Brand Name: PIRFEDONE
Generic Name: Pirfenidone
Preparation: 200 mg / 400 mg Tablet
Pharmacological Category: Antifibrotic agent

Mechanism of Action (MOA)
Precise mechanism of action has not been fully elucidated. However, existing data suggests that PIRFEDONE (Pirfenidone) exerts both antifibrotic and anti-inflammatory properties.
PIRFEDONE attenuates fibroblast proliferation, production of fibrosis-associated proteins and cytokines, and increased biosynthesis and accumulation of extracellular matrix in response to cytokine growth factors such as, transforming growth factor-beta (TGF-β) and platelet-derived growth factor (PDGF).

Also, PIRFEDONE has been shown to reduce the accumulation of inflammatory cells in response to various stimuli.

 

Pharmacokinetics
Absorption: Gastrointestinal tract
Peak Plasma Time: 0.5 to 4 hours
Protein Binding: 58%
Metabolism: Liver (primarily by CYP1A2 into major metabolite, 5-carboxy-pirfenidone0
Elimination Half-life: 2.4 hours
Excretion: About 80% via urine; less than 1% as unchanged drug

Indications and Dosage
Mild to moderate idiopathic pulmonary fibrosis: To be taken with food
Initial dose titration:
Days 1-7: 200 mg TID
Days 8-14: 400 mg TID
Days 15 and thereafter: 800 mg TID

Maintenance dose:
800 mg TID with food
Not to exceed 2400 mg/day

If 14 or more consecutive days of treatment are missed, treatment should be restarted using the 2-week titration schedule. If the interruption in treatment is less thant 14 days, treatment can be resumed at the previous daily dose without titration.

Side Effects
COMMON: Nausea, diarrhoea, dyspepsia, fatigue, rash, photosensitivity reactions, dizziness, and weight loss
OTHERS: Jaundice, hepatic failure, and blood dyscrasias such as agranulocytosis, leucopenia, and neutropenia
Reported: Raised liver transaminases

Contraindications
Hypersensitivity, history of angioedema, concomitant use of fluvoxamine, severe hepatic impairment or end liver disease, and severe renal impairment (creatinine clearance < 30 ml/min) or end stage renal disease requiring dialysis

Warnings/ Precautions
• Liver function tests should be carried out before starting treatment and at monthly intervals for the first 6 months of treatment, then every 3 months thereafter.
• Caution to avoid or minimize expose to direct sunlight and to apply sunblock daily during treatment.
• Caution in driving or operating machinery.

Drug Interactions
• Fluvoxamine inhibits metabolism of pirfenidone resulting in a significant increase in pirfenidone exposure, and therefore concomitant administration of these two drugs is contraindicated.
• Tobacco smoking has been reported to increase the clearance of pirfenidone by 50%.

Pregnancy Category: No data is available; however, it is preferable to avoid the use during pregnancy.

Presentation
PIRFEDONE: 10 X 10’s