Domperidone general information

The Protocols for Induced Lactation — A Guide for Maximising Breastmilk Production 
By Jack Newman, MD, FRCPC and Lenore Goldfarb, Ph.D., CCC, IBCLC

Based on the original Induced Lactation Protocol conceived and published by Jack Newman MD

The Newman-Goldfarb protocols were developed from information published in Dr. Newman’s book “Dr. Jack Newman’s Guide to Breastfeeding” (Harper-Collins, 2000). In the US the title is “The Ultimate Breastfeeding Book of Answers” by Dr. Jack Newman (Prima Publishing, 2000).

Effect of domperidone on milk production in mothers of premature newborns: a randomized, double-blind, placebo-controlled trial

Reproduced from the Canadian Medical Association Journal

Copyright © 2001, Canadian Medical Association or its licensors. CMAJ. 2001 January 9; 164 (1): 17 - 21 Orlando Silva,*David C. Knoppert,† Michelle M. Angelini,‡ Penelope A. Forret‡

From the Departments of *Pediatrics, †Pharmacy and ‡Nursing, University of Western Ontario and St. Joseph's Health Care London, London, Ont.

Reprint requests to: Dr. Orlando P. da Silva, Department of Pediatrics, St. Joseph's Health Care London, 268 Grosvenor St., London ON N6A 4V2; fax 519 646-6123; This email address is being protected from spambots. You need JavaScript enabled to view it.

Abstract

Background

Varying degrees of success have been reported with strategies to increase milk production when lactation is failing. The objective of this study was to investigate the efficacy of domperidone in augmenting milk production in mothers of premature newborns.

Methods

Twenty patients were randomly assigned to receive either domperidone or placebo for 7 days. Milk volume was measured daily. Domperidone levels were measured in randomly selected milk and serum samples on day 5 of the study. Serum prolactin levels were measured before the start of the study, on day 5 and on day 10 (3 days after the last dose of the study medication).

Results

Data from 16 patients were available for analysis (7 in the domperidone group and 9 in the placebo group). When compared with baseline values, the mean increase in the volume of milk production from day 2 to 7 was 49.5 (standard deviation [SD] 29.4) mL in the domperidone group and 8.0 (SD 39.5) mL in the placebo group (p < 0.05); proportionally this represented an increase of 44.5% and 16.6% respectively. The serum prolactin levels were similar in the 2 groups at baseline; by day 5 they were significantly higher in the domperidone group than in the placebo group, returning to baseline levels in both groups 3 days after the last dose of the study medication. Very small amounts of domperidone were detected in the breast milk samples.

Interpretation

In the short term domperidone increases milk production in women with low milk supply and is detected at low levels in breast milk.

Introduction

Breastfeeding is recommended as the optimal form of nutrition for term and premature infants. 1 ,2 There are several advantages to breastfeeding, including the psychological benefits of maternal-infant bonding, gastrointestinal trophic aspects and anti-infective benefits for the infant. 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 In addition, there is some evidence that the use of human milk may be associated with long-term benefits for intellectual development even when used for a short period. 11, 12, 13When direct breastfeeding is not possible, the use of expressed mother's milk, fortified when necessary, is recommended to achieve the high nutrient demands of the very-low-birth-weight infant. 1, 2, 3, 4, 5However, mothers who wish to express milk for their hospitalized premature newborns are faced with numerous stressful situations. The often unstable clinical condition of the infant combined with concerns about prognosis and survival, and the distance from home, frequently have a detrimental effect on milk supply.

Varying degrees of success have been reported with strategies to increase milk production when lactation is failing, including support, relaxation techniques, mechanical expression and drug therapy. 14, 15,16, 17 Of all the pharmacological interventions to augment lactation, metoclopramide, a central dopamine antagonist, has been the most widely studied. 15, 18, 19, 20, 21 However, it crosses the blood-brain barrier, is secreted in significant amounts in breast milk 17, 22, 23, 24 and has been reported to affect dopamine-mediated responses in offspring of nursing rats. 25

Domperidone is a peripheral dopamine antagonist that is indicated for use as an upper gastrointestinal motility modifier. 26 Unlike metoclopramide, it does not readily cross the blood-brain barrier. 26, 27, 28 Preliminary data suggest that domperidone may be useful in augmenting milk production in women with insufficient lactation. 29, 30 However, these studies had several methodological shortcomings, including inappropriate control groups and no information on the blinding of subjects or the method of randomization, and in both studies the infants were weighed before and after breastfeeding, an unreliable method at best.

