Other safety alerts
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| European Union: Modified-release paracetamol-containing products to be suspended from EU market |
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The European Medicines Agency (EMA)’s Co-ordination Group for Mutual Recognition and Decentralised Procedures – Human (CMDh) has endorsed by majority a European Medicines Agency recommendation to suspend marketing of modified- or prolonged-release products containing paracetamol (designed to release paracetamol slowly over a longer period than the usual immediate-release products). The recommendation was made by the Agency’s experts in medicines safety, the Pharmacovigilance Risk Assessment Committee (PRAC).
CMDh agreed with the Agency’s advice that the advantages of a longer-acting product did not outweigh the complications of managing an overdose of the medicine, since the treatment procedures for immediate-release products are not appropriate for modified-release paracetamol. In many cases, it may not be known whether an overdose of paracetamol involves immediate-release or modified-release products, making it difficult to decide how the overdose should be managed.
CMDh noted the PRAC conclusion that practical measures to sufficiently reduce the risk to patients had not been identified. Furthermore, it had not proved possible to agree a feasible and standardised way to adapt the management of overdose across the EU to cover both immediate- and modified-release paracetamol products. The CMDh therefore endorsed the PRAC recommendation that the marketing authorisations for medicines containing modified-release paracetamol, alone or combined with the opioid medicine tramadol, should be suspended.
The medicines will remain suspended unless the companies that hold the marketing authorisations can provide evidence of appropriate and practical EU-wide measures to help prevent overdose with these products and adequately reduce its risks.
Immediate-release paracetamol products, which are not affected by this review, will continue to be available as before.
Because the CMDh decision was agreed by majority vote, it will now be sent to the European Commission which will issue a final legally binding decision valid throughout the EU.
Healthcare professionals are advised of the followings:
• Modified-release paracetamol (alone or combined with tramadol) is being removed from the EU market since overdoses with modified-release paracetamol products can be unpredictable in their pharmacokinetics, and complex to manage.
• The established treatment guidelines for paracetamol overdose are based on the immediate-release products and may not be effective for treatment of overdoses with modified-release paracetamol.
• There are no issues with modified-release paracetamol preparations when used in accordance with their product information. Patients can safely continue treatment in the approved indication and doses with any remaining supply. Prescribers should discuss switching to an appropriate alternative if necessary once patients’ supply runs out.
• Until modified-release products have been removed from the market, adaptations of the standard protocol for paracetamol overdose should be considered. Although this should be determined at local level in consultation with local Poison Information Centres, the following general guidance may be helpful unless local guidelines have already been adapted or already recommend a more conservative approach:
- where overdose with ≥10 g of paracetamol (or ≥150 mg/kg body weight in children) is known or suspected, or where dose is unknown, treatment with antidote (N-acetylcysteine, NAC) should be started immediately regardless of the initial serum paracetamol level, since serum paracetamol level after acute overdose with modified-release products may peak up to 24 hours after ingestion;
- where <10 g of paracetamol has been ingested and time since ingestion is known, multiple serum paracetamol samples should be taken at suitable intervals (e.g. 4, 6, and 8 hours after ingestion). Additional samples should be considered if serum paracetamol concentrations are not declining to low levels. If serum paracetamol levels exceed the treatment nomogram at any time point, treatment with antidote (NAC) is indicated;
- if time since ingestion is unknown or serum paracetamol concentration cannot be obtained within 8 hours of the overdose, it is recommended that treatment with antidote (NAC) should be initiated without waiting for serum paracetamol concentrations to be available;
- if NAC treatment has been initiated, it should be prolonged beyond the first 21-hour NAC course if paracetamol level remains above the limit of detection (or greater than 10 mg/L) or if ALT is increasing (greater than 100 U/L), and should be continued until paracetamol is below the limit of detection (or 10 mg/L) or if ALT is falling below 100 U/L;
- antidote should be dosed as recommended by the local Poison Information Centre.
Please refer to the following website in EMA for details:
http://www.ema.europa.eu/../news_detail_002876.jsp&mid=WC0b01ac058004d5c1
In Hong Kong, there are 7 registered pharmaceutical products containing paracetamol in modified-/prolonged-release dose form and they belong to non-prescription medicines. The 7 products include Clariflu Sustained Release Tab (HK-47205) which is registered by Bayer Healthcare Ltd; Panadol Joint Extended Release Caplet 665mg (HK-59436), Panadol Long Lasting Tab 665mg (HK-51314), Panadol Extend Tab 665mg (HK-51316) and Panadol Extend Tab 665mg (Ireland) (HK-52683) which are registered by GlaxoSmithKline Consumer Healthcare (Hong Kong) Limited; Xykaa Extend Prolonged Release Tablet 650mg (HK-61400) which is registered by Evercare Pharmaceutical Co. Ltd; and Ensid-ER Extended Release Tablet 650mg (HK-62272) which is registered by LSB (HK) Ltd.
So far, the Department of Health (DH) has received 10 adverse drug reaction cases related to overdose/ liver injury after taking paracetamol. In February 2011, the Registration Committee of the Pharmacy and Poisons Board had discussed the risk of liver toxicity related to paracetamol, and decided that the sales packs of paracetamol products should include warnings on the potential risks of liver toxicity and damage, and advices against using more than the recommended dose and against using more than one product containing paracetamol. Related news of PRAC recommendation was posted on Drug Office Website on 2 September 2017 and 2 December 2017. A letter to inform healthcare professionals to draw their attention on the EMA recommendation was issued on 4 September 2017.
As previously reported, the matter with the above information announced by the EMA will be discussed by the Registration Committee of the Pharmacy and Poisons Board.
Ends/ Saturday, December 16, 2017
Issued at HKT 15:15
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