Drugs that are not FDA approved: Is there a time to prescribe them?

Here’s an interesting clinical dilemma brought to my attention by another physician.

She was asked to refill a prescription for a drug called domperidone to help a patient with lactation. Domperidone is not FDA approved in the United States for any indication. However, in Europe and in Canada it is approved as a promotility agent for patients with a condition called gastroparesis, which causes the stomach to empty very slowly and results in chronic nausea and vomiting. As a side effect the drug is also known to increase the production of prolactin, a hormone that stimulates milk production. In the case of this physician’s patient, she had adopted a child and found that the medication had effectively enabled her to produce milk and nurse, with seemingly no untoward effects. It’s unclear who had initially prescribed the drug, but various online lactation support forums discuss it as an option  for women who have trouble with lactation.

The questions: Is it legal, ethical or good medical practice for a physician in the United States to write a prescription for domperidone for a patient who has been using it for lactation with good results? How about for gastroparesis? Where does one get the drug? Is it even legal to sell the drug in the United States?

I’ve cared for at least two patients who have used domperidone. In both instances it was ordered by prescription from an overseas source by a local gastroenterologist. In these two cases my patients had tried just about everything on the market in the United States for gastroparesis and were still struggling with debilitating symptoms. In one case, my patient had required hospitalizations and ultimately a feeding tube because of intractable vomiting. The drug was ineffective in both patients and it was eventually discontinued.

As I read more about this medication I discovered that the FDA cautions:

FDA warned healthcare professionals and breastfeeding women not to use an unapproved drug, domperidone, to increase milk production (lactation). The agency is concerned with the potential public health risks associated with domperidone. FDA took these actions because it has become aware that some women are purchasing this drug from compounding pharmacies and from foreign sources. Although domperidone is approved in several countries outside the U.S. to treat certain gastric disorders, it is not approved in any country, including the U.S., for enhancing breast milk production in lactating women and is also not approved in the U.S. for any indication.

The concern over domperidone is its potential to induce potentially fatal cardiac arrhythmias through QT prolongation (an alteration of electrical activity in the heart). This risk has been recognized in Europe and is currently under study. Nonetheless, at least one expert panel in Canada has endorsed the safety of the drug for use in lactation (though not currently approved for this use in Canada).

As my colleague and I discussed the situation with her patient we both concluded that it would not be prudent to refill this prescription for the purpose of lactation. In fact, it would likely be construed as medical malpractice, in light of the drug’s status with the FDA, should the patient or her baby suffer any toxicity. However, clearly there are gastroenterologists who feel that prescribing this medication in United States for cases of severe gastroparesis is justifiable—and I would concur that in certain situations this might be a compassionate and reasonable option despite the regulatory concerns.

To further extend this discussion — physicians do frequently prescribe drugs that are on the market and FDA approved for off-label use. For example, just yesterday I prescribed gabapentin for hot flashes. One interesting study published in Archives of Internal Medicine found that 21% of sampled medications were being prescribed for off-label use.

The authors concluded:

The Food and Drug Administration (FDA) focuses on market entry for prescription drugs rather than regulating physicians’ prescribing practices, allowing off-label use of medications for indications beyond those formally evaluated by the manufacturer. Off-label prescribing of medications is legal, often thought to be supported by scientific evidence, and common in certain clinical settings. Although this practice provides a pathway to innovation in clinical practice, it raises key concerns about risks to patients and costs to the health care system.

Whereas prescribing approved medications for off-label use falls into the realm of acceptable clinical practice, one has to be very circumspect about prescribing drugs that are not deemed adequately safe or effective to market in the United States for any indication. Unfortunately for those who feel that the FDA is too slow, political, or conservative in its approval process, these are the regulatory constraints under which physicians must practice in the United States.

Juliet K. Mavromatis is an internal medicine physician who blogs at Dr Dialogue.

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  • guest

    Four years ago I was part of a due diligence team where we had the opportunity to replace a $1,000 per week drug treatment for cancer patients with a $50 per week commonly available drug. This was a procedural change that effected a $7 billion per year market, equally divided between 2 giant pharma companies.

    As we examined medical and financial records of several oncology practices, we learned that each oncologist focused on one of these two drugs and as we plotted the data, we noticed a spike in use of these drugs towards the end of each quarter.

    Oncologists get a legal quarterly commission from pharma companies, a commission rate that grows rapidly based on quarterly usage of the

    Examining medical records revealed that many dying cancer patients were routinely injected with unnecessary drugs in order for the practice to meet quarterly goals.

    Our show stopper discovery was that as a new patient walks into an oncologist office, the patient gets an exam from the Dr while the patient’s insurance card is examed by the business office and in 96% of the time, the physicians selected the most profitable course of treatment for their patients.

    It’s disgusting to think that the physician that is charged with saving your life is in the grips of the pharm companies, more interested in making a buck than your well being.

    Such is the state of medicine-for-profit as practiced in our country where legislatures are either sleep at the switch or in the packets of drug lobby!

    • Suzi Q 38

      I try to avoid doctors that work in this manner.
      Thanks for letting us know.

      • Guest

        “Thanks for letting us know.”

        Please don’t take every anonymous comment on the internet as gospel truth. As tiredoc points out, the other guest’s comment is close to libelous.

        • Suzi Q 38

          Good point.
          You are yet another poster with the name “guest.”
          It would be better for me and others if you would choose a fake name. This way, I won’t think that you are a “troll.”
          Your comment is too reasonable to come from such.

          • Annie

            Fair enough. Better? :)

          • Suzi Q 38

            Nice name, Thanks.

