Which medications can be used to increase milk production for improved breastfeeding?

Comment by InpharmD Researcher

There is limited evidence to suggest the use of medications and/or natural products to increase human milk production (galactagogues) improve health-related outcomes in nursing mothers or infants. The majority of the study for galactagogues is in domperidone, a drug not available for human use in the United States. The American College of Obstetricians and Gynecologists (ACOG) does not recommend the first-line use of galactagogues due to lack of efficacy and potential adverse effects. A 2020 Cochrane review cited poor quality of evidence when conducting a meta-analysis of galactagogue safety and efficacy. While the Academy of Breastfeeding Medicine (ABM) does not recommend any specific galactagogues, they do offer a clinical protocol and list of commonly used galactagogues (see Table 1).

Background

American College of Obstetricians and Gynecologists’ Breastfeeding Expert Work Group states, “galactagogues should not be considered a first-line therapy because current research on the effectiveness of pharmaceutical and herbal galactagogues is relatively inconclusive and all substances have potential adverse effects.” [1]

The Academy of Breastfeeding Medicine (ABM) does not recommend any specific galactagogues. They developed a clinical protocol that details stepwise management for insufficient milk production in lactating patients. Nursing mothers should first be screened for pregnancy, medications, primary mammary glandular insufficiency, breast surgery, polycystic ovarian syndrome, hypothyroidism, retained placenta, ingestion of placenta capsules, theca lutein cyst, loss of prolactin secretion following postpartum hemorrhage, heavy smoking or alcohol use. In addition, low-weight infants should be screened to rule out other causes than poor feeding. Next, ensure that the expressing technique and any breast pumps used are effective as galactagogues will not increase the milk supply if there is infrequent or inadequate breast drainage. If clinicians recommend galactagogues they should ensure the patient is aware of medication timing, duration, and potential adverse effects. [2]

The majority of the study of galactagogues is in domperidone. However, per the FDA, "domperidone is not currently a legally marketed human drug and it is not approved for sale in the U.S. On June 7, 2004, FDA issued a public warning that distributing any domperidone-containing products is illegal." They cite risks of cardiac arrhythmias, cardiac arrest, and sudden death associated with domperidone as rationale. [3]

A 2020 Cochrane review identified and analyzed randomized controlled trials of pharmacologic and natural galactagogues to stimulate lactation in mothers. From their search, the pharmacologic regimens consisted of domperidone, metoclopramide, sulpiride, and thyrotropin-releasing hormone. Three studies reported improved milk volume (domperidone, metoclopramide, and sulpiride), and one reported weight gain in infants from receiving mother's milk (metoclopramide); however, these results were limited by a low quality of evidence. [4]

Supplemental/natural galactagogues identified for the meta-analysis included banana flower, fennel, fenugreek, ginger, ixbut, levant cotton, moringa, palm dates, pork knuckle, shatavari, silymarin, torbangun leaves, or other natural mixtures. The overall results observed benefit or little to no difference for improving milk volume. Adverse events were limited but consisted of minor complaints in mother and infant. Ultimately, the benefit of galactagogues for breastfeeding mothers is uncertain as the data were extremely limited, of low quality, and heterogeneous. [4]

References:

[1] American College of Obstetricians and Gynecologists’ Breastfeeding Expert Work Group. Breastfeeding challenges. Number 820. https://www.acog.org/clinical/clinical-guidance/committee-opinion/articles/2021/02/breastfeeding-challenges. Updated February 2021. Accessed October 4, 2021.
[2] Brodribb W, the Academy of Breastfeeding Medicine. Abm clinical protocol #9: use of galactogogues in initiating or augmenting maternal milk production, second revision 2018. Breastfeeding Medicine. 2018;13(5):307-314. DOI: 10.1089/bfm.2018.29092.wjb
[3] Food and Drug Administration. How to Request Domperidone for Expanded Access Use. https://www.fda.gov/drugs/investigational-new-drug-ind-application/how-request-domperidone-expanded-access-use Updated February 2, 2021. Access October 4, 2021.
[4] Foong SC, Tan ML, Foong WC, Marasco LA, Ho JJ, Ong JH. Oral galactagogues (natural therapies or drugs) for increasing breast milk production in mothers of non-hospitalised term infants. Cochrane Database Syst Rev. 2020;5(5):CD011505. Published 2020 May 18. doi:10.1002/14651858.CD011505.pub2
Literature Review

A search of the published medical literature revealed 1 study investigating the researchable question:

Which medications can be used to increase milk production for improved breastfeeding?

