{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,4]],"date-time":"2025-10-04T01:16:22Z","timestamp":1759540582538,"version":"3.40.4"},"reference-count":22,"publisher":"FapUNIFESP (SciELO)","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. bras. pneumol."],"published-print":{"date-parts":[[2014,6]]},"abstract":"<jats:p>Venlafaxine is a serotonin-norepinephrine reuptake inhibitor used as an antidepressant. Interindividual variability and herb-drug interactions can lead to drug-induced toxicity. We report the case of a 35-year-old female patient diagnosed with synchronous pneumonitis and acute cardiomyopathy attributed to venlafaxine. The patient sought medical attention due to dyspnea and dry cough that started three months after initiating treatment with venlafaxine for depression. The patient was concomitantly taking Centella asiatica and Fucus vesiculosus as phytotherapeutic agents. Chest CT angiography and chest X-ray revealed parenchymal lung disease (diffuse micronodules and focal ground-glass opacities) and simultaneous dilated cardiomyopathy. Ecocardiography revealed a left ventricular ejection fraction (LVEF) of 21%. A thorough investigation was carried out, including BAL, imaging studies, autoimmune testing, right heart catheterization, and myocardial biopsy. After excluding other etiologies and applying the Naranjo Adverse Drug Reaction Probability Scale, a diagnosis of synchronous pneumonitis\/cardiomyopathy associated with venlafaxine was assumed. The herbal supplements taken by the patient have a known potential to inhibit cytochrome P450 enzyme complex, which is responsible for the metabolization of venlafaxine. After venlafaxine discontinuation, there was rapid improvement, with regression of the radiological abnormalities and normalization of the LVEF. This was an important case of drug-induced cardiopulmonary toxicity. The circumstantial intake of inhibitors of the CYP2D6 isoenzyme and the presence of a CYP2D6 slow metabolism phenotype might have resulted in the toxic accumulation of venlafaxine and the subsequent clinical manifestations. Here, we also discuss why macrophage-dominant phospholipidosis was the most likely mechanism of toxicity in this case.<\/jats:p>","DOI":"10.1590\/s1806-37132014000300015","type":"journal-article","created":{"date-parts":[[2014,7,14]],"date-time":"2014-07-14T12:40:45Z","timestamp":1405341645000},"page":"313-318","source":"Crossref","is-referenced-by-count":15,"title":["Simultaneous interstitial pneumonitis and cardiomyopathy induced by venlafaxine"],"prefix":"10.1590","volume":"40","author":[{"given":"Pedro Gon\u00e7alo","family":"Ferreira","sequence":"first","affiliation":[{"name":"University Center, Portugal"}]},{"given":"Susana","family":"Costa","sequence":"additional","affiliation":[{"name":"University Center, Portugal"}]},{"given":"Nuno","family":"Dias","sequence":"additional","affiliation":[{"name":"University Center, Portugal"}]},{"given":"Ant\u00f3nio Jorge","family":"Ferreira","sequence":"additional","affiliation":[{"name":"University Center, Portugal"}]},{"given":"F\u00e1tima","family":"Franco","sequence":"additional","affiliation":[{"name":"University Center, Portugal"}]}],"member":"530","reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"30s","DOI":"10.1183\/09031936.01.18s320030","article-title":"Interstitial lung disease induced by exogenous agents: factors governing susceptibility","volume":"32","author":"Nemery B","year":"2001","journal-title":"Eur Respir J Suppl"},{"issue":"12","key":"ref2","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.2165\/0002018-200831120-00008","article-title":"Role of cytochrome P450 polymorphisms in the development of pulmonary drug toxicity","volume":"31","author":"Wijnen PA","year":"2008","journal-title":"Drug Saf"},{"issue":"5","key":"ref3","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1097\/MCP.0b013e32833c06f1","article-title":"Relationship between drug-induced interstitial lung diseases and cytochrome P450 polymorphisms","volume":"16","author":"Wijnen P","year":"2010","journal-title":"Curr Opin Pul Med"},{"issue":"7","key":"ref4","doi-asserted-by":"crossref","first-page":"958","DOI":"10.1164\/rccm.200207-739CR","article-title":"Drug-induced pneumonitis and heart failure simultaneously associated with venlafaxine","volume":"167","author":"Drent M","year":"2003","journal-title":"Am J Respir Crit Care Med"},{"issue":"1","key":"ref5","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1176\/appi.psy.49.1.84","article-title":"Pneumonitis related to venlafaxine","volume":"49","author":"V\u00e1zquez MJ","year":"2008","journal-title":"Psychosomatics"},{"issue":"4","key":"ref6","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1592\/phco.25.4.626.61029","article-title":"Venlafaxine-associated interstitial pneumonitis","volume":"25","author":"Turner RC","year":"2005","journal-title":"Pharmacotherapy"},{"issue":"10","key":"ref7","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1016\/S1579-2129(08)60104-4","article-title":"Hypersensitivity pneumonitis due to venlafaxine","volume":"44","author":"Border\u00edas Clau L","year":"2008","journal-title":"Arch