Paracetamol Fixed-dose Combination Research Articles

Paracetamol and ibuprofen combination for the management of acute mild-to-moderate pain in children: expert consensus using the Nominal Group Technique (NGT)

BackgroundAcute pain is a common symptom in children of all ages, and is associated with a variety of conditions. Despite the availability of guidelines, pain often remains underestimated and undertreated. Paracetamol and ibuprofen are the most commonly used drugs for analgesia in Pediatrics. Multimodal pain management by using a combination of paracetamol and ibuprofen results in greater analgesia.MethodsAn investigation using the Nominal Group Technique was carried out between May and August 2022. Two open (non-anonymous) questionnaires were consecutively sent to a Board of ten clinicians to understand their opinions on the use of the oral paracetamol and ibuprofen association. Answers were examined in a final meeting where conclusions were drawn.ResultsThe board achieved a final consensus on a better analgesic power of paracetamol and ibuprofen in fixed-dose combination as compared to monotherapy, without compromising safety. Strong consensus was reached on the opinion that the fixed-dose combination of paracetamol and ibuprofen may be a useful option in case of inefficacy of one or other drug as monotherapy, especially in case of headaches, odontalgia, earache, and musculoskeletal pain. The use of the fixed combination may be also considered suitable for postoperative pain management.ConclusionsThe use of the fixed-dose combination may represent advantage in terms of efficacy and safety, allowing a better control of the dose of both paracetamol and ibuprofen as monotherapy, thus minimizing the risk of incorrect dosage. However, the limited evidence available highlights the need for future well designed studies to better define the advantages of this formulation in the various therapeutic areas.

A Simple Stability-Indicating UPLC Method for the Concurrent Assessment of Paracetamol and Caffeine in Pharmaceutical Formulations

A fixed-dose combination of paracetamol (PCM) and caffeine (CAF) tablets/capsules is the most frequently used over-the-counter medicine for fever and headache. In this paper, a simple, reliable, sensitive, rapid, and stability-indicating ultra-performance liquid chromatography (UPLC) analytical method was proposed for simultaneously assessing PCM and CAF in pharmaceutical formulations. The UPLC method was developed on an Acquity UPLC® CSHTM C18 column, and the column oven temperature was maintained at 35 ± 5 °C with isocratic elution by using a solution of methanol and water (30:70, v/v). The maximum absorbance of PCM and CAF was observed at 272.5 nm. The flow rate was 0.2 mL/min, and the injection volume was 1 µL, with the total run time of 2 min for the separation of PCM and CAF. The proposed UPLC method was validated according to the ICH guidelines, and it demonstrated excellent linearity, with correlation coefficients of 0.9995 and 0.9999 over the concentration ranges of 40–400 and 7–70 ng/mL for PCM and CAF, respectively. The mean retention times of 0.82 ± 0.0 and 1.16 ± 0.02 were observed for PCM and CAF, respectively. The limits of detection and quantification were 16.62 and 3.86 for PCM, respectively, and 50.37 and 11.70 for CAF, respectively. PCM and CAF were subjected to acidic, alkali, oxidative, phytochemical, dry-heat, and wet-heat degradation. The method was found to well separate the analytes’ peaks from degradation peaks, with no alterations in retention times. The proposed method is linear, precise, accurate, specific, and robust, and it can indicate stability and be used for the quantitative assessment of pharmaceutical formulations comprising PCM and CAF within a short period of time.

Efficacy and Safety of Ibuprofen Plus Paracetamol in a Fixed-Dose Combination for Acute Postoperative Pain in Adults: Meta-Analysis and a Trial Sequential Analysis.

