The Transfer of Drugs and Other Chemicals into Human Breast Milk · Chlorotrianisene None 51 3H-norethynodrel None 94 19 norsteroid None 95 Contraceptive pill with estrogen/progester-

0

0 PEDIATRICS (ISSN 0031 4005). Copyright © 1983 by the

American Academy of Pediatrics.

0 Committee on Drugs

PEDIATRICS Vol. 72 No. 3 September 1983 375

The Transfer of Drugs and Other Chemicalsinto Human Breast Milk

In this statement, lists of the pharmacologic infant but indicates that there are no reports in the

agents transferred into human breast milk and their literature. These tables should assist the physician

possible effects on the infant or on lactation if in counseling a patient regarding breast-feedingknown are provided (Tables 1 to 4). The fact that when the patient has a condition for which a drug

TABLE 1. Drugs That Are Contraindicated During Breast-Feeding

Drug Reported Sign or Symptom in Infant or Effect on Lactation Reference

Amethopterin* Possible immune suppression; unknown effect on growth or association 1with carcinogenesis

Bromocriptine Suppresses lactation 2Cimetidinet May suppress gastric acidity in infant, inhibit drug metabolism, and 3

cause CNS stimulation

Clemastine Drowsiness, irritability, refusal to feed, high-pitched cry, neck stiffness 4Cyclophosphamide* Possible immune suppression; unknown effect on growth or association 5

with carcinogenesis

Ergotamine Vomiting, diarrhea, convulsions (doses used in migraine medications) 6Gold salts Rash, inflammation of kidney and liver 7, 8

Methimazole Potential for interfering with thyroid function 9Phenindione Hemorrhage 10Thiouracil Decreased thyroid function; does not apply to propylthiouracil 11

* Data not available for other cytotoxic agents. t Drug is concentrated in breast milk.

TABLE 2. Drugs That Require Temporary Cessation of Breast-Feeding

Drug Recommended Alteration in Breast-Feeding Pattern Reference

Metronidazole Discontinue breast-feeding 12-24 h to allow excretion of dose 12, 13Radiopharmaceuticals Radioactivity present in milk, consult nuclear medicine physi-

cian before performing diagnostic study so that radionuclidewhich has shortest excretion time in breast milk can be

used; prior to study the mother should pump her breast andstore enough milk in freezer for feeding the infant; afterstudy the mother should pump her breast to maintain milkproduction but discard all milk pumped for the requiredtime that radioactivity is present in milk.

Gallium-69 (69Ga) Radioactivity in milk present for 2 wk 14

Iodine-125 (125!) � Risk of thyroid cancer; radioactivity in milk present for 12 d 15Iodine-131 (‘�‘I) Radioactivity in milk present 2-14 d depending on study. 16-19Radioactive sodium Radioactivity in milk present 96 h 20Technetium-99m (9SmTc) Radioactivity in milk present 15 h to 3 d 21-25

99mTc macroaggregates,9SmTc 04

a pharmacologic agent does not appear on the listsis not meant to imply that it is not transferred into

breast milk or that it does not have an effect on the

is medically indicated.

These reports have been obtained from a search

of the medical literature. Because methodologies

used to quantitate drugs in breast milk continue to

improve, current information will require continu-

ous updating of the tables. Brand names are listed

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TABLE 3. Maternal Medication Usually Compatible with Breast-Feeding

Drug Reported Sign or Symptom in Infant or Effect Referenceon Lactation

ANESTHETICS, SEDATIVES oAlcohol Drowsiness, diaphoresis, deep sleep, weak- 26, 27

ness, decrease in linear growth, abnormalweight gain; maternal ingestion of 1 g/kg

daily decreases milk ejection reflexBarbiturate None; see antiepileptic drugs 28

Bromide Rash, weakness, absence of cry with mater- 29nal intake of 5.4 g/d

Chloral hydrate Sleepiness 30Chloroform None 31

Halothane None 32Magnesium sulfate None 33Methyprylon Drowsiness 34Secobarbital None 35

ANTICOAGULANTSBishydroxycoumarin None 36Warfarin None 37

ANTIEPILEPTICSCarbamazepine None 38Ethosuximide None 39Phenobarbital Methemoglobmemia (1 case); decreased re- 40, 41

sponsiveness, decreased weight gain, ex-cessive sleeping if mother’s plasma level�30 �g/mL

Phenytoin Methemoglobinemia (1 case) 41Primidone None 40, 42

Thiopental None 28Valproic acid None 43

ANTIHISTAMINES, DECONGESTANTS,AND BRONCHODILATORS

Dexbrompheniramine maleate with d-iso- Crying, poor sleeping patterns, irritability 44ephedrine

