• Colleen M Culley and Edward P Krenzelok.
• University of Pittsburgh Medical Center/University of Pittsburgh School of Pharmacy, PA 15213, USA.
• Toxicol Rev. 2005 Jan 1; 24 (2): 131-43.

AbstractParacetamol (acetaminophen) poisoning remains the most common exposure reported to US poison information centres and the leading cause of poisoning-related fatalities, despite the availability of an effective antidote, acetylcysteine. Oral acetylcysteine solution has been approved for the management of acetaminophen poisoning in the US for four decades. Until the recent approval of intravenous acetylcysteine in the US, it was necessary to compound the oral solution for intravenous administration. The effectiveness and tolerability of oral and intravenous acetylcysteine for the prevention of hepatotoxicity induced by paracetamol poisoning are well established in the literature. Intravenous acetylcysteine may be preferred over oral administration based on improved tolerability, ease of administration and the shortened course of therapy (20 hours intravenous vs 72 hours oral). The two intravenous acetylcysteine regimens documented in the literature, 48 hours and 20 hours, have similar efficacy when started within 8-10 hours of ingestion. Although there are no legal concerns with continuing the routine compounding of the oral solution to an intravenous product, new standards for pharmacy compounding of sterile preparations set forth by the US Pharmacopoeia highlight that the risk of compounding products for intravenous use must be assessed carefully. Changing the route of administration of a sterile oral solution to an intravenous preparation, when a commercial sterile and pyrogen-free product is available, may not be advisable. The best cost-containment strategies must be used for introduction of the more costly sterile, pyrogen-free intravenous acetylcysteine formulation by hospitals and healthcare systems. The intravenous acetylcysteine product is more cost effective when given for 20 hours than other treatment protocols based on the costs of acetylcysteine and hospitalisation. If used per protocol, the 20-hour intravenous acetylcysteine regimen may decrease hospital length of stay, thereby, offsetting the increased drug cost. Data conflict on the efficacy and administration of intravenous acetylcysteine for off-label uses, such as radiographic contrast media-induced nephropathy prevention and reperfusion in orthotopic liver transplantation. The costs for the intravenous formulation for these indications is significantly higher than use of the oral formulation for oral administration in radiographic contrast media-induced nephropathy prevention and compounded for intravenous use in orthotopic liver transplantation. The oral solution should be retained by healthcare systems for oral and inhalation applications, such as respiratory conditions, oral administration for radiographic contrast media nephropathy prevention, or the use of the 72-hour oral protocol to treat paracetamol poisoning, when the intravenous preparation cannot be used.

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