Pirfenidone
Tablet, Film Coated · Oral
Uses
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 )
Dosage and administration
Take with food. Recommended dosage: 801 mg three times daily (2403 mg/day). (2) Upon initiation of treatment, titrate to the full dosage of 2403 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 (1602 mg/day) Days 15 onward 801 mg three times daily (2403 mg/day) Consider temporary dosage reduction, treatment interruption, or discontinuation for management of adverse reactions. ( 2.3 , 5.1 , 5.2 , 5.3 , 5.4 ) Prior to treatment, conduct liver function tests. (2.1) 2.1 Testing Prior to Pirfenidone Capsules Administration Conduct liver function tests prior to initiating treatment with pirfenidone capsules [see Warnings and Precautions (5.1) ]. 2.2 Recommended Dosage The recommended daily maintenance dosage of pirfenidone capsules is 801 mg three times daily for a total of 2403 mg/day. Doses should be taken with food at the same time each day. Upon initiation of treatment, titrate to the full dosage of 2403 mg/day over a 14-day period as follows: Table 1. Dosage Titration for Pirfenidone Capsules in Patients with IPF Treatment days Dosage Days 1 through 7 267 mg three times daily (801 mg/day) Days 8 through 14 534 mg three times daily (1602 mg/day) Days 15 onward 801 mg three times daily (2403 mg/day) Dosages above 2403 mg/day are not recommended for any patient. Patients should not take 2 doses at the same time to make up for a missed dose. Patients should not take more than 3 doses per day. 2.3 Dosage Modifications due to Adverse Reactions Patients who miss 14 or more days of pirfenidone capsules should re-initiate treatment by undergoing the initial 2-week titration regimen up to the full maintenance dosage [see Dosage and Administration (2.2) ] . For treatment interruption of less than 14 days, the dosage prior to the interruption can be resumed. If patients experience significant adverse reactions (i.e., gastrointestinal, photosensitivity reaction or rash, severe cutaneous adverse reactions (SCAR)), consider temporary dosage reductions or interruptions of pirfenidone capsules to allow for resolution of symptoms. If a SCAR is confirmed, permanently discontinue pirfenidone capsules [see Warnings and Precautions (5.1 , 5.2 , 5.3 , 5.4) ] . Dosage Modification due to Elevated Liver Enzymes Dosage modifications or interruptions may also be necessary when liver enzyme and bilirubin elevations are exhibited. For liver enzyme elevations, modify the dosage as follows: If a patient exhibits >3 but ≤5 × the upper limit of normal (ULN) ALT and/or AST without symptoms or hyperbilirubinemia after starting pirfenidone capsules therapy: Discontinue confounding medications, exclude other causes, and monitor the patient closely. Repeat liver chemistry tests as clinically indicated. The full daily dosage may be maintained, if clinically appropriate, or reduced or interrupted (e.g., until liver chemistry tests are within normal limits) with subsequent re-titration to the full dosage as tolerated. If a patient exhibits >3 but ≤5 × ULN ALT and/or AST accompanied by symptoms or hyperbilirubinemia: Permanently discontinue pirfenidone capsules. Do not rechallenge patient with pirfenidone capsules. If a patient exhibits >5 × ULN ALT and/or AST: Permanently discontinue pirfenidone capsules. Do not rechallenge patient with pirfenidone capsules. 2.4 Dosage Modification due to Drug Interactions Strong CYP1A2 Inhibitors (e.g., fluvoxamine, enoxacin) Reduce pirfenidone capsules to 267 mg three times a day (801 mg/day). Moderate CYP1A2 Inhibitors (e.g., ciprofloxacin) With use of ciprofloxacin at a dosage of 750 mg twice daily, reduce pirfenidone capsules to 534 mg three times a day (1602 mg/day).
