2. Learning objectives
1. To understand the various issues and challenges arising from prescribing in
pregnancy and lactation
2. The physiological changes & pharmacokinetics in pregnancy
3. Implications of drugs in pregnancy i.e effectiveness, suitability, teratogenicity
4. Risk to mother vs fetus / neonate
5. Categorization of drug safety in pregnancy
6. Drugs and lactation
7. Understand the types of medications in labour and post partum
8. Gynae - commonly used drugs
3. Overview
1. Prescribing in pregnancy
a. General principle
b. Pharmacokinetics in pregnancy
c. Teratogenicity
d. Safe prescribing in common medical disorders / antibiotics use
e. Drugs used in labour / post-partum
2. Drugs and lactation
3. Gynaecological drugs
a. Hormone replacement therapy / alternative therapy
B. Contraception e.g COCP, Injectables
C. Drugs used in endometriosis/ PCOS / Infertility
D. Urinary incontinence
4. Prescribing in pregnant- General principles
When possible:
● Use medication only if absolutely indicated- any non pharmacological options
● Avoid initiating therapy during the first trimester.
● Select a medication with a proven track record in human pregnancy.
● Use a single-agent.
● Use the lowest effective dose.
● Discourage the use of over-the counter drugs that might interact with prescription
medications.
Modified from: Norwitz ER, Greenberg JA.Antibiotics in pregnancy: are they safe? Rev Obstet Gynecol. 2009 Summer;2(3):135-6. PMID: 19826569
5. 4 scenarios to think about drug use in pregnancy
1. A pregnant woman who has ingested a drug and is seeking information
2. A pregnant woman with a known medical disorder on a usually prescribed
drug - what is the safest yet most effective option
3. Pre-pregnancy advice - long term medical condition on treatment and worries
about teratogenic effects and seeks advice
4. A pregnant woman requiring treatment with for a medical condition arising in
pregnancy - what is safe to prescribe?
6. Pharmacokinetics in pregnancy
Pregnant women undergo several adaptations in many organ systems.
These changes affect : distribution, absorption, metabolism, and excretion of drugs
1. Increased maternal fat and total body water
2. Decreased plasma protein concentrations, especially albumin
3. Increased maternal blood volume, cardiac output, and blood flow to the kidneys
and uteroplacental unit - The maternal blood volume expansion occurs at a larger
proportion than the increase in red blood cell mass, which results in physiologic
anemia and hemodilution.
4. Decreased blood pressure.
Physiologic and pharmacokinetic changes in pregnancy Maged M. Costantine* Front Pharmacol. 2014; 5: 65
7.
8. Risk of using drugs in pregnancy
Most medicines cross the placenta
Taken into account the known harmful effects of medicines on the developing baby,
including the potential to cause:
● birth defects
● unwanted pharmacological effects around the time of birth, which may or may not
be reversible
● problems in later life
9. Categorization of drugs in pregnancy
While some medicines are genuinely teratogenic, and carry a category X, for most medicines the
risk of developing birth defects is also dependent on:
● Systemic exposure of the mother
● Exposure of the fetus, which may be affected by:
○ Dose
○ Route of administration
○ Dosing regimen
Thus, a low dose, limited topical application of a medicine for a particular indication may have a
less restrictive category (such as A) compared to a more restrictive category for the same
medicine given long-term or at higher doses orally for a different indication.
10.
11. Categorization of drugs in pregnancy-Australia
Category A
Drugs which have been taken by a large number of pregnant women and women of
childbearing age without any proven increase in the frequency of malformations or
other direct or indirect harmful effects on the fetus having been observed.
12. Categorization of drugs in pregnancy-Australia
Category B1
Drugs which have been taken by only a limited number of pregnant women and women of childbearing age, without an increase in the
frequency of malformation or other direct or indirect harmful effects on the human fetus having been observed. Studies in animals have
not shown evidence of an increased occurrence of fetal damage.
