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The Drug-Induced Respiratory Disease Website and App

Frequency - Incidence

Incidence of respiratory adverse event(s) due to the specific drug as assessed by number of reported/published cases in the literature. Red digits in stars indicate: 0 = Very rare, questionable signal · 1 = < 10 cases · 2 = 10-50 cases · 3 = 50–100 cases · 4 = 100-200 cases · 5 = >200 cases

Evidence level/grade

Evidence level for respiratory adverse event(s) due to the specific drug as estimated using Hill’s (1965), Naranjo’s (1981), and Bégaud’s (1985) criteria applied to published cases. Blue digits in stars indicate: 0 = Questionable · 1 = Low · 2 = Moderate · 3 = Robust · 4 = Definite · 5 = Unquestionable, pathognomonic

VIII.a

Angioedema (may cause UAO, asphyxia and death)

Risk is increased in smokers and in patients with renal failure or in solid organ transplant recipients. Can be unilateral (PMID 14595286). Severe cases can fatal due to asphyxia. Ecallantide and icatibant are significant additions to the management of angioedema-UAO cases with compromised airway patency (PMID 24096073, 25328718, 25635988, 25944565. Significant upper airway angioedema is a potentially life-threatening condition capable of causing asphyxia. Management include maintenance or airway patency. In recalcitrant cases, in addition to icatibant (PMID 22936825, 22944544, 25646708), C1-inhibitor concentrate (PMID 22944544) or fresh-frozen plasma (FFP) (PMID 15191027, 24096073) are indicated (PMID 18206518). A report indicates that patients on this class of medications may develop unusually severe oral allergy syndrome with mouth or throat swelling (PMID: 25727650). ACEI-associated angioedema may also involve the genitalia or intestines, causing cramping, diarrhea or an acute abdomen with or without systemic hypotension (PMID 11773949)

Publications

Briggs B, Cline D, Husain I

Disposition of emergency department patients presenting with angiotensin-converting enzyme inhibitor-induced angioedema.

International journal of emergency medicine. 2025;18(1):11

Landry L, Witten T, Anwar AI, Jackson CN, Talbot NC, Ahmadzadeh S, Varrassi G, Shekoohi S, Kaye AD

Angiotensin-Converting Enzyme Inhibitors and Other Medications Associated With Angioedema.

Cureus. 2023;15(11):e49306

Day C, Van der Walt J, Crombie K, Hendrikse C, Peter J

Acute angioedema in Cape Town emergency centres and a suggested algorithm to simplify and improve management.

South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde. 2023;113(8):51-57

Weisman DS, Arnouk N, Asghar MB, Qureshi MR, Kumar A, Desale S, Camire L, Pineda S

ACE inhibitor angioedema: characterization and treatment versus non-ACE angioedema in acute hospitalized patients.

Journal of community hospital internal medicine perspectives. 2020;10(1):16-18

Burd M, McPheeters C, Scherrer LA

Orolingual Angioedema After Tissue Plasminogen Activator Administration in Patients Taking Angiotensin-Converting Enzyme Inhibitors.

Advanced emergency nursing journal. 2019;41(3):204-214

Ducote C, Kesterke MJ, Bhattacharjee R, Read-Fuller A, Reddy LV

Macroglossia secondary to lisinopril-induced acute angioedema.

Proceedings (Baylor University. Medical Center). 2019;32(1):70-72

Alharbi FA, Alharthi AA, Alsaadi FN

Perindopril-induced angioedema of the lips and tongue: a case report.

Journal of medical case reports. 2018;12(1):359

Sczepanski M, Bozyk P

Institutional Incidence of Severe tPA-Induced Angioedema in Ischemic Cerebral Vascular Accidents.

Critical care research and practice. 2018;2018:9360918

Depetri F, Tedeschi A, Cugno M

Angioedema and emergency medicine: From pathophysiology to diagnosis and treatment.

European journal of internal medicine. 2019;59:8-13

Jackeviciute J, Pilvinis V, Pilviniene R

Fatal outcome of late-onset angiotensin-converting enzyme inhibitor induced angioedema: A case report.

