Tramadol may increase risk of prolonged, persistent or recurrent hiccups

A safety review by Health Canada examined the potential risk of prolonged, persistent or recurrent hiccups (singultus) with the use of tramadol. The safety review was triggered by published case reports in Canada and internationally.1Although hiccups are generally not harmful, the occurrence of prolonged, persistent or recurrent hiccups can negatively affect a person’s quality of life, including their ability to eat, sleep and communicate.1Tramadol is a widely used prescription opioid drug authorized for sale in Canada to manage acute or chronic pain in adults. It is available as single-entity products and in combination with acetaminophen.1Health Canada’s safety review included information from searches of the Canada Vigilance database and the scientific literature. Eight cases (2 Canadian, 6 international) of prolonged, persistent or recurrent hiccups in patients taking tramadol were identified. Prolonged hiccups was defined as lasting 48 hours but < 1 month, and recurrent hiccups as occurring often or repeatedly. In spite of the presence of other factors that may have contributed to the occurrence of prolonged, persistent or recurrent hiccups (e.g., underlying medical conditions, use of other prescription drugs), all eight cases were found to be possibly linked to the use of tramadol.1The possible biologic mechanism for tramadol-induced hiccups might relate to tramadol’s inhibition of serotonin and norepinephrine reuptake leading to stimulation of the central component of the hiccup reflex arc.2,3Hiccups generally resolve quickly when tramadol is discontinued, although some patients were treated with metoclopramide and/or baclofen for a few days to relieve the hiccups.2,4 Health Canada concludes that tramadol use is possibly linked to an increased risk of developing prolonged, persistent or recurrent hiccups. Canadian product monographs for all tramadol-containing products are being updated to include the risk of prolonged, persistent or recurrent hiccups.References:Health Canada. Summary safety review - tramadol - assessing the potential risk of prolonged, persistent or recurrent hiccups. (accessed May 20, 2026).Ali HT, Mohamed ZE, Shalaby MM, et al. Persistent hiccups shortly after tramadol intake: a case report and literature review. Curr Drug Saf 2025;20(1):78-83. (accessed May 20, 2026).Jha AN, Gaikwad VR, Noman AA, et al. Tramadol-induced persistent singultus: a case report on diagnosis, and management. Published online February 19, 2025. (accessed May 20, 2026).Panchal R, Bhutt V, Anovadiya A, et al. Tramadol-induced hiccups: a report of two cases. Drug Saf Case Rep 2018 5;5:3. (accessed May 20, 2026).

Tramadol may increase risk of prolonged, persistent or recurrent hiccups

Register for free access or login.

Related Topics