choice, dosage reductions are recommendeddiclofenacSerious - Use Alternative (1)diclofenac will increase the level or effect of pirfenidone by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug. Avoid; coadministration of pirfenidone and moderate CYP1A2 inhibitors result in moderately increased exposure to pirfenidone; if unable to avoid, decrease dose of moderate CYP1A2 inhibitorepcoritamabMonitor Closely (1)epcoritamab, pirfenidone. affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor. Epcoritamab causes release of cytokines that may suppress activity of CYP enzymes, resulting in increased exposure of CYP substrates. For certain CYP substrates, minimal changes in their concentration may lead to serious adverse reactions. If needed, modify therapy as recommended in the substrate's prescribing information. .fexinidazoleMonitor Closely (1)fexinidazole will increase the level or effect of pirfenidone by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.fluoxetineSerious - Use Alternative (1)fluoxetine will increase the level or effect of pirfenidone by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug. Avoid; coadministration of pirfenidone and moderate CYP1A2 inhibitors result in moderately increased exposure to pirfenidone; if unable to avoid, decrease dose of moderate CYP1A2 inhibitorfluvoxamineSerious - Use Alternative (1)fluvoxamine will increase the level or effect of pirfenidone by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug. Use of strong CYP1A2 inhibitors should be discontinued before initiating treatment and avoided during treatment; if strong CYP1A2 inhibitor is only option, dosage reduction recommendedgemfibrozilSerious - Use Alternative (1)gemfibrozil will increase the level or effect of pirfenidone by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug. Avoid; coadministration of pirfenidone and moderate CYP1A2 inhibitors result in moderately increased exposure to pirfenidone; if unable to avoid, decrease dose of moderate CYP1A2 inhibitorgivosiranSerious - Use Alternative (1)givosiran will increase the level or effect of pirfenidone by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP1A2 substrates with givosiran. If unavoidable, decrease the CYP1A2 substrate dosage in accordance with approved product labeling.glofitamabMonitor Closely (1)glofitamab, pirfenidone. affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor. Glofitamab causes release of cytokines that may suppress activity of CYP enzymes, resulting in increased exposure of CYP substrates. For certain CYP substrates, minimal changes in their concentration may lead to serious adverse reactions. If needed, modify therapy as recommended in the substrate's prescribing information. .leniolisibSerious - Use Alternative (1)leniolisib will increase the level or effect of pirfenidone by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug. If unable to avoid coadministration, decrease pirfenidone doselonapegsomatropinMonitor Closely (1)lonapegsomatropin will decrease the level or effect of pirfenidone by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor. Limited published data indicate that growth hormone treatment increases cytochrome P450 (CYP450)-mediated antipyrine clearance. Caution with sensitive CYP substratesmethoxsalenSerious - Use Alternative (1)methoxsalen will increase the level or effect of pirfenidone by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug. Use of strong CYP1A2 inhibitors should be discontinued before initiating pirfenidone and avoided during treatment; if strong CYP1A2 inhibitors are the only drug of choice, dosage reductions are recommendedmethyl aminolevulinateSerious - Use Alternative (1)pirfenidone, methyl aminolevulinate. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Each drug may increase the photosensitizing effect of the other.mexiletineSerious - Use Alternative (1)mexiletine will increase the level or effect of pirfenidone by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug. Use of strong CYP1A2 inhibitors should be discontinued before initiating pirfenidone and avoided during treatment; if strong CYP1A2 inhibitors are the only drug of choice, dosage reductions are recommendednifedipineSerious - Use Alternative (1)nifedipine will increase the level or effect of pirfenidone by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug. Avoid; coadministration of pirfenidone and moderate CYP1A2 inhibitors result in moderately increased exposure to pirfenidone; if unable to avoid, decrease dose of moderate CYP1A2 inhibitorofloxacinSerious - Use Alternative (1)ofloxacin will increase the level or effect of pirfenidone