Domperidone_patient_handout

Domperidone for Improving Breastmilk Production

What is domperidone?
Domperidone (Motilium) is a peripheral dopamine antagonist general y used for
control ing nausea and vomiting, dyspepsia (upset stomach), diabetic gastroparesis
(poor stomach emptying which occurs in diabetics) and gastric reflux (heartburn). It
blocks peripheral dopamine receptors in the intestinal wal and in the nausea center of
the brainstem. Unlike metoclopramide (Reglan), it does not enter the brain
compartment to any appreciable degree and has few central nervous system effects
(such as depression and tardive dyskinesia with Reglan). (1)
It was developed by Janssen Pharmaceutical Products and first marketed in Belgium in
1978. It is currently approved for use in over 80 countries including the European
Union, Australia, New Zealand, Canada, and Mexico. It is available without a
prescription (OTC) in several countries, including Belgium, Ireland, Italy, Netherlands,
United Kingdom, Switzerland and South Africa.
What are the pharmacokinetics of domperidone?
Domperidone is rapidly absorbed with peak plasma concentration approximately 1 hr
after oral administration. It has a low bio-availability (~15%) due to first-pass hepatic
and intestinal metabolism. It is 91-93% bound to plasma proteins with a plasma half-life
of 7-9 hrs. Concentrations of domperidone reported in human milk do vary with maternal
dose, but are extremely low, from 0.28 to 2.6 ug/L milk in various studies, resulting in a
negligible mean relative infant dose (RID) of 0.009-0.012% of maternal dose. (1)
Why is domperidone used for breastfeeding/breastmilk-expressing women?
Human milk is a medicine in the NICU, reducing NEC and other infections, and
decreasing length of stay and cost. Insufficient milk supply is the number one cause of
stopping breastfeeding and is a severe problem in the NICU where mothers often must
pump (instead of breastfeeding) for weeks to months. In addition to increased milk
expression, galactogogues (substances that increase milk supply) are often used to
help mothers maintain and recover their milk supply. Options are herbal galactogogues
such as fenugreek (no control ed studies but general y recognized as safe),
metoclopramide (Reglan) and domperidone (Motilium). (2) Both metoclopramide and
domperidone increase prolactin (the milk-making hormone) secretion from the anterior
pituitary, but domperidone appears the safer drug as it rarely causes extrapyramidal
(motor nerve) or any side effects. (1, 3)
Does domperidone work to increase milk supply?
There is an abundance of clinical experience and anecdotal reports of improved milk
supply with domperidone over the last 30 years. There are now 5 studies (albeit each
with smal numbers of subjects) which demonstrate clinical y insignificant concentrations
of domperidone in human milk, no side effects in infants, minimal to no side effects in
mothers, and increased milk supply in most mothers. (3-7)
Is domperidone safe?
The American Academy of Pediatrics (AAP) lists domperidone as a drug compatible
with breastfeeding. (8) It is also listed in pharmacy resources such as DrugDex and
MicroMedex, and as a preferred galactogogue by the Academy of Breastfeeding
Medicine.(9) According to the manufacturer, adverse side effects include very rare
al ergic reactions; very rare extrapyramidal side effects; rare intestinal symptoms
including cramps; rare galactorrhea (milk production), gynecomastia (increased breast
size) and amenorrhea (lack of menstrual periods). There have been several
published reports of cardiac arrhythmias, cardiac arrest, and sudden death in
severely ill patients receiving an intravenous form of domperidone. (10) The
intravenous form was removed from the market approximately 20 years ago.
There are no reports of cardiotoxicity (heart problems) for the oral form of
domperidone. Despite this, the Federal Drug Administration (FDA) issued an Alert in
June 2004, warning women against the use of domperidone to increase milk production.
(11)