Bronconeumol"},{"issue":"1","key":"ref8","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1183\/09031936.00.15120500","article-title":"Eosinophilic pneumonia and respiratory failure associated with venlafaxine treatment","volume":"15","author":"Fleisch MC","year":"2000","journal-title":"Eur Respir J"},{"issue":"5","key":"ref9","first-page":"610","article-title":"Drug-induced pneumonitis in a patient treated with venlafaxine and propanolol [Article in French]","volume":"25","author":"Priou P","year":"2008","journal-title":"Rev Mal Respir"},{"issue":"2","key":"ref10","doi-asserted-by":"crossref","first-page":"256.e1","DOI":"10.1016\/j.ajem.2009.05.010","article-title":"Cardiogenic shock associated with reversible dilated cardiomyopathy during therapy with regular doses of venlafaxine","volume":"28","author":"Charniot JC","year":"2010","journal-title":"Am J Emerg Med"},{"issue":"2","key":"ref11","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1038\/clpt.1981.154","article-title":"A method for estimating the probability of adverse drug reactions","volume":"30","author":"Naranjo CA","year":"1981","journal-title":"Clin Pharmacol Ther"},{"issue":"1","key":"ref12","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1016\/S0022-3565(24)35098-0","article-title":"Mechanism of sodium channel block by venlafaxine in guinea pig ventricular myocites","volume":"291","author":"Khalifa M","year":"1999","journal-title":"J Pharmacol Exp Ther"},{"issue":"8","key":"ref13","doi-asserted-by":"crossref","first-page":"939","DOI":"10.2174\/138920006779010575","article-title":"Xenobiotic-metabolizing enzymes in human lung","volume":"7","author":"Zhang JY","year":"2006","journal-title":"Curr Drug Metab"},{"issue":"2","key":"ref14","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1097\/00007691-200004000-00011","article-title":"Venlafaxine serum levels and CYP2D6 genotype","volume":"22","author":"Veefkind AH","year":"2000","journal-title":"Ther Drug Monit"},{"issue":"10-11","key":"ref15","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1111\/j.1440-1681.1996.tb01154.x","article-title":"Influence of pharmacogenetics on drug disposition and response","volume":"23","author":"Eichelbaum M","year":"1996","journal-title":"Clin Exp Pharmacol Physiol"},{"issue":"5","key":"ref16","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1111\/j.1365-2710.2006.00763.x","article-title":"CYP2D6 polymorphism and clinical effect of the antidepressant venlafaxine","volume":"31","author":"Shams ME","year":"2006","journal-title":"J Clin Pharm Ther"},{"issue":"2","key":"ref17","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/j.jep.2010.05.002","article-title":"In vitro modulatory effects on three major human cytochrome P450 enzymes by multiple active constituents and extracts of Centella asiatica","volume":"130","author":"Pan Y","year":"2010","journal-title":"J Ethnopharmacol"},{"issue":"2-3","key":"ref18","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/j.phytochem.2009.10.020","article-title":"In vitro chemopreventive potential of fucophlorethols from the brown alga Fucus vesiculosus L. by anti-oxidant activity and inhibition of selected cytochrome P450 enzymes","volume":"71","author":"Parys S","year":"2010","journal-title":"Phytochemistry"},{"issue":"1","key":"ref19","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1293\/tox.21.9","article-title":"Drug-induced phospholipidosis-pathological aspects and its prediction","volume":"21","author":"Nonoyama T","year":"2008","journal-title":"J Toxicol Pathol"},{"issue":"23","key":"ref20","doi-asserted-by":"crossref","first-page":"5533","DOI":"10.1016\/j.febslet.2006.08.061","article-title":"Drug-induced phospholipidosis","volume":"580","author":"Anderson N","year":"2006","journal-title":"FEBS Lett"},{"issue":"2","key":"ref21","first-page":"262","article-title":"Influence of external factors on self-aggregation of amphiphilic antidepressant drug: a thermodynamic study","volume":"35","author":"Jamal MA","year":"2013","journal-title":"J Chem Soc Pakistan"},{"issue":"2","key":"ref22","doi-asserted-by":"crossref","first-page":"18","DOI":"10.14227\/DT150208P18","article-title":"Effect of superdisintegrants on dissolution of cationic drugs","volume":"15","author":"Balasubramaniam J","year":"2008","journal-title":"Dissolut Technol"}],"container-title":["Jornal Brasileiro de Pneumologia"],"original-title":[],"link":[{"URL":"http:\/\/www.scielo.br\/pdf\/jbpneu\/v40n3\/1806-3713-jbpneu-40-03-00313.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,3]],"date-time":"2025-05-03T19:58:47Z","timestamp":1746302327000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.scielo.br\/scielo.php?script=sci_arttext&pid=S1806-37132014000300313&lng=en&tlng=en"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,6]]},"references-count":22,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2014,6]]}},"alternative-id":["S1806-37132014000300313"],"URL":"https:\/\/doi.org\/10.1590\/s1806-37132014000300015","relation":{},"ISSN":["1806-3713"],"issn-type":[{"type":"electronic","value":"1806-3713"}],"subject":[],"published":{"date-parts":[[2014,6]]}}}