Maternal Medication, Drug Use, and Breastfeeding

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Key points

  • Drugs transfer into milk as a function of molecular weight. The higher the molecular weight, the less the drug transfers into human milk.

  • Drugs transfer into human milk as a function of the maternal plasma level. The higher the plasma level, the higher the transfer into human milk.

  • Drugs with poor oral bioavailability seldom produce significant clinical levels in human milk, and are generally poorly absorbed by the infant.

  • Drugs that transfer into the brain compartment also likely transfer into

Key concepts of medication entry into breast milk

Although all medications enter milk to some degree, clinically relevant levels are seldom attained. Most drugs simply transfer in and out of the milk compartment by passive diffusion from a region of high concentration to a region of low concentration. Some active transport systems exist for immunoglobulins, electrolytes, and particularly iodine, but facilitated transport systems are limited. Fewer than 10 drugs are known to be selectively transported into human milk.

Medications that enter

Calculating infant exposure

Perhaps the most useful tool in clinical practice is to calculate the actual dose received by the infant. To do this, the actual concentration of medication in the milk and the volume of milk transferred must be known. Although not always available, data on milk levels are available for many drugs. More recent studies now calculate the average area under the curve (AUC) value for the medication (Cave).4 This methodology accurately estimates the average daily level of the drug in milk, and hence

Unique infant factors

To evaluate the risk of the medication, infants should be categorized as low, moderate, or high risk. Infants at low risk are generally older (6–18 months), receive lower volumes of breast milk, and are able to metabolize and handle drugs more efficiently. Mothers in the terminal stage of lactation (>1 year) often produce relatively lower quantities of milk. Thus, the absolute clinical dose transferred is often low.

Infants at moderate risk are term infants who are aged between 2 weeks and 6

Psychiatric conditions

Recent data from 17 American states indicate that postpartum depression affects 12% to 20% of women.6 Fortunately for practitioners, there is increasing information available about the use of antidepressants during lactation that support the treatment of the condition while breastfeeding (Table 1). The selective serotonin reuptake inhibitors (SSRIs) are presently the mainstay of antidepressant therapy in women who are breastfeeding. Table 1 provides the RID for common SSRIs. Clinical studies in

Recreational drugs

Alcohol readily transfers into human milk, with an average milk/plasma ratio of about 1.0. Yet the clinical dose of alcohol in human milk is not necessarily high. In a well-controlled study of 12 women who ingested 0.3 g/kg of ethanol, the mean maximum concentration of ethanol in milk was only 320 mg/L.25 In an interesting study of the effect of alcohol on milk ingestion by infants, the rate of milk consumption by infants during the 4 hours immediately after exposure to alcohol (0.3 g/kg) in 12

Pain/analgesia

Analgesics are one of the most commonly used medications while breastfeeding. Options for pain control include acetaminophen, nonsteroidal antiinflammatory drugs (NSAIDs), and opioids. Most NSAIDs are used to reduce pain and inflammation and are generally a suitable choice in breastfeeding women. Ibuprofen, acetaminophen, and naproxen are probably the most commonly used analgesics in North America. Their RID in milk ranges from 0.65% for ibuprofen,36 8.81% for acetaminophen,37 to 3.3% for

Hypertension

Several medications are used to treat hypertension, including diuretics, β-adrenergic blockers, calcium channel blockers, angiotensin-converting enzyme inhibitors (ACEIs), and angiotensin receptor blockers (ARBs). Many of these medications are suitable during breastfeeding; however, some in the β-blocker family are known to cause problems for breastfed infants. The β-blockers of choice are metoprolol (RID 1.4%) and propranolol (RID 0.3%); neither medication has been associated with any adverse

Liver/gastrointestinal tract

The use of histamine-2 (H2) antagonists and proton pump inhibitors (PPIs) for gastroesophageal reflux disease (GERD) and nausea/vomiting in pregnancy is increasing. Famotidine is a preferred H2 antagonist. In a study of 8 women who were given famotidine 40 mg/d, the RID was estimated to be the lowest of the H2 antagonists at 1.9%.57 Although ranitidine has a high milk/plasma ratio, it is also a preferred agent because the amount of ranitidine that enters breast milk is low; the RID ranges

