Acetaminophen (Paracetamol): Use beyond Pain Management and Dose Variability.

Abstract

Inappropriate prescribing of analgesics or self-administration through over the counter formulations results in regular often negative reporting within the media. Indeed, their abuse within elite through to recreational sport is not uncommon (Feucht and Patel, 2010; Warden, 2010; Tscholl and Dvorak, 2012; Brewer et al., 2014). For example, acetaminophen (ACT; commonly known as paracetamol) use is even prevalent in young sub-elite athletes, who consume ACT or other analgesics [e.g., non-steroidal anti-inflammatory drugs (NSAIDs)] to decrease pain from previous athletic exertion or prophylactically to reduce pain in subsequent training/competition (Garcin et al., 2005). Related recent headlines include a former FIFA Chief Medical Officer stating that “about half of players competing at the past three World Cups routinely took NSAIDs like ibuprofen” whilst former players report pressure to use such drugs “to get through games” (BBCSport, 2017). NSAIDs and ACT are the most commonly used antipyretic and analgesic drugs worldwide (Hinz and Brune, 2012). Given they are available over the counter, their use even with careful club/team physician oversight can be difficult to police within a professional sport environment. If team clinicians ban over the counter analgesia use, players can and do simply self-administer, increasing risk of drug interaction with clinician prescribed medications and/or over-dose risk (inadvertently or otherwise). ACT has been used globally since 1955 and is considered a safe effective analgesic (Bunchorntavakul and Reddy, 2013). The analgesic properties of ACT are similar to NSAIDs, yet ACT does not share similar NSAID mediated anti-inflammatory actions (Graham et al., 2013). ACT carries fewer, if any, side-effects when used at appropriate dosages compared to NSAIDs (Towheed et al., 2006; Jones et al., 2015). NSAIDs side-effects can include gastrointestinal and arterial wall damage, gastrointestinal ulcers, arterial blood clotting, myocardial infarction, stroke and hemorrhage perforation, amongst others (Ong et al., 2007; Van Wijck et al., 2012). The well evidenced and publicized side-effect of ACT is liver necrosis in cases of acute overdose [e.g., ACT at 250 mg.kg, ~15 g for a 60 kg human (Prescott et al., 1971; Prescott, 1980; Raffa et al., 2014)], evidently not seen under appropriate acute and/or regular use (Skoglund et al., 1991; Dippel et al., 2003a). Although uncommon relative to ACT chronic use, liver necrosis has been reported when concomitant with other factors such as fasting/malnutrition, alcoholism and the use of cytochrome P450 enzyme inducing drugs (Vitols, 2003). Novel research has seen ACT used outside of its typical clinical parameters, including exercise performance domains (Mauger et al., 2010, 2014; Foster et al., 2014) and to induce mild hypothermia within afebrile humans (Foster et al., 2016, 2017). ACT use whilst safe in many scenarios (Ong et al., 2007; Graham et al., 2013) does present risk in others (Hinz and Brune, 2012; Aminoshariae and Khan, 2015), across research and clinical agendas. This opinion piece will detail the variable acute dose and chronic dosages, and their pharmacological safety across established and emerging research fields. In particular, this article will present evidence to support the following opinions: ACT should not be advocated for use within a sporting context, given the present evidence is from tightly controlled laboratory studies which do not replicate the multifaceted physiological, biochemical, and environmental perturbations to homeostasis during sporting performance. ACT may provide a useful tool in determining fundamental biochemical thermoregulatory mechanisms in vivo in humans, when appropriate experimental controls and designs are employed.