Drug Reaction Probability Scale Score Research Articles

Teclistamab-Associated Sclerouveitis with Hypopyon.

To report a case of presumed teclistamab-associated sclerouveitis with hypopyon. Case report. A 62-year-old female with relapsed refractory multiple myeloma presented with right eye pain and decreased vision one week after starting teclistamab, and was found to have sclerouveitis with hypopyon. She received intravitreal vancomycin and ceftazidime due to concern for infectious endophthalmitis, but cultures were negative. Systemic workup for infectious and inflammatory etiologies was unremarkable. Her signs and symptoms improved with topical steroids and a one-week pause in teclistamab. This case constituted a Naranjo Adverse Drug Reaction Probability Scale score of 5, representing a "probable" association. Teclistamab, a novel bispecific antibody recently approved for the treatment of relapsed or refractory multiple myeloma, may be associated with sclerouveitis with hypopyon.

Asymptomatic Eosinophilia Induced by Systemic Colistin Therapy: A Brief Case Report

Colistin is a polymyxin group antibiotic, and colistimethate-sodium is the prodrug form of colistin and is inactive. Colistin is often the last optional drug for nosocomial infections caused by multidrug-resistant gram-negative microorganisms. We present a case of asymptomatic eosinophilia due to systemic colistin therapy. The increasing trend of absolute eosinophil counts appeared with recurrent colistin therapy and decreased when colistin was discontinued. The Naranjo Adverse Drug Reaction Probability Scale score was 7, and this score was classified as 'probable' for this case. Clinicians should consider this drug reaction in a patient with eosinophilia and avoid unnecessary laboratory tests and treatments.

Stevens-Johnson syndrome/toxic epidermal necrolysis overlap following sulfadoxine-pyrimethamine overdose: a case report

Stevens-Johnson syndrome/toxic epidermal necrolysis overlap is a rare but severe delayed-type hypersensitivity reaction that presents with widespread blistering, ulceration and necrosis of the skin and mucosa in the genetically predisposed and leads to significant morbidity and mortality. Sulfadoxine-pyrimethamine has been reported to cause a spectrum of drug hypersensitivity reaction (Stevens-Johnson syndrome, toxic epidermal necrolysis or Stevens-Johnson syndrome/toxic epidermal necrolysis overlap), but in rare occasions, hence this report. We report a 5-year-old boy who presented with fever and extensive mucocutaneous blistering and ulcerations 10 days following the ingestion of an overdose of sulfadoxine-pyrimethamine administered by a community health extension worker. Skin involvement was about 19%. The Naranjo Adverse Drug Reaction Probability Scale score of 6 was assigned (implying probable association between the ingested drug and the hypersensitivity reaction). The severity-of-illness score of toxic epidermal necrolysis of 1 was also assigned to this patient (implying low severity). He was managed conservatively with fluid, antibiotics, nutritional support and wound care measures. He recovered completely and satisfactorily. The patient's sister and father had reacted similarly but less severely when exposed to sulfadoxine-pyrimethamine. Health workers should pay close attention to every patient's family drug allergy history before administering any medications. Also, basic pharmacogenetic testing should be introduced into health facilities, especially for drugs known to cause serious adverse drug reactions. Furthermore, health workers should keep abreast with updates on treatment guidelines and also dutifully report all cases of adverse drug reactions to relevant bodies.

