What is the recommended treatment for Idiopathic Pulmonary Fibrosis (IPF)?

Treatment of Idiopathic Pulmonary Fibrosis

Start antifibrotic therapy with either pirfenidone or nintedanib immediately upon diagnosis in all patients with IPF, as these are the only two medications proven to slow disease progression and reduce mortality risk. 1, 2

First-Line Antifibrotic Therapy

Both pirfenidone and nintedanib should be initiated early—do not wait for disease progression or functional decline, as FVC decline is linear regardless of baseline severity. 2, 3

Pirfenidone Dosing

• Titrate over 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) 4
• Take with food at the same time each day 4
• Approved for mild-to-moderate IPF (FVC >50% predicted, DLCO >35% predicted), though this restriction may limit early treatment opportunities 1, 2
• Reduces progression-free survival risk by 30% compared to placebo 1, 2

Nintedanib Dosing

• Standard dose: 150 mg twice daily 1
• Demonstrated efficacy in slowing FVC decline in phase 2 and 3 trials 1, 2
• Intracellular tyrosine kinase inhibitor targeting VEGF, FGF, and PDGF receptors 1

Choosing Between Pirfenidone and Nintedanib

Both drugs have similar efficacy in slowing FVC decline. Base your choice on side effect profile and patient comorbidities: pirfenidone causes more photosensitivity and GI upset (nausea predominant), while nintedanib causes more diarrhea. 2, 5

Critical Therapies to AVOID

These treatments are contraindicated and can cause harm:

• Triple therapy (prednisone + azathioprine + N-acetylcysteine): NEVER USE. The PANTHER-IPF trial was stopped early due to increased mortality and hospitalizations. 1, 2, 6
• Ambrisentan (selective endothelin receptor antagonist): CONTRAINDICATED. Causes documented respiratory decline and disease progression. 1, 2, 6
• Warfarin and oral anticoagulants: Do not use for IPF treatment in patients without other indications. 1, 2
• Interferon gamma-1b: Strong recommendation against use based on lack of survival benefit in 826-patient INSPIRE trial. 2
• Corticosteroid monotherapy: NOT recommended as no RCTs demonstrate efficacy. 1, 6

Essential Adjunctive Therapies

Gastroesophageal Reflux Management

Prescribe proton pump inhibitors (PPIs) or H2-receptor antagonists to ALL IPF patients regardless of symptoms. Up to 90% have abnormal GER (often silent), and observational data shows survival benefit (HR 0.47; 95% CI 0.24-0.93) and smaller FVC decline (mean difference 0.07 L; P=0.05). 2

Supplemental Oxygen

Prescribe for patients with oxygen saturation <88% during 6-minute walk test or resting hypoxemia. 2, 6

Vaccinations

• Annual influenza vaccination: Required 1, 2, 6
• Pneumococcal vaccination: Required (use polysaccharide pneumococcal vaccine) 1, 2, 6

Pulmonary Rehabilitation

Recommend for all patients with exercise limitation—improves walking distance, symptoms, and quality of life. 1, 2

Monitoring Requirements

Pulmonary Function Tests

• Perform FVC and DLCO every 3-6 months to assess treatment response and disease progression 2, 6, 7
• Monitor oxygen saturation at rest and with exercise at each visit 2

Liver Function Monitoring (for Pirfenidone)

• Before starting treatment: Check ALT, AST, and bilirubin 4
• Monthly for first 6 months, then every 3 months thereafter 1, 2, 4
• If ALT/AST >3-5× ULN without symptoms: Discontinue confounding medications, monitor closely, may continue full dose or reduce/interrupt 4
• If ALT/AST >3-5× ULN WITH symptoms or hyperbilirubinemia: Permanently discontinue pirfenidone 4
• If ALT/AST >5× ULN: Permanently discontinue pirfenidone 4

Managing Adverse Effects

Pirfenidone Side Effects

Most common (≥10%): nausea, rash, photosensitivity, fatigue, diarrhea, dyspepsia 1, 4

Management strategies:

• For GI symptoms: Take with food, consider temporary dose reduction 1, 4
• For photosensitivity: Avoid sun exposure, wear sunscreen (SPF 50+) and protective clothing daily, consider temporary dose reduction 1, 4
• For rash: May require temporary interruption or dose reduction 4
• If Stevens-Johnson syndrome, TEN, or DRESS suspected: Interrupt immediately; if confirmed, permanently discontinue 4

Nintedanib Side Effects

Most common: diarrhea (most frequent), nausea, abdominal pain, vomiting, elevated liver enzymes 6, 7

Management: Dose reduction or temporary interruption for severe diarrhea 6

Dose Modification Protocol

• If patient misses <14 days: Resume prior dose 4
• If patient misses ≥14 days: Re-titrate over 14 days 4
• Temporary dose reductions are effective at managing side effects without compromising efficacy 3

Drug Interactions (Pirfenidone)

• Fluvoxamine (strong CYP1A2 inhibitor): Discontinue before starting pirfenidone OR reduce pirfenidone to 267 mg three times daily (801 mg/day) 4
• Ciprofloxacin (moderate CYP1A2 inhibitor): Consider dose reduction 4
• Smoking: Discontinue prior to and during treatment (increases pirfenidone metabolism) 1
• Omeprazole: Avoid concomitant use (may alter pirfenidone pharmacokinetics) 1

Lung Transplantation Referral

Refer ALL patients aged <65 years to a transplant center at the time of diagnosis for early evaluation. Do not wait for severe disease. 1, 2, 6

Transplant should be strongly considered when:

• DLCO <39% predicted 1
• FVC decline >10% over 6 months 1
• Severe or worsening disease despite antifibrotic therapy 2, 6

The age limit of <65 years is relative and depends on physiological age and comorbidities. 1 Lung transplantation is the only treatment proven to increase life expectancy in IPF. 2

Common Pitfalls to Avoid

1. Waiting for disease progression before starting antifibrotics: FVC decline is linear from diagnosis—early treatment preserves more lung function 3, 8
2. Discontinuing therapy due to mild side effects: Most patients tolerate treatment with dose adjustments 3, 5
3. Using corticosteroids or immunosuppressants: These are harmful in IPF and increase mortality 1, 2
4. Missing silent GER: Treat all IPF patients with PPIs regardless of symptoms 2
5. Delaying transplant referral: Refer at diagnosis, not when FVC is already severely reduced 2, 6