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Drug overview for ESBRIET (pirfenidone):
Generic name: PIRFENIDONE (pir-FEN-i-done)
Drug class: Pulmonary Fibrosis Treatment Agents - Antifibrotic Therapy
Therapeutic class: Respiratory Therapy Agents
Pirfenidone, a synthetic pyridone, is an antifibrotic agent.
No enhanced Uses information available for this drug.
Generic name: PIRFENIDONE (pir-FEN-i-done)
Drug class: Pulmonary Fibrosis Treatment Agents - Antifibrotic Therapy
Therapeutic class: Respiratory Therapy Agents
Pirfenidone, a synthetic pyridone, is an antifibrotic agent.
No enhanced Uses information available for this drug.
DRUG IMAGES
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The following indications for ESBRIET (pirfenidone) have been approved by the FDA:
Indications:
Idiopathic pulmonary fibrosis
Professional Synonyms:
Cryptogenic fibrosing alveolitis
Idiopathic fibrosing alveolitis
Indications:
Idiopathic pulmonary fibrosis
Professional Synonyms:
Cryptogenic fibrosing alveolitis
Idiopathic fibrosing alveolitis
The following dosing information is available for ESBRIET (pirfenidone):
No enhanced Dosing information available for this drug.
Pirfenidone is administered orally 3 times daily with food, at the same time every day. If a dose of pirfenidone is missed, the next dose should be administered as soon as it is remembered; a double dose should not be administered to make up for a missed dose. No more than 3 doses should be taken per day. Store capsules and tablets at 25degreesC; excursions permitted between 15-30degreesC.
| DRUG LABEL | DOSING TYPE | DOSING INSTRUCTIONS |
|---|---|---|
| ESBRIET 267 MG TABLET | Maintenance | Adults take 3 tablets (801 mg) by oral route 3 times per day at the same times each day |
| ESBRIET 801 MG TABLET | Maintenance | Adults take 1 tablet (801 mg) by oral route 3 times per day at the same times each day |
| DRUG LABEL | DOSING TYPE | DOSING INSTRUCTIONS |
|---|---|---|
| PIRFENIDONE 267 MG TABLET | Maintenance | Adults take 3 tablets (801 mg) by oral route 3 times per day at the same times each day |
| PIRFENIDONE 801 MG TABLET | Maintenance | Adults take 1 tablet (801 mg) by oral route 3 times per day at the same times each day |
The following drug interaction information is available for ESBRIET (pirfenidone):
There are 0 contraindications.
There are 2 severe interactions.
These drug interactions can produce serious consequences in most patients. Actions required for severe interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration scheduling, and providing additional patient monitoring. Review the full interaction monograph for more information.
| Drug Interaction | Drug Names |
|---|---|
| Pirfenidone/Strong CYP1A2 Inhibitors SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Pirfenidone is primarily metabolized by CYP1A2 which is responsible for about 50% of its conversion to inactive drug. CYP2C9, 2C19, 2D6 and 2E1 are additional minor contributors to pirfenidone metabolism.(1,2) Strong inhibitors of CYP1A2 may inhibit the metabolism of pirfenidone.(1,2) Fluvoxamine is a strong inhibitor of CYP1A2 and CYP2C19, and a weak inhibitor of CYP2C9 and so inhibits both primary and secondary pirfenidone metabolic pathways.(3,4) CLINICAL EFFECTS: Concurrent pirfenidone use with strong inhibitors of CYP1A2 may lead to increased systemic concentrations and toxicity from pirfenidone, including serious liver injury.(1,2) PREDISPOSING FACTORS: A greater risk of adverse events may result from concomitant treatment with fluvoxamine, which also inhibits CYP2C19, or with strong or moderate inhibitors of one or more other CYP isoenzymes involved in the metabolism of pirfenidone such as CYP2C9 (e.g. amiodarone, fluconazole), CYP2C19 (e.g. fluconazole, fluoxetine, ticlopidine) and CYP2D6 (e.g. fluoxetine, paroxetine). The magnitude of this interaction may be reduced in cigarette smokers. Cigarette smoking induces production of CYP1A2 and, in the absence of a CYP1A2 inhibitor, leads to decreased systemic concentrations of pirfenidone.