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ESBRIET is a brand name for Pirfenidone, supplied as a tablet. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: ESBRIET® (pirfenidone) is indicated for treatment of idiopathic pulmonary fibrosis (IPF) in adults. 1.1. Pediatrics Pediatrics (<18 years of age): The safety and effectiveness of ESBRIET in pediatric patients have not been established. 1.2. Geriatrics No dose adjustment is necessary in patients 65 years and older (see…
Verbatim from this product's HC label. Tap a section to expand.
and 9 DRUG INTERACTIONS). Page 5 of 42 Strong and Selective Inhibitors of CYP1A2 In vitro-in vivo extrapolations indicate that strong and selective inhibitors of CYP1A2 have the potential to increase the exposure to pirfenidone by approximately 2 to 4-fold.
If concomitant use of ESBRIET with a strong and selective inhibitor of CYP1A2 cannot be avoided, the dose of ESBRIET should be reduced to 801 mg daily (267 mg, three times a day). Patients should be closely monitored for emergence of adverse reactions associated with ESBRIET therapy.
Discontinue ESBRIET if necessary (see 4 DOSAGE AND ADMINISTRATION and 9 DRUG INTERACTIONS). , CYP2C9, 2C19, 2D6, and 2E1) should be avoided during ESBRIET treatment. ESBRIET should be used with caution in patients treated with moderate inhibitors of CYP1A2 that do not inhibit other CYP isoenzymes (see 9 DRUG INTERACTIONS).
1. Dosing Considerations • Treatment with ESBRIET should be initiated and supervised by specialist physicians experienced in the diagnosis and treatment of IPF. • ESBRIET should be taken with food (see 9 DRUG INTERACTIONS). • ESBRIET should not be taken concomitantly with fluvoxamine (see 2 CONTRAINDICATIONS, 7 WARNINGS AND PRECAUTIONS and 9 DRUG INTERACTIONS).
• Reduction of the ESBRIET dose may be required for ciprofloxacin and strong but selective inhibitors of CYP1A2 (see 7 WARNINGS AND PRECAUTIONS and 9 DRUG INTERACTIONS). 2. Recommended Dose and Dosage Adjustment Adults The recommended daily dose of ESBRIET for patients with IPF is 801 mg three times a day with food, for a total dose of 2403 mg/day.
Upon initiating treatment, the dose should be titrated to the recommended daily dose of 2403 mg/ day over a 14-day period to improve tolerability as follows: Days 1 to 7: a dose of 267 mg administered, three times a day (801 mg/day) with food Days 8 to 14: a dose of 534 mg administered, three times a day (1602 mg/day) with food Day 15 onward: a dose of 801 mg administered, three times a day (2403 mg/day) with food Doses above 2403 mg/day are not recommended for any patient (see
, Post-Market Adverse Reactions). Liver chemistry tests (ALT, AST, and bilirubin) should be performed prior to the initiation of treatment with ESBRIET, and subsequently at monthly intervals for the first 6 months and then every 3 months thereafter.
In addition, liver function tests should be promptly measured in patients who report symptoms that may indicate liver injury, including fatigue, anorexia, right upper abdominal discomfort, dark urine, or jaundice. In the event of elevations of ALT and/or AST, or clinical signs and symptoms of liver injury, the dose of ESBRIET may need to be reduced or treatment discontinued (see 7 WARNINGS AND PRECAUTIONS, Monitoring and Laboratory Tests and 4 DOSAGE AND ADMINISTRATION, Recommendations in Case of ALT, AST, Bilirubin Elevations).
, Child-Pugh Class B), ESBRIET exposure was increased by 60%. , Child-Pugh Class A and B) given the potential for increased ESBRIET exposure. Patients should be monitored closely for signs of toxicity especially if they are concomitantly taking a known CYP1A2 inhibitor (see 9 DRUG INTERACTIONSand10 CLINICAL PHARMACOLOGY).
ESBRIET has not been studied in individuals with severe hepatic impairment. ESBRIET should not be used in patients with severe hepatic impairment or end-stage liver disease (see 2 CONTRAINDICATIONS). Immune Angioedema Reports of angioedema (some serious) such as swelling of the face, lips and/or tongue which may be associated with difficulty breathing or wheezing have been received in association with use of ESBRIET in the post-marketing setting.
Therefore, patients who develop signs or symptoms of angioedema following administration of ESBRIET should immediately discontinue treatment. Patients with angioedema should be managed according to standard of care. ESBRIET should not be used in patients with a history of angioedema due to ESBRIET (see 2 CONTRAINDICATIONS).
). • Concomitant use of fluvoxamine (see 7 WARNINGS AND PRECAUTIONS and 9 DRUG INTERACTIONS). • Severe hepatic impairment or end-stage liver disease (see 7 WARNINGS AND PRECAUTIONS). • Severe renal impairment (CrCl <30 mL/min) or end stage renal disease requiring dialysis (see 7 WARNINGS AND PRECAUTIONS).
