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Australian Journal of General Practice Apr 2019Paracetamol is a widely used analgesic to which hypersensitivity reactions are rare. Reactions to paracetamol may be due to the pharmacological effects of...
BACKGROUND
Paracetamol is a widely used analgesic to which hypersensitivity reactions are rare. Reactions to paracetamol may be due to the pharmacological effects of cyclooxygenase-1 inhibition or, more rarely, due to a selective allergy against paracetamol.
OBJECTIVE
This article aims to review the current literature in the context of two cases seen in the authors' allergy practice.
DISCUSSION
Paracetamol allergy is uncommon and, as a result, may be overlooked as a cause for immediate hypersensitivity, which can lead to a significant delay in diagnosis. Currently, specialist referral for a supervised oral challenge is required for formal diagnosis.
Topics: Acetaminophen; Allergy and Immunology; Anti-Inflammatory Agents, Non-Steroidal; Drug Hypersensitivity; Humans; Referral and Consultation
PubMed: 31256492
DOI: 10.31128/AJGP-08-18-4689 -
Health Promotion and Chronic Disease... Apr 2020We examined trends in emergency department (ED) presentation rates for acetaminophenrelated poisonings across Canada. A total of 27123 cases of poisoning were seen in...
We examined trends in emergency department (ED) presentation rates for acetaminophenrelated poisonings across Canada. A total of 27123 cases of poisoning were seen in the electronic Canadian Hospitals Injury Reporting and Prevention Program (eCHIRPP) sentinel sites between April 2011 and February 2019; of these, 13.7% were related to acetaminophen use. A significant decreasing trend for both sexes was observed for unintentional poisonings (males: -10.3%; females: -8.0%). For intentional poisonings, there was a significant decrease among females only (-5.9%). Females have consistently displayed higher rates of ED presentations for both unintentional and intentional poisoning.
Topics: Acetaminophen; Adolescent; Adult; Age Distribution; Analgesics, Non-Narcotic; Canada; Child; Child, Preschool; Emergency Service, Hospital; Female; Humans; Male; Middle Aged; Poisoning; Sex Factors; Young Adult
PubMed: 32270671
DOI: 10.24095/hpcdp.40.4.05 -
Pharmacology Research & Perspectives Aug 2022Semaglutide is a glucagon-like-peptide-1 (GLP-1) analogue marketed for once-weekly subcutaneous administration for type 2 diabetes mellitus. Like other long-acting GLP-1...
Semaglutide is a glucagon-like-peptide-1 (GLP-1) analogue marketed for once-weekly subcutaneous administration for type 2 diabetes mellitus. Like other long-acting GLP-1 analogues, semaglutide reduces gastric emptying and, potentially, alters the rate of absorption of orally co-administered drugs. The objective of the current analysis was to evaluate the effects on the gastric emptying rate caused by semaglutide on pharmacokinetic model parameters of paracetamol and atorvastatin in healthy subjects. Non-linear mixed effect modeling was used to estimate population pharmacokinetic model parameters of paracetamol and atorvastatin after single doses with or without semaglutide. The absorption rate (ka) of paracetamol decreased by 53% when co-administered with semaglutide. For atorvastatin, ka and transit compartment rate (ktr) decreased by 72% and 91%, respectively. Thus, gastric emptying, measured as T50, i.e., drug disappearance from the absorption compartments, showed an additional 5-min delay for paracetamol and a 67-min delay for atorvastatin when co-administered with semaglutide. Semaglutide affected pharmacokinetic model parameters of paracetamol and atorvastatin, and minor quantitative differences in gastric emptying between placebo vs. semaglutide administration were observed. However, these effects of semaglutide were considered not to be of clinical relevance.
