AWHONN Lifeline 2003; 7:54-60
Amanda Henderson, RN, BSN, BS, IBCLC
Amanda Henderson, RN, BSN, BS, IBCLC, is a lactation consultant at Eastern Maine Medical Center in Bangor, ME.
Lactating mothers face a variety of challenges including maintaining a sufficient milk supply. And although there are a number of behavioral and other approaches to helping lactating mothers increase their milk, as a final option, pharmaceutical intervention for lactating mothers to increase milk production is a viable option.
Medications that stimulate lactation are known as galactagogues.
The galactagogue now most frequently used, metoclopramide (Reglan) (Gabay, 2002 ), has known side effects of fatigue, irritability and depression. These effects raise concern (Starr & Starr, 1999 ) and, as such, have rendered the drug an ineffective choice for many nursing women (Newman, 1998 ).
Domperidone (Motilium) is a drug used to treat gastrointestinal disorders; as a side effect it increases prolactin production.
Domperidone may be a new and superior choice for increasing milk production, although it’s currently not available in the U.S. In Canada, however, it is being used on an "off-label" milk supply in lactating women. The American basis for increasing
Academy of Pediatrics (AAP, 2001 ), citing a report in the medical journal The Lancet , reports no known contraindications with the drug in lactating women.
Nearly all cultures have promoted one substance or another as a galactagogue to encourage the synthesis and secretion of breastmilk.
In the U.S., beer, brewer’s yeast and fenugreek, as well as other natural products (i.e., blessed thistle, fennel), have been popular recommendations for improving milk supply (Riordan & Auerbach,
1998 ). Much of what is known about many natural promotion products is anecdotal and lacks evidence for their to improve lactation (Gabay, 2002 ; Lawrence, 2000 ). The Association of Women’s Health,
Obstetric and Neonatal Nurses (AWHONN) recognizes the importance of breastfeeding (AWHONN, 1999 ) and advocates for research on new ways to support and reduce barriers to breastfeeding success (AWHONN,
2001 ) (see Box 1 for more information on getting involved in ongoing research).

Box 1. Calling All Breastfeeding Advocates
The need for research to investigate new ways of understanding and promoting breastfeeding human milk lowers health care costs and reduces human suffering." cannot be underestimated. Riordan (1997 , p. 96) points out that "breastfeeding is disease prevention in its purest form . .
.
Individuals who are likely to experience decreased milk production, and may benefit from pharmacological intervention, are individuals who should not have to cope with the potential side effects from metoclopramide, the galactagogue currently available and most commonly used in the U.S.
Further investigations need to be made to determine the best choices for pharmacological intervention for IMS.
If you are interested in conducting a clinical trial or would like to know more about new drug development and investigational new drug applications, contact the Center for Drug Evaluation and Research at http://www.fda.gov/cder/about/smallbiz/faq.htm
.
Insufficient milk supply (IMS) is the major reason cited for early cessation of breastfeeding, yet actual IMS is rare, as IMS is associated with insufficient glandular tissue, breast
(Riordan & Auerbach, 1998 ).
surgery, postpartum hemorrhage or anemia
There are many behaviors mothers can practice to promote milk
This behavior increases serum prolactin production (see Table 1 ). Mothers that breastfeed, or express milk by mechanical means, early and frequently after delivery, maximize milk production. levels and promotes the secretion of oxytocin, the two primary hormones necessary for lactation to occur.
Prolactin is the hormone responsible for the production of milk.
It’s present during pregnancy but its action is suppressed until delivery of the placenta. Delayed lactation can occur retained. Serum prolactin in the event placental fragments are levels are naturally elevated immediately following delivery and increase with breast stimulation from a baby and/or milk expression (Riordan & Auerbach, 1998 ).
The milk ejection reflex (MER), or "let-down," occurs under the influence of oxytocin. The release of oxytocin is dependent on nipple stimulation and various psychological factors. Stress,
MER. Mothers are encouraged fatigue and pain can all inhibit to find a comfortable position and use relaxation techniques (i.e., guided imagery, breathing), breast massage, and/or warm production (Riordan & Auerbach, 1998 ).
moist heat to enhance let down and, ultimately, milk
Lactating mothers should consume a well-balanced diet, maintain adequate fluid intake and avoid substances known to decrease milk supply. A diet with increased protein (Lawrence, 1999 ) and approximately 500 extra calories above and beyond what they need to maintain their weight will promote maximum milk production.
Fluid intake should be enough to satisfy the mother’s thirst, keep her urine clear to light yellow and prevent constipation.
Too much fluid can actually decrease a mother’s milk production.
Other common substances that can decrease milk supply are hormonal contraceptives, nicotine and alcohol (Riordan & Auerbach, 1998 ).
For mothers who must pump when their child cannot breastfeed, a hospital-grade electric breast pump with a double collection kit are recommended for maximum milk production. Skin-to-skin contact (also known as kangaroo care) and nonnutritive sucking at the breast are other behaviors mothers and their infants can practice together, especially with a preterm or critically ill child, to promote milk ejection and increase milk volumes
(Meir, Brown, & Hurst, 1998 ).

