Critique of the Health Canada-Endorsed Domperidone Advisory
The following has been published by the group at Newman Breastfeeding Clinic and Institute.
For some background, see the following posts/links:
- The Health Advisory
- Blog Post outlining implications on breastfeeding
- CBC piece on the Health Advisory
Critique of the Canada Health-Endorsed Advisory about Domperidone
The recent Health Canada-endorsed warning about the use of domperidone was based on two studies published in 2010 (1,2). The information in these studies was taken from databases (one in the Netherlands (2) and one in Saskatchewan(1)) and did not demonstrate that domperidone caused any adverse health effects.
The warning was based on information gathered from an entirely different population than those who would be taking domperidone for breastfeeding purposes and is thus not generalizable to the lactating population. The average age of the patients in the studies was 72.5 years in one(2) and 79.4 years in the other(1). Many of the patients in the studies had pre-existing health problems such as high blood pressure, coronary artery disease, and congestive heart failure.
There were, however, some notable trends that, when extrapolated to the breastfeeding population largely comprised of younger, healthier women, are quite reassuring. In one study1, the authors concluded that the risk of a cardiac problem related to taking domperidone in younger patients was much lower than in older patients. In fact, the risk quoted in younger patients was almost the same as that outcome occurring by chance alone (OR of 1.1 in those younger than age 60 compared with an OR of 1.64 in those older than age 60). That study also specifies that the risk in females was significantly lower than in males (OR of 1.25 in females compared with an OR of 2.23 in males). It is also important to highlight that the risk decreased the longer the patient had been on domperidone(1) which is important to note because mothers taking domperidone for the purposes of breastfeeding are often on it for many months.
The warning regarding the use of domperidone in higher doses (>30mg per day) was based on only one of the two studies(2); the other study(1) did not include any information about dosing. In the one study where dosing information was included, out of the 1304 deaths that were studied, only 10 patients were taking domperidone at the time of death. Of those 10 taking domperidone, only FOUR patients were documented to be taking higher doses of domperidone (>30mg per day). Thus this Health Canada-endorsed dose-related warning came from dosing data compiled from a total of FOUR patients. In fact, the authors were not specifically cautioning physicians not to prescribe higher doses, but rather were suggesting that “it is important to avoid prescribing domperidone to patients with a high risk of sudden cardiac death”. It is very hard to make a case for a drastic reduction in domperidone dose in lactating women (wherein a dose of
Domperidone is generally used to treat gastro-intestinal problems such as acid reflux.Some of the symptoms of heart disease may mimic symptoms of a gastro-intestinal illness. It is possible that some patients were taking domperidone for what was thought to be a gastro-intestinal problem when, in fact, the symptoms may have been related to a heart problem. While the authors attempted to account for this possible protopathic bias(2), it is hard to tease out the etiology of the potentially overlapping symptomatology, thus potentially affecting the results. Furthermore, because domperidone is available over-the-counter in parts of Europe, it is conceivable that the number of people self-medicating with domperidone is higher than the rate actually quoted in the Dutch study
(as the study only took into account prescriptions for domperidone(2) and not over-the-counter use). This important fact may have skewed the results. Some other important limitations of the studies include the fact that key pieces of information are unavailable including smoking status, use of other non-prescription drugs, all of which can be important factors(1) in affecting the study results.
In summary, breastfeeding mothers using domperidone are generally younger, healthy females. They do not fall into the same demographics as the patients involved in the studies from which the warning was generated. Furthermore, with caution about the use of higher doses of domperidone stemming from a study where so few patients were actually on those higher doses, the Health Canada-endorsed warning regarding the use of domperidone in higher doses seems to be an over-reaction. Finally, taking into account the other drawbacks of these studies as outlined above, there is no evidence that domperidone actually causes ventricular arrhythmias or sudden cardiac death.
1 Johannes CB et al. Risk of serious ventricular arrhythmia and sudden cardiac death in a cohort of users of domperidone: a nested case-control study. Pharmacoepidemiol Drug Saf. 2010 Sep; 19(9): 881-888.
2 van Noord C et al. Domperidone and ventricular arrhythmia or sudden cardiac death: a population-based case-control study in the Netherlands. Drug Saf. 2010 Nov 1; 33(11):1003-1014.