Drug Treatment in Pregnancy and Lactation

Question 1

What are the associated risks with drugs in early pregnancy?

Answer 1

Major defects in various organ systems due to problem arising during organogenesis (17 - 70 days)

Question 2

How are drugs categorized based on danger to foetus?

Answer 2

Category A (taken by large number of pregnant women with no evidence of malformations)

Category B1 - 3

Category C

Category D

Category X

Question 3

Does a malformation in a foetus mean that a drug was responsible?

Answer 3

Not necessarily. Drugs only cause 2.5% of congenital abnormalities.

Question 4

Which drugs should be checked for in reproductive age women?

Answer 4

Do not prescribe class X drugs unless a pregnancy test is negative and effective contraception is being used.

Question 5

What are the guidelines to prescribing drugs to pregnant women?

Answer 5

Avoid guilt by association

Category X drugs should not be given unless not being pregnant is confirmed.

Know where to find information when it is needed

Balance risk of prescribing against risk of not prescribing.

Give the correct dose for the shortest time possible (some drug doses change during pregnancy, some drugs need to be monitored)

Question 6

What factors should be considered when balancing risk of prescribing a drug vs not prescribing a drug?

Answer 6

Take opportunity to discuss drugs in pregnancy prior to conception

Take opportunity to discuss the effects of non-prescribed drugs during pregnancy

Review drug prescriptions later in pregnancy (Is drug still needed? Is the correct dose being used? What are the risks to the neonate?

Question 7

Why do some drugs have pregnancy induced effects?

Answer 7

Increased body water and fat

Altered protein binding

Increased liver metabolism

Increased renal blood flow

Slower GI motility

Placental drug metabolism

Question 8

What analgesics can be prescribed in pregnancy?

Answer 8

Paractemol (Cat A)

Low-dose aspitin is OK but avoid high dose

Codeine is ok (cat C)

NSAIDs (cat C) but be careful [low risk from 27 - 32 weeks until delivery]

Question 9

What are the potential harms that can arise from NSAIDs in pregnancy?

Answer 9

1st trimester use is associated with early pregnancy loss.

Small risk of foetal harm from 27 - 32 weeks until delivery due to:

Premature closure of the ductus arteriosis and pulmonary hypertesion

Necrotising enterocolitis

Renal failure

Neonatal intracranial haemorrhage

Question 10

What are the potential harms that can arise from opioids in pregnancy?

Answer 10

Probably safe in early pregnancy but possible potential for long-term behavioural effects

Neonatal respiratory depression at birth

Neonatal withdrawal

Question 11

Are anti-emetics and anticonvulsants safe during pregnancy?

Answer 11

Most anti-emetics appear to be safe to use.

Gabapentin (cat B1) and pregabalin (cat B3) safety has not been established but are used

Clonidine is safe (cat B3)

Question 12

Are antibiotics safe to use during pregnancy?

Answer 12

All penicillins (cat A and some B), early generation cephalosporins (cat A or B), erythromycin (cat A and other macrolides cat B), clindamycin, and metronidazole are all safe to use.

Sulphonamides, nitrofurantoins, aminoglycosides, and anti-retrovirals have possible risk,

Question 13

Which cardiovascular drugs should be avoided?

Answer 13

ACE inhibitors cause malformations

Amiodarone (cat C but cause hypothyroidism and bradycardia)

Thiazide diuretics (cat C but cause neonatal electrolyte derangements)

Spironolactone (cat B3 due to feminisation of the male fetus)

Question 14

Which cardiovascular drugs are ok during pregnancy?

Answer 14

Methyldopa (cat A)

Beta-blockers (labetolol is safe; avoid atenolol)

Calcium channel blockers

Hydralazine (cat C)

Question 15

Are respiratory drugs ok during pregnancy?

Answer 15

Almost all are ok

Steroids should be avoided with high-doses

Question 16

Should diabetic drugs be used during pregnancy?

Answer 16

Sulphonylureas are cat C but not recommended

Rosiglitazone is not recommended

Metformin is category C but probably safe

Insulin is recommended.

Question 17

Can psychotropic drugs be used during pregnancy?

Answer 17

Risk from prescribing (foetal death or abnormality, growth retardation, neonatal toxicity, and developmental effects) and risks from not prescribing.(foetal abuse/neglect, adverse neonatal care, maternal distress, self-harm, use of harmful substitutes)

Typical anti-psychotics are probably ok, atypical anti-psychotics unclear but limited data suggests ok

Lithium best to avoid if possible (Foetal loss, birth defects)

SSRIs (cat C) appear safe, venlafaxine mianeserin MAOIs (cat B2), tricyclic antidepressants (cat C)

Question 18

Should anticonvulsants be prescribed for pregnant women?

Answer 18

Risk of abnormalities is 1.5 - 3x higher but not prescribing leads to seizures which lead to foetal death and childhood IQ reduction.

Aim is to drop dose as low as possible and to change drugs pre-conception if possible to prevent defects.

Question 19

Should anti-migraine drugs be used during pregnancy?

Answer 19

Should be avoided if possible and swapped for other drugs.

Sumatriptan and dihrdro-ergotamine - AVOID if possible

Atenolol and propanolol - foetal bradycardia, hypoglycaemia in late pregnancy so avoid if possible.

Question 20

Should steroids be used during pregnancy?

Answer 20

Prednisolone (cat C) use avoided with cleft palate but hard to stop so continue with lowest effective dose if possible.

Hydroxychloroquine (cat D): avoid if possible

Azathioprine (cat D) and cyclosporine (cat C): Usually continue for organ transplant.

Question 21

Which drugs should be completely avoided during pregnancy?

Answer 21

Retinoids and interferon

Statins (unlikely to be teratogenic but cholesterol is important to foetal development so currently avoided)

Tetracyclins (safe in early pregnancy but after 18 weeks dangerous so avoid throughout pregnancy)

Question 22

What factors influence diffusion of drugs into milk?

Answer 22

Passage into milk by diffusion: molecular weight, lipid solubility, ionisation, protein binding, milk composition, volume, and intake.

Passage into infant via gut absorption: Influenced by fat content and metabolic maturity of infant which varies with gestation.

Question 23

What is RID?

Answer 23

Relative Infant Dose (in breast milk)

RTD < 10% of a drug that is largely free of serious side effects is considered acceptable

Question 24

What is infant exposure?

Answer 24

Concentration of drug in infant plasma as a percentage of that in maternal plasma.

Question 25

What are the problems associated with studying effect of drug on baby? What are the solutions?

Answer 25

Often low levels of information:

Pharmaceutical companies aren’t interested

Finding large numbers of women willing to be studied is challenging

Often only animal research or very small case series describing breast milk concentrations

Drug pharmacokinetics in the infant is rarely available

Solutions are only partial solutions and involve:

Ignore pharmaceutical companies’ advice unless supported by evidence.

Use human breast milk data to estimate infant exposure

Consider potential drug toxicity and adverse event reports.

Question 26

Which drugs should be avoided in pregnany and breastfeeding women and what should they be replaced with?

Answer 26

ACE inhibitors + Angiotensin Receptor Blockers (ARBs)

Warfarin

Aminoglycosides and tetracyclines

NSAIDs

Sulfonylureas (use insulin)

Amiodarone (use digoxin)

Sodium valproate (use lamotrigine)

Phenytoin (use carbemazepine)

Codeine and morphine