Paracetamol Coumarins

Gadisseur AP, Van Der Meer FJ, Rosendaal FR. Sustained intake of paracetamol (acetaminophen) during oral anticoagulant therapy with coumarins does not cause chnicaUy important INR changes a randomized double-blind clinical trial. J Thromb Haemost 2003 1(4) 714-17. 

In an early, double-blind, placebo-controlled study of the interaction between coumarin anticoagulants and paracetamol, there was a statistically significant lengthening of the prothrombin time (124). The effect, although statistically significant, was very small and was considered to be clinically unimportant. 

Boeijinga JK, Boerstra EE, Ris P, et al. De invloed van paracetamol op antistollingsbehandeling met coumarine-derivaten. Pharm Weekbl 1983 118 209. 

It is imperative that patients taking bulk laxatives be advised to maintain fluid intake because of the risk of physical obstruction of the intestine or oesophagus by what is termed a phytobezoar. It is also noteworthy that the absorption of other drugs taken at the same time as bulk laxatives can be delayed. This particularly affects coumarin anticoagulants, digoxin, antibiotics, paracetamol... 

In one study, dextropropoxyphene did not alter the prothrombin time in patients taking unspecified coumarins. There are isolated cases of patients on warfarin who have shown a marked increase in prothrombin times and/or bleeding when given co-proxamol (dextropropoxyphene with paracetamol). 

Not understood. The effect dextropropoxyphene has on the metabolism of the warfarin enantiomers does not appear to have been studied. Dextropropoxyphene does not interact with other cytochrome P450 isoenzyme CYP2C9 substrates such as tolbutamide , (p.486), although it does interact with the CYP3A4 substrate carbamazepine , (p.527). There is also the possibility that the paracetamol component had some part to play (see also Coumarins + Paracetamol (Acetaminophen) , p.438). Alternatively, these eases may just represent idiosyncratic reactions. 

An equal number of randomised studies have found a modest increase in the anticoagulant effect (e.g. an increase in HSR of 1) of coumarins as have reported no effect. One retrospective cohort study reported that concurrent use tends to increase the incidence of upper gastrointestinal bleeding, but other cohort studies found no evidence of a change in anticoagulant effect. There are isolated case reports of an increase in anticoagulant effects in patients taking warfarin or acenocoumarol and paracetamol... 

There are only 5 published case reports of a possible interaction between paracetamol without opioids and a coumarin (warfarin or acenocoumarol), which are summarised in Table 12.5 , (p.439). In addition, there are two reports of a possible interaction with paracetamol combined with codeine or dihydrocodeine listed in Table 12.5 , (p.439), and 7 others with paracetamol combined with dextropropoxyphene (propoxyphene) , (p.436). Note that this incidence is very rare, given the widespread use of paracetamol, and the fact that it is generally considered safe for use with warfarin. 

Table 12.5 Summary of tbe evidence for and against an interaction between paracetamol (acetaminophen) and coumarins...

Study type (yeor) Group Coumarin Paracetamol Outcome Refs... 

Study type (year) Group Coumarin Paracetamol Outcome Re ... 

Boeijinga J, Boerstra EE, Ris P, Breimer DD, Jeletich-Bastiaanse A. Interaction between paracetamol and coumarin anticoagulants. Lancet 19S2 1, 506. 

M. Oliva, R. A. Olsina, and A. N. Masi, Selective spectrofluorimetric method for paracetamol determination through coumarinic compound formation, Talanta, vol. 66, no. 1, pp. 229-235, 2005. 

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