Abstract
The enhancement of therapeutic efficacy of drugs by their combinations is common in medicine. Fixed-dose combinations of some antidiabetics, antihypertensives, antimicrobials are now common.
Nevertheless, a general scepticism to usefullness of oral analgesic combinations still prevails, even though a higher analgesic efficacy in some of them has been well established under rigorous conditions (by isobolographic analyses, meta-analyses of randomized controlled trials). The aim of the present paper is to review evidence of increased analgesic efficacy in combinations of paracetamol (acetaminophen) with other drugs.
The increased analgesic efficacy was well proven in combinations of paracetamol with opioid analgesics or with nonsteroidal antiinflammatory drugs or with metamizole (dipyrone). A supraaditivity (synergy) was found in these combinations with isobolographic analysis.
Drugs interacting in all these combinations act by diffferent mechanisms. Also several meta-analyses of numerous randomized controlled trials have brought evidence for increased analgesic efficacy in combinations of paracetamol with opioid analgesics or with nonsteroidal antiinflammatory drugs.
There are also the evidences, though less rigorous, for improving pain management with combinations of paracetamol with other drugs, such as caffeine, guaifenesin and pyrazolone analgesics. Thus, at present there are good evidences showing that some analgesic combinations given per os are better than their components alone in pain management.
A general refutation of analgesic combinations is not substantiated and reasonable.