Pirfenidone Dosage and Treatment Protocol for Idiopathic Pulmonary Fibrosis
Pirfenidone should be administered at a maintenance dose of 801 mg three times daily (total 2,403 mg/day) with food, following a 14-day titration period to minimize adverse effects. 1
Patient Selection
- Pirfenidone is indicated for patients with mild-to-moderate idiopathic pulmonary fibrosis (IPF), defined as FVC > 50% predicted and DLCO > 35% predicted 2, 3
- Treatment should be initiated and supervised by physicians experienced in the diagnosis and management of IPF 2, 3
- Pirfenidone is contraindicated in patients taking fluvoxamine and those with severe hepatic or renal impairment 2
Dosing Protocol
Initial Titration (14-day period)
- Days 1-7: 267 mg three times daily (801 mg/day) 1
- Days 8-14: 534 mg three times daily (1,602 mg/day) 1
- Days 15 onward: 801 mg three times daily (2,403 mg/day) 1
Administration Guidelines
- All doses should be taken with food at the same time each day 1
- Patients should not take more than 3 doses per day 1
- If a dose is missed, patients should not take 2 doses at the same time to make up for it 1
Pre-Treatment Assessment and Monitoring
Before Starting Treatment
- Conduct liver function tests 1
- Assess baseline pulmonary function (FVC, DLCO) 2, 3
- Ensure patient is not smoking (must be discontinued prior to treatment) 2, 3
- Verify patient is not taking contraindicated medications (fluvoxamine) 2
Ongoing Monitoring
- Liver function tests: monthly for first 6 months, then every 3 months thereafter 2, 3
- Regular assessment of clinical tolerance and disease progression 2, 3
- Monitor for photosensitivity reactions and advise patients about UV protection 2, 1
Dosage Modifications
For Adverse Reactions
- For significant adverse reactions (gastrointestinal, photosensitivity, rash), consider temporary dosage reductions or interruptions 1
- If treatment is interrupted for ≥14 days, restart with the initial 2-week titration regimen 1
- If treatment is interrupted for <14 days, resume at the previous dosage 1
For Elevated Liver Enzymes
- ALT/AST >3 but ≤5 × ULN without symptoms: Monitor closely, maintain or reduce dose as clinically appropriate 1
- ALT/AST >3 but ≤5 × ULN with symptoms or hyperbilirubinemia: Permanently discontinue pirfenidone 1
- ALT/AST >5 × ULN: Permanently discontinue pirfenidone 1
For Drug Interactions
- With strong CYP1A2 inhibitors (e.g., fluvoxamine): Reduce pirfenidone to 267 mg three times daily 1
- With moderate CYP1A2 inhibitors (e.g., ciprofloxacin 750 mg twice daily): Reduce pirfenidone to 534 mg three times daily 1
- Avoid concomitant use of omeprazole as it may alter pirfenidone pharmacokinetics 2, 3
Clinical Efficacy
- Pirfenidone reduces the risk of disease progression by approximately 30% compared to placebo 2, 3, 4
- Treatment significantly reduces the decline in FVC in patients with mild-to-moderate IPF 2, 4
- Real-world data shows an average decline in %FVC of only -0.75% after 12 months of treatment 5
Common Adverse Effects
- Most common adverse reactions (≥10%): nausea, rash, abdominal pain, upper respiratory tract infection, diarrhea, fatigue, headache, decreased appetite, dyspepsia, dizziness, vomiting, gastroesophageal reflux disease 1
- Photosensitivity reactions are common; patients must be warned about UV exposure and advised to use sunscreen and protective clothing 2, 3, 1
- Liver enzyme elevations may occur; regular monitoring is essential 2, 1
Important Precautions
- Smoking increases pirfenidone metabolism and should be discontinued prior to and during treatment 2, 3
- Severe cutaneous adverse reactions (SCAR) including Stevens-Johnson syndrome have been reported; permanently discontinue if SCAR is confirmed 1
- Annual influenza vaccination and anti-pneumococcal vaccination are recommended for patients with IPF 2