Topics: Acetaminophen; Atorvastatin; Diabetes Mellitus, Type 2; Glucagon-Like Peptide 1; Glucagon-Like Peptides; Humans; Hypoglycemic Agents
PubMed: 35799471
DOI: 10.1002/prp2.962 -
CNS Drug Reviews 2007The combination of numerous classic drugs with nitric oxide donors has led to the development of new compounds with promising therapeutic activities in a great variety... (Review)
Review
The combination of numerous classic drugs with nitric oxide donors has led to the development of new compounds with promising therapeutic activities in a great variety of situations, including cardiovascular and respiratory systems, ocular pressure, inflammation, and pain. One of the first compounds developed was NCX-701 or nitroparacetamol, resulting from the combination of paracetamol, a classic and popular analgesic used in a great number of over-the-counter medications because of its antipyretic and analgesic properties, and a nitrooxybutyroyl moiety, which releases nitric oxide at a low but steady level. Although paracetamol is devoid of most of the gastrointestinal toxicity associated with aspirin-like drugs, this type of compounds was first designed to take advantage of the cytoprotective properties of nitric oxide when released at low concentrations. However, the combination of these molecules also resulted in an unexpected enhancement of the analgesic activity of paracetamol. In fact, NCX-701 has been shown to be effective in acute nociception as well as in neuropathic pain, situations in which paracetamol and other COX inhibitors are devoid of any effect. In addition, NCX-701 is more potent and, in some circumstances, more effective than its parent compound in different models of inflammatory pain. Furthermore, whereas paracetamol lacks any effective antiinflammatory action, NCX-701 might reduce inflammation. All these results taken together imply that the mechanism of action of NCX-701 is different from that of paracetamol, although it is not yet established for either molecule. NCX-701 appears to be a promising compound in the treatment of different types of pain, with a likely better profile of side effects than its parent molecule, paracetamol. Although recent clinical trials provided data consistent with the preclinical profile of NCX-701, further studies are needed to support its clinical use.
Topics: Acetaminophen; Analgesics; Animals; Humans; Nitrates; Pain
PubMed: 17894645
DOI: 10.1111/j.1527-3458.2007.00016.x -
Journal of Medical Internet Research Jul 2021Individuals frequently turning to social media to discuss medical conditions and medication, sharing their experiences and information and asking questions among...
BACKGROUND
Individuals frequently turning to social media to discuss medical conditions and medication, sharing their experiences and information and asking questions among themselves. These online discussions can provide valuable insights into individual perceptions of medical treatment, and increasingly, studies are focusing on the potential use of this information to improve health care management.
OBJECTIVE
The objective of this infodemiology study was to identify social media posts mentioning paracetamol-containing products to develop a better understanding of patients' opinions and perceptions of the drug.
METHODS
Posts between January 2003 and March 2019 containing at least one mention of paracetamol were extracted from 18 French forums in May 2019 with the use of the Detec't (Kap Code) web crawler. Posts were then analyzed using the automated Detec't tool, which uses machine learning and text mining methods to inspect social media posts and extract relevant content. Posts were classified into groups: Paracetamol Only, Paracetamol and Opioids, Paracetamol and Others, and the Aggregate group.
RESULTS
Overall, 44,283 posts were analyzed from 20,883 different users. Post volume over the study period showed a peak in activity between 2009 and 2012, as well as a spike in 2017 in the Aggregate group. The number of posts tended to be higher during winter each year. Posts were made predominantly by women (14,897/20,883, 71.34%), with 12.00% (2507/20,883) made by men and 16.67% (3479/20,883) by individuals of unknown gender. The mean age of web users was 39 (SD 19) years. In the Aggregate group, pain was the most common medical concept discussed (22,257/37,863, 58.78%), and paracetamol risk was the most common discussion topic, addressed in 20.36% (8902/43,725) of posts. Doliprane was the most common medication mentioned (14,058/44,283, 31.74%) within the Aggregate group, and tramadol was the most commonly mentioned drug in combination with paracetamol in the Aggregate group (1038/19,587, 5.30%). The most common unapproved indication mentioned within the Paracetamol Only group was fatigue (190/616, with 16.32% positive for an unapproved indication), with reference to dependence made by 1.61% (136/8470) of the web users, accounting for 1.33% (171/12,843) of the posts in the Paracetamol Only group. Dependence mentions in the Paracetamol and Opioids group were provided by 6.94% (248/3576) of web users, accounting for 5.44% (342/6281) of total posts. Reference to overdose was made by 245 web users across 291 posts within the Paracetamol Only group. The most common potential adverse event detected was nausea (306/12843, 2.38%) within the Paracetamol Only group.
CONCLUSIONS
The use of social media mining with the Detec't tool provided valuable information on the perceptions and understanding of the web users, highlighting areas where providing more information for the general public on paracetamol, as well as other medications, may be of benefit.
Topics: Acetaminophen; Adult; Analgesics, Opioid; Data Mining; Female; Humans; Male; Perception; Social Media
PubMed: 34255645
DOI: 10.2196/25049 -
Molecules (Basel, Switzerland) Mar 2022The analytical performance of the clay paste electrode and graphene paste electrode was compared using square wave voltammetry (SWV) and cyclic voltammetry (CV). The...
