Fast-release paracetamol 650 mg achieves faster onset of analgesia and greater temperature reductionFast-release paracetamol lowers fever and pain faster than standard versions

AimParacetamol is widely used for management of fever/pain. With increasing emphasis on rapid symptom relief, this study compared the response following a single 650 mg oral dose of four commercially available tablets in acute febrile and febrile-pain conditions.MethodsThis multicenter, open-label trial (CTRI/2025/12/098995) included adults (18–60 years) with oral temperature ≥38 °C (with/without pain) and symptom onset within ≤72 h. Consenting participants were randomized (1:1:1:1) to receive a single dose of the test fast release test paracetamol (A) and conventional paracetamol (B, C, D) drug. Oral body temperature(digital thermometer) and pain (numerical rating scale (NRS) were assessed at predefined intervals till 90 ± 2 min. Outcomes included magnitude and onset of antipyretic and analgesic effects, adverse events (AEs), and patient satisfaction.ResultsAmong 220 febrile participants (55% women; mean temperature 38.51 °C), 169 reported pain (mean NRS score 7.31). At 90 ± 2 min, fast release paracetamol demonstrated significantly greater reduction in temperature (1.54 °C), along with the fastest rate of decline (1.03 °C/hr), and the shortest restricted mean time to defervescence (84.27 min), resulting in majority of participants (60.0%) experiencing defervescence (temperature ≤37 °C). Pain reduction was also significantly greater with fast release test paracetamol (5.2 units; 3.4 units/hr), with onset of analgesia (≥30% reduction in NRS score) after a comparatively shorter median time (30 min; conventional, 60–90 min). By 90 ± 2 min, pain resolved (NRS score = 0) in 23.2% (A), 22.5% (B), 11.9% (C), and 6.8% (D) participants, with restricted mean times to resolution being 90.00, 89.25, 89.29, and 90.00 min, respectively. Overall, 82.2% participants reported treatment satisfaction, with likelihood highest for fast-release test paracetamol (A). Four participants reported unrelated, mild/moderate AEs.ConclusionAll evaluated paracetamol 650 mg formulations demonstrated antipyretic and analgesic activity within 90 min, while the fast-release formulation showed earlier and, for several assessed outcomes, greater reductions in temperature and pain. These findings may support consideration of formulation choice when rapid early symptomatic relief is desired.Clinical Trial RegistrationCTRI/2025/12/098995.