What is the recommended dosage and treatment protocol for Pirfenidone (Idiopathic Pulmonary Fibrosis treatment)?

Pirfenidone Dosage and Treatment Protocol for Idiopathic Pulmonary Fibrosis

Pirfenidone should be initiated at 801 mg three times daily (2,403 mg/day total) after a 14-day titration period, taken with food, in patients with mild-to-moderate IPF (FVC >50% predicted and DLCO >35% predicted). 1

Patient Selection Criteria

Pirfenidone is indicated for patients with mild-to-moderate IPF, specifically defined as:

• FVC >50% predicted 2, 3
• DLCO >35% predicted 2, 3
• Clinically and radiologically confirmed IPF diagnosis 2

Treatment must be initiated and supervised by physicians experienced in IPF diagnosis and management. 2

Dosage Titration Protocol

The FDA-approved titration schedule over 14 days is mandatory: 1

• Days 1-7: 267 mg three times daily (801 mg/day total)
• Days 8-14: 534 mg three times daily (1,602 mg/day total)
• Day 15 onward: 801 mg three times daily (2,403 mg/day total - maintenance dose)

All doses must be taken with food at the same time each day. 1

Pre-Treatment Requirements

Before initiating pirfenidone, you must: 1

• Perform liver function tests (ALT, AST, bilirubin) 2, 3, 1
• Ensure patient is not taking fluvoxamine (absolute contraindication) 2
• Confirm absence of severe hepatic or renal impairment 2
• Verify patient will discontinue smoking 2, 3

Monitoring Protocol

Liver function monitoring schedule: 2, 3

• Monthly for the first 6 months
• Every 3 months thereafter
• Immediately if symptoms of liver injury develop

Clinical monitoring includes: 2, 3

• Regular assessment of clinical tolerance
• Pulmonary function tests to monitor disease progression
• Evaluation for adverse events

Dosage Modifications for Adverse Events

For elevated liver enzymes: 1

• ALT/AST >3 but ≤5 × ULN without symptoms: Discontinue confounding medications, monitor closely, may maintain full dose or reduce/interrupt with subsequent re-titration
• ALT/AST >3 but ≤5 × ULN WITH symptoms or hyperbilirubinemia: Permanently discontinue pirfenidone
• ALT/AST >5 × ULN: Permanently discontinue pirfenidone

For gastrointestinal or photosensitivity reactions: 1

• Consider temporary dose reduction or interruption until symptoms resolve
• Do not take 2 doses simultaneously to make up for missed doses

For treatment interruptions: 1

• <14 days: Resume previous dose
• ≥14 days: Restart with full 14-day titration protocol

Drug Interaction Dosage Adjustments

Strong CYP1A2 inhibitors (e.g., fluvoxamine, enoxacin): 1

• Fluvoxamine: Discontinue prior to pirfenidone or reduce pirfenidone to 267 mg three times daily (801 mg/day)

Moderate CYP1A2 inhibitors (e.g., ciprofloxacin 750 mg twice daily): 1

• Reduce pirfenidone to 534 mg three times daily (1,602 mg/day)

Omeprazole: 2, 3

• Avoid concomitant use as it may alter pirfenidone pharmacokinetics

Critical Patient Counseling Points

Patients must be warned about: 2, 3, 1

• UV exposure and photosensitivity: Avoid sunlight and sunlamps, wear sunscreen and protective clothing daily
• Smoking cessation: Mandatory discontinuation as smoking increases pirfenidone metabolism
• Common adverse events: Nausea (most common), rash, fatigue, diarrhea, dyspepsia, photosensitivity, weight loss 2, 1
• Severe cutaneous adverse reactions: Stevens-Johnson syndrome, toxic epidermal necrolysis, and DRESS have been reported—interrupt treatment immediately if suspected and permanently discontinue if confirmed 1

Expected Treatment Outcomes

Pirfenidone demonstrates: 4

• 43.8% reduction in proportion of patients with ≥10% FVC decline or death at 1 year
• 30% reduction in risk of disease progression (HR 0.70,95% CI 0.56-0.88) 2
• Reduction in FVC decline of approximately 3.5% predicted over 72 weeks compared to placebo 2

Real-world data shows: 5

• Change from baseline in %FVC of -0.75% after 12 months
• Adverse event discontinuation rate of 16.6%
• Adverse event incidence of 56.4%

Common Pitfalls to Avoid

• Do not skip the titration period—abrupt initiation at full dose increases gastrointestinal adverse events 1
• Do not continue pirfenidone with confirmed severe cutaneous adverse reactions—permanent discontinuation is required 1
• Do not overlook drug interactions—particularly with CYP1A2 inhibitors and omeprazole 2, 1
• Do not forget to counsel on sun protection—photosensitivity is a significant and manageable adverse event 2, 3