The analytical performance of the clay paste electrode and graphene paste electrode was compared using square wave voltammetry (SWV) and cyclic voltammetry (CV). The comparison was made on the basis of a paracetamol (PA) determination on both working electrodes. The influence of pH and SWV parameters was investigated. The linear concentration ranges were found to be 6.0 × 10-3.0 × 10 and 2.0 × 10-8.0 × 10 mol L for clay paste electrode (ClPE) and graphene paste electrode (GrPE), respectively. The detection and quantification limits were calculated as 1.4 × 10 and 4.7 ×10 mol L for ClPE and 3.7 × 10 and 1.2 × 10 mol L for GrPE, respectively. Developed methods were successfully applied to pharmaceutical formulations analyses. Scanning electron microscopy and energy-dispersive X-ray spectroscopy were used to characterize ClPE and GrPE surfaces. Clay composition was examined with wavelength dispersive X-ray (WDXRF).
Topics: Acetaminophen; Carbon; Clay; Electrochemical Techniques; Electrodes; Graphite
PubMed: 35408436
DOI: 10.3390/molecules27072037 -
The Cochrane Database of Systematic... Jun 2016Tension-type headache (TTH) affects about 1 person in 5 worldwide. It is divided into infrequent episodic TTH (fewer than one headache per month), frequent episodic TTH... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Tension-type headache (TTH) affects about 1 person in 5 worldwide. It is divided into infrequent episodic TTH (fewer than one headache per month), frequent episodic TTH (two to 14 headaches per month), and chronic TTH (15 headache days a month or more). Paracetamol (acetaminophen) is one of a number of analgesics suggested for acute treatment of headaches in frequent episodic TTH.
OBJECTIVES
To assess the efficacy and safety of paracetamol for the acute treatment of frequent episodic TTH in adults.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (CRSO), MEDLINE, EMBASE, and the Oxford Pain Relief Database to October 2015, and also reference lists of relevant published studies and reviews. We sought unpublished studies by asking personal contacts and searching online clinical trial registers and manufacturers' websites.
SELECTION CRITERIA
We included randomised, double-blind, placebo-controlled studies (parallel-group or cross-over) using oral paracetamol for symptomatic relief of an acute episode of TTH. Studies had to be prospective, with participants aged 18 years or over, and include at least 10 participants per treatment arm.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed studies for inclusion and extracted data. We used the numbers of participants achieving each outcome to calculate the risk ratio (RR) and number needed to treat for one additional beneficial outcome (NNT) or one additional harmful outcome (NNH) for oral paracetamol compared to placebo or an active intervention for a range of outcomes, predominantly those recommended by the International Headache Society (IHS).We assessed the evidence using GRADE (Grading of Recommendations Assessment, Development and Evaluation) and created 'Summary of findings' tables.
MAIN RESULTS
We included 23 studies, all of which enrolled adults with frequent episodic TTH. Twelve studies used the IHS diagnostic criteria or similar, six used the older classification of the Ad Hoc Committee, and five did not describe specific diagnostic criteria but generally excluded participants with migraines. Participants had moderate or severe pain at the start of treatment. While 8079 people with TTH participated in these studies, the numbers available for any analysis were lower than this because outcomes were inconsistently reported and because many participants received active comparators.None of the included studies were at low risk of bias across all domains considered, although for most studies and domains this was likely to be due to inadequate reporting rather than poor methods. We judged five studies to be at high risk of bias for incomplete outcome reporting, and seven due to small size.For the IHS preferred outcome of being pain free at two hours the NNT for paracetamol 1000 mg compared with placebo was 22 (95% confidence interval (CI) 15 to 40) in eight studies (5890 participants; high quality evidence), with no significant difference from placebo at one hour. The NNT was 10 (7.9 to 14) for pain-free or mild pain at two hours in five studies (5238 participants; high quality evidence). The use of rescue medication was lower with paracetamol 1000 mg than with placebo, with an NNTp to prevent an event of 7.8 (6.0 to 11) in six studies (1856 participants; moderate quality evidence). On limited data, the efficacy of paracetamol 500 mg to 650 mg was not superior to placebo, and paracetamol 1000 mg was not different from either ketoprofen 25 mg or ibuprofen 400 mg (low quality evidence).Adverse events were not different between paracetamol 1000 mg and placebo (RR 1.1 (0.94 to 1.3); 5605 participants; 11 studies; high quality evidence). Studies reported no serious adverse events.The quality of the evidence using GRADE comparing paracetamol 1000 mg with placebo was moderate to high. Where evidence was downgraded it was because a minority of studies reported the outcome. For comparisons of paracetamol 500 mg to 650 mg with placebo, and of paracetamol 1000 mg with active comparators, we downgraded the evidence to low quality or very low quality because of the small number of studies and events.