Medicine. 2018;97(31):e11695

Kostis WJ, Shetty M, Chowdhury YS, Kostis JB

ACE Inhibitor-Induced Angioedema: a Review.

Current hypertension reports. 2018;20(7):55

Gandhi J, Jones R, Teubner D, Gabb G

Multicentre audit of ACE-inhibitor associated angioedema (MAAAA).

Australian family physician. 2015;44(8):579-83

Bukhari E, Safdar OY, Shalaby M, AlSharif SM, Alsufiany K, Kari JA

Potentially lethal ACE-inhibitor-induced angioedema in a child.

Clinical case reports. 2015;3(6):427-30

Javaud N, Floccard B, Gontier F, Lapostolle F, Boccon-Gibod I, Martin L, Amarger S, Boumedienne A, Boubaya M, Asfar P, Coppere B, Ollivier Y, Bouillet L, Adnet F, Fain O

Bradykinin-mediated angioedema: factors associated with admission to an intensive care unit, a multicenter study.

European journal of emergency medicine : official journal of the European Society for Emergency Medicine. 2016;23(3):219-23

Berhe DF, Juhlin K, Star K, Beyene KG, Dheda M, Haaijer-Ruskamp FM, Taxis K, Mol PG

Adverse drug reaction reports for cardiometabolic drugs from sub-Saharan Africa: a study in VigiBase.

Tropical medicine & international health : TM & IH. 2015;20(6):797-806

Baş M, Greve J, Stelter K, Havel M, Strassen U, Rotter N, Veit J, Schossow B, Hapfelmeier A, Kehl V, Kojda G, Hoffmann TK

A randomized trial of icatibant in ACE-inhibitor-induced angioedema.

The New England journal of medicine. 2015;372(5):418-25

Felder S, Curtis RM, Ball I, Borici-Mazi R

Prognostic factors in outcome of angioedema in the emergency department.

Allergy and asthma proceedings. 2014;35(5):362-70

Chan NJ, Soliman AM

Angiotensin converting enzyme inhibitor-related angioedema: onset, presentation, and management.

The Annals of otology, rhinology, and laryngology. 2015;124(2):89-96

Loftus PA, Tan M, Patel G, Lin J, Helman S, Badhey A, Du E, Smith RV, Fried MP, Ow TJ

Risk factors associated with severe and recurrent angioedema: an epidemic linked to ACE-inhibitors.

The Laryngoscope. 2014;124(11):2502-7

Baram M, Kommuri A, Sellers SA, Cohn JR

ACE inhibitor-induced angioedema.

The journal of allergy and clinical immunology. In practice. 2013;1(5):442-5

Brook CD, Devaiah AK, Davis EM

Angioedema of the upper aerodigestive tract: risk factors associated with airway intervention and management algorithm.

International forum of allergy & rhinology. 2014;4(3):239-45

Rasmussen ER, Mey K, Bygum A

Angiotensin-converting enzyme inhibitor-induced angioedema--a dangerous new epidemic.

Acta dermato-venereologica. 2014;94(3):260-4

Bertazzoni G, Spina MT, Scarpellini MG, Buccelletti F, De Simone M, Gregori M, Valeriano V, Pugliese FR, Ruggieri MP, Magnanti M, Susi B, Minetola L, Zulli L, D'Ambrogio F

Drug-induced angioedema: experience of Italian emergency departments.

Internal and emergency medicine. 2014;9(4):455-62

Lewis LM

Angioedema: etiology, pathophysiology, current and emerging therapies.

The Journal of emergency medicine. 2013;45(5):789-96

Winters ME, Rosenbaum S, Vilke GM, Almazroua FY

Emergency department management of patients with ACE-inhibitor angioedema.

The Journal of emergency medicine. 2013;45(5):775-80

Leung E, Hanna MY, Tehami N, Francombe J

Isolated unilateral tongue oedema: the adverse effect of Angiotensin converting enzyme inhibitors.

