Promoting Drug Safety During Breastfeeding

The American Academy of Pediatrics (AAP), and the CDC endorse exclusive breastfeeding for the first 6 months of life.^1,2 Breastfed babies are less likely to experience otitis media, respiratory tract infections, asthma, and dermatitis.³ Mothers experience benefits such as accelerated recovery from childbirth and reduced rates of ovarian and breast cancer compared to women who never breastfed.³ Psychological benefits such as infant/maternal bonding are also improved with breastfeeding.³ The economic burden associated with not breastfeeding (increased direct costs of formula and indirect costs associated with disease risk) is estimated to be over $13 billion annually.¹

The Department of Health and Human Services Healthy People 2020 objective plan promoted breastfeeding initiation as one of the priorities to improve the nation’s health.⁴ The CDC published a breastfeeding report card that captured the rates of meeting the 2020 targets based on 2016 data.² Despite this strong support, persistence patterns and exclusive use of breast milk as a nutrition source require attention because half of all women who start breastfeeding have stopped by 6 months.⁴

Pharmacists can help promote breastfeeding and keep women from weaning their babies too early by identifying and providing solutions to barriers that affect breastfeeding persistence.⁵

There are few medical contraindications to breastfeeding, such as HIV, untreated tuberculosis, or herpes simplex virus (HSV) lesions on the breast.⁵ Medication contraindications include illicit drug use, antimetabolites, chemotherapy, and radioactive treatments.

Related article: Babies Should Receive HepB Vaccine Immediately After Birth

Some of the perceived barriers include a lack of knowledge of the benefits of breastfeeding, social norms, little family or health professional support, and lactation complications.⁵ Despite the positive outcomes associated with breastfeeding, patient knowledge of the benefits of nursing over formula is low.⁶ If education about the benefits breastfeeding is lacking, then pharmacists are well positioned to provide this education to women and their families and provide women with support so they can persist with breastfeeding for the first 12 months of their baby’s life.

Complications of breastfeeding may influence persistence rates. Commonly reported maternal complications associated with nursing include insufficient milk supply, sore nipples or breast pain, engorged breasts, infection, and the infant improperly latching onto nipple.^7,8 Poor latching can contribute to problems such as insufficient nutrition for the baby and cracked nipples, blocked milk ducts, and infections in the mother. 

Approximately half of all mothers who initiate breastfeeding stop nursing because of insufficient milk supply, which may be due to infrequent feedings or poor technique. 

Pharmacists can refer patients to their health-care professional and/or to a lactation consultant to review the patient’s technique and provide additional education. Pharmacists should assess the patient’s OTC and prescription medication lists associated with reduced milk supply. These could include estrogen-containing contraceptives, oral decongestants and antihistamines, nicotine use, and diuretics.⁹ Although complementary herbal products such as fenugreek and milk thistle to boost milk production are used by many patients, safety data on them is limited and their use should be discouraged.^7-9 Furthermore, some herbal products may contain pesticides that may be harmful to the infant.

Pharmacists should encourage patients to apply a few drops of expressed breast milk to nipples after feeding and allowing the area to air dry. Over the counter options that can be applied directly to the nipples after feeding include purified lanolin and hydrogel dressings to promote healing. Patients should be triaged for self-care exclusions such as bacterial or fungal infection. Red flags for infection include fever, breast pain, and burning nipples with pain and redness. These patients should be referred to their health-care professional for evaluation.

Although mothers may be advised to discontinue breastfeeding if they are taking some medications or to stop taking medications while they breastfeed, this is not always necessary.^5,8 The benefits of nursing need to be considered along with any risks associated with medication exposure. Pharmacists are best equipped to assess drug properties associated with increased exposure in breast milk, such as high bioavailability, small molecular weight, low serum protein binding, lack of ionization, high lipid solubility, or a long half-life.^8-11 The timing and duration of the medication regimen also influences exposure to the infant. For example, the risk associated with a single dose treatment is much less than if the same product was administered daily for a week.

Pharmacists can develop a medication schedule for the patient that can minimize systemic infant exposure (Table 1). Patients can be instructed to take their medication immediately after feeding the baby so that the baby’s exposure is minimized. They can also collaborate with the mother’s health-care provider to identify medication formulations that minimize risk, such as switching from sustained release to immediate release or choosing a formulation with less systemic absorption such as a topical or inhaled product. Systemic exposure is also influenced by the infant’s age. Premature infants and or those with organ dysfunction may be more prone to systemic exposure compared to those born full-term. 

