Sirolimus-Induced Angioedema

Wadei, Hani M.; Gruber, Scott A.; El-Amm, Jose M.; Garnick, James; West, Michael O.; Granger, Darla K.; Sillix, Dale H.; Migdal, Stephen D.; Haririan, Abdolreza

doi:10.1111/j.1600-6143.2004.00429.x

Cited by 38 publications

(27 citation statements)

References 15 publications

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“…In both trials, the incidence of angioedema in ACEi-treated populations ranged between 0.3% and 0.68%. Our observation is in good agreement with previously published reports, suggesting a higher frequency of ACEi-associated angioedema (1% to 5%) in patients who underwent transplantation (9,(11)(12)(13). It has been suggested that ACEis increase bradykinin levels, which could be a critical step for development of angioedema (3,15,16).…”

Section: Discussionsupporting

confidence: 83%

“…The authors suggested a causal relationship between sirolimus and nonurticarial angioedema at least in 4 of 12 patients. This observation is in line with the report of Wadei et al (13) describing three cases of sirolimus-induced angioedema in African-American renal allograft recipients. None of the patients were receiving any other drug potentially associated with angioedema.…”

Section: Discussionsupporting

confidence: 82%

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Increased Incidence of Angioedema with ACE Inhibitors in Combination with mTOR Inhibitors in Kidney Transplant Recipients

Duerr¹,

Glander²,

Diekmann³

et al. 2010

Clinical Journal of the American Society of Nephrology

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Background and objective: The clinical manifestation of angioedema ranges from minor facial edema up to life-threatening swelling of mouth and throat. Hereditary defects, drugs, and food allergies may play a role in the development of angioedema. We systematically investigated the incidence of angioedema in renal allograft recipients treated with mTOR inhibitors (mTORis).Design, setting, participants, & measurements: All patients in the authors' electronic database who had received mTORis (n ‫؍‬ 309) between 2000 and 2008 were identified. Of these, 137 were additionally treated with angiotensin-converting enzyme inhibitors (ACEis).Results: Nine patients (6.6%, 3.8 per 100 treatment years) developed angioedema after a mean period of 123 days under combined therapy with mTORi and ACEi. Among the remaining 172 patients on mTORi, including 119 patients treated with angiotensin-receptor blockers, only two developed angioedema (1.2%, 0.5 per 100 treatment years, P ‫؍‬ 0.01). In patients receiving mycophenolate and ACEi (n ‫؍‬ 462), 10 instances of angioedema were found (2.1%, 0.8 per 100 treatment years, P ‫؍‬ 0.004).Conclusions: This systematic investigation demonstrated a noticeable incidence of 6.6% angioedema under combined therapy with mTORi and ACEi in kidney transplant recipients. Treatment with either ACEi or mTORi alone resulted in a significantly lower incidence of angioedema, suggesting that this combination should be avoided.

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Section: Discussionsupporting

confidence: 83%

Section: Discussionsupporting

confidence: 82%

Increased Incidence of Angioedema with ACE Inhibitors in Combination with mTOR Inhibitors in Kidney Transplant Recipients

Duerr¹,

Glander²,

Diekmann³

et al. 2010

Clinical Journal of the American Society of Nephrology

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“…Several more recent reports focused on the putative role of tacrolimus and rapamycins (i.e. sirolimus and everolimus), a new family of immunosuppressive agents, in the pathogenesis of angioedema in organ transplant recipients [4,5,6,7,8,9]. …”

Section: Introductionmentioning

confidence: 99%

Angioedema in Renal Transplant Recipients on Sirolimus

Mahé

Morélon²,

Lechaton³

et al. 2007

Dermatology

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Background:Most drug-associated angioedemas are induced by angiotensin-converting enzyme inhibitors, angiotensin II receptor antagonists, or nonsteroidal anti-inflammatory drugs. Recently, the responsibility of immunosuppressive agents given to transplant recipients in the development of angioedema has been discussed. Objective: To describe, in detail, angioedema episodes in renal transplant recipients (RTRs) on sirolimus. Methods: A cross-sectional study in a university hospital. Eighty consecutive RTRs on sirolimus were studied. Results: Angioedema without urticaria occurred a mean of 5 times in 12/80 (15%) RTRs taking sirolimus. It was predominantly located on the face (83%), with mucous membrane involvement in 7 (58%) patients, and was life threatening in 1. Another putative cofactor for angioedema without urticaria was identified in 9 (75%) patients: drugs (n = 8), food allergy or physical activity (n = 3). Tacrolimus intake was significantly associated with sirolimus-associated angioedema. Conclusion: Our results suggested a causal relationship between sirolimus and angioedema in RTRs.

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“…This effect is seen with both calcineurin and mTOR inhibitors but is greater with the latter 2, 8. Reports have demonstrated episodes of facial and sublingual angioedema in kidney transplant patients on mTOR inhibitors without concomitant use of an ACE‐inhibitor 4, 9. In September 2015, the Food and Drug Administration (FDA) issued an update on the safety of ACE inhibitors stating that use in combination with mTOR inhibitors may increase the risk for angioedema 10.…”

Section: Discussionmentioning

confidence: 99%

“…Despite the increasing incidence of ACE inhibitor‐induced angioedema in patients taking calcineurin inhibitors,2, 3, 4, 5, 6, 7, 8, 9 extrapolation of basic science studies suggests that mTOR inhibitors pose a greater risk to interact with ACE inhibitors. Physicians prescribing mTOR inhibitors should have knowledge of the potential interaction.…”

Section: Discussionmentioning

confidence: 99%

ACE inhibitor‐associated intestinal angioedema in orthotopic heart transplantation

2017

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Angiotensin‐converting enzyme inhibitor induced angioedema commonly involves the head and neck area. We report a case of angiotensin‐converting enzyme inhibitor induced intestinal angioedema in a heart transplant recipient on mTOR immunosuppression. A 36‐year‐old Caucasian woman with history of heart transplantation on sirolimus, tacrolimus and prednisone presented to the Emergency Department with abdominal pain, one day following lisinopril initiation. A computer tomography scan demonstrated diffuse bowel wall thickening consistent with pancolitis and edema. She was subsequently diagnosed with angiotensin‐converting enzyme inhibitor induced angioedema. Patients on mTOR immunosuppression are at higher risk for this potentially life‐threatening side effect. Knowledge of this interaction is critical for providers prescribing mTOR agents.

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Sirolimus-Induced Angioedema

Cited by 38 publications

References 15 publications

Increased Incidence of Angioedema with ACE Inhibitors in Combination with mTOR Inhibitors in Kidney Transplant Recipients

Increased Incidence of Angioedema with ACE Inhibitors in Combination with mTOR Inhibitors in Kidney Transplant Recipients

Angioedema in Renal Transplant Recipients on Sirolimus

ACE inhibitor‐associated intestinal angioedema in orthotopic heart transplantation

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