The Transfer Of Drugs And Other Chemicals Into Human Breast Milk
- 1. The Transfer of Drugs and Other Chemicals into Human Breast Milk Committee on Drugs Pediatrics 1983;72;375-383 The online version of this article, along with updated information and services, is located on the World Wide Web at: http://www.pediatrics.org PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly publication, it has been published continuously since 1948. PEDIATRICS is owned, published, and trademarked by the American Academy of Pediatrics, 141 Northwest Point Boulevard, Elk Grove Village, Illinois, 60007. Copyright © 1983 by the American Academy of Pediatrics. All rights reserved. Print ISSN: 0031-4005. Online ISSN: 1098-4275. Downloaded from www.pediatrics.org by on August 20, 2009
- 2. 0 Committee on Drugs The Transfer of Drugs and Other Chemicals into 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-feeding known 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 1 with carcinogenesis Bromocriptine Suppresses lactation 2 Cimetidinet 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 4 Cyclophosphamide* Possible immune suppression; unknown effect on growth or association 5 with carcinogenesis Ergotamine Vomiting, diarrhea, convulsions (doses used in migraine medications) 6 Gold salts Rash, inflammation of kidney and liver 7, 8 Methimazole Potential for interfering with thyroid function 9 Phenindione Hemorrhage 10 0 Thiouracil 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, 13 Radiopharmaceuticals Radioactivity present in milk, consult nuclear medicine physi- cian before performing diagnostic study so that radionuclide which has shortest excretion time in breast milk can be used; prior to study the mother should pump her breast and store enough milk in freezer for feeding the infant; after study the mother should pump her breast to maintain milk production but discard all milk pumped for the required time 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 15 Iodine-131 (‘‘I) Radioactivity in milk present 2-14 d depending on study. 16-19 Radioactive sodium Radioactivity in milk present 96 h 20 Technetium-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 lists is medically indicated. is not meant to imply that it is not transferred into These reports have been obtained from a search breast milk or that it does not have an effect on the of the medical literature. Because methodologies used to quantitate drugs in breast milk continue to 0 PEDIATRICS (ISSN 0031 4005). Copyright © 1983 by the improve, current information will require continu- American Academy of Pediatrics. ous updating of the tables. Brand names are listed PEDIATRICS Vol. 72 No. 3 September 1983 375 Downloaded from www.pediatrics.org by on August 20, 2009
- 3. TABLE 3. Maternal Medication Usually Compatible with Breast-Feeding Drug Reported Sign or Symptom in Infant or Effect Reference on Lactation ANESTHETICS, SEDATIVES o Alcohol Drowsiness, diaphoresis, deep sleep, weak- 26, 27 ness, decrease in linear growth, abnormal weight gain; maternal ingestion of 1 g/kg daily decreases milk ejection reflex Barbiturate None; see antiepileptic drugs 28 Bromide Rash, weakness, absence of cry with mater- 29 nal intake of 5.4 g/d Chloral hydrate Sleepiness 30 Chloroform None 31 Halothane None 32 Magnesium sulfate None 33 Methyprylon Drowsiness 34 Secobarbital None 35 ANTICOAGULANTS Bishydroxycoumarin None 36 Warfarin None 37 ANTIEPILEPTICS Carbamazepine None 38 Ethosuximide None 39 Phenobarbital Methemoglobmemia case); decreased (1 re- 40, 41 sponsiveness, decreased weight gain, ex- cessive sleeping if mother’s plasma level 30 g/mL Phenytoin Methemoglobinemia (1 case) 41 Primidone None 40, 42 Thiopental None 28 Valproic acid None 43 ANTIHISTAMINES, DECONGESTANTS, AND BRONCHODILATORS Dexbrompheniramine maleate with d-iso- Crying, poor sleeping patterns, irritability 44 ephedrine Diphenhydramine None 45 Dyphyllinet None 46 lodides Affects thyroid activity; see miscellaneous 47, 48 iodine Theophylline Irritability 49, 50 Trimeprazine None 51 Tripelennamine None 52 ANTIHYPERTENSIVE AND CARDIO- VASCULAR DRUGS Atenolol None 53 Captopril None 54 Digoxin None 55 Disopyramide None 56 Guanethidine None 47 Hydralazine None 57 Methyldopa None 58 Metoprololt None 53 Nadololt None 59 Propranolol None 60-62 Quinidine None 63 Reserpine Galactorrhea 64 ANTIINFECTIVE DRUGS (ALL antibiotics transfer into breast milk in limited amounts) Amantadine Urinary retention, vomiting, and skin rash 51 Cefadroxil None 65 Cefazolin None 66 Cefotaxime None 65 t Drug is concentrated in breast milk. 376 AGENTS TRANSFERRED INTO HUMAN BREAST MILK Downloaded from www.pediatrics.org by on August 20, 2009
- 4. TABLE 3.-Continued Drug Reported Sign or Symptom in Infant or Effect Reference on Lactation 0 Chloramphenicol None 67, 68 Chloroquine None 69 Clindamycin None 70 Ethambutol None 71 Isoniazid None 72 Nalidixic acid Hemolysis in infant with glucose-6-phos- 73 phate deficiency (G-6-PD) Nitrofurantoin Hemolysis in infant with G-6-PD 74 Pyrimethamine None 75 Quinine None 76 Rifampin None 71 Salicylazosulfapyridine (sulfasalazine) None 77, 78 Sulfapyridine Caution in infant with jaundice or G-6-PD, 77 and ill, stressed, or premature infant Sulfathiazole None; nonabsorbable by mother 79 Sulfisoxazole Caution in infant with jaundice or G-6-PD, 80 and ill, stressed, or premature infant Tetracycline None; negligible absorption by infant 81, 82 Trimethoprim None 83 ANTITHYROID DRUGS Carbimazole Goiter 47, 51 Propylthiouracil None 84 CATHARTICS (Drugs that cause abdominal Abdominal cramping, colic-like syndrome cramping in mother) Danthron Increased bowel activity 85 DIAGNOSTIC AGENTS Iodine Goiter; see miscellaneous, iodine 16 lopanoic None 86 Metrizamide None 87 0 DIURETICS Bendroflumethiazide Suppresses lactation, thrombocytopenia (1 88 case) Chlorothiazide May suppress lactation, therefore avoid 89, 90 prescribing in 1st month of lactation; this may also apply to other thiazides; ques- tionably dose related Chlorthalidone Excreted slowly 91 Methyclothiazide None 92 Spironolactone None 93 HORMONES Chlorotrianisene None 51 3H-norethynodrel None 94 19 norsteroid None 95 Contraceptive pill with estrogen/progester- Breast enlargement, dose related; decrease 96-101 one in milk production and protein content Estradiol Withdrawal, vaginal bleeding 102, 103 MUSCLE RELAXANTS Baclofen None 104 Carisoprodol Drowsiness, intestinal upset 105 Methocarbamol None 106 NARCOTICS, NON-NARCOTIC ANALGE- SICS, ANTIINFLAMMATORY AGENTS Acetaminophen None 107-109 Butorphanol None 110 Codeine None 79 Flufenamic acid None 111 Heroin None 112 O Ibuprofen Indomethacin None Seizure (1 case) 113 115 114, AMERICAN ACADEMY OF PEDIATRICS 377 Downloaded from www.pediatrics.org by on August 20, 2009
- 5. TABLE 3.-Continued Drug Reported Sign or Symptom in Infant or Effect Reference on Lactation Mefenamic acid None 116 Meperidine None 51 0 Methadone None if mother receiving 20 mg/24 h 117 Morphine None 76 Naproxen None 118 Phenylbutazone None 119 Prednisolone, prednisone None 120, 121 Propoxyphene None 122 Salicylates Metabolic acidosis (dose related); may af- 123, 124 fect platelet function, rash PSYCHOTROPIC AGENTS Antianxiety Chlordiazepoxide Conflicting reports of drowsiness 47, 125-127 Clorazepate Diazepam Meprobamatet 51 Oxazepam Prazepamt Antidepressants Amitriptyline None 51, 128-132 Amoxapine Desipramine Dothiepin Imipramine Lithium 133-135 Tranylcypromine 51 Antipsychotic Chlorpromazine Galactorrhea in adult; drowsiness and leth- 136, 137 argy in infant Haloperidol None 138 Mesoridazine None 139 Piperacetazine 0 Prochlorperazine Thioridazine Trifluoperazine Other Marijuanat Unknown, only 1 report in literature 140 STIMULANTS Amphetamine Irritability, poor sleeping pattern 141 Caffeine Irritability, poor