sirolimus and Angioedema

Sirolimus is a potent immunosuppressant drug with a novel mechanism of action. It inhibits the mammalian target of rapamycin (mTOR) and blocks the cell cycle of various cell types, including T- and B-lymphocytes. Sirolimus is widely used as a maintenance immunosuppressive agent in organ transplantation. Also, a potentially benefit of this valuable drug in some immunologic and malignant diseases is currently under scrutiny.Classical side effects: hematological (anaemia, leucopenia, thrombocytopenia), hypercholesterolemia, arthralgias, extremity oedema and impaired wound healing have been frequently associated with the use of sirolimus. Additionally with its increased use, transplant professionals are encountering a variety of previously unreported and potentially more severe side effects.Here, we review the most recent data on sirolimus unexpected side effects (with an emphasis on pulmonary and renal toxicity), its use in renal transplantation and its new potential therapeutic indications (chronic glomerulopathies, polycystic kidney disease, different types of cancer). A brief description of the current knowledge of sirolimus therapeutic drug monitoring, methods of analysis, pharmacokinetics and drug interactions with calcineurin inhibitors is also included.

Topics: Angioedema; Animals; Humans; Immunosuppressive Agents; Kidney Diseases; Kidney Transplantation; Pneumonia; Polycystic Kidney Diseases; Sirolimus; Uveitis

Drug-induced angioedema has been reported as an adverse effect of many different drugs. But small bowel angioedema associated with sirolimus (SRL) used was barely understood. It must be necessary to report a case suffering from small bowel angioedema with detailed discussion and literature review.. A 38-year-old Chinese woman presented with generalized gastric pain in the following day after renal transplantation. The patient began to crampy abdominal pain accompanied by nausea, vomiting, and diarrhea on postoperative day 6 (POD).. We strongly suspected the angioedema was an adverse reaction to SRL.. The immunosuppressive regimen was switched from tacrolimus (TAC), SRL, and prednisone to TAC, mycophenolate and prednisone.. The symptoms were relieved within next 48 hours after withdrawing the SRL. One more CT scan showed complete resolution of bowel wall thickening and ascites.. This was the first report of small bowel angioedema associated with SRL. Drug-induced-angioedema is a relatively common presentation and is potentially fatal. It must be aware of potential adverse effects.

Topics: Adult; Angioedema; Female; Humans; Immunosuppressive Agents; Intestinal Diseases; Intestine, Small; Kidney Transplantation; Postoperative Complications; Sirolimus

Topics: Angioedema; Cyclosporine; Everolimus; Humans; Immunosuppressive Agents; Kidney Transplantation; Mycophenolic Acid; Polycystic Kidney Diseases; Sirolimus

Topics: Aged; Angioedema; Angiotensin-Converting Enzyme Inhibitors; Bradykinin; Bradykinin B2 Receptor Antagonists; Drug Synergism; Everolimus; Female; Humans; Quinapril; Remission Induction; Sirolimus; Tetrahydroisoquinolines; TOR Serine-Threonine Kinases

Topics: Adult; Allografts; Anemia, Sickle Cell; Angioedema; Angiotensin-Converting Enzyme Inhibitors; Female; Hematopoietic Stem Cell Transplantation; Humans; Male; Middle Aged; Sirolimus

Topics: Adrenal Cortex Hormones; Amlodipine; Angioedema; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Antineoplastic Agents; Calcium Channel Blockers; Carcinoma, Renal Cell; Drug Administration Schedule; Drug Interactions; Everolimus; Female; Humans; Kidney Neoplasms; Lisinopril; Middle Aged; Sirolimus; TOR Serine-Threonine Kinases

Topics: Angioedema; Anti-Allergic Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Carcinoma, Renal Cell; Diphenhydramine; Epinephrine; Everolimus; Humans; Kidney Neoplasms; Male; Methylprednisolone; Middle Aged; Sirolimus; Tongue Diseases

Proliferation signal inhibitors (PSI) could help to lower the calcineurine inhibitors level to minimize their toxicity and improve long-term graft survival. Side effects of this drugs are specific and must been known. Hyperlipidemia and cutaneous side-effects are the most frequent, angioedema and interstital pneumonitis the most serious. In majority of cases, early and adapted management could limit the impact of these side effects.