Category B2
Drugs which have been taken by only a limited number of pregnant women and women of childbearing age, without an increase in the
frequency of malformation or other direct or indirect harmful effects on the human fetus having been observed. Studies in animals are
inadequate or may be lacking, but available data show no evidence of an increased occurrence of fetal damage.
Category B3
Drugs which have been taken by only a limited number of pregnant women and women of childbearing age, without an increase in the
frequency of malformation or other direct or indirect harmful effects on the human fetus having been observed.Studies in animals have
shown evidence of an increased occurrence of fetal damage, the significance of which is considered uncertain in humans.
13. Categorization of drugs in pregnancy-Australia
Category C
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. Accompanying texts should be consulted for further
details.
Category D
Drugs which have caused, are suspected to have caused or may be expected to cause, an increased incidence of human fetal
malformations or irreversible damage. These drugs may also have adverse pharmacological effects. Accompanying texts should be
consulted for further details.
Category X
Drugs which have such a high risk of causing permanent damage to the fetus that they should not be used in pregnancy or when there
is a possibility of pregnancy.
14. Teratogenicity-drugs
Most drugs cross the placenta freely BUT only a handful have been shown to be
harmful with some defects being relatively minor.
Risk depends on fetal age at time of exposure, drug potency and dosage
Reversible vs irreversible e.g anti-depressants vs Thalidomide
Known teratogenic agents ( category X ):
Isoretinoin, Folics acid antagonists e.g Methotrexate, Warfarin, Anti-epileptics,
tetracycline etc
15. Safe prescribing - common medical disorders
Common medical disorders in pregnancy - often pre-exisiting:
1. Cardiac diseases
2. Endocrine disorders e.g NIDDM, Hyperthyroidism
3. Pre-existing Hypertension
4. Autoimmune disorders e.g SLE +/- multi-organ involvement
5. Neurological disorders e.g Epilepsy, Migraine
6. Asthma in pregnancy
7. Infections in pregnancy
https://jfmo.cchs.ua.edu/files/2013/09/Drugs_Pregnancy.pdf
16. Drugs in labour & post-partum care
1. Analgesics e.g pethidine, epidural agents, entonox, tramadol
2. Oxytoxics e.g oxytocin / pitocin, ergometrine, Prostaglandins
3. Anti-convulsants e.g Magnesium sulfate, diazepam
4. Anti-coagulant e.g IV heparin
5. Anti-retroviral ( AZT )
6. Antibiotics
Various scenarios:
1. Induction of labour in a case of GDM at 40 weeks
2. Management of eclampsia in labour
3. Primip in labour with incoordinate contractions requiring augmentation
4. Primary PPH in a G6P6 secondary to uterine atony with chronic hypertension
17. Drugs in labour & postpartum care
Be aware of :
Indications
Mechanism of action
Dosage
Side effects
Contraindication ( absolute / relative )
Drug interactions
18. PPH - Uterotonics
Uterotonics are routinely used to prevent and treat postpartum haemorrhage.
● Synthetic oxytocin (Syntocinon) is used in the prevention and treatment of PPH. Oxytocin has a direct relaxant
effect on the vascular smooth muscle and rapid intravenous bolus injections have been associated with
profound hypotension, particularly in the presence of hypovolaemia. As it is structurally similar to vasopressin,
its antidiuretic effects can lead to water intoxication and hyponatraemia. The RCOG recommends that 10iu
oxytocin is administered intramuscularly at vaginal birth and as a 5 iu oxytocin bolus by slow intravenous
injection at caesarean section. For treatment of atony it is normally given IV at a rate of 10iu per hour (40iu in
500mls crystalloid at a rate of 125mls/hr).