We conducted a randomized, double-blind, placebo-controlled trial to assess the efficacy of domperidone in augmenting lactation in mothers of premature infants. Secondary objectives included the determination of serum prolactin levels in response to orally administered domperidone and of domperidone levels in serum and breast milk.

Methods

The study design was approved by the University of Western Ontario Ethics Committee on Research Involving Human Subjects and the Hospital Clinical Research and Pharmacy and Therapeutics Committees.

The study group included puerperal subjects who had their infants admitted to the neonatal intensive care unit at St. Joseph's Health Care London, in London, Ont. All mothers were mechanically expressing breast milk to be fed to their infants through a nasogastric tube. The women were assessed by our team of lactation consultants and extensively counselled before entering the study. If the milk production remained low (did not meet the infant's daily oral feeding requirements) mothers were informed about our study. They were eligible to participate if they were using an electric breast pump with a double collection kit, were not receiving any medication known to affect serum prolactin levels and did not have a chronic or debilitating illness.

After informed consent was obtained, mothers were randomly assigned to receive either domperidone (10 mg orally 3 times daily) or placebo for 7 days. Domperidone tablets were crushed and mixed with lactose. The resulting powder was placed in clear capsules, as was plain lactose powder, which acted as the placebo.

Breast milk was collected using the Lactinadouble breast pump (Medela Canada, Mississauga, Ont.). Each subject received an ample supply of collection bottles. These one-time use sterile containers accurately measure the volume of milk to the millilitre. The women were instructed to use a new container for each pumping and not to add milk together from 2 different pumpings. They were given recording sheets and adhesive labels to record the amount of milk collected, the date and the time. Milk volume was measured daily. A small amount of milk was retained from all patients on study day 5 for the measurement of domperidone concentrations. The mothers were instructed to record any side effects during treatment, particularly dry mouth, headache, insomnia, abdominal cramps, diarrhea, nausea and urinary retention. The record was reviewed with each woman on day 5 and on day 10 (3 days after the last dose of the study medication), at the time of the visit for blood sampling.

Three blood samples were obtained from each patient to determine serum domperidone and prolactin concentrations before the initial dose, on day 5 and on day 10. All serum and milk samples were kept frozen at -20 oC for later analysis. Serum prolactin concentrations were determined using the IMx prolactin assay (Abbott Laboratories, Abbott Park, Ill.), a microparticle enzyme immunoassay. The analyzer used was an Abbott IMx Automated Immunoassay Analyzer. Domperidone concentrations were determined by means of isocratic reversed-phase high-performance liquid chromatography with mass selective detection. 31

We calculated that 20 subjects would need to be enrolled to demonstrate an increase of at least 25% in milk production (considered clinically significant) from baseline in the study group compared with the placebo group at a power of 80% and an αlevel of 0.05. Categorical data between the 2 groups were compared with the χ 2 test, and continuous data were compared with Student's t-test. The mean increase in the volume of milk from baseline in the 2 groups was compared with the Wilcoxon rank sum test. Simple randomization was achieved using a random numbers table, and patient allocation was carried out in the hospital pharmacy using opaque sealed envelopes. Neither the patients nor the practitioners knew the treatment assignment.

Results

Of the 23 eligible women 20 agreed to participate in the study ( Fig. 1). Four of the 20 women were excluded from the final analysis: no milk records were returned in 3 cases, and in 1 case the infant died of neonatal complications shortly after enrolment. The mean maternal age, gestational age at delivery, post-delivery day at study entry, parity, smoking habits, reasons for preterm delivery and previous breast-feeding experience were similar in the 2 groups (Table 1).

The baseline milk production (the volume produced in the 24 hours before the start of the study medication) was not available for 4 of the remaining 16 subjects (3 in the placebo group and 1 in the domperidone group); the volume of milk produced in the 24 hours following enrolment was taken as the baseline in these cases. The mean volume of milk at baseline was 112.8 (standard deviation [SD] 128.7) mL in the domperidone group and 48.2 (SD 63.3) mL in the placebo group. The mean daily volume of milk collected during study days 2 to 7 was 162.2 (SD 127.5) mL in the domperidone group and 56.1 (SD 48.0) mL in the placebo group. Compared with baseline values the mean increase was significantly greater in the domperidone group than in the placebo group (49.5 [SD 29.4] mL versus 8.0 [SD 39.5] mL respectively, p < 0.05). Proportionally this represented an increase from baseline of 44.5% and 16.6% respectively. The daily milk records for each patient are shown in Table 2.

