What is the recommended treatment and management plan for an older adult patient, typically over 60 years old, with a history of respiratory issues and possibly a history of smoking, diagnosed with idiopathic pulmonary fibrosis (IPF) and prescribed Pirfenidone (Pirfenidone)?

Pirfenidone Treatment for Idiopathic Pulmonary Fibrosis

Pirfenidone 2,403 mg/day (801 mg three times daily with food) is recommended for patients with mild-to-moderate IPF, defined as FVC >50% predicted and DLCO >35% predicted, and must be initiated and supervised by a physician experienced in IPF management. 1

Patient Eligibility and Initiation

Confirm the patient meets diagnostic and severity criteria:

• Clinically and radiologically confirmed IPF diagnosis 1
• FVC >50% predicted and DLCO >35% predicted (mild-to-moderate disease) 1, 2
• Age typically 40-80 years (mean 67 years in clinical trials) 3

Exclude contraindications before starting:

• Severe hepatic or renal impairment 1
• Concurrent fluvoxamine use (strong CYP1A2 inhibitor) 1, 3
• Perform baseline liver function tests (ALT, AST, bilirubin) 1, 3

Dosing and Titration

Standard 14-day titration schedule (recommended for most patients): 3

• 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)

Alternative slower titration schedules (4-8 weeks) may be used for patients with gastrointestinal intolerance, with most patients ultimately achieving full dose. 4

Critical administration requirement:

• Take all doses with substantial meals to minimize gastrointestinal adverse events 4

Mandatory Smoking Cessation

The patient must completely discontinue smoking before and during pirfenidone treatment, as smoking increases pirfenidone metabolism through CYP1A2 enzyme induction, reducing drug efficacy. 1, 2

Monitoring Requirements

Liver function monitoring schedule: 1, 2, 3

• Baseline: ALT, AST, and bilirubin before treatment initiation
• Monthly for the first 6 months
• Every 3 months thereafter

Pulmonary function monitoring:

• Regular assessment of FVC and DLCO to evaluate disease progression 2
• Disease progression defined as ≥10% decline in FVC or ≥15% decline in DLCO 1

Clinical tolerance assessment at each visit for adverse events 1, 2

Expected Efficacy

Pirfenidone reduces disease progression by 30% (HR 0.70,95% CI 0.56-0.88) and slows FVC decline compared to placebo. 1, 2

In clinical trials:

• Mean FVC decline was -235 mL with pirfenidone versus -428 mL with placebo (193 mL treatment difference) at 52 weeks 3
• Approximately 62-70% of patients maintain stable disease on treatment 5, 6

Adverse Event Management

Gastrointestinal events (most common): 1, 3

• Nausea, diarrhea, dyspepsia, vomiting, gastroesophageal reflux, abdominal pain
• Management: Ensure dosing with substantial meals, consider temporary dose reduction or treatment interruption 3, 4
• Approximately 85% of patients experience some adverse events, but most are manageable 5

Photosensitivity and rash: 1, 2, 3

• Warn patients to avoid UV exposure and sunlight
• Recommend daily sunscreen use, sun avoidance, wearing hats, and UV-protective clothing 4
• Consider temporary dose reduction if severe

Severe cutaneous adverse reactions (rare but serious): 3

• Stevens-Johnson syndrome, toxic epidermal necrolysis, DRESS syndrome reported in postmarketing surveillance
• Interrupt pirfenidone immediately if signs/symptoms occur
• Permanently discontinue if confirmed

Hepatotoxicity: 3

• Drug-induced liver injury, including fatal cases, reported in postmarketing surveillance
• If ALT/AST elevations occur, consider dose reduction or temporary interruption based on severity
• Discontinue if severe liver injury develops

Drug Interactions to Avoid

Fluvoxamine (strong CYP1A2 inhibitor): 1, 3

• Contraindicated—discontinue before pirfenidone initiation or reduce pirfenidone to 267 mg three times daily if unavoidable

Ciprofloxacin (moderate CYP1A2 inhibitor): 3

• Consider pirfenidone dose reduction during concurrent use

Omeprazole: 1, 2

• Avoid concomitant use as it may alter pirfenidone pharmacokinetics

Adjunctive Management

Vaccinations (strongly recommended): 1

• Annual influenza vaccination
• Pneumococcal vaccination (polysaccharide vaccine)

Long-term oxygen therapy: 1

• Initiate if severe hypoxemia at rest develops (severe chronic respiratory failure)

Pulmonary rehabilitation: 1

• Consider for patients with exercise limitation causing significant impairment
• May include exercise training, psychosocial support, and supportive care

Lung transplantation evaluation: 1

• Refer patients <65 years with severe or worsening disease for early transplant assessment
• Provide information about transplantation early in disease course

Treatment Discontinuation Considerations

Approximately 13-20% of patients discontinue pirfenidone due to adverse events, most commonly gastrointestinal intolerance. 5, 6

Reasons to consider discontinuation:

• Unmanageable adverse events despite dose modifications
• Confirmed severe cutaneous adverse reaction 3
• Severe drug-induced liver injury 3
• Disease progression to advanced stage where rehabilitation is no longer feasible 1

Common Pitfalls to Avoid

• Failing to ensure complete smoking cessation before treatment initiation 1, 2
• Not dosing with substantial meals, leading to increased gastrointestinal adverse events 4
• Inadequate liver function monitoring, missing early hepatotoxicity 1, 3
• Not warning patients about photosensitivity and UV protection measures 1, 2
• Prescribing to patients with severe disease (FVC <50% or DLCO <35%) outside approved indications 1
• Concurrent use of contraindicated medications (fluvoxamine, omeprazole) 1, 3