FDA Domperidone Transcript

The following is an unofficial, but accurate, transcript of the FDA Domperidone Warning.

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FDA Warning on Domperidone Conference Call on June 7 -11, 2004.
Tel: 1-800-947-5189 Program pass code # 1673

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Good afternoon and thank you for standing by. At this time all participants are in a listen only mode. After the presentation, we will conduct a question and answer session. To ask a question you may press * 1. This conference is being recorded. If you have any objections you may disconnect at this time. I’d now like to turn the meeting over to your host for today’s conference, Miss Crystal Wright, Miss Wright you may begin.

Crystal Wright: “Thank you Theresa. Good afternoon everyone. Thank you so much for joining us this afternoon for this important announcement. I’m here with the office of compliance and we’d like to talk with you today about an unapproved drug that is affecting women of the breastfeeding community. At this time I’d like to introduce Dr. Susan Allen.”

Dr. Susan Allen: “Good afternoon. Thank you very much for joining us on this call to discuss actions that our agency has taken today related to the drug domperidone. By way of introduction my name is Dr. Susan Allan. I am the associate director of scientific and medical affairs in the office of compliance and the centre for drug evaluation and research at the FDA.

As you know, a few hours ago we released a public statement describing enforcement actions that FDA has taken today against several pharmacies that are compounding domperidone, against firms supplying the bulk drug for compounding in the United States, and against importation of the drug.

This drug is not approved in the United States for any indication and it is illegal to compound, import, or distribute this product in the United States.

We have become aware of numerous pharmacies compounding this drug for use by breastfeeding women. And we’re also aware that this product is being offered for sale from foreign sources via the internet. We’re concerned about the growing and potentially extensive use of this product by breastfeeding women to enhance milk production and the potential safety risks that could be posed to both the woman and her breastfeeding infant by use of the drug in this way.

As we noted in our public statement released earlier today, we recognize the immense health benefits that breastfeeding provides for a nursing infant and we want to be very clear that we are taking these actions today not to discourage women from breastfeeding but rather to warn them against using this particular drug while they are breastfeeding.

I thought it would be helpful if I took a few minutes to provide you with more detailed background information about why we have taken these enforcement actions and issued a public statement about this today.

Over the past few months, we’ve become aware of an increasing number of pharmacies compounding this product in the United States. We’ve received reports about more than 20 pharmacies compounding this drug in more than a dozen states. We’ve also become aware of the drug’s promotion for use by breastfeeding women to enhance lactation and its sale online from several foreign sources.

As I mentioned the drug is not approved for any use in the US and it’s not approved for enhancement of milk production in any country. This product is approved in some other countries. However, in several of those countries where the product is marketed, labels for the product contain specific warnings against the use of domperidone by breastfeeding women and note that the drug is excreted in breastmilk which could expose a breastfeeding infant to unknown risks.

Our concerns about the use of this drug by breastfeeding women fall primarily into the following 5 categories:

First: Lack of approval of this drug for this indication.
Second: The extent of use of this drug by breastfeeding women in the United States.
Third: Potential maternal safety risks associated with the dosing and the dosing regimen suggested for use to increase lactation.
Fourth: Potential safety risks for a newborn or an infant.
And Fifth: Potential risks associated with purchasing a drug via the internet.

So let me start with the first issue, which is lack of FDA approval for this drug. The safety and the efficacy of this drug for this indication has not been determined by FDA or by any other regulatory agency. There are a handful of published studies about the use of this product to enhance lactation. However, the majority of these reports are based upon small-scale studies involving very limited duration of administration of the drug. And by that I mean anywhere from a single dose of the drug to no more than 7 to 10 days of use. None of the studies investigated the safety of higher doses or longer treatment duration with domperidone.

Some of these studies were conducted in patient populations other than the target population. For example, studies conducted in healthy male volunteers, or non-lactating women. Most often, these studies focused on the volume of milk production and serum prolactin levels without measurement of drug concentrations in maternal serum or milk. In those studies that did measure domperidone concentrations in serum and milk, single time point or random measures of these end points were often made which do not permit an assessment of time concentration profiles of the drug in serum and milk, and therefore can’t adequately estimate drug exposure in a breastfed infant.

None of these studies were designed to evaluate maternal or infant safety. And none looked at infant exposure via blood levels of the drug. The design of these studies, were insufficient to provide a complete phameco-kinetic profile of the drug, much less substantial evidence of safety and efficacy for this use indication.

So in short, adequate and well controlled clinical studies to evaluate the safety and the efficacy of this drug for use as a galactogogue simply have not been conducted.