RECURRENT ANGIOEDEMA FOLLOWING ANGIOTENSIN CONVERTING ENZYME INHIBITOR DISCONTINUATION

TOPIC: Critical Care TYPE: Medical Student/Resident Case Reports INTRODUCTION: Angiotensin converting enzyme inhibitors (ACEIs) are guideline recommended first-line treatment for hypertension. Angioedema is a recognized side effect of ACEI therapy, yet clinicians are often unaware that limited case reports describe recurrent angioedema following ACEI discontinuation. This is a case of ACEI-induced angioedema occurring after discontinuing ACEI therapy. CASE PRESENTATION: An elderly male with medical history of hypothyroidism, hypertension, and heart failure presented from his long-term care facility complaining of face, tongue, and throat swelling with dysphagia and voice changes starting 24 hours prior. Examination showed normal vital signs and edema of aforementioned areas. He denied family history of similar occurrences. It was reported 12 days prior he was seen for unilateral lip swelling and his enalapril was discontinued without further treatment. Medication administration record review showed ACEI was appropriately discontinued by his care facility. He was given methylprednisolone, diphenhydramine, intramuscular epinephrine, C1 esterase inhibitor, and 2 units of fresh frozen plasma prior to admission. The patient was monitored in the intensive care unit due to mild airway compromise but did not require invasive airway protection. A serum complement factor 4 level was checked and returned normal. He was discharged after 5 days in stable condition with resolution of symptoms. DISCUSSION: ACEIs are the most common cause of drug induced angioedema in the United States. ACEI-induced angioedema is a self-limiting swelling that may involve the lips, tongue, upper airway, and rarely intestinal wall. Swelling is said to occur because of ACEI inhibition on the angiotensin converting enzyme preventing degradation of vasoactive substances such as bradykinin (1). Recurrence of angioedema after ACEI discontinuation was reported in 46% of cases in one retrospective study (2). The precise etiology of this delayed reaction is not well described, though it is reasonable to hypothesize in part, a drug washout period must occur. The adverse drug reaction probability scale score was 5 (probable) in this patient (3). Recurrence has been documented more commonly in elderly male patients (2). The mainstay of treatment for non-allergic angioedema caused by ACEIs is discontinuation of the offending drug and acute airway management if needed. No drug therapy has been proven effective in the treatment of this condition (1). CONCLUSIONS: Increased awareness of delayed ACEI-induced angioedema following ACEI discontinuation is important among health care providers for appropriate diagnosis and monitoring. While self-limiting without a known effective treatment, close airway monitoring is critical for patient survival. Improved awareness would also allow patients with a history of ACEI-induced angioedema to be cognizant of the potential for recurrence early following drug discontinuation. REFERENCE #1: Erickson DL, Coop CA. Angiotensin-converting enzyme inhibitor-associated angioedema treated with c1-esterase inhibitor: A case report and review of the literature. Allergy Rhinol (Providence). 2016;7(3):168-171. REFERENCE #2: Beltrami L, Zanichelli A, Zingale L, Vacchini R, Carugo S, Cicardi M. Long-term follow-up of 111 patients with angiotensin-converting enzyme inhibitor-related angioedema. J Hypertens. 2011 Nov;29(11):2273-7. REFERENCE #3: LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-. Adverse Drug Reaction Probability Scale (Naranjo) in Drug Induced Liver Injury. [Updated 2019 May 4]. DISCLOSURES: No relevant relationships by Mark Malesker, source=Web Response No relevant relationships by Shraddha Narechania, source=Web Response No relevant relationships by Bryton Perman, source=Web Response

A Cause of Pancreatitis in a Commonly Used Antibiotic: Metronidazole-induced Pancreatitis

