Effect of tramadol and DOACs with special attention to dabigatran on concomitant use, on the risk of mayor bleeding using BIFAP database in Spain

• Published in: Pharmacoepidemiology and drug safety 2023-04, Vol.32 (4), p.397-406
• Main Authors: Burgos‐Gonzalez, Airam de, Huerta, Consuelo, Peñalver, María José, Sordo, Luis, Pulido, José, Soriano, Lucía Cea
• Format: Article
• Language: English
• Subjects: Administration, Oral; Anticoagulants - adverse effects; Atrial Fibrillation - complications; Atrial Fibrillation - drug therapy; Atrial Fibrillation - epidemiology; Bleeding; bleeds; Dabigatran - adverse effects; drug safety; Gastrointestinal Hemorrhage - chemically induced; Gastrointestinal Hemorrhage - epidemiology; Homeostasis; Humans; interaction; oral anticoagulants; Rivaroxaban - adverse effects; Sensitivity analysis; Spain - epidemiology; Stroke - chemically induced; Tramadol; Tramadol - adverse effects; Vitamin K
• ISSN: 1053-8569; 1099-1557
• DOI: 10.1002/pds.5525

Background Tramadol, a weak opioid, inhibits the reuptake of serotonin, a key feature on vascular homeostasis. A suspected interaction exists between dabigatran and tramadol, which might trigger an excess on risk of bleeding however, there is a gap in knowledge on this topic. Purpose To estimate the effects of tramadol, dabigatran and concomitant use on the risk of hospitalized major bleeds (Gastrointestinal bleeding and intra‐extracranial bleeds). Methods Among a validated established cohort of new users of oral anticoagulants for non‐valvular atrial fibrillation (NVAF) aged 18 years or older, we identified all hospitalized bleed episodes (GIB and extra/intracranial bleeds) within 2008–2015. A nested case–control analysis was conducted using conditional logistic regression. Adjusted odds ratios (aORs) with 95% confidence intervals (CIs) were calculated for dabigatran, tramadol, and concomitant use. Several sensitivity analyses were carried out. Results aORs (95%CIs) for current use of only dabigatran, only tramadol and concomitant users were 1.73 (1.37–2.18) and 1.38 (1.13–1.67) and 2.04 (0.74–5.67) compared with non‐users of both drugs (>365 days). aORs for current continuers and non‐continuer users of dabigatran were 1.36 (1.00–1.86) and 2.19 (1.61–2.98), respectively. For the latter, non‐continuer users with a short duration of dabigatran cumulated the highest risk (3.36 [1.88–5.99]). There also was an increased risk with concomitant use of tramadol and rivaroxaban (2.24 [1.19–4.21]), or antagonist of vitamin K (1.30 [1.00–1.69]). Conclusion There was a trend towards and increased risk of excess bleeds when using concomitantly with dabigatran. The effect decreases with a narrower definition of current use.