Nausea

The 3 medications that are considered most suitable for short-term treatment of nausea and vomiting during lactation are dimenhydrinate (see section on psychiatric conditions for more information), ondansetron, and metoclopramide. Although the milk levels of ondansetron are unknown, it is a preferred agent because it is commonly used during pregnancy and in young infants without any major reports of safety concerns.61, 62 Metoclopramide is an alternative for short-term use (due to maternal side

Infectious disease

Most antibiotics, such as penicillins and cephalosporins, have been well studied and are compatible with breastfeeding because of poor entry into breast milk (Table 3).63 Although side effects are uncommon, those reported in infants exposed to antibiotics in breast milk are usually selflimiting, such as diarrhea and rash.64 Two classes of antibiotics that have known complications in children and are generally perceived by clinicians and patients as contraindicated in breastfeeding mothers, are

Hematology

The use of antiplatelet and anticoagulant medications is increasing in women for prevention of cardiovascular disease, treatment of venous thrombosis during pregnancy, prevention of procedure-related thrombosis, and numerous other indications (Table 4). Older studies of aspirin are poor and were done using relatively high doses as opposed to the doses of 81 to 325 mg used today. In the older studies and using a 1-g oral dose, the RID was reported as 9.4%.74 Thus, the risk in using daily doses

Endocrine medications

The rate of diabetes is increasing and more mothers require insulin and oral hypoglycemics in pregnancy and throughout lactation. One of the first-line medications used for type 2 diabetes mellitus is metformin; this medication is part of the biguanide class of antidiabetic medications and has been studied in 5 lactating women and 3 infants.75 The average peak and trough concentrations in breast milk for metformin were 0.42 μg/mL and 0.39 μg/mL, resulting in an RID of 0.65%.75 In this study, 3

Contraceptives

It is hypothesized that the withdrawal of progesterone in the early postpartum period initiates lactogenesis.78 Consequently, it has been suggested that if a mother begins progesterone or combined oral contraceptives (COCs) early postpartum (the first few days), it may interrupt the establishment of lactation.78

A recently published, double-blind, randomized trial compared the effect of initiating progesterone-only contraceptives (0.35 mg norethindrone) with COCs (0.035 mg ethinyl estradiol + 1

Drugs that stimulate milk production

During gestation, prolactin levels can be as high as 400 ng/mL. After delivery and in the first 6 months postpartum, maternal prolactin levels decrease steadily to approximately 75 ng/mL at 6 months, even though milk production is unchanged.82 In many mothers who are unable to produce an adequate supply of breast milk, prolactin levels are believed to have decreased to inadequate levels (<75 ng/mL). Therefore, in some cases, milk production may be restored with the use of dopamine antagonists

Summary

The number of new medications that are available to breastfeeding mothers requiring drug therapy is expanding daily. This makes it difficult for clinicians to assess the safety of medications in breast milk; however, knowing how to assess the key factors that influence a medication’s suitability while breastfeeding allows clinicians to make collaborative clinical decisions with their patients to encourage breastfeeding. In reality, women can breastfeed safely while ingesting most medications,

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References (119)

  • A. Kauppila et al.

    A dose response relation between improved lactation and metoclopramide

    Lancet

    (1981)
  • K. Schmidt et al.

    Citalopram and breast-feeding: serum concentration and side effects in the infant

    Biol Psychiatry

    (2000)
  • B.M. Lester et al.

    Possible association between fluoxetine hydrochloride and colic in an infant

    J Am Acad Child Adolesc Psychiatry

    (1993)
  • M.M. Stahl et al.

    Thrombocytopenic purpura and anemia in a breast-fed infant whose mother was treated with valproic acid

    J Pediatr

    (1997)
  • Centers for Disease Control and Prevention. Breastfeeding Report Card-United States, 2012. Available at:...
  • E.E. Stultz et al.

    Extent of medication use in breastfeeding women

    Breastfeed Med

    (2007)
  • T.W. Hale

    Medication and mothers' milk

    (2012)
  • T.W. Hale et al.

    Textbook of human lactation

    (2007)
  • P.N. Bennett

    Drugs and human lactation

    (1996)
  • Centers for Disease Control and Prevention (CDC)

    Prevalence of self-reported postpartum depressive symptoms–17 states, 2004-2005

    MMWR Morb Mortal Wkly Rep

    (2008)
  • Z.N. Stowe et al.

