Warfarin Dextropropoxyphene

Cimetidine, erythromycin, and dextropropoxyphene had no effect on the pharmacokinetics of MHD. Results with warfarin show no evidence of interaction with either single or repeated doses of oxcarbazepine. 

Prolongation of the prothrombin time was observed in a patient concurrently taking warfarin and a compound analgesic containing dextropropoxyphene (21). 

Noninterfering acetaminophen, cefuroxime, cloxaciUin, dextropropoxyphene, digoxin, dox-ycycline, erythromycin, furosemide, metronidazole, netilmicin, penicillin G, prednisolone, salicylic acid, sulfamethoxazole, trimethoprim, warfarin Interfering norfloxacin... 

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. ... 

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. 

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. 

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