AUTHORS' CONCLUSIONS
Paracetamol 1000 mg provided a small benefit in terms of being pain free at two hours for people with frequent episodic TTH who have an acute headache of moderate or severe intensity.
Topics: Acetaminophen; Administration, Oral; Adult; Analgesics, Non-Narcotic; Humans; Pain Measurement; Randomized Controlled Trials as Topic; Tension-Type Headache; Time Factors
PubMed: 27306653
DOI: 10.1002/14651858.CD011889.pub2 -
British Journal of Clinical Pharmacology Nov 2015The antiviral agent favipiravir is likely to be co-prescribed with acetaminophen (paracetamol). The present study evaluated the possiblility of a pharmacokinetic...
AIMS
The antiviral agent favipiravir is likely to be co-prescribed with acetaminophen (paracetamol). The present study evaluated the possiblility of a pharmacokinetic interaction between favipiravir and acetaminophen, in vitro and in vivo.
METHODS
The effect of favipivir on the transformation of acetaminophen to its glucuronide and sulfate metabolites was studied using a pooled human hepatic S9 fraction in vitro. The effect of acute and extended adminstration of favipiravir on the pharmacokinetics of acetaminophen and metabolites was evaluated in human volunteers.
RESULTS
Favipiravir inhibited the in vitro formation of acetaminophen sulfate, but not acetaminophen glucuronide. In human volunteers, both acute (1 day) and extended (6 days) administration of favipiravir slightly but significantly increased (by about 20 %) systemic exposure to acetaminophen (total AUC), whereas Cmax was not significantly changed. AUC for acetaminophen glucuronide was increased by 23 to 35 % above control by favipiravir, while AUC for acetaminophen sulfate was reduced by about 20 % compared to control. Urinary excretion of acetaminophen sulfate was likewise reduced to 44 to 65 % of control values during favipiravir co-administration, while excretion of acetaminophen glucuronide increased to 17 to 32 % above control.
CONCLUSION
Favipiravir inhibits acetaminophen sulfate formation in vitro and in vivo. However the increase in systemic exposure to acetaminophen due to favipiravir co-administration, though statistically significant, is small in magnitude and unlikely to be of clinical importance.
Topics: Acetaminophen; Adult; Amides; Analgesics, Non-Narcotic; Antiviral Agents; Drug Interactions; Female; Humans; In Vitro Techniques; Inhibitory Concentration 50; Male; Middle Aged; Pyrazines; Young Adult
PubMed: 25808818
DOI: 10.1111/bcp.12644 -
Environment International Nov 2023Paracetamol/acetaminophen (N-acetyl-p-aminophenol, APAP) is a top selling analgesic used in more than 600 prescription and non-prescription pharmaceuticals. To study...
Paracetamol/acetaminophen (N-acetyl-p-aminophenol, APAP) is a top selling analgesic used in more than 600 prescription and non-prescription pharmaceuticals. To study efficiently some of the potential undesirable effects associated with increasing APAP consumption (e.g., developmental disorders, drug-induced liver injury), there is a need to improve current APAP biomonitoring methods that are limited by APAP short half-life. Here, we demonstrate using high-resolution mass spectrometry (HRMS) in several human studies that APAP thiomethyl metabolite conjugates (S-methyl-3-thioacetaminophen sulfate and S-methyl-3-thioacetaminophen sulphoxide sulfate) are stable biomarkers with delayed excretion rates compared to conventional APAP metabolites, that could provide a more reliable history of APAP ingestion in epidemiological studies. We also show that these biomarkers could serve as relevant clinical markers to diagnose APAP acute intoxication in overdosed patients, when free APAP have nearly disappeared from blood. Using in vitro liver models (HepaRG cells and primary human hepatocytes), we then confirm that these thiomethyl metabolites are directly linked to the toxic N-acetyl-p-benzoquinone imine (NAPQI) elimination, and produced via an overlooked pathway called the thiomethyl shunt pathway. Further studies will be needed to determine whether the production of the reactive hepatotoxic NAPQI metabolites is currently underestimated in human. Nevertheless, these biomarkers could already serve to improve APAP human biomonitoring, and investigate, for instance, inter-individual variability in NAPQI production to study underlying causes involved in APAP-induced hepatotoxicity. Overall, our findings demonstrate the potential of exposomics-based HRMS approach to advance towards a better precision for human biomonitoring.