Please see Table 1 for your response.

 

Medications and Natural Products for Increased Milk Production

 

Domperidone*

Fenugreek**

Metoclopramide

Silymarin**

Drug/Chemical Class

Dopamine antagonist

A commonly used spice; active constituents are trigonelline, 4hydroxyisoleucine, and sotolon.

Dopamine antagonist

 Flavolignans (presumed active ingredient)

Lactation Effect

 Increased rate of milk secretion in both pump dependent mothers of preterm infants and other mothers with low milk supply. Insufficient evidence; likely a significant placebo effect Possible increased rate of milk secretion; possible responders versus nonresponders Inconclusive. Possible increase in milk secretion in the short term

Observed Dosage

 10mg, orally, 3 times per day used in most of the Level IB studies; one Level 1B study compared 10mg 3 times per day with 20mg 3 times per day and found higher milk production using the higher dose. Doses >60mg per day have not been studied in this context. Herbal tea (200ml 3 times per day); 570–600mg 3 times per day. 10mg, orally, 3 to 4 times per day

Micronized silymarin, 420mg, orally;

Silymarinphosphatidylserine and galega (5g per day)

Anecdotal, strained tea (simmer 1 tsp of crushed seeds in 8 oz of water for 10 minutes), 2–3 cups per day

Duration Studied

 Various commencement times from 2 days to 3 to 4 weeks postpartum in Level 1B studies. Duration of therapy between 7 and 28 days. Maximum effect usually reached by 7–14 days.  1–3 weeks  7–14 days in various studies Micronized silymarin was studied for 63 days; silymarinphosphatidylserine and galega were used for 28 days

Adverse Effects

Maternal: Dry mouth, headache (resolved with decreased dosage), and abdominal cramps. One case reported of psychomotor withdrawal symptoms from a dose of 160 mg per day.

Although not reported in studies of lactation, rare complications (1.3/ 10,000 postpartum women) of cardiac arrhythmias due to a prolonged QTc interval have been reported, but all these women had a past history of ventricular arrhythmias.

 Generally well tolerated. Diarrhea (most common), unusual body odor similar to maple syrup, cross-allergy with Asteraceae/Compositae family (ragweed and related plants), peanuts, and Fabaceae family such as chickpeas, soybeans, and green peas— possible anaphylaxis. Theoretically, asthma, bleeding, dizziness, flatulence, hypoglycemia, loss of consciousness, skin rash, or wheezing—but no reports in lactating women. Reversible CNS effects with short-term use, including sedation, anxiety, depression/ agitation, motor restlessness, dystonic reactions, and extrapyramidal symptoms. Rare reports of tardive dyskinesia (usually irreversible), causing the FDA to place a black box warning on this drug in the United States. Generally well tolerated; occasional mild gastrointestinal side effect; cross-allergy with Asteraceae/ Compositae family (ragweed and related plants)—possible anaphylaxis

Interactions

 Increased blood levels of domperidone when combined with some substrates metabolized by CYP3A4 enzyme inhibitors, for example, fluconazole, macrolide antibiotics, grapefruit juice, cannabinoids, antipsychotics, and others Hawthorne, hypoglycemics, including insulin, antiplatelet drugs, aspirin, heparin, warfarin, feverfew, primrose oil, and many other herbals Monoamine oxidase inhibitors, tacrolimus, antihistamines, any drugs with CNS effects (including antidepressants) Caution with CYP2C9 substrates—may increase levels of the drugs. Possible increased clearance of estrogens (decreased blood levels). Possible increased levels of statins.

ABM Comments/

Recommendations

Do not advise exceeding the maximum recommended dosage.

Tapering of dose is usually recommended.

 If patient develops diarrhea, reducing the dose is often helpful. Some studies suggest tapering off the dose at the end of treatment.  No prescription required



References:

*Domperidone is not currently a legally marketed human drug and it is not approved for sale in the U.S.
**Ensure a reliable source of standard preparation without contaminants

Adapted from: Brodribb W, the Academy of Breastfeeding Medicine. Abm clinical protocol #9: use of galactogogues in initiating or augmenting maternal milk production, second revision 2018. Breastfeeding Medicine. 2018;13(5):307-314. DOI: 10.1089/bfm.2018.29092.wjb