chapter
Paracetamol
Pages 2

Warn patients that the action of paracetamol may be delayed. This will not be the case when paracetamol is taken regularly

PARACETAMOL ANTIBIOTICS

PARACETAMOL ISONIAZID Risk of paracetamol toxicity at regular, therapeutic doses when co-administered with isoniazid

Uncertain; it seems that formation of toxic metabolites is ≠ in fast acetylators when isoniazid levels ↓ (i.e. at the end of a dosing period)

There have been cases of hepatic pathology; regular paracetamol should be avoided in patients taking isoniazid

PARACETAMOL RIFAMPICIN Rifampicin ↓ paracetamol levels Rifampicin ≠ glucuronidation of paracetamol

Warn patients that paracetamol may be less effective

PARACETAMOL ANTICANCER AND IMMUNOMODULATING DRUGS – BUSULFAN

Busulfan levels may be ≠ by coadministration of paracetamol

Uncertain; paracetamol probably inhibits metabolism of busulfan

Manufacturers recommend that paracetamol should be avoided for 3 days before administering parenteral busulfan

PARACETAMOL ANTICOAGULANTS – ORAL Possible ≠ anticoagulant effect when paracetamol is taken regularly (but not occasionally)

Uncertain; possibly due to competitive inhibition of CYPmediated metabolism of warfarin

Monitor INR closely for the first 1-2 weeks of starting or stopping regular paracetamol

PARACETAMOL ANTIDEPRESSANTS – TCAs TCAs may slow the onset of action of intermittent-dose paracetamol

Anticholinergic effects delay gastric emptying and absorption

Warn patients that the action of paracetamol may be delayed. This will not be the case when paracetamol is taken regularly

PARACETAMOL ANTIEMETICS Cyclizine may slow the onset of action of intermittent-dose paracetamol

Anticholinergic effects delay gastric emptying and absorption

Warn patients that the action of paracetamol may be delayed. This will not be the case when paracetamol is taken regularly

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Mechanism Precautions

action of intermittent-dose paracetamol

Anticholinergic effects delay gastric emptying and absorption

Warn patients that the action of paracetamol may be delayed. This will not be the case when paracetamol is taken regularly

PARACETAMOL ANTIMUSCARINICS Atropine, benzatropine, orphenadrine, procyclidine and trihexyphenidyl may slow the onset of action of intermittent-dose paracetamol

Anticholinergic effects delay gastric emptying and absorption

Warn patients that the action of paracetamol may be delayed. This will not be the case when paracetamol is taken regularly

PARACETAMOL ANTIPARKINSON’S DRUGS – DOPAMINERGICS

Amantadine, bromocriptine, levodopa, pergolide, pramipexole and selegiline may slow the onset of action of intermittent-dose paracetamol

Anticholinergic effects delay gastric emptying and absorption

Warn patients that the action of paracetamol may be delayed. This will not be the case when paracetamol is taken regularly

PARACETAMOL ANTIVIRALS Cases of hepatotoxicity have been reported when paracetamol was added to either didanosine or zidovudine

Uncertain; possible additive hepatotoxic effect

Monitor liver function regularly during co-administration

PARACETAMOL CNS STIMULANTS – MODAFINIL

May cause ↓ paracetamol levels if CYP1A2 is the predominant metabolic pathway and alternative metabolic pathways are either genetically deficient or affected

Modafinil is moderate inducer of CYP1A2 in a concentrationdependent manner

Be aware

PARACETAMOL LIPID-LOWERING DRUGS Colestyramine ↓ paracetamol by 60% when they are given together

Colestyramine binds paracetamol in the intestine

Give colestyramine and paracetamol at least 1 hour apart

PARACETAMOL MUSCLE RELAXANTS – SKELETAL

Baclofen may slow the onset of action of intermittent-dose paracetamol

Anticholinergic effects delay gastric emptying and absorption

Warn patients that the action of paracetamol may be delayed. This will not be the case when paracetamol is taken regularly