C. Zip, MD, FRCPC
Department of Medicine, University of Calgary, Calgary, Alberta, Canada
Use of medications by breast-feeding mothers is not uncommon. When prescribing a medication to a nursing mother, the physician must weigh the potential risk of exposing the infant to the medication or the risks of not breast-feeding against the benefits of the medication to the mother. Information regarding the safety of common dermatological medications during lactation will be reviewed. Based on this information, treatment recommendations will be made.
breast-feeding, antimicrobials, antihistimines, immunomodulators, antipsoriatics, steriods, scabicides, anti-acne agents
Breast-feeding provides optimal nutrition in the first 6 months of life. Well documented benefits of breast-feeding include a decreased incidence of infantile diarrhea1 and infection.2 Other studies show a possible protective affect against sudden infant death syndrome,3 insulin dependent diabetes mellitus,4 Crohn’s disease,5 ulcerative colitis,5 lymphoma,6 and allergic disorders.7 The American Academy of Pediatrics (AAP) recommends exclusive breastfeeding for the first six months of life, continuing to a year or beyond with the addition of solid food at 6 months of age.8 In Canada, approximately 80% of new mothers initiate breast-feeding,9 while 30-40% are still nursing 6 months postpartum.10 Corresponding US figures are 64% and 29%, respectively.11
The use of prescription and over-the-counter (OTC) medications is common for nursing mothers. In one study of 14,000 pregnant or breastfeeding women, 79% of them took at least one medication, while on average, 3.3 drugs were taken while breastfeeding.12 Fortunately, severe adverse effects resulting from the presence of common medications in breast milk are uncommon. Of 838 infants exposed to medications through breast milk, 11% experienced minor reactions, and no serious reactions requiring medical attention or cessation of breastfeeding occurred.13 The adverse reactions that did occur were consistent with the known pharmacological affects of the causative agent.
Transfer of Medications into Breast Milk
A number of factors determine the passage of a drug into breast milk. These include characteristics of the mother, the infant and the drug itself. In general, drugs given to a nursing mother reach the infant in much lower concentrations than those given to a pregnant woman reach the fetus.14
Penicillins and cephalosporins are present only in trace amounts in breast milk, and are compatible with breast-feeding.15 Their use is associated with a remote risk of alterations in gastrointestinal flora causing diarrhea and allergic sensitization of the infant.16 Erythromycin is excreted into breast milk, but no adverse effects in infants exposed to this drug in breast milk have been reported,16 and it is considered compatible with breastfeeding by the AAP. Caution may be in order in when prescribing erythromycin to lactating mothers of newborns however, because of recent reports of pyloric stenosis in neonates treated with erythromycin.17,18 It has been reported that the calcium present in breast milk may inhibit absorption of the small amount of tetracycline, however, use of tetracycline while breastfeeding is not advised, because the threshold for its affect on teeth and bone is unknown.14 Topical clindamycin is partially absorbed through the skin and small amounts may pass into breast milk. No problems have been reported in nursing infants with maternal use of topical clindamycin,19 although bloody diarrhea was reported in an infant of a mother on intravenous clindamycin.20 No adverse effects on the infant have been reported with use of topical metronidazole during lactation, however the manufacturer advises against its use while breast-feeding.21
Acyclovir is considered safe during breast-feeding.15,16 Experience with the use of valacyclovir and famciclovir during human lactation is lacking.16
Terbinafine and itraconazole are both excreted in breast milk, and the safety of their use during lactation is unknown. Parenteral fluconazole has been safely used in neonates with candidiasis, and based on this, Briggs states that its use is probably safe during breast-feeding.16 The manufacturers of these three antifungals do not recommend their use while breast-feeding and the AAP has no rating.22,23,24
Small amounts of antihistamines are excreted in breast milk. Their use is not recommended during breast-feeding because infants may be more susceptible to their adverse effects, particularly drowsiness and irritability.19,25 Antihistamines may also reduce milk production in some women.
Both cyclosporine and methotrexate are excreted into breast milk, and considered contraindicated during breast-feeding by the AAP because of the possibility of immunosuppression, neutropenia, carcinogenesis and unknown affects on growth.15 Hydroxychloroquine is excreted in small amounts in breast milk and because of its slow elimination rate and potential to accumulate to toxic levels in infants, caution is advised with daily dosing.26 The AAP, however, considers hydroxychloroquine to be compatible with breast-feeding.15 Tacrolimus is excreted in human milk. Topical tacrolimus is not recommended by the manufacturer during breastfeeding, because of the potential for systemic absorption with topical use.27 The AAP does not rate tacrolimus.
