination with high-dose moderate CYP1A2 inhibitor (ex: ciprofloxacin 750mg twice daily)
- Strong/moderate CYP1A2 inhibitors combined with other CYP inhibitors: Discontinue or avoid combinations due to unpredictable clearance effect
- Strong CYP1A2 inducers: Co-administration not recommended due to expected reduction in pirfenidone exposure and loss of efficacy
- Temporary dose reductions may be required to allow resolution of symptoms
Discontinuation Guidelines
- Temporarily discontinue for mildly elevated liver function tests or moderate severity adverse reactions (rash, photosensitivity, gastrointestinal, or other)
- Permanently discontinue for: severe adverse drug reactions, liver function test abnormalities per monitoring criteria, significant nonadherence to therapy, or smoking
- Consider discontinuation for perceived treatment failure based on serial pulmonary function trends
Special Populations & Clinical Considerations
- Pregnancy Category C; women of childbearing potential require contraceptive counseling; use during pregnancy only if maternal benefit outweighs fetal risk
- Unknown excretion in breast milk; decide to discontinue nursing or pirfenidone based on drug importance to mother
- Limited data for severe IPF (FVC < 50%); randomized controlled trials did not enroll patients with severe disease
- Lung transplant wait list: Inadequate data; case-specific assessment of risks and benefits recommended due to short median wait times and high mortality rates among listed patients