What are the common adverse effects of Esbriet (pirfenidone) and how are they managed?

Common Adverse Effects of Esbriet (Pirfenidone) and Their Management

The most common adverse effects of Esbriet (pirfenidone) include gastrointestinal symptoms, photosensitivity reactions, rash, fatigue, and liver enzyme elevations, which require regular monitoring and specific management strategies to ensure treatment adherence and optimize outcomes. 1

Most Common Adverse Effects

Gastrointestinal Effects

• Nausea: Affects 36% of patients (vs 16% on placebo) 1
• Diarrhea: Affects 26% of patients (vs 20% on placebo) 1
• Abdominal pain: Affects 24% of patients (vs 15% on placebo) 1
• Dyspepsia: Affects 19% of patients (vs 7% on placebo) 1
• Vomiting: Affects 13% of patients (vs 6% on placebo) 1
• Gastroesophageal reflux disease: Affects 11% of patients (vs 7% on placebo) 1

Dermatological Effects

• Rash: Affects 30% of patients (vs 10% on placebo) 1
• Photosensitivity reactions: Affects 9% of patients (vs 1% on placebo) 1
• Pruritus: Affects 8% of patients (vs 5% on placebo) 1
• Severe cutaneous adverse reactions (SCAR): Reported in post-marketing surveillance 1

Other Common Effects

• Fatigue: Affects 26% of patients (vs 19% on placebo) 1
• Decreased appetite: Affects 21% of patients (vs 8% on placebo) 1
• Dizziness: Affects 18% of patients (vs 11% on placebo) 1
• Weight decreased: Affects 10% of patients (vs 5% on placebo) 1
• Insomnia: Affects 10% of patients (vs 7% on placebo) 1

Management Strategies

Gastrointestinal Adverse Effects

1. Take with food: Administer pirfenidone with food at the same time each day to decrease nausea and dizziness 1
2. Dosage modification: Required in 18.5% of patients (vs 5.8% on placebo) 1
   • Temporary dose reduction or interruption may be necessary
   • Gradually titrate dose when restarting
3. Supportive medications: Consider anti-emetics for nausea or anti-diarrheal agents for diarrhea
4. Monitoring: Gastrointestinal events are highest early in treatment (first 3 months) and typically decrease over time 1

Photosensitivity and Skin Reactions

1. Sun protection: Use SPF 50 sunscreen, wear protective clothing and hats 1
2. Avoid UV exposure: Limit sun exposure and avoid tanning beds 2, 1
3. Patient education: Warn patients about photosensitivity risk before starting treatment 2
4. Topical steroids: For mild to moderate skin reactions 3
5. Severe reactions: May require systemic steroids and temporary drug discontinuation in severe cases 4

Liver Enzyme Elevations

1. Baseline testing: Perform liver function tests before starting treatment 2
2. Regular monitoring: Monthly for first 6 months, then every 3 months thereafter 2, 1
3. Dose adjustment: Modify dose or interrupt treatment based on severity of enzyme elevations 1
4. Contraindications: Avoid in patients with severe hepatic impairment 2

Other Management Considerations

1. Smoking cessation: Patients must not smoke during pirfenidone treatment as smoking increases enzyme activity involved in pirfenidone metabolism 2
2. Drug interactions:
   • Avoid fluvoxamine and other strong CYP1A2 inhibitors 1
   • Avoid concomitant use of omeprazole as it may alter pirfenidone pharmacokinetics 2
   • Dose adjustments needed with ciprofloxacin and other moderate CYP1A2 inhibitors 1

Monitoring Protocol

1. Liver function: Before treatment initiation, monthly for 6 months, then every 3 months 2
2. Clinical assessment: Regular evaluation of adverse effects, especially during first 3 months
3. Weight monitoring: Due to decreased appetite and weight loss potential
4. Skin examination: Regular assessment for rash or photosensitivity reactions

Discontinuation Rates and Considerations

• 14.6% of patients on pirfenidone permanently discontinued treatment due to adverse events (vs 9.6% on placebo) 1
• Most common reasons for discontinuation were rash and nausea 1
• Most common reasons for dose reduction were rash, nausea, diarrhea, and photosensitivity 1

Special Considerations

• Elderly patients: No specific dose adjustment required, but monitor more closely
• Renal impairment: Avoid in severe renal impairment 1
• Hepatic impairment: Avoid in severe hepatic impairment 2, 1
• Pregnancy: Not recommended as safety has not been established 1

By understanding and proactively managing these adverse effects, clinicians can help patients maintain adherence to pirfenidone therapy, which has been shown to reduce disease progression in IPF by slowing the decline in lung function and improving progression-free survival 2, 5.