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The Pan African Medical Journal 2020fever is the primary symptom of most childhood illnesses and a cause of concern to their caregivers. The antipyretics commonly used to treat fever are ibuprofen and... (Comparative Study)
Comparative Study Randomized Controlled Trial
INTRODUCTION
fever is the primary symptom of most childhood illnesses and a cause of concern to their caregivers. The antipyretics commonly used to treat fever are ibuprofen and paracetamol. Most studies on the effectiveness of ibuprofen and paracetamol in treating fever in under-fives were conducted in Europe and North America with very few in African children. This study was aimed at assessing the effectiveness and safety of a single dose therapy of ibuprofen versus paracetamol for treating childhood fever in Nigeria.
METHODS
a randomized, controlled clinical trial was conducted in the University of Calabar Teaching Hospital, in Nigeria. A total of 140 eligible children aged 6-59 months with tympanic temperature of 38°C-40°C were enrolled, and 70 of them were assigned to one arm that received a single dose of ibuprofen (10mg/kg) and 70 had paracetamol (15mg/kg). After drug administration, the children were admitted and observed in the hospital for six hours during which period a half-hourly temperature measurement and monitoring for adverse events were done.
RESULTS
the overall result showed that ibuprofen had a better fever reducing effect compared to paracetamol. The proportion of afebrile children in the ibuprofen versus paracetamol group at 1.5-2.5 hours of administration of the drugs was statistically significant (p = 0.04). The adverse events of both drugs were mild and quite comparable with vomiting being the commonest.
CONCLUSION
ibuprofen is more effective in the treating fever in under-fives compared to paracetamol. The adverse events of both drugs were mild and comparable.
Topics: Acetaminophen; Antipyretics; Body Temperature; Child, Preschool; Female; Fever; Hospitals, Teaching; Humans; Ibuprofen; Infant; Male; Nigeria; Vomiting
PubMed: 33224416
DOI: 10.11604/pamj.2020.36.350.21393 -
Trials Jan 2021To compare the efficacy and safety of bioavailable turmeric extract versus paracetamol in patients with knee osteoarthritis (OA). (Comparative Study)
Comparative Study
BACKGROUND
To compare the efficacy and safety of bioavailable turmeric extract versus paracetamol in patients with knee osteoarthritis (OA).
METHODS
In this randomized, non-inferiority, controlled clinical study, patients of knee OA were randomized to receive bioavailable turmeric extract (BCM-95®) 500 mg capsule two times daily or paracetamol 650 mg tablet three times daily for 6 weeks. The primary outcome measure was Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale. The secondary outcome measures were WOMAC total, WOMAC stiffness, and WOMAC physical function scores. Responder analysis of individual patients at different levels (≥ 20%, ≥ 50%, and ≥ 70%) for WOMAC score was calculated. TNF alpha and CRP levels were evaluated and adverse events (AE) were also recorded.
RESULTS
Seventy-one and seventy-three knee OA patients, respectively in bioavailable turmeric extract and paracetamol groups, completed the study. Non-inferiority (equivalence) test showed that WOMAC scores were equivalent in both the groups (p value < 0.05) in all the domains within the equivalence limit defined by effect size (Cohen's d) of 0.5 whereas CRP and TNF-α were better reduced with turmeric extract than paracetamol. After 6 weeks of treatment, WOMAC total score, pain, stiffness, and function scores got a significant improvement of 23.59, 32.09, 28.5, and 20.25% respectively with turmeric extract. In the turmeric extract group, 18% of patients got more than 50% improvement and 3% of patients got more than 70% improvement in WOMAC pain and function/stiffness score and none of the patients in the paracetamol group met the criteria. CRP and TNF-α got significantly reduced (37.21 and 74.81% respectively) in the turmeric extract group. Adverse events reported were mild and comparatively less in the turmeric extract group (5.48%) than in the paracetamol group (12.68%).
CONCLUSION
The results of the study suggest that bioavailable turmeric extract is as effective as paracetamol in reducing pain and other symptoms of knee osteoarthritis and found to be safe and more effective in reducing CRP and TNF-α.
TRIAL REGISTRATION
Clinical Trials Registry - India CTRI/2017/02/007962 . Registered on 27 February 2017.