Dosage forms and strengths
Pirfenidone Capsules USP, 267 mg are white opaque cap/white opaque body, hard gelatin capsule shells imprinted with “P 267” on cap with brown ink contains white to off white granular powder. Capsules: 267 mg (3)
Contraindications
None. None
Warnings and precautions
Elevated liver enzymes and drug-induced liver injury: ALT, AST, and bilirubin elevations have occurred with pirfenidone including cases of drug-induced liver injury. In the postmarketing setting, non-serious and serious cases of drug-induced liver injury, including severe liver injury with fatal outcomes, have been reported. Monitor ALT, AST, and bilirubin before and during treatment. Temporary dosage reductions or discontinuations may be required. ( 2.1 , 5.1 ) Photosensitivity and rash: Photosensitivity and rash have been noted with pirfenidone. Avoid exposure to sunlight and sunlamps. Wear sunscreen and protective clothing daily. Temporary dosage reductions or discontinuations may be required. ( 5.2 ) Severe Cutaneous Adverse Reactions (SCAR): Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reactions with eosinophilia and systemic symptoms (DRESS) have been reported in association with the use of pirfenidone in the postmarketing setting. Interrupt pirfenidone in case of signs or symptoms of SCAR. Permanently discontinue pirfenidone if a SCAR is confirmed. ( 5.3 ) Gastrointestinal disorders: Nausea, vomiting, diarrhea, dyspepsia, gastro-esophageal reflux disease, and abdominal pain have occurred with pirfenidone. Temporary dosage reductions or discontinuations may be required. ( 5.4 ) 5.1 Elevated Liver Enzymes and Drug-Induced Liver Injury Cases of drug-induced liver injury (DILI) have been observed with pirfenidone. In the postmarketing period, non-serious and serious cases of DILI, including severe liver injury with fatal outcome, have been reported. Patients treated with pirfenidone 2403 mg/day in three Phase 3 trials had a higher incidence of elevations in ALT or AST ≥3x ULN than placebo patients (3.7% vs 0.8%, respectively). Elevations ≥10xULN in ALT or AST occurred in 0.3% of patients in the pirfenidone 2403 mg/day group and in 0.2% of patients in the placebo group. Increases in ALT and AST ≥3x ULN were reversible with dose modification or treatment discontinuation. Conduct liver function tests (ALT, AST, and bilirubin) prior to the initiation of therapy with pirfenidone, monthly for the first 6 months, every 3 months thereafter, and as clinically indicated. Measure liver function tests promptly in patients who report symptoms that may indicate liver injury, including fatigue, anorexia, right upper abdominal discomfort, dark urine, or jaundice. Dosage modification or interruption may be necessary for liver enzyme elevations [see Dosage and Administration (2.1 , 2.3) ]. 5.2 Photosensitivity Reaction or Rash Patients treated with pirfenidone 2403 mg/day in the three Phase 3 studies had a higher incidence of photosensitivity reactions (9%) compared with patients treated with placebo (1%). The majority of the photosensitivity reactions occurred during the initial 6 months. Instruct patients to avoid or minimize exposure to sunlight (including sunlamps), to use a sunblock (SPF 50 or higher), and to wear clothing that protects against sun exposure. Additionally, instruct patients to avoid concomitant medications known to cause photosensitivity. Dosage reduction or discontinuation may be necessary in some cases of photosensitivity reaction or rash [see Dosage and Administration (2.3) ] . 5.3 Severe Cutaneous Adverse Reactions Severe cutaneous adverse reactions (SCAR), including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS), have been reported in association with the use of pirfenidone in the postmarketing setting. If signs or symptoms of SCAR occur, interrupt pirfenidone treatment until the etiology of the reaction has been determined. Consultation with a dermatologist is recommended. If a SCAR is confirmed, permanently discontinue pirfenidone. 5.4 Gastrointestinal Disorders In the clinical studies, gastrointestinal events of nausea, diarrhea, dyspepsia, vomiting, gastro-esophageal reflux disease, and abdominal pain were more frequently reported by patients in the pirfenidone treatment groups than in those taking placebo. Dosage reduction or interruption for gastrointestinal events was required in 18.5% of patients in the 2403 mg/day group, as compared to 5.8% of patients in the placebo group; 2.2% of patients in the pirfenidone 2403 mg/day group discontinued treatment due to a gastrointestinal event, as compared to 1.0% in the placebo group. The most common (>2%) gastrointestinal events that led to dosage reduction or interruption were nausea, diarrhea, vomiting, and dyspepsia. The incidence of gastrointestinal events was highest early in the course of treatment (with highest incidence occurring during the initial 3 months) and decreased over time. Dosage modifications may be necessary in some cases of gastrointestinal adverse reactions [see Dosage and Administration (2.3) ].