(1) PATIENT MANAGEMENT: The US manufacturer of pirfenidone states that concurrent use with strong inhibitors of CYP1A2 is not recommended. Use of strong CYP1A2 inhibitors should be discontinued prior to administration of pirfenidone and avoided during treatment with pirfenidone. Combinations of strong or moderate CYP1A2 inhibitors with strong or moderate CYP2C9, CYP2C19, and/or CYP2D6 inhibitors should also be discontinued prior to and avoided during pirfenidone treatment. If concurrent therapy of pirfenidone and strong CYP1A2 inhibitors cannot be avoided, reduce pirfenidone to one-267 mg capsule three times a day (total daily dose of 801 mg/day).(2) The Canadian(1) and Indian(5) manufacturers of pirfenidone states that fluvoxamine is contraindicated with pirfenidone and fluvoxamine should be discontinued prior to initiation of pirfenidone therapy. The concurrent use of pirfenidone and other strong or moderate CYP1A2 inhibitors should be used with caution. DISCUSSION: Pirfenidone is converted to inactive metabolites prior to elimination. CYP1A2 is responsible for approximately half of this metabolism. In an interaction study conducted in non-smokers and smokers, coadministration of pirfenidone with fluvoxamine (a strong CYP1A2 inhibitor), an agent which inhibits multiple pirfenidone elimination pathways (CYP1A2, CYP2C9, CYP2C19), led to an approximately 4-fold and 7-fold, respectively, increase in pirfenidone exposure.(2) Strong CYP1A2 inhibitors include: angelica root (angelica dahurica radix), enasidenib, enoxacin, fluvoxamine, and rofecoxib.(4) |
FLUVOXAMINE MALEATE, FLUVOXAMINE MALEATE ER, IDHIFA |
| Pirfenidone/Ciprofloxacin (Greater Than or Equal To 750 mg BID) SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Pirfenidone is primarily metabolized by CYP1A2 which is responsible for about 50% of its conversion to inactive drug. CYP2C9, 2C19, 2D6 and 2E1 are additional minor contributors to pirfenidone metabolism.(1,2) Moderate inhibitors of CYP1A2 may inhibit the metabolism of pirfenidone.(1,2) Ciprofloxacin is a moderate inhibitor of CYP1A2.(3,4) CLINICAL EFFECTS: Concurrent pirfenidone use with ciprofloxacin may lead to increased systemic concentrations and toxicity from pirfenidone, including serious liver injury.(1,2) PREDISPOSING FACTORS: A greater risk of adverse events may result from concomitant treatment strong or moderate inhibitors of one or more other CYP isoenzymes involved in the metabolism of pirfenidone such as CYP2C9 (e.g. amiodarone, fluconazole), CYP2C19 (e.g. fluconazole, fluoxetine, ticlopidine) and CYP2D6 (e.g. fluoxetine, paroxetine). The magnitude of this interaction may be reduced in cigarette smokers. Cigarette smoking induces production of CYP1A2 and, in the absence of a CYP1A2 inhibitor, leads to decreased systemic concentrations of pirfenidone.(1) PATIENT MANAGEMENT: The manufacturer of pirfenidone recommends avoiding concurrent use of ciprofloxacin at doses of 750 mg twice daily or higher. If concurrent use cannot be avoided, reduce pirfenidone dose to 534 mg three times daily (total daily dose of 1,602 mg/day). Monitor patients closely when ciprofloxacin is used at a daily dosage of 250 mg to 1,000 mg.(1,2) Combinations of ciprofloxacin with strong or moderate CYP2C9, CYP2C19, and/or CYP2D6 inhibitors should also be discontinued prior to and avoided during pirfenidone treatment.(2) DISCUSSION: Pirfenidone is converted to inactive metabolites prior to elimination. CYP1A2 is responsible for approximately half of this metabolism. In a single-dose study in 27 healthy subjects, coadministration of 801 mg of pirfenidone and 750 mg of ciprofloxacin on Day 6 (ciprofloxacin was dosed at 750 mg twice daily from Day 2 to Day 7) increased the exposure to pirfenidone by 81%.(2) |
CIPRO, CIPROFLOXACIN, CIPROFLOXACIN HCL, CIPROFLOXACIN-D5W |
There are 2 moderate interactions.
