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  • Esbriet 267 mg
    / Roche


    Active Ingredient
    Pirfenidone 267 mg

    Status in Israel
    RX

    Presentation and Status in Health Basket

    Presentation Basket Yarpa Pharmasoft

    Hard Capsules

    270 X 267 mg

    partial basket chart 18875 5591

    Related information


    Dosage

    Adults: Upon initiating treatment, the dose should be titrated to the recommended daily dose of nine capsules per day over a 14-day period as follows:
    Days 1 to 7: one capsule, three times a day (801 mg/day).
    Days 8 to 14: two capsules, three times a day (1602 mg/day).
    Day 15 onward: three capsules, three times a day (2403 mg/day).
    The recommended daily dose of Pirfenidone for patients with IPF is three 267 mg capsules three times a day with food for a total of 2403 mg/day. Doses above 2403 mg/day are not recommended for any patient. Patients who miss 14 consecutive days or more of Pirfenidone treatment should re-initiate therapy by undergoing the initial 2-week titration regimen up to the recommended daily dose. For treatment interruption of less than 14 consecutive days, the dose can be resumed at the previous recommended daily dose without titration. 
    Dose adjustments and other considerations for safe use:
    Gastrointestinal events: In patients who experience intolerance to therapy due to gastrointestinal side effects, patients should be reminded to take the medicinal product with food. If symptoms persist Pirfenidone may be reduced to 1-2 capsules (267 mg – 534 mg) 2-3 times/day with food with re-escalation to the recommended daily dose as tolerated. If symptoms continue, patients may be instructed to interrupt treatment for 1 to 2 weeks to allow symptoms to resolve.
    Photosensitivity reaction or rash: Patients who experience a mild to moderate photosensitivity reaction or rash should be reminded of the instruction to use a sunblock daily and to avoid sun exposure.  The dose of Pirfenidone may be reduced to 3 capsules/day (1 capsule three  times a day). If the rash persists after 7 days, Pirfenidone  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 interrupt the dose and to seek medical advice. Once the rash has resolved, Pirfenidone may be re-introduced and re-escalated up to the recommended daily dose at the discretion of the physician.
    Hepatic function: In the event of significant elevation of alanine and/or aspartate aminotransferases (ALT/AST) with or without bilirubin elevation, the dose of Pirfenidone  should be adjusted or treatment discontinued according to the guidelines.
    Special populations: Older people: No dose adjustment is necessary in patients 65 years and older.
    Hepatic impairment: No dose adjustment is necessary in patients with mild to moderate hepatic impairment (i.e. Child-Pugh Class A and B). However, since plasma levels of pirfenidone may be increased in some individuals with mild to moderate hepatic impairment, caution should be used with Pirfenidone treatment in this population. Patients should be monitored closely for signs of toxicity especially if they are concomitantly taking a known CYP1A2 inhibitor. Pirfenidone has not been studied in patients with severe hepatic impairment or end stage liver disease, and it should not be used in patients with these conditions. It is recommended to monitor liver function during treatment, and dose adjustments may be necessary in the event of elevations.
    Renal impairment: No dose adjustment is necessary in patients with mild to moderate renal impairment. Pirfenidone therapy should not be used in patients with severe renal impairment (CrCl <30 ml/min) or end stage renal disease requiring dialysis. See prescribing information for full details.
    Paediatric population: There is no relevant use of Pirfenidone in the paediatric population in the treatment of IPF.
    Method of administration: Pirfenidone is to be swallowed whole with water and taken with food to reduce the possibility of nausea and dizziness.
    See prescribing information for full details.


    Indications

    Treatment of mild to moderate idiopathic pulmonary fibrosis in adults.


    Contra-Indications

    Hypersensitivity to the active substance or to any of the excipients. History of angioedema with pirfenidone. Concomitant use of fluvoxamine. Severe hepatic impairment or end stage liver disease. Severe Renal Impairment (CrCl <30 Ml/Min) or end stage renal disease requiring dialysis.
    For full details see prescribing information.