Side effects
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, dizziness, vomiting, gastro-esophageal reflux disease, sinusitis, insomnia, weight decreased, and arthralgia. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Aurobindo Pharma USA, Inc. at 1-866-850-2876 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety of pirfenidone has been evaluated in more than 1400 subjects with over 170 subjects exposed to pirfenidone for more than 5 years in clinical trials. Pirfenidone was studied in 3 randomized, double-blind, placebo-controlled trials (Studies 1, 2, and 3) in which a total of 623 patients received 2403 mg/day of pirfenidone and 624 patients received placebo. Subjects ages ranged from 40 to 80 years (mean age of 67 years). Most patients were male (74%) and Caucasian (95%). The mean duration of exposure to pirfenidone was 62 weeks (range: 2 to 118 weeks) in these 3 trials. At the recommended dosage of 2403 mg/day, 14.6% of patients on pirfenidone compared to 9.6% on placebo permanently discontinued treatment because of an adverse event. The most common (>1%) adverse reactions leading to discontinuation were rash and nausea. The most common (>3%) adverse reactions leading to dosage reduction or interruption were rash, nausea, diarrhea, and photosensitivity reaction. The most common adverse reactions with an incidence of ≥10% and more frequent in the pirfenidone than placebo treatment group are listed in Table 2. Table 2. Adverse Reactions Occurring in ≥10% of Pirfenidone-Treated Patients and More Commonly Than Placebo in Studies 1, 2, and 3 Adverse Reaction % of Patients (0 to 118 Weeks) Pirfenidone 2403 mg/day (N = 623) Placebo (N = 624) Nausea 36% 16% Rash 30% 10% Abdominal Pain 1 24% 15% Upper Respiratory Tract Infection 27% 25% Diarrhea 26% 20% Fatigue 26% 19% Headache 22% 19% Decreased Appetite 21% 8% Dyspepsia 19% 7% Dizziness 18% 11% Vomiting 13% 6% Gastro-esophageal Reflux Disease 11% 7% Sinusitis 11% 10% Insomnia 10% 7% Weight Decreased 10% 5% Arthralgia 10% 7% 1 Includes abdominal pain, upper abdominal pain, abdominal distension, and stomach discomfort. Adverse reactions occurring in ≥5 to <10% of pirfenidone-treated patients and more commonly than placebo are photosensitivity reaction (9% vs. 1%), pruritus (8% vs. 5%), asthenia (6% vs. 4%), dysgeusia (6% vs. 2%), and non-cardiac chest pain (5% vs. 4%). 6.2 Postmarketing Experience In addition to adverse reactions identified from clinical trials the following adverse reactions have been identified during post-approval use of pirfenidone. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency. Blood and Lymphatic System Disorders: Agranulocytosis Hepatobiliary Disorders: Drug-induced liver injury Immune System Disorders: Angioedema Skin and Subcutaneous Tissue Disorders: Severe Cutaneous Adverse Reactions (SCAR)
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. Strong CYP1A2 Inhibitors The concomitant administration of pirfenidone and fluvoxamine or other strong CYP1A2 inhibitors (e.g., enoxacin) is not recommended because it significantly increases exposure to pirfenidone [see Clinical Pharmacology (12.3) ]. Use of fluvoxamine or other strong CYP1A2 inhibitors should be discontinued prior to administration of pirfenidone and avoided during pirfenidone treatment. In the event that fluvoxamine or other strong CYP1A2 inhibitors are the only drug of choice, dosage reductions are recommended. Monitor for adverse reactions and consider discontinuation of pirfenidone as needed [ see Dosage and Administration (2.4) ] . Moderate CYP1A2 Inhibitors Concomitant administration of pirfenidone and ciprofloxacin (a moderate inhibitor of CYP1A2) moderately increases exposure to pirfenidone [see Clinical Pharmacology (12.3) ] . If ciprofloxacin at the dosage of 750 mg twice daily cannot be avoided, dosage reductions are recommended [see Dosage and Administration (2.4) ]. Monitor patients closely when ciprofloxacin is used at a dosage of 250 mg or 500 mg once daily. Concomitant CYP1A2 and other CYP Inhibitors Agents or combinations of agents that are moderate or strong inhibitors of both CYP1A2 and one or more other CYP isoenzymes involved in the metabolism of pirfenidone (i.e., CYP2C9, 2C19, 2D6, and 2E1) should be discontinued prior to and avoided during pirfenidone treatment. 7.2 CYP1A2 Inducers The concomitant use of pirfenidone and a CYP1A2 inducer may decrease the exposure of pirfenidone and this may lead to loss of efficacy. Therefore, discontinue use of strong CYP1A2 inducers prior to pirfenidone treatment and avoid the concomitant use of pirfenidone and a strong CYP1A2 inducer [see Clinical Pharmacology (12.3) ] .
