1. Clinical Overview
Pirfenidone is an orally administered antifibrotic agent, specifically indicated for the treatment of mild to moderate Idiopathic Pulmonary Fibrosis (IPF). It is a pyridone derivative that modulates multiple pathways involved in fibrosis, including the suppression of pro-fibrotic and pro-inflammatory cytokines. In the Indian context, it is a critical therapy for slowing disease progression in IPF, a condition with limited treatment options and poor prognosis.
| Onset | Duration | Bioavailability |
|---|---|---|
| Therapeutic effects on disease progression are observed over months of treatment. Clinical trials (CAPACITY, ASCEND) demonstrated a reduction in the rate of forced vital capacity (FVC) decline over 52 weeks. | The pharmacological effect is sustained with continuous daily dosing. The terminal half-life is approximately 24 hours, supporting a three-times-daily dosing regimen. | Approximately 80% following oral administration under fed conditions. Food significantly increases bioavailability. |
2. Mechanism of Action
Pirfenidone's exact mechanism in IPF is not fully elucidated but is believed to involve the downregulation of key mediators involved in fibroblast proliferation, collagen synthesis, and tissue fibrosis. It exhibits combined anti-fibrotic, anti-inflammatory, and antioxidant properties.
3. Indications & Uses
- Idiopathic Pulmonary Fibrosis (IPF) - mild to moderate disease (as defined by clinical, radiological, and/or histological diagnosis)
4. Dosage & Administration
Adult Dosage: Maintenance dose: 801 mg (three capsules of 267 mg) three times daily (TID) with food, totaling 2403 mg/day. Initiate with a 14-day titration: Days 1-7: 267 mg TID (801 mg/day). Days 8-14: 534 mg TID (1602 mg/day). Day 15 onward: 801 mg TID (2403 mg/day). The 200mg capsule is often used for precise dose adjustment or in combination with other strengths to achieve the target dose.
Administration: ALWAYS administer with food to reduce nausea and dizziness and to enhance absorption. Swallow capsule whole with a full glass of water. Do not crush or chew. If a dose is missed, skip it and take the next dose at the regular time. Do not double the dose.
5. Side Effects
Common side effects may include:
- Nausea
- Dyspepsia (indigestion)
- Vomiting
- Anorexia (loss of appetite)
- Diarrhea
- Photosensitivity reaction or rash
- Fatigue
- Dizziness
- Abdominal discomfort
6. Drug Interactions
| Drug | Effect | Severity |
|---|---|---|
| Fluvoxamine (strong CYP1A2 inhibitor) | Markedly increases pirfenidone exposure (AUC increased by ~240%). Risk of toxicity. | Contraindicated / Major |
| Enoxacin (strong CYP1A2 inhibitor) | Significantly increases pirfenidone exposure. | Contraindicated / Major |
| Ciprofloxacin (moderate CYP1A2 inhibitor) | Increases pirfenidone exposure. Consider dose reduction or monitor for adverse effects. | Moderate |
| Omeprazole (CYP2C19 inducer) | May moderately decrease pirfenidone exposure. | Moderate |
| Smoking/Tobacco (CYP1A2 inducer) | Decreases pirfenidone exposure by up to 50%. May reduce efficacy. Patients should be advised to quit smoking. | Moderate |
| Other photosensitizing drugs (e.g., tetracyclines, fluoroquinolones, phenothiazines) | Increased risk of severe photosensitivity. | Moderate |
7. Patient Counselling
- DO take with food at the same times each day.
- DO complete the 2-week dose escalation as prescribed.
- DO use broad-spectrum sunscreen (SPF 50+), wear protective clothing, and avoid direct sunlight/UV light (including tanning beds).
- DO report any nausea, vomiting, rash, fatigue, or yellowing of skin/eyes to your doctor.
- DO attend all scheduled appointments for lung function and liver tests.
- DONT smoke, as it reduces the drug's effectiveness.
- DONT crush or chew the capsules.
- DONT take a double dose if you miss one.
- DONT start any new medication (including OTC, herbal) without consulting your doctor.
8. Toxicology & Storage
Overdose: Symptoms may include severe nausea, vomiting, dizziness, lethargy, and photosensitivity. No specific experience with massive overdose.
Storage: Store at room temperature (15°C to 30°C). Protect from light and moisture. Keep in the original blister pack or container. Keep out of reach of children.