There are special situations that put mothers at risk for IMS.
Mothers of preterm and/or critically ill newborns
(Meir et al., 1998 ), mothers of multiples (Leonard, 2002 ), and adoptive mothers (Cheales-Siebenaler, 1999 ) may find themselves in need of greater interventions, such as drug therapy, to help increase milk production.
Since breastmilk is the ideal infant nutrition, and the health benefits to both mother and child are numerous, every effort must be made to allow mothers to lactate and provide infants with breastmilk (AWHONN, 1999 ).
Infants considered at highest risk, such as those who were born preterm or who are critically ill, have the most to gain from the exclusive feeding of breastmilk. Breastmilk allows them to better tolerate enteral feedings sooner, lowers their risk and severity of infection, improves developmental and neurocognitive outcomes, and when they do go to breast there is greater physiologic stability than with bottle feeding (Meir et al., 1998 ).
Many mothers of nonnursing preterm or critically ill infants initiate and maintain lactation by expressing their breastmilk with a breast pump. They may need to pump for only a few days, but others may pump for weeks or even months, until the infant is able to effectively feed at the breast. Mothers that pump over a long period of time commonly experience a drop in milk supply, especially after four weeks (Meir et al., 1998 ).
Some mothers may wish to resume lactation if a child becomes ill (Thompson, 1996 ) or induce lactation in the event of adoption (Cheales-Siebenaler, 1999 ). Adoptive mothers, particularly if they have never been pregnant, will need to use additional interventions.
A course of some combination of estrogen and progesterone therapy must be initiated to "set the stage" before other action is
Without taken to increase prolactin levels (Lawrence, 1999 ). the hormonal influence of pregnancy, primarily of estrogen and progesterone, a woman’s breast tissue does not go through the final stage of development that prepares the breast for lactation (Riordan & Auerbach,
1998 ).
Not all mothers respond in the same manner. Therefore, another important tool for the adoptive mother is a supplemental nursing system that delivers artificial milk while the infant feeds at the breast (Cheales-Siebenaler,
1999 ). Mothers need to focus on the nurturing aspect, versus the nourishment, of trying to provide breastmilk for their babies (Lawrence, 1999 ). Support from family, as well as professionals, is important for breastfeeding success. And in special situations, that support becomes critical (Cheales-Siebenaler, 1999 ; Krouse, 2002 ;
Leonard, 2002 ; Thompson, 1996 ).
When behavioral changes alone aren’t enough, some mothers may be advised to use metoclopramide, the drug most commonly used in the U.S. to improve milk production. Metoclopramide has been well studied and deemed effective and safe for women and infants. Most prescription drugs used to promote lactation do so by increasing serum prolactin. Metoclopramide is a central acting dopamine antagonist. It raises serum prolactin by decreasing dopamine. Oral administration of 10 mg, three times a day for production within two to five days (Gabay, 2002 ).
one to two weeks improves milk
Metoclopramide is typically indicated for gastroesophageal reflux, diabetic gastroparesis and as an anti-emetic.
Because of its action on the central nervous system, extrapyramidal effects have been observed with its use
(Gabay, 2002 ). Of particular concern for new mothers in special situations is the potential known common side effects: fatigue, anxiety, for some of its insomnia and depression (
Nurse Practitioner’s Drug Handbook,
2000 ).
Other drugs that are available in the U.S. that increase milk supply include chlorapromazine, growth hormone and thyrotrophin-releasing hormone (TRH). Chlorapromazine is an antipsychotic that binds and blocks