Use in specific populations
Hepatic Impairment: Monitor for adverse reactions and consider dosage modification or discontinuation of pirfenidone as needed. Pirfenidone is not recommended for use in patients with severe hepatic impairment. ( 8.6 , 12.3 ) Renal Impairment: Monitor for adverse reactions and consider dosage modification or discontinuation of pirfenidone as needed. Pirfenidone is not recommended for use in patients with end stage renal disease on dialysis. ( 8.7 , 12.3 ) Smokers: Decreased exposure has been noted in smokers which may alter the efficacy profile of pirfenidone. (8.8) 8.1 Pregnancy Risk Summary The data with pirfenidone use in pregnant women are insufficient to inform on drug associated risks for major birth defects and miscarriage. In animal reproduction studies, pirfenidone was not teratogenic in rats and rabbits at oral doses up to 3 and 2 times, respectively, the maximum recommended daily dose (MRDD) in adults [see Data] . In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Data Animal Data Animal reproductive studies were conducted in rats and rabbits. In a combined fertility and embryofetal development study, female rats received pirfenidone at oral doses of 0, 50, 150, 450, and 1000 mg/kg/day from 2 weeks prior to mating, during the mating phase, and throughout the periods of early embryonic development from gestation days (GD) 0 to 5 and organogenesis from GD 6 to 17. In an embryofetal development study, pregnant rabbits received pirfenidone at oral doses of 0, 30, 100, and 300 mg/kg/day throughout the period of organogenesis from GD 6 to 18. In these studies, pirfenidone at doses up to 3 and 2 times, respectively, the maximum recommended daily dose (MRDD) in adults (on mg/m 2 basis at maternal oral doses up to 1000 mg/kg/day in rats and 300 mg/kg/day in rabbits, respectively) revealed no evidence of impaired fertility or harm to the fetus due to pirfenidone. In the presence of maternal toxicity, acyclic/irregular cycles (e.g., prolonged estrous cycle) were seen in rats at doses approximately equal to and higher than the MRDD in adults (on a mg/m 2 basis at maternal doses of 450 mg/kg/day and higher). In a pre- and post-natal development study, female rats received pirfenidone at oral doses of 0, 100, 300, and 1000 mg/kg/day from GD 7 to lactation day 20. Prolongation of the gestation period, decreased numbers of live newborn, and reduced pup viability and body weights were seen in rats at an oral dosage approximately 3 times the MRDD in adults (on a mg/m 2 basis at a maternal oral dose of 1000 mg/kg/day). 8.2 Lactation Risk Summary No information is available on the presence of pirfenidone in human milk, the effects of the drug on the breastfed infant, or the effects of the drug on milk production. The lack of clinical data during lactation precludes clear determination of the risk of pirfenidone to an infant during lactation; therefore, the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for pirfenidone and the potential adverse effects on the breastfed child from pirfenidone or from the underlying maternal condition. Data Animal Data: A study with radio-labeled pirfenidone in rats has shown that pirfenidone or its metabolites are excreted in milk. There are no data on the presence of pirfenidone or its metabolites in human milk, the effects of pirfenidone on the breastfed child, or its effects on milk production. 8.4 Pediatric Use Safety and effectiveness of pirfenidone in pediatric patients have not been established. 8.5 Geriatric Use Of the total number of subjects in the clinical studies receiving pirfenidone, 714 (67%) were 65 years old and over, while 231 (22%) were 75 years old and over. No overall differences in safety or effectiveness were observed between older and younger patients. No dosage adjustment is required based upon age. 8.6 Hepatic Impairment Pirfenidone should be used with caution in patients with mild (Child Pugh Class A) to moderate (Child Pugh Class B) hepatic impairment. Monitor for adverse reactions and consider dosage modification or discontinuation of pirfenidone as needed [ see Dosage and Administration (2.3) ] . The safety, efficacy, and pharmacokinetics of pirfenidone have not been studied in patients with severe hepatic impairment. Pirfenidone is not recommended for use in patients with severe (Child Pugh Class C) hepatic impairment [see Clinical Pharmacology (12.3) ] . 