Medications and breastfeeding 4

Question 1

What are the benefits of breastfeeding for mothers?

Answer 1

• assist in losing weight
• reduces risk of T2DM, blood pressure and heart disease
• lowers rates of breast and ovarian cancer
• promote bonding, its convenient and free

Question 2

What are the benefits of breastfeeding for baby?

Answer 2

• all nutritional requirements for growth & development
• breast milk is easier to digest
• contains antibodies and immunoglobulins
• reduces risk of infectious diseases
• reduces risk of SIDS

Question 3

Is medication through breastmilk a danger?

Answer 3

• most medications transfer into milk
• however, the amount received by breastfed infant is LOW
• very few pose significant risk

Question 4

What are some adverse drug rxn reports in infants from medication in breast milk?

Answer 4

• opioids 25%
• antidepressants 15%
• multiple drug classes 11%
• anticonvulsants 11%
• iodine 6%
• antimicrobials 6%
• antipsychotics 4%
• cardiovascular drugs 4%
• sedatives 4%

Question 5

What are the aims in treating a breastfeesding mother?

Answer 5

• treat mother effectively
• minimse infant exposure
• minimally disrupt nursing
• withholding breastfeeding is not a RISK FREE option as mother and baby will be DEPRIVED of benefits

Question 6

How do drugs transfer into milk?

Answer 6

• mainly by passive diffusion
• in the early days following delivery there are large gaps inbetween the alveolar cells in the breast tissue and that allows the passage of immunoglobins and maternal proteins
• because theres a small amount of breast milk being transferred at this time its not a concern in terms of medication
• over the first

Question 7

How does the drug get into the milk and how is it cleared from the milk?

Answer 7

• once drug is in the system, it goes into the maternal plasma and then transferred across into the breast milk
• once its in the plasma, mum starts to clear it through renal and hepatic systems
• the drug that goes from the maternal plasma to the breast milk is a two way process
  
  • once the maternal plasma concentration is dropping through clearance, the drug comes back out of the breast milk
  • the drug doesnt just go into the breast milk and sit there, once mum is metabolising the drug, it does actually come out as a concentration gradient
• in the breast milk, the baby will ingest the drug and it will also clear the drug

Question 8

What are the 3 factors that effect infant exposure to the drug?

Answer 8

• drug properties
• maternal factors
• infant factors

Question 9

1. Drug properties

Answer 9

• protein binding
  
  • if a drug is highly bound (>90%)–> very difficult to diffuse into breastmilk
  • ibuprofen, warfarin
• molecular weight
  
  • if a drug is quite small (<200daltons)–> likely to cross readily into breastmilk
  • between 800-1000 daltons–> might cross
  • >1000daltons–> unlikely to cross
• lipid solubility
  
  • milk is more lipophilic and crosses more easily
  • drugs will cross more easily if they’re lipophilic
  • e.g. benzodiazepines
• volume of distribution
  
  • if VOD is high this means the drug is distibuted in high concentrations in remote parts of the body & may not stay in the blood for long therefore may not cross into the breastmilk
  • the higher the VOD, the less likely the drug is going to cross into the breast milk
• ionisation
  
  • pKa measures pH at which drug is equally ionic and non ionic
  • the more ionic a drug, the less it can transfer from milk to the plasma, so pKa>7.2 can be ion trapped in milk

Question 10

2. Maternal factors

Answer 10

• pharmacogenomics
  
  • influenced by metabolism differences
  • e.g. codeine- each person will have a different rate of metabolising codeine
  • ultrametabolisers of codeine-morphine; are at greater risk of concentrations of morphine being high in the breast milk
• maternal bioavailability
  
  • if a drug has low bioavailability, it has low plasma levels and therefore low concentrations in the breast milk
  • e.g. pyrantel, <10% absorbed through the gut
• maternal plasma concentration
  
  • drug in high plasma concentration, more likely to cross into breastmilk
  • via passive diffusion

Question 11

3. Infant factors

Answer 11

• amount of drug ingested by infant
  
  • dependent on milk concentration and daily milk intake
  • ~150mL/kg/day
  • if we know the milk conc we can determine how much of the drug the baby is exposed to
• oral bioavailability in infant
  
  • infants stomach acidity denatures many drugs
  • if small amt of drug which is not orallly bioavailable present in the breastmilk, baby wont absorb any
• age of infant
  
  • the younger the baby, the more likely there is for an adverse effect
  • pre term infants have immature metabolism
• use in infants
  
  • if used therapeutically unlikely to be toxic via breastmilk

Question 12

How is infant exposure interpreted?