sleeping pattern excreted 50, 142, 143 slowly Nicotine (excess) Shock, vomiting, diarrhea, rapid heart rate, 27 restlessness; decreased milk production VITAMINS B1 None 45 B12 None 144 D Increased calcium levels 145 Folic acid None 146 K1 None 147 Pyridoxine None 148, 149 Riboflavin None 150 Thiamin None 150 MISCELLANEOUS Atropine, scopolamine None 79, 151 Bethanechol Abdominal pain, diarrhea 34 Diphenoxylate with atropine None 152 Iodine (providone-iodine/vaginal douche) Elevated iodine levels in breast milk, odor 48 of iodine on infant’s skin Tolbutamide Jaundice 153 0 378 AGENTS TRANSFERRED INTO HUMAN BREAST MILK Downloaded from www.pediatrics.org by on August 20, 2009
- 6. TABLE 4. Food and Environmental Agents: Effect on Breast-Feeding Agent Reported Sign or Symptom in Infant or Effect on Lactation Reference Aspartame Caution in patient carrier of phenylketonuria 154 Bromide (photographic labora- Potential absorption and bromide transfer into milk; 29, 155 see “Anesthetics, Sedatives” 0 tory) Chlordane None reported 156 Chocolate Irritability or increased bowel activity if excess 50, 157 amounts ( 16 oz/d) consumed by mother Cyclamate None 158 DDT, benzenehexachlorides, None 159-162 dieldrin, aldrin, hepatachlore- poxide Fava beans Hemolysis in patient with glucose-6-phosphate defi- 163 ciency (G-6-PD) Fluorides None 164 Hexachlorobenzene Skin rash, diarrhea, vomiting, dark urine, neurotoxic- 165 ity, death Hexachlorophene None; contamination of milk from nipple washing 166 Lead Neurotoxicity 167 Methyl mercury Affects neurodevelopment 168, 169 Monosodium glutamate (MSG) None 170 Polychlorinated biphenyls and Lack of endurance, hypotonia, sullen expressionless 171-173 polybrominated biphenyls facies Saccharin None 51 Tetrachlorethylene (cleaning Obstructive jaundice, dark urine 174 fluid) Vegetarian diet Signs of B12 deficiency 175 t Drug is concentrated in breast milk. at the end of the tables in accordance with the 4th ANTIEPILEPTICS Edition AMA Drug Evaluation. The reference list carbamazepine-Tegretol ethosuximide-Zarontin is not inclusive of all articles published. phenytoin-Dilantin Physicians who encounter adverse effects in in- primidone-Mysoline fants fed breast milk due to exposure to drugs that thiopental-Pentothal are not included here are urged to document the valproic acid-Depakene effects in a communication to the Committee on Drugs of the American Academy of Pediatrics in ANTIHISTAMINES, DECONGESTANTS, AND Evanston. Such communication should include: the BRONCHODILATORS clemastine-Tavegil, Tavist generic and brand name of the drug; the maternal dexbrompheniramine maleate with d-isoephedrine-Drix- dose and mode of administration; the concentration oral, Disophrol Chronotab of the drug in breast milk and maternal and infant diphenhydramine-Benadryl, Benylin cough syrup blood in relation to time of ingestion; the age of the dyphylline-Dilor infant; and the method used for laboratory identi- theophylline-Theo-Dur, Elixophyllin, Slo-Phyllin, Bron- kodyl fication. Such reports may significantly increase trimeprazine tartrate-Temaril the pediatric community’s fund of knowledge re- tripelennamine-Pyribenzamine garding drug transfer into breast milk and the potential risk to the infant. Drugs cited in Tables 1 to 4 are listed here by ANTIHYPERTENSIVE AND CARDIOVASCULAR AGENTS category, in alphabetical order by generic name. For atenolol-Tenormin convenience, one or more examples are also given. captopril-Capoten digoxin-Lanoxin, SK-Digoxin ANESTHETICS, SEDATIVES disopyramide-Norpace methyprylon-Noludar guanethidine sulfate-Ismelin secobarbital-Seconal, Seco-8 hydralazine-Apresoline methyldopa-Aldomet ANTICOAGULANTS metoprolol-Lopressor bishydroxycoumarin-Dicumarol nadolol-Corgard 0 phenindione-Hedulin, Eridione propranolol-Inderal warfarin-Coumadin, Panwarfin reserpine-Serpasil, Reserpoid, Hiserpia AMERICAN ACADEMY OF PEDIATRICS 379 Downloaded from www.pediatrics.org by on August 20, 2009