The clinician should assess the patient’s characteristics and take action as needed. Actions required for moderate interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration.
| Drug Interaction | Drug Names |
|---|---|
| Pirfenidone/Moderate CYP1A2 Inhibitors SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Pirfenidone is primarily metabolized by CYP1A2 which is responsible for about 50% of its conversion to inactive drug. CYP2C9, 2C19, 2D6 and 2E1 are additional minor contributors to pirfenidone metabolism.(1) Inhibitors of CYP1A2 may inhibit the metabolism of pirfenidone.(1) CLINICAL EFFECTS: Concurrent pirfenidone use with moderate inhibitors of CYP1A2 may lead to increased systemic concentrations and toxicity from pirfenidone, including serious liver injury.(1) PREDISPOSING FACTORS: A greater risk of adverse events may result from concomitant treatment with strong or moderate inhibitors of one or more other CYP isoenzymes involved in the metabolism of pirfenidone such as CYP2C9 (e.g. amiodarone, fluconazole), CYP2C19 (e.g. fluconazole, fluoxetine, ticlopidine) and CYP2D6 (e.g. fluoxetine, paroxetine).(1) The magnitude of this interaction may be reduced in cigarette smokers. Cigarette smoking induces production of CYP1A2 and, in the absence of a CYP1A2 inhibitor, leads to decreased systemic concentrations of pirfenidone.(1) PATIENT MANAGEMENT: The manufacturer of pirfenidone states that for concurrent use with moderate inhibitors of CYP1A2, dose reduction is recommended. Reduce the dose of pirfenidone to two-267 mg capsules three times a day (total daily dose of 1602 mg/day).(1) Combinations of strong or moderate CYP1A2 inhibitors with strong or moderate CYP2C9, CYP2C19, and/or CYP2D6 inhibitors should be discontinued prior to and avoided during pirfenidone treatment.(1) DISCUSSION: Pirfenidone is converted to inactive metabolites prior to elimination. CYP1A2 is responsible for approximately half of this metabolism. In an interaction study conducted in non-smokers and smokers, coadministration of pirfenidone with fluvoxamine (a strong CYP1A2 inhibitor), an agent which inhibits multiple pirfenidone elimination pathways (CYP1A2, CYP2C9, CYP2C19), led to an approximately 4-fold and 7-fold, respectively, increase in pirfenidone exposure.(1) In a single-dose study in 27 healthy subjects, coadministration of 801 mg of pirfenidone and 750 mg of ciprofloxacin on Day 6 (ciprofloxacin was dosed at 750 mg twice daily from Day 2 to Day 7) increased the exposure to pirfenidone by 81%.(1) Moderate CYP1A2 inhibitors linked to this monograph include: capmatinib, dipyrone, fexinidazole, genistein, hormonal contraceptives, methoxsalen, mexiletine, osilodrostat, phenylpropanolamine, pipemidic acid, rucaparib, troleandomycin, vemurafenib, and viloxazine.(2) |
