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Pirfenidone

Medically reviewed by Drugs.com. Last updated on Jul 22, 2020.

Pronunciation

(pir FEN i done)

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Capsule, Oral:

Esbriet: 267 mg

Tablet, Oral:

Esbriet: 267 mg, 801 mg

Brand Names: U.S.

  • Esbriet

Pharmacologic Category

  • Anti-inflammatory Agent
  • Antifibrotic Agent

Pharmacology

Precise mechanisms of action have not been fully elucidated; however, pirfenidone may exert antifibrotic properties by decreasing fibroblast proliferation and the production of fibrosis-associated proteins and cytokines; may decrease the formation and accumulation of extracellular matrix (ie, collagen) in response to transforming growth factor-beta and platelet derived growth factor. Pirfenidone is also believed to exert anti-inflammatory properties by decreasing the accumulation of inflammatory cells resulting from a variety of stimuli.

Distribution

~59 to 71 L

Metabolism

Hepatic primarily via CYP1A2 and to a lesser extent via CYP2C9, 2C19, 2D6, and 2E1; major metabolite (5-carboxy-pirfenidone) is inactive

Excretion

Urine (~80%; >99% as metabolite)

Time to Peak

Plasma: Median: 0.5 hours (fasting); 3 hours (with food)

Half-Life Elimination

~3 hours

Protein Binding

Mean: 58% (primarily to albumin)

Special Populations: Renal Function Impairment

Systemic exposure (AUC0 to ∞) increased ~1.4, 1.5, and 1.2-fold in mild, moderate, and severe renal impairment, respectively. The corresponding AUC0 to ∞ of 5-carboxy-pirfenidone increased 1.7, 3.4, and 5.6-fold. The renal clearance of 5-carboxy-pirfenidone decreased significantly in patients with moderate to severe impairment.

Special Populations: Hepatic Function Impairment

In patients with moderate impairment (Child Pugh class B), mean exposure, AUC0 to ∞ and Cmax increased ~1.6- and ~1.4-fold in moderate hepatic impairment, respectively.

Use: Labeled Indications

Idiopathic pulmonary fibrosis: Treatment of idiopathic pulmonary fibrosis (IPF)

Contraindications

There are no contraindications listed in the manufacturer’s labeling.

Canadian labeling: Additional contraindications (not in US labeling): Hypersensitivity to pirfenidone or any component of the formulation; history of angioedema with pirfenidone; concomitant use of fluvoxamine; severe hepatic impairment or end-stage liver disease; severe renal impairment (CrCl <30 mL/minute) or end-stage renal disease (ESRD) requiring dialysis.

Dosing: Adult

Idiopathic pulmonary fibrosis (IPF): Oral:

Days 1 to 7: 267 mg 3 times daily (total dose: 801 mg/day)

Days 8 to 14: 534 mg 3 times daily (total dose: 1,602 mg/day)

Day 15 and thereafter: 801 mg 3 times daily (total dose: 2,403 mg/day). Maximum dose: 2,403 mg/day.

Reinitiation of therapy following interruption: If interruption <14 consecutive days, may reinitiate therapy at previous daily dose without retitration; if interruption ≥14 consecutive days, reinitiate therapy with the initial 2-week titration period up to recommended daily dose.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Adjustment for Toxicity

Gastrointestinal (eg, nausea, diarrhea, dyspepsia, vomiting): There are no specific dosage adjustments provided in the manufacturer’s labeling; however, consider temporary dosage reduction and/or therapy interruption to allow for resolution of symptoms.

Photosensitivity reaction or rash: There is no specific dosage adjustment provided in the manufacturer’s labeling; however, consider temporary dosage reduction and/or therapy interruption to allow for resolution of symptoms.

Administration

Oral: Administer with food at the same time each day.

Dietary Considerations

Take with food to decrease frequency of dizziness or nausea. Limit or avoid grapefruit juice.

Storage

Store at 25°C (77°F); excursions are permitted between 15°C and 30°C (59°F and 86°F).

Drug Interactions

Abametapir: May increase the serum concentration of CYP1A2 Substrates (High risk with Inhibitors). Avoid combination

Aminolevulinic Acid (Systemic): Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid (Systemic). Avoid combination

Aminolevulinic Acid (Topical): Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid (Topical). Monitor therapy

Broccoli: May decrease the serum concentration of CYP1A2 Substrates (High risk with Inducers). Monitor therapy

Cannabis: May decrease the serum concentration of CYP1A2 Substrates (High risk with Inducers). Monitor therapy

Ciprofloxacin (Systemic): May increase the serum concentration of Pirfenidone. Management: With ciprofloxacin doses of 1,500 mg/day, the pirfenidone dose should be reduced to 1,602 mg per (534 mg three times a day). With lower daily doses of ciprofloxacin, use pirfenidone with caution. Consider therapy modification

CYP1A2 Inducers (Moderate): May decrease the serum concentration of Pirfenidone. Monitor therapy

CYP1A2 Inhibitors (Moderate): May increase the serum concentration of Pirfenidone. Management: Avoid concomitant use of pirfenidone and moderate CYP1A2 inhibitors whenever possible. If combined, decrease the pirfenidone dose to 1,602 mg per day (534 mg three times daily) and monitor for increased pirfenidone toxicities. Exceptions: Ciprofloxacin (Systemic). Consider therapy modification