It is not known whether calcipotriol is excreted into breast milk. The manufacturer recommends its use only if the anticipated benefits outweigh the potential risks.28 Methoxsalen excretion in human milk is also unknown and although there are no reports of adverse effects with its use during lactation, the manufacturer recommends use only when the probable benefits outweigh the potential risks.29 Briggs recommends that breast-feeding be interrupted for at least 24 hours after administration of the drug because of its photosensitizing affect.16
Trace amounts of prednisone and its metabolite prednisolone are excreted in breast milk.16 The AAP considers prednisone to be compatible with breastfeeding.15 Hypertension was reported in the infant of a woman who used a corticosteroid on the nipples.30 Use of topical corticosteroids on the breasts prior to nursing should be avoided.
Because estrogen decreases the quantity and protein content of breast milk, the use of combination oral contraceptive pills should be avoided whenever possible in lactating mothers, especially in the first two months postpartum.31
It is not known if permethrin is excreted in human milk. Citing evidence of teratogenicity in animals, the manufacturer recommends temporary discontinuation of nursing or avoidance during lactation.32 Anderson considers its use to be safe during lactation.33
Significant salicylate levels have been found in breast-fed neonates of mothers taking salicylates, raising concerns about metabolic acidosis, bleeding, altered pulmonary circulation and Reye’s syndrome.26 There is one report of salicylate intoxication in an infant exposed through her mother’s milk.34 The AAP recommends that it be used with caution in nursing mothers.15 Widespread use of topical salicylic acid should be avoided because of the potential for significant systemic absorption. Of the nonsteroidal anti-inflammatories, ibuprofen and flurbiprofen have the best documentation of safety during lactation because they do not enter breast milk in significant quantities.14 The AAP considers ibuprofen, indomethacin, and naprosyn to be compatible with breast-feeding.15 There is one case report of seizures in an infant exposed to indomethacin through breast milk.35
There have been no reports of adverse effects from use of topical benzoyl peroxide and topical tretinoin during lactation.19 It is not known whether adapalene or tazarotene pass into breast milk. The manufacturers recommend caution with their use during lactation.36,37 Spironolactone may pass into breast milk, but has not been reported to cause problems in nursing babies.19 The AAP considered spironolactone to be compatible with breastfeeding, 15 although its use during lactation is not recommended by the manufacturer.38
|Class of Medication||Choices Compatible with Breast-Feeding||Comment|
Penicillins, Cephalosporins, Erythromycin (caution with neonates), Topical clindamycin, Topical metronidazole
Possibility of diarrhea, thrush and allergic sensitization of the infant
Considered safe during breastfeeding
Manufacturer does not recommend its use during lactation.
Infants may be more susceptible to their adverse effects
Methotrexate and cyclosporine are not recommended
No reports of adverse effects
Trace amounts of prednisone are present in breast milk. Avoid use of topical corticosteroids on breasts prior to nursing. Delay use until milk production established; may reduce milk production.
Probably safe; consider temporary discontinuation of breastfeeding.
Ibuprofen does not enter breast milk in significant amounts.
No reports of adverse effects
Table 1: Compatibility of some dermatologic drugs during breastfeeding.
When considering a medication for a lactating mother, the benefits of breast-feeding need to be weighed against the potential risk of exposure of the infant to the drug in question. For the majority of dermatological conditions, alternatives that are compatible with breast-feeding are available, or treatment can be safely postponed until lactation is completed.
- Popkin BM, Adair L, Akin JS, et al. Breast-feeding and diarrheal morbidity. Pediatrics 1990; 86: 874-882.
- Beaudry M., Dufour R, Marcoux S. Relation between infant feeding and infections during the first six months of life. J Pediatr 1995; 126: 191-197.
- Ford RPK, Taylor BJ, Mitchell EA, et al. Breastfeeding and the risk of sudden infant death syndrome. Int J Epidermiol 1993; 22: 885-890.
- Mayer EJ, Hamman RF, Gay EC, et al. Reduced risk of IDDM among breast-fed children. Diabetes 1988; 37:1625-1632.
- Rigas A, Rigas B, Glassman M, et al. Breast-feeding and maternal smoking in the etiology of Crohn’s disease and ulcerative colitis in childhood. Ann Epidemiol 1993; 3:387-392.
- Davis MK, Savitz DA, Graubard BI. Infant feeding and childhood cancer. Lancet 1988; 2:365-368.
- Gdalevich M, Mimouni D, David M, Mimouni M. Breast-feeding and the onset of atopic dermatitis in childhood: A systematic review and meta-analysis of prospective studies. J Am Acad Dermatol 2001; 45: 520-527.
- American Academy of Pediatrics, Work Group on Breastfeeding. Breastfeeding and the use of human milk. Pediatrics 1997; 100: 1035-1039.
- Barber CM, Abernathy T, Steinmetz B, Charlebois J. Using a breastfeeding prevalence survey to identify a population for targeted programs. Can J Public Health 1997; 88:242-245.