dopamine. The risk of extrapyramidal side effects and weight gain limit its use. Although its exact mechanism of action is unknown, growth hormone has shown to increase milk production in cows. There is little data on its efficacy and safety for women and infants. TRH increases serum thyroid stimulating prolactin. Documented use of TRH as a galactagogue hormone (TSH) and is limited, and its long-term use is associated with hyperthyroidism (Gabay, 2002 ).
Domperidone, like metoclopramide, is a dopamine antagonist (see galactagogue is a result
Table 2 ). Its "off-label use" as a of its ability to increase serum prolactin levels (Brown, Fernandes, Grant, Hutsul, &
McCoshen, 2000 ; Hofmeyr, Van Iddekinge, & Blott, 1985 ; Petraglia et al., 1985 ; Silva, Knoppert, Angelini,
& Forret, 2001 ). It also increases the movements treat and contractions of the stomach and bowel and is used to nausea and vomiting (MEDLINEplus, 2000 ), gastroparesis (National Digestive Diseases Information
Clearinghouse [NDDIC], 1999 ), postprandial dyspepsia and reflux esophagitis (Gabay, 2002 ).
What makes domperidone different from metoclopramide is that it does not cross the blood-brain barrier.
Untoward effects on the central nervous system (CNS) are limited (Silvers et excreted in breastmilk in much lower al., 1998 ), and the drug is levels (Hofmeyr et al., 1985 ). This is due to the fact that it’s a peripheral acting dopamine antagonist, is highly
2001 ).
protein bound, and has a relatively high molecular weight (Silva et al.,
Although rare (Petraglia et al., 1985 ), some adverse reactions cited by mothers treated with domperidone for insufficient milk supply include dry mouth, abdominal cramping and headache (Newman, 1998 ). Domperidone is contraindicated for individuals with hypersensitivity to domperidone, gastrointestinal obstruction, perforation, or hemorrhage, and prolactinoma. Caution should be used in patients with hepatic disease and with those taking anticholinergics, since they may antagonize the effect of domperidone in the gastrointestinal
(Canadian Medical Association, 2002 ).
(GI) tract
The usual dosage of domperidone for insufficient milk supply is 20 mg (two 10 mg tablets) four times a day for three to eight weeks. Increased milk production can occur within 24 hours, but generally it takes three to four days, and maximum effect is reached in two to three weeks (Newman, 1998 ).
For decades, numerous studies on domperidone have demonstrated galactagogue (Hofmeyr its efficacy for GI disorders and as a et al., 1985 ; Petraglia et al., 1985 ; Silva et al., 2001 ; Silvers et al., 1998 ).
Domperidone is used practically worldwide. Though currently unavailable in the U.S. (Gabay, 2002 ), it is under review by the U.S. Food and Drug Administration (FDA) (NDDIC, 1999 ). At present, it’s only available in North America in Canada under the trade name Motilium (MEDLINEplus, 2000 ).
Very little research on domperidone has occurred in the U.S.
The Janssen Research Foundation, in Titusville,
NJ, supported the 1998 (Silvers et al., 1998 ) study "Domperidone in the Management
Gastroparesis: Efficacy, Tolerability, of Symptoms of Diabetic and Quality-of-Life Outcomes in a Multicenter Controlled Trial." In this study, researchers found that those who received domperidone reported fewer symptoms of gastroparesis and experienced significant improvements in quality of life compared with the placebo group.
Domperidone is currently being used as one of the investigational drugs in the study examining the "Effects of Monoamine
Reuptake
Inhibitor NS2330 in Parkinson’s Disease" (National Institutes of Health, 2002 ). The lead investigator, Thomas Chase, is using domperidone for its role as an anti-emetic while observing the effects of
NS2330. He maintains that it’s not currently under commercial development in the U.S. (personal communication, March 11, 2002).

Of particular importance is a recent study done in London, Ontario, domperidone on milk production
Canada that examined the effect of in mothers of premature newborns (Silva et al., 2001 ). This investigation makes domperidone the only galactagogue that has been scientifically evaluated through a randomized, doubleblind placebo-controlled study (Gabay, 2002 ).
In the study, 16 consenting mothers of nonnursing preterm infants, using the same model electric breast pump and collection kit, received either a placebo (nine mothers) or 10 mg of domperidone three times a day for seven days. Those
(seven mothers) orally receiving domperidone had a more significant rise in both serum prolactin levels and total milk production, compared with the placebo group. In addition, only small concentrations of domperidone were found in breastmilk. The authors indicate that further research needs to be conducted, specifically a large multicenter trial, before domperidone can be routinely recommended to improve lactation. For more information on domperidone and the research under way, see Box 2 .
Box 2. Getting All the Facts