Current drug safety. 2012;7(5):382-3

Montoro de Francisco A, García-Luque A, Fernández M, Puerro M

Side effects of angiotensin converting enzyme inhibitors and angiotensin II receptor antagonists: are we facing a new syndrome.

The American journal of cardiology. 2012;110(10):1552-3

Javaud N, Karami A, Stirnemann J, Pilot F, Branellec A, Boubaya M, Chassaignon C, Adnet F, Fain O

Bradykinin-mediated angioedema: factors prompting ED visits.

The American journal of emergency medicine. 2013;31(1):124-9

Holm JP, Ovesen T

Increasing rate of angiotensin-converting enzyme inhibitor-related upper airway angio-oedema.

Danish medical journal. 2012;59(6):A4449

Stojiljkovic L

Renin-angiotensin system inhibitors and angioedema: anesthetic implications.

Current opinion in anaesthesiology. 2012;25(3):356-62

Andrew N, Gabb G, Del Fante M

ACEI associated angioedema - a case study and review.

Australian family physician. 2011;40(12):985-8

Gallitelli M, Alzetta M

Icatibant: a novel approach to the treatment of angioedema related to the use of angiotensin-converting enzyme inhibitors.

The American journal of emergency medicine. 2012;30(8):1664.e1-2

Caballero T, Baeza ML, Cabañas R, Campos A, Cimbollek S, Gómez-Traseira C, González-Quevedo T, Guilarte M, Jurado-Palomo J, Larco JI, López-Serrano MC, López-Trascasa M, Marcos C, Muñoz-Caro JM, Pedrosa M, Prior N, Rubio M, Sala-Cunill A, Spanish Study Gr

Consensus statement on the diagnosis, management, and treatment of angioedema mediated by bradykinin. Part II. Treatment, follow-up, and special situations.

Journal of investigational allergology & clinical immunology. 2011;21(6):422-41; quiz 442-3

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.

Journal of hypertension. 2011;29(11):2273-7

Bramante RM, Rand M

Images in clinical medicine. Angioedema.

The New England journal of medicine. 2011;365(2):e4

Beavers CJ, Dunn SP, Macaulay TE

The role of angiotensin receptor blockers in patients with angiotensin-converting enzyme inhibitor-induced angioedema.

The Annals of pharmacotherapy. 2011;45(4):520-4

Kloth N, Lane AS

ACE inhibitor-induced angioedema: a case report and review of current management.

Critical care and resuscitation : journal of the Australasian Academy of Critical Care Medicine. 2011;13(1):33-7

Sánchez-Borges M, González-Aveledo LA

Angiotensin-converting enzyme inhibitors and angioedema.

Allergy, asthma & immunology research. 2010;2(3):195-8

Duerr M, Glander P, Diekmann F, Dragun D, Neumayer HH, Budde K

Increased incidence of angioedema with ACE inhibitors in combination with mTOR inhibitors in kidney transplant recipients.

Clinical journal of the American Society of Nephrology : CJASN. 2010;5(4):703-8

Taki M, Watanabe H, Hasegawa T, Bamba H, Shimada T, Hisa Y

Angioedema: 6 years experience with fourteen cases.

Auris, nasus, larynx. 2010;37(2):199-204

Hoover T, Lippmann M, Grouzmann E, Marceau F, Herscu P

Angiotensin converting enzyme inhibitor induced angio-oedema: a review of the pathophysiology and risk factors.

Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology. 2010;40(1):50-61

Banerji A, Clark S, Blanda M, LoVecchio F, Snyder B, Camargo CA Jr

Multicenter study of patients with angiotensin-converting enzyme inhibitor-induced angioedema who present to the emergency department.

Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology. 2008;100(4):327-32

Miller DR, Oliveria SA, Berlowitz DR, Fincke BG, Stang P, Lillienfeld DE

Angioedema incidence in US veterans initiating angiotensin-converting enzyme inhibitors.

Hypertension (Dallas, Tex. : 1979). 2008;51(6):1624-30

Weber MA, Messerli FH

Angiotensin-converting enzyme inhibitors and angioedema: estimating the risk.