8.7 Renal Impairment Pirfenidone should be used with caution in patients with mild (CL cr 50 to 80 mL/min), moderate (CL cr 30 to 50 mL/min), or severe (CL cr less than 30 mL/min) renal impairment [see Clinical Pharmacology (12.3) ]. Monitor for adverse reactions and consider dosage modification or discontinuation of pirfenidone as needed [ see Dosage and Administration (2.3) ] . The safety, efficacy, and pharmacokinetics of pirfenidone have not been studied in patients with end-stage renal disease requiring dialysis. Use of pirfenidone in patients with end-stage renal diseases requiring dialysis is not recommended. 8.8 Smokers Smoking causes decreased exposure to pirfenidone [see Clinical Pharmacology (12.3) ], which may alter the efficacy profile of pirfenidone. Instruct patients to stop smoking prior to treatment with pirfenidone and to avoid smoking when using pirfenidone.
Pregnancy
8.1 Pregnancy Risk Summary The data with pirfenidone use in pregnant women are insufficient to inform on drug associated risks for major birth defects and miscarriage. In animal reproduction studies, pirfenidone was not teratogenic in rats and rabbits at oral doses up to 3 and 2 times, respectively, the maximum recommended daily dose (MRDD) in adults [see Data] . In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Data Animal Data Animal reproductive studies were conducted in rats and rabbits. In a combined fertility and embryofetal development study, female rats received pirfenidone at oral doses of 0, 50, 150, 450, and 1000 mg/kg/day from 2 weeks prior to mating, during the mating phase, and throughout the periods of early embryonic development from gestation days (GD) 0 to 5 and organogenesis from GD 6 to 17. In an embryofetal development study, pregnant rabbits received pirfenidone at oral doses of 0, 30, 100, and 300 mg/kg/day throughout the period of organogenesis from GD 6 to 18. In these studies, pirfenidone at doses up to 3 and 2 times, respectively, the maximum recommended daily dose (MRDD) in adults (on mg/m 2 basis at maternal oral doses up to 1000 mg/kg/day in rats and 300 mg/kg/day in rabbits, respectively) revealed no evidence of impaired fertility or harm to the fetus due to pirfenidone. In the presence of maternal toxicity, acyclic/irregular cycles (e.g., prolonged estrous cycle) were seen in rats at doses approximately equal to and higher than the MRDD in adults (on a mg/m 2 basis at maternal doses of 450 mg/kg/day and higher). In a pre- and post-natal development study, female rats received pirfenidone at oral doses of 0, 100, 300, and 1000 mg/kg/day from GD 7 to lactation day 20. Prolongation of the gestation period, decreased numbers of live newborn, and reduced pup viability and body weights were seen in rats at an oral dosage approximately 3 times the MRDD in adults (on a mg/m 2 basis at a maternal oral dose of 1000 mg/kg/day).
Pediatric use
8.4 Pediatric Use Safety and effectiveness of pirfenidone in pediatric patients have not been established.
Geriatric use
8.5 Geriatric Use Of the total number of subjects in the clinical studies receiving pirfenidone, 714 (67%) were 65 years old and over, while 231 (22%) were 75 years old and over. No overall differences in safety or effectiveness were observed between older and younger patients. No dosage adjustment is required based upon age.
Overdosage
There is limited clinical experience with overdosage. Multiple dosages of pirfenidone up to a maximum tolerated dose of 4005 mg per day were administered as five 267 mg capsules three times daily to healthy adult volunteers over a 12-day dose escalation. In the event of a suspected overdosage, appropriate supportive medical care should be provided, including monitoring of vital signs and observation of the clinical status of the patient.