Topics: Acetaminophen; Adult; Curcuma; Double-Blind Method; Female; Humans; India; Male; Middle Aged; Osteoarthritis, Knee; Pain Measurement; Plant Extracts; Prospective Studies; Treatment Outcome
PubMed: 33516238
DOI: 10.1186/s13063-021-05053-7 -
Clinical Drug Investigation Oct 2015Previously published studies have suggested the lack of a pharmacokinetic interaction between ibuprofen and paracetamol when they are delivered as a fixed-dose oral... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND AND OBJECTIVES
Previously published studies have suggested the lack of a pharmacokinetic interaction between ibuprofen and paracetamol when they are delivered as a fixed-dose oral combination. The aim of this study was to determine the pharmacokinetic profile and safety of a fixed-dose intravenous (IV) combination, containing 3 mg/mL ibuprofen and 10 mg/mL paracetamol, in comparison with its individual components. The study also assessed the relative bioavailability of the same doses of the active ingredients when they were administered as an oral formulation.
METHODS
A single-dose, open-label, randomized, five-period cross-over sequence pharmacokinetic study was undertaken in 30 healthy volunteers. Serial plasma samples were assayed for both paracetamol and ibuprofen concentrations, using validated liquid chromatography-tandem mass spectrometry methods. Pharmacokinetic parameters were computed using standard non-compartmental analyses. Adverse events were also assessed. The ratios of the maximum measured plasma concentration (C max), the area under the plasma concentration-time curve (AUC) from time zero to the time of the last measurable plasma concentration (AUCt ) and AUC from time zero to infinity (AUC∞) were analysed for bioequivalence as determined by 90% confidence intervals.
RESULTS
The pharmacokinetic parameters of ibuprofen and paracetamol were very similar for the combination and monotherapy IV preparations; the ratios of the C max, AUC t and AUC∞ values fell within the 80-125% acceptable bioequivalence range. Precise dose proportionality for both compounds was also determined for the half dose of the IV formulation in comparison with the full dose. The relative bioavailability of paracetamol (93.78%) and ibuprofen (96.45%) confirmed the pharmacokinetic equivalence of the oral and IV formulations of the fixed-dose combination.
CONCLUSION
Concomitant administration of 3 mg/mL ibuprofen and 10 mg/mL paracetamol in a fixed-dose IV combination does not alter the pharmacokinetic profiles of either drug. The IV and oral dose forms of such a combination are pharmacokinetically equivalent.
Topics: Acetaminophen; Administration, Intravenous; Administration, Oral; Adolescent; Adult; Area Under Curve; Biological Availability; Cross-Over Studies; Drug Combinations; Female; Healthy Volunteers; Humans; Ibuprofen; Male; Middle Aged; Therapeutic Equivalency; Young Adult
PubMed: 26334726
DOI: 10.1007/s40261-015-0320-8 -
Italian Journal of Pediatrics Mar 2023Acute 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...
BACKGROUND
Acute 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.
METHODS
An 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.
RESULTS
The 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.
CONCLUSIONS
The 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.
Topics: Child; Humans; Acetaminophen; Acute Pain; Analgesics, Non-Narcotic; Consensus; Drug Combinations; Ibuprofen; Pain, Postoperative; Pain Management; Health Care Surveys; Administration, Oral
PubMed: 36945023
DOI: 10.1186/s13052-023-01445-4 -
European Journal of Clinical... Dec 2021Effect size estimates of analgesic drugs can be misleading. Ibuprofen (400 mg, 600 mg, 800 mg), paracetamol (1000 mg, 500 mg), paracetamol 1000 mg/codeine 60 mg,... (Randomized Controlled Trial)
Randomized Controlled Trial
Analgesic effect of oral ibuprofen 400, 600, and 800 mg; paracetamol 500 and 1000 mg; and paracetamol 1000 mg plus 60 mg codeine in acute postoperative pain: a single-dose, randomized, placebo-controlled, and double-blind study.
PURPOSE
Effect size estimates of analgesic drugs can be misleading. Ibuprofen (400 mg, 600 mg, 800 mg), paracetamol (1000 mg, 500 mg), paracetamol 1000 mg/codeine 60 mg, and placebo were investigated to establish the multidimensional pharmacodynamic profiles of each drug on acute pain with calculated effect size estimates.