Diphenhydramine None 45Dyphyllinet None 46lodides Affects thyroid activity; see miscellaneous 47, 48

iodineTheophylline Irritability 49, 50Trimeprazine None 51

Tripelennamine None 52

ANTIHYPERTENSIVE AND CARDIO-VASCULAR DRUGS

Atenolol None 53Captopril None 54Digoxin None 55Disopyramide None 56Guanethidine None 47Hydralazine None 57Methyldopa None 58Metoprololt None 53Nadololt None 59Propranolol None 60-62Quinidine None 63Reserpine Galactorrhea 64

ANTIINFECTIVE DRUGS (ALL antibioticstransfer into breast milk in limitedamounts)

Amantadine Urinary retention, vomiting, and skin rash 51Cefadroxil None 65Cefazolin None 66Cefotaxime None 65

t Drug is concentrated in breast milk.

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TABLE 3.-Continued

Drug Reported Sign or Symptom in Infant or Effect Referenceon Lactation

0 Chloramphenicol None 67, 68Chloroquine None 69Clindamycin None 70Ethambutol None 71

Isoniazid None 72Nalidixic acid Hemolysis in infant with glucose-6-phos- 73

phate deficiency (G-6-PD)Nitrofurantoin Hemolysis in infant with G-6-PD 74Pyrimethamine None 75Quinine None 76Rifampin None 71Salicylazosulfapyridine (sulfasalazine) None 77, 78

Sulfapyridine Caution in infant with jaundice or G-6-PD, 77and ill, stressed, or premature infant

Sulfathiazole None; nonabsorbable by mother 79Sulfisoxazole Caution in infant with jaundice or G-6-PD, 80

and ill, stressed, or premature infantTetracycline None; negligible absorption by infant 81, 82Trimethoprim None 83

ANTITHYROID DRUGSCarbimazole Goiter 47, 51Propylthiouracil None 84

CATHARTICS (Drugs that cause abdominal Abdominal cramping, colic-like syndromecramping in mother)

Danthron Increased bowel activity 85

DIAGNOSTIC AGENTSIodine Goiter; see miscellaneous, iodine 16lopanoic None 86Metrizamide None 87

0 DIURETICSBendroflumethiazide Suppresses lactation, thrombocytopenia (1 88

case)Chlorothiazide May suppress lactation, therefore avoid 89, 90

prescribing in 1st month of lactation; thismay also apply to other thiazides; ques-tionably dose related

Chlorthalidone Excreted slowly 91Methyclothiazide None 92Spironolactone None 93

HORMONESChlorotrianisene None 513H-norethynodrel None 9419 norsteroid None 95Contraceptive pill with estrogen/progester- Breast enlargement, dose related; decrease 96-101one in milk production and protein contentEstradiol Withdrawal, vaginal bleeding 102, 103

MUSCLE RELAXANTSBaclofen None 104Carisoprodol Drowsiness, intestinal upset 105Methocarbamol None 106

NARCOTICS, NON-NARCOTIC ANALGE-SICS, ANTIINFLAMMATORYAGENTS

Acetaminophen None 107-109Butorphanol None 110Codeine None 79Flufenamic acid None 111Heroin None 112

O Ibuprofen None 113Indomethacin Seizure (1 case) 114, 115

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Drug Reported Sign or Symptom in Infant or Effect Reference

on Lactation

Conflicting reports of drowsiness

None

51

51, 128-132

0

0

0

153

TABLE 3.-Continued

378 AGENTS TRANSFERRED INTO HUMAN BREAST MILK

Mefenamic acidMeperidine

MethadoneMorphine

NaproxenPhenylbutazone

Prednisolone, prednisonePropoxyphene

Salicylates

PSYCHOTROPIC AGENTSAntianxiety

ChlordiazepoxideClorazepate

DiazepamMeprobamatetOxazepamPrazepamt

AntidepressantsAmitriptyline

AmoxapineDesipramineDothiepin

ImipramineLithium

Tranylcypromine

Antipsychotic

Chlorpromazine

HaloperidolMesoridazine

PiperacetazineProchlorperazineThioridazineTrifluoperazine

Other

Marijuanat

STIMULANTSAmphetamineCaffeine

Nicotine (excess)

VITAMINSB1B12DFolic acidK1PyridoxineRiboflavin

Thiamin

MISCELLANEOUS

Atropine, scopolamineBethanecholDiphenoxylate with atropineIodine (providone-iodine/vaginal douche)