    The pharmacokinetics of sertraline excretion into human breast milk: determinants of infant serum concentrations

    J Clin Psychiatry

    (2003)
  • S. Hagg et al.

    Excretion of fluvoxamine into breast milk

    Br J Clin Pharmacol

    (2000)
  • R. Ohman et al.

    Excretion of paroxetine into breast milk

    J Clin Psychiatry

    (1999)
  • J.H. Kristensen et al.

    Distribution and excretion of fluoxetine and norfluoxetine in human milk

    Br J Clin Pharmacol

    (1999)
  • J.H. Kanto

    Use of benzodiazepines during pregnancy, labour and lactation, with particular reference to pharmacokinetic considerations

    Drugs

    (1982)
  • V. Rindi

    La eliminazione degli antistaminici di sintesi con il latte e l'azione latto-goga de questi

    Riv Ital Ginecol

    (1951)
  • I. Matheson et al.

    The excretion of zopiclone into breast milk

    Br J Clin Pharmacol

    (1990)
  • R.C. Hill et al.

    Risperidone distribution and excretion into human milk: case report and estimated infant exposure during breast-feeding

    J Clin Psychopharmacol

    (2000)
  • S. Croke et al.

    Olanzapine excretion in human breast milk: estimation of infant exposure

    Int J Neuropsychopharmacol

    (2002)
  • J. Rampono et al.

    Quetiapine and breast feeding

    Ann Pharmacother

    (2007)
  • D.H. Wiles et al.

    Chlorpromazine levels in plasma and milk of nursing mothers

    Br J Clin Pharmacol

    (1978)
  • L.P. Hackett et al.

    Methylphenidate and breast-feeding

    Ann Pharmacother

    (2006)
  • K.F. Ilett et al.

    Transfer of dexamphetamine into breast milk during treatment for attention deficit hyperactivity disorder

    Br J Clin Pharmacol

    (2006)
  • G.E. von Unruh et al.

    Valproic acid in breast milk: how much is really there?

    Ther Drug Monit

    (1984)
  • T. Tomson et al.

    Lamotrigine in pregnancy and lactation: a case report

    Epilepsia

    (1997)
  • D.J. Newport et al.

    Lamotrigine in breast milk and nursing infants: determination of exposure

    Pediatrics

    (2008)
  • I. Ohman et al.

    Topiramate kinetics during delivery, lactation, and in the neonate: preliminary observations

    Epilepsia

    (2002)
  • J.A. Mennella et al.

    The transfer of alcohol to human milk. Effects on flavor and the infant's behavior

    N Engl J Med

    (1991)
  • J.A. Mennella

    Regulation of milk intake after exposure to alcohol in mothers' milk

    Alcohol Clin Exp Res

    (2001)
  • E. Ho et al.

    Alcohol and breast feeding: calculation of time to zero level in milk

    Biol Neonate

    (2001)
  • M. Perez-Reyes et al.

    Presence of delta9-tetrahydrocannabinol in human milk

    N Engl J Med

    (1982)
  • K. Tennes et al.

    Marijuana: prenatal and postnatal exposure in the human

    NIDA Res Monogr

    (1985)
  • D. Jutras-Aswad et al.

    Neurobiological consequences of maternal cannabis on human fetal development and its neuropsychiatric outcome

    Eur Arch Psychiatry Clin Neurosci

    (2009)
  • K.F. Ilett et al.

    Use of nicotine patches in breast-feeding mothers: transfer of nicotine and cotinine into human milk

    Clin Pharmacol Ther

    (2003)
  • E.E. Tyrala et al.

    Caffeine secretion into breast milk

    Arch Dis Child

    (1979)
  • J.E. Ryu

    Caffeine in human milk and in serum of breast-fed infants

    Dev Pharmacol Ther

    (1985)
  • R.T. Weibert et al.

    Lack of ibuprofen secretion into human milk

    Clin Pharm

    (1982)
  • P.O. Bitzen et al.

    Excretion of paracetamol in human breast milk

    Eur J Clin Pharmacol

    (1981)
  • F. Jamali et al.

    Naproxen excretion in milk and its uptake by the infant

    Drug Intell Clin Pharm

    (1983)
  • V.L. Feilberg et al.

    Excretion of morphine in human breast milk

    Acta Anaesthesiol Scand

    (1989)
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