Metronidazole is a nitroimidazole antibacterial medication used in the treatment of anaerobic bacteria and protozoa. The main adverse effects include headache, nausea, vaginitis, metallic taste, neuropathy and rarely pancreatitis. Acute Pancreatitis is characterized by abdominal pain and elevated pancreatic enzymes including lipase. Here we present a case of elderly female who had pancreatitis associated with metronidazole therapy. The patient was an 85 year old female with medical history of colon cancer s/p resection, atrial fibrillation, hypertension, diabetes mellitus type 2 and hypothyroidism who presented with abdominal pain, nausea. One month prior to presentation she was treated for a urinary infection with cefpodoxime. She started having diarrhea and tested positive for Clostridium Difficile toxin. She was started on metronidazole. Two weeks later, she developed abdominal pain and nausea. Epigastric tenderness was present on exam with a negative murphy sign. Her lipase level was 17604 U/L. Liver function tests were unremarkable; ALT of 26 U/L, AST of 19 U/L, alkaline phosphatase of 46 U/L and a total bilirubin of 0.2 mg/dL. Serum triglycerides were 122. A right upper quadrant ultrasound was done which showed normal gallbladder size, wall thickness and normal common bile duct of 5.5mm. Metronidazole was stopped with resolution of abdominal pain and elevated lipase. No other obvious etiology of her pancreatitis was found. The Naranjo adverse drug reaction probability scale score was calculated to be a 4, indicating a possibility of adverse reaction from metronidazole. Approximately 2% of pancreatitis cases are drug-induced. Per our literature review there have been only 9 cases of pancreatitis associated with metronidazole. Although the mechanism is unknown, one possibility is redox cycling of metronidazole yielding hydrogen peroxide, superoxide and other free radicals which are toxic to pancreatic beta-cells. If metronidazole-induced pancreatitis is suspected, we recommend discontinuation of the medication and supportive care. In summary, physicians should be aware of the possibility of metronidazole as a possible etiology of pancreatitis, given that several million prescriptions of this medication dispensed every year in the United States.

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Highly Probable Drug Reaction With Eosinophilia and Systemic Symptoms Syndrome Associated With Lenalidomide.

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a life-threatening hypersensitivity reaction to medications. We report a case of a 75-year-old African American female who presented with generalized rash with desquamation and malodorous secretions. She was febrile and hypotensive, and required vasopressors for hemodynamic instability. Sepsis secondary to skin or soft tissue infection was considered initially. However, she recently was started on lenalidomide for treatment of her multiple myeloma, and her white blood cell count of 17 K/µL with 55% eosinophils along with peripheral smear showing eosinophilia suggested lenalidomide-induced rash. Lenalidomide was discontinued, and methylprednisolone was initiated. Four days after lenalidomide discontinuation, vasopressors were discontinued. Blood cultures did not exhibit any growth. The Niranjo Adverse Drug Reaction Probability Scale score of 9 suggests lenalidomide was a highly probable cause of DRESS syndrome. The temporal relation of lenalidomide administration and development of symptoms plus improvement of rash with the discontinuation of lenalidomide and reappearance on restarting lenalidomide in the follow-up clinic strengthens our suspicion of lenalidomide-induced DRESS syndrome. Cases of lenalidomide-induced DRESS syndrome are sparse; however, DRESS syndrome is fatal in approximately 10% of patients. Providers should be aware and keep a vigilant eye out for this adverse reaction with lenalidomide.

Linezolid Induced Black Hairy Tongue an Uncommon Phenomenon: A Case Report with Update of Review of Literature

As the use of newer antibiotics like Linezolid is tremendously increasing due to their efficacy and safety against methicilin resistant staphylococcus aureus and Vancomycin resistant entero-cocci, its rarer side effect like black hairy tongue is often overlooked. Case presentation: A 26 year-old-male, reported with asymptomatic black hairy tongue (BHT) on tenth day after taking Linezolid 600mg twice daily for his left foot infection. His tongue examination was consistent with black hairy tongue. He neither exhibited any predisposing factor nor any history of substance abuse or drug except Linezolid and prompt withdrawal of drug led to complete resolution of BHT on seventh day. Re-challenge test revoked similar response on tenth day. WHO-UMC causality scale showed certain adverse drug reaction and on Naranjo’s adverse drug reaction probability scale score of 10 indicates definite association. Conclusion: This case report is highlighted due to its rarity, self-limiting and reversible condition. The purpose of the paper is to create awareness amongst medical fraternity about Linezolid induced Adverse Drug Reaction.

