Anaphylaxis to intravenous paracetamol containing povidone. A case report and narrative review of excipient allergy related to anaesthesia

Abstract

Investigation of intraoperative anaphylaxis includes the exclusion of potential trigger agents the individual was exposed to within a plausible interval preceding the reaction. Occasionally, none of these agents will test positive. In this situation it is important to consider that excipients may be responsible for anaphylaxis, that the dilutions prepared to test the medication may not contain an appropriate concentration of the excipient to induce a positive skin reaction, or if an alternative formulation of the medication is tested, it may not contain the culprit excipient. This case describes a patient, who previously experienced an anaphylactic reaction to Betadine® (Sanofi-Aventis Australia Pty Ltd, North Ryde BC, NSW) experiencing anaphylaxis in the recovery period after general anaesthesia where Betadine was avoided. The recently administered therapeutics were excluded by skin testing, however further investigation determined that a povidone-containing formulation of paracetamol had been administered. Skin testing with povidone-containing paracetamol resulted in a positive reaction in the patient, but not in a volunteer control. Pharmaceutical excipients are added to medications to increase absorption, shelf-life and efficacy. Different brands of the same drug may contain different excipients. When testing for anaphylaxis with such compounds one must be sure the dilution is appropriate for both the parent compound and the excipient to ensure the accuracy of skin-prick and intradermal testing. This case demonstrates the potential for excipients to cause severe allergy and the importance of detailed history pertaining to previous allergic episodes as even the most unlikely of medications can potentially result in anaphylaxis due to excipients.

Diagnostic Value of Oral Provocation Tests in Drug Hypersensitivity Reactions Induced by Nonsteroidal Anti-Inflammatory Drugs and Paracetamol

“…Usually, after a negative DPT, the patient receives information that he can use the active substance, but, in his daily life, he can buy and take many generic drugs containing different excipients ( Tables S1–S4 ). Many of them have allergenic potential and can cause hypersensitivity reactions, as shown in Table 4 [ 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 ]. An excellent illustration of this is the case series by Cox et al [ 81 ].…”

“…In our group A2, symptoms reported after reexposure to ASA despite negative challenge were urticaria (5 persons), urticaria and erythema (1 person), angioedema (2 persons), dyspnea (1 person). In fact, many excipients in ASA generics ( Table S1 ) can trigger such reactions: carmine [ 34 ], citric acid [ 38 ], cochineal red [ 39 ], glycine [ 44 ], hypromellose [ 48 ], macrogol [ 50 ], mannitol [ 52 , 53 , 54 , 55 ], polysorbate 80 [ 56 , 57 ], potato starch [ 63 ], and povidone [ 60 , 61 , 62 ]. Another patient developed urticaria after reexposure to MEL.…”

“…Excipients in MEL generics ( Table S3 ) can be responsible for an immediate immune reaction: potassium acesulfame [ 31 ], aspartame [ 33 ], citric acid [ 38 ], mannitol [ 52 , 53 , 54 ], and povidone [ 60 , 61 , 62 ].The next case of urticaria has been reported after reexposure to DIC. The following excipients found in generics of DIC have been reported to cause immediate reactions, among others, cochineal red [ 39 ], Hypromellose [ 22 ], mannitol [ 52 , 53 , 54 , 55 ], polysorbate 80 [ 56 , 57 ], and povidone [ 60 , 61 , 62 ] ( Table S4 ). Finally, one of our patients, after reexposure to PRC, reported erythema several hours after exposure.…”

Comparative Effects of Iv Injection of Ketoprofen and Paracetamol in the Treatment of Tension-Type Headache

“…In terms of a drug-induced allergic reaction, Paracetamol was found safer than Ketoprofen. However, some studies [17,18] have already demonstrated the hypersensitivity to paracetamol in patients. Similarly, ketoprofen allergy is also described in a report by [19].…”

Antiseptic drugs and disinfectants with special scrutiny of COVID-19 pandemic related side effects

“…A case of anaphylaxis in a 55-year-old woman was described who received an intravenous infusion containing paracetamol with povidone as excipient. The authors stressed the potential of excipients to cause severe allergy ( Preuss, Goddard, Clarke, Platt, & Sadleir, 2020 ) [A].…”