METHODS
A randomized, double-blind, single-dose, placebo-controlled, parallel-group, single-centre, outpatient, and single-dose study used 350 patients (mean age 25 year, range 18 to 30 years) of homogenous ethnicity after third molar surgery. Primary outcome was sum pain intensity over 6 h. Secondary outcomes were time to analgesic onset, duration of analgesia, time to rescue drug intake, number of patients taking rescue drug, sum pain intensity difference, maximum pain intensity difference, time to maximum pain intensity difference, number needed to treat values, adverse effects, overall drug assessment as patient-reported outcome measure (PROM), and the effect size estimates NNT and NNTp.
RESULTS
Ibuprofen doses above 400 mg do not significantly increase analgesic effect. Paracetamol has a very flat analgesic dose-response profile. Paracetamol 1000/codeine 60 mg gives similar analgesia as ibuprofen from 400 mg, but has a shorter time to analgesic onset. Active drugs show no significant difference in maximal analgesic effect. Other secondary outcomes support these findings. The frequencies of adverse effects were low, mild to moderate in all active groups. NNT and NTTp values did not coincide well with PROMs.
CONCLUSION
Ibuprofen doses above 400 mg for acute pain offer limited analgesic gain. Paracetamol 1000 mg/codeine 60 mg is comparable to ibuprofen doses from 400 mg. Calculated effect size estimates and PROM in our study seem not to relate well as clinical analgesic efficacy estimators.
TRIAL REGISTRATION
NCT00699114.
Topics: Acetaminophen; Adolescent; Adult; Analgesics; Codeine; Dose-Response Relationship, Drug; Double-Blind Method; Drug Combinations; Drug Therapy, Combination; Female; Humans; Ibuprofen; Male; Pain Measurement; Pain, Postoperative; Young Adult
PubMed: 34655316
DOI: 10.1007/s00228-021-03231-9 -
Scandinavian Journal of Pain Oct 2017Acetaminophen is thought to be the safest analgesic and antipyretic medicine for pregnant women, and it is widely used all over the world. However, prenatal... (Review)
Review
Acetaminophen is thought to be the safest analgesic and antipyretic medicine for pregnant women, and it is widely used all over the world. However, prenatal acetaminophen was reported to be associated with asthma, lower performance intelligence quotient (IQ), shorter male infant anogenital distance (predicting poor male reproductive potential), autism spectrum disorder, neurodevelopmental problems (gross motor development, communication), attention-deficit/hyperactivity disorder, poorer attention and executive function, and behavioral problems in childhood. Each article has poor power to show risks of acetaminophen, however, the integration of the articles that showed adverse effects of acetaminophen may have power to show them. Acetaminophen use in childhood was associated with autism spectrum disorder, asthma symptoms, wheezing, and allergic disease. Acetaminophen is the safest medicine as analgesics for nociceptive pain and antipyretics in childhood and pregnancy. There is no alternative medication of acetaminophen. Acetaminophen should not be withheld from children or pregnant women for fears it might develop adverse effects. Acetaminophen should be used at the lowest effective dosage and for the shortest time. When we know the possible, rare but serious complications, we should use acetaminophen in pregnancy only when needed and no safer option for pain or fever relief is available. Health care providers should help inform the general lay public about this difficult dilemma.
Topics: Acetaminophen; Adult; Analgesics; Antipyretics; Child; Female; Humans; Pregnancy; Prenatal Exposure Delayed Effects
PubMed: 28986045
DOI: 10.1016/j.sjpain.2017.09.007 -
The Journal of Pediatrics Aug 2021
Review
Topics: Acetaminophen; Bronchopulmonary Dysplasia; Gestational Age; Humans; Infant, Newborn; Intensive Care Units, Neonatal; Liver; Lung
PubMed: 33617854
DOI: 10.1016/j.jpeds.2021.02.026 -
Nursing Open May 2022To understand the prevalence and epidemiology of paracetamol-induced hypotension and clinical implications for contemporaneous practice. (Review)
Review
AIM
To understand the prevalence and epidemiology of paracetamol-induced hypotension and clinical implications for contemporaneous practice.