Pentoxifylline-Induced Thrombocytopenia

Pentoxifylline-induced thrombocytopenia is rare, and information is lacking about its presentation. We describe a 72-year-old Chinese male who developed thrombocytopenia after initiation of pentoxifylline for the treatment of chronic lower limb ischemia due to peripheral artery disease. Venous thromboembolism had been ruled out with an ultrasound. Vascular surgeons had also determined there was no indication for surgical intervention. Four days after initiation of pentoxifylline, he developed thrombocytopenia, and his platelets were 68 × 103/μL. He was not in overt disseminated intravascular coagulation (DIC), based on his International Society for Thrombosis and Hemostasis (ISTH) DIC score of 4. Dengue fever, which is endemic in Singapore, was ruled out. Pseudothrombocytopenia was also excluded with a peripheral blood film. When his platelets continued to fall, pentoxifylline was discontinued on the fifth day of treatment, and platelets normalized 48 hours after discontinuation. Pentoxifylline was a probable cause of thrombocytopenia using the Naranjo Adverse Drug Reaction Probability Scale (score = 7). The patient did not receive further doses of pentoxifylline. Prescribers should be aware of the risk of thrombocytopenia with pentoxifylline therapy and discontinue its use promptly if it is suspected.

Herbal drug related warfarin intoxication

Warfarin is a widely used antithrombotic drug in prevention of both arterial and venous thrombosis. Glucosamine is a popular dietary supplement used in symptomatic treatment of osteoarthritis. The interaction mechanism between these two drugs is not known yet. 63 year old woman, who was taking warfarin therapy 5 mg /day for 5;months for pulmonary embolism (therapeutic INR range:2.0–3.0), visited the emergency room with haematuria and rash. She had synchronous breast and colonic tumours for which right mastectomy and right hemicolectomy were done 5 months ago. Her INR (Internatıonal Normalized Ratio) values were highly increased (12.5) due to consumption of a herbal drug involving glucosamine hydrochloride 250 mg , boswellia extract and grapefruit extract at that day for arthralgia. Boswellia extracts are used in management of osteoarthritis. Naranjo adverse drug reaction probability scale score was 6, which indicated a probable relationship between the patient’s elevated INR and use of two drugs (warfarin and herbal drug) at the same time. After discontinuation of both drugs, two units of fresh frozen plasma were given. Her INR reduced to 2.5; as a result haematuria and rash regressed. This case report suggests a potential interaction between warfarin and both glucosamine and grapefruit extract. The inhibitory effect of grapefruit extract on cytochrome P450 isoenzymes is combined with the effect of glucosamine. Clinicians should be aware of patients taking herbal medicines with such drugs like warfarin which has narrow therapeutic index.

Memory loss during lenalidomide treatment: a report on two cases

BackgroundThere are many reports of cognitive dysfunction in patients receiving chemotherapy or targeted therapies. Many antineoplastic agents may be involved in the condition also known as “chemo brain” or “chemo fog”.Case presentationTwo male patients (aged 41 and 70) with multiple myeloma developed severe, rapidly progressing cognitive impairment (mostly involving episodic memory) and loss of independence in activities of daily living during lenalidomide-based treatment. On withdrawal of the drug, one patient recovered normal cognitive function and independence in activities of daily living, whereas mild cognitive impairment persisted in the other patient. The Naranjo Adverse Drug Reaction Probability Scale score was 6 out of 13 for the first patient and 5 out of 13 for the second, suggesting a probable causal relationship between the adverse event and lenalidomide administration.ConclusionLenalidomide may induce particular cognitive disorders (notably episodic memory impairments) in some patients. The drug’s putative neurotoxicity is probably promoted by specific risk factors (such as previous chemotherapy, prior mild cognitive impairment, age and the presence of cerebrovascular lesions).

