Possible Interaction: Acetaminophen and Caffeine

“The pharmacokinetic calculations in men demonstrated an interaction between paracetamol and caffeine which was indicated by a decrease in plasma paracetamol levels, by a smaller surface under the curve of changes of paracetamol levels indicating faster elimination of the drug after simultaneous administration with caffeine.”

“ Caffeine caused a highly significant (p < 0.01) increase in AUC and AUMC, a significant (p < 0.05) increase in Cmax, and a significant (p < 0.05) decrease in clearance (Cl/F) of acetaminophen.”

“We conclude that caffeine taken in doses commonly available commercially or in a cup of coffee can significantly potentiate the therapeutic potential of acetaminophen in man.”

“Recent studies have demonstrated that caffeine acts as an analgesic adjuvant when combined with acetaminophen , aspirin, or their mixture.”

“We conclude that caffeine enhances the analgesic efficacy of acetaminophen.”

“In preclinical studies, caffeine produces intrinsic antinociceptive effects in several rodent models, and augments the actions of NSAIDs and acetaminophen.”

“Low doses of caffeine given systemically inhibit antinociception by several analgesics ( acetaminophen , amitriptyline, oxcarbazepine, cizolirtine), probably reflecting block of a component of action involving adenosine A(1) receptors.”

“However, the analgesic adjuvant effects of caffeine have not been seriously investigated since a pooled analysis conducted in 1984 showed that caffeine reduces the amount of paracetamol (acetaminophen) necessary for the same effect by approximately 40%.”

“Because salicylates have been reported to augment the stimulatory effects of caffeine on the CNS, attention was focused on the possibility that the presence of acetaminophen (52 micrograms/mL) reduced the CNS toxicity of caffeine.”

“Studies in …) pretreatment with acetaminophen (100 mg/… administration of caffeine (300 to 450 mg/kg IP) and the onset of fatal convulsions by a factor of about two; and 2) …) reduced the incidence of audiogenic seizures produced in the presence of caffeine (12.5 to 75 mg/kg IP).”

“The frequency of sound-induced seizures after 12.5 or 25 mg/kg caffeine was reduced from 50 to 5% by acetaminophen.”

“Thus the mechanism by which acetaminophen antagonizes the actions of caffeine in the CNS remains unknown.”

“ Caffeine markedly exacerbated acetaminophen toxicity by suppressing ATM activity in otherwise nontoxic 2.5 millimolar amount.”

“We concluded that hepatic DNA damage, mitochondrial impairment and growth-arrest after combined caffeine and acetaminophen toxicity will be harmful for premature infants.”

“Compared with analgesic medication alone, combinations of caffeine with analgesic medications, including acetaminophen , acetylsalicylic acid, and ibuprofen, showed significantly improved efficacy in the treatment of patients with TTH or migraine, with favorable tolerability in the vast majority of patients.”

“They are used as drugs separately or in combination with others to support and strengthen the action of other drugs - for example, the combination of caffeine and paracetamol.”