Fenidone

• Approved Indications:
  Treatment of idiopathic pulmonary fibrosis (IPF) to slow disease progression and improve lung function.
• Off-label/Clinically Accepted Uses:
  Investigational use in other fibrotic diseases such as systemic sclerosis-related interstitial lung disease (SSc-ILD) and liver fibrosis (ongoing clinical trials). Occasionally used in other chronic fibrotic conditions under specialist supervision.

• Route: Oral capsules/tablets.
• Adults:
• Initiation phase: 267 mg three times daily (TID) for the first week.
• Titration phase: 534 mg TID during the second week.
• Maintenance dose: 801 mg TID (total daily dose 2,403 mg) from the third week onward, depending on tolerability.
• Elderly:
  No specific dosage adjustment, but monitor closely for side effects.
• Renal impairment:
  Not recommended in severe renal impairment (eGFR <30 mL/min). Use with caution in mild to moderate impairment; no formal dose adjustment.
• Hepatic impairment:
  Not recommended in moderate or severe hepatic impairment.
• Duration:
  Long-term continuous treatment is recommended unless intolerance or contraindications develop.

Pirfenidone has antifibrotic, anti-inflammatory, and antioxidant effects. It inhibits the production of transforming growth factor-beta (TGF-β) and tumor necrosis factor-alpha (TNF-α), which are critical in promoting fibrosis. By suppressing fibroblast proliferation and collagen synthesis, pirfenidone decreases the accumulation of extracellular matrix in lung tissue, thereby slowing fibrosis progression and preserving lung function in idiopathic pulmonary fibrosis.b

• Absorption: Rapid oral absorption with peak plasma levels achieved within 0.5 to 4 hours; bioavailability is increased when taken with food.
• Distribution: Moderate volume of distribution (~70 L); highly protein-bound (~99%).
• Metabolism: Metabolized primarily in the liver by CYP1A2 to inactive metabolites; minor metabolism by CYP2C9, CYP2C19, and CYP2D6.
• Elimination: Excreted mainly as metabolites in urine (~80%) and feces (~15%).
• Half-life: Approximately 2.4 to 2.9 hours.
• Onset of effect: Clinical benefits generally observed after several weeks of therapy.

• Pregnancy: FDA pregnancy category C. Animal studies have shown adverse effects at high doses. Use during pregnancy only if the potential benefit justifies the potential risk.
• Lactation: It is unknown if pirfenidone is excreted into human milk. Caution is advised; breastfeeding is generally not recommended during treatment.

• Antifibrotic agent

• Known hypersensitivity to pirfenidone or any of its excipients.
• Severe hepatic impairment.
• Severe renal impairment (eGFR <30 mL/min).
• Concomitant use with strong CYP1A2 inhibitors due to increased risk of toxicity.

• Monitor liver function tests prior to treatment initiation, monthly for the first 6 months, and periodically thereafter.
• Patients should be advised to avoid excessive sun exposure and use sun protection due to risk of photosensitivity.
• Gastrointestinal adverse effects are common; administration with food reduces these effects.
• Use caution in patients with mild to moderate renal or hepatic impairment.
• Avoid concomitant use with strong CYP1A2 inhibitors such as fluvoxamine.
• Discontinue treatment immediately if severe liver injury or serious skin reactions occur.

• Common:
  Nausea, dyspepsia, diarrhea, vomiting, anorexia, rash, photosensitivity reactions, dizziness, fatigue, headache.
• Serious (rare):
  Elevated liver enzymes, hepatitis, severe skin reactions (e.g., Stevens-Johnson syndrome), worsening of interstitial lung disease.
• Side effects are often dose-dependent and usually improve with dose adjustments or symptomatic treatment.

• Strong CYP1A2 inhibitors (e.g., fluvoxamine) increase pirfenidone plasma concentrations and risk of toxicity.
• CYP1A2 inducers (e.g., cigarette smoking) may reduce pirfenidone efficacy by lowering plasma levels.
• Avoid concomitant use with other hepatotoxic drugs when possible.
• No significant food interactions; however, taking with food reduces gastrointestinal side effects.

• Current guidelines recommend pirfenidone as a first-line antifibrotic agent in idiopathic pulmonary fibrosis.
• Updated safety recommendations emphasize regular liver function monitoring and patient education on photosensitivity risks.
• Ongoing research is evaluating its use in other fibrotic diseases.
• No major recent changes in dosing or approved indications.

• Store at 20°C to 25°C (68°F to 77°F).
• Protect from moisture and light.
• Keep tablets in original packaging until use.
• Do not refrigerate.
• Keep out of reach of children.