Gastrointestinal bleeding secondary to interaction of Artemisia absinthium with warfarin

Artemisia absinthium, also known as wormwood, is used widely as an herbal medicine. In this report, we introduce an 82-year-old Turkish woman who was treated with warfarin for atrial fibrillation and was hospitalized for gastrointestinal bleeding as a result of extremely elevated international normalized ratio (INR) after consumption of A. absinthium. Naranjo adverse drug reaction probability scale score was 6, which indicated a probable relationship between the patient's elevated INR and her concomitant use of wormwood and warfarin. Clinicians should be vigilant about potential dangers of herbal medicines taken with conventional drugs, and patients taking drugs with a narrow therapeutic index, such as warfarin, should be educated about avoiding consumption of herbal medicines.

Probable levetiracetam-related serum alkaline phosphatase elevation

BackgroundLevetiracetam (LEV) is an antiepileptic drug with a favorable tolerability and safety profile with little or no effect on liver function.Case presentationHere, we reported an epileptic pediatric patient who developed a significant elevation in serum alkaline phosphatase level (ALP) during LEV monotherapy. Moreover, the serum ALP level was surprisingly decreased to normal after LEV discontinuation. The Naranjo Adverse Drug Reaction Probability Scale score was 6, indicating firstly LEV was a probable cause for the increased serum ALP.ConclusionsCautious usage and concerns of the LEV-associated potential ALP elevation should be considered when levetiracetam is prescribed to epilepsy patients, especially pediatric patients.

Probable Association of Tachyarrhythmia With Nebulized Albuterol in a Child With Previously Subclinical Wolff Parkinson White Syndrome

We present the case of a 2-year-old asthmatic boy with atrioventricular (AV)-reentry tachycardia following albuterol inhalation, who was later diagnosed with Wolff-Parkinson-White (WPW) syndrome. The Naranjo adverse drug reaction probability scale score for this adverse event was 7, indicating that the association between his AV-reentry tachycardia and inhalation of albuterol is probable. To our knowledge, this is the first case report that shows the potential arrhythmogenic effects of albuterol in a child with WPW syndrome. We urge clinicians to be aware of this potentially life-threatening adverse effect and to closely monitor these patients when they need beta-adrenergic drugs in case of emergency. Furthermore, this report highlights the dilemma regarding the safe treatment of pediatric patients with both asthma and WPW syndrome.

Hypotension associated with menaquinone

A case of mild symptomatic hypotension after treatment with menaquinone (vitamin K(2)) is reported. A 62-year-old white man with a medical history of hyperlipidemia, coronary artery disease, and benign prostatic hyperplasia was started on a regimen of menaquinone 100 μg daily as a supplement to his medications for coronary artery disease. Approximately two hours after taking the first dose of menaquinone, the patient experienced sudden weakness and dizziness. At that time, his blood pressure was 110/55 mm Hg. On day 2 of treatment, his blood pressure was 105/50 mm Hg two hours after taking menaquinone; however the patient was asymptomatic. On day 3, the patient's blood pressure was 100/50 mm Hg two hours after menaquinone ingestion, with symptoms of generalized weakness and dizziness, at which point menaquinone was discontinued. All of the patient's heart rate measurements were within normal limits during this time. The day after discontinuing menaquinone, the patient's blood pressure was 115/65 mm Hg, after which his readings were within normal limits on subsequent days. After a 10-day menaquinone-free period, the patient was rechallenged. On rechallenge day 1, the patient's blood pressure was 115/60 mm Hg two hours after menaquinone ingestion; on rechallenge day 2, his blood pressure was 100/55 mm Hg. The patient was asymptomatic on both days of the rechallenge. The Naranjo et al. adverse drug reaction probability scale score was 7, indicating a probable adverse reaction to menaquinone. The drug interaction probability scale score for this case was 6, indicating that a drug interaction was probable. A 62-year-old white man developed mild symptomatic hypotension while receiving menaquinone therapy.

