Breastfeeding and analgesia

 

List:

·        Main considerations

·        Main recommendations

·        CYP2D6

·        Opioid analgesics

·        Non-opioid analgesics

·        Anaesthetics and sedatives

 

Main considerations:

Drug properties

·     Relative infant dose (RID): % of the weight-adjusted maternal dose

o   Prefer <10%

·     Oral bioavailability (OBA): % of dose exempt from first pass metabolism

Administration

·     Dose

·     Duration

Child factors

Pharmacokinetics:

·     ↓Kidney/liver clearance if young, small, premature

·     Especially if repeat doses -> accumulation

·     Especially if exclusive breastfeeding

Pharmacodynamics:

·     ↑Sensitivity to sedation and resp depression if young, small, premature

·     Especially if big dose

Important PMAs:

·     Term: 46 weeks

·     Prem: 54-60 weeks (∝ degree of prematurity)

Maternal factors

Pharmacokinetics:

·     CYP450 phenotype

Pharmacodynamics:

·     Opioid tolerance

·     Additional narcotics

 

Main recommendations:

Anaesthetics

·     Breastfeeding ok as soon as the mother is properly awake

o  Low RID (relative infant dose) once awake

o  Low OBA (oral bioavailability)

Analgesics

·     Breastfeeding safe for some drugs but not others

o  Variable RID

o  Variable OBA

·     Opioids:

o  Fentanyl good (low RID and low OBA)

o  Morphine ok (low RID and moderate OBA)

o  CYP2D6 drugs bad: codeine, oxycodone, tramadol

o  If oxycodone: <30-40mg/day

o  Monitor baby for sedation

Discussion

Mother:

·     Benefits of medications

·     Pain relief is important

·     Pain relief promotes breast milk production

·     If not breastfeeding, must pump or else engorgement/mastitis/dry up

Baby:

·     Risk of medications

·     Signs of toxicity: especially drowsiness

Logistical support

·     Equipment for pumping

·     Private space to feed / pump

·     Place to store breast milk / formula

·     Room for partner to come and help

·     Support from lactation consultant in person or telehealth

 

CYP2D6:

Relevance

·     15% Oxycodone -> oxymorphone (14x analgesic efficacy)

·     10% Codeine -> morphine (10x analgesic efficacy)

·     Tramadol -> M1 (200x MOP affinity, 4x analgesic efficacy)

Problem

·     Highly variable activity

·     Non-inducible

Poor phenotype

·     30% Hong Kong Chinese

·     10% Caucasians

->↓Clearance

->↑Risk of toxicity

Ultra-rapid phenotype

·     30% North Africans, Ethiopians, Arabs

·     10% Greeks, Portuguese

·     1-3% other

-> ↑% Contribution of metabolite

-> ↑ Risk of toxicity

 

Opioid analgesics:

Morphine

·     RID 2-3%

·     Post-partum use not associated with neonatal adverse events

·     M6G oral bioav 10% in adults, unknown in children

·     Clearance is reduced in neonates

·     Limited studies of morphine PCA

Oxycodone

·     JCP: RID 2.5% (up to 10%)

·     AAGBI: RID >10%

·     Case reports of death

·     Retrospective analysis showed CNS depression in infants

·     Greater risk than other opioids

·     Beware >30-40mg/day

Fentanyl

·     RID 2-3%

·     OBA low

·     Short-term use safe. Lack of long-term data.

Codeine

·     UK MHRA: take in moderation and for a short duration

·     FDA: not safe

·     NPS: not safe. If taken, discard breast milk for 15 hours

Tramadol

·     Case reports of neonatal death

·     FDA: warns against use

·     UKDILAS: use with caution

 

Non-opioid analgesics:

Paracetamol

·     Safe

·     Dose that gets to baby is significantly less than therapeutic

NSAIDs

·     Aspirin: RID 10%. Risks: toxicity (if analgesic dose), Reye’s syndrome

·     Ibuprofen safe

·     Diclofenac safe

·     Naproxen safe

·     Celecoxib: safe

·     Parecoxib: safe

Ketamine

·     No data on transfer into breast milk

Clonidine

·     May reduce prolactin secretion

·     Minimally secreted into milk

·     Safe for the child

Local anaesthetics

·     Safe

Tapentadol

·     No data

·     Less opioid effect cf. oxycodone

·     No active metabolites cf. tramadol

·     CYP2D6 is a minor pathway cf. tramadol

 

Anaesthetics and sedatives:

Volatiles

·     Safe

Propofol

·     Safe

Ketamine

·     No data

Midazolam

·     Moderate first pass metabolism

Diazepam

·     Active metabolite with very long half life

·     Significant transfer into breast milk

Dexmedetomidine

·     No data

·     RID negligible

 

 

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