{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T16:00:19Z","timestamp":1790265619946,"version":"4.1.0"},"reference-count":24,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2021,1,6]],"date-time":"2021-01-06T00:00:00Z","timestamp":1609891200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,1,6]],"date-time":"2021-01-06T00:00:00Z","timestamp":1609891200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100006447","name":"University of Zurich","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100006447","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Eur J Clin Pharmacol"],"published-print":{"date-parts":[[2021,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Purpose<\/jats:title>\n                <jats:p>Tizanidine, an alpha-adrenergic substance with antinociceptive and antihypertensive effects, is extensively metabolized via cytochrome P450 (CYP) 1A2. Therefore, coadministration with potent CYP1A2 inhibitors, such as ciprofloxacin, is contraindicated. However, both drugs are broadly utilized in various countries. Their concomitant use bears an inherent high risk for clinically significant symptoms, especially in multimorbid patients experiencing polypharmacy. This study aims to investigate the impact of coadministration of tizanidine and ciprofloxacin using real-world pharmacovigilance data and to raise awareness of this potentially underestimated safety issue.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>We conducted a retrospective study including Individual Case Safety Reports (ICSR) registered until March 1, 2017, in the World Health Organization (WHO) global database. Demographic data, drug administration information, the course of the adverse drug reaction (ADR), its severity, and outcomes were analyzed for cases reporting ciprofloxacin comedication.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>In 91 (2.0%) of the identified 4192 worldwide ICSR on tizanidine, coadministration of ciprofloxacin was reported. Most of the patients were female (<jats:italic>n<\/jats:italic> = 59, 64.8%) with a median age of 54 years (range 13\u201385 years). The countries contributing most reports were the USA (<jats:italic>n<\/jats:italic> = 54, 59.3%) and Switzerland (<jats:italic>n<\/jats:italic> = 16, 17.6%). ADRs reported most often affected the nervous system and the cardiac function, especially with large tizanidine doses or drugs with CNS and cardiovascular depressant effects. In two cases, a fatal outcome was reported.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>Despite the existing formal contraindication, the concomitant use of tizanidine and ciprofloxacin can be observed in real-world clinical practice. Reactions mainly affected the central nervous and the cardiovascular system resulting in potentially severe adverse effects. The concomitant use of tizanidine and ciprofloxacin should absolutely be avoided.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s00228-020-02981-2","type":"journal-article","created":{"date-parts":[[2021,1,6]],"date-time":"2021-01-06T08:03:41Z","timestamp":1609920221000},"page":"895-902","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Coadministration of tizanidine and ciprofloxacin: a retrospective analysis of the WHO pharmacovigilance database"],"prefix":"10.1007","volume":"77","author":[{"given":"Annette","family":"Rudolph","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hendrike","family":"Dahmke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hugo","family":"Kupferschmidt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Burden","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1087-7597","authenticated-orcid":false,"given":"Stefan","family":"Weiler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,1,6]]},"reference":[{"key":"2981_CR1","unstructured":"Sirdalud\/Sirdalud MR (tizanidine) [product information]. Novartis Pharma Schweiz AG, Risch Switzerland; 2017"},{"issue":"3","key":"2981_CR2","doi-asserted-by":"publisher","first-page":"435","DOI":"10.2165\/00003495-199753030-00007","volume":"53","author":"AJ Wagstaff","year":"1997","unstructured":"Wagstaff AJ, Bryson HM (1997) Tizanidine. A review of its pharmacology, clinical efficacy and tolerability in the management of spasticity associated with cerebral and spinal disorders. Drugs. 53(3):435\u2013452","journal-title":"Drugs."},{"key":"2981_CR3","unstructured":"European Medicines Agency. Tizanidine: list of nationally authorized products. Last updated: October 17th, 2016. Available at: https:\/\/www.ema.europa.eu\/en\/documents\/psusa\/tizanidine-list-nationally-authorised-medicinal-products-psusa\/00002977\/201412_en.pdf, last accessed: February 27th, 2020; 11:53"},{"key":"2981_CR4","doi-asserted-by":"publisher","first-page":"314","DOI":"10.1111\/j.1742-1241.2007.01660.x","volume":"62","author":"HR Henney","year":"2008","unstructured":"Henney HR, Runyan JD (2008) Clinically relevant review of tizanidine hydrochloride dose relationships to pharmacokinetics. Int J Clin Pract 62:314\u2013324","journal-title":"Int J Clin Pract"},{"key":"2981_CR5","doi-asserted-by":"publisher","first-page":"703","DOI":"10.1002\/cpt.1233","volume":"105","author":"S Chaugai","year":"2019","unstructured":"Chaugai S, Dickson AL, Shuey MM (2019) Co-prescription of strong CYP1A2 inhibitors and the risk of tizanidine-associated hypotension: a retrospective cohort study. 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The views expressed in this article are the personal views of the authors and may not be understood or quoted as being made on behalf of or reflecting the position of the EMA or one of its committees or working parties. AR, HD, AMB, and HK have no conflicts of interest to declare. The authors used data from the VigiBase, the WHO global database of individual case safety reports (ICSRs) as a source of information. However, the conclusions do not represent the opinion of the UMC or the WHO.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"The data for this work were obtained from the WHO Collaborating Centre for International Drug Monitoring, Uppsala, Sweden. Data from spontaneous reporting are inhomogeneous because of different reporting policies worldwide and are vulnerable to underreporting and reporting bias. The information contained in this work related to the Pharmacovigilance Database is therefore not homogeneous.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Accompanying statement"}}]}}