Acute Hypotensive Transfusion Reaction With Concomitant Use of Angiotensin-Converting Enzyme Inhibitors

Hypotension can be a manifestation of transfusion reactions, including acute hemolysis, bacterial contamination, transfusion-related acute lung injury, and anaphylaxis. In addition to hypotension, these reactions usually present with other characteristic symptoms and signs. In rare cases, hypotension is the only manifestation of a transfusion reaction. This reaction, characterized by early and abrupt onset of hypotension that resolves quickly once the transfusion is stopped, is referred to as acute hypotensive transfusion reaction (AHTR). We report a case of AHTR observed in a patient on angiotensin-converting enzyme inhibitor therapy. The Naranjo adverse drug reaction probability scale score indicated that the association between angiotensin-converting enzyme inhibitor therapy and AHTR was probable. If a patient on angiotensin-converting enzyme inhibitor therapy develops AHTR, it is important to recognize the need to switch to another class of antihypertensive medication, at least while the patient continues to require transfusion.

Interstitial Lung Disease Associated With Azacitidine Use

Azacitidine is a pyrimidine nucleoside analog licensed for treatment of adult patients with myelodysplastic syndrome. Azacitidine acts as an inducer of cell differentiation by causing demethylation and re-expression of genes silenced by hypermethylation. We report a 56-year-old man with myelodysplastic syndrome who developed interstitial lung disease after azacitidine therapy. Open lung biopsy revealed a nonresolving organizing pneumonia pattern and bronchocentric granulomatous pattern suggestive of drug-induced lung injury. Treatment with steroids and discontinuation of azacitidine led to resolution of interstitial lung disease. The Naranjo adverse drug reaction probability scale score indicated that the association between azacitidine and interstitial lung disease was probable. Interstitial lung disease is a serious but uncommon side effect of this relatively safe drug. The mechanism underlying this is still unclear. The patient was subsequently treated with decitabine with no recurrence of interstitial lung disease.

Psoriasis Induced by Losartan Therapy: A Case Report and Review of the Literature

Psoriasis is a papulosquamous disease of multifactorial etiology. A combination of genetic and environmental agents is implicated in its pathogenesis. A variety of triggers, including infection, stress, and medications, have been recognized as precipitants of this disease. Nonsteroidal anti-inflammatory drugs, beta-blockers, lithium, synthetic antimalarials, and gold are the most common drugs implicated in precipitating psoriasis. We report a patient with psoriasis induced by initiation of losartan therapy, which resolved with discontinuation of the drug. The Naranjo adverse drug reaction probability scale score indicated that the association between losartan use and psoriasis was probable.

Reversal of refractory sulfasalazine-related renal failure after treatment with corticosteroids

Background: Sulfasalazine is a combination of sulfapyridine and 5-aminosalicylic acid and is used as a first-line treatment in inflammatory bowel disease. Objective: We describe a case of acute interstitial nephritis that presented after 7 months of sulfasalazine therapy. Despite the discontinuation of the drug, the patient's renal function continued to deteriorate and recovered only when systemic corticosteroid treatment was initiated. Case summary: A 19-year-old white male (weight, 65 kg) presented in November 2006 with upper abdominal pain, fever ≥38°C, bloody diarrhea, anorexia, and weight loss. Ulcerative colitis involving the left colon was diagnosed based on results of a colonoscopy and intestinal biopsy, and treatment was initiated with cefprozil 1 g/d, mesalamine 3 g/d, methylprednisolone 32 mg/d, and ranitidine 300 mg/d. All drugs were administered orally. Cefprozil and ranitidine were discontinued after 10 days. Mesalamine was discontinued 1 month later because of gastrointestinal adverse effects (vomiting and diarrhea), and methylprednisolone was tapered over the next 3 months to zero. The patient then had a relapse, and sulfasalazine 2 g/d orally was administered. Seven months after the initiation of sulfasalazine, the patient developed fatigue, nausea, fever more prominent in the afternoon (increased from 38°C to 40°C), and nocturia, and he was admitted to the hospital. He had no history of renal impairment. Laboratory test results showed elevated serum urea and creatinine levels (170 and 7 mg/dL, respectively), while kidney ultrasound showed normal kidneys without obstruction. The patient had a Naranjo Adverse Drug Reaction Probability scale score of 6, indicating a probable adverse drug reaction with sulfasalazine. Based on these findings, sulfasalazine-related nephrotoxicity was suspected, and the drug was discontinued. During the next 4 days, serum urea and creatinine values increased to 212 and 8.3 mg/dL, respectively, and then remained stable for 3 days. A renal biopsy was performed, which revealed changes compatible with granulomatous interstitial nephritis. The patient received methylprednisolone 500 mg IV for 3 days, followed by oral administration of methylprednisolone 16 mg/d for 1 month. Renal function recovered completely a few days after initiation of corticosteroids, and the patient's condition continued to be stable 1 year later (eg, serum urea, 34 mg/dL; creatinine level, 0.9 mg/dL). Conclusions: Although this isolated case of sulfasalazine- related interstitial nephritis cannot lead to definite conclusions, treatment with corticosteroids was effective in this patient and should be considered irrespective of the time of exposure to sulfasalazine. However, randomized controlled trials are needed to provide evidence regarding the efficacy and tolerability profile of corticosteroids.