Description
Pirfenidone belongs to the chemical class of pyridone. Pirfenidone capsule, USP is available as a white opaque cap/white opaque body, hard gelatin capsule containing 267 mg of pirfenidone, USP for oral administration. Pirfenidone has a molecular formula of C 12 H 11 NO and a molecular weight of 185.23. Pirfenidone has the following structural formula, which has been referred to as 5-methyl-1-phenyl-2-1(H)-pyridone or 5-methyl-1-phenyl-2-(1H)-pyridone. Pirfenidone, USP is a white to pale yellow, non-hygroscopic crystalline powder. It is sparingly to slightly soluble in water, freely soluble in ethanol (96 %), slightly to very slightly soluble in n-Heptane. The melting point is approximately 109°C. Pirfenidone capsules, USP contain pirfenidone, USP and the following inactive ingredients: croscarmellose sodium, lactose monohydrate, magnesium stearate, polysorbate 80. In addition, the capsule shell contains gelatin and titanium dioxide. The capsule brown printing ink contains black iron oxide, brown iron oxide, potassium hydroxide and shellac. FDA approved dissolution test specifications differ from USP. structure
Mechanism of action
12.1 Mechanism of Action The mechanism of action of pirfenidone in the treatment of IPF has not been established.
How supplied
Pirfenidone Capsules USP, 267 mg are White opaque cap/white opaque body, hard gelatin capsule shells imprinted with “P 267” on cap with brown ink contains white to off white granular powder. The capsule is supplied either in a bottle, a 14-day titration blister pack or a 4-week maintenance blister pack. NDC 59651-244-27, bottle for a 30-day supply containing 270 capsules and closed with a child-resistant closure NDC 59651-244-42, 14-day titration blister pack, carton containing a total of 63 capsules in two blister cards – a Week 1 blister card containing 21 capsules (1 capsule per blister well) and a Week 2 blister card containing 42 capsules (2 capsules per blister well) NDC 59651-244-28, 4-week maintenance blister pack, carton containing a total of 252 capsules in four blister cards each with 63 capsules (3 capsules per blister well) Storage Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature]. Keep the bottle tightly closed. Do not use if the seal over the bottle opening is broken or missing. Safely throw away any pirfenidone capsules, USP that are out of date or no longer needed.
Patient information
Advise the patient to read the FDA-approved patient labeling ( Patient Information ). Liver Enzyme Elevations Advise patients that they may be required to undergo liver function testing periodically. Instruct patients to immediately report any symptoms of a liver problem (e.g., skin or the white of eyes turn yellow, urine turns dark or brown [tea colored], pain on the right side of stomach, bleed or bruise more easily than normal, lethargy) [see Warnings and Precautions (5.1) ] . Photosensitivity Reaction or Rash Advise patients to avoid or minimize exposure to sunlight (including sunlamps) during use of pirfenidone capsules because of concern for photosensitivity reactions or rash. Instruct patients to use a sunblock and to wear clothing that protects against sun exposure. Instruct patients to report symptoms of photosensitivity reaction or rash to their physician. Temporary dosage reductions or discontinuations may be required [see Warnings and Precautions (5.2) ] . Severe Cutaneous Adverse Reactions Advise patients about signs and symptoms of severe cutaneous adverse reactions (SCAR). Advise patients to contact their healthcare provider immediately if they experience signs and symptoms of SCAR [see Warnings and Precautions (5.3) ]. Gastrointestinal Events Instruct patients to report symptoms of persistent gastrointestinal effects including nausea, diarrhea, dyspepsia, vomiting, gastro-esophageal reflux disease, and abdominal pain. Temporary dosage reductions or discontinuations may be required [see Warnings and Precautions (5.4) ]. Smokers Encourage patients to stop smoking prior to treatment with pirfenidone capsules and to avoid smoking when using pirfenidone capsules [see Clinical Pharmacology (12.3) ] . Take with Food Instruct patients to take pirfenidone capsules with food to help decrease nausea and dizziness. Distributed by: Aurobindo Pharma USA, Inc. 279 Princeton-Hightstown Road East Windsor, NJ 08520 Manufactured by: Aurobindo Pharma Limited Hyderabad-500 032, India Issued: August 2024
Label text from the FDA structured product label by Aurobindo Pharma Limited (revised Apr 22, 2026). Long sections are shortened; the complete label is on DailyMed.
