Multiple drugs

Abstract

Acute hypersensitivity to excipient: 6 case reports In a case series, 6 women aged 25–44 years were described, who developed acute hypersensitivity during treatment with ascorbic-acid, diclofenac, domperidone, esomeprazole, esomeprazole/naproxen, ibuprofen, lidocaine/prilocaine, medroxyprogesterone, paracetamol/codeine-phosphate/caffeine, PEG-3350/sodium-chloride/sodium-sulfate/potassium-chloride/ ascorbic-acid, PEG-3350/sodium-sulfate/sodium-bicarbonate/sodium-chloride/potassium-chloride, monosodium phosphate or povidone iodine. The allergy was attributed to excipient polyethylene glycol (PEG) present in these formulations [dosages not stated; not all routes, indications, duration of treatments to reactions onsets and outcomes stated]. Case 1: A 35-year-old woman experienced anaphylaxis after administration of IM medroxyprogesterone [Depo-Provera]. Anaphylaxis presented as rapid-onset sneezing, ocular irritation, rhinorrhoea, urticaria, profound hypotension, chest tightness, respiratory compromise and biphasic urticaria. She was treated with two doses of IM epinephrine [adrenaline], steroids, and nebulised salbutamol. She was diagnosed with acute hypersensitivity. Subsequently, symptoms improved. However, 6 hours following the initial treatment, she experienced further urticaria. She had recently tolerated similar progesterone as a oral contraceptive. Therefore, she was suspected with allergy to an excipient ingredient. The IM formulation of medroxyprogesterone contained PEG-3350 as excipient. Skin-prick testing (SPT) was positive to PEG-3350, and she was advised to avoid PEG-3350 containing preparations. Case 2: A 25-year-old woman developed acute urticaria, angioedema and respiratory compromise after ingestion of ibuprofen and esomeprazole [Nexium], containing Macrogols. She was initially suspected with nonsteroidal anti-inflammatory drug (NSAID) sensitivity. While she was awaiting for further investigation, she developed urticaria, angioedema, hypotension, pruritus and swelling of hands and feet after minimal ingestion of the PEG-3350 containing osmotic laxative PEG-3350/sodium-chloride/sodiumsulfate/potassium-chloride/ascorbic-acid [Movi-Prep]. She was diagnosed with acute hypersensitivity. Her symptoms improved after treatment with steroids and antihistamine. However, she experienced further urticaria after 6 hours. Additionally, she also reported biphasic urticaria and contact urticaria with certain cosmetics containing PEG-100. PEG was suspected as a common trigger agent. SPT was also positive to PEG-3350. The SPT was negative for celecoxib [Celebrex] and pantoprazole. Case 3: A 40-year-old woman developed urticaria and syncope within minutes of ascorbic-acid [effervescent vitamin C], containing HMW-PEG. Additionally, she developed urticaria, angioedema, and throat tightness associated with difficulty swallowing after treatment with osmotic laxative PEG-3350/sodium-sulfate/sodium-bicarbonate/sodium-chloride/potassium-chloride [KleanPrep], containing PEG-3350. She also had a history of urticaria and presyncope associated with esomeprazole/naproxen [Vimovo], containing PEG-8000. She also developed similar symptoms including generalized pruritus during a dental procedure with a use of topical anesthetic lidocaine/prilocaine [EMLA], which contained HMW-PEG. She was diagnosed with acute hypersensitivity. All identified agents contained HMW-PEG. However, SPT was inconclusive because of dermographism. A provocation challenge to HMW-PEG (Movicol), PEG-400 and PEG-3350 were positive. After a PEG avoidance strategy, she remained completely symptomfree. Also, she well tolerated challenges with PEG-free medications. The SPT was negative for desogestrel [Cerazette] and PEG-free pantoprazole. Case 4: A 44-year-old woman developed anaphylaxis presenting as perioral paresthesia, angioedema, dyspnoea, stridor, visual disturbance and syncope to osmotic laxative PEG-3350/sodium-sulfate/sodium-bicarbonate/sodium-chloride/potassium-chloride [Klean-Prep], containing PEG-3350. She was suspected with a PEG-3350 allergy and advised to avoid it until formal review. In the subsequent months, while awaiting assessment, she had a second anaphylaxis presenting as angioedema, dyspnoea and presyncope, within minutes of taking a PEG-4000 containing monosodium phosphate [effervescent phosphate replacement preparation; Phosphate Sandoz]. She was diagnosed with acute hypersensitivity. SPT was positive to PEG-3350, which was later avoided. She also developed urticaria following treatment with cosmetics containing LMW and HMW-PEG. Case 5: A 36-year-old woman was referred for assessment of multiple allergic drug reactions, presenting as chronic spontaneous urticaria, angioedema, paresthesia and throat tightness. The first episode occurred within minutes of a domperidone [Motilium] suppository, containing PEG-400 and 1000. She was managed with IM epinephrine [adrenaline], hydrocortisone, chlorphenamine, and fluid resuscitation. The second episode (presenting as angioedema, paresthesia and throat tightness) was secondary to PEG-6000 containing oral ibuprofen [Nurofen], again requiring epinephrine treatment. She was diagnosed with acute hypersensitivity. PEG was suspected a likely trigger and SPT was also positive for PEG-3350. Subsequently, she well tolerated PEGfree domperidone and ibuprofen. The SPT was negative for PEG-free oral domperidone tablet and ibuprofen syrup. Case 6: A 38-year-old woman developed multiple adverse drug reactions, including anaphylaxis, on a background of chronic spontaneous urticaria and angioedema (CSUA). The initial allergic episode consisting of urticaria and presyncope, developed following a PEG-400 and 6000 containing povidone iodine [Betadine] dressing to a wound. Additionally, she had systaemic symptoms of urticaria, angioedema, respiratory distress and hypotension with oral diclofenac [Voltorol] containing PEG-8000, IM diclofenac containing HMW-PEG, oral paracetamol/codeine-phosphate/caffeine [paracetamol and codeine; Solpadeine]. She also developed contact urticaria with various cosmetics, containing LMWand HMW-PEG. Subsequently, she tolerated PEG-free forms of NSAIDs and codeine. PEG was suspected as a common triggering agent. SPT was also positive to PEG-3350. It was recommended to strictly avoid PEG. She was diagnosed with acute hypersensitivity. After diagnosis, she also experienced anaphylaxis while shaving with a product containing PEG. At this time, she self-administered an epinephrine [adrenaline] autoinjector. The SPT test was negative for PEG-free celecoxib [Celebrex] and ibuprofen tablet.