Domperidone: Discovering New Choices for Lactating Mothers

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.

Introduction

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" basis for increasing
milk supply in lactating women. The American 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 products is anecdotal and lacks evidence for their
promotion 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 cannot be
underestimated. Riordan (1997 , p. 96) points out that "breastfeeding is disease prevention in its purest form . . .
human milk lowers health care costs and reduces human suffering." 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 surgery, postpartum hemorrhage or anemia
(Riordan & Auerbach, 1998 ).

Behavior Methods for Improving Supply

There are many behaviors mothers can practice to promote milk production (see Table 1 ). Mothers that
breastfeed, or express milk by mechanical means, early and frequently after delivery, maximize milk production.
This behavior increases serum prolactin 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 in the event placental fragments are
retained. Serum prolactin 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, fatigue and pain can all inhibit
MER. Mothers are encouraged to find a comfortable position and use relaxation techniques (i.e., guided
imagery, breathing), breast massage, and/or warm moist heat to enhance let down and, ultimately, milk
production (Riordan & Auerbach, 1998 ).

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 ).

Special Lactation Situations

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 taken to increase prolactin levels (Lawrence, 1999 ).
Without 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 ).

Galactagogues

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 one to two weeks improves milk
production within two to five days (Gabay, 2002 ).

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 for some of its
known common side effects: fatigue, anxiety, 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 hormone (TSH) and
prolactin. Documented use of TRH as a galactagogue is limited, and its long-term use is associated with
hyperthyroidism (Gabay, 2002 ).

What is Domperidone?
Domperidone, like metoclopramide, is a dopamine antagonist (see Table 2 ). Its "off-label use" as a
galactagogue is a result 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 and contractions of the stomach and bowel and is used to
treat 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 al., 1998 ), and the drug is
excreted in breastmilk in much lower levels (Hofmeyr et al., 1985 ). This is due to the fact that it’s a peripheral
acting dopamine antagonist, is highly protein bound, and has a relatively high molecular weight (Silva et al.,
2001 ).

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 (GI) tract
(Canadian Medical Association, 2002 ).

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 ).

Research on Domperidone

For decades, numerous studies on domperidone have demonstrated its efficacy for GI disorders and as a
galactagogue (Hofmeyr 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 of Symptoms of Diabetic
Gastroparesis: Efficacy, Tolerability, 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, Canada that examined the effect of
domperidone on milk production in mothers of premature newborns (Silva et al., 2001 ). This investigation
makes domperidone the only galactagogue that has been scientifically evaluated through a randomized, double-
blind 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 (seven mothers) orally
three times a day for seven days. Those 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

References

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/Domperidone.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
Association Journal, 164(1), 17–21. Retrieved February 10, 2002, from
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.[CrossRef][Medline]

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  Hypersensitivity, GI obstruction, perforation, or

 Antiemetic hemorrhage, prolactinoma (pituitary tumor), and
 Galactagogue hepatic disease

Indications: Adverse reactions:

 Nausea and vomiting  Dry mouth, H/A, abdominal cramping, diarrhea,

 Gastroparesis nausea, rash, pruritus, uticaria, prolactinemia,
 Lactation improvement galactorrhea, gynecomastia and menstrual
irregularities

Pharmacodynamics: For gastroparesis

Drug interactions:
 Increases movements, or contractions, of
the stomach and bowel  Drugs with anticholinergic properties may antagonize
the effects on the GI tract
For lactation improvement

 Inhibits dopamine, thereby increasing

Usual dosage:
prolactin, the primary hormone
 responsible for milk synthesis
 10–20 mg 3–4 x/day po

Pharmacokinetics:
Patient education: For lactation improvement:
 Absorption: GI tract
 Distribution: poorly penetrates the blood-  Take 30 minutes before meals
brain barrier, > 90 percent protein bound,  Effects may not be seen for 3–4 days, but may be seen
high molecular weight in 24 hours
 Metabolized: in the liver  Maximum effect takes 2–3 weeks
 Excretion: in breastmilk in low levels  Most mothers take medication for 3–8 weeks

Newman (1998), MEDLINEplus (2000), Silva et al. (2001), and CMA (2002).