Pirfenidone

Indications

Pirfenidone is used for: Idiopathic pulmonary fibrosis.

Adult Dose

Oral Idiopathic pulmonary fibrosis Adult: Initially, 267 mg tid for 7 days, then increase dose to 534 mg tid for 7 days, then to usual maintenance dose: 801 mg tid. Max: 2403 mg daily. Adjust dosage according to toxicity.

Child Dose

Renal Dose

ESRD requiring haemodialysis: Contraindicated. CrCl (mL/min) Dosage <30 Contraindicated.

Administration

Contra Indications

Severe hepatic and renal impairment, ESRD requiring haemodialysis.

Precautions

Smokers. Mild to moderate hepatic and renal impairment. Pregnancy and lactation. Patient taking fluvoxamine and ciprofloxacin.

Pregnancy-Lactation

Interactions

Increased toxicity with strong (e.g. fluvoxamine) and moderate (e.g. ciprofloxacin) CYP1A2 inhibitors. Decreased efficacy with CYP1A2 inducers (e.g. omeprazole).

Adverse Effects

Side effects of Pirfenidone : Significant: Nausea, vomiting, diarrhoea, dyspepsia, GERD, abdominal pain, photosensitivity, weight loss, dizziness, increased ALT/AST, angioedema. Rarely, hyperbilirubinaemia. Gastrointestinal disorders: Constipation, flatulence, gastritis. General disorders and administration site conditions: Fatigue, asthenia, lethargy, non-cardiac chest pain. Investigations: Increased γ-glutamyl transferase. Metabolism and nutrition disorders: Anorexia, decreased appetite. Musculoskeletal and connective tissue disorders: Myalgia, arthralgia. Nervous system disorders: Headache, dysgeusia. Psychiatric disorders: Insomnia, somnolence. Renal and urinary disorders: UTI. Respiratory, thoracic and mediastinal disorders: Dyspnoea, cough, upper respiratory tract infection. Skin and subcutaneous tissue disorders: Rash, pruritus, erythema, dry skin, sunburn. Vascular disorders: Hot flush.

Mechanism of Action

Pirfenidone, a synthetic pyridone, is an antifibrotic agent. Its exact mechanism of action is still unknown. In idiopathic pulmonary fibrosis, it may decrease the amount of pro-inflammatory cells [e.g. interleukin-1-β (IL-1β), IL-6, tumour necrosis factor-α (TNF-α)] and the production of fibroblast and of fibrosis-associated proteins and cytokines. It may also decrease accumulation of extracellular matrix and lung fibrosis due to transforming growth factor-β (TGF-β) and platelet derived growth factor (PDGF).