FDA Meeting on Compounding Domperidone

On October 28, 2015 there was an FDA meeting to discuss the request from the Pharmacy Compounding Advisory Committee (PCAC) to allow compounding pharmacies in the United States to compound domperidone.    Below are notes from that meeting.

The FDA presented information that, in the past 6 years in the United States, 7500-11600 prescriptions were written for domperidone annually.  77% of the prescriptions were written for women and most commonly for gastroparesis.

There have been three trials that proved the efficacy of domperidone for gastroparesis and nausea and vomiting trial showed clinical relevance for improvement of nausea and vomiting.

The FDA brought up the following safety concerns:

  1. QT Prolongation
  2. Proarrythmia Risk

If there is a heart event, it usually happens in the first week.  It most commonly happens in doses greater than 30 mg a day for individuals over age 65, or those taking other drugs that can cause OT prolongation.

From prior studies, it shows a 1.5 to 2.0 fold risk of sudden cardiac death.  And they indicated that there may be an under-reporting of adverse events because it is not an approved drug.

The final recommendation was that there are enough safety concerns to say that there could be significant harms to the public if domperidone is used without important safeguards.  It was NOT recommended to be added.

They did explain that domperidone is available through the IND program, but there was considerable discussion about the difficulty involved in this process and problems that physicians in individual practices might have in completing the requirements of the process.

A presenter for the other side of the argument dug deeper into the statistical studies to show that most studies were not statistically significant and that the mean age of 72.5 years shows that they started with a population that was historically a higher risk group.   In addition, not all the studies showed doses so you cannot make a determination based on the results of that study.

In addition, there are many approved drugs that increase the long QT interval.  Also, the countries that have increased restrictions for domperidone have also restricted reglan even more due to safety concerns.   He showed information that indicated that there were more adverse events with reglan that were life-threatening than there were with domperidone.  He admits that there is a risk but says that we need to evaluate better the scope of the risk.

He also brought up the May FDA meeting and the number of patients who expressed the amount of relief they get from domperidone and how difficult it is to obtain.   He also said that many doctors are not willing to deal with the IND process.

Dr. Moon said that prescribers and patients approach compounding pharmacists many times monthly asking for domperidone to be dispensed.  He said that there are plenty of nausea and vomiting drugs but they do not have the prokinetic effects.   He said that patients should not have to go outside of the country to get their medications.   He said that if a patient and physician choose an option that is available worldwide, then they should be able to obtain it.

In the public comments, Dr. Mark Burns (gastroenterologist) said that domperidone serves a vital need for those with gastroparesis.  He currently has 46 patients, ages 17 to 89, who are getting regular prescriptions for domperidone.  He appealed to the FDA to allow this drug to be compounded because of its efficacy for numerous gastrointestinal diseases.   For side effects, he saw higher prolactin in 3 and some cases of lactation. Even his older population shows no change in their regular EKG’s.  He said it is ideal for long-term use for upper and lower gastrointestinal diseases.

Baxter Phillips, from Neurogastrics, spoke of his company’s support of the FDA’s denial of the addition of domperidone.  His company is currently developing a new formulation that will work for gastroparesis.

The final speaker, Dr. Alan Diamond (gastroenterologist), spoke of the difficulty of prescribing reglan since he considers it to be a dangerous drug.  Many of his patients will refuse reglan when he explains the side effects.  People are also frightened by the lack of FDA approval for domperidone, so they take nothing.    The IND Process is cumbersome and time consuming and no one is willing to do it.

After considerable discussion by the committee, both pro and con, the committee voted 8-3 NOT to approve domperidone to be added to the bulk compounding list.  The majority seem to think that the IND process should be sufficient but that it might need to be streamlined so that more doctors are able to use that process to prescribe for their patients.