3 SERIOUS WARNINGS AND PRECAUTIONS BOX Drug Interactions with Inhibitors of CYP1A2 and Other CYP Isoenzymes Fluvoxamine ESBRIET is contraindicated in patients with concomitant use of fluvoxamine (a strong inhibitor of CYP1A2 with inhibitory effects on CYP2C9, 2C19, and 2D6).
Fluvoxamine should be discontinued prior to the initiation of treatment with ESBRIET and avoided during ESBRIET therapy due to the potential for reduced clearance of pirfenidone (see 2 CONTRAINDICATIONS and 9 DRUG INTERACTIONS). Ciprofloxacin Co-administration of ESBRIET and 750 mg of ciprofloxacin (a moderate and selective inhibitor of CYP1A2) increased the exposure to pirfenidone by 81%.
If ciprofloxacin at the dose of 750 mg twice daily (a total daily dose of 1500 mg) cannot be avoided, the dose of ESBRIET should be reduced to 1602 mg daily (a dose of 534 mg, three times a day). ESBRIET should be used with caution when ciprofloxacin is used at a total daily dose of 250 to 1000 mg (see 4 DOSAGE AND ADMINISTRATION and 9 DRUG INTERACTIONS).
Page 5 of 42 Strong and Selective Inhibitors of CYP1A2 In vitro-in vivo extrapolations indicate that strong and selective inhibitors of CYP1A2 have the potential to increase the exposure to pirfenidone by approximately 2 to 4-fold.
If concomitant use of ESBRIET with a strong and selective inhibitor of CYP1A2 cannot be avoided, the dose of ESBRIET should be reduced to 801 mg daily (267 mg, three times a day). Patients should be closely monitored for emergence of adverse reactions associated with ESBRIET therapy.
Discontinue ESBRIET if necessary (see 4 DOSAGE AND ADMINISTRATION and 9 DRUG INTERACTIONS). , CYP2C9, 2C19, 2D6, and 2E1) should be avoided during ESBRIET treatment. ESBRIET should be used with caution in patients treated with moderate inhibitors of CYP1A2 that do not inhibit other CYP isoenzymes (see 9 DRUG INTERACTIONS).
• Hypersensitivity to this drug or to any ingredient in the formulation, including any non-medicinal ingredient, or component of the container. For a complete listing, see 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING section of the product monograph.
• History of angioedema with pirfenidone (see 7 WARNINGS AND PRECAUTIONS). • Concomitant use of fluvoxamine (see 7 WARNINGS AND PRECAUTIONS and 9 DRUG INTERACTIONS). • Severe hepatic impairment or end-stage liver disease (see 7 WARNINGS AND PRECAUTIONS).
• Severe renal impairment (CrCl <30 mL/min) or end stage renal disease requiring dialysis (see 7 WARNINGS AND PRECAUTIONS).
Not medical advice. Always read the patient information leaflet and follow your prescriber or pharmacist.
Other brands of Pirfenidone in Canada.
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Brand names are compiled from public regulatory records for active-ingredient mapping only. Drugvu is not affiliated with any manufacturer. This is not medical advice.
Monitoring and Laboratory Tests Liver chemistry tests (ALT, AST and bilirubin) should be performed prior to the initiation of treatment with ESBRIET, and subsequently at monthly intervals for the first 6 months and then every 3 months thereafter.
In addition, liver function tests should be promptly measured in patients who report symptoms that may indicate livery injury, including fatigue, anorexia, right upper abdominal discomfort, dark urine, or jaundice. In the event of elevation in ALT, AST and/or bilirubin or clinical signs and symptoms of liver injury, the dose of ESBRIET may need to be reduced or treatment discontinued (see 4 DOSAGE AND ADMINISTRATION: Recommendations in case of elevations in ALT, AST, bilirubin).
If a patient exhibits any ALT and/or AST elevation accompanied by clinical signs and symptoms of liver injury or accompanied by hyperbilirubinaemia, ESBRIET should be discontinued promptly. The patient should be monitored closely until resolution of elevated ALT, AST and bilirubin and symptoms.
The patient should NOT be re-challenged with ESBRIET. If a patient exhibits ALT and/or AST elevation to ≥5 × ULN regardless of the level of serum bilirubin, ESBRIET should be discontinued promptly and the patient monitored closely until resolution of ALT and AST.
The patient should NOT be re-challenged with ESBRIET. Neurologic Dizziness Dizziness has been reported in patients treated with ESBRIET. , driving or using machinery). Patients who experience intolerance to therapy due to dizziness should be reminded to take ESBRIET with food to reduce dizziness.
If dizziness does not improve or worsens in severity, dose adjustment or discontinuation of ESBRIET may be warranted. Renal Page 11 of 42 ESBRIET should not be used in patients with severe renal impairment, or end-stage renal disease requiring dialysis (CrCl <30 mL/min, per Cockcroft-Gault equation) (see 2 CONTRAINDICATIONS).
ESBRIET should be used with caution in patients with mild (CrCl 51-80 mL/min) and moderate renal impairment (CrCl 30-50 mL/min) (see 10 CLINICAL PHARMACOLOGY- Renal Insufficiency).
