Drugs Affecting Breast Milk & Lactation

Objectives:
1. Recognize the main pharmacological characters that control the
passage of drugs from milk to baby.
2. Identify the adverse effects of major pharmacological categories on
babies.
3. Describe the best and safest medication to be given to breast feeding
women if she is suffered from different diseases as epilepsy,
infection, diabetes, heart failure, hypertension.
4. Know drugs that can inhibit lactation and should be avoided in
breastfeeding
5. Know drugs that may enhance lactation.

Color index:
Important Note Extra
 Lac󰉃󰈀󰉄󰈏on
✓ Breastfeeding is very important because breast milk is the healthiest
form of milk for babies.
✓ It provides the baby with immunoglobulins (IgA, IgM) that are
essential for protection against gastroenteritis.

Drugs and Lactation

❖ Drugs ingested by the mother diffuse or are transported from the maternal
plasma to the alveolar cells of the breast.
❖ The concentration of drugs achieved in breast milk is usually low (< 1 %).
❖ However, even small amounts of some drugs may be of significance for the
suckling child.
❖ Few drugs are absolutely contraindicated.
❖ Some drugs may increase or decrease milk yield.

Pharmacokinetics changes in pediatrics

❖ Premature babies have very limited capacity for metabolism and excretion.

So some drugs will get

destroyed Higher gastric pH
I’m a normally
born baby
Higher concentration of free drug
Bc newborns have low protein-binding
capacity → high free amounts

Higher percentage of body water

Water soluble drugs have higher
volume of distribution

Lower rate of metabolism (due to

immaturity of liver enzymes

Renal clearance is less efficient (reduced

renal blood flow → ↓ GFR
Physiologic Differences between Neonates and Adults of Pharmacokinetic Importance (Hilligoss 1980)

Neonate Adult

Gastric acid output (mEq/10 kg/hr) 0.15 ↓ 2

Gastric emptying time (min) 87 ↑ 65

Total body water (% of body weight) 78 ↑ 60

Adipose tissue (% of b.wt.) 12 ↓ 12-25

Serum albumin (gm/dL) 3.7 ↓ 4.5

Glomerular filtration rate (ml/min/m2) 11 ↓ 70

You don’t have to memorize it

Factors Controlling Passage of Drugs Into

Breast Milk

Factors related to drugs Maternal factors Infant factors

❖ Dose of drug ❖ Age

❖ Molecular weight
❖ Route of administration ❖ Body weight
❖ Lipid solubility
❖ Time of breastfeeding ❖ Health status
❖ Degree of ionization
❖ Health status
❖ Drug pH
❖ Maternal drug
❖ Protein binding
concentration
❖ Half life
❖ Oral bioavailability
 Fac󰉃󰈡󰈹s R󰇵󰈗a󰉄󰈩d 󰉃󰈢 Dru󰈇󰈼
1. Molecular Weight

Very small (<200

Large (>800 Daltons)
Daltons)

less likely to be transferred

Equilibrate rapidly between
to breast milk than low
plasma and breast milk via
molecular weight.
the aqueous channels
↠ E.g. Insulin (>6,000
surrounding alveoli
daltons).
↠ E.g. alcohol
Heparin (40,000
+ Lithium
daltons)

❖ Monoclonal antibodies, pass very poorly into milk after the first
1st week postpartum.
❖ The epithelium of the breast alveolar cells is most permeable to
drugs during the 1st week postpartum, so drug transfer to
milk may be greater during the 1st week of an infant's life.

2. Lipid Solubility of the Drug

❖ Lipid soluble drugs pass more freely into the breast milk than water
soluble drugs.

3. Degree of Ionization

❖ Ionized form of drugs are less likely to be transferred into breast

milk.
❖ e.g., heparins pass poorly into breast milk
4. pH of the Drug

❖ pH of milk is slightly more acidic than maternal blood.