At baseline the mean serum prolactin levels were similar in the domperidone and placebo groups (12.9 [SD 7.7] μg/L and 15.6 [SD 17] μg/L respectively, p = 0.70). By day 5 there was a significantly greater increase in the serum prolactin levels in the domperidone group than in the placebo group (119.3 [SD 97.3] μg/L v. 18.1 [SD 14.7] μg/L, p = 0.008). These values returned to baseline levels by day 10 (3 days after the last dose of the study medication): 12.1 (SD 5.1) μg/L in the domperidone group and 16.5 (SD 5.2) μg/L in the control group (p = 0.11).

On day 5, subjects in the treatment group had a mean domperidone concentration (as measured in randomly selected serum and milk samples) of 6.6 (SD 5.7) ng/mL in serum (n = 6) and 1.2 (SD 0.6) ng/mL in breast milk (n = 6). The serum and milk domperidone levels in the placebo group were below the limit of detection of the assay used.

Compliance was monitored by capsule count. All subjects complied with the assigned treatment group. In one instance a subject assigned to the domperidone group stopped taking the drug on day 4 of the study because she started to breastfeed her infant successfully. One woman in the placebo group failed to return milk records during the latter part of the study period. Data on these patients were included in the final analysis. No side effects were reported during the study. No obvious adverse effects were identified after reviewing the infants' records. The proportion of infants discharged home who were breastfeeding did not differ between the 2 groups.

Interpretation

There is a paucity of information in the literature regarding the role of domperidone as a galactagogue. Given the importance of breast milk in the feeding of newborns, every effort should be made to enhance breast milk production in lactating mothers of infants admitted to a neonatal intensive care unit. These mothers are usually faced with many barriers to initiating and sustaining lactation given the baby's critical clinical condition and the limitations of breast pumping in the long term. Our study has shown that domperidone is a safe and effective medication in the short term.

Because the infants in our study were not yet nursing we could accurately measure the milk volume collected on a daily basis. Women in the domperidone group experienced a steady increase in milk volume, starting 48 hours after initiation of the medication and continuing gradually up to the last day of treatment. We could not correlate this steady increase in milk volume with the raise in hormone levels, because the serum prolactin level was measured only 3 times during the study period.

How domperidone increases milk production is not well understood. It is hypothesized that the drug stimulates prolactin secretion. 24, 29 Our results support this hypothesis: we found a significantly greater rise in the serum prolactin levels in the domperidone group than in the placebo group.

Very small concentrations of domperidone were found in the breast milk samples randomly selected on day 5; this finding is in keeping with the findings of other investigators. 23, 24 The milk:serum ratio in our study (0.4) is within the range reported for a small number of women in an earlier study. 24 This relatively low value is likely related to domperidone's high protein binding (greater than 90%) 32 and to its relatively high molecular weight. The amount of domperidone that would be ingested by the infant would be extremely small (less than 0.2 μg/kg daily, assuming a daily milk intake of 150 mL/kg and a milk domperidone concentration of 1.2 ng/mL found in this study). This amount is much lower than the level of metoclopramide (approximately 125 ng/mL) that has been measured in the breast milk of nursing mothers treated with this drug. 23, 24 Upon reviewing the infants' charts, we found no reported side effects attributable to domperidone.

Milk production at baseline was higher in the domperidone group than in the placebo group. One possible explanation could be that 3 patients in the domperidone group had delivered multiples (2 sets of triplets and 1 set of twins), as compared with only one set of multiples in the placebo group. Proportionally these patients did not experience a greater response to domperidone than the ones with a lower milk output. The relatively long delay between delivery and study entry is explained by the fact that all women failing lactation in our centre received extensive teaching by our team of lactation consultants. The majority of women responded favourably with improvement in milk production. The women who continued to have problems with lactation after the teaching were eligible to enter the study.

We did not evaluate long-term milk production because most of the women initiated some level of breastfeeding soon after the end of the 7-day trial, and it was not practical to measure milk volume beyond the study period. Therefore we were unable to determine whether the increase in milk volume with domperidone was sustained.

Many questions need to be answered before domperidone can be routinely recommended to increase lactation. In particular, it is not known whether the short-term benefit of domperidone will be sustained. Also, the long-term effects of this drug on the infant, if any, need to be determined. A large multicentre trial should be conducted to address these questions.