    • C.L.J. Murphy

      If you have evidence that physicians are placing their own profit and financial considerations ahead of the best interests of their patients, I hope you’ve reported these physicians.

      I for one have never met an American doctor who does this.

      • ninguem

        There has been a number of scandals with oncologists (and pharmacists) over chemotherapy.

        This pharmacist was diluting chemotherapeutic drugs for cancer. The manufacturer (Lilly) saw the discrepancy between what the pharmacist claimed to be billing, and the amount of drug purchased from the manufacturer.

        Of interest, it was the drug rep (the people we always make fun of) that “smelled a rat”, and brought up the suspicion to Lilly, and then to an oncologist, who went on to have the drug tested and found it was diluted.

        http://en.wikipedia.org/wiki/Robert_Courtney

        And there have been some serious bad cases with the oncologists as well.

        http://www.myfoxdetroit.com/story/23120297/hearing-set-today-in-michigan-cancer-doctors-fraud-case

        Not saying this happens often……just saying “never say never”

    • Tiredoc

      You are incorrect and possibly libelous. There is no such thing as a legal quarterly commission. You are assuming nefarious motives where none exist other than basic financial incompetence. Chemotherapy drugs administered in-office are “buy and bill,” meaning that the oncologist buys the drug and bills the insurance company. The practices you’re looking at are playing catch-up with their billing in order to get paid before the end of the quarter when to doctors actually pay attention to the bottom line.

  • Steven Park

    How often do you prescribe water for patients that are mildly dehydrated? Water is NOT FDA approved for dehydration.

  • Suzi Q 38

    Why not? Are Vitamins FDA approved?

  • Ron Smith

    I don’t think bilirubin lights for neonatal hyperbilirubinemia ever got approved?

    Pediatrics tended to be a pioneer in by-gone years, because we didn’t have anyone that would do studies for the new drugs. Same for procedures I suppose. The first cardiac repair I think was on a child with Tetralogy of Fallot.

    Ron Smith, MD
    www (adot) ronsmithmd (adot) com

    • Tiredoc

      For drugs, the FDA requires that they are safe AND effective. For medical devices and procedures, the FDA requires that they are safe. The US is a generation ahead of the world in surgery and equipment, but a generation behind in pharmaceuticals. The best thing the Congress could do for the health of this country is remove the requirement for the FDA to certify the effectiveness of drugs.

  • Dave

    I’ve always found FDA’s stance on domperidone to be puzzling, especially considering the side effect profile for the drugs that ARE currently approved for gastroparesis.

  • C.L.J. Murphy

    When I practiced in Australia, I used domperidone with great success in a patient with porphyria (HCP) for years. This patient had an acute attack exacerbated once when she was administered metoclopramide in an ER, where she presented for vomiting and nausea, and I knew that at least domperidone wouldn’t be porphyrinogenic.

    I also agree with commenter Dave: of course there are potential side effects with any drug, but given some of the drugs that America’s FDA *does* give their “seal of approval” to, it’s surprising to see domperidone getting the cold shoulder.

  • doc99

    Now that you mention unapproved drugs, isn’t it about time the FDA reclassified cannabis from Schedule I to Schedule II?

    • guest

      Why does the FDA even have anything to do with pot? Do they also give their seal of approval to ecstasy or crack?

  • Tiredoc

    I don’t think that there is any legal justification for prescribing a non-FDA approved drug for lactation. I had one case where domperidone for gastroparesis was prescribed for an inpatient, but that is potentially a life-threatening ailment, and the proper FDA channels were involved. There is a process by which the FDA will allow medications to be imported, but they have to pass a certain level of severity. A trip to Canada for the patient is probably safer.

    • Michael Rack

      agree. Domperidone is useful for gastroparesis- its decreased likelihood for causing neurologic side effects makes it attractive (compared to metoclopramide). In my personal opinion, due to the potential cardiac risks, using it for lactation purposes is malpractice

  • Fat Rasputin

    Just to throw this out there, I have a rare disease and everything I take is off label. Should I get nothing?

    • Michael Rack

      No, of course not. Drugs are used off label all the time- this is very different from prescribing a drug that is not FDA approved for any indication.

      • Fat Rasputin

        I was kind of being snarky there but my real point is the FDA approval is not the end all be all. Just because a drug is not approved for any indication by the FDA or not for a specific indication does not mean it is not a valid use. The FDA drug approval process is let us say nicely that it is flawed.

        • Michael Rack

          If a drug is not approved for any indication in the US, how does a doc prescribe it? I agree that the FDA approval process is flawed

  • Michael Rack

    I wish Dr. Mavromatis had written more about the process of prescribing a FDA non-approved drug. Does one write out a prescription? Where does the patient take it (to a foreign pharmacy?)? Is this potentially illegal? This is not a common situation for docs to deal with, and I am curious.

  • KJK

    I work in a compounding pharmacy, and domperidone is something which we compound pretty regularly. I would be interested to know what panel it was in canada. because if it was mothersrisk. I know from my clinical experience that they do quite a bit of research both in canada as well as looking in many other countries and at case reports to determine their recommendations on medications prior to putting any of them in print. I think that there are times in our professional careers that we must look at the research for ourself and make judgements based on risk vs. benefit for each individual patient. It is impossible for us as clinicians to believe that the FDA has the time to look at every study that is done for every medication and re-adress these medications after previously being un-aproved. I think when a new drug comes out, or when new situations arise such as severe side effects then they step in. But sometimes, they make mistakes.

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