FDA labelling changes for new prescription products provide more guidance to health-care professionals on the safety of medications during breastfeeding.¹² The three categories added to the lactation section include risk summary and clinical considerations and data, compared to previous recommendations that cautioned against breastfeeding in conjunction with medication administration. Unfortunately, this labelling change does not affect OTC products or previously approved prescription agents. Pharmacists should become familiar with readily accessible resources available to assess medication exposure and interpret the clinical risk (Table 2).

Lactation Considerations: Nicotine and Alcohol Avoidance

Mothers who use illicit substances should not breastfeed.⁹ They should avoid alcohol because it may contribute to reduced milk production and also because it passes into breast milk. An occasional, small alcoholic drink is acceptable, but breastfeeding should be avoided 2 hours after consumption of any alcoholic beverage. Mothers who smoke may still breastfeed, but infant exposure to secondhand smoke should be minimized and mothers should be supported and encouraged to quit smoking.

Infant and Maternal Supplements

Prenatal vitamins may be continued during breastfeeding and are considered safe.¹ Breastmilk does not contain adequate amounts of Vitamin D or iron.⁸ The AAP recommends that all breastfed infants receive 400 IU vitamin D daily within the first few days of life.¹ Once the child reaches 1 year of age and switches to at least 1 quart of whole cow’s milk daily, vitamin D supplementation may be discontinued. Iron supplementation is recommended for full-term breastfed infants until around 6 months when solid foods are introduced. Vitamin D and iron are available in most multivitamin supplements so that a parent can synchronize doses. Pharmacists can evaluate supplementation products to support the health and development breastfed infants since most infant vitamin products are OTC.

Contraception 

Women who resume contraception after delivery need to consider how many weeks postpartum they are and which method of birth control they wish to use.^13,14 Progestin-only products are safe for use during breastfeeding, but are safest if postponed until 6 weeks postpartum. Combined oral contraceptives containing estrogen should be avoided during the first month of breastfeeding. Estrogen can cause a decrease in milk production resulting in an inadequate supply for the infant.

OTC Products

Breastfeeding mothers should take many precautions while using OTC medications for pain, cough, cold, and allergies.^15,16 Acetaminophen is the safest OTC analgesic for nursing mothers. The amount of acetaminophen exposure in breast milk is less than concentrations observed using therapeutic doses administered to infants. If an NSAID is preferred, ibuprofen is optimal because of its short half-life and reduced systemic exposure. The lowest dose and frequency should be used. NSAIDS with a longer half-lives such as naproxen should be avoided. Aspirin use is discouraged because of the risk to the baby of Reye’s syndrome.

Saline nasal spray is the safest option for congestion.¹⁶ Oral decongestants are associated with reduced milk supply and infant irritability. If the mother requires a decongestant, pseudoephedrine is preferred over phenylephrine due to the lack of human data reports on phenylephrine, but this option should be discussed with the health-care professional. Instruct the mother to take the dose right after breastfeeding her baby and recommend that she use immediate-release formulations rather than sustained-release and combination products to minimize drug exposure. Nasal pseudoephedrine may minimize systemic concentrations. Intranasal steroids are acceptable to use while breastfeeding because the detectable amounts of these drugs found in breast milk have not been linked to harm or damage to the infant if used appropriately.

Related article: FDA Issues New Label Change for Codeine and Tramadol

Second-generation antihistamines such as loratadine, cetirizine, fexofenadine, and desloratadine are preferred because the anticholinergic properties of first-generation agents may contribute to reduced milk supply and infant irritability.^16,17 Second-generation agents are detected in small amounts in breast milk, but are associated with less sedation and milk supply reduction than first generation products such as diphenhydramine and chlorpheniramine. Loratadine and cetirizine need to be taken at the lowest possible dose, but there are no dosing restrictions for fexofenadine and desloratadine. Encourage moms to take the antihistamine dose at bedtime to minimize exposure.

