Dextropropoxyphene interaction

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. 

An alleged adverse interaction between dextropropoxyphene and orphenadrine, which is said to cause mental confusion, anxiety, and tremors, seems to be very rare, if indeed it ever occurs. 

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. 

Carbamazepine serum levels can be raised by dextropropoxyphene. Toxicity may develop unless suitable dosage reductions are made. Oxcarbazepine appears not to interact with dextropro-pox3q hene. 

The interaction between carbamazepine and dextropropoxyphene is very well established and clinically important. If concurrent use is necessary reduce the dosage of carbamazepine appropriately to prevent the development of toxicity. In many cases it may be simpler to use a non-interacting analgesic, although the occasional single dose of dextropropoxyphene probably does not matter. No special precautions seem necessary with oxcarbazepine. 

Although no interaction generaiiy appears to occur between phenyiioin and dextropropoxyphene, a case report describes phenydoin toxicity in a patient given both drugs. 

Apart from these two isolated reports, there seems to be no other clinical evidence of adverse interactions between MAOIs and dextropropoxyphene. For reports of the serotonin syndrome seen with pethidine (meperidine) and MAOIs, see MAOIs or RIMAs + Opioids Pethidine (Meperidine) , p.ll40. 

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