Active ingredients
- Pirfenidone in 56 products
Pirfenidone NDC products (56)
| NDC | Strength & form | Labeler | Type |
|---|---|---|---|
| 16729-467 | Pirfenidone 267 mg/1 Tablet, Film Coated | Accord Healthcare Inc. | ANDA |
| 16729-468 | Pirfenidone 801 mg/1 Tablet, Film Coated | Accord Healthcare Inc. | ANDA |
| 62332-479 | Pirfenidone 267 mg/1 Tablet, Coated | Alembic Pharmaceuticals Inc. | ANDA |
| 62332-480 | Pirfenidone 801 mg/1 Tablet, Coated | Alembic Pharmaceuticals Inc. | ANDA |
| 46708-480 | Pirfenidone 801 mg/1 Tablet, Coated | Alembic Pharmaceuticals Limited | ANDA |
| 46708-479 | Pirfenidone 267 mg/1 Tablet, Coated | Alembic Pharmaceuticals Limited | ANDA |
| 60219-1642 | Pirfenidone 267 mg/1 Capsule | Amneal Pharmaceuticals NY LLC | ANDA |
| 60219-1641 | Pirfenidone 801 mg/1 Tablet, Film Coated | Amneal Pharmaceuticals NY LLC | ANDA |
| 60219-1640 | Pirfenidone 267 mg/1 Tablet, Film Coated | Amneal Pharmaceuticals NY LLC | ANDA |
| 69238-1640 | Pirfenidone 267 mg/1 Tablet, Film Coated | Amneal Pharmaceuticals NY LLC | ANDA |
| 69238-1641 | Pirfenidone 801 mg/1 Tablet, Film Coated | Amneal Pharmaceuticals NY LLC | ANDA |
| 69238-1642 | Pirfenidone 267 mg/1 Capsule | Amneal Pharmaceuticals NY LLC | ANDA |
| 70954-870 | Pirfenidone 801 mg/1 Tablet, Film Coated | ANI Pharmaceuticals, Inc. | ANDA |
| 70954-869 | Pirfenidone 267 mg/1 Tablet, Film Coated | ANI Pharmaceuticals, Inc. | ANDA |
| 60505-4681 | Pirfenidone 267 mg/1 Tablet | Apotex Corp. | ANDA |
| 60505-4682 | Pirfenidone 801 mg/1 Tablet | Apotex Corp. | ANDA |
| 59651-244 | Pirfenidone 267 mg/1 Capsule | Aurobindo Pharma Limited | ANDA |
| 59651-239 | Pirfenidone 801 mg/1 Tablet | Aurobindo Pharma Limited | ANDA |
| 59651-238 | Pirfenidone 267 mg/1 Tablet | Aurobindo Pharma Limited | ANDA |
| 42291-491 | Pirfenidone 267 mg/1 Tablet, Film Coated | AvKARE | ANDA |
| 42291-490 | Pirfenidone 267 mg/1 Capsule | AvKARE | ANDA |
| 42291-492 | Pirfenidone 801 mg/1 Tablet, Film Coated | AvKARE | ANDA |
| 71335-2984 | Pirfenidone 801 mg/1 Tablet, Coated | Bryant Ranch Prepack | ANDA |
| 72162-2466 | Pirfenidone 801 mg/1 Tablet, Coated | Bryant Ranch Prepack | ANDA |
| 72162-2465 | Pirfenidone 267 mg/1 Tablet, Coated | Bryant Ranch Prepack | ANDA |
| 71335-2944 | Pirfenidone 267 mg/1 Tablet, Coated | Bryant Ranch Prepack | ANDA |
| 31722-872 | Pirfenidone 267 mg/1 Tablet, Film Coated | Camber Pharmaceuticals, Inc. | ANDA |
| 31722-873 | Pirfenidone 801 mg/1 Tablet, Film Coated | Camber Pharmaceuticals, Inc. | ANDA |
| 69097-940 | Pirfenidone 267 mg/1 Capsule | Cipla USA Inc. | ANDA |
| 69097-987 | Pirfenidone 267 mg/1 Tablet, Coated | Cipla USA Inc. | ANDA |
| 69097-988 | Pirfenidone 801 mg/1 Tablet, Coated | Cipla USA Inc. | ANDA |
| 76282-715 | Pirfenidone 267 mg/1 Capsule | EXELAN PHARMACEUTICALS INC. | ANDA |
| 76282-716 | Pirfenidone 801 mg/1 Tablet, Coated | EXELAN PHARMACEUTICALS INC. | ANDA |