by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug. Use of strong CYP1A2 inhibitors should be discontinued before initiating pirfenidone and avoided during treatment; if strong CYP1A2 inhibitors are the only drug of choice, dosage reductions are recommendedphenobarbitalContraindicated (1)phenobarbital will decrease the level or effect of pirfenidone by affecting hepatic enzyme CYP1A2 metabolism. Contraindicated. Use of strong CYP1A2 inducers should be discontinued before initiating pirfenidone and avoided during treatmentprimaquineSerious - Use Alternative (1)primaquine will increase the level or effect of pirfenidone by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug. Use of strong CYP1A2 inhibitors should be discontinued before initiating pirfenidone and avoided during treatment; if strong CYP1A2 inhibitors are the only drug of choice, dosage reductions are recommendedprimidoneContraindicated (1)primidone will decrease the level or effect of pirfenidone by affecting hepatic enzyme CYP1A2 metabolism. Contraindicated. Use of strong CYP1A2 inducers should be discontinued before initiating pirfenidone and avoided during treatmentpropofolSerious - Use Alternative (1)propofol will increase the level or effect of pirfenidone by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug. Avoid; coadministration of pirfenidone and moderate CYP1A2 inhibitors result in moderately increased exposure to pirfenidone; if unable to avoid, decrease dose of moderate CYP1A2 inhibitorrifampinContraindicated (1)rifampin will decrease the level or effect of pirfenidone by affecting hepatic enzyme CYP1A2 metabolism. Contraindicated. Use of strong CYP1A2 inducers should be discontinued before initiating pirfenidone and avoided during treatmentritlecitinibMonitor Closely (1)ritlecitinib will increase the level or effect of pirfenidone by affecting hepatic enzyme CYP1A2 metabolism. Modify Therapy/Monitor Closely. Ritlecitinib inhibits CYP1A2 substrates; coadministration increases AUC and peak plasma concentration sensitive substrates, which may increase risk of adverse reactions. Additional monitoring and dosage adjustment may be needed in accordance with product labeling of CYP1A2 substrates. rucaparibMonitor Closely (1)rucaparib will increase the level or effect of pirfenidone by affecting hepatic enzyme CYP1A2 metabolism. Modify Therapy/Monitor Closely. Adjust dosage of CYP1A2 substrates, if clinically indicated.somapacitanMonitor Closely (1)somapacitan will decrease the level or effect of pirfenidone by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor. Limited published data indicate that growth hormone treatment increases cytochrome P450 (CYP450)-mediated antipyrine clearance. Caution with sensitive CYP substratessomatrogonMonitor Closely (1)somatrogon will decrease the level or effect of pirfenidone by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor. Limited published data indicate that growth hormone treatment increases cytochrome P450 (CYP450)-mediated antipyrine clearance. Caution with sensitive CYP substratessomatropinMonitor Closely (1)somatropin will decrease the level or effect of pirfenidone by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor. Limited published data indicate that growth hormone treatment increases cytochrome P450 (CYP450)-mediated antipyrine clearance. Caution with sensitive CYP substratesstiripentolMonitor Closely (1)stiripentol, pirfenidone. affecting hepatic enzyme CYP1A2 metabolism. Modify Therapy/Monitor Closely. Stiripentol is a CYP1A2 inhibitor and inducer. Monitor CYP1A2 substrates coadministered with stiripentol for increased or decreased effects. CYP1A2 substrates may require dosage adjustment.tranylcypromineSerious - Use Alternative (1)tranylcypromine will increase the level or effect of pirfenidone by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug. Avoid; coadministration of pirfenidone and moderate CYP1A2 inhibitors result in moderately increased exposure to pirfenidone; if unable to avoid, decrease dose of moderate CYP1A2 inhibitorzileutonSerious - Use Alternative (1)zileuton will increase the level or effect of pirfenidone by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug. Use of strong CYP1A2 inhibitors should be discontinued before initiating pirfenidone and avoided during treatment; if strong CYP1A2 inhibitors are the only drug of choice, dosage reductions are recommended >10% Nausea (36%) Rash (30%) Upper respiratory tract infection (27%) Diarrhea (26%) Fatigue (26%) Abdominal pain (24%) Headache (22%) Decreased appetite (21%) Dyspepsia (19%) Dizziness (18%) Vomiting (13%) Gastroesophageal reflux disease (GERD) (11%) Sinusitis (11%) 1-10% Insomnia (10%) Weight decreased (10%) Arthralgia (10%) Photosensitivity (9%) Decreased appetite (8%) Pruritus (8%) Asthenia (6%) Dysgeusia (6%) Noncardiac chest pain (5%) AST/ALT ≥3 x ULN (3.7%) <1% AST/ALT ≥10 x ULN (0.3%) Postmarketing Reports Blood and lymphatic system disorders: Agranulocytosis Immune system disorders: Angioedema Hepatobiliary disorders: Drug-induced liver injury Skin and Subcutaneous Tissue Disorders: Severe Cutaneous Adverse Reactions (SCAR) Contraindications None Cautions Photosensitivity and rash reported; 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 Nausea, vomiting, diarrhea, dyspepsia, gastroesophageal reflux disease, and abdominal pain reported; incidence of gastrointestinal events reported to be highest early in the course of treatment (with highest incidence occurring during initial 3 months); may decrease over time; temporary dosage reductions or discontinuations may be required Drug-induced liver injury Conduct liver function tests (ALT, AST, and bilirubin) before initiating, monthly for 6 months, and then q3months thereafter and, as clinically indicated Patients treated with 2403 mg/day reported having higher incidence of elevated ALT/AST in clinical trials 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 modifications, interruption, or discontinuation may be necessary to reverse liver enzyme elevation 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), reported in association with therapy in the postmarketing setting If signs or symptoms of SCAR occur, interrupt treatment until etiology of the reaction has been determined; consultation with a dermatologist recommended; if a SCAR is confirmed, permanently discontinue therapy Drug interaction overview Pirfenidone is a CYP1A2 substrate; discontinue moderate or strong CYP1A inhibitors before initiating pirfenidone and avoid use during therapy; if unable to avoid, pirfenidone dose reduction required Discontinue strong CYP1A2 inducers before initiating pirfenidone and avoid use during therapy; likely to decrease exposure and lead to loss of pirfenidone efficacy Smoking associated with decreased systemic exposure; encourage patient to quit smoking Pregnancy: Data in pregnant women are insufficient to inform on drug associated risks for major birth defects and miscarriage Lactation: No information is available on presence of pirfenidone in human milk, effects of drug on breastfed infant, or effects of drug on milk production; lack of clinical data during lactation precludes clear determination of risk of pirfenidone to infant during lactation; developmental and health benefits of breastfeeding should be considered along with mother’s clinical need for therapy and potential adverse effects on breastfed child from pirfenidone or from underlying maternal conditionPregnancy Categories A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk. B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available. Mechanism of Action Precise mechanism by which pirfenidone may work in pulmonary fibrosis has not been established Inhibits transforming growth factor (TGF)-beta, a chemical mediator that controls many cell functions including proliferation and differentiation Also inhibits the synthesis of TNF-alpha, a cytokine that is known to have an active role in inflammation Absorption Peak plasma time: 0.5-4 hr Food decreased the rate and extent of absorption; Cmax and AUC decreased by ~49% and 16% with food, respectively A reduced incidence of adverse reactions was observed in the fed group when compared with the fasted group; administered with food in clinical trials Distribution Protein bound: 58% Vd: 59-71 L Metabolism Metabolized in the liver by CYP1A2 to inactive metabolites Elimination Half-life: 3 hr Majority of dose excreted as 5-carboxy-pirfenidone metabolite (99.6%) Excretion: 80% urine Oral Administration Take with food Take doses at same time each day Missed doses If ≥14 days: Reinitiate treatment by undergoing the initial 2-week titration regimen up to the full maintenance dosage If <14 days: Resume the dosage prior to the interruption BRAND FORM. UNIT PRICE PILL IMAGE pirfenidone oral- 267 mg capsulepirfenidone oral- 801 mg tabletpirfenidone oral- 267 mg tabletpirfenidone oral- 267 mg tabletpirfenidone oral- 267 mg capsulepirfenidone oral- 267 mg tabletpirfenidone oral- 267 mg capsulepirfenidone oral- 801 mg tabletpirfenidone oral- 801 mg tabletCopyright © 2010 First DataBank, Inc.Print Patient Educationpirfenidone oral PIRFENIDONE - ORAL (pir-FEN-i-done) COMMON BRAND NAME(S): Esbriet USES: Pirfenidone is used to treat a certain lung disease called idiopathic pulmonary fibrosis (IPF). This disease causes the