Topics: Humans; Acetaminophen; Biological Monitoring; Mass Spectrometry; Liver; Biomarkers; Sulfates
PubMed: 37951015
DOI: 10.1016/j.envint.2023.108299 -
The Cochrane Database of Systematic... May 2016This is an updated version of the original Cochrane review published in Issue 10, 2011. Paracetamol (acetaminophen) is the most commonly prescribed analgesic for the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This is an updated version of the original Cochrane review published in Issue 10, 2011. Paracetamol (acetaminophen) is the most commonly prescribed analgesic for the treatment of acute pain. It may be administered orally, rectally, or intravenously. The efficacy and safety of intravenous (IV) formulations of paracetamol, IV paracetamol, and IV propacetamol (a prodrug that is metabolized to paracetamol), compared with placebo and other analgesics, is unclear.
OBJECTIVES
To assess the efficacy and safety of IV formulations of paracetamol for the treatment of postoperative pain in both adults and children.
SEARCH METHODS
We ran the search for the previous review in May 2010. For this update, we searched the Cochrane Central Register of Controlled Trials (CENTRAL 2016, Issue 1), MEDLINE (May 2010 to 16 February 2016), EMBASE (May 2010 to 16 February 2016), LILACS (2010 to 2016), a clinical trials registry, and reference lists of reviews for randomized controlled trials (RCTs) in any language and we retrieved articles.
SELECTION CRITERIA
Randomized, double-blind, placebo- or active-controlled single dose clinical trials of IV paracetamol or IV propacetamol for acute postoperative pain in adults or children.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data, which included demographic variables, type of surgery, interventions, efficacy, and adverse events. We contacted study authors for additional information. We graded each included study for methodological quality by assessing risk of bias and employed the GRADE approach to assess the overall quality of the evidence.
MAIN RESULTS
We included 75 studies (36 from the original review and 39 from our updated review) enrolling a total of 7200 participants.Among primary outcomes, 36% of participants receiving IV paracetamol/propacetamol experienced at least 50% pain relief over four hours compared with 16% of those receiving placebo (number needed to treat to benefit (NNT) = 5; 95% confidence interval (CI) 3.7 to 5.6, high quality evidence). The proportion of participants in IV paracetamol/propacetamol groups experiencing at least 50% pain relief diminished over six hours, as reflected in a higher NNT of 6 (4.6 to 7.1, moderate quality evidence). Mean pain intensity at four hours was similar when comparing IV paracetamol and placebo, but was seven points lower on a 0 to 100 visual analog scale (0 = no pain, 100 = worst pain imaginable, 95% CI -9 to -6, low quality evidence) in those receiving paracetamol at six hours.For secondary outcomes, participants receiving IV paracetamol/propacetamol required 26% less opioid over four hours and 16% less over six hours (moderate quality evidence) than those receiving placebo. However, this did not translate to a clinically meaningful reduction in opioid-induced adverse events.Meta-analysis of efficacy comparisons between IV paracetamol/propacetamol and active comparators (e.g., opioids or nonsteroidal anti-inflammatory drugs) were either not statistically significant, not clinically significant, or both.Adverse events occurred at similar rates with IV paracetamol or IV propacetamol and placebo. However, pain on infusion occurred more frequently in those receiving IV propacetamol versus placebo (23% versus 1%). Meta-analysis did not demonstrate clinically meaningful differences between IV paracetamol/propacetamol and active comparators for any adverse event.
AUTHORS' CONCLUSIONS
Since the last version of this review, we have found 39 new studies providing additional information. Most included studies evaluated adults only. We reanalyzed the data but the results did not substantially alter any of our previously published conclusions. This review provides high quality evidence that a single dose of either IV paracetamol or IV propacetamol provides around four hours of effective analgesia for about 36% of patients with acute postoperative pain. Low to very low quality evidence demonstrates that both formulations are associated with few adverse events, although patients receiving IV propacetamol have a higher incidence of pain on infusion than both placebo and IV paracetamol.
Topics: Acetaminophen; Acute Pain; Adult; Analgesics; Child; Humans; Injections, Intravenous; Pain Measurement; Pain, Postoperative; Randomized Controlled Trials as Topic; Time Factors
PubMed: 27213715
DOI: 10.1002/14651858.CD007126.pub3