| 76282-717 | Pirfenidone 267 mg/1 Tablet, Coated | EXELAN PHARMACEUTICALS INC. | ANDA |
| 51407-913 | Pirfenidone 267 mg/1 Tablet | Golden State Medical Supply, Inc. | ANDA |
| 51407-914 | Pirfenidone 801 mg/1 Tablet | Golden State Medical Supply, Inc. | ANDA |
| 42385-923 | Pirfenidone 267 mg/1 Capsule | Laurus Labs Limited | ANDA |
| 42385-924 | Pirfenidone 267 mg/1 Tablet, Film Coated | Laurus Labs Limited | ANDA |
| 42385-925 | Pirfenidone 534 mg/1 Tablet, Film Coated | Laurus Labs Limited | ANDA |
| 42385-926 | Pirfenidone 801 mg/1 Tablet, Film Coated | Laurus Labs Limited | ANDA |
| 0904-7398 | Pirfenidone 801 mg/1 Tablet, Film Coated | MAJOR PHARMACEUTICALS | ANDA |
| 0904-7397 | Pirfenidone 267 mg/1 Tablet, Film Coated | MAJOR PHARMACEUTICALS | ANDA |
| 42571-335 | Pirfenidone 267 mg/1 Tablet, Film Coated | Micro Labs Limited | ANDA |
| 42571-336 | Pirfenidone 801 mg/1 Tablet, Film Coated | Micro Labs Limited | ANDA |
| 72603-258 | Pirfenidone 267 mg/1 Tablet, Film Coated | Northstar Rx LLC | ANDA |
| 72603-259 | Pirfenidone 801 mg/1 Tablet, Film Coated | Northstar Rx LLC | ANDA |
| 72205-181 | Pirfenidone 267 mg/1 Tablet, Film Coated | Novadoz Pharmaceuticals LLC | ANDA |
| 72205-182 | Pirfenidone 801 mg/1 Tablet, Film Coated | Novadoz Pharmaceuticals LLC | ANDA |
| 0781-8086 | Pirfenidone 801 mg/1 Tablet, Film Coated | Sandoz Inc | ANDA |
| 0781-8085 | Pirfenidone 267 mg/1 Tablet, Film Coated | Sandoz Inc | ANDA |
| 0781-2158 | Pirfenidone 267 mg/1 Capsule | Sandoz Inc | ANDA |
| 50228-441 | Pirfenidone 267 mg/1 Capsule | ScieGen Pharmaceuticals, Inc. | ANDA |
| 50228-442 | Pirfenidone 267 mg/1 Tablet | ScieGen Pharmaceuticals, Inc. | ANDA |
| 50228-443 | Pirfenidone 801 mg/1 Tablet | ScieGen Pharmaceuticals, Inc. | ANDA |
| 0480-3611 | Pirfenidone 801 mg/1 Tablet, Film Coated | Teva Pharmaceuticals, Inc. | ANDA |
| 0480-3610 | Pirfenidone 267 mg/1 Tablet, Film Coated | Teva Pharmaceuticals, Inc. | ANDA |
Pirfenidone recalls
- D-0419-2023 Mar 8, 2023 · Class II · Terminated
CGMP Deviations: recalling drug products following an FDA inspection. - D-0420-2023 Mar 8, 2023 · Class II · Terminated
CGMP Deviations: recalling drug products following an FDA inspection.
Frequently asked questions
What is Pirfenidone used for?
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 )
What are the side effects of Pirfenidone?
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)… See the full label for the complete list.
Who makes Pirfenidone?
Pirfenidone is listed by 21 labelers in the FDA NDC directory, including Accord Healthcare Inc., Alembic Pharmaceuticals Inc., Alembic Pharmaceuticals Limited, Amneal Pharmaceuticals NY LLC.
Has Pirfenidone been recalled?
The FDA enforcement database lists 2 recalls for Pirfenidone, most recently D-0419-2023 (class ii): CGMP Deviations: recalling drug products following an FDA inspection.