Combined and alternating paracetamol and ibuprofen therapy for febrile children

Background Health professionals frequently recommend fever treatment regimens for children that either combine paracetamol and ibuprofen or alternate them. However, there is uncertainty about whether these regimens are better than the use of single agents, and about the adverse effect profile of combination regimens. Objectives To assess the effects and side effects of combining paracetamol and ibuprofen, or alternating them on consecutive treatments, compared with monotherapy for treating fever in children. Search methods In September 2013, we searched Cochrane Infectious Diseases Group Specialized Register; Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE; EMBASE; LILACS; and International Pharmaceutical s (2009–2011). Selection criteria We included randomized controlled trials comparing alternating or combined paracetamol and ibuprofen regimens with monotherapy in children with fever. Data collection and analysis One review author and two assistants independently screened the searches and applied inclusion criteria. Two authors assessed risk of bias and graded the evidence independently. We conducted separate analyses for different comparison groups (combined therapy versus monotherapy, alternating therapy versus monotherapy, combined therapy versus alternating therapy). Main results Six studies, enrolling 915 participants, are included. Compared to giving a single antipyretic alone, giving combined paracetamol and ibuprofen to febrile children can result in a lower mean temperature at one hour after treatment (MD −0.27 °Celsius, 95% CI −0.45 to −0.08, two trials, 163 participants, moderate quality evidence). If no further antipyretics are given, combined treatment probably also results in a lower mean temperature at four hours (MD −0.70 °Celsius, 95% CI −1.05 to −0.35, two trials, 196 participants, moderate quality evidence), and in fewer children remaining or becoming febrile for at least four hours after treatment (RR 0.08, 95% CI 0.02 to 0.42, two trials, 196 participants, moderate quality evidence). Only one trial assessed a measure of child discomfort (fever associated symptoms at 24 hours and 48 hours), but did not find a significant difference in this measure between the treatment regimens (one trial, 156 participants, evidence quality not graded). In practice, caregivers are often advised to initially give a single agent (paracetamol or ibuprofen), and then give a further dose of the alternative if the child's fever fails to re