X Weak basic drugs tend to concentrate in breast milk and become
trapped secondary to ionization.
✓ Weak acidic drugs don't enter the milk to a significant extent and
tend to be concentrated in plasma. Remember the renal block? Imagine milk same as urine

Maternal Blood
Milk
Circulation
Plasma pH is 7.4 Plasma pH is 7.2
(more acidic)
Excreted into a high concentration

Ionized alkaline drug will

Alkaline drug
be captured

Trapped in the mother’s circulation

non-Ionized acidic drug

Acidic drug will diffuse back

‫ﻟﻣﺎ ﯾﻼﻗﻲ اﻟدواء ﻧﻔس وﺳطﮫ راح ﯾﺻﯾر ﻟﮫ اﻋﺎدة اﻣﺗﺻﺎص )ﻓﻲ ﺣﺎﻟﺗﻧﺎ اذا ﻛﺎن اﻟدواء ﺣﻣﺿﻲ واﻟوﺳط اﻟﻠﻲ راﯾﺢ ﻟﮫ ﺣﻣﺿﻲ ﻛذﻟك )اﻟﺣﻠﯾب( ﻓراح‬
‫ ھﻧﺎ ﺑﯾﺗﻼﻗﻰ اﻟﻣﺗﺿﺎدان وﺑﯾﺣﺻل ﺑﯾﻧﮭم ﻣﺿﺎرﺑﺔ وھم ﻣﺗﺷﺎﺑﻛﯾن‬،‫ ﻟﻛن اذا اﻟدواء ﻗﺎﻋدي واﻟوﺳط اﻟﻠﻲ راﯾﺢ ﻟﮫ ﺣﻣﺿﻲ‬،‫ﯾﺻﯾر ﻟﻠدواء اﻋﺎدة اﻣﺗﺻﺎص‬
‫ﻣﻊ ﺑﻌض ﻟﻣﺎ ﯾطﻠﻌون ﻣن اﻟﺟﺳم‬
From team 435

5. Plasma Protein Binding

❖ Drugs circulate in maternal circulation in unbound (free) or bound

forms to albumin.
❖ ONLY unbound form gets into maternal milk.
❖ Definition of good protein binding > 90% e.g. warfarin

Important note: warfarin can cross placental blood barrier but CANNOT cross to breast
milk, so it's not safe during pregnancy but can be used during breastfeeding
6. Half Life Drugs will be excreted before feeding

❖ Avoid the use of drugs with long half lives.

❖ short half life (t ½) are preferable.
❖ Oxazepam vs diazepam (oxazepam has short duration of action so, it
has less exposure to the baby, while diazepam has long duration of
action. So oxazepam good, diazepam not good:) )
In pregnancy imagine the fetus as another organ so if we have
high Vd it will definitely go to it, so low Vd is preferable in
pregnancy, but in case of breastfeeding if it’s low it means it’s
7. Volume of Distribution concentrated in blood thus transports to milk and that is why
high Vd is preferable in pregnancy

❖ Transfer of drugs from maternal blood to milk is low with drugs that
have large volume of distribution (Vd).
‫ﻷن اﻻم ﻟﻣﺎ ﺗﺎﺧذ دواء ﻟﮫ ﻓوﻟﯾوم دﺳﺗرﺑﯾوﺷن ﻋﺎﻟﻲ ﻓﺎﻟدواء راح ﯾﺗوزع ﻓﻲ ﻛل اﻻﻧﺳﺟﺔ وﯾﻘل اﻟﺗرﻛﯾز ﺑﺎﻟدم وﻣﺎﯾﺻﯾر ﻓﻲ اﻟﺣﻠﯾب‬
‫ ﻟﻛن ﻟو ﻛﺎن ﻗﻠﯾل ﻣﺎراح ﯾﺗوزع ﻓﻲ اﻻﻧﺳﺟﺔ وﯾﺗرﻛز ﺑﺎﻟدم ﻓﯾوﺻل اﻟﺣﻠﯾب اﻛﻣﯾﺔ اﻛﺑر‬.‫اﻻ ﻛﻣﯾﺔ ﻗﻠﯾﻠﺔ‬.

Factors Related to Neonates

Age & Health

status The amount of a drug to which the baby is
exposed as a result of breastfeeding
depends on:
Body weight ○ The amount of milk consumed.
○ The amount of drug absorbed from GI.
○ The ability of the baby to eliminate the
drug.

Special precautions are required in:

○ Premature infants
○ Low birth weight
○ Infants with G6PD deficiency
○ Infants with impaired ability to metabolize /excrete drugs e.g. hyperbilirubinemia.
 Factors Related to Mother

Time of Route of
breastfeeding administration

Route of administration
The concentration of the
affect the concentration
drug in the milk at the
of the drug in maternal
time of feeding.
blood.