● Ergometrine is an α-adrenoceptor and dopamine receptor agonist which causes strong sustained uterine
contractions and is effective in treating obstetric haemorrhage. It also causes vasoconstriction resulting in
transient hypertension and is contraindicated in women with hypertension and severe cardiac disease. Other
side effects include nausea and vomiting and concomitant administration of an anti-emetic should be
considered. In prevention of PPH it is given in combination with oxytocin as IM Syntometrine (oxytocin 5 units,
ergometrine 500 micrograms). For treatment of PPH, it is normally given as a dose of 500 micrograms by slow
intravenous or intramuscular injection.
19. PPH - Uterotonics
● Carboprost (Haemabate, PGF2α) is a synthetic prostaglandin and can be used when
ergometrine is contraindicated or ineffective. Its adverse effects include
bronchospasm, vasodilatation, hypertension and increased risk of infection. It should
be avoided in cardiac and pulmonary disease.The administered dose is 250
micrograms, repeated if required at 15 minute intervals to a maximum dosage of 2
mg.
● Misoprostol (Cytotec, PGE1) is a synthetic prostaglandin which is cheap, stable and
can be used in under-resourced countries where other, more expensive, options may
be scarce. Its side-effects include gastrointestinal disturbance, dizziness, headache and
fever. It can be administered sublingually, orally or rectally as an 800 microgram dose.
Royal College of Obstetricians and Gynaecologists. Postpartum haemorrhage, Prevention and management.
Green-top Guideline 52. London: RCOG; 2016.
20. Drugs & Lactation
Most drugs cross into breast milk through passive diffusion and are safe in
breastfeeding BUT best to avoid unnecessary medication including
complementary and alternative medicines
DRUGS ABSOLUTELY CONTRAINDICATED:
Antineoplastics, Iodide,
Click to read further:
https://www.racgp.org.au/download/documents/AFP/2011/September/201109amir
.pdf
21. Drugs & Lactation
Drugs and Lactation Database (LactMed) - A peer-reviewed and fully referenced
database of drugs to which breastfeeding mothers may be exposed. Among the
data included are maternal and infant levels of drugs, possible effects on
breastfed infants and on lactation, and alternate drugs to consider.
https://www.nlm.nih.gov/toxnet/Accessing_LactMed_Content_from_NCBI_Booksh
elf.pdf
WHO - drugs and breastfeeding :
https://apps.who.int/iris/bitstream/handle/10665/62435/55732.pdf;jsessionid=13D0
24575E51C3DCFF21FE39037CDFD8?sequence=1
25. Gynaecological drugs
2. Contraception
https://www.fsrh.org/ukmec/
3. Drugs used in endometriosis / PCOS / infertility
https://www.jeanhailes.org.au/health-professionals/tools
4. Drugs used in Urinary incontinence
https://www.racgp.org.au/afp/2012/november/overactive-bladder-syndrome/
26. What to expect at our session?
1. Scenario discussions on Pre eclampsia, eclampsia, VTE post-partum, PPH
2. Clinical scenarios approached using MCQ’s on PPROM/ Chorio / GBS
3. Kahoot quiz on contraception & HRT
So, pre- read around the drugs used in these commonly seen conditions.
Click on the links in this powerpoint to help guide your further reading.
When checking up a drug, use a good formulary e.g MIMS, BNF.APF etc
In Malaysia - MIMS is the gold-standard:
https://specialty.mims.com/obstetrics-gynaecology/disease
27. Resources
1. https://www.tga.gov.au/australian-categorisation-system-prescribing-
medicines-pregnancy ( Drug categorization )
2. http://www.perinatology.com/Reference/Prescription%20Drugs%20of%20Cho
ice%20During%20Pregnancy.htm
3. https://www.nhstaysideadtc.scot.nhs.uk/TAPG%20html/Specialist%20Lists/P
DF/ObsandGynae.pdf ( O&G Formulary list - Scotland )
4. http://archives.who.int/eml/wmf/2004/English/Drugs%20used%20in%20obstet
rics.pdf ( WHO drugs in obs )
5. http://archives.who.int/eml/wmf/2004/English/Drugs%20used%20in%20obstet
rics.pdf ( Antimicrobial use )
