Tramadol Hydrochloride at Steady State Lacks Clinically Relevant QTc Interval Increases in Healthy Adults

Massarella, Joseph; Ariyawansa, Jay; Natarajan, Jaya; Francke, Stephan; Murtaugh, Thomas; DeLemos, Byron; Vaughan, Subusola; Fonseca, Sónia

doi:10.1002/cpdd.473

Cited by 11 publications

(7 citation statements)

References 32 publications

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“…Important to note, buprenorphine, fentanyl and alfentanil could be used as a valid alternative to morphine in opioid rotation in ribociclib-treated patients since no QTc prolongation-related issues were reported for these drugs [48]. No QTc effects were observed at supratherapeutic doses of the opioid/ nonopioid analgesics tramadol [50] and tapentadol [51].…”

Section: Pharmacodynamic-based Ddismentioning

confidence: 99%

Drug-drug interactions in breast cancer patients treated with CDK4/6 inhibitors

Fogli

Curigliano

et al. 2019

Cancer Treatment Reviews

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CDK4/6 inhibitors are a new class of anticancer drugs used for the treatment of women with hormone receptorpositive, human epidermal growth factor receptor 2-negative advanced or metastatic breast cancer with disease progression following endocrine therapy. Polypharmacy is a well-known problem in advanced cancer causing potential drug-drug interactions (DDIs), which, in turn, may limit the therapeutic value of CDK4/6 inhibitors. Therefore, understanding the mechanisms underlying potential DDIs in patients taking CDK4/6 inhibitors may be useful in decision-making processes and represent an important step towards treatment personalization. The present review is aimed at describing the potential DDIs that might occur in breast cancer patients receiving CDK4/6 inhibitors based on direct evidence from the literature and mechanistic considerations tailored on specific class of drugs used in combination.

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Section: Pharmacodynamic-based Ddismentioning

confidence: 99%

Drug-drug interactions in breast cancer patients treated with CDK4/6 inhibitors

Fogli

Curigliano

et al. 2019

Cancer Treatment Reviews

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“…25 The study using supra-therapeutic doses of tramadol in health volunteers showed a relatively high proportion of patients suffering from hiccups, suggesting that this adverse reaction might be dose related. 12 Accordingly, of the 50 available cases in EudraVigilance, the dose of tramadol was ⩾150 mg/day in 24 cases (48%) and <150 mg/ day in 17 cases (dose was unknown for 9 cases).…”

Section: Discussionmentioning

confidence: 99%

“…This proportion was higher in those on 600 mg/day, with 7.8% of them suffering from hiccups. 12 The third clinical trial compared the efficacy and safety of tramadol versus fentanyl in pediatric patients undergoing upper gastrointestinal endoscopy. Patients were divided into three subgroups: 0-2 years, 2-12 years, and >12 years.…”

Section: Review Of the Literaturementioning

confidence: 99%

Tramadol-induced hiccups: a case–noncase study in the European pharmacovigilance database

García

Lertxundi

Aguirre

2021

Therapeutic Advances in Drug Safety

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Background: Hiccups are usually benign and self-limiting, but can sometimes be persistent. If left untreated, they can provoke severe discomfort, and even death. Hiccups can be idiopathic, organic, psychogenic, and caused by drugs. Although some case reports have suggested a possible association between tramadol and hiccups, to our knowledge, no study has analyzed this possible relationship. The aim of this study was to analyze whether a disproportionate number of cases of hiccups are reported for tramadol in the EudraVigilance database. Methods: A case–noncase study was conducted to assess the association between hiccups and tramadol, calculating reporting odds ratios (RORs) from 1 January 1995 to 11 September 2020. Cases were selected using the preferred term ‘Hiccups’. The noncases used as controls were all other adverse drug reaction reports recorded in EudraVigilance during the same period. Exposure was defined as exposure to tramadol among cases and noncases. To reduce the risk of confounding by indication, the RORs for tramadol compared with other opioids were obtained. Additionally, we performed a confirmatory analysis in the World Health Organization pharmacovigilance database, VigiBase®. Results: There were 3089 cases of hiccups in the 7,213,623 reports. Tramadol was involved in 50 cases. The ROR for tramadol exposure was 3.35 [95% confidence interval (CI) 2.53–4.43]. This association persisted when comparing tramadol with other opioids; ROR: 2.13 (95% CI 1.52–2.99). Disproportionality was also observed in VigiBase®: ROR 1.69 (95% CI 1.47–1.93). Conclusion: Our study confirms, for the first time, a possible signal for a tramadol–hiccups association. Nevertheless, observational analytical studies are needed to confirm these results Plain Language Summary Evaluation of the relationship between the tramadol and the risk of hiccups Introduction: Hiccups are sudden involuntary contractions of the diaphragm. This involuntary contraction causes the vocal cords to close very briefly, which produces the characteristic sound of a hiccup. Hiccups are usually benign and self-limiting, but can sometimes be persistent. If left untreated, they can provoke severe discomfort, depression, disability, and in the most extreme cases, even death. Drugs are a rare cause of hiccups. Methods: This study investigated the possible association between tramadol and hiccups (an unmentioned adverse drug reaction in the Summary of Product Characteristics) in the European pharmacovigilance database (EudraVigilance) and a confirming analysis in the World Health Organization pharmacovigilance database (VigiBase). Results: Our analysis shows that hiccups is relatively more frequently reported in association with tramadol than with other medicinal products, with EudraVigilance and VigiBase confirming this association. Conclusion: Tramadol is an opioid analgesic indicated, alone or in combination with dexketoprofen or paracetamol for pain with various causes, so healthcare professionals and patients should be aware of this possible association.

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“…With the exception of methadone, which has been shown to cause QTc prolongation [140][141][142][143][144][145][146][147][148] and is strongly associated with TdP (at doses as low as 40 mg/day) [140][141][142] , most opioids used in the perioperative setting have no effect on QTc when used at clinically relevant doses. This is true for fentanyl 149,150 , alfentanil 151 , remifentanil 149,152,153 , morphine 139 , and tramadol 139,154 .…”

Section: Opioidsmentioning

confidence: 97%