Tolbutamide

None

None

None if mother receiving �20 mg/24 hNone

None

None

None

None

Metabolic acidosis (dose related); may af-fect platelet function, rash

Galactorrhea in adult; drowsiness and leth-argy in infant

None

None

Unknown, only 1 report in literature

Irritability, poor sleeping patternIrritability, poor sleeping pattern excreted

slowlyShock, vomiting, diarrhea, rapid heart rate,

restlessness; decreased milk production

None

None

Increased calcium levels

None

None

None

NoneNone

None

Abdominal pain, diarrheaNone

Elevated iodine levels in breast milk, odorof iodine on infant’s skin

Jaundice

116

51

117

76

118

119

120, 121

122

123, 124

47, 125-127

133-135

51

136, 137

138

139

140

141

50, 142, 143

27

45

144

145

146147

148, 149

150

150

79, 151

34

152

48


Reference

154

29, 155

156

50, 157

158159-162

TABLE 4. Food and Environmental Agents: Effect on Breast-Feeding

AMERICAN ACADEMY OF PEDIATRICS 379

Agent

AspartameBromide (photographic labora-

0 tory)ChlordaneChocolate

CyclamateDDT, benzenehexachlorides,

dieldrin, aldrin, hepatachlore-poxide

Fava beans

Fluorides

Hexachlorobenzene

Hexachlorophene

LeadMethyl mercuryMonosodium glutamate (MSG)Polychlorinated biphenyls and

polybrominated biphenylsSaccharinTetrachlorethylene (cleaning

fluid)Vegetarian diet

t Drug is concentrated in breast milk.

Reported Sign or Symptom in Infant or Effect on Lactation

Caution in patient carrier of phenylketonuriaPotential absorption and bromide transfer into milk;

see “Anesthetics, Sedatives”None reportedIrritability or increased bowel activity if excess

amounts ( 16 oz/d) consumed by motherNoneNone

Hemolysis in patient with glucose-6-phosphate defi-ciency (G-6-PD)

NoneSkin rash, diarrhea, vomiting, dark urine, neurotoxic-

ity, deathNone; contamination of milk from nipple washingNeurotoxicityAffects neurodevelopment

NoneLack of endurance, hypotonia, sullen expressionless

facies

NoneObstructive jaundice, dark urine

Signs of B12 deficiency

163

164165

166

167

168, 169

170

171-173

51

174

175

at the end of the tables in accordance with the 4th

Edition AMA Drug Evaluation. The reference list

is not inclusive of all articles published.

Physicians who encounter adverse effects in in-

fants fed breast milk due to exposure to drugs thatare not included here are urged to document the

effects in a communication to the Committee on

Drugs of the American Academy of Pediatrics in

Evanston. Such communication should include: the

generic and brand name of the drug; the maternal

dose and mode of administration; the concentrationof the drug in breast milk and maternal and infant

blood in relation to time of ingestion; the age of the

infant; and the method used for laboratory identi-fication. Such reports may significantly increase

the pediatric community’s fund of knowledge re-

garding drug transfer into breast milk and the

potential risk to the infant.

Drugs cited in Tables 1 to 4 are listed here by

category, in alphabetical order by generic name. For

convenience, one or more examples are also given.

ANESTHETICS, SEDATIVESmethyprylon-Noludar

secobarbital-Seconal, Seco-8

ANTICOAGULANTSbishydroxycoumarin-Dicumarol

0 phenindione-Hedulin, Eridionewarfarin-Coumadin, Panwarfin

ANTIEPILEPTICS

carbamazepine-Tegretolethosuximide-Zarontinphenytoin-Dilantinprimidone-Mysolinethiopental-Pentothalvalproic acid-Depakene

ANTIHISTAMINES, DECONGESTANTS, ANDBRONCHODILATORS

clemastine-Tavegil, Tavistdexbrompheniramine maleate with d-isoephedrine-Drix-

oral, Disophrol Chronotabdiphenhydramine-Benadryl, Benylin cough syrupdyphylline-Dilortheophylline-Theo-Dur, Elixophyllin, Slo-Phyllin, Bron-

kodyltrimeprazine tartrate-Temariltripelennamine-Pyribenzamine

ANTIHYPERTENSIVE AND CARDIOVASCULARAGENTS

atenolol-Tenormincaptopril-Capotendigoxin-Lanoxin, SK-Digoxindisopyramide-Norpaceguanethidine sulfate-Ismelinhydralazine-Apresolinemethyldopa-Aldometmetoprolol-Lopressornadolol-Corgardpropranolol-Inderalreserpine-Serpasil, Reserpoid, Hiserpia


