What is the recommended dosage of pirfenidone (Idiopathic Pulmonary Fibrosis (IPF) treatment) for Interstitial Lung Disease (ILD)?

Pirfenidone Dosage for Interstitial Lung Disease (ILD)

The recommended dosage of pirfenidone for mild-to-moderate ILD is 801 mg three times daily (2,403 mg/day), titrated over 14 days to minimize side effects. 1, 2

Dosing Protocol

Pirfenidone requires a careful titration schedule to reach the full therapeutic dose:

1. Initial titration period (14 days):

   • 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) 1

2. Administration guidelines:

   • Take with food at the same time each day
   • Do not take more than 3 doses per day
   • Do not take 2 doses at the same time to make up for a missed dose 1

Patient Selection

Pirfenidone is primarily indicated for:

• Idiopathic pulmonary fibrosis (IPF) 1
• Mild-to-moderate disease (defined as FVC ≥50% predicted and DLCO ≥35% predicted) 2

Monitoring Requirements

• Before starting: Baseline liver function tests 1
• During treatment:
  • Monthly liver function tests for first 6 months
  • Every 3 months thereafter 2
  • Regular assessment of clinical tolerance and adverse effects

Dosage Modifications

For adverse reactions:

• If treatment is interrupted for ≥14 days: Re-initiate with the 2-week titration regimen
• If interruption is <14 days: Resume at previous dosage 1

For liver enzyme elevations:

• ALT/AST >3 but ≤5 × ULN without symptoms: May maintain, reduce, or interrupt dosage
• ALT/AST >3 but ≤5 × ULN with symptoms or hyperbilirubinemia: Permanently discontinue
• ALT/AST >5 × ULN: Permanently discontinue 1

For drug interactions:

• With strong CYP1A2 inhibitors (e.g., fluvoxamine): Reduce to 267 mg three times daily
• With moderate CYP1A2 inhibitors (e.g., ciprofloxacin 750 mg twice daily): Reduce to 534 mg three times daily 1

Clinical Efficacy

Pirfenidone has demonstrated efficacy in slowing disease progression:

• Reduces decline in forced vital capacity (FVC) 2
• Reduces risk of disease progression by 30% 2
• May reduce IPF-related mortality (HR 0.48,95% CI 0.24–0.95) 2

Common Adverse Effects

• Gastrointestinal: Nausea, dyspepsia, diarrhea, vomiting, anorexia
• Skin-related: Photosensitivity reactions, rash
• Other: Fatigue, dizziness 2, 3

Important Precautions

• Contraindications: Fluvoxamine use, severe hepatic or renal impairment 2
• Smoking: Must be discontinued prior to and during treatment (increases metabolism of pirfenidone) 2
• UV exposure: Patients should be warned against UV exposure due to photosensitivity risk 2
• Drug interactions: Avoid concomitant use of omeprazole (may alter pirfenidone pharmacokinetics) 2

Clinical Pearls

• Tablet formulation (801 mg) reduces pill burden compared to capsules (267 mg) 3
• Gastrointestinal side effects are common but generally manageable 3
• Treatment should be initiated and supervised by physicians experienced in the diagnosis and management of IPF 2
• While primarily indicated for IPF, emerging evidence suggests potential benefit in other progressive fibrotic ILDs 4

Emerging Evidence

Recent research suggests pirfenidone may attenuate disease progression in non-IPF fibrotic ILDs, including:

• Connective tissue disease-associated ILDs
• Fibrotic non-specific interstitial pneumonia
• Chronic hypersensitivity pneumonitis
• Asbestos-induced lung fibrosis 4

However, this evidence is still emerging and the primary approved indication remains IPF 2, 4.