Reproductive Health:
Female and Male Potential Fertility No adverse effects on fertility were observed in preclinical studies (see 16 NON-CLINICAL TOXICOLOGY). Skin Photosensitivity Reaction and Rash Photosensitivity reaction and rash have been reported in patients treated with ESBRIET.
Patients treated with ESBRIET should be advised to avoid or minimize exposure to direct and indirect sunlight, including through windows and from sunlamps, and to avoid other medicinal products known to cause photosensitivity. Patients should be instructed to use daily an effective sun block (at least SPF 50 against UVA and UVB), and to wear clothing that protects against sun exposure such as wide- brimmed hats and long sleeves.
Patients should be instructed to report promptly to their physician symptoms of photosensitivity reaction or rash. Severe photosensitivity reactions are uncommon. Dose reduction and temporary treatment discontinuation may be necessary in the event of photosensitivity reaction or rash.
ESBRIET may be reintroduced with re-escalation to the tolerated dose in the same manner as the dose-escalation period (see 4 DOSAGE AND ADMINISTRATION). Severe Cutaneous Adverse Reactions Severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS), which can be life-threatening or fatal, have been reported post-marketing in association with the use of ESBRIET.
If signs or symptoms of SCARs occur, ESBRIET should be withdrawn immediately. If the patient has developed SJS or TEN or DRESS with the use of ESBRIET, treatment with ESBRIET must not be restarted and should […]
1. Dosing Considerations • Treatment with ESBRIET should be initiated and supervised by specialist physicians experienced in the diagnosis and treatment of IPF. • ESBRIET should be taken with food (see 9 DRUG INTERACTIONS). • ESBRIET should not be taken concomitantly with fluvoxamine (see 2 CONTRAINDICATIONS, 7 WARNINGS AND PRECAUTIONS and 9 DRUG INTERACTIONS).
• Reduction of the ESBRIET dose may be required for ciprofloxacin and strong but selective inhibitors of CYP1A2 (see 7 WARNINGS AND PRECAUTIONS and 9 DRUG INTERACTIONS). 2. Recommended Dose and Dosage Adjustment Adults The recommended daily dose of ESBRIET for patients with IPF is 801 mg three times a day with food, for a total dose of 2403 mg/day.
Upon initiating treatment, the dose should be titrated to the recommended daily dose of 2403 mg/ day over a 14-day period to improve tolerability as follows: Days 1 to 7: a dose of 267 mg administered, three times a day (801 mg/day) with food Days 8 to 14: a dose of 534 mg administered, three times a day (1602 mg/day) with food Day 15 onward: a dose of 801 mg administered, three times a day (2403 mg/day) with food Doses above 2403 mg/day are not recommended for any patient (see 5 OVERDOSAGE).
Patients who miss 14 consecutive days or more of ESBRIET treatment should re-initiate therapy by undergoing the initial 2 week titration regimen up to the recommended daily dose. Page 6 of 42 If treatment is interrupted for less than 14 consecutive days, the dose can be resumed at the previous recommended daily dose without titration.
Dose Adjustments Gastrointestinal Events:
In patients who experience intolerance to therapy due to gastrointestinal side effects, patients should be reminded to take ESBRIET with food. If gastrointestinal events do not improve, or worsen in severity, dose reduction or discontinuation of ESBRIET may be warranted.
The dose of ESBRIET may be reduced to 267 mg – 534 mg, two to three times a day with food with re- escalation to the recommended daily dose as tolerated.
Photosensitivity Reaction or Rash:
Patients who experience a mild to moderate photosensitivity reaction or rash should be reminded to use a sunblock daily and to avoid exposure to the sun. The dose of ESBRIET may be reduced to 801 mg each day. If the rash persists after 7 days, ESBRIET should be discontinued for 15 days, with re-escalation to the recommended daily dose in the same manner as the dose escalation period.
Patients who experience severe photosensitivity reaction or rash should be instructed to discontinue ESBRIET promptly and to seek medical advice without delay (see 7 WARNINGS AND PRECAUTIONS). Once the rash has resolved, ESBRIET may be re-introduced and re escalated up to the recommended daily dose at the discretion of the physician.
Ciprofloxacin:
Co-administration of ESBRIET and 750 mg of ciprofloxacin (a moderate and selective inhibitor of CYP1A2) increased the exposure to pirfenidone by 81%. If ciprofloxacin at the dose of 750 mg twice daily (a total daily dose of 1500 mg) cannot be avoided, the dose of ESBRIET should be reduced to 1602 mg daily (a dose of 534 mg, three times a day).
ESBRIET should be used with caution when ciprofloxacin is used at a total daily dose of 250 to 1000 mg (see 7 WARNINGS AND PRECAUTIONS and 9 DRUG INTERACTIONS).
Geriatrics:
No dose adjustment is necessary in patients 65 years and older.
Pediatrics:
ESBRIET has not been studied in pediatric patients, and is not recommended for use in this patient population.
Hepatic Impairment:
No dose adjustment is necessary in patients with mild to moderate hepatic […]