CYP1A2 Inhibitors (Strong): May increase the serum concentration of Pirfenidone. Management: Avoid concomitant use of pirfenidone and strong CYP1A2 inhibitors whenever possible. If combined, decrease the pirfenidone dose to 801 mg per day (267 mg three times daily) and monitor for increased pirfenidone toxicities. Consider therapy modification

Grapefruit Juice: May increase the serum concentration of Pirfenidone. Management: Consider advising patients to limit or avoid grapefruit juice consumption during treatment with pirfenidone. Canadian product labeling states that grapefruit juice should be avoided during pirfenidone treatment. Monitor therapy

Porfimer: Photosensitizing Agents may enhance the photosensitizing effect of Porfimer. Monitor therapy

Tobacco (Smoked): May decrease the serum concentration of Pirfenidone. Avoid combination

Verteporfin: Photosensitizing Agents may enhance the photosensitizing effect of Verteporfin. Monitor therapy

Adverse Reactions

>10%:

Central nervous system: Fatigue (26%), headache (22%), dizziness (18%)

Dermatologic: Skin rash (30%)

Gastrointestinal: Nausea (36%), diarrhea (26%), abdominal pain (24%), dyspepsia (19%), anorexia (13%), vomiting (13%), gastroesophageal reflux disease (11%)

Respiratory: Upper respiratory tract infection (27%), sinusitis (11%)

1% to 10%:

Central nervous system: Insomnia (10%), noncardiac chest pain (5%)

Dermatologic: Skin photosensitivity (9%), pruritus (8%)

Endocrine & metabolic: Weight loss (10%)

Gastrointestinal: Decreased appetite (8%), dysgeusia (6%)

Hepatic: Increased serum transaminases (ALT and AST; ≥3 x ULN: 4%)

Neuromuscular & skeletal: Arthralgia (10%), asthenia (6%)

Postmarketing: Agranulocytosis, angioedema, hepatotoxicity

Warnings/Precautions

Concerns related to adverse effects:

• CNS effects: May cause dizziness and/or fatigue which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving). Incidence of dizziness may be reduced by administering with food. Dose reduction or discontinuation may be necessary if symptoms fail to improve or worsen.

• GI effects: Adverse effects including nausea/vomiting, diarrhea, dyspepsia, gastroesophageal reflux disease, and abdominal pain have been reported; incidence may be reduced by administering with food. The incidence of gastrointestinal events was highest early in the course of treatment (initial 3 months) and decreased over time. Consider dose reduction or discontinuation of therapy if lack of improvement or worsening of symptoms.

• Hepatic effects: Serious and nonserious cases of drug-induced liver injury (including severe liver injury with fatal outcome) have been reported. Elevations of ALT and AST were reversible with dose modification or discontinuation of therapy. Obtain LFTs (ALT, AST, bilirubin) prior to initiation of treatment, monthly during the first 6 months, then every 3 months thereafter, and as clinically indicated. Dosage modification or interruption of therapy may be necessary for elevated LFTs.

• Photosensitivity: Photosensitivity reactions and rash have been reported with the majority of reactions occurring during the initial 6 months of therapy (severe reactions are uncommon); instruct patients to avoid or minimize exposure to the sun and/or sun lamps, to apply sunscreen (SPF ≥50 against UVA and UVB), wear protective clothing/hats, and to avoid concurrent use of other photosensitizing drugs. Patients should promptly report symptoms, reaction, or rash; dose reduction or therapy interruption may be necessary. If appropriate, may reinitiate therapy with re-escalation of dose as tolerated.

• Weight loss: Weight loss/anorexia have been reported with use; monitor weight during therapy.

Disease-related concerns:

• Hepatic impairment: Use with caution in mild to moderate impairment (Child-Pugh class A and B); pirfenidone systemic exposure increased by 60% in moderate impairment. Use in severe impairment (Child-Pugh class C) is not recommended (has not been studied).

• Renal impairment: Use with caution in patients with renal impairment; consider dose reduction and/or discontinuation as necessary; use in patients with end stage renal disease requiring dialysis is not recommended.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

• Cigarette smokers: Clearance may be increased and systemic exposure decreased in cigarette smokers due to hepatic enzyme (ie, CYP1A2) induction. Patients should be instructed to quit smoking prior to initiation of therapy; cigarette smoking should be avoided during therapy.

Monitoring Parameters

Hepatic function (prior to initiation, monthly for first 6 months, then every 3 months thereafter and as clinically indicated); signs of photosensitivity; gastrointestinal events (eg, diarrhea, nausea, vomiting); weight loss.

Pregnancy Considerations

Adverse events have been observed in animal reproduction studies.

Patient Education

What is this drug used for?

• It is used to treat idiopathic pulmonary fibrosis.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Dizziness

• Fatigue

• Heartburn

• Common cold symptoms

• Joint pain

• Lack of appetite

• Diarrhea

• Nausea

• Vomiting

• Change in taste

• Loss of strength and energy

• Trouble sleeping

• Headache

• Abdominal pain

• Weight loss

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Liver problems like dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin

• Chest pain

• Severe diarrhea

• Severe nausea

• Vomiting

• Severe abdominal pain

• Sunburn

• Bleeding

• Bruising

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine's uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.