Breastfeeding mothers seeking cough relief should first try nonpharmacological options, such as using a humidifier, drinking warm beverages, and remaining hydrated, due to the lack of data on other agents.^11,16 There are limited published data on the excretion of dextromethorphan and guaifenesin in breast milk. These agents are unlikely to cause any harm to infants over 2 months old. Avoid any OTC antitussives/expectorant products containing alcohol to minimize potential sedation in the infant. If the mother isinstructed by her doctor to use a medication to relieve symptoms of a cough, an alcohol-free version is preferred. Codeine products should be avoided during breastfeeding because toxicity such as drowsiness, sedation, and difficulty breathing may occur. This is especially true the mother has a 2D6 enzyme mutation that results in a faster metabolic breakdown and increased opiate concentrations. Mothers with this mutation are at a greater risk of morphine toxicity when taking codeine.

Vitamin C and echinacea are often used by patients to manage or prevent colds.^11,16 Echinacea should be avoided women who are breastfeeding because some echinacea products have been found to be contaminated. ^R Vitamin C may be used when dosing adjustments are considered. Adult patients should not exceed 2 g/day of vitamin C.

Vaccinations

Vaccines provide an excellent source of protection and should be considered in breastfeeding mothers where indicated.¹⁸ Most pregnant women receive pertussis (Tdap) and inactivated influenza vaccinations during their pregnancy to protect the baby from serious complications and to provide some short-term immunity. Influenza vaccine should be offered to breastfeeding mothers if there are no other contraindications, but live influenza vaccine is not recommended. Table 3 summarizes the CDC recommendations for various vaccines.

Anti-infectives

The majority of antibiotics are excreted in breast milk in small concentrations.^1,8 There is a theoretical concern regarding the safety of breastfed infants whose mothers, are taking antibiotics because of alteration of normal bowel flora, possible abnormal culture results if a fever occurs in the breastfed infant, and allergic reactions.

The AAP considers penicillins, cephalosporins and erythromycin compatible with breastfeeding.¹ Side effects that may occur with these antibiotics include diarrhea, rash, and thrush. Other macrolides such as azithromycin and clarithromycin have low systemic concentrations in infants of breastfeeding mothers, although some evidence suggests that infants may be at higher risk of gastric outlet obstruction with use. Sulfamethoxazole/trimethoprim is considered compatible with breastfeeding, but it should be avoided in jaundiced, sick, stressed, or premature babies due to the possibility of bilirubin displacement and kernicterus. Short-term use of tetracycline and fluoroquinolones is also compatible with breastfeeding, but absorption by the infant may be reduced by the calcium in breast milk. Topical ophthalmic and otic quinolones are believed to have reduced exposure to the infant.

Metronidazole is excreted in breast milk in concentrated amounts.⁸ Case reports have shown diarrhea as well as oral and rectal Candida infection in infants. Women should be instructed to postpone breastfeeding for 12 to 24 hours following a 2-gram single dose. Topical and vaginal formulations of metronidazole are believed to have reduced concentrations in breast milk.

Azole antifungals are used for Candida infection of the nipples, milk ducts, and vagina in breastfeeding mothers.⁸ Topical formulations may be applied to the nipples after feeding and wiped off prior to the next feeding. Oral fluconazole is considered second line, but may be used for more severe infections.¹

Gastrointestinal Diseases

Nonpharmacological intervention for nausea is preferred and includes practices such as smaller meals, a bland diet, and hydration. Antihistamines including meclizine, doxylamine, and diphenhydramine should be avoided because of the milk-supply-lowering anticholinergic effects.^17,19 Occasional low doses of hydroxyzine are not likely to have any adverse effects on the infant. Limited data is available for metoclopramide, ondansetron, and phenothiazines. If these are used, the infant should be monitored for drowsiness.

There are limited data about the use of simethicone for flatulence, but it is minimally absorbed.¹⁸ Loperamide for diarrhea is considered compatible with breastfeeding. Magnesium hydroxide (milk of magnesia), bisacodyl, and senna are preferred pharmacologic agents for constipation. 

Calcium-containing products such as calcium carbonate are acceptable for gastroesophageal reflux disease in lactating women.¹⁹ Famotidine is preferred if an H² antagonist is preferred for longer-term use because it is excreted in a smaller amount compared to other products in the class. Proton pump inhibitors such as 20 mg of esomeprazole and omeprazole or 40 mg of pantoprazole have not been shown to cause adverse effects in babies and are only slightly excreted in breastmilk. Use of sucralfate for peptic ulcer disease and gastroesophageal reflux disease is considered acceptable due to its low absorption potential.