Why the FDA alert?
In a phone conference with breastfeeding and pharmacology experts in 2004, the FDA
cited 4 issues of concern:
1. Absence of credible scientific data to establish the safety and efficacy of domperidone as a galactogogues – data available and dismissed. 2. Domperidone is dangerous for breastfeeding women – inappropriately citing deaths of critical y il patients given IV domperidone over 20 years ago. 3. Domperidone may be dangerous to the breastfed infant – no evidence to date, and unlikely as clinical y insignificant amounts are in breastmilk. Almost al the drugs in the PDR are labeled as not to be used in breastfeeding women – for legal, not medical reasons (tests not done as too expensive). 4. The FDA is concerned with unsafe cross border importation of drugs and internet distribution of drugs – a legitimate concern, made worse by threatening compounding pharmacies in the US if they provide domperidone with a legitimate prescription.
The FDA asserts that compounding of domperidone is il egal in the US as domperidone
is a new drug. This is disputed by the International Association of Compounding
Pharmacists (IACP) and legal precedent. Letters sent to compounding pharmacists
state: “FDA does not sanction its use in pharmacy compounding and will not exercise
its enforcement discretion for compounded products containing domperidone.” (12)
According to Loyd Allen Jr. PhD, Editor-in-Chief of the International Journal of
Pharmaceutical Compounding: “Compounded drugs, when created for an individual
patient pursuant to a prescription from a licensed practitioner, are implicitly exempt from
the new drug definitions.” (13)
Is domperidone being prescribed today in the US?
Domperidone is in such wide use and acceptance by US gastroenterologists that it is
even cited in the medical literature and advice regarding how to obtain it is provided.
After the 2004 FDA alert, the Gastroparesis and Dysmotilities Association wrote an
extensive letter (14) to the FDA objecting to the FDA’s assertion that compounding
domperidone is il egal (as it is a “new, unapproved drug”). “Although never released for
commercial use in this country, Domperidone is available as a raw compound for which
standards were detailed in a US Pharmacopoeia monograph published in November
2000. Therefore, it can be compounded for patient use.” (15) Domperidone is
prescribed by gastroenterologists for adult gastric motility problems and by thousands of
family practice, obstetric, neonatal and pediatric practitioners as a galactogogue in the
US and worldwide.
Summary.
The evidence and expert consensus is that domperidone is a safer drug than
metoclopramide (Reglan). Many experts believe that the US FDA 2004 alert was
motivated by drug importation political issues, not sound medical science. Responsible
physicians have an obligation to prescribe the safest, most effective drug to meet
patients’ needs, but also need to obey State and Federal regulations. Unfortunately, as
domperidone is not FDA approved for any use in the US, some authorities believe that it
is il egal for a US physician to prescribe it.
Physicians also have an obligation to give ful information so each patient (or parent)
can make a ful y informed decision. This handout is for your general information only,
and should not be used as a recommendation for, or against, domperidone. For
information specific to you, please consult your healthcare provider. For more
information about domperidone, you can refer to the fol owing web sites and their links:
http://www.fda.gov/cder/news/domperidone.htm
http://www.aap.org/healthtopics/breastfeeding.cfm
click on drugs and breastfeeding – Table 6 – Drugs compatible with BFing
http://www.bfmed.org/ace-files/protocol/prot9galactogoguesEnglish.pdf
http://www.breastfeedingonline.com/domperidone.shtml
http://www.digestivedistress.com/files/pdf/FDA_letter_re_Domperidone.pdf
http://www.fda.gov/bbs/topics/answers/2004/ans01292.html
http://www.mayoclinic.com/health/drug-information/DR600561
http://www.medicinenet.com/domperidone-oral/article.htm
http://pediatrics.about.com/cs/breastfeeding/a/domperidone.htm
http://www.digestivedistress.com/main/page.php?page_id=55
References:
1. Hale TW, Medications & Mothers’ Milk, 13th Edition, 2008, Hale Publishing LP, Amarillo, TX 2. Wight NE, Morton JA. Human milk, breastfeeding and the preterm infant. In Hale & Hartmann’s Textbook of Human Lactation, 1st ed, eds Hale TW, Hartmann PE, Hale Publishing LP, Amarillo, TX 2007; 479-489 3. Wan EW-X, Davey K, Page-Sharp M, Hartmann PE, Simmer K, Ilett KF. Dose-effect study of domperidone as a galactogogue in preterm mothers with insufficient milk supply, and its transfer into milk. Brit J Clin Pharm 2008; 66(2):283-289 4. Hoffmeyr G, Van Iddekinge B, Blott J. Domperidone: Secretion in breast milk and effect on puerperal prolactin levels. Brit J Obstet and Gynaecol 1985; 92:141-144 5. Petraglia F, De Leo V, Sardelli S, Pieroni M, Antona N, Genazzani A. Domperidone in defective and insufficient lactation. Eur J Obstet Gynecol Reprod Biol 1985; 19:281-287 6. daSilva O, Knoppert DC, Angelini MM, Forret PA. Effect of domperidone on milk production in mothers of premature newborns: A randomized, double-blind, placebo-controlled trial. Canadian Med Assn J 2001; 164(1): 17-21 7. Campbell-Yeo M, Allen AC, Joseph KS, Ledwidge J, Allen V, Dooley K. A Double-Blind Placebo Controlled Trial Examining the Effect of Domperidone on the Composition of Human Breast Milk. Abstract, PAS, May 2008, Hawaii 8. AAP Committee on Drugs. The Transfer of Drugs and Other Chemicals Into Human Milk. 9. Montgomery A, Wight N. ABM Protocol #9: Use of galactogogues in initiating or augmenting maternal milk supply. Academy of Breastfeeding Medicine, 2004; www.bfmed.org 10. Drolet B, Rousseau G, Daleau P, Cardinal R, Turgeon J. Domperidone Should Not Be Considered a No-Risk Alternative to Cisapride in the Treatment of Gastrointestinal Motility Disorders. Circulation 2000; 102:1883-1885 11. FDA Talk Paper: FDA Warns Women Against Using Unapproved Drug, Domperidone, to Increase Milk Production. June 7, 2004; www.fda.gov/bbs/topics/ANSWERS/2004/ANS01292.html 12. Warning Letter: FDA to Spectrum Chemicals & Laboratory Products, June 7, 2004; www.casewatch.org/fdawarning/comp/spectrum.shtml 13. Statement of Loyd V. Allen Jr, PhD, RPh, Editor-n-Chief, International Journal of Pharmaceutical Compounding, Before the US Senate Special Committee on Aging, Washington, DC, April 19, 2007; http://aging.senate.gov/minority/_files/hr171la.pdf http://www.digestivedistress.com/files/pdf/FDA_letter_re_Domperidone.pdf 15. Jones MP. Management of diabetic gastroparesis. Nutr Clin Pract 2004; 19(2):145-153 Nancy E. Wight MD, IBCLC, FABM, FAAP 12/17/08

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