AAP: Breastfeeding and the Use of Human Milk: http://www.aap.org/policy/re9729.html
AWHONN: Position Statement on Breastfeeding: http://www.awhonn.org/awhonn/?pg=875-4730-
7240
 AWHONN:
Position Statement on Women’s Health
Research: http://www.awhonn.org/awhonn/?pg=875-4810-5620-7380


Breastfeeding Information, Support and Attitude: http://www.breastfeeding.com
Breastfeeding Pharmacology: Thomas Hale, RPh, PhD: http://neonatal.ttuhsc.edu/lact/
 Bright Future Lactation Resource Center: http://www.bflrc.com
 FDA:
FAQ’s on Drug Development and Investigational New Drug
Applications:
 http://www.fda.gov/cder/about/smallbiz/faq.htm
DHHS: Blueprint for Action on Breastfeeding:
 http://www.4women.gov/Breastfeeding/bluprntbk2.pdf
National Institute of Neurological Disorders and Stroke: Clinical Pharmacology Section, Thomas
Chase MD, Senior Investigator, Division of Intramural Research: http://www.ninds.nih.gov/about_ninds/labs/66.htm
American Academy of Pediatrics. (2001). The transfer of drugs and other chemicals into human milk.
Pediatrics , 108 (3), 776–789. Retrieved November 16, 2001, from http://www.aap.org/policy/0063.html[Abstract/ Free Full Text]
Association of Women’s Health, Obstetric and Neonatal Nurses. (1999). Breastfeeding: Clinical position statement.
Retrieved November 22, 2002, from http://www.awhonn.org/awhonn/?pg=875-4730-7240
Association of Women’s Health, Obstetric and Neonatal Nurses. (2001). Women’s health research: Policy position statement . Retrieved November 22, 2002, from http://www.awhonn.org/awhonn/?pg=875-4810-5620-
7380
Brown, T., Fernandes, A., Grant, L., Hutsul, J., & McCoshen, J. (2000). Effect of parity on prolactin response to metoclopramide and domperidone: Implications for the enhancement of lactation. Journal of the Society of
Gynecological Investigation , 7 (1), 65–69.
[CrossRef]

Canadian Medical Association. (2002). Domperidone. Drugs of choice . Retrieved December 4, 2002, from http://www.cma.ca/cma/common/displayPage.do?pageId=/staticContent/HTML/N0/l2/drugs/synopses/Domperi done.htm
Cheales-Siebenaler, N. (1999). Induced lactation in an adoptive mother. Journal of Human Lactation , 15 (1),
41–43.
[Medline]
Gabay, M. (2002). Galactogogues: Medications that induce lactation. Journal of Human Lactation , 18 (3), 274–
279.
[Medline]
Hofmeyr, G., Van Iddekinge, B., & Blott, J. (1985). Domperidone: Secretion in breast milk and effect on puerperal prolactin levels. British Journal of Obstetrics and Gynaecology , 92 , 141–144.
[Medline]
Krouse, A. (2002). The family management of breastfeeding low birth weight infants. Journal of Human
Lactation , 18 (2), 155–165.
[Medline]
Lawrence, R. (1999). Induced lactation and relactation (including nursing the adopted baby) and cross-nursing.
In R. M. Lawrence & R. Lawrence (Eds.), Breastfeeding: A guide for the medical profession (5th ed., pp. 633–
652). St. Louis, MO: Mosby.
Lawrence, R. (2000). Herbs and breastfeeding. From our experts . Retrieved November 23, 2002, from http://www.breastfeeding.com/reading_room/herbs.html
Leonard, L. (2002). Breastfeeding higher order multiples: Enhancing support during the postpartum hospitalization period. Journal of Human Lactation , 18 (4), 386–392.
[Medline]
MEDLINEplus. (2000). Domperidone (Systemic). Drug information. Retrieved February 13, 2002, from http://www.nlm.nih.gov/medlineplus/druginfo/domperidonesystemic 500149.html
Meir, P., Brown, L., & Hurst, N. (1998). Breastfeeding the preterm infant. In J. Riordan & K. G. Auerbach
(Eds.), Breastfeeding and human lactation (2nd ed., pp. 449–481). Sudbury, MA: Jones and Bartlett.
National Digestive Diseases Information Clearinghouse. (1999). Gastroparesis and diabetes . NIH Publication
No. 99-4348. Retrieved December 4, 2002, from http://www.niddk.nih.gov/health/digest/pubs/gastro/gastro.htm
National Institutes of Health. (2002). Effects of monoamine reuptake inhibitor NS2330 in Parkinson’s disease.
Clinical research studies. Protocol Number: 00-N-0187. Retrieved December 4, 2002, from http://clinicalstudies.info.nih.gov/detail/B_2000-N0187.html
Newman, J. (1998). Domperidone, #19. Dr. Newman’s Pages. Retrieved February 14, 2002, from http://www.bflrc.com/newman/breastfeeding/domperid.htm
Nurse Practitioner’s Drug Handbook
(3rd ed.). (2000). Springhouse, PA: Springhouse Corp.
Petraglia, F., De Leo, V., Sardelli, S., Pieroni, M., Antona, N., & Genazzani, A. (1985). Domperidone in defective and insufficient lactation. European Journal of Obstetrics, Gynecology, and Reproductive Biology ,
19 , 281–287.
[Medline]
Riordan, J. (1997). The cost of not breastfeeding. Journal of Human Lactation , 13 (2), 93–97.
[Medline]