DESIGN
Narrative review.
METHODS
In May and June 2020, an open-date literature search of English publications indexed in ProQuest, PubMed, and EBSCO was conducted with the search terms 'acetaminophen' and 'hypotension' and related search combinations ('paracetamol', 'propacetamol', 'low blood pressure', 'fever', 'sepsis', and 'shock') to identify peer-reviewed publications of blood pressure changes after paracetamol administration in humans.
RESULTS
A pattern of blood pressure reduction following the administration of paracetamol is demonstrated in the 27 studies included in this review. Haemodynamic intervention often followed persistent blood pressure reduction, and was greatest in febrile critically ill patients who received parenteral paracetamol.
Topics: Acetaminophen; Critical Illness; Fever; Humans; Hypotension; Hypotension, Controlled
PubMed: 34102027
DOI: 10.1002/nop2.943 -
Journal of Food and Drug Analysis Apr 2018Acetaminophen (paracetamol or APAP) is an analgesic and antipyretic drug that can induce oxidative stress-mediated hepatotoxicity at high doses. Several studies reported... (Review)
Review
Acetaminophen (paracetamol or APAP) is an analgesic and antipyretic drug that can induce oxidative stress-mediated hepatotoxicity at high doses. Several studies reported that antioxidant nutraceuticals, in particular phenolic phytochemicals from dietary food, spices, herbs and algae have hepatoprotective effects. Others, however, suggested that they may negatively impact the metabolism, efficacy and toxicity of APAP. The aim of this review is to discuss the pros and cons of the association of antioxidant nutraceuticals and APAP by reviewing the in vivo evidence, with particular reference to APAP pharmacokinetics and hepatotoxicity. Results from the murine models of APAP-induced hepatotoxicity showed amelioration of liver damage with nutraceuticals coadministration, as well as reductions in tissue markers of oxidative stress, and serum levels of hepatic enzymes, bilirubin, cholesterol, triglycerides and inflammatory cytokines. On the other hand, both increased and decreased APAP plasma levels have been reported, depending on the nutraceutical type and route of administration. For example, studies showed that repeated administration of flavonoids causes down-regulation of cytochrome P450 enzymes and up-regulation of uridine diphosphate glucuronosyltransferases (UGT). Moreover, nutraceuticals can alter the levels of APAP metabolites, such as mercapturate glucuronide, sulfate and cysteine conjugates. Overall, the reviewed in vivo studies indicate that interactions between APAP and nutraceuticals or plant foods exist. However, the majority of data come from animal models with doses of phytochemicals far from dietary ones. Human studies should investigate gene-diet interactions, as well as ethnic variability in order to clarify the pros and cons of co-administering antioxidant nutraceuticals and APAP.
Topics: Acetaminophen; Animals; Antioxidants; Dietary Supplements; Herb-Drug Interactions; Humans; Oxidative Stress
PubMed: 29703389
DOI: 10.1016/j.jfda.2017.11.004 -
The association between acetaminophen and asthma: is there anything to learn from the upper airways?Current Opinion in Allergy and Clinical... Feb 2014To examine the literature evidence for the association between acetaminophen (paracetamol) use and development of rhinitis. (Review)
Review
PURPOSE OF REVIEW
To examine the literature evidence for the association between acetaminophen (paracetamol) use and development of rhinitis.
RECENT FINDINGS
Increased use of acetaminophen (paracetamol) as the favored antipyretic during pregnancy and infancy has been hypothesized to be a risk factor for the development of asthma. There is a paucity of well designed birth cohort studies to examine paracetamol as a risk factor in the development of rhinitis. Confounding by antibiotic use, viral infections, and recall bias are problematic for many of the studies that are published.
SUMMARY
Prospective birth cohorts need to dedicate sufficient time and research personnel to adequately assess paracetamol exposure as a primary variable of interest rather than as an incidental exposure variable collected during routine questionnaire administration.
Topics: Acetaminophen; Anti-Bacterial Agents; Asthma; Cohort Studies; Confounding Factors, Epidemiologic; Female; Humans; Infant; Infant, Newborn; Pregnancy; Research Design; Respiratory System; Risk; Virus Diseases
PubMed: 24322007
DOI: 10.1097/ACI.0000000000000026