Hypertension (Dallas, Tex. : 1979). 2008;51(6):1465-7

Symvoulakis EK, Kyrmizakis DE, Drivas EI, Bizakis J, Velegrakis GA, Lionis C

Angiotensin-converting enzyme inhibitor (ACE-I)- and angiotensin receptor blocker (ARB)-related angioedema: a neglected issue in daily practice in Greece.

The European journal of general practice. 2007;13(4):239-41

Cupido C, Rayner B

Life-threatening angio-oedema and death associated with the ACE inhibitor enalapril.

South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde. 2007;97(4):244-5

Sarkar P, Nicholson G, Hall G

Brief review: angiotensin converting enzyme inhibitors and angioedema: anesthetic implications.

Canadian journal of anaesthesia = Journal canadien d'anesthesie. 2006;53(10):994-1003

Bas M, Hoffmann TK, Kojda G

Evaluation and management of angioedema of the head and neck.

Current opinion in otolaryngology & head and neck surgery. 2006;14(3):170-5

Hurst M, Empson M

Oral angioedema secondary to ACE inhibitors, a frequently overlooked association: case report and review.

The New Zealand medical journal. 2006;119(1232):U1930

Shiber JR

Images in clinical medicine. Angioedema of the arytenoids.

The New England journal of medicine. 2005;353(17):e15

Sondhi D, Lippmann M, Murali G

Airway compromise due to angiotensin-converting enzyme inhibitor-induced angioedema: clinical experience at a large community teaching hospital.

Chest. 2004;126(2):400-4

Ducroix JP, Outurquin S, Benabes-Jezraoui B, Gras V, Chaby G, Strunski V, Salle V, Smail A, Lok C, Andrejak M

[Angioedema and angiotensin converting enzyme inhibitors: a report of 19 cases].

La Revue de medecine interne. 2004;25(7):501-6

Warrier MR, Copilevitz CA, Dykewicz MS, Slavin RG

Fresh frozen plasma in the treatment of resistant angiotensin-converting enzyme inhibitor angioedema.

Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology. 2004;92(5):573-5

Elinav E, Rabinowitz Y, Lorberbaum M, Nisanewitz V

Episodic macroglossia as the sole manifestation of angiotensin-converting enzyme inhibitor-induced angioedema.

The Annals of otology, rhinology, and laryngology. 2004;113(3 Pt 1):223-4

Amen F, Thirlwall A, Lale A, Corbridge R

Acute airway obstruction secondary to ACE inhibitors: a growing concern.

The Journal of laryngology and otology. 2004;118(1):70

Hill MD, Lye T, Moss H, Barber PA, Demchuk AM, Newcommon NJ, Green TL, Kenney C, Cole-Haskayne A, Buchan AM

Hemi-orolingual angioedema and ACE inhibition after alteplase treatment of stroke.

Neurology. 2003;60(9):1525-7

Dean DE, Schultz DL, Powers RH

Asphyxia due to angiotensin converting enzyme (ACE) inhibitor mediated angioedema of the tongue during the treatment of hypertensive heart disease.

Journal of forensic sciences. 2001;46(5):1239-43

Chiu AG, Newkirk KA, Davidson BJ, Burningham AR, Krowiak EJ, Deeb ZE

Angiotensin-converting enzyme inhibitor-induced angioedema: a multicenter review and an algorithm for airway management.

The Annals of otology, rhinology, and laryngology. 2001;110(9):834-40

Warner KK, Visconti JA, Tschampel MM

Angiotensin II receptor blockers in patients with ACE inhibitor-induced angioedema.

The Annals of pharmacotherapy. 2000;34(4):526-8

Assadi FK, Wang HE, Lawless S, McKay CP, Hopp L, Fattori D

Angiotensin converting enzyme inhibitor-induced angioedema: a report of two cases.

Pediatric nephrology (Berlin, Germany). 1999;13(9):917-9

Gibbs CR, Lip GY, Beevers DG

Angioedema due to ACE inhibitors: increased risk in patients of African origin.