Lactating mother should

take medication just Maternal use of topical
after nursing and 3-4 preparations (creams,
hours before the next nasal sprays or inhalers)
feeding. are expected to carry
(to allow time for drug less risk to a breastfed
to be cleared from the infant than systemically
mother’s blood → drug administered drugs
concentration in milk (oral).
will be low).

Maternal drug
Dose of the drug Health status
concentration

It means if we can reduce the dose

Breastfeeding is contraindicated in case of:
and still get therapeutic effect in
mother we should lower the dose ○ HIV-positive women
○ Active, untreated TB in mother
○ Herpes on breast
○ Use of illegal drugs by mother
○ Certain medications used on a
chronic basis.
Mindmap credits for
team 435
 Oxidizing drugs
Examples: antibiotics (sulfonamides, trimethoprim), antimalarials (primaquine)

Neonatal Hyperbilirubinemia Neonatal Methemoglobinemia

Premature infants or infants Infants under 6 months of age

with inherited G6PD deficiency are particularly prone to
are susceptible to oxidizing develop methemoglobinemia
drugs that can cause
upon exposure to some
hemolysis of RBCS →
oxidizing drugs.
↑bilirubin (hyperbilirubinemia)
→ ↑Kernicterus.

RECALL, Methemoglobin is an oxidized form of hemoglobin

that has a decreased affinity for oxygen → tissue hypoxia

Drugs & Lactation

1. Drugs contraindicated during lactation
Only few drugs are totally contraindicated

Drug Contraindication

Anticancer drugs ❖ Cytotoxicity & neutropenia

(doxorubicin, cyclophosphamide,
methotrexate)
❖ Cyclophosphamide is C.I in pregnancy too

Radiopharmaceuticals -
(radioactive iodine)
 CNS acting drugs -
(amphetamine, heroin, cocaine)

Immunosuppressants -
(cyclosporine)

❖ They have high milk to plasma rate.

Alcohol & Lithium ❖ Low molecular weight.

Chloramphenicol ❖ Bone marrow suppression

Atenolol ❖ Beta-blocker, C.I because of its conc. Is high in milk

Potassium iodide ❖ Thyroid effect

❖ Vomiting
Ergotamine ❖ Diarrhea
Used for migraine headache
❖ Convulsions in infants

❖ Vomiting
❖ Diarrhea
Tobacco smoke ❖ restlessness for the baby
❖ decreased milk production
❖ increase respiratory and ear infections.

Dopamine and Drugs & Lactation

prolactin have
inverse relationship
2. Drugs that can suppress Lactation
These drugs reduce prolactin. (without harmful effect, it just reduce the volume of milk)

Drug info.

Levodopa ❖ dopamine precursor

Bromocriptine ❖ dopamine agonist

❖ Or oral contraceptives that contain

Estrogen high-dose of estrogen and a progestin.

Androgens -

Different from the others, doesn’t work

Thiazide diuretics centrally on prolactin
 Drugs & Lactation Still no harm to the baby

3. Drugs that can augment lactation

Dopamine antagonists : they stimulate prolactin secretion → galactorrhea

Drug info.

Metoclopramide ❖ antiemetic

Domperidone ❖ antiemetic

Haloperidol ❖ antipsychotic

Methyldopa ❖ antihypertensive

Theophylline ❖ used in asthma

Antibiotics
Back to harmful drugs

Note: drugs mentioned are same as pregnancy, what is okay for pregnant is okay for breastfeeding

Drug info.

Penicillins ✓ No significant adverse effect

(Ampicillin, amoxicillin) ❖ allergic reactions, diarrhea

Cephalosporins
✓ No significant adverse effect
Macrolides ❖ Alterations to infant bowel flora
(erythromycin, clarithromycin)

❖ Theoretical risk of arthropathies

Quinolones X Should be avoided

❖ “Gray baby” syndrome

Chloramphenicol X Should be avoided

❖ Absorption by the baby is probably

prevented by chelation with milk calcium.
Tetracyclines X Avoid due to possible risk of teeth
discoloration.
 ❖ hyperbilirubinemia → neonatal jaundice
Sulfonamides X Should be avoided in premature infants or
(co-trimoxazole)
infants with G6PD deficiency

Sedatives/Hypnotics
Barbiturates X Lethargy, sedation, poor suck reflexes with
(phenobarbitone) prolonged use.