2-METHOXYESTRADIOL, ABIGALE, ABIGALE LO, ACTIVELLA, AFIRMELLE, ALTAVERA, ALYACEN, AMETHIA, AMETHYST, ANGELIQ, ANNOVERA, APRI, ARANELLE, ASHLYNA, AUBRA, AUBRA EQ, AUROVELA, AUROVELA 24 FE, AUROVELA FE, AVERI, AVIANE, AYUNA, AZURETTE, BALCOLTRA, BALZIVA, BEYAZ, BIJUVA, BLISOVI 24 FE, BLISOVI FE, BRIELLYN, CAMRESE, CAMRESE LO, CAZIANT, CHARLOTTE 24 FE, CHATEAL EQ, CLIMARA, CLIMARA PRO, COMBIPATCH, CONJUGATED ESTROGENS, COVARYX, COVARYX H.S., CRYSELLE, CYRED, CYRED EQ, DASETTA, DAYSEE, DELESTROGEN, DEPO-ESTRADIOL, DESOGESTR-ETH ESTRAD ETH ESTRA, DIETHYLSTILBESTROL, DIVIGEL, DOLISHALE, DOTTI, DROSPIRENONE-ETH ESTRA-LEVOMEF, DROSPIRENONE-ETHINYL ESTRADIOL, DUAVEE, EEMT, EEMT H.S., ELESTRIN, ELINEST, ELURYNG, ENILLORING, ENPRESSE, ENSKYCE, ESTARYLLA, ESTRACE, ESTRADIOL, ESTRADIOL (ONCE WEEKLY), ESTRADIOL (TWICE WEEKLY), ESTRADIOL BENZOATE, ESTRADIOL CYPIONATE, ESTRADIOL HEMIHYDRATE, ESTRADIOL HEMIHYDRATE MICRO, ESTRADIOL MICRONIZED, ESTRADIOL VALERATE, ESTRADIOL-NORETHINDRONE ACETAT, ESTRATEST H.S., ESTRIOL, ESTRIOL MICRONIZED, ESTROGEL, ESTROGEN-METHYLTESTOSTERONE, ESTRONE, ETHINYL ESTRADIOL, ETHYNODIOL-ETHINYL ESTRADIOL, ETONOGESTREL-ETHINYL ESTRADIOL, EVAMIST, FALMINA, FEIRZA, FEMLYV, FEMRING, FINZALA, FYAVOLV, GALBRIELA, GEMMILY, HAILEY, HAILEY 24 FE, HAILEY FE, HALOETTE, ICLEVIA, INTROVALE, ISIBLOOM, ISTURISA, JAIMIESS, JASMIEL, JINTELI, JOLESSA, JOYEAUX, JULEBER, JUNEL, JUNEL FE, JUNEL FE 24, KAITLIB FE, KALLIGA, KARIVA, KELNOR 1-35, KURVELO, LARIN, LARIN 24 FE, LARIN FE, LESSINA, LEVONEST, LEVONORG-ETH ESTRAD ETH ESTRAD, LEVONORG-ETH ESTRAD-FE BISGLYC, LEVONORGESTREL-ETH ESTRADIOL, LO LOESTRIN FE, LO-ZUMANDIMINE, LOESTRIN, LOESTRIN FE, LOJAIMIESS, LORYNA, LOW-OGESTREL, LUIZZA, LUTERA, LYLLANA, MARLISSA, MENEST, MENOSTAR, METHOXSALEN, MEXILETINE HCL, MIBELAS 24 FE, MICROGESTIN, MICROGESTIN FE, MILI, MIMVEY, MINIVELLE, MINZOYA, MONO-LINYAH, MYFEMBREE, NATAZIA, NECON, NEXTSTELLIS, NIKKI, NORELGESTROMIN-ETH ESTRADIOL, NORETHIN-ETH ESTRA-FERROUS FUM, NORETHINDRON-ETHINYL ESTRADIOL, NORETHINDRONE-E.ESTRADIOL-IRON, NORGESTIMATE-ETHINYL ESTRADIOL, NORTREL, NUVARING, NYLIA, OCELLA, ORIAHNN, ORTHO TRI-CYCLEN, ORTHO-NOVUM, PHILITH, PIMTREA, PORTIA, PREMARIN, PREMPHASE, PREMPRO, QELBREE, RECLIPSEN, RIVELSA, ROSYRAH, RUBRACA, SAFYRAL, SETLAKIN, SIMLIYA, SIMPESSE, SLYND, SPRINTEC, SYEDA, TABRECTA, TARINA 24 FE, TARINA FE, TARINA FE 1-20 EQ, TAYTULLA, TILIA FE, TRI-ESTARYLLA, TRI-LEGEST FE, TRI-LINYAH, TRI-LO-ESTARYLLA, TRI-LO-MARZIA, TRI-LO-MILI, TRI-LO-SPRINTEC, TRI-MILI, TRI-SPRINTEC, TRI-VYLIBRA, TRI-VYLIBRA LO, TURQOZ, TWIRLA, TYBLUME, TYDEMY, UVADEX, VALTYA, VELIVET, VESTURA, VIENVA, VIORELE, VIVELLE-DOT, VOLNEA, VYFEMLA, VYLIBRA, WERA, WYMZYA FE, XARAH FE, XELRIA FE, XULANE, YASMIN 28, YAZ, ZAFEMY, ZARAH, ZELBORAF, ZOVIA 1-35, ZUMANDIMINE |