British journal of clinical pharmacology. 1999;48(6):861-5

Mchaourab A, Sarantopoulos C, Stowe DF

Airway obstruction due to late-onset angioneurotic edema from angiotensin-converting enzyme inhibition.

Canadian journal of anaesthesia = Journal canadien d'anesthesie. 1999;46(10):975-8

Abbosh J, Anderson JA, Levine AB, Kupin WL

Angiotensin converting enzyme inhibitor-induced angioedema more prevalent in transplant patients.

Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology. 1999;82(5):473-6

Agah R, Bandi V, Guntupalli KK

Angioedema: the role of ACE inhibitors and factors associated with poor clinical outcome.

Intensive care medicine. 1997;23(7):793-6

Brown NJ, Snowden M, Griffin MR

Recurrent angiotensin-converting enzyme inhibitor--associated angioedema.

JAMA. 1997;278(3):232-3

Gabb GM, Ryan P, Wing LM, Hutchinson KA

Epidemiological study of angioedema and ACE inhibitors.

Australian and New Zealand journal of medicine. 1996;26(6):777-82

Minnisola S, Tirafili C, Rosso R, Costa G, Mazzouli G

Ultrasonic parameters of bone in young normals: effect of age and sex.

European journal of clinical investigation. 1996;26(11):947-50

Brown NJ, Ray WA, Snowden M, Griffin MR

Black Americans have an increased rate of angiotensin converting enzyme inhibitor-associated angioedema.

Clinical pharmacology and therapeutics. 1996;60(1):8-13

Thompson T, Frable MA

Drug-induced, life-threatening angioedema revisited.

The Laryngoscope. 1993;103(1 Pt 1):10-2

Oike Y, Ogata Y, Higashi D, Matsumura T, Numata Y

Fatal angioedema associated with enalapril.

Internal medicine (Tokyo, Japan). 1993;32(4):308-10

Pigman EC, Scott JL

Angioedema in the emergency department: the impact of angiotensin-converting enzyme inhibitors.

The American journal of emergency medicine. 1993;11(4):350-4

Waldfahrer F, Leuwer A, Krause J, Iro H

[Severe oropharyngeal angioedema caused by ACE inhibitor. A case report].

HNO. 1995;43(1):35-8

Warner NJ, Rush JE

Safety profiles of the angiotensin-converting enzyme inhibitors.

Drugs. 1988;35 Suppl 5:89-97

Cooper WD, Sheldon D, Brown D, Kimber GR, Isitt VL, Currie WJ

Post-marketing surveillance of enalapril: experience in 11,710 hypertensive patients in general practice.

The Journal of the Royal College of General Practitioners. 1987;37(301):346-9

Huwyler T, Wüthrich B, Mühlethaler K, Kuhn H, Jungbluth H, Späth P, Hochreutener H

[Angioedema caused by enalapril (Reniten)].

Schweizerische medizinische Wochenschrift. 1989;119(37):1253-6

Zech J, Tasman A, Maier H

[Angioneurotic edema of the tongue, induced by administration of ACE inhibitors].

HNO. 1990;38(4):143-4

Seidman MD, Lewandowski CA, Sarpa JR, Potesta E, Schweitzer VG

Angioedema related to angiotensin-converting enzyme inhibitors.

Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery. 1990;102(6):727-31

Roberts JR, Wuerz RC

Clinical characteristics of angiotensin-converting enzyme inhibitor-induced angioedema.

Annals of emergency medicine. 1991;20(5):555-8

Hedner T, Samuelsson O, Lunde H, Lindholm L, Andrén L, Wiholm BE

Angio-oedema in relation to treatment with angiotensin converting enzyme inhibitors.

BMJ (Clinical research ed.). 1992;304(6832):941-6

Kharasch ED

Angiotensin-converting enzyme inhibitor-induced angioedema associated with endotracheal intubation.

Anesthesia and analgesia. 1992;74(4):602-4