Codeine

5-10% Caucasians are CYP2D6 poor-metabolisers, an hepatic enzyme necessary to convert codeine to morphine. These patients will not obtain equivalent analgesia using codeine-containing analgesics.[1-3] This bioactivation is markedly inhibited by antipsychotics (chlorpromazine, haloperidol, levomepromazine, and thioridazine), metoclopramide, and tricyclic antidepressants (amitriptyline etc.).[4] If hepatic metabolism is decreased in patients taking these drugs, or with liver disease, the analgesic action of codeine may also be compromised.[5]

Co-proxamol

Systematic reviews suggest that co-proxamol is no more effective as an analgesic than paracetamol.[6] However this view has been challenged on the basis that most studies are on single dose administration, and not for cancer-related pain.[7] Dextropropoxyphene has a longer elimination half-life than paracetamol and will therefore accumulate to higher blood levels during repeated dosing.[8] It also has other effects such as NMDA-receptor antagonism[9,10] which may be relevant to some cancer-related pain.