其 他 安 全 警 示
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| The United Kingdom: Pirfenidone (Esbriet): risk of serious liver injury; updated advice on liver function testing (English only) |
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Medicines and Healthcare products Regulatory Agency (MHRA) announces that serious liver injury has been reported during treatment with pirfenidone in the first year after initiation, including 2 cases with a fatal outcome.
Pirfenidone is known to commonly cause elevation of liver transaminases, alanine aminotransferase (ALT) and aspartate aminotransferase (AST), with associated concomitant increases in bilirubin in rare cases. A recent European review of safety data identified severe cases of drug-induced liver injury associated with pirfenidone reported post-marketing, including isolated cases with a fatal outcome. Reported events included hepatitis, liver injury, and liver failure. Reports of serious liver injury are considered to be uncommon (may occur in between 1 in 100 and 1 in 1000 people who take pirfenidone) and the benefit-risk profile of pirfenidone in the approved indications remains favourable. Although the aetiology is unclear, idiosyncratic reactions may underlie the occurrence of drug-induced liver injury following treatment with pirfenidone.
Two fatal cases consistent with drug-induced liver injury were reported in the literature in association with pirfenidone. These events of drug-induced liver injury and subsequent liver failure occurred at 1 month and 12 months after initiation of treatment with pirfenidone.
Following the findings of the review, existing warnings for the potential for hepatotoxicity in the product information will be strengthened to include the risk of clinically relevant drug-induced liver injury with pirfenidone. While the recommendation for liver function monitoring before and during treatment has not changed, new advice will be added to minimise risk in patients taking pirfenidone. New warnings in the summary of product characteristics will ask for prompt liver function testing in patients who report symptoms or have clinical signs that might indicate liver injury, and adjustment of the dose of pirfenidone or discontinuation of treatment if necessary.
It is recommended to perform liver function tests (ALT, AST, and bilirubin) before initiating treatment with pirfenidone, and subsequently at monthly intervals for the first 6 months. and then every 3 months thereafter. Clinically evaluate and perform liver function tests 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 significant elevation of liver aminotransferases or clinical signs and symptoms of hepatic injury, adjust the dose or discontinue treatment according to the new guidance.
Advice for healthcare professionals:
- Serious cases of drug-induced liver injury, including liver failure, have been reported in patients treated with pirfenidone; cases have been estimated to be of uncommon frequency but 2 reports worldwide had a fatal outcome.
- Continue to monitor ALT, AST, and bilirubin levels before initiation, at monthly intervals during the first 6 months of treatment and every 3 months thereafter.
- Advise patients to seek medical help immediately if they have signs and symptoms that may indicate liver injury, including fatigue, anorexia, right upper abdominal discomfort, dark urine, or jaundice.
- Perform prompt clinical evaluation and measure liver function in patients who report symptoms that may indicate liver injury.
- In the event of significant elevation of liver enzymes or clinical signs and symptoms of liver injury, adjust the dose of pirfenidone or discontinue treatment.
- Monitor closely for signs of toxicity if pirfenidone is being used concomitantly with inhibitors of one or more other CYP isoenzymes involved in the metabolism of pirfenidone.
Please refer to the following website in MHRA for details:
http://www.gov.uk/drug-safety-update/pirfenidone-esbriet-risk-of-serious-liver-injury-updated-advice-on-liver-function-testing
In Hong Kong, Esbriet Capsules 267mg (HK-64288) is a registered pharmaceutical product containing pirfenidone. The product is registered by Roche Hong Kong Limited, and is a prescription-only medicine. So far, the Department of Health (DH) has received one case of adverse drug reaction related to pirfenidone, but this case is not related to liver injury. Related news was previously issued by Singapore Health Sciences Authority and Health Canada, and was posted on the Drug Office website on 19 Dec 2019 and 15 Sep 2020 respectively. Letters to inform local healthcare professionals were issued by the DH on 19 Dec 2019. As previously reported, the matter will be discussed by the Registration Committee of the Pharmacy and Poisons Board.
Ends/Tuesday, Nov 17, 2020
Issued at HKT 16:00
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