✓ Single use of low doses is probably safe.

Benzodiazepines,
X Lethargy, sedation in infants with prolonged
Diazepam, Lorazepam use.

Antidiabetics
Insulin ✓ Safe

Remember it’s contraindicated in

Oral antidiabetics ✓ compatible pregnancy

Metformin X avoid due to lactic acidosis

Analgesics

Paracetamol ✓ Safe

Ibuprofen ✓ compatible

X avoid due to theoretical risk of Reye's

Aspirin syndrome

Antithyroid drugs

Propylthiouracil ❖ May suppress thyroid function in infants.

Carbimazole ✓ Propylthiouracil should be used rather than
Methimazole
carbimazole or methimazole.
potassium iodide
 Anticoagulants
Heparin ✓ Safe, not present in breast milk

✓ Warfarin can be used, very small quantities

Warfarin found in breast milk, monitor the infant's
prothrombin time during treatment.

Anti-convulsants (antiepileptics)
✓ Preferable over others
Carbamazepine ❖ Compatible with breastfeeding
Not in pregnancy
❖ Amounts entering breast milk are not
Phenytoin sufficient to produce adverse effects

❖ Infants must be monitored for CNS

Valproic acid depression, hepatotoxicity

Lamotrigine X AVOID

Antihistamines
Sedating antihistamines
X AVOID
(Diphenhydramine)

Non-sedating ✓ low levels of transfer into breast milk and these would be
considered the preferred choice antihistamines for a
antihistamines (Loratadine) breastfeeding mother.

Others
✓ Non hormonal method should be used.
X Avoid estrogens containing pills
Oral contraceptives ○ Estrogens → ↓ milk quantity
✓ Progestin only pills or mini pills are
preferred for birth control.

✓ Paroxetine is the preferred SSRI in

Antidepressants: SSRI breastfeeding women. Imp bc postpartum depression
is common

Antiasthmatics ✓ Inhaled corticosteroids - prednisone

 Sum󰈚󰈀󰈹y 󰇾󰈢󰈹 c󰈊o󰈎󰇸󰇵 of 󰇷󰈹󰉉g
❖ Drugs known to have serious toxic effects in adults are
avoided
✓ Route of administration (topical, local, inhalation) instead of
an oral form.
✓ Short acting
✓ Highly protein bound
✓ Low lipid solubility
✓ High molecular weight
✓ Poor oral bioavailability
✓ No active metabolites
✓ well-studied drugs in infants

Gen󰈩󰈸󰇽󰈘 Con󰈻󰈎󰇶󰇵ra󰉃󰈎󰈢󰈞s

1. Infants should be monitored for adverse effects e.g. feeding,

sedation, irritability, rash, etc.
2. Drugs with no safety data should be avoided or lactation
should be discontinued
3. Do not guess
4. Use the following sources:
a. Use Medication and Mothers’ Milk
(www.iBreastfeeding.com)
b. Use lactmed or toxnet (http://toxnet.nlm.nih.gov )
 Qu󰈎z
Q1: which one of the following characteristics would you look for when prescribing a drug
to a lactating mother?
A. Low molecular weight
B. Lipid soluble
C. High degree of ionization
D. Long half life.

Q2: all of the following drugs can augment lactation except:

A. Metoclopramide
B. Levodopa
C. Domperidone
D. Theophylline

Q3: sulfonamides should be avoided by a lactating mother in case of :

A. Prematurity
B. Low birth weight
C. Infants with G6PD deficiency
D. Infants with respiratory distress

Q4: a woman has postpartum depression ,which antidepressant is preferred if she’s

breastfeeding
A. Paroxetine
B. Amitriptyline
C. Sertraline
D. Imipramine

Q5: which of the following drugs will suppress lactation :

A. Bromocriptine
B. Metoclopramide
C. Domperidone
D. Haloperidol

Q6: a baby known to have G6PD deficiency develops jaundice while

breastfeeding. What drug most likely was taken by the mother?
A. Penicillin
B. Erythromycin
C. Primaquine
D. Tetracycline
6) C
5) A
4) A
3) C
2) B
1) C
Answers: