{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T22:46:11Z","timestamp":1787957171560,"version":"build-2784847793"},"reference-count":16,"publisher":"BMJ","issue":"3","content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Case Rep"],"accepted":{"date-parts":[[2022,2,27]]},"published-print":{"date-parts":[[2022,3]]},"abstract":"<jats:p>Two postmenopausal women with breast cancer developed acute confusion and seizures, less than 24 hours after the first cycle of neoadjuvant chemotherapy with fluorouracil, epirubicin and low-dose cyclophosphamide. They were found to have severe, life-threatening hyponatraemia with sodium levels of 113 and 115 mEq\/L, respectively. Both women made a full recovery within 24 hours of admission with slow correction of sodium levels. Following investigational workup, the most likely diagnosis was cyclophosphamide-associated syndrome of inappropriate antidiuretic hormone secretion (SIADH). Aprepitant - a commonly used antiemetic and moderate cytochromeP450 3A4 inhibitor was identified as the precipitating factor. Aprepitant was discontinued and both women were successfully re-challenged with full dose cyclophosphamide in an outpatient setting with no subsequent adverse events. This is a typical case of a rare cause of a common medical problem. A systematic approach to diagnosis and treatment of hyponatraemia in an oncology patient requires awareness of toxicities of systemic anticancer agents.<\/jats:p>","DOI":"10.1136\/bcr-2021-248408","type":"journal-article","created":{"date-parts":[[2022,3,22]],"date-time":"2022-03-22T11:50:47Z","timestamp":1647949847000},"page":"e248408","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":5,"title":["Severe hyponatraemia in two patients with breast cancer caused by low-dose cyclophosphamide and precipitated by aprepitant"],"prefix":"10.1136","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4031-1172","authenticated-orcid":false,"given":"Shefali","family":"Parikh","sequence":"first","affiliation":[{"name":"Oncology, Royal Shrewsbury Hospitals NHS Trust, Shrewsbury, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Pettit","sequence":"additional","affiliation":[{"name":"Oncology, Royal Shrewsbury Hospitals NHS Trust, Shrewsbury, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huzeifa","family":"AbdelGadir","sequence":"additional","affiliation":[{"name":"Oncology, Royal Shrewsbury Hospitals NHS Trust, Shrewsbury, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2022,3,22]]},"reference":[{"key":"2025082702214100000_15.3.e248408.1","first-page":"157","article-title":"Acute hyponatremia complicated with seizure after adjuvant chemotherapy with cyclophosphamide and epirubicin in a breast cancer patient","volume":"2","author":"Lin","year":"2015","journal-title":"J Cancer Res Pract"},{"key":"2025082702214100000_15.3.e248408.2","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2016101139"},{"key":"2025082702214100000_15.3.e248408.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjmed.2005.08.055"},{"key":"2025082702214100000_15.3.e248408.4","doi-asserted-by":"publisher","DOI":"10.1053\/j.ajkd.2011.08.029"},{"key":"2025082702214100000_15.3.e248408.5","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjmed.2009.01.027"},{"key":"2025082702214100000_15.3.e248408.6","doi-asserted-by":"crossref","first-page":"40","DOI":"10.20517\/2394-4722.2019.14","article-title":"Prognostic and predictive role of hyponatremia in cancer patients","volume":"2019","author":"Peri","year":"2019","journal-title":"J Cancer Metastasis Treat"},{"key":"2025082702214100000_15.3.e248408.7","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1177\/23993693211002216","article-title":"Cancer therapy-induced hyponatremia: a case-illustrated review","volume":"5","author":"Pelletier","year":"2021","journal-title":"J Onco-Nephrol"},{"key":"2025082702214100000_15.3.e248408.8","doi-asserted-by":"crossref","first-page":"201","DOI":"10.31053\/1853.0605.v74.n3.14766","article-title":"[Hyponatremia induced by high-dose cyclophosphamide therapy: a retrospective cohort study Cyclophosphamide and Hyponatremia]","volume":"74","author":"Bonella","year":"2017","journal-title":"Rev Fac Cien Med Univ Nac Cordoba"},{"key":"2025082702214100000_15.3.e248408.9","doi-asserted-by":"crossref","unstructured":"Tono Y , Mizuno T , Oda H , et al . Low-Dose cyclophosphamide-induced hyponatremia in primary breast cancer. Clin Case Rep Rev 2020;6.doi:10.15761\/CCRR.1000491","DOI":"10.15761\/CCRR.1000491"},{"key":"2025082702214100000_15.3.e248408.10","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(197909)44:3<896::AID-CNCR2820440316>3.0.CO;2-9"},{"key":"2025082702214100000_15.3.e248408.11","first-page":"122","article-title":"Anticancer medications and sodium dysmetabolism","volume":"16","author":"Krishnamurthy","year":"2020","journal-title":"Eur Endocrinol"},{"key":"2025082702214100000_15.3.e248408.12","doi-asserted-by":"publisher","DOI":"10.1345\/aph.1R296"},{"key":"2025082702214100000_15.3.e248408.13","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1200\/jco.2009.27.15_suppl.588","article-title":"Effect of aprepitant (AP) on cyclophosphamide (CPA) pharmacokinetics (pK) in early breast cancer patients","volume":"27","author":"Walko","year":"2009","journal-title":"Journal of Clinical Oncology"},{"key":"2025082702214100000_15.3.e248408.14","doi-asserted-by":"crossref","first-page":"1641","DOI":"10.2147\/OTT.S66350","article-title":"Cyclophosphamide-Induced symptomatic hyponatremia, a rare but severe side effect: a case report","volume":"7","author":"Elazzazy","year":"2014","journal-title":"Onco Targets Ther"},{"key":"2025082702214100000_15.3.e248408.15","doi-asserted-by":"crossref","first-page":"38","DOI":"10.4103\/jpp.JPP_182_16","article-title":"Ifosfamide-Induced encephalopathy precipitated by aprepitant: a rarely manifested side effect of drug interaction","volume":"8","author":"Kataria","year":"2017","journal-title":"J Pharmacol Pharmacother"},{"key":"2025082702214100000_15.3.e248408.16","first-page":"1056","article-title":"The hyponatremic patient: a systematic approach to laboratory diagnosis","volume":"166","author":"Milionis","year":"2002","journal-title":"CMAJ"}],"container-title":["BMJ Case Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bcr-2021-248408","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,27]],"date-time":"2025-08-27T09:21:52Z","timestamp":1756286512000},"score":1,"resource":{"primary":{"URL":"https:\/\/casereports.bmj.com\/lookup\/doi\/10.1136\/bcr-2021-248408"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3]]},"references-count":16,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2022,3,22]]},"published-print":{"date-parts":[[2022,3]]}},"alternative-id":["10.1136\/bcr-2021-248408"],"URL":"https:\/\/doi.org\/10.1136\/bcr-2021-248408","relation":{},"ISSN":["1757-790X"],"issn-type":[{"value":"1757-790X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3]]}}}