Tramadol Hydrochloride

In a phase I, double‑blind, placebo‑ and positive‑controlled, multiple‑dose, four‑way crossover study (68 healthy adults, 57 completers), therapeutic (400 mg/day) and supratherapeutic (600 mg/day) doses of tramadol were noninferior to placebo regarding QTc prolongation. Moxifloxacin (400 mg) served as a positive control and prolonged QTc as expected. Most treatment‑emergent adverse events were mild, with nausea being the most common. The authors conclude that tramadol at doses up to 600 mg/day does not cause clinically relevant QT prolongation.

Fig. 1 Study design and participant disposition. (Massarella J, et al., 2019)

In a phase IV double‑blind RCT (538 patients with moderate‑to‑severe acute low back pain), the primary endpoint (time to first achieve NRS‑PI <4 or ≥30% pain reduction within 8 hours after first dose) was not statistically significant for dexketoprofen/tramadol 25/75 mg vs. placebo (46.1% vs. 42.6%, HR 1.11). However, dexketoprofen/tramadol was superior to tramadol alone in total pain relief at 4, 6, and 8 hours, and produced significantly greater NRS‑PI reduction vs. placebo from 1 hour onward. The combination is effective and safe, with secondary endpoints supporting its use.

Fig. 2 Changes in total pain relief (TOTPAR) at 4, 6, and 8 h after the first dose (T4h, T6h, T8h) in the modified intent-to-treat population. (Varrassi G, et al., 2024)