Ibuprofen with codeine
Management of Pain and Fever in
Pregnancy
Neil Hotham
Aust Medicines Handbook
(formerly) Specialist Drug Information Pharmacist,
Women’s and Children’s Hospital, Adelaide
2012
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Analgesics used in pregnancy


NSAIDs
Australian Category C
NSAIDs (eg ibuprofen)
 decrease amniotic fluid, affect fetus, delay labour
 affect implantation and increase miscarriage
(Li D-K, BMJ 327:368 2003)
Medications used by 85% of pregnant women
Vitamins are the most common, then analgesics

Greater than 50% use analgesics during their
pregnancy

Henry A, Crowther C. Patterns of medication use during and prior to pregnancy:
the MAP study. Aust NZ J Obstet Gynaecol 2000;40:165-172.
COX 2 inhibitors (eg celecoxib)
 affect ovulation
(Norman R, Fertility and Sterility :81;3, P 493-494,
Mar 2004 )
Glucosamine
 influences follicle stimulating hormone
(Thompson J, J Reprod and Develop:2006)
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NSAIDs and increased miscarriage
Update 2012


Gestational exposure to
any type or dosage of
non-aspirin NSAIDs
may increase the risk of
spontaneous abortion.

CMAJ, Oct 18, 2011,
183(15) 1713-20

NSAIDs and Birth Defects?
Amer J O & G 2012 206 228 e1-8
nested case–control design,
data from Quebec Pregnancy
Registry: 4705 women who had a
spontaneous abortion. For each
instance, randomly selected 10
controls etc

Results: Use of non-aspirin NSAIDs
during pregnancy was significantly
associated with the risk of
spontaneous abortion (odds ratio
[OR] 2.43, 95% confidence interval
[CI] 2.12–2.79).

Specifically, use of diclofenac (OR
3.09, 95% CI 1.96–4.87), naproxen
(OR 2.64, 95% CI 2.13–3.28),
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Outline

Treatments

Aust. Categorisation of Risk of Drugs

Using the Internet for information
Migraine: treatments/prophylaxis

Paracetamol and Codeine (Panadeine Forte®)

Mersyndol® (cat A)
codeine, paracetamol, doxylamine

pethidine, morphine
sumatriptan (cat B3) – more information required
ergotamine (cat C) – contraindicated

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Dose and Timing


Resources

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Prophylaxis: a choice of drugs
pizotifen, beta blockers, tricyclics, cyproheptadine
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Categorisation of Risk in Pregnancy
Australian Category C
http://www.tga.gov.au/hp/medicines-pregnancy-categorisation.htm

No increase in malformations

Pharmacological effects on newborn & fetus

Effects may be reversible
Advisory Committee on Prescription Medicines in 2010
replaced Aust Drug Evaluation Committee (ADEC) as
the subcommittee of the TGA tasked with categorisation

codeine (cat A), oxycodone, morphine (cat C)
–
–
“Rules of Thumb”
–
–
–
–
–
if prolonged high dose used near term:
respiratory depression, withdrawal symptoms in newborn
[ reminder: prochlorperazine (cat C)
– used at time of delivery, can cause dystonic reaction in newborn
– however, safely used in early pregnancy]
Category A
Category B1, B2, B3
Category C
Category D
Category X
Good
Animal
Newborn
Real concerns
Contraindicated
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Safety categories are only a guide
US FDA:
Different Categories of Safety in Pregnancy
USA: FDA Category C

Categories are allocated by the TGA when the
drug is registered but may not change with
experience

Clinical experience is also very important

Either studies have revealed adverse effects on the fetus
(teratogenic or embryocidal or other) and there are no controlled
studies in women, or studies in women and animals are not
available.
Australia: TGA Category C

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Drugs which, owing to their pharmacological effects, have
caused or may be suspected of causing, harmful effects on the
human fetus or neonate without causing malformations. These
effects may be reversible.
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Google: Treating pain in pregnancy
Google: Fever in pregnancy
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Google
Glucosamine pre pregnancy
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Known Causes of Birth Defects
Suspected Causes - multifactorial
Genetic
Maternal Conditions
Maternal Infections
Mechanical
Drugs, Chemicals, Radiation, Heat
Unknown
20 - 25%
4%
3%
1 - 2%
1%
65%
Miscarriage rate
15%
Background rate of congenital defects at birth
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3%
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Critical periods in human prenatal
development Moore/Persaud Before We Are Born. 2003
Dose and Time

Dose to fetus / infant

Time of exposure
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Paracetamol in pregnancy and risk of childhood
asthma.
“..non-causal explanations could not be ruled out…”
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Cases: Ductal closure with paracetamol
Pediatrics 128 6 e1618-e1621 Dec 1 2011
Clinical Epidemiology 31 Jan 2012.
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Breastfeeding : Analgesics safe to use

NSAIDs
ibuprofen
diclofenac
paracetamol
aspirin – avoid? - Reye’s Syndrome
WHO and Motherisk say: OK to use

opioids
codeine, morphine
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Codeine and Breastfeeding
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Google LactMed (part of Toxnet)
“Pharmacogenetics of morphine poisoning in a breastfed
neonate of a codeine-prescribed mother”
Rapid metabolizer of codeine to morphine
Koren et al Lancet Vol 368 p 704 August 19, 2006
www.motherisk.org
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Internet sites: Pregnancy and Lactation
Google: cdc pregnancy
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
Australian Medicines Handbook (on subscription)

OTIS: www.otispregnancy.org

Motherisk: www.motherisk.org

LACTMed : Google – part of Toxnet
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