| Pirfenidone/Ciprofloxacin (Less Than 750 mg BID) SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Pirfenidone is primarily metabolized by CYP1A2 which is responsible for about 50% of its conversion to inactive drug. CYP2C9, 2C19, 2D6 and 2E1 are additional minor contributors to pirfenidone metabolism.(1,2) Moderate inhibitors of CYP1A2 may inhibit the metabolism of pirfenidone.(1,2) Ciprofloxacin is a moderate inhibitor of CYP1A2.(3,4) CLINICAL EFFECTS: Concurrent pirfenidone use with ciprofloxacin may lead to increased systemic concentrations and toxicity from pirfenidone, including serious liver injury.(1,2) PREDISPOSING FACTORS: A greater risk of adverse events may result from concomitant treatment strong or moderate inhibitors of one or more other CYP isoenzymes involved in the metabolism of pirfenidone such as CYP2C9 (e.g. amiodarone, fluconazole), CYP2C19 (e.g. fluconazole, fluoxetine, ticlopidine) and CYP2D6 (e.g. fluoxetine, paroxetine). The magnitude of this interaction may be reduced in cigarette smokers. Cigarette smoking induces production of CYP1A2 and, in the absence of a CYP1A2 inhibitor, leads to decreased systemic concentrations of pirfenidone.(1) PATIENT MANAGEMENT: The manufacturer of pirfenidone recommends avoiding concurrent use of ciprofloxacin at doses of 750 mg twice daily or higher. If concurrent use cannot be avoided, reduce pirfenidone dose to 534 mg three times daily (total daily dose of 1,602 mg/day). Monitor patients closely when ciprofloxacin is used at a daily dosage of 250 mg to 1,000 mg.(1,2) Combinations of ciprofloxacin with strong or moderate CYP2C9, CYP2C19, and/or CYP2D6 inhibitors should also be discontinued prior to and avoided during pirfenidone treatment.(2) DISCUSSION: Pirfenidone is converted to inactive metabolites prior to elimination. CYP1A2 is responsible for approximately half of this metabolism. In a single-dose study in 27 healthy subjects, coadministration of 801 mg of pirfenidone and 750 mg of ciprofloxacin on Day 6 (ciprofloxacin was dosed at 750 mg twice daily from Day 2 to Day 7) increased the exposure to pirfenidone by 81%.(2) |
CIPRO, CIPROFLOXACIN HCL, CIPROFLOXACIN-D5W |
The following contraindication information is available for ESBRIET (pirfenidone):
Drug contraindication overview.
