Letter to FDA re Domperidone

From: Doreen Fisher
Sent: Friday, June 18, 2004
To: Fitzpatrick, Cynthia
Subject: Re: FDA Warning on Domperidone

Dear Cynthia,

I have been out of town and unable to reply to you until now. Thank you for your response, but it fails to address my concerns over the FDA advisory. Although the FDA advisory is clear on it's position, it isn't clear on the reasons behind same.

I am again writing to the FDA as a concerned citizen and a lactating mother. The FDA's actions to cease importation of Domperidone from outside the USA, and compounding of Domperidone from within, directly jeopardizes the ability of many mothers in this country to be able to adequately nourish their babies with the only healthy food available to them. Babies are intended to drink breastmilk - it is specifically made for them. To deny a lactating mother - who is unfortunate enough to suffer from low milk supply - the ability to take a perfectly safe drug which increases her supply and enables her to provide nutrition to her baby is unconscionable.

To issue a blanket warning against the use of Domperidone by lactating mothers in this country, based upon the potential risks from intravenous use, is effectively warning against incongruent drugs. The intravenous use is a dosage significantly higher than that which is being ingested by lactating mothers:

Domperidone is only 13-17% bioavailable orally. 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. FDA Warning on Domperidone, Thomas W. Hale, R.Ph., Ph.D., Professor of Pediatrics.

http://neonatal.ama.ttuhsc.edu/lact/html/
fda_warning_on_domperidone.html

In case you are not aware of the qualifications of Dr. Thomas Hale (see above insert), Dr. Hale is the author of three breastfeeding reference books, Medications and Mothers' Milk, Clinical Therapy in Breastfeeding Mothers, and Drug Therapy and Breastfeeding: From Theory to Clinical Practice, that are used throughout the world by physicians, nurses, NICUs, Obstetrical units, Lactation consultants, and LLLs.

Further, the American Academy of Pediatrics (AAP) has stated that Domperidone is approved, without qualification, for use in breastfeeding mothers by the American Academy of Pediatrics Committee on Drugs. AMERICAN ACADEMY OF PEDIATRICS: The Transfer of Drugs and Other Chemicals Into Human Milk PEDIATRICS Vol. 108 No. 3 September 2001, pp. 776-789 http://pediatrics.aappublications.org/cgi/content/full/108/3/776

The AAP further has found as follows:

Domperidone showed the highest mean volume on day7 & day14 followed by metoclopramide, malunggay & the control group. No major side effects were reported by the mothers & no untoward effects were noted in the infant fed milk expressed while their mothers were taking the galactogogues. Breastfeeding and Respiratory Hospitalizations: A Meta-Analysis, V. Bachrach,1 E. Schwarz,2 L. Bachrach2, 1Palo Alto, CA, 2UCSF, San Francisco, CA. http://www.aap.org/advocacy/bf/2002NCEAbstracts.pdf

When studying the efficacy of Domperidone in comparison to Metoclopramide (Reglan, which incidentally, is approved by the FDA for use in the USA), it was determined that:

Domperidone crosses the blood brain barrier and into the breast milk to a lesser extent than metoclopramide, decreasing the risk of toxicity to both mother and infant possibly making it an attractive alternative. J Hum Lact. 2002 Aug;18(3):274-9.

Further, the Physician's Desk Reference (PDR) indicates that Reglan has a side effect of serious depression - which as you may not know can be catastrophic for a postpartum woman and her baby. The PDR also indicates that the use of Reglan can produce the following side effects:

Breast development in males, confusion, congestive heart failure, continual discharge of milk from the breasts, depression, diarrhea, dizziness, fluid retention, frequent urination, hallucinations, headache, high or low blood pressure, high fever, hives, impotence, inability to hold urine, insomnia, menstrual irregularities, nausea, rapid or slow heartbeat, rash, rigid muscles, slow movement, swollen tongue or throat, tremor, vision problems, wheezing, yellowed eyes and skin.