Riordan, J., & Auerbach, K. (1998). Breastfeeding and Human Lactation (2nd ed.). Sudbury, MA: Jones and
Bartlett.
Silva, O., Knoppert, D. C., Angelini, M. M., & Forret, P. A. (2001). Effect of domperidone on milk production in mothers of premature newborns: A randomized, double-blind, placebo-controlled trial. Canadian Medical from Association Journal , 164 (1), 17–21. Retrieved February 10, 2002, http://www.pubmedcentral.gov/articlerender.fcgi?tool=pubmed&pubmedid=s11202662[Abstract/ Free
Full Text]
Silvers, D., Kipnes, M., Broadstone,V., Patterson, D., Quigley, E., McCallum, R., et al. (1998). Domperidone in the management of symptoms of diabetic gastroparesis: Efficacy, tolerability, and quality-of-life outcomes in a multicenter controlled trial. Clinical Therapeutics , 20 (3), 438–453.
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Starr, D., & Starr, S. E. (1999). Breastfeeding and adoption (Letter to the Editor). Journal of Human Lactation ,
15 (3), 206–207.
Thompson, N. (1996). Relactation in a newborn intensive care setting. Journal of Human Lactation , 12 (3), 233–
235.
[Medline]
Table 1. Non-Phamacological Methods of Increasing Milk Supply
Increase frequency and duration of feedings and/or milk expression
 Express milk with a hospital-grade electric pump
 Practice simultaneous pumping with a double collection kit
 Use of a supplemental nursing system that delivers artificial milk while the infant suckles may be

needed if the mother’s own milk supply is insufficient
Rest and relaxation
 Guided imagery
 Deep breathing
 Avoid known stressors
Appropriate nutrition and fluid intake
 Adequate iron
 High protein
Avoid substances known to decrease milk supply



Cigarettes
Hormonal contraception with estrogen
Alcohol
Increase skin-to-skin contact with infant
 Also known as "Kangaroo Care”, KC, KMC, or Kangaroo Mother Care"
Provide opportunities for nonnutritive suckling at breast
 Avoid pacifiers
Adapted from Meir et al. (1998), Riordan and Auerbach (1998), and Lawrence (1999).
Table 2. Exploring Domperidone
Classification: Contraindications and precautions:

 Dopamine antagonist
 Antiemetic
 Galactagogue
 Hypersensitivity, GI obstruction, perforation, or hemorrhage, prolactinoma (pituitary tumor), and hepatic disease
Indications: Adverse reactions:


Nausea and vomiting
 Gastroparesis
Lactation improvement
Pharmacodynamics: For gastroparesis
 Increases movements, or contractions, of the stomach and bowel
Drug interactions:
 Drugs with anticholinergic properties may antagonize the effects on the GI tract
For lactation improvement
 Dry mouth, H/A, abdominal cramping, diarrhea, nausea, rash, pruritus, uticaria, prolactinemia, galactorrhea, gynecomastia and menstrual irregularities
 Inhibits dopamine, thereby increasing prolactin, the primary hormone responsible for milk synthesis
Usual dosage:
 10–20 mg 3–4 x/day po
Pharmacokinetics:


Absorption: GI tract
Distribution: poorly penetrates the blood-brain barrier, > 90 percent protein bound, high molecular weight
 Metabolized: in the liver
 Excretion: in breastmilk in low levels
Patient education: For lactation improvement:




Take 30 minutes before meals
Effects may not be seen for 3–4 days, but may be seen in 24 hours
Maximum effect takes 2–3 weeks
Most mothers take medication for 3–8 weeks
Newman (1998), MEDLINEplus (2000), Silva et al. (2001), and CMA (2002).