Dextropropoxyphene /Paracetamol

Pharmaceuticals) Ethinyl oestradiol, paracetamol, aspirin, dextropropoxyphene, clofibrate and oxytetracycline Aire river (UK), Lambro river (Italy) and Rur river (Germany) Surface water - Product consumption - Worst-case influent - Excreted post-metabolism - WWTP removal - River water die-away [50]... 

Something of a stereotype now follows, but in a good cause to illustrate some practical points in management of minor opioid misuse. I would contend that there is a syndrome of a classic case of someone who becomes dependent on paracetamol and codeine combinations, or dihydrocodeine, dextropropoxyphene or something similar, with the following features ... 

Analgesic efficacy and clinical use Dextropropoxyphene (Grover, 1988) is a moderately potent opioid analgesic often combined with paracetamol or acetylsalicylic acid or other NSAIDs (Collins et al., 2000). As the hydrochloride or napsylate it is used orally for the treatment of mild, moderate, or severe pain (Beaver, 1984). 

Collins, S.L., Edwards, J.E., Moore, R.A., McQuay, H.J. Single dose dextropropoxyphene, alone and with paracetamol (acetaminophen), for postoperative pain, Cochrane Database Syst. Rev. 2000, CD001440. 

Lloyd, R.S., Costello, F., Eves, M.J., James, I.G., Miller, A.J. The efficacy and tolerability of controlled-release dihydrocodeine tablets and combination dextropropoxyphene/paracetamol tablets in patients with severe osteoarthritis of the hips, Curr. Med. Res. Opin. 1992, 13, 37-48. 

Dextropropoxyphene Dextropropoxyphene, a drug of abuse, and any misuse or overdose of which causes intoxication if taken along with paracetamol or alcohol. The individual develops serious CNS depression leading to death.40-42 Adverse effects can be treated by gastric lavage and administration of activated charcoal and naloxone 43... 

The crucial facts to be determined are the identity, and then the level(s), of the chemical(s) in the blood and when they were taken. The poisoning due to the most dangerous chemical that is at the highest level in the blood can then be treated. For example, if someone has taken an overdose of the drug combination Distalgesic, which contains paracetamol and dextropropoxyphene, the immediate treatment would be for the latter drug which can rapidly cause death from depression of the respiratory system. 

Tablets containing paracetamol (325 mg) plus dextropropoxyphene (32.5 mg) (co-proxamol, Distal-gesic), in a dose of 1-2 tablets, provide an effective dose of both drugs and have been extremely...

Hypersensitivity pneumonitis has been associated with co-proxamol (paracetamol plus dextropropoxyphene) (5). 

Nerve deafness in a 44-year-old woman, dependent on co-proxamol (dextropropoxyphene plus paracetamol), has been reported (SEDA-17, 80). 

Four cases each of necrotizing anorectitis and proctitis have been reported after long-term (2-24 months) use of suppositories containing dextropropoxyphene and paracetamol (SEDA-10, 62). Perineal ulceration can also occur (7). 

A 43-year-old woman, who had taken antibiotics and analgesics, including dextropropoxyphene, for parotitis, developed generalized erythema with numerous pustules on the trunk followed by a pyrexia. Patch testing was positive with dextropropoxyphene only and negative with paracetamol, spiramycin, aspirin, and tenoxicam. 

Dextropropoxyphene is widely prescribed in combination with aspirin or paracetamol. It is particularly dangerous when taken in overdose (14). A mortality rate of 8% was described in a series of 222 self-harm patients (15). 

Fulton JD, McGonigal G. Steroid responsive haemolytic anaemia due to dextropropoxyphene paracetamol combination. J R Soc Med 1989 82(4) 228. 

Paracetamol plus dextropropoxyphene, the combination known as co-proxamol, is available as a prescription-only analgesic in many countries. Self-poisoning can be lethal, as respiratory depression can occur from an excessive dose of dextropropoxyphene. In England and Wales, co-proxamol alone accounts for 5% of all suicides, and overdose is more likely to result in death than overdose with paracetamol alone or tricyclic antidepressants (81). Furthermore, although it is often prescribed, it is no more effective than paracetamol for short-term relief of pain. It should not be prescribed without good... 

Dextropropoxyphene (Coproxamol - with paracetamol) Dipipanone (Diconal - with cyclizine)... 

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. 

Including 11 cases and 6 controls who reported taking a preparation of paracetamol in combination vmh an opioid, mostly codeine and oxycodone There are also cases reported with dextropropoxyphene/paracetamol. 

Cimetidine 1.2 g daily for 5 days had no effect on the pharmacokinetics of a single 120-mg dose of terfenadine in 12 healthy subjects. Another study in two groups of 6 healthy subjects confirmed that cimetidine 600 mg every 12 hours or ranitidine 150 mg every 12 hours had no effect on the pharmacokinetics of terfenadine 60 mg every 12 hours. No adverse ECG changes were seen. However, an isolated case report describes a 63-year-old woman who had 8 episodes of syncope (later identiiied as being due to torsade de pointes) and a convulsion 2 days after starting terfenadine 60 mg twice daily and cimetidine 400 mg twice daily. She was also taking chiorphenamine and co-proxamol (paracetamol (acetaminophen) and dextropropoxyphene (propoxyphene)). ... 

Distalgesic Dextropropoxyphene with paracetamol Lilly Analgesic... 

Death Co-proxamol, a combination of dextropropoxyphene and paracetamol, was gradually withdrawn from the UK market following a change in legislation in 2005. In a retrospective observational study of mortality data in Scotland over the period 2000-2006, the change in legislation was associated with a reduction in co-proxa-mol-related deaths, without a compensatory rise in mortality from other analgesics [49 ]. 

Tavassoli N, Lapeyre-Mestre M, Sommet A, Montastruc J-L. Reporting rate of adverse drug reactions to the French pharmacovigilance system with three step 2 analgesic drugs dextropropoxyphene, tramadol and codeine (in combination with paracetamol). Br J Clin Pharmacol 2009 68 (3) 422-6. 

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