- 7. ANTIINFECTIVE AGENTS prednisolone-Delta-Cortef, Sterane amantadine-Symmetrel propoxyphene-Darvon, SK65, Dolene cefadroxil-Duricef PSYCHOTROPIC AGENTS cefazolin-Ancef, Kefzol amitriptyline-Elavil, Endep cefotaxime-Claforan amoxapine-Asendin 0 chloramphenicol-Chloromycetin chlordiazepoxide-Librium, Libritabs, Menrium, SK-Ly- chloroquine-Aralen gen clindamycin-Cleocin chlorpromazine-Thorazine ethambutol-Myambutol clorazepate-Tranxene isoniazid-INH desipramine-Norpramin, Pertofrane metronidazole-Flagyl diazepam-Valium nalidixic acid-NegGram dichloralphenazone-Fenzal, Welldorm nitrofurantoin-Furadantin, Nitrofor, Macrodantin dothiepin-Prothiaden pyrimethainine-Daraprim haloperidol-Haldol quinine-Quine imipramine-Tofranil, SK-Pramine, Imavate rifampin-Rifamycin, Rifadin, Rimactane meprobamate-Equanil, Miltown, Meprospan, 5K-Ba- salicylazosulfapyridine-Azulfidine mate sulfisoxazole-Gantrisin mesoridazine-Lidanar tetracycline-Achromycin, SK-Tetracycline oxazepam-Serax trimethoprim with sulfamethoxazole-Bactrim, Septra, piperacetazine-Quide Septra DS prazepam-Centrax ANTITHYROID AGENTS prochlorperazine-Compazine carbimazole-Neo-mercazole thioridazine-Mellaril methimazole-Tapazole tranylcypromine-Parnate propylthiouracil-Propacil trifluoperazine-Stelazine thiouracil-Thiouracil STIMULANTS CANCER CHEMOTHERAPY AGENTS amphetamine (dexamphetamine sulfate)-Dexedrine amethopterin-Methotrexate bromocriptine-Parlodel cyclophosphamide-Cytoxan ergotamine tartrate with caffeine-Cafergot MISCELLANEOUS CATHARTICS acetamide-Colchicine danthron-Dorbane, Modane bethanechol chloride-Urecholine DIAGNOSTIC AGENTS cimetidine-Tagamet iopanoic acid-Telepaque diphenoxylate with atropine-Lomotil 0 metrizamide-Amipaque tolbutamide-Orinase, SK-Tolbutamide DIURETICS FOOD ADDITIVES bendroflumethiazide-Naturetin monosodium glutamate-MSG chlorothiazide-Diuril, Chlotride saccharin-Sucaryl chlorthalidone-Hygroton, Combipres methyclothiazide-Aquatensen, Enduron COMMITTEE ON DRUGS, 1982-1983 spironolactone-Aldactone Albert W. Pruitt, MD, Chairman HORMONES Walter R. Anyan, Jr, MD chlorotrianisene-TACE estradiol-Estrace Reba M. Hill, MD 3H-norethynodrel-Enovid Ralph E. Kauffman, MD prednisone-Deltasone, Meticorten, SK-Prednisone Howard C. Mofenson, MD Harvey S. Singer, MD MUSCLE RELAXANTS baclofen-Lioresal Stephen P. Spielberg, MD, PhD carisoprodol-Rela, Soma Liaison Representatives methocarbamal-Robaxin John C. Ballin, PhD NARCOTICS, NON -NARCOTIC ANALGESICS, Charlotte Catz, MD ANTIINFLAMMATORY AGENTS acetaminophen-Tylenol, Tylenol Extra Strength, Tern- Louis Farchione, MD pra, Phenaphen Martha M. Freeman, MD butorphanol-Stadol Jennifer Niebyl, MD flufenamic acid-Arlef Dorothy L. Smith, PharmD gold sodium thiomalate-Myochrysine Sam A. Licata, MD ibuprofen-Motrin indomethacin-Indocin Godfrey Oakley, MD mefenamic acid-Ponstel Steven Sawchuk, MS meperidine-Demerol, Pethadol Section Representatives methadone-Westadone naproxen-Naprosyn Earl J. Brewer, MD 0 phenylbutazone-Azolid, Butazolidin John A. Leer, MD 380 AGENTS TRANSFERRED INTO HUMAN BREAST MILK Downloaded from www.pediatrics.org by on August 20, 2009
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- 11. The Transfer of Drugs and Other Chemicals into Human Breast Milk Committee on Drugs Pediatrics 1983;72;375-383 Updated Information including high-resolution figures, can be found at: & Services http://www.pediatrics.org Citations This article has been cited by 14 HighWire-hosted articles: http://www.pediatrics.org#otherarticles Permissions & Licensing Information about reproducing this article in parts (figures, tables) or in its entirety can be found online at: http://www.pediatrics.org/misc/Permissions.shtml Reprints Information about ordering reprints can be found online: http://www.pediatrics.org/misc/reprints.shtml Downloaded from www.pediatrics.org by on August 20, 2009