0

0


ANTIINFECTIVE AGENTSamantadine-Symmetrelcefadroxil-Duricef

cefazolin-Ancef, Kefzolcefotaxime-Claforanchloramphenicol-Chloromycetinchloroquine-Aralenclindamycin-Cleocinethambutol-Myambutolisoniazid-INHmetronidazole-Flagylnalidixic acid-NegGramnitrofurantoin-Furadantin, Nitrofor, Macrodantinpyrimethainine-Daraprimquinine-Quinerifampin-Rifamycin, Rifadin, Rimactanesalicylazosulfapyridine-Azulfidinesulfisoxazole-Gantrisintetracycline-Achromycin, SK-Tetracyclinetrimethoprim with sulfamethoxazole-Bactrim, Septra,

Septra DS

ANTITHYROID AGENTScarbimazole-Neo-mercazolemethimazole-Tapazolepropylthiouracil-Propacilthiouracil-Thiouracil

CANCER CHEMOTHERAPY AGENTSamethopterin-Methotrexatecyclophosphamide-Cytoxan

CATHARTICSdanthron-Dorbane, Modane

DIAGNOSTIC AGENTSiopanoic acid-Telepaquemetrizamide-Amipaque

DIURETICSbendroflumethiazide-Naturetinchlorothiazide-Diuril, Chlotridechlorthalidone-Hygroton, Combipresmethyclothiazide-Aquatensen, Enduronspironolactone-Aldactone

HORMONESchlorotrianisene-TACEestradiol-Estrace3H-norethynodrel-Enovidprednisone-Deltasone, Meticorten, SK-Prednisone

MUSCLE RELAXANTSbaclofen-Lioresalcarisoprodol-Rela, Somamethocarbamal-Robaxin

NARCOTICS, NON -NARCOTIC ANALGESICS,ANTIINFLAMMATORY AGENTS

acetaminophen-Tylenol, Tylenol Extra Strength, Tern-pra, Phenaphen

butorphanol-Stadolflufenamic acid-Arlefgold sodium thiomalate-Myochrysineibuprofen-Motrinindomethacin-Indocinmefenamic acid-Ponstelmeperidine-Demerol, Pethadolmethadone-Westadonenaproxen-Naprosynphenylbutazone-Azolid, Butazolidin

prednisolone-Delta-Cortef, Steranepropoxyphene-Darvon, SK65, Dolene

PSYCHOTROPIC AGENTSamitriptyline-Elavil, Endepamoxapine-Asendinchlordiazepoxide-Librium, Libritabs, Menrium, SK-Ly-

genchlorpromazine-Thorazineclorazepate-Tranxenedesipramine-Norpramin, Pertofrane

diazepam-Valiumdichloralphenazone-Fenzal, Welldormdothiepin-Prothiadenhaloperidol-Haldolimipramine-Tofranil, SK-Pramine, Imavatemeprobamate-Equanil, Miltown, Meprospan, 5K-Ba-

matemesoridazine-Lidanaroxazepam-Seraxpiperacetazine-Quideprazepam-Centraxprochlorperazine-Compazine

thioridazine-Mellariltranylcypromine-Parnatetrifluoperazine-Stelazine

STIMULANTS

amphetamine (dexamphetamine sulfate)-Dexedrinebromocriptine-Parlodelergotamine tartrate with caffeine-Cafergot

MISCELLANEOUSacetamide-Colchicinebethanechol chloride-Urecholinecimetidine-Tagametdiphenoxylate with atropine-Lomotiltolbutamide-Orinase, SK-Tolbutamide

FOOD ADDITIVESmonosodium glutamate-MSGsaccharin-Sucaryl

COMMITTEE ON DRUGS, 1982-1983

Albert W. Pruitt, MD, Chairman

Walter R. Anyan, Jr, MD

Reba M. Hill, MDRalph E. Kauffman, MDHoward C. Mofenson, MD

Harvey S. Singer, MD

Stephen P. Spielberg, MD, PhD

Liaison Representatives

John C. Ballin, PhDCharlotte Catz, MD

Louis Farchione, MD

Martha M. Freeman, MD

Jennifer Niebyl, MD

Dorothy L. Smith, PharmD

Sam A. Licata, MD

Godfrey Oakley, MD

Steven Sawchuk, MS

Section Representatives

Earl J. Brewer, MD 0John A. Leer, MD



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The Transfer of Drugs and Other Chemicals into Human Breast Milk · Chlorotrianisene None 51 3H-norethynodrel None 94 19 norsteroid None 95 Contraceptive pill with estrogen/progester-

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