What is the recommended dose of Pirfenidone for Interstitial Lung Disease (ILD)?

Recommended Dosage of Pirfenidone for Interstitial Lung Disease (ILD)

The recommended daily maintenance dosage of pirfenidone for ILD is 2,403 mg/day, administered as 801 mg three times daily with food. 1

Dosing Protocol

Initial Titration

• Pirfenidone requires a 14-day titration schedule to minimize adverse effects 1:
  • Days 1-7: 267 mg three times daily (801 mg/day)
  • Days 8-14: 534 mg three times daily (1,602 mg/day)
  • Day 15 onward: 801 mg three times daily (2,403 mg/day)

Patient Population

• Pirfenidone is primarily indicated for patients with mild-to-moderate ILD, specifically those with 2:
  • FVC > 50% predicted
  • DLCO > 35% predicted

Administration Considerations

• Doses should be taken with food at the same time each day 1
• Tablet formulation (801 mg) reduces pill burden compared to capsules (267 mg) 3
• Patients should not take more than 3 doses per day or double-dose to make up for missed doses 1

Evidence for Efficacy

• Pirfenidone has demonstrated efficacy in reducing the decline in forced vital capacity (FVC) in patients with IPF 2
• The CAPACITY trials showed that pirfenidone 2403 mg/day reduced FVC decline by 4.4% compared to placebo over 72 weeks 4
• Pooled analysis of clinical trials showed pirfenidone reduced the risk of disease progression by 30% (HR 0.70,95% CI 0.56–0.88) 2
• Treatment with pirfenidone showed favorable trends for both all-cause mortality and IPF-related mortality 2

Special Considerations

Dose Modifications

• For patients who miss 14 or more days of treatment, restart the 2-week titration regimen 1
• For interruptions less than 14 days, resume the previous dosage 1
• Dose reductions may be necessary for significant adverse reactions 1:
  • Gastrointestinal effects
  • Photosensitivity reactions
  • Rash or severe cutaneous adverse reactions (SCAR)

Liver Function Monitoring

• Conduct liver function tests prior to initiating treatment 1
• For liver enzyme elevations 1:

  • 3 but ≤5 × ULN without symptoms: Consider dose reduction or interruption

  • 3 but ≤5 × ULN with symptoms or hyperbilirubinemia: Permanently discontinue

  • 5 × ULN: Permanently discontinue

Drug Interactions

• With strong CYP1A2 inhibitors (e.g., fluvoxamine): Reduce to 267 mg three times daily 1
• With moderate CYP1A2 inhibitors (e.g., ciprofloxacin 750 mg twice daily): Reduce to 534 mg three times daily 1
• Avoid concomitant use of omeprazole as it may alter pirfenidone pharmacokinetics 2

Common Adverse Effects

• Gastrointestinal effects: nausea (36%), dyspepsia (19%), vomiting (14%), anorexia (11%) 4
• Skin-related: photosensitivity (12%), rash (32%) 4
• Other: fatigue, dizziness (18%) 4
• Most adverse events occur during the titration period rather than maintenance 5

Important Clinical Considerations

• Smoking should be discontinued prior to and during treatment as it increases the metabolism of pirfenidone 2
• Patients should be warned about UV exposure and photosensitivity risk 2
• Recent pharmacokinetic analysis suggests that a lower dose of 1500 mg/day (500 mg TID) might provide 80% of maximum efficacy for some patients 6
• Treatment should be initiated and supervised by physicians experienced in the diagnosis and management of ILD 2

Monitoring Requirements

• Liver function tests 2, 1:
  • Prior to treatment initiation
  • Monthly for the first 6 months
  • Every 3 months thereafter
• Regular assessment of clinical tolerance 2
• Monitoring for disease progression with pulmonary function tests 2