    Special Precautions

    Hepatic function: Elevations in ALT and AST >3 × upper limit of normal (ULN) have been reported in patients receiving therapy with this drug.  Rarely these have been associated with concomitant elevations in total serum bilirubin. Liver function tests (ALT, AST and bilirubin) should be conducted prior to the initiation of treatment with Esbriet, and subsequently at monthly intervals for the first 6 months and then every 3 months thereafter.
    Recommendations in case of ALT/AST elevations: If a patient exhibits an aminotransferase elevation to >3 to ≤5 x ULN after starting Pirfenidone therapy, confounding medicinal products should be discontinued, other causes excluded, and the patient monitored closely. If clinically appropriate the dose of Pirfenidone should be reduced or interrupted. Once liver function tests are within normal limits Pirfenidone may be re-escalated to the recommended daily dose if tolerated. If a patient exhibits an aminotransferase elevation to ≤5 x ULN accompanied by symptoms or hyperbilirubinaemia, Pirfenidone should be discontinued and the patient should not be rechallenged. If a patient exhibits an aminotransferase elevation to >5 x ULN, Pirfenidone should be discontinued and the patient should not be rechallenged.
    Hepatic impairment: In subjects with moderate hepatic impairment (i.e. Child-Pugh Class B), Pirfenidone exposure was increased by 60%. Pirfenidone should be used with caution in patients with pre-existing mild to moderate hepatic impairment (i.e. Child-Pugh Class A and B) given the potential for increased Pirfenidone exposure.
    Patients should be monitored closely for signs of toxicity especially if they are concomitantly taking a known CYP1A2 inhibitor. Pirfenidone has not been studied in individuals with severe hepatic impairment and Pirfenidone should not be used in patients with severe hepatic impairment.
    Photosensitivity reaction and rash: Exposure to direct sunlight (including sunlamps) should be avoided or minimised during treatment with Pirfenidone . Patients should be instructed to use a sunblock daily, to wear clothing that protects against sun exposure, and to avoid other medicinal products known to cause photosensitivity. Patients should be instructed to report symptoms of photosensitivity reaction or rash to their physician. Severe photosensitivity reactions are uncommon. Dose adjustments or temporary treatment discontinuation may be necessary in mild to severe cases of photosensitivity reaction or rash.
    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 Pirfenidone in the post-marketing setting. Therefore, patients who develop signs or symptoms of angioedema following administration of Pirfenidone should immediately discontinue treatment. Patients with angioedema should be managed according to standard of care. Pirfenidone should not be used in patients with a history of angioedema due to Pirfenidone.
    Dizziness: Dizziness has been reported in patients taking Pirfenidone. Therefore, patients should know how they react to this medicinal product before they engage in activities requiring mental alertness or coordination.
    Fatigue: Fatigue has been reported in patients taking Pirfenidone. Therefore, patients should know how they react to this medicinal product before they engage in activities requiring mental alertness or coordination.
    Weight loss: Weight loss has been reported in patients treated with Pirfenidone. Physicians should monitor patients’ weight, and when appropriate encourage increased caloric intake if weight loss is considered to be of clinical significance.
    See prescribing information for full details.


    Side Effects

    Upper respiratory tract infection; urinary tract infection, anorexia, insomnia, headache, hot flush.
    See prescribing information for full details.


    Drug interactions

    Approximately 70–80% of pirfenidone is metabolised via CYP1A2 with minor contributions from other CYP isoenzymes including CYP2C9, 2C19, 2D6, and 2E1. Consumption of grapefruit juice is associated with inhibition of CYP1A2 and should be avoided during treatment with pirfenidone.
    This drug  should be used with caution in patients treated with other moderate inhibitors of CYP1A2 (e.g. amiodarone, propafenone).
    See prescribing information for full details.


    Pregnancy and Lactation

    Pregnancy: There are no data from the use of this drug in pregnant women.
    Lactation: It is unknown whether pirfenidone or its metabolites are excreted in human milk.
    See prescribing information for full details. 


    Overdose

    There is limited clinical experience with overdose. Multiple doses of pirfenidone up to a dose of 4806 mg/day were administered as six 267 mg capsules three times daily to healthy adult volunteers over a 12-day dose escalation period. Adverse reactions were mild, transient, and consistent with the most frequently reported adverse reactions for pirfenidone. In the event of a suspected overdose, supportive medical care should be provided including monitoring of vital signs and close observation of the clinical status of the patient.


    Important notes

    Effects on ability to drive and use machines: No studies on the effects of the ability to drive and use machines have been performed. This drug may cause dizziness and fatigue, which could influence the ability to drive or use machines.
    Storage: Store below 30°C.
    Shelf life after first opening: 2 months.           


    Manufacturer
    F. Hoffmann - La Roche Ltd.
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