Conclusion

Pharmacists are well-positioned to influence new mothers to continue with breastfeeding. Patient education can include providing information on the benefits of breastfeeding, offering referral and education to address complications with lactation, selecting products to enhance nutrition in the breastfed infant, and identifying the safest drug selection and schedules to minimize infant exposure.  

References

1. American Academy of Pediatrics. Breastfeeding and the Use of Human Milk. Pediatrics 2012; 129(3) e827-e841.

2. Centers for Disease Control and Prevention. Breastfeeding Report Card; 2016. Available at https://www.cdc.gov/breastfeeding/pdf/2016breastfeedingreportcard.pdf. Accessed on Oct. 17. 2017/

3. Ip S, Chung M, Raman G, et al. Breastfeeding and Maternal and Infant Health Outcomes in Developed Countries. Evidence Report/Technology Assessment No. 153 (Prepared by Tufts-New England Medical Center Evidence-based Practice Center, under Contract No. 290-02-0022). AHRQ Publication No. 07-E007. Rockville, MD: Agency for Healthcare Research and Quality. April 2007.

4. U.S. Department of Health and Human Services, Office of Disease Prevention and Health Promotion Healthy People 2020. Available at https://www.healthypeople.gov/2020/topics-objectives/topic/maternal-infant-and-child-health. Accessed on Aug. 1, 2017.

5. U.S. Preventive Services Task Force, Bibbins-Domingo K, Grossman DC, et al. Primary care interventions to support breastfeeding: U.S. Preventive Services Task Force recommendations statement. JAMA 2016;316:1688-93.

6. Li R, Fein SB, Chen J, Grummer-Strawn LM. Why mothers stop breastfeeding: Mothers‘ self-reported reasons for stopping during the first year. Pediatrics 2008; Oct;122, (Suppl 2):S69–S76.

7. PL Detail-Document, Common breastfeeding complications. Pharmacist’s Letter/Prescriber’s Letter. December 2016.

8. American Academy of Pediatrics Committee on Drugs. Transfer of drugs and other chemicals into human milk.Pediatrics 2001;108:776-89.

9. Organization of Teratology Experts. Mother to baby. Available at https://mothertobaby.org/. Accessed on Aug. 1, 2017.

10. Briggs, G., Freeman, R., Towers C., Forinash A. 2017 Drugs in Pregnancy And Lactation: A Reference Guide to Fetal and Neonatal Risk. Philadelphia, PA: Lippincott Williams & Wilkins.

11. National institutes of Health. LactMed Database Available at https://toxnet.nlm.nih.gov/newtoxnet/lactmed.htm. Accessed on Aug. 1, 2017.

12. Food and Drug Administration. Pregnancy and Lactation Labeling: Final Rule [cited 10/13/17]. Available from: https://www.fda.gov/drugs/developmentapprovalprocess/developmentresources/labeling/ucm093307.htm

Curtis KM, Tepper NK, Jatlaoui TC, et al. U.S. Medical Eligibility Criteria for Contraceptive Use, 2016. MMWR Recomm Rep 2016;65(No. RR-3):1–104. DOI: http://dx.doi.org/10.15585/mmwr.rr6503a1

13. Berens, P, Labbok, M, and The Academy of Breastfeeding Medicine. Breastfeeding Medicine. January 2015, 10(1): 3-12. https://doi.org/10.1089/bfm.2015.9999

14. Clinical Resource. Analgesics in pregnancy and lactation. Pharmacist’s Letter/Prescriber’s Letter. June 2017.

15. PL Detail-Document. Cough and cold meds in pregnancy and lactation. Pharmacist’s Letter/Prescriber’s Letter. November 2013.

16. So M, Bozzo P, Inoue M, Einarson A. Safety of antihistamines during pregnancy and lactation. Canadian Family Physician. 2010;56(5):427-429.

17. Centers for Disease Control [internet]. Breastfeeding and Vaccinations [accessed 8/1/17]. https://www.cdc.gov/breastfeeding/recommendations/vaccinations.htm

18. PL Detail-Document, GI Med use in pregnancy and lactation. Pharmacist’s Letter/Prescriber’s Letter. June 2013.