Side-effects of domperidone

Is domperidone safe?

Like any medication, domperidone can cause side-effects. These include headaches, the most common side-effect; diarrhea, nausea, mood swings, and allergic reactions which are less common; and heart problems and movement disorders, which are rare. Domperidone has the potential to cause abnormal heart rhythms that result in fainting, seizures, and sudden death. That risk is increased in mothers who have a particular heart condition or are taking more than 30 mg each day. Certain medications and some citrus fruits can also increase the risk and should not be taken with domperidone. Mothers should not take domperidone if it is not effective and if it causes side-effects or they are at an increased risk of them. A few mothers develop problems when stopping domperidone. There have not been any side-effects reported in babies whose mothers took domperidone.

A) Describing the side effects of domperidone

Allergic reaction to domperidone causing a generalized rash. The right side of the tummy is shown.

Domperidone is a medication that is sometimes used to increase milk supply. One study of breastfeeding Australian mothers showed that, of those who were taking domperidone, 45% experienced side-effects (McBride 2021). Reported side effects include (Asztalos 2017):

  • Most common: mild chronic buzzing headache, diarrhea, nausea, weight gain
  • Less common: mood swings, dry mouth, allergic reactions such as rashes or hives
  • Least common: anxiety, panic attacks, insomniamovement disorders, seizures, abnormal heart rhythms causing dizziness, abnormal heart poundings, fainting, heart stopping, death

Stopping domperidone can also cause side-effects.  

Please work with your health-care providers if you experience any symptoms while taking or stopping domperidone.

B) Risk of sudden cardiac death

1) Describing long QT syndrome

Long QT syndrome is a heart rhythm condition that can cause quick, irregular heartbeats which are relatively ineffective at moving blood through the body. The lack of blood flow can cause: 

  • Fainting spells
  • A heart beat you can feel (palpitations)
  • Seizures
  • Sudden death

Long QT syndrome can be inherited and present at birth. One study (Schwartz 2009) estimated that one in 2000 babies are born with it. It can also develop later in life when caused by domperidone or other medications or by having low blood levels of potassium, magnesium or calcium. The risk of long QT syndrome is increased in: (Anderson 2017; Leelakanok 2016):

  • Women.
  • Individuals who:
    • Are obese.
    • Have a history of abnormal heart rhythms.
    • Are older. 

2) Domperidone and heart problems

Domperidone has the potential to create a long QT syndrome, abnormal heart rhythms (ventricular arrhythmia), and death (Arana 2015; Buffery 2015; Frommeyer 2017; Leelakanok 2016; Morris 2016; Smolina 2016). While rare, this consequence is tragic. These side-effects are more likely to occur if the individual taking domperidone:  

  • Is taking doses above 30 mg each day.
  • Is older than 60 years.
  • Has other health conditions.
  • Is taking other medication that can affect the heart rhythms.

As of March 2017, Health Canada had reported 19 serious heart events (no deaths) in patients taking domperidone since its use started, about 30 years ago. Most were thought to be related to the medication (Health Canada 2017).

One study estimated that the risk of sudden cardiac death in women of primary child-bearing age (20 to 39) who are treated for 2 to 4 weeks with domperidone (30 milligrams a day) is about 112 deaths per million days of taking 30 mg of domperidone (Hondeghem 2017). 

The European Medicine Agency reviewed this medication and concluded that domperidone had “extremely limited evidence of efficacy” and that the risk of cardiac death outweighed its potential benefits (EMA 2014).

Metoclopramide can have similar negative effects on the heart rhythm but the risk is lower.

C) When not to take domperidone

Mothers should not take domperidone if:

  • It is not effective.
  • It causes side-effects.
  • They had a particular problem with their stomach or bowels (blockages, bleeding, rupture of the wall of the stomach or intestine).
  • They have:
    • A problem with the muscle of their heart.
    • Moderate or severe liver disease.
    • Known long QT syndrome.
  • They combine domperidone with other medications:
    • That increase the blood levels of domperidone.
    • That cause abnormal heart rhythms. 
  • Continue to eat certain citrus fruits or juice that increase the blood levels of domperidone.

