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      Pulmonary Toxicity in a Renal Transplant Recipient Treated with Amiodarone and Everolimus: A Case of Hypothetical Synergy and a Proposal for a Screening Protocol

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          Abstract

          Pneumotoxic drugs like amiodarone and m-TOR inhibitors (m-TORi) may be administered contemporaneously in therapy for patients who had renal transplants. We present a case of amiodarone pulmonary toxicity (APT) in a patient treated with amiodarone and everolimus. A 57-year-old Caucasian male, under treatment with both everolimus (for 3 years) and amiodarone (for 2 months), presented with fever, dyspnoea and a negative chest X-ray after his second kidney transplant with suboptimal serum creatinine (3 mg/dl). A non-contrastive high-resolution CT scan showed bilateral interstitial lung disease with an associated reduction in carbon monoxide diffusing capacity. Bronchoalveolar lavage (BAL) was negative for an infection, but BAL cytology was suitable for APT (50% of ‘foamy' macrophages). A complete recovery was achieved after amiodarone interruption and an oral steroid therapy increase. Everolimus was continued. His kidney function remained unchanged in the upcoming months. In conclusion, we suggest a possible synergistic effect between m-TORi and amiodarone. Furthermore, we propose a diagnostic algorithm that can be used as a surveillance tool to identify a potential initial lung damage in patients treated with 1 or more pneumotoxic drugs.

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          Most cited references 20

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          Prescribing amiodarone: an evidence-based review of clinical indications.

          Although amiodarone is approved by the US Food and Drug Administration only for refractory ventricular arrhythmias, it is one of the most frequently prescribed antiarrhythmic medications in the United States. To evaluate and synthesize evidence regarding optimal use of amiodarone for various arrhythmias. Systematic search of MEDLINE to identify peer-reviewed clinical trials, randomized controlled trials, meta-analyses, and other studies with clinical pertinence. The search was limited to human-participant, English-language reports published between 1970 and 2007. Amiodarone was searched using the terms adverse effects, atrial fibrillation, atrial flutter, congestive heart failure, electrical storm, hypertrophic cardiomyopathy, implantable cardioverter-defibrillator, surgery, ventricular arrhythmia, ventricular fibrillation, and Wolff-Parkinson-White. Bibliographies of identified articles and guidelines from official societies were reviewed for additional references. Ninety-two identified studies met inclusion criteria and were included in the review. Amiodarone may have clinical value in patients with left ventricular dysfunction and heart failure as first-line treatment for atrial fibrillation, though other agents are available. Amiodarone is useful in acute management of sustained ventricular tachyarrythmias, regardless of hemodynamic stability. The only role for prophylactic amiodarone is in the perioperative period of cardiac surgery. Amiodarone may be effective as an adjunct to implantable cardioverter-defibrillator therapy to reduce number of shocks. However, amiodarone has a number of serious adverse effects, including corneal microdeposits (>90%), optic neuropathy/neuritis (< or =1%-2%), blue-gray skin discoloration (4%-9%), photosensitivity (25%-75%), hypothyroidism (6%), hyperthyroidism (0.9%-2%), pulmonary toxicity (1%-17%), peripheral neuropathy (0.3% annually), and hepatotoxicity (elevated enzyme levels, 15%-30%; hepatitis and cirrhosis, <3% [0.6% annually]). Amiodarone should be used with close follow-up in patients who are likely to derive the most benefit, namely those with atrial fibrillation and left ventricular dysfunction, those with acute sustained ventricular arrhythmias, those about to undergo cardiac surgery, and those with implantable cardioverter-defibrillators and symptomatic shocks.
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            Drug-induced phospholipidosis.

            Drug-induced phospholipidosis is characterized by intracellular accumulation of phospholipids with lamellar bodies, most likely from an impaired phospholipid metabolism of the lysosome. Organs affected by phospholipidosis exhibit inflammatory reactions and histopathological changes. Despite significant advances in the understanding of drug-altered lipid metabolism, the relationship between impaired phospholipid metabolism and drug-induced toxicity remains enigmatic. Here we review molecular features of inheritable lysosomal storage disorders as a molecular mimicry of drug-induced phospholipidosis for an improved understanding of adverse drug reaction.
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              A practical guide for clinicians who treat patients with amiodarone: 2007.

              Amiodarone is commonly used to treat supraventricular and ventricular arrhythmias in various inpatient and outpatient settings. Over- and under-use of amiodarone is common, and data regarding patterns of use are sparse and largely anecdotal. Because of adverse drug reactions, proper use is essential to deriving optimal benefits from the drug with the least risk. This guide updates an earlier version published in 2000, reviews indications for use of amiodarone and recommends strategies to minimize adverse effects. The recommendations included herein are based on the best available data and the collective experience of the member of the writing committee.
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                Author and article information

                Journal
                CRU
                CND
                10.1159/issn.2296-9705
                Case Reports in Nephrology and Dialysis
                S. Karger AG
                2296-9705
                2014
                January – April 2014
                12 April 2014
                : 4
                : 1
                : 75-81
                Affiliations
                aRenal Transplantation Unit ‘A. Vercellone', Division of Nephrology Dialysis and Transplantation, Department of Medical Sciences, and bLung Disease Unit, Cardiovascular and Thoracic Department, AOU Città della Salute e della Scienza Hospital, University of Turin, Turin, Italy
                Author notes
                *Alberto Mella, MD, Department of Medical Sciences, Città della Salute e della Scienza Hospital, University of Turin, Corso Bramante 88, IT-10126 Turin (Italy), E-Mail albertomella@libero.it
                Article
                362361 PMC4025156 Case Rep Nephrol Urol 2014;4:75-81
                10.1159/000362361
                PMC4025156
                24847349
                © 2014 S. Karger AG, Basel

                Open Access License: This is an Open Access article licensed under the terms of the Creative Commons Attribution-NonCommercial 3.0 Unported license (CC BY-NC) ( http://www.karger.com/OA-license), applicable to the online version of the article only. Distribution permitted for non-commercial purposes only. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                Page count
                Figures: 3, Pages: 7
                Categories
                Published: April 2014

                Cardiovascular Medicine, Nephrology

                Renal transplant, Amiodarone, Pulmonary toxicity, Everolimus

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