Wednesday, July 14, 2010

Drugs Contraindicated During Lactation


All drugs of abuse are contraindicated during lactation e.g. amphetamine, cocaine, heroin, phecyclidine and marijuana, accumulate in breast milk and cause irritability and poor sleep patterns.

• Antineoplastics: potential for immune suppression
• Bromocriptine: suppresses lactation
• Ergotamine: potential for suppressing lactation, vomiting, diarrhoea and convulsions
• Immunosuppressants: potential for immunosuppression
• Lithium: milk contains 40% of maternal serum concentration
• Misoprostol: produces severe diarrhoea in infants
• Nicotine (smoking): decreased milk production
• Phenindione:massive scrotal haematoma and wound oozing after herniotomy

Drugs requiring temporary cessation of breast-feeding
• Metronidazole: diarrhoea and secondary lactose intolerance.
• Radiopharmaceuticals:Stop breastfeeding temporarily to allow clearing from milk according to the chemical nature of the isotope.
• Quinolones: potential arthropathy in infants.

Reducing risk of Infant Exposure to Drugs in Breast Milk


A drug should be used only if medically necessary and treatment cannot be delayed until the infant is ready to be weaned.

Drug selection
• Consider whether the drug can be safely given directly to the infant
• Select the drug that passes poorly into breast milk with the lowest milk-to-plasma ratio
• Avoid long-acting formulations e.g. sustained release
• Determine length of therapy and if possible avoid long-term usage

Feeding pattern
• Avoid nursing during times of peak drug concentration
• If possible, plan breast-feeding before administration of the next dose

Other considerations

• Always observe the infant for unusual signs or symptoms e.g. sedation, irritability, rash, decreased appetite, failure to thrive
• Discontinue breastfeeding during the course of therapy if the risks to the fetus outweigh the benefit of nursing
• Provide adequate patient education to increase the understanding of risk factors.

Drug Excretion in Human milk


Breast milk is the optimal source of nutrition for infants. The risk to the infant depends on the amount of drug bioavailable to the mother, the amount reaching breast milk and the actual amount of drug ingested and bioavailable to the nursing infant.

Mechanism of transfer from blood to milk

The basic mechanisms are the same as those across other biologic membranes.

• Diffusion of low molecular weight substances through small water- filled pores
• Diffusion of lipid soluble compounds through lipid membranes
• Active transport carrier-mediated

Factors affecting drug excretion in breast milk

The drug dose, route and frequency of administration and metabolism are important factors in determining the amount of drug available for excretion into milk.

Maternal parameters
• Drug dosage and duration of therapy
• Route and frequency of administration
• Drug metabolism and renal clearance
• Blood flow to the breasts
• pH of milk
• Milk composition
Drug parameters
• Oral bioavailability (to mother and infant)
• Molecular weight
• Lipid solubility
• Protein binding
Infant parameters
• Infant age
• Feeding pattern
• Amount of breast milk consumed
• Drug absorption, distribution, metabolism and elimination

Proven Human Teratogens


Numerous drugs are associated with congenital malformation e.g. aminopterin/methotrexate, ACE-Inhibitors, antineoplastics, anti-thyroids, barbiturates, carbamazepine, cocaine, coumarin derivatives, diethylstilbesterol, ethanol (large dose), iodides, radioactive iodine, lithium, methadone, phenytoin, retinoid, vitamin A (>18,000 IU/day), tetracycline and valproic acid.

FDA categories (teratogenic risks of drugs):
Category A

Controlled studies in women fail to demonstrate a risk to the fetus in the first trimester and the fetal harm appears remote.

Category B

Animal reproduction studies have not demonstrated a fetal risk, but there are no controlled studies in pregnant women. Or animal reproduction studies have shown an adverse effect that was not confirmed in controlled studies in women in the first trimester.

Category C

Studies in animals have revealed ad- verse effects on foetus and no controlled studies in women are available. Or, studies in women and animals are not available. Drugs should be given only if the potential benefit justifies the potential risk to the foetus.

Category D

Evidence of human foetal risk is positive, but the benefits from use in pregnant women may be acceptable despite the risk.

Category X

Studies in animals or humans have demonstrated foetal anomalies or there is evidence of foetal risk based on human experience or both and the risk of the drug in pregnant women

clearly outweighs any possible benefits. The drug is contraindicated in women who are or may become pregnant.