The second issue that I mentioned had to do with the extent of use by breastfeeding women in the United States. We don’t know the exact extent of use of this product by breastfeeding women, but we are concerned that such use may be extensive because of the fact that numerous pharmacies in the United States are compounding this product and it’s offered for sale online. Some online groups for breastfeeding women promote the use of this product as a galactogogue. And we know that this product has also been promoted as a safe and legal product for breastfeeding women to use. And as I stated, we do not believe the safety of this product has been ascertained and it is clearly not legal to compound, sell, import or distribute this product in the United States.

The third concern related to potential maternal risks. One of our greatest concerns about use of this product by breastfeeding women is related to the dose and the dosing regimens that are being suggested for use of the product as a galactogogue. In those countries where domperidone is approved for use to treat gastric disorders, the maximum daily dose recommended for use is a total of 80 milligrams. We know that doses up to 5 times the recommended dose and twice the maximum total daily dose approved in other countries have been suggested for use by breastfeeding women to enhance milk production. These high doses could be used by women for many months at a time, and we’re concerned about the potential safety risks associated with such use for that time.

Some of the labels in countries where this product is approved recommend a patient taking this drug be re-evaluated after 4 weeks, to discuss the need for continued treatment with the drug. And others note that the safety and efficacy of the drug beyond six months of use has not been established. In those countries where the product is approved for the treatment of gastric disorders, the labels for the product contain specific contraindications for use, including things such as prolactin releasing tumours, concomitant use of certain medications, gastric haemorrhage, obstruction or perforation.

A woman who is obtaining this unapproved drug from a compounding pharmacy or from an online source, may not receive complete information about the potential risks with the product including interactions with other drugs that she may be taking, specifically, drugs that inhibit the enzyme that breaks domperidone down, such as certain anti-fungal medications like Tioconazole, and certain antibiotics like erythromycin could result in increased blood levels of domperidone with associated safety risks. If a woman is not informed about these potential drug-drug interactions, she could be exposed to high serum levels of domperidone without knowing it.

We know that there were several reports of cardiac arrest, and sudden death associated with an intravenous dosage form of this drug. That dosage form was withdrawn from marketing. It is possible that high doses of the oral form of this drug or drug-drug interactions between domperidone and certain other drugs that a woman is taking could result in blood levels of domperidone similar to those associated with adverse cardiac events following the intravenous administration of the drug.

The third category of risk related to potential risks to the newborn or the infant. I’ve already mentioned the fact that no studies have been conducted specifically to evaluate infant exposure to this drug via breastfeeding or safety related to this drug in a breastfeeding infant. This drug is known to be excreted in breastmilk and labels for the product in several countries where it is approved, specifically state that it is unknown whether the amount of domperidone excreted in breastmilk is harmful to newborns and they recommend that women taking this drug not breastfeed. The amount of drug that’s excreted in breastmilk as stated in these labels is based upon maternal consumption of a maximum daily dose of 80 milligrams of the drug, which may be much less than the amount that women are taking to enhance milk production.

Neurological side effects are mentioned in the approved label for the product and since the blood-brain barrier is not fully developed in an infant during the first few months of life, the risks of neurological side effects of this drug in younger children is higher than in an adult’s. One approved label for the product notes that extrapyramidal symptoms, disturbance of consciousness and convulsions can occur in children taking domperidone and it recommends that this drug be administered with extreme caution in infants under one year of age and notes that duration of administration should not exceed 7 consecutive days of use in children less than 3 years of age.

The last category of concern has to do with the potential risks from online purchasing of this drug. We believe that online purchasing of this product has inherent risks associated with the purchase of an unknown product that may or may not be the product advertised for sale on the website. The product may have no accompanying directions for use and the product and any accompanying materials may not contain adequate safety information.

In addition to these concerns we’re also concerned from a public health perspective that breastfeeding women may be receiving misleading, inaccurate, or incomplete information about the safety and effectiveness of this product for use as a galactogogue. And for these reasons, we believed it was important today to take the enforcement and educational actions that we have taken.

That ends the statement that I wanted to make and we will be glad to answer any questions that you have about what we’ve just shared with you.”

Crystal Wright: “Theresa, this is Crystal, we’re ready for the question and answer session.”

Theresa: Thank you, at this time we are ready to begin the formal question and answer session. If you would like to ask a question press * 1. You will be announced prior to asking your question. To withdraw your question please press * 2. Once again to ask a question please press * 1. One moment….There are no questions at this time.

Crystal Wright: “Thank you Theresa. Thank you everyone. Please again review the materials on our website at www.fda.gov. Thanks again for participating and have a great day.

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