*None.
*None.
There are 0 contraindications.
There are 2 severe contraindications.
Adequate patient monitoring is recommended for safer drug use.
| Severe List |
|---|
| Gastroesophageal reflux disease |
| Tobacco smoker |
There are 7 moderate contraindications.
Clinically significant contraindication, where the condition can be managed or treated before the drug may be given safely.
| Moderate List |
|---|
| Child-pugh class A hepatic impairment |
| Child-pugh class B hepatic impairment |
| Child-pugh class C hepatic impairment |
| Chronic kidney disease stage 4 (severe) GFR 15-29 ml/min |
| Chronic kidney disease stage 5 (failure) GFr<15 ml/min |
| Disease of liver |
| Kidney disease with likely reduction in glomerular filtration rate (GFr) |
The following adverse reaction information is available for ESBRIET (pirfenidone):
Adverse reaction overview.
Adverse effects reported in >=10% of patients receiving pirfenidone include nausea, rash, abdominal pain, upper respiratory tract infection, diarrhea, fatigue, headache, dyspepsia, dizziness, vomiting, decreased appetite, GERD, sinusitis, insomnia, decreased weight, and arthralgia.
Adverse effects reported in >=10% of patients receiving pirfenidone include nausea, rash, abdominal pain, upper respiratory tract infection, diarrhea, fatigue, headache, dyspepsia, dizziness, vomiting, decreased appetite, GERD, sinusitis, insomnia, decreased weight, and arthralgia.
There are 10 severe adverse reactions.
| More Frequent | Less Frequent |
|---|---|
| None. |
Abnormal hepatic function tests Increased alanine transaminase Increased aspartate transaminase |
| Rare/Very Rare |
|---|
|
Agranulocytosis Angioedema DRESS syndrome Drug-induced hepatitis Hyperbilirubinemia Stevens-johnson syndrome Toxic epidermal necrolysis |
There are 20 less severe adverse reactions.
| More Frequent | Less Frequent |
|---|---|
|
Acute abdominal pain Arthralgia Diarrhea Dizziness Dyspepsia Fatigue Gastroesophageal reflux disease Headache disorder Insomnia Nausea Sinusitis Skin rash Upper respiratory infection Vomiting Weight loss |
Anorexia Dysgeusia Non-cardiac chest pain Pruritus of skin Skin photosensitivity |
| Rare/Very Rare |
|---|
| None. |
The following precautions are available for ESBRIET (pirfenidone):
Safety and efficacy of pirfenidone have not been established in pediatric patients.
Contraindicated
Severe Precaution
Management or Monitoring Precaution
Contraindicated
| None |
Severe Precaution
| None |
Management or Monitoring Precaution
| None |
Data on the use of pirfenidone in pregnant females are insufficient to determine the drug-associated risks of birth defects and miscarriage. In animal reproductive studies, pirfenidone was not teratogenic when administered at oral doses up to 2 and 3 times the maximum recommended adult dosage.
No data is available on the presence of pirfenidone or its metabolites in human milk, the effects of the drug on the breastfed child, or the effects of the drug on milk production. The known benefits of breastfeeding should be considered along with the mother's clinical need for pirfenidone and any potential adverse effects on the breast-fed infant from either the drug or the underlying maternal condition. Pirfenidone or its metabolites are distributed into milk in rats; it is not known whether the drug is distributed into human milk.
In clinical studies of pirfenidone, 67% of patients were >=65 years of age and 22% were >=75 years of age. No overall differences in safety and efficacy were observed between geriatric patients and younger adults.
The following prioritized warning is available for ESBRIET (pirfenidone):
No warning message for this drug.
No warning message for this drug.
The following icd codes are available for ESBRIET (pirfenidone)'s list of indications:
| Idiopathic pulmonary fibrosis | |
| J84.112 | Idiopathic pulmonary fibrosis |
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