Footnotes

This article has been peer reviewed.

Acknowledgements

We thank Courtney MacDonald for performing the domperidone assays and Janssen Pharmaceutica for supplying the pure domperidone samples for the assay.

This study was funded by a grant from the Research and Education Foundation of the Canadian Society of Hospital Pharmacists.

Competing interests: None declared.

References

  1. American Academy of Pediatrics, Work Group on Breastfeeding. Breastfeeding and the use of human milk. Pediatrics1997;100:1035-9. [PubMed]
  2. Canadian Paediatric Society clinical practice guideline: nutrition for healthy term infants. Paediatr Child Health 1998;3:109-12.
  3. Schanler RJ, Hurst NM. Human milk for the hospitalized preterm infant. Semin Perinatol 1994;18:476-86. [PubMed]
  4. Schanler RJ, Shulman RJ, Lau C. Feeding strategies for premature infants: beneficial outcomes of feeding fortified human milk versus preterm formula. Pediatrics 1999;103:1150-7. [PubMed]
  5. Nutrition Committee, Canadian Paediatric Society. Nutrient needs and feeding of premature infants. CMAJ 1995;152(11):1765-84. Available: [PubMed]
  6. Tudehope DI, Steer PA. Which milk for preterm infant? J Paediatr Child Health 1996;32:275-7. [PubMed]
  7. Ogra PL, Rassin DK. Human breast milk. In: Remington JS, Klein JO, editors. Infectious diseases of the fetus and newborn infant. 4th ed. Philadelphia: WB Saunders; 1995. p. 108-39.
  8. Delneri MT, Carbone SB, Silva ML, Palmeira P, Carneiro-Sampaio MM. Inhibition of enteropathogenic Escherichia coli adhesion to HEp-2 cells by colostrum and milk from mothers delivering low-birth-weight neonates. Eur J Pediatr 1997;156:493-8. [PubMed]
  9. Scariati PD, Grummer-Strawn LM, Fein SB. A longitudinal analysis of infant morbidity and the extent of breastfeeding in the United States. Pediatrics 1997;99(6):E5.
  10. Hylander MA, Strobino DM, Dhanireddy R. Human milk feedings and infection among very low birth weight infants. Pediatrics1998;102(3):E38.
  11. Morley R. The influence of early diet on later development. J Biosoc Sci 1996;28:481-7. [PubMed]
  12. Lucas A, Morley R, Cole TJ, et al. Early diet in preterm babies and development status at 18 months. Lancet 1990;335:1477-81.[PubMed]
  13. Lucas A, Morley R, Cole TJ, Lister G, Leeson-Payne C. Breast milk and subsequent intelligence quotient in children born preterm.Lancet 1992;339:261-4. [PubMed]
  14. Feher SDK, Berger LR, Johnson JD, Wilde JB. Increasing breast milk production for premature infants with a relaxation/imagery audiotape. Pediatrics 1989;83:57-60. [PubMed]
  15. Emery MM. Galactogogues: drugs to induce lactation. J Hum Lact1996;12:55-7. [PubMed]
  16. Hill PD, Aldag JC, Chatterton RT. The effect of sequential and simultaneous breast pumping on milk volume and prolactin levels: a pilot study. J Hum Lact 1996;12:193-9. [PubMed]
  17. Lewis PJ, Devenish C, Kahn C. Controlled trial of metoclopramide in the initiation of breast feeding. Br J Clin Pharmacol 1980;9:217-19.[PubMed]
  18. Ehrenkranz RA, Ackerman BA. Metoclopramide effect on faltering milk production by mothers of premature infants. Pediatrics1986;78:614-20. [PubMed]
  19. Kauppila A, Kivinen S, Ylikorkala O. A dose response relation between improved lactation and metoclopramide. Lancet1981;1:1175-7. [PubMed]
  20. Budd SC, Erdman SH, Long DM, Trombley SK, Udall JN. Improved lactation with metoclopramide. Clin Pediatr 1993;35:53-7.
  21. Gupta AP, Gupta PK. Metoclopramide as a lactogogue. Clin Pediatr1985;24: 269-72.
  22. Kauppila A, Arvela P, Koivisto M, Kiniven S, Ylikorkala O, Pelkonen O. Metoclopramide and breast feeding: transfer into milk and the newborn. Eur J Clin Pharmacol 1983;25:819-23. [PubMed]
  23. Hofmeyr GJ, Van Iddekinge B. Domperidone and lactation. Lancet1983;1:647.
  24. Hofmeyr GJ, Van Iddekinge B, Blott JA. Domperidone: secretion in breast milk and effect on puerperal prolactin levels. Br J Obstet Gynaecol 1985;92:141-4. [PubMed]
  25. Engel JA, Lundborg P. Behavioral and biochemical effects in offspring of nursing rats exposed to dopamine receptor antagonists. In vol 1 of 13th Congress of the Collegium Internationale Neuro-Psychopharmacologicum; 1982 June 22; Jerusalem. Abstract 198.
  26. Brogden RN, Carmine AA, Heel RC, Speight TM, Avery GS. Domperidone: a review of its pharmacological activity, pharmacokinetics and therapeutic efficacy in the symptomatic treatment of chronic dyspepsia and as an antiemetic. Drugs1982;24:360-400. [PubMed]
  27. Cann PA, Read NW, Holdsworth CD. Galactorrhoea as a side effect of domperidone [letter]. BMJ 1983;286:1395-6. [PubMed]
  28. Brouwers JR, Assies J, Wiersinga WM, Huizing G, Tytgat GN. Plasma prolactin levels after acute and subchronic oral administration of domperidone and metoclopramide: a cross-over study in healthy volunteers. Clin Endocrinol (Oxf) 1980;12:435-40. [PubMed]
  29. Petraglia F, De leo V, Sardelli S, Pieroni ML, D'Antona N, Genazzani AR. Domperidone in defective and insufficient lactation. Eur J Obstet Gynecol Reprod Biol 1985;19:281-7. [PubMed]
  30. Rolfini G, De Rosa D, Lupi AM, Petrelli V. [Hypogalactia: therapeutic possibilities] [Italian]. Clin Ter 1989;129:185-91. [PubMed]
  31. Zavitsanos AP, MacDonald C, Bassoo E, Gopaul D. Determination of domperidone in human serum and human milk by high-performance liquid chromatography-electrospray mass spectrometry. J Chromatogr B 1999;730:9-24.
  32. Heykants J, Hendriks R, Meuldermans W, Michiels M, Scheygrond H, Reyntjens H. On the pharmacokinetics of domperidone in animals and man. IV: the pharmacokinetics of intravenous domperidone and its bioavailability in man following intramuscular, oral and rectal administration. Eur J Drug Metab Pharmacokinet 1981;6:61-70.[PubMed]