Allergic shock and death associated with protamine administration in a diabetic patient

Background: Insulin is used to treat patients with both type 1 and type 2 diabetes mellitus. Allergic reac- tions to insulin might be triggered by insulin itself or inactive ingredients in the insulin formulation, includ- ing proteins such as protamine in neutral protamine Hagedorn (NPH) insulin. The use of highly purified animal insulin and human recombinant insulin has reduced the incidence of anaphylactic reactions to insulin from ~30% to <1%. Objective: We report a case of fatal allergic shock after the administration of protamine in a patient with a history of allergy to fish and a protamine-containing insulin. Case summary: A 72-year-old Chinese male patient (height, 175 cm; weight, 80 kg) with a history of diabetes and progressive limb weakness was diagnosed with spinal vascular malformations after admission to the Xuan Wu Hospital of Capital Medical University, Beijing, People's Republic of China. He underwent epidural spinal cord arteriovenous fistula embolization with a liquid embolic agent (ethylene vinyl alcohol copolymer) after spinal cord angiography. During the operation, heparin was infused every hour with 6250, 2500, 2500, and 1250 IU, respectively. The last dose of heparin was administered ~10 minutes before the opera- tion was completed. This was followed by the admin-istration of protamine to neutralize the remaining heparin in the patient's body. Blurry vision and dizziness 5 minutes after protamine administration were followed by pruritus and hives over his neck and face. Oxygen was administered and 10 mg of dexamethasone with 2 mg of epinephrine was injected. The patient's heart rate dropped, his blood pressure decreased, and his arterial oxygen saturation (SaO 2) declined progressively. About 10 minutes after the administration of protamine sulfate, the patient developed bradycardic arrest. Cardiopulmonary resuscitation efforts were undertaken and the patient was administered epinephrine 2 mg IV, atropine 0.5 mg IV, and subsequently, intravenous dopamine (50 mg/h). Ten minutes later, the patient's heart rate gradually increased, but blood pressure fluctuated, and SaO 2 ranged from 90% to 100%. Despite the initial response, the patient lost consciousness and heart rate declined progressively within 5 hours. Vasoactive agents including dopamine, norepinephrine, and adrenaline were administered. After all these measures proved inef- fectual, the patient died. It was later determined that the patient had a history of allergic reactions to fish as well as to a premixed insulin that contained soluble human insulin 30% and low-protein intensive insulin zinc 70% (NPH). The Naranjo adverse drug reaction probability scale score for the association of protamine with the allergic reaction was 4, suggesting a possible relationship. Conclusion: This case report highlights a preventable fatal allergic reaction possibly associated with protamine administration in a patient with a history of allergy to a protamine-containing insulin.