- Bourgoin G, Lahaie N, Rheaume B, et al. Factors influencing the duration of breastfeeding in the Sudbury region. Can J Public Health 1997; 88: 238-241.
- Ryan AS. The resurgence of breastfeeding in the United States. Pediatrics 1997; 99:E12.
- Collaborative Group on Drug Use in Pregnancy. Medication during pregnancy: An intercontinental cooperative study. Int J Gynecol Obstet 1992; 39:185–196.
- Ito S, Blajchman A, Stephenson M, et al. Prospective follow-up of adverse reactions in breastfed infants exposed to maternal medication. Am J Obstet Gynecol 1993; 168:1393-1399.
- Howard CR, Lawrence RA. Drugs and breastfeeding. Clin Perinatology 1999; 26: 447-478.
- American Academy of Pediatrics Committee on Drugs. The transfer of drugs and other chemicals into human milk. Pediatrics 1994; 93:137-150.
- Briggs GG, Freeman RK, Yaffee SL. Drugs in pregnancy and lactation, Fifth Edition, Baltimore: Williams and Wilkins, 1998.
- Anonymous. Erythromycin – induced pyloric stenosis in infants. Prescrire International 2001; 10:16.
- Honein MA, Paulozzi LJ, Himelright IM, et al. Infantile hypertrophic pyloric stenosis after pertussis prophylaxis with erythromycin: A case review and cohort study. Lancet 1999; 354: 2101-2105.
- USP- DI. Drug Information for the Health Care Professional, Vol. 1, Nineteenth Edition, Taunton, MA: Rand McNally, 1999.
- Mann CF. Clindamycin and breast-feeding. Pediatrics 1980; 66:1030-1031.
- Metronidazole product monograph, Galderma Canada Inc., Thornhill, ON, Canada, 1996.
- Terbinafine product monograph, Novartis Pharmaceuticals Canada Inc., Dorval, QC, Canada, 2002.
- Itraconazole product monograph, Janssen-Ortho Inc., Toronto, ON, Canada, 2002.
- Fluconazole product monograph, Pfizer Canada Inc., Kirkland, QC, Canada, 2001.
- Reed BR, Dermatologic drug use during pregnancy and lactation. Dermatol Clinics 1997; 15:197-202.
- Janssen NM, Genta MS. The effects of immunosuppressive and antiinflammatory medications on fertility, pregnancy and lactation. Arch Intern Med 2000; 160:610-619.
- Tacrolimus product monograph, Fujisawa Canada Inc., Markham, ON, Canada, 2001.
- Calcipotriol product monograph, Leo Pharma Inc., Thornhill, ON, Canada, 2001
- Methoxsalen product monograph, ICN Canada Ltd. Montreal, QC, Canada, 1992.
- DeStefano P, Bongo C, Borgna – Pignatti C, et al. Factitious hypertension with mineralocorticoid excess in infants. Helv Paediatr Acta 1983; 38:185-189.
- Spencer JP,Gonzalez LS, Barnhart DJ. Medications in the breast-feeding mother. Am Fam Phys 2001; 64:119-126.
- Permethin product monograph, Glaxo Smith Kline,Mississauga, ON, Canada, 2002.
- Anderson PO. Drug use during breast-feeding. Clin Pharm 1991; 10:594-624.
- Clark JH, Wilson WG. A 16-day-old breast-fed infant with metabolic acidosis caused by salicylate. Clin Pediatr 1981; 20:53-54.
- Eeg-Olofsson O,Malmros I, Elwin CE, Steen B. Convulsions in a breast-fed infant after maternal indomethacin. Lancet 1978; 2:215.
- Adapalene product monograph, Galderma Canada Inc., Thornhill, ON, Canada, 2002.
- Tazarotene product monograph, Allergan, Markham, ON, Canada, 2001.
- Spironolactone product monograph, Pharmacia Canada Inc., Mississauga, ON, Canada, 2001.
Schering-Plough Recalls Specific Lots of Claritin-D® 12-hour Tablets
In February 2002, Shering-Plough announced a voluntary recall of specific lots of Claritin-D® 12-hour (5mg loratidine/120mg pseudoephedrine sulfate) tablets directed to wholesale accounts and retail pharmacies. These products were manufactured between August 1999, and June 2001. They are indicated for the relief of symptoms of seasonal allergic rhinitis.
Schering-Plough as part of its standard quality-control procedures conducted stability testing of specific lots of this product including dissolution tests to determine the rate that tablets dissolve and the amount of active ingredients released. Test results indicated that some tablets in these lots did not demonstrate full release of pseudoephedrine at the 5th hour per specification, although be 25 minutes later all tested samples met specifications for releasing the decongestant component. The company believes that this short delay poses no medical risk to patients.
This recall is being conducted with the knowledge of the US FDA.