Home' Australian Pharmacist : Australian Pharmacist August 2015 Contents Australian Pharmacist August 2015 I ©Pharmaceutical Society of Australia Ltd.
CONTINUING PROFESSIONAL DEVELOPMENT
signs and symptoms of CNS depression,
the infant should also be assessed.
If opioid toxicity is suspected based on
clinical signs and symptoms, the mother
and infant should have morphine level
19 For example,
breastfed neonates would typically
have a maximum plasma morphine
concentration of 2.2 ng/mL following
maternal administration of 60 mg
codeine daily. This maximal level is
likely to be exceeded in individuals with
ultra-rapid CYP2D6 metabolism.
We have primarily considered
breastfed infants in this article but
pharmacogenomics is also relevant
when considering vulnerability
to harmful effects before birth,
as reviewed elsewhere, and for children
prescribed codeine for minor or
intermediate surgical procedures such
as tonsillectomy for sleep apnoea,
which can make children acutely
sensitive to the respiratory depressant
effects of codeine.36,37
While CYP2D6 genotype testing has
not been readily accessible in the past,
it is available in Australia through some
accredited pathology laboratories
and, as discussed in a recent article
(see Australian Pharmacist, May 2015),
is also being piloted in a small selection
of Australian pharmacies.
Campbell et al39 propose that codeine
dose recommendations may need to
be adjusted depending on a patient’s
CYP2D6 metabolism type. The Clinical
Consortium (CPIC) guidelines suggest
that, for poor metabolisers, codeine
should be avoided due to lack of efficacy
and replaced by alternative analgesics
not affected by CYP2D6 genotype.
For intermediate metabolisers failing to
respond to standard doses, alternative
analgesics including non-opioids or
morphine could be considered.2,8 Standard
codeine doses based on age and weight
may be used for extensive metabolisers.
For ultra-rapid metabolisers, where
long-term or chronic use may be
potentially dangerous, alternative
analgesics not affected by the individual’s
genetic variants are recommended to
prevent potential toxicity.
Further research is needed to assess
the clinical utility, potential error rates2
and cost effectiveness of widespread
CYP2D6 genotype testing post-partum.
While discrimination by health insurers
or others is unlikely in this context, how
genotyping test costs will be covered
remains to be determined.
Following discharge from hospital
post-partum, pharmacists need to
remain vigilant when breastfeeding
mothers present with prescriptions
and over-the-counter (OTC) requests
for codeine. Providing individualised
counselling regarding the potential
risks versus the benefits of codeine
use during breastfeeding is essential.
Patient education is critical as a
preventive strategy to avoid neonatal
adverse outcomes when codeine is
prescribed to lactating women.
Case scenario continued
Morphine level testing of the mother and
infant were performed, which indicated
higher than normal levels. Hospital staff
notified the woman’s general practitioner
(GP) and obstetrician who ceased
codeine and commenced diclofenac
suppositories. The infant’s condition
improved over the next couple of days.
Prior to discharge the mother was
counselled that one possible reason
for her infant’s response to codeine
could be due to the way in which her
body metabolises codeine. She was
also alerted to the possibility that her
body may respond inappropriately to
certain other drugs and to seek medical
advice prior to taking any medicines in
Useful information sources
• Mothersafe – 02 9382 6539 (Sydney
metropolitan area), 1800 647 848
• Therapeutic Guidelines – Drugs and
their categories in pregnancy and
breastfeeding. At: www.tg.org.au
TAKE HOME MESSAGE
• Expanding knowledge of
may play an increasingly significant
role in drug selection.
• In the future, pharmacogenomics
may facilitate the development of
personalised medicine to prevent
potential adverse outcomes for both
the mother and infant.
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