Topics: Angioedema; Calcineurin Inhibitors; Cicatrix; Cyclosporine; Graft Rejection; Graft Survival; Hematologic Diseases; Humans; Hyperlipidemias; Immunosuppressive Agents; Intracellular Signaling Peptides and Proteins; Kidney Diseases; Lymphocele; Pneumonia; Protein Serine-Threonine Kinases; Sirolimus; Skin Diseases; TOR Serine-Threonine Kinases

A 67-year-old man who had been heart transplanted ten years before was admitted to our hospital because of diarrhea. During his stay he developed a severe lingual and facial angioedema. After excluding hereditary angioedema caused by a deficiency in functional C1 esterase inhibitor we focused on adverse effects of his drugs. The medication was composed of Aspirin, Enalapril, Diltiazem, Everolimus, Mycophenolate Mofetil, Bisoprolol, Pravastatin, Esomeprazol and Allopurinol. The angioedema disappeared with anti-allergic treatment. The administration of the suspected trigger enalapril was stopped. However weeks later the patient was admitted again with angioedema. Due to missing urticaria Aspirin was unlikely the causer. The only new drug the patient had been medicated with was Everolimus for 30 days. We assumed a link between the angioedema and Everolimus. Consequently we changed the immunosuppressive regime. After stopping Everolimus no angioedema occurred.. Everolimus is a potential trigger of angioedema.

Topics: Aged; Angioedema; Deglutition Disorders; Diarrhea; Everolimus; Humans; Immunosuppressive Agents; Male; Sirolimus; Speech Disorders

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.. To describe, in detail, angioedema episodes in renal transplant recipients (RTRs) on sirolimus.. A cross-sectional study in a university hospital. Eighty consecutive RTRs on sirolimus were studied.. 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.. Our results suggested a causal relationship between sirolimus and angioedema in RTRs.

Topics: Angioedema; Child, Preschool; Cross-Sectional Studies; Facial Dermatoses; Female; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Postoperative Complications; Sirolimus

Everolimus (Certican; Novartis Pharma AG, Basel, Switzerland) represents the latest generation of proliferation signal inhibitors (PSIs). Everolimus is indicated for use as an immunosuppressive drug in renal and heart transplantation. This report reflects the recommendations of the second German-Austrian Certican Consensus Conference, held in January 2006, for the clinical use of everolimus.

Topics: Angioedema; Coronary Disease; Drug Interactions; Drug Monitoring; Everolimus; Heart Diseases; Heart Transplantation; Humans; Hypertension; Immunosuppressive Agents; Lipids; Lung Diseases, Interstitial; Renal Insufficiency; Sirolimus; Skin Diseases; Transplantation, Homologous; Wound Healing

Everolimus has recently received approval for immunosuppressive therapy in heart transplant recipients in Austria and Germany. At our heart center we have treated 114 patients with everolimus since January 2004. Here we describe 6 cases of lingual angioedema (corresponding to 5.3% of the patients). Symptoms occurred within 2 to 41 days after initiation of therapy. In 5 out of the 6 patients, lingual angioedema disappeared with anti-allergic treatment alone. However, in one patient, two severe recurrent episodes of lingual angioedema occurred so that therapy had to be discontinued. We conclude that the potentially life-threatening condition of lingual angioedema should be considered a severe drug reaction after initiation of everolimus therapy in heart transplant recipients.

Topics: Angioedema; Everolimus; Heart Transplantation; Humans; Immunosuppression Therapy; Sirolimus

Sirolimus (SRL) is a macrolide immunosuppressant that has gained widespread use in organ transplantation. Its full spectrum of side-effects is yet to be defined. We describe herein three cases of SRL-induced angioedema (AE) in African-American (AA) primary renal allograft recipients who received SRL in combination with mycophenolate mofetil and steroids. In two cases, AE manifested after SRL was restarted after a period of discontinuation. The third case presented upon initial exposure to the drug. None of the patients was receiving any drug that has been previously associated with AE. Complete resolution occurred only after SRL was withdrawn. AE has not recurred in any of the patients during a follow-up period of up to 21 months. We conclude that AE is a previously unrecognized adverse event associated with SRL use. Close monitoring for this side-effect, especially in AA patients, is warranted.

Topics: Angioedema; Black or African American; Drug Therapy, Combination; Follow-Up Studies; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Mycophenolic Acid; Postoperative Care; Retreatment; Sirolimus; Transplantation, Homologous