Editing Paracetamol (section)

==Interactions==

[[Prokinetic agent]]s such as [[metoclopramide]] accelerate gastric emptying, shorten time (t<sub>max</sub>) to paracetamol [[Cmax (pharmacology)|peak blood plasma concentration]] (C<sub>max</sub>), and increase C<sub>max</sub>. Medications slowing gastric emptying such as [[propantheline]] and [[morphine]] lengthen t<sub>max</sub> and decrease C<sub>max</sub>.<ref name="pmid4694406">{{cite journal |vauthors=Nimmo J, Heading RC, Tothill P, Prescott LF |title=Pharmacological modification of gastric emptying: effects of propantheline and metoclopromide on paracetamol absorption |journal=Br Med J |volume=1 |issue=5853 |pages=587–9 |date=March 1973 |pmid=4694406 |pmc= 1589913 |doi= 10.1136/bmj.1.5853.587}}</ref><ref name="pmid15662293">{{cite journal |vauthors=Toes MJ, Jones AL, Prescott L |title=Drug interactions with paracetamol |journal=Am J Ther |volume=12 |issue=1 |pages=56–66 |date=2005 |pmid=15662293 |doi=10.1097/00045391-200501000-00009 |s2cid=39595470}}</ref> The interaction with morphine may result in patients failing to achieve the therapeutic concentration of paracetamol; the clinical significance of interactions with metoclopramide and propantheline is unclear.<ref name="pmid15662293"/>

There have been suspicions that [[List of cytochrome P450 modulators|cytochrome inducers]] may enhance the toxic pathway of paracetamol metabolism to [[NAPQI]] (see [[Paracetamol#Pharmacokinetics]]). By and large, these suspicions have not been confirmed.<ref name="pmid15662293"/> Out of the inducers studied, the evidence of potentially increased liver toxicity in paracetamol overdose exists for [[phenobarbital]], [[primidone]], [[isoniazid]], and possibly [[St John's wort]].<ref name= "pmid27147854">{{cite journal |vauthors=Kalsi SS, Wood DM, Waring WS, Dargan PI |title=Does cytochrome P450 liver isoenzyme induction increase the risk of liver toxicity after paracetamol overdose? |journal=Open Access Emerg Med |volume=3 |issue= |pages=69–76 |date=2011 |pmid=27147854 |pmc=4753969 |doi=10.2147/OAEM.S24962 |doi-access=free }}</ref> On the other hand, the anti-tuberculosis drug [[isoniazid]] cuts the formation of NAPQI by 70%.<ref name="pmid15662293"/>

[[Ranitidine]] increased paracetamol [[Area under the curve (pharmacokinetics)|area under the curve]] (AUC) 1.6-fold. AUC increases are also observed with [[nizatidine]] and [[cisapride]]. The effect is explained by these drugs inhibiting [[glucuronidation]] of paracetamol.<ref name="pmid15662293"/>

Paracetamol raises plasma concentrations of [[ethinylestradiol]] by 22% by inhibiting its sulfation.<ref name="pmid15662293"/> Paracetamol increases [[Prothrombin time|INR]] during [[warfarin]] therapy and should be limited to no more than 2 g per week.<ref name="pmid23736105">{{cite journal |vauthors=Pinson GM, Beall JW, Kyle JA |title=A review of warfarin dosing with concurrent acetaminophen therapy |journal=J Pharm Pract |volume=26 |issue=5 |pages=518–21 |date=October 2013 |pmid=23736105 |doi=10.1177/0897190013488802 |s2cid=31588052}}</ref><ref name="pmid21923443">{{cite journal |vauthors=Hughes GJ, Patel PN, Saxena N |title=Effect of acetaminophen on international normalized ratio in patients receiving warfarin therapy |journal=Pharmacotherapy |volume=31 |issue=6 |pages=591–7 |date=June 2011 |pmid=21923443 |doi=10.1592/phco.31.6.591 |s2cid=28548170}}</ref><ref name="pmid21191575">{{cite journal |vauthors=Zhang Q, Bal-dit-Sollier C, Drouet L, Simoneau G, Alvarez JC, Pruvot S, Aubourg R, Berge N, Bergmann JF, Mouly S, Mahé I |title=Interaction between acetaminophen and warfarin in adults receiving long-term oral anticoagulants: a randomized controlled trial |journal=Eur J Clin Pharmacol |volume=67 |issue=3 |pages=309–14 |date=March 2011 |pmid=21191575 |doi=10.1007/s00228-010-0975-2 |s2cid=25988269}}</ref>