Angioedema induced by tramadol—a potentially life-threatening condition


Tramadol is increasingly used for treatment of moderate-to-severe pain [7]. It differs from other opioids by combining weak opioid and monoaminergic modes of action. It is often considered effective and safe with a low potential for interactions, serious adverse drug reactions (ADR), and abuse, thus representing a drug of first choice in moderate-to-severe pain states both for short-term and long-term use [16, 24]. During the last few years, however, concerns have been raised about the side-effect profile of tramadol. For instance, hallucinations [8, 15, 18], serotonergic syndrome when combined with SSRIs [12, 17, 19], increased effect of oral anticoagulants with bleeding complications [1, 11, 22], risk of dependence and abuse even in patients with no history of drug abuse, and withdrawal symptoms even after recommended doses, have been reported [2, 5, 20, 23]. In Sweden, sales have increased during recent years. This has been accompanied by increased ADR reporting. For instance, 11 cases of angioedema possibly related to medication with tramadol have been reported to the Swedish Medical Products Agency. Angioedema is an uncommon but potentially life-threatening condition associated with some drugs [13], involving a vascular reaction characterized by non-pitting oedema of the dermis and subcutaneous fat or of the mucous membrane of the gastro-intestinal tract. Involvement of the oral cavity/pharynx and/or the upper respiratory tract can lead to acute respiratory distress due to airway obstruction, resulting in death unless emergency treatment is given [6, 9, 13]. Typical angioedema differs from urticaria because it usually lasts longer (2–4 days instead of hours) and is non-pruritic, non-painful, and nonerythematous [3]. However, angioedema and urticaria frequently co-exist. Because tramadol-induced angioedema has not been well-described, we present the six most serious cases of angioedema reported to us, involving the oral cavity/ pharynx and/or the upper respiratory tract. Four patients needed emergency treatment, and two of these at the ICU. Concomitant, on-going medication is given in Table 1.


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