C H A P T E R 1 6
Anti-inflammatory, antiarthritis and related agents
251
(aspirin may mask Reye’s syndrome in children); and for
the relief of musculoskeletal pain associated with arth
ritis (see Table 16.2).
Pharmacokinetics
Paracetamol is rapidly absorbed from the GI tract,
reaching peak levels in 30 minutes to 2 hours. It is
extensively metabolised in the liver and excreted in the
urine, with a half-life of about 2 hours. Caution should
be used in people with hepatic or renal impairment,
which could interfere with metabolism and excretion of
the drug, leading to toxic levels. Paracetamol crosses the
placenta and enters breast milk; it should be used cau-
tiously during pregnancy or breastfeeding because of the
potential adverse effects on the fetus or neonate.
Contraindications and cautions
Paracetamol is contraindicated in the presence of allergy
to paracetamol. It should be used cautiously in preg-
nancy or breastfeeding and in hepatic dysfunction or
chronic alcoholism
because of associated toxic effects
on the liver.
Adverse effects
Adverse effects associated with paracetamol use include
headache, haemolytic anaemia, renal dysfunction, skin
rash and fever. Hepatotoxicity is a potentially fatal
adverse effect that is usually associated with chronic
use and overdose, and is related to direct toxic effects
on the liver. The dose that could prove toxic varies
with the age of the person, other drugs that the person
might be taking and the underlying hepatic function
of that person. When overdose occurs, acetylcysteine
can be used as an antidote. Life support measures may
also be necessary.
Clinically important drug–drug interactions
There is an increased risk of bleeding with oral anti
coagulants because of effects on the liver; of toxicity
with chronic ethanol ingestion because of toxic effects
on the liver; and of hepatotoxicity with barbiturates,
carbamazepine, hydantoins, rifampicin or sulfinpyra-
zone. These combinations should be avoided, but if they
must be used, appropriate dose adjustment should be
made and the person should be monitored closely.
Prototype summary: Paracetamol
Indications:
Treatment of mild to moderate pain,
fever, or signs and symptoms of the common
cold or flu; musculoskeletal pain associated with
arthritis and rheumatic disorders.
Actions:
Acts directly on the hypothalamus to cause
vasodilation and sweating, which will reduce
fever; mechanism of action as an analgesic is not
understood.
Pharmacokinetics:
Route Onset
Peak
Duration
Oral
Varies
0.5–2 hours 3–6 hours
T
1/2
:
1 to 3 hours; metabolised in the liver and
excreted in the urine.
Adverse effects:
Rash, fever, chest pain, liver toxicity
and failure, bone marrow suppression.
In December 2009 the Medicines Adverse Reactions
Committee (MARC) reviewed the benefits and risk of
dextropropoxyphene-containing medicines.
1
The MARC
assessed the published literature; adverse reactions
reported in New Zealand (NZ) and internationally;
NZ Poisons Centre data, the results of a Paradex
utilisation study conducted in New Zealand in 2007.
The MARC also considered reviews conducted by other
medicine regulators.
After analysis and discussion of the available data the
MARC concluded there is evidence that:
• These medicines are no more effective than maximum
recommended doses of paracetamol alone.
• These medicines have the potential to cause
more adverse reactions than paracetamol used at
recommended doses.
• These medicines are more dangerous than other
simple analgesics in overdose, particularly when
combined with alcohol. Deaths have occurred in
association with dextropropoxyphene use in NZ.
• Deaths related to dextropropoxyphene overdose
have occurred within 1 hour of ingestion and before
medical intervention could be obtained.
Prescribing restrictions introduced in 2006 have
failed to ensure that these medicines were only used in
people for whom the benefits are likely to outweigh the
risks. Overall the risks of these medicines exceed their
benefits. Therefore, in the interests of public safety, the
MARC has recommended that Capadex and Paradex be
withdrawn from New Zealand.
1
%20review%20concludes%20risk-benefit%20balance%20
unfavourable.htm
Source: MEDSAFE – NZ Medicines and Medical Devices Safety
Authority (2010)
■■
BOX 16.6
Withdrawal of Paradex and
Capadex (in New Zealand)—
DEXTROPROPOXYPHENE AND
PARACETAMOL COMBINATION