Domperidone, Stopping

How long can I use domperidone?

When domperidone was being used for babies (and now that cisapride is off the market, it is being used again), it was common for the babies to be on the medication for several months, even longer. Since the amount of domperidone that gets into the milk is very small indeed, from the baby’s point of view, there should be no issue in the mother taking it to increase milk supply for several months. Our experience with this drug is that short-term side effects are very few and almost always very mild. Worldwide experience with domperidone over at least two decades suggests that long-term side effects also are rare. Some of the mothers in our clinic, breastfeeding adopted babies, have been on the medication for 18 months without any apparent side effects. As mentioned in the information sheet Domperidone, Getting Started, patients using domperidone for stomach disorders may be on it for many years. We hope you won’t need domperidone for very long, but if it’s necessary and helpful, stay on it.

How long does it take for domperidone to work?

It depends on the situation. In a situation where the mother had had a good milk supply, but it decreased for some reason (e.g. going on the birth control pill, see the information sheet Slow Weight Following Early Good Weight Gain), domperidone often works very rapidly to increase the milk supply. Often, within a day or two the mother is seeing a difference (and so does her baby). But this is not always so, and in many situations, it may take a week or more for the mother to start getting an effect. On occasion, we have had mothers only starting to get an increase in their milk supplies a month or more after starting to take it. Therefore, we generally recommended that the mother take the domperidone for at least six weeks in order to be sure whether it has worked or not.

It is our impression that domperidone works best after the first few weeks after the mother has given birth (usually after about four weeks). This has not been proved, but there are theoretical reasons why it may be so. For this reason, we have often waited to prescribe it until the baby is at least three weeks, mainly because we did not want the mother to become discouraged if she did not see any rapid increase in her milk supply. If you keep this in mind, taking domperidone before three or four weeks after the birth of the baby is worth a try because sometimes it does work very well early on.

