Prothrombin time paracetamol

Most studies investigating paracetamol pharmacokinetics in patients with liver disease used single doses only. A 50% reduction in clearance and a corresponding increase in half-life have been seen in severe acute hepatitis, the longest half-life being seen in patients with a raised prothrombin time (PT). It may therefore be prudent to extend the dose interval in these patients. Cirrhotic patients with a low albumin and a raised PT were also noted to have a prolonged paracetamol half-life, although no accumulation or hepatotoxicity was observed when normal therapeutic doses were administered to these patients for up to five days. In contrast, cirrhotic patients with normal albumin and PT demonstrated... 

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. 

Williams R. Serial prothrombin time as prognostic indicator in paracetamol induced fulminant hepatic failure. BMJ 1990 301 964-8. 

A 21 -year-old woman who had heen taking isoniazid 300 mg for 6 months took 3.25 g of paracetamol for abdominal cramping. Within about 6 hours she developed marked evidence of liver damage (prolonged prothrombin time, elevated ammonia, transaminases, hyperbilirubinaemia). ... 

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). 

This interaction has been reported in 5 other patients taking warfarin. " The prothrombin time of one of them rose from 28 to 44 seconds up to 80 seconds within 3 days of substituting paracetamol with two tablets of co-proxamol four times a day. Another developed a prothrombin time of more than 50 seconds after taking 30 tablets of Darvocet-N 100 (dextropropoxyphene 100 mg, paracetamol 650 mg) and possibly an unknown amount of ibuprofen over a 3-day period. Increased warfarin effects leading to severe retroperitoneal haemorrhage have also been briefly reported in a patient taking co-proxamol. ... 

Case report (1991) 66-year-old Vy rfarin Paracetamol/codeine about 1.6 g daily of paracetamol over 10 days Increase in prothrombin time from range of 15 to 19 up to 96 seconds. Haematuria and gingival bleeding 19... 

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