Overview
11 DESCRIPTION Pirfenidone, USP belongs to the chemical class of pyridone. Pirfenidone capsules, USP are available as a opaque white to off-white hard gelatin capsule containing 267 mg of pirfenidone, USP for oral administration. Pirfenidone, USP has a molecular formula of C12H11NO and a molecular weight of 185.22 g/mol.
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action The mechanism of action of pirfenidone in the treatment of IPF has not been established. 12.2 Pharmacodynamics Cardiac Electrophysiology The effect of pirfenidone on QT interval was evaluated in a randomized, placebo, and positive controlled parallel study in 160 healthy adult volunteers. Volunteers received pirfenidone 2,403 mg/day (recommended dose) and 4,005 mg/day (1.6 times recommended dose) or placebo for 10 days or a single-dose of 400 mg moxifloxacin (active control). Relative to placebo, the maximum mean change from baseline in study-specific QT interval was 3.2 milliseconds (ms) and 2.2 ms for pirfenidone 2,403 mg/day and 4,005 mg/day, respectively.
Indications
- 1 INDICATIONS AND USAGE Pirfenidone capsules are indicated for the treatment of idiopathic pulmonary fibrosis (IPF). Pirfenidone is a pyridone indicated for the treatment of idiopathic pulmonary fibrosis (IPF). (1)
Common Doses
- 801 mg
- 403 mg
- 267 mg
- 534 mg
Dosage
2 DOSAGE AND ADMINISTRATION Take with food. Recommended dosage: 801 mg three times daily (2,403 mg/day). (2) Upon initiation of treatment, titrate to the full dosage of 2,403 mg/day over a 14-day period as follows: Treatment days Dosage Days 1 through 7 267 mg three times daily (801 mg/day) Days 8 through 14 534 mg three times daily (1,602 mg/day) Days 15 onward 801 mg three times daily (2,403 mg/day) Consider temporary dosage reduction, treatment interruption, or discontinuation for management of adverse reactions. ( 2.3 , 5.1 , 5.2 , 5.3 , 5.
Contraindications
- 4 CONTRAINDICATIONS None. None
Side Effects
- 6 ADVERSE REACTIONS The following adverse reactions are discussed in greater detail in other sections of the labeling: Liver Enzyme Elevations and Drug-Induced Liver Injury [see Warnings and Precautions (5.1) ] Photosensitivity Reaction or Rash [see Warnings and Precautions (5.2) ] Severe Cutaneous Adverse Reactions [see Warnings and Precautions (5.3) ] Gastrointestinal Disorders [see Warnings and Precautions (5.4) ] The most common adverse reactions (≥ 10%) are nausea, rash, abdominal pain, upper respiratory tract infection, diarrhea, fatigue, headache, decreased appetite, dyspepsia,...
Interactions
- 7 DRUG INTERACTIONS Moderate (e.g., ciprofloxacin) and strong inhibitors of CYP1A2 (e.g., fluvoxamine) increase systemic exposure of pirfenidone and may alter the adverse reaction profile of pirfenidone. Discontinue fluvoxamine prior to administration of pirfenidone or reduce to 267 mg three times a day. Consider dosage reduction with use of ciprofloxacin. ( 7.1 ) 7.1 CYP1A2 Inhibitors Pirfenidone is metabolized primarily (70% to 80%) via CYP1A2 with minor contributions from other CYP isoenzymes including CYP2C9, 2C19, 2D6 and 2E1.