Aspirin/paracetamol/caffeine

All active treatments except caffeine differed significantly from placebo, with superior efficacy of the triple combination; well tolerated; low incidence of adverse events.{{Cite web |date=2025-04-21 |title=The fixed combination of acetylsalicylic acid, paracetamol and caffeine is more effective than single substances and dual combination for the treatment of headache: a multicentre, randomized, double-blind, single-dose, placebo-controlled parallel group study - PubMed |url=https://web.archive.org/web/20250421083606/https://pubmed.ncbi.nlm.nih.gov/16162254/ |access-date=2025-04-21 |website=web.archive.org}}{{Cite web |date=2025-04-21 |title=The efficacy and tolerability of a fixed combination of acetylsalicylic acid, paracetamol, and caffeine in patients with severe headache: a post-hoc subgroup analysis from a multicentre, randomized, double-blind, single-dose, placebo-controlled parallel group study - PubMed |url=https://web.archive.org/web/20250421083743/https://pubmed.ncbi.nlm.nih.gov/21908446/ |access-date=2025-04-21 |website=web.archive.org}}

{{See also|Aspirin#Adverse effects|Paracetamol#Adverse effects|Caffeine#Adverse effects}}

The recommended dosing has a low risk profile when taken occasionally in a well hydrated state.{{Cite web |date=2025-04-21 |title=The fixed combination of acetylsalicylic acid, paracetamol and caffeine is more effective than single substances and dual combination for the treatment of headache: a multicentre, randomized, double-blind, single-dose, placebo-controlled parallel group study - PubMed |url=https://web.archive.org/web/20250421083606/https://pubmed.ncbi.nlm.nih.gov/16162254/ |access-date=2025-04-21 |website=web.archive.org}} As with all medications containing paracetamol (acetaminophen), concomitant use with alcohol carries a significant risk of hepatotoxicity.{{cite book|title=Austria-Codex| veditors = Haberfeld H |at=Thomapyrin-Tabletten|publisher=Österreichischer Apothekerverlag|location=Vienna|year=2019|language=German}} The combination of paracetamol with aspirin also creates the risk of renal papillary necrosis if large doses are taken chronically. This is because paracetamol yields a toxic metabolite that can accumulate in the kidney while aspirin works to deplete the glutathione stores necessary to oxidize it. Additionally, chronic aspirin usage is associated with increased risk of gastrointestinal bleeding.{{cite journal | vauthors = Henrich WL, Agodoa LE, Barrett B, Bennett WM, Blantz RC, Buckalew VM, D'Agati VD, DeBroe ME, Duggin GG, Eknoyan G | display-authors = 6 | title = Analgesics and the kidney: summary and recommendations to the Scientific Advisory Board of the National Kidney Foundation from an Ad Hoc Committee of the National Kidney Foundation | journal = American Journal of Kidney Diseases | volume = 27 | issue = 1 | pages = 162–5 | date = January 1996 | pmid = 8546133 | doi = 10.1016/S0272-6386(96)90046-3 | url = http://www.ajkd.org/article/S0272-6386%2896%2990046-3/abstractref }}

The combination of these three compounds can be detected in pharmaceutical formulations, urine and blood serum in trace quantities using electrochemical methods.{{cite journal|title=Simultaneous voltammetric determination of acetaminophen, aspirin and caffeine using an in situ surfactant-modified multiwalled carbon nanotube paste electrode|vauthors=Sanghavi BJ, Srivastava AK|journal=Electrochimica Acta|volume=55|year=2010|pages=8638–8648 |url= |doi=10.1016/j.electacta.2010.07.093|issue=28}}

The combination was first introduced as the name Trigesic, as the formula of 125 mg paracetamol, 230 mg aspirin, and 30 mg caffeine, in July 1950 by Squibb, which is now Bristol Myers Squibb, but was recalled in the following year due to several reports that the drug might cause blood dyscrasia.Spooner, J. B., & Harvey, J. G. (1976). The history and usage of paracetamol. Journal of International Medical Research, 4(4_suppl), 1-6. In 1964 it was marketed under the trade name Vanquish by Sterling Drug,{{citation needed|date=November 2019}} which after a series of mergers and acquisitions became a unit of Bayer AG.{{cite news|last=Olmos|first=David | name-list-style = vanc |title=German Firm to Reclaim Bayer Aspirin Name : Drugs: It will acquire Sterling Winthrop's over-the-counter business and recover the rights it lost after WWI|url=https://www.latimes.com/archives/la-xpm-1994-09-13-fi-38019-story.html|access-date=May 3, 2013|newspaper=Los Angeles Times|date=September 14, 1994}}

In the UK it is sold as Anadin Extra. In Germany, it is sold as dolomo, Dolopyrin AL, HA-Tabletten, Melabon K, Neuralgin, ratiopyrin, Thomapyrin Classic, Thomapyrin Intensiv,{{cite web|url=https://www.rote-liste.de/|title=Rote Liste|access-date=2020-01-24}} in Austria as Thomapyrin, and InfluASS, in Israel as Acamol Focus, Paramol Target and Exidol, in Romania as Antinevralgic P {{cite web | title = Antinevralgic P comprimate | url = https://www.anm.ro/_/_PRO/pro_5499_14.07.05.pdf | work = Agenția Natională a Medicamentului și a Dispozitivelor Medicale din România }} and Antinevralgic Forte,{{cite web | vauthors = Blanaru C | date = 26 June 2013 | work = Branding Business | publisher = AdHugger | title = The launch of Antinevralgic Forte – reinventing a traditional brand | url = https://www.adhugger.net/2013/06/26/the-launch-of-antinevralgic-forte-reinventing-a-traditional-brand/}} and in Russia, Belarus and Eastern Europe as Citramon.{{cite web|url=https://www.drugs.com/international/|publisher=Drugs.com|title=International Drug Names|access-date=2020-01-24}}

In South Africa and neighbouring countries, it is known as Grand-Pa, and is most commonly sold as a powder{{cite web|url=https://www.grand-pa.co.za/products/ |title=Products }}

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