How do I know how long to take domperidone?

Usually, we ask the mother take it for at least two weeks at a minimum and then re-evaluate the situation. There are several possibilities.

  • The milk supply has increased substantially, to the point where there is no longer a consideration of using supplements, or the mother has been able to stop supplements with the baby continuing to gain well on breastfeeding alone.
  • The milk supply has increased to a point that the mother feels is satisfactory. For example, she may still need to supplement, but the baby does not fuss any more at the breast and drinks contentedly.
  • There has been little or no effect with the Protocol to Manage Breastmilk Intake and the domperidone. Often waiting or increasing the dose may help.

In the first situation (but not necessarily always in that situation), we may suggest the mother start weaning herself from the domperidone in this way:

  1. When you are ready to start weaning from the domperidone, drop one pill, so that now, instead of nine pills a day, you will be taking eight.
  2. Wait four or five days, a week if you wish. If you see no change in your milk supply, drop another pill.
  3. Wait another four or five days. If you see no change in your milk supply, drop another pill.
  4. Continue in this way until you are down to no pills a day. If there has been no decrease in your milk supply, or if there has been a small decrease that does not affect the breastfeeding and baby’s weight gain, that’s just what we hope to have happened, and many mothers manage this.
    • If, however, your supply diminishes significantly, return to the previous effective dose and do not drop any pills for a couple of weeks at least.
    • If you are keen to go off the domperidone, after a couple of weeks on the same dose, start dropping a pill a day, as in step 1 above. Some mothers, who were not able to get off the domperidone with steps 1-4 above the first time, can do it the second or the third time.
    • You may find that you have to continue a certain dose to maintain your milk supply. But following steps 1-4 above will get you to the lowest effective dose.

It is possible, however, that after two weeks of taking domperidone, you are not where you want to be. In that case, you should continue using the domperidone. If you are still not where you want to be after two to six weeks of domperidone, it is time to think some more about the domperidone. If you are supplementing, and have managed to reduce the amount of supplement from 400 ml to 300 ml (14 ounces to 10 ounces), is it really worth taking a drug in order to do this? I would say yes, but this is up to you. If you feel it is, then continue with the domperidone, but try weaning the number of pills down to minimum number that maintain your milk supply, as above. If you do not feel it is worth it, try weaning down as above, and if you don’t see any change once you get to no pills a day, fine. However, if you do notice a real change in the milk supply as you lower the dose, maybe the domperidone is more effective than you had thought (remember, after several weeks, your baby is significantly heavier, and it may be that instead of needing 400 ml (14 ounces) without domperidone, the baby might actually need 20 ounces to maintain good weight gain, in which case the domperidone is actually doing something).

Remember: Before using domperidone, the breastfeeding should be fixed, and as quickly as possible. This means:

Stopping the Domperidone

Although most women do not experience discomfort when stopping the medication, gradual weaning from the medication will help the mother’s milk supply to adjust without frustrating the baby or causing her discomfort.

It is very important to stop the domperidone slowly.

  • Decrease the domperidone to 20 mg 3 times a day for 2 weeks.
  • Decrease the domperidone to 10 mg 4 times a day for two weeks.
  • Continue to decrease the domperidone to 10 mg 3 times a day for two weeks.
  • Decrease the domperidone to 10 mg 2 times a day for two weeks.
  • Decrease the domperidone to 10 mg once a day for two weeks.
  • Then stop.

Domperidone Dosage Instructions for Induced Lactation

The maximum dose for domperidone is 20 mg 4 times per day. The suggested beginning dose is 10 mg 4 times per day for 1 week, then increasing to 20 mg 4 times per day. This should be increased gradually as per the instructions in the individual protocols. It is advisable to continue to take the domperidone from the initiation of lactation until weaning. Most mothers find that when they forget a dose their milk supply decreases. However, once lactation is well established and the baby is breastfeeding well, the mother may consider slowly decreasing the domperidone. If her milk supply drastically decreases, she can always increase the dose back to 20 mg 4 times per day.

On the FDA and Domperidone

As a paediatrician who deals now only with mothers and babies who are having difficulty with breastfeeding, I am very concerned about the warning about domperidone which was issued by the Federal Drug Administration in the US on June 7, 2004. It warns breastfeeding mothers about getting domperidone to enhance milk supply because it conceivably can cause cardiac arrhythmias.