Answer 12

Question 13

How do we assess the risk to the infant?

Answer 13

• infant
  
  • age- premature and newborn at greater risk
  • size- calculate dose
  • stability- unstable infants may increase risk
• drug
  
  • paediatric use
  • inherent toxicity
• dose based on milk transfer
  
  • what is the relative infant dose? (RID)
  • infant dose- compare this to therapeutic use
  • milk/ plasma ratio

Question 14

What is a safe dose?

Answer 14

• relative infant dose (RID) <10%
• lower dose if infant preterm or in first month of life
• less if drug is inherently toxic
• less where doses are uncontrolled- prn dosage
• check literature for reports of adverse effects

Question 15

How do we minimse drug exposure?

Answer 15

• withhold drug
• delay treatment
• consider alternative routes of administration
• use lowest appropriate dose
• select drug within class having lowest RID
• avoid nursing when milk concentraton is high
• withhold feeding temporarily for short time
• discontinue feeding

Question 16

What are examples of drugs that are contraindicated in breastfeeding?

Answer 16

• amiodarone
  
  • long half life, iodide containing, may affect infant thyroid function
• antineoplastics
  
  • leukopenia, bone marrow suppression
• gold salts
  
  • rash, hepatitis, haematological abnormalities
• lithium
  
  • breastfeeding only with rigorous monitoring
• radio pharmaceuticals
  
  • radiation exposure, often long acting e.g. iodide
• retinoids (oral)
  
  • wide distribution, anaemias, LFTs raised

Question 17

Is flucloxacillin okay to use in breastfeeding?

Answer 17

• pregnancy and breastfeeding medicines guideline says its safe to use as levels are low
• flucloxacillin is excreted in breast milk in trace amounts

Question 18

Which analgesics are OK to use in breastfeeding?

Answer 18

• paracetamol
• NSAIDs
  
  • avoid in 3rd trimester
• opioids OK short term, watch for opioid toxicity in long term
• TCAs for chronic pain
• gabapentin, pregabalin, limited date, probably ok to use, monitor baby

Question 19

Which analgesics are not OK to use in breastfeeding?

Answer 19

• aspirin
  
  • avoid if analgesic dose
  • low dose of 50-150mg/day ok to use
• codeine
• NSAIDs
  
  • avoid in third trimester

Question 20

What are galactagogues? Which drugs are used?

Answer 20

• they help to improve milk supply
• and are most effective if commenced ASAP after delivery
• domperidone & metocloperamide used because they block the dopamine receptors in pituitary
• metocloperamide crosses BBB due to potential to cause dystonic reactions
  
  • use >4weeks is associated with low mood
  • max of 30g, max 5 days
• domperidone
  
  • used today because it doesn’t cross the BBB
  • recommended dose of 10mg
  • higher cardiac risk in women with hx of ventricular arrhythmias with IV in elderly
  • interacts with azoles, macrolide antibiotics
  • take for 7 days for up to 6 weeks, beyond that likely to be unhelpful
  • taper dose at course completion

Question 21

What about herbal preparations?

Answer 21

• used by majority of the population
• contain pharmacologically active components
• use with caution
• do not exceed recommended dose
• use minimal amounts
• avoid large mixtures of unknown herbal

Question 22

What questions do we need to ask when assessing a medication for breastfeeding?

Answer 22

• age of baby?
• full term or premature?
• baby well?
• indication- new or previous?
• duration of treatment?
• medication history?
• what happens if drug not taken?
• has taken before or during pregnancy?
• any other drugs tried in the past?

Question 23

What is the evidence for sertraline for breastfeeding?

Answer 23

• eMIMS says not recommended
• AMH says otherwise
  
  • used in postnatal depression
• pregnancy & breastfeeding medicines guide
  
  • says its ok
  • low amounts excreted
  • only very small amounts of sertraline are found in breast milk
  • serious effects have not been found
    
    • but observe for restlessness, irritability, poor feeding
  • considered safe
  • benefits outweight risks