In addition, Reglan may cause symptoms similar to those of Parkinson's disease, such as slow movements, rigidity, tremor, or a mask-like facial appearance.

Especially in older people, Reglan may produce tardive dyskinesia, a syndrome of jerky or writhing involuntary movements, particularly of the tongue, face, mouth, or jaw. In children and adults under 30, Reglan may cause involuntary movements of the arms and legs, and sometimes loud or labored breathing, usually in the first day or two of treatment.

Reglan may cause intense restlessness with associated symptoms such as anxiety, agitation, foot-tapping, pacing, inability to sit still, jitteriness, and insomnia. These symptoms may disappear as your body gets used to Reglan, or if your dosage is reduced. (emphasis added)

http://www.pdrhealth.com/drug_info/
rxdrugprofiles/drugs/reg1369.shtml

As Reglan does cross the blood-brain barrier, this makes it a higher risk for the above emphasized symptoms than Domperidone -- especially in the dosage commonly used and recommended for use by lactating mothers. Why is the FDA not concerned about the risks to public health caused by Reglan?

There are a plethora of drugs out there that have pages of side effects indicated in the PDR, yet the FDA approves their use without regard for "potential public health risks". There are also many drugs that are used for off-label use, yet the FDA neglects to remove these drugs from use in the medical profession. For example, the FDA is fully advised of the warnings and severe side effects of Cytotec, as cited on the FDA website:

CYTOTEC (MISOPROSTOL) ADMINISTRATION TO WOMEN WHO ARE PREGNANT CAN CAUSE ABORTION, PREMATURE BIRTH, OR BIRTH DEFECTS. UTERINE RUPTURE HAS BEEN REPORTED WHEN CYTOTEC WAS ADMINISTERED IN PREGNANT WOMEN TO INDUCE LABOR OR TO INDUCE ABORTION BEYOND THE EIGHTH WEEK OF PREGNANCY (see also PRECAUTIONS, and LABOR AND DELIVERY). CYTOTEC SHOULD NOT BE TAKEN BY PREGNANT WOMEN TO REDUCE THE RISK OF ULCERS INDUCED BY NON-STEROIDAL ANTI-INFLAMMATORY DRUGS (NSAIDS) (See CONTRAINDICATIONS, WARNINGS and PRECAUTIONS). http://www.fda.gov/cder/foi/label/2002/19268slr037.pdf

Yet, Cytotec is administered in hospitals around the country for its off-label use to induce labor in pregnant women. The FDA is not actively administering a public health advisory for this medication, or actively interfering with a pharmacies issuance of same. The FDA is totally inconsistent in it's approach and therefore, seemingly insincere in it's concern about the potential public health risks allegedly cause by Domperidone.

Finally, to address your comment, "[Domperidone] is an unapproved drug, an therefore importation of domperidone-containing products violates the law," I would request that you forward the legal cite to me indicating that this is true. It is my understanding that the FDA regulations state that it is legal for US residents to import medications from outside the US provided the following conditions are met: (a) The product was purchased for personal use and does not exceed a 3 month supply; (b) The product is not for resale; (c) The intended us of the product is appropriately identified; (d) The patient seeking to import the product affirms in writing that it's for the patient's own use; and (e) the medication is not a controlled substance, e.g. sleeping pills, Valium, narcotics.

Through it's directive, the FDA has effectively jeopardized the health of tens of thousands of nursing mothers and their babies. Mothers are forced to make the unfair decision to either use a galactagogue that has been documented and evidenced to create severe side effects (to the extent that many are forced to stop taking [Reglan, Metformin], or put their babies on formula and thereby increase their babies risk and exposure to a variety of serious side effects such as diabetes, otitus media, obesity, SIDS, etc. As far as my research indicates, the FDA has no new evidence to indicate such a rash and hasty decision, nor does it have substantial evidence to support its position. I beg the FDA to reconsider and retract this decision and enable lactating mothers with low milk supply the ability to acquire Domperidone for their health and the health of their babies.

Thank you,
Doreen Fisher, Lactating Mother of two
Garland, Texas