The FDA has basically come up with a political statement. They seem really bothered because people were going around using a drug which they have not approved. The deaths (and I believe there were two) occurred with intravenous domperidone, which is never used any more and has never been used for enhancing milk supply. Domperidone was given intravenously in huge doses to patients who were sick with other problems as well, notably cancer for which they were getting chemotherapy. Domperidone was being used to decrease nausea and vomiting. Some patients were getting 1000 mg of domperidone every 4 hours intravenously, compared to our usual dose of 30 mg 3 times a day, taken by mouth. It is also likely that some of the chemotherapy drugs the patients would have received have cardiac side effects (for example, doxorubicin) and it was the combination of the huge doses of domperidone intravenously plus other drugs that caused the problem. Furthermore, unlike what the FDA has led people to believe, perhaps unintentionally, these are not new cases, but 2 decades old.

Why didn’t they mention metoclopramide in their warning, which is far more dangerous (it can cause severe depression in oral doses, which domperidone does not) and is also being used off label to increase milk supply in the US, but which, on the other hand, is available and approved for gastric motility problems in the US? Can it be that they are not concerned about the danger but rather the threat to their authority? Here is part of a letter I received about metoclopramide and domperidone as a result of this to do about domperidone. “...my mother...is on domperidone for gastroparesis. She’s 5 feet tall, and lost over 20 lbs...down to 82 lbs. And why is she on domperidone? Because she had depression and SEVERE panic attacks with the Reglan (metoclopramide). She was in and out of the senior psych ward all last spring. So my folks get domperidone from outside the US.”

Why didn’t they mention the danger to diabetics, if they are so concerned, for whom some endocrinologists in the US are prescribing domperidone for gastric paresis? Why specifically for breastfeeding women? Why not specifically for diabetics who are at much greater risk of cardiac arrhythmias than women of reproductive age?

Why did this warning come out exactly on the day that the National Breastfeeding Campaign was to begin in the US?

I have used domperidone, in infants (for spitting up) but mostly to increase milk supply in women, in thousands of women, without any more than the occasional mother getting mild headaches or occasional menstrual irregularities or mild abdominal cramping as side effects. I cannot say the same for metoclopramide which I saw causing severe CNS side effects, aside from depression.

I have personally seen two children die of Stevens-Johnson Syndrome after taking Septra. If I have seen two, how many have actually occurred in the US and Canada? Why no such warnings on Septra? I have, as a medical resident, seen at least one person die and several get severely ill after taking ASA, from gastric bleeding. In overdose, many children have died and many have become seriously ill over the years because of ASA. Why no such warning on aspirin?

Many women have died and many more severely injured from taking the birth control pill. Why is it not banned?

The issue comes up about providing a drug for women in good health and that we should not be treating healthy women with a drug. I disagree. With all the talk about preventive medicine, when it actually comes down to trying to prevent illness, it is all lip service. The data are clear. Breastfeeding decreases the risk of breast cancer and type 2 diabetes in the mother. In the baby it decreases the risk of diabetes (type 1 and 2), obesity, hypertension, high LDL/HDL levels, otitis media, asthma, and allergies, gastroenteritis, and and in premature babies, necrotizing enterocolitis. The first 4 of these are all risk factors for atherosclerosis, the most significant degenerative disease in affluent societies and the biggest killer. The data are clear that breastfeeding results in better cognitive development in children. The data are less clear, but suggestive, that breastfeeding decreases the risk of certain cancers in children (Hodgkin’s and non Hodgkin’s lymphoma, breast cancer in later life), multiple sclerosis and inflammatory bowel disease.

Thus, we should do all that is reasonable to maintain and increase the success of woman who are breastfeeding. If this means that, in some cases, we use a drug that, in my experience of using it with thousands of women, is safe, with only minor side effects, we should have that option. Of course, there is no such thing as a drug which never causes side effects, and there are probably very few approved drugs (yes, even approved drugs) out there that haven’t killed someone, but if one weighs the risk against the benefits, domperidone can do much good. I will continue to prescribe domperidone to women when I feel it will be useful. It’s a shame, though, for women in the US to be deprived of this drug. The FDA says that it will monitor the border to make sure none gets through. Good for them. With heroine and cocaine getting through their borders as through a sieve, it’s great that the US can now be sure that their borders are safe against an influx of the dreaded domperidone. What a waste of manpower! What a waste!

First written in June 2004 by Jack Newman, MD, FRCPC
Revised February 2009

Page 1 of 2