D) Medications that can interact with domperidone

Many medications should not be combined with domperidone, as they can increase the levels of domperidone in the mother’s body or have the same side-effect as domperidone on the heart, increasing the risk of this effect.

Always discuss combining domperidone and other medications with your health-care providers.  

1) Fluconazole

Breastfeeding mothers who develop nipple yeast should not combine domperidone with the anti-fungal medication fluconazole. If fluconazole is the only treatment option, mothers should stop domperidone until the yeast treatment is completed.

Domperidone levels in the body fall by one-half by 16 hours and levels would be extremely low within 80 hours (3 1/3 days). In comparison, fluconazole remains in the body twice as long. It takes about 31 hours for the blood levels to decrease by one half (Debruyne 1993), and takes about 155 hours (6 1/2 days) for levels to be very low.

Following these numbers:

  • Fluconazole could be started 3 days hours after the last dose of domperidone.
  • Domperidone could be restarted 6 days after the last dose of fluconazole.

2) Other medication

There are more than 150 medications that can cause a long QT interval and the number is increasing (Arunachalam 2018). The following are a few of the more commonly encountered medications: 

  • Antibiotics: fluoroquinolones: (ciprofloxacin, moxifloxacin), macrolide antibiotics (clarithromycin, erythromycin), pentamidine
  • Antifungals: fluconazole, miconazole
  • Drugs that prevent abnormal heart rhythms: amiodarone, disopyramide, ibutilide, procainamide, quinidine, sotalol,
  • Antipsychotics: droperidol, haloperidol, pimozide, ziprasidone,  
  • Antidepressants: amitriptyline, citalopram, desipramine, doxepin, imipramine, maprotiline, nortriptyline, trazodone
  • Others: dolasetron, doxepin, methadone, ondansetron

E) Citrus fruits that can interact with domperidone

Some citrus fruits, whether taken as whole fruit or fruit juice, contain chemicals (furanocoumarins) that interfere with the body’s ability to breakdown some medication, causing levels to rise and increasing the risk of side-effects.

These fruits are:

  • Grapefruit
  • Limes
  • Seville oranges (often used for marmalade)
  • Pomelos

Domperidone is one such medication and side effects can be significant and include developing abnormal heart rhythms and death. Mothers taking domperidone should avoid all of the above citrus fruits.

F) Becoming dependent

A few mothers become dependent on domperidone and develop side-effects when stopping it. These include (Anderson 2017; Doyle 2017; Manzouri 2017; Papastergiou 2013; Seeman 2015):

  • Anxiety, panic attacks, agitation, shaking
  • Headaches
  • Difficulty sleeping 
  • Rapid heart rate
  • Nausea

In such cases, domperidone needs to be slowly decreased. 

This may be more of a problem for mothers on doses above 30 mg each day. We have seen this twice in our clinic, with one mother developing anxiety symptoms and the other depression.  

G) Prolactinoma growth

There is a concern that a certain brain tumour (prolactinoma) that makes prolactin may increase in size with domperidone use, but the research supporting this is limited (Van Seters 1985).

If you have a prolactinoma and are considering domperidone, please discuss this with your health-care providers.

H) Effects on the baby

There have not been any side-effects reported in babies whose mothers took domperidone. About 0.01% of the mother’s dose gets into breast milk (NIH). This is extremely low. Furthermore, only about 15% of the medication taken in through breast milk leaves the gut and enters the baby’s body (Asztalos 2018).

Some researchers have suggested the baby’s brain is less able to screen out some medication than the adult brain, which could increase the effect of even a small amount of medication (Ghersi-Egea 2018; Saunders 2012). This is another reason for the judicious use of domperidone. 

References

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