All active treatments except caffeine differed significantly fromplacebo, with superior efficacy of thetriple combination; well tolerated; low incidence of adverse events.[2][3]
The recommended dosing has a low risk profile when taken occasionally in a well hydrated state.[2] As with all medications containingparacetamol (acetaminophen), concomitant use withalcohol carries a significant risk ofhepatotoxicity.[4] The combination of paracetamol withaspirin also creates the risk ofrenal 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 theglutathione stores necessary to oxidize it. Additionally, chronic aspirin usage is associated with increased risk of gastrointestinal bleeding.[5]
The combination of these three compounds can be detected in pharmaceutical formulations, urine and blood serum in trace quantities usingelectrochemical methods.[6]
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 nowBristol Myers Squibb, but was recalled in the following year due to several reports that the drug might cause blooddyscrasia.[7] In 1965 it was marketed under the trade name Vanquish bySterling Drug,[8] which after a series of mergers and acquisitions became a unit ofBayer AG.[9]
In the UK it is sold as Anadin Extra. In the US, it is the brandExcedrin's flagship product. In Germany, it is sold as Dolomo, Dolopyrin AL, HA-Tabletten, Melabon K, Neuralgin, ratiopyrin, Thomapyrin Classic, Thomapyrin Intensiv,[10] in Austria as Thomapyrin, and InfluASS, in Israel as Acamol Focus, Paramol Target and Exidol, in Romania as Antinevralgic P[11] and Antinevralgic Forte,[12] and in Russia, Belarus and Eastern Europe as Citramon.[13]
In South Africa and neighbouring countries, it is known as Grand-Pa, and is most commonly sold as a powder.
^Sanghavi BJ, Srivastava AK (2010). "Simultaneous voltammetric determination of acetaminophen, aspirin and caffeine using an in situ surfactant-modified multiwalled carbon nanotube paste electrode".Electrochimica Acta.55 (28):8638–8648.doi:10.1016/j.electacta.2010.07.093.