Drugs

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Drugs lactation
Prof.Aboubakr Elnashar
Benha University Hospital, Egypt Email
elnashar53_at_hotmail.com
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• 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
• Transfer of drug into Breast Milk
• 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
• 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
mothers 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 infants 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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Thank you
Prof. Aboubakr Elnashar
Benha University Hospital, Egypt Email
elnashar53_at_hotmail.com