Ibuprofen and paracetamol (acetaminophen) are very commonly used for analgesia and pain. In 2020, the US FDA gave its first approval of a fixed-dose combination (FDC) of the two drugs in the same tablet for postoperative pain. There has been no quantitative, summative analysis of the FDC effect size measures against postoperative pain in adults. Similar analyses exist, but only in pediatric patients. This was the first meta-analysis to compare the efficacy and safety outcomes of the ibuprofen/paracetamol FDC against placebo, administered postoperatively, for moderate to severe pain relief in adults. The MEDLINE, EMBASE, and Cochrane CENTRAL databases, in addition to the grey literature, were searched for clinical trials until April 2020, to identify comparative literature studies of the ibuprofen/paracetamol FDC in acute postoperative pain in adults. No restrictions on doses, formulations (oral, intravenous), and underlying type of surgery were applied. Independent reviewers performed the study selection, data extraction, and the risk-of-bias and quality-of-evidence assessments based on the Cochrane criteria. The outcome measures of interest in the meta-analysis were ≥ 50% pain relief , need for rescue medications, and occurrence of adverse drug events. Statistical analyses using a random-effects model were performed, at a statistical significance of p < 0.05. The RevMan software was used for analysis. A trial sequential analysis (TSA) was conducted to assess how precise and conclusive the meta-analysis outcomes are. Seven double-blind, randomized controlled trials with 2947 participants were included. The FDC dose was at three different levels: 75-100mg ibuprofen/250mg paracetamol, 150-200mg ibuprofen/500mg paracetamol (FDA-approved dose level), and 292.5-400mg ibuprofen/975-1000mg paracetamol. The ≥ 50% pain relief outcome was more achieved with the FDC compared to placebo (risk ratio [RR] 2.60, 95% confidence interval [CI] 2.11-3.20, p < 0.00001), as was the reduced need for rescue medications (RR 0.51, 95% CI 0.37-0.71, p < 0.0001). While inconclusive based on TSA, the FDC was at the highest doses at least as well tolerated as placebo regarding the occurrence of adverse events, including severe, common, and treatment-related adverse events, as well as those that lead to discontinuation, but it was also significantly associated with lower rates of headache and nausea. Subgroup analyses confirmed that the efficacy and safety of the FDC were maintained regardless of doses and formulations. The sensitivity analysis confirmed outcomes against potential publication bias and identified sources of heterogeneity in analyses. The ibuprofen plus paracetamol FDC is conclusively an effective analgesic against placebo in acute postoperative, moderate to severe pain in adults. It is also superiorly well tolerated, including at the higher dose of 292.5-400mg ibuprofen/975-1000mg paracetamol; however, safety outcomes were inconclusive. Future studies need to confirm the safety of FDC and itsbenefits against other marketed analgesics in postoperative pain.

An oral fixed-dose combination of paracetamol and tramadol in surgical and traumatology practice: efficacy and safety

An oral fixed-dose combination of paracetamol and tramadol in surgical and traumatology practice: efficacy and safety

Angioedema caused by over the counter use of dicyclomine hydrochloride and paracetamol fixed dose combination in a child: a case report

Authors describe a case of angioedema in a male child due to over-the-counter (OTC) use of fixed dose combination (FDC) of Tab. dicyclomine hydrochloride (20mg) and paracetamol (500mg) for abdominal pain. Use of OTC drugs in children without a doctor’s suggestion can lead to unnecessary medication use and is not free of risks. Here, there is a probable causal relationship between the suspected drug and angioedema according to WHO-UMC criteria for Causality Assessment. This case was also reported to the Pharmacovigilance Programme of India (PvPI) through PvPI ADR android application.

Symptomatic treatment of the common cold with a fixed-dose combination of paracetamol, chlorphenamine and phenylephrine: a randomized, placebo-controlled trial

BackgroundThe common cold and other viral airway infections are highly prevalent in the population, and their treatment often requires the use of medications for symptomatic relief. Paracetamol is as an analgesic and antipyretic; chlorphenamine is an antihistamine; and phenylephrine, a vasoconstrictor and decongestant. This randomized, double-blind, placebo-controlled trial sought to evaluate the efficacy and safety of a fixed-dose combination of paracetamol, chlorphenamine and phenylephrine in the symptomatic treatment of the common cold and flu-like syndrome in adults.MethodsThis study enrolled 146 individuals aged 18 to 60 years who had moderate to severe flu-like syndrome or common cold. After clinical examination and laboratory tests, individuals were randomly assigned to receive the fixed-dose combination (73) or placebo (73), five capsules per day for 48 to 72 hours. The primary efficacy endpoint was the sum of the scores of 10 symptoms on a four-point Likert-type scale. To evaluate treatment safety, the occurrence of adverse events was also measured.ResultsMean age was 33.5 (±9.5) years in the placebo group and 33.8 (±11.5) in the treatment group. There were 55 women and 18 men in the placebo group, and 46 women and 27 men in the treatment group. Comparison of overall symptom scores in the two groups revealed a significantly greater reduction in the treatment group than in the placebo group (p = 0.015). Analysis at the first 13 dose intervals (± 66 h of treatment) showed a greater reduction of symptom scores in the treatment group than in the placebo group (p < 0.05). The number and distribution of adverse events were similar in both groups.ConclusionA fixed-dose combination of paracetamol, chlorphenamine and phenylephrine was safe and more effective than placebo in the symptomatic treatment of the common cold or flu-like syndrome in adults.Trial registrationNCT01389518