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Articles: Thomas W. Hale Pharmacology Review: Drug Therapy and Breastfeeding: Pharmacokinetics, Risk Factors, and Effects on Milk Production Neoreviews 2004; 5: e164-e172 [Full text] [PDF]

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Domperidone and the FDA Warning

Kathleen S Bohanon, MD   (22 July 2004)

Response to Dr Bohanon

Thomas W Hale   (22 July 2004)

Domperidone and the FDA Warning 22 July 2004
Kathleen S Bohanon, MD, Neonatologist St Mary's Hospital and Medical Center, Grand Junction, Colorado Send letter to journal: Re: Domperidone and the FDA Warning DoctorBoh{at}aol.com Kathleen S Bohanon, MD	Given the recent FDA warning about use of domperidone to increase milk production (FDA Talk Paper, June 7, 2004), I am curious about Dr. Hale's reaction to the FDA warning. The FDA warning cites side effects from the IV form of the drug, and "potential threats" to the infant because domperidone is excreted in breast milk. However, Dr. Hale makes a good arguement for its safety. Since much of the prescribing done in the practice of neonatology uses medications outside of or beyond FDA approved labeling, most of us come to rely on reputable publications as our medical sources to justify such use. Is the FDA warning one we should pay attention to or is it just the FDA getting annoyed and raising a false alarm because the medication comes from outside the US and some US pharmacies are violating Federal law? Is domperidone any more hazardous than using metoclopramide or Fenugreek?
Response to Dr Bohanon 22 July 2004
Thomas W Hale, Professor of Pediatrics Texas Tech University,School of Medicine Send letter to journal: Re: Response to Dr Bohanon Thomas.Hale{at}TTUHSC.edu Thomas W Hale	The issue over domperidone is in my opinion largely political. The FDA noticed that domperidone was becoming increasingly popular in the USA for use as a galactagogue even though it was not cleared for such purpose. One of the primary sources of the medication was from compounding pharmacies, which by law are regulated by State law, not FDA law...so there is some controversy between these two groups. The reality is that the FDA has brought forward some old intravenous data(1985) that is simply not clinically relevant to our situation. In the cases cited by the FDA, many of the patients were undergoing high dose cancer chemotherapy (cisplatin, adriamycin, or cyclophosphamide), they were reportedly hypokalemic, and received excessively high doses of domperidone (20 mg IV stat, followed by 10 mg/kg/over 24 hours). A second reported toxicity involved a patient who received 200 mg IV. Subsequent to these two reports at least three letters to the editor complained about the relevance of these reports. The bioavailability of domperidone is important. Domperidone is only 13-17% bioavailable orally due to significant first-pass hepatic and intestinal metabolism. Peak plasma levels in recipients following 20 mg orally is only 15-18 ng/ml. Peak plasma levels following a 10 mg intravenous dose is reported to be 1200 ng/ml, almost 80-150 fold more than oral administration. I can't even imagine how high the levels must have been in these hypokalemic cancer patients receiving approximately 200-700 mg/24 hours intravenously. There is simply no relevance in these reported studies to how it is used in breastfeeding women (orally, 10-20 mg TID-QID). Domperidone has been used in more than 33 countries world-wide for more than 30 years. It is approved for use in all the worlds largest and finest countries, including England, Australia, Canada, etc, and is available over-the-counter in many countries. The majority of reported side effects include occasional headache and GI cramping and only rarely cardiac arrhythmias as sited above. Dr. Jack Newman of Canada has reportedly used domperidone as a galactagogue in more than 1000 women with only occasional reports of headache and gastric cramping. Not a single case of arrhythmia. There are two major advantages of domperidone. One is that it does not pass the blood-brain barrier, hence it does not induce maternal depression, or extrapyramidal symptoms, as is commonly reported with metoclopramide (Reglan). And secondly, the dose of domperidone to the infant via milk is almost 100 times less than the amount of Reglan transferred. So exposure of the infant is significantly less. The reality is that I still believe domperidone is the safest product we can use for stimulating milk production in women. We have several small but good studies (and experience in thousands of clinical cases) that confirm that in breastfeeding women with hypoprolactinemia, it significantly increases milk production. In many instances it offers the only hope for many mothers with premature infants to continue providing human milk to their infants. It is unfortunate that this useful drug had to become mired in the politics of importation, and of compounding. Tom Hale Ph.D. Professor of Pediatrics Reference List (1) Osborne RJ, Slevin ML, Hunter RW, Hamer J. Cardiac arrhythmias during cytotoxic chemotherapy: role of domperidone. Hum Toxicol. 1985;4:617-626. (2) Cameron HA, Reyntjens AJ, Lake-Bakaar G. Cardiac arrest after treatment with intravenous domperidone. Br Med J (Clin Res Ed). 1985;290:160. (3) Quinn N, Parkes D, Jackson G, Upward J. Cardiotoxicity of domperidone. Lancet. 1985;2:724. (4) Critchley P, Langdon N, Parkes JD et al. Domperidone. Br Med J (Clin Res Ed). 1985;290:788.