Drugs & lactation

Drugs&Lactation

Prof Aboubakr Elnashar Benha University Hospital, Egypt Email: [email protected]

Aboubakr Elnashar

•Breast-feeding has many benefits.

•Potential harm to the nursing infant

from maternal drugs is a reason to discontinue

breast-feeding.

•Physicians receive little education about breast-

feeding and even less training on the effects of

maternal drugs on the nursing infant.

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•The mammary tissue in the breast is composed

of clusters of milk-producing alveolar cells

surrounding a central lumen.

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A ducts

B lobules

C dilated section of duct to hold milk

D nipple

E fat

F pectoralis major muscle

G chest wall/rib cage

Enlargement:

A normal duct cells

B basement membrane

C lumen (center of duct)

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The effect of drugs on the nursing infant

depends on 1.Transfer of drug into Breast Milk

2.The amount of breast milk consumed by the

infant.

3. The pharmacologic activity of the drug:

absorption, distribution, metabolism and

elimination by the infant.

4. Condition of the infant: Greater precaution for infants

premature or

compromised or

in the first week of life than for older, healthy infants.

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Transfer of dugs into Breast Milk

•Nearly all drugs transfer into breast milk to some

extent.

•Notable exceptions are heparin and insulin {too

large to cross biological membranes}.

•Drug transfer from maternal plasma to milk is,

with rare exceptions, by passive diffusion across

biological membranes.

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• Factors affecting drug transfer

I. The maternal serum drug concentration.

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II. Drugs:

protein binding,

lipid solubility,

molecular weight and

ionization

•Transfer is greatest

low protein binding

high lipid solubility.

Small molecular weight

weakly basic drugs

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III. Milk composition

Milk at the end of a feed (hindmilk) contains

considerably more fat than foremilk and may

concentrate fat-soluble drugs.

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IV. Age of infant:

•In the early postpartum period, large gaps

between the mammary alveolar cells allow many

dugs to pass. These gaps close by the 2nd week

of lactation.

•Premature babies & infants less than 1 month

have a different capacity to absorb and excrete

drugs than older infants.

Thus, extra caution is needed for these infants.

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Calculation of infant exposure to drugs

The infant dose (mg/kg)

I. D infant (mg/kg/day)= C maternal (mg/L) x

M/PAUC x V infant (L/kg/day) •Cmaternal= maternal plasma concentration • M/PAUC ratio = milk to plasma concentration ratio area under curve. •Vinfant= volume of milk ingested

II. As a percentage of the maternal dose (mg/kg).

The volume of milk ingested by infants is

commonly estimated as 0.15 L/kg/day. An arbitrary cut-off of 10% has been selected as a

guide to the safe use of drugs during lactation.

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WHO classification of drugs during

breastfeeding (2002)

1. Compatible with breastfeeding

2. Compatible with breastfeeding {occasional mild side

effects} Monitor infant for side effects

3. Avoid if possible. {significant side effects} Monitor

infant for side-effects

4. Avoid if possible. {May inhibit lactation}. Monitor for

amount of milk

5. Contraindicated {dangerous side effects}

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WHO Classification DRUGS during

BREASTFEEDING (2002)

1. Compatible with breastfeeding

There are no known or theoretical

contraindications for their use, and it is

considered safe for the mother to take the drug

and continue to breastfeed.

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2. Compatible with breastfeeding {Occasional mild side-effects} Monitor infant for side-effects

•If side-effects:

stop the drug, and

find an alternative.

If the mother cannot stop the drug, she may need

to stop breastfeeding and feed her baby artificially

until her treatment is completed.

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3. Avoid if possible {significant side effects}

Monitor infant for side-effect

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Psychotropic drugs,

anti-anxiety,

antidepressant, and

antipsychotic ,

when given to nursing mothers for long periods

could alter short-term and long-term central

nervous system function.

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4. Avoid if possible {May inhibit lactation}

However, if a mother has to take one of these drugs for a short period, she does not need to give artificial milk to her baby. She can off set the possible decrease in milk production by encouraging her baby to suckle more frequently. Estrogen COC Ergometrin Thiazides

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5. Contraindicated {Dangerous side-effects}.

If they are essential:

stop breast feeding until treatment is completed.

If treatment is prolonged, she may need to stop

breastfeeding altogether.

There are very few drugs in this category apart

from anticancer drugs and radioactive

substances.

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lithium (infant dose as high as 80% of the weight-

adjusted maternal dose) and

amiodarone (infant dose up to 50%) should be

avoided due to high infant exposure and potential

for significant toxicity.

For drugs with greater inherent toxicity such as

cytotoxic agents,

ergotamine,

gold salts,

immunosuppressives and

isotretinoin, the cut-off of 10% is too high and

breastfeeding is contraindicated.

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AMERICAN

ACADEMY

OF

PEDIATRICS

(2001)

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Before prescribing drugs to lactating women

1. Is drug really necessary? If drugs are required,

consultation between the pediatrician and the

mother’s physician can be most useful in

determining what options to choose.

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2. The safest drug should be chosen e.g. acetaminophen rather than aspirin for analgesia. 3. If there is a possibility that a drug may present

a risk to the infant, consideration should be given

to measurement of blood concentrations in the

nursing infant.

4. Drug exposure to the nursing infant may be

minimized

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Minimizing Potential Risk to Nursing Infants

from Maternal Medications

General considerations

•Use topical therapy when possible.

•Drugs that are safe for the nursing infant’s age

are generally safe for the breast-feeding mother.

•Drugs that are safe in pregnancy are not always

safe in breast-feeding mothers {nursing infant must independently metabolize and excrete the medication}.

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Medication selection

•Choose medications with the shortest half-life

and highest protein-binding ability.

•Choose medications that are well-studied in

infants.

•Choose medications with the poorest oral

absorption.

•Choose medications with the lowest lipid

solubility.

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Medication dosing

•Administer single daily-dose drugs just before

the longest sleep interval for the infant, usually

after the bed-time feeding.

•Breast-feed infant immediately before medication

dose when multiple daily doses are needed.

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Aboubakr Elnashar