Received from a drug co selling domperidone.

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Safety information about Domperidone

 

Subsequent to a recent meeting held by the Pharmacovigilance Committee of the Medicines Control Council, we wish to bring to your attention safety information regarding an interaction between domperidone and ketoconazole and other concomitantly administered medicines.  This interaction may lead to QT prolongation which in some instances may cause life threatening cardiac arrythmias.

 

Domperidone is contraindicated with co-administration of ketoconazole.

 

Interaction studies with oral ketoconazole in healthy subjects have shown a marked inhibition of domperidone's first pass metabolism by ketoconazole and an approximately three-to ten-fold increase in Cmax and AUC of domperidone. In a study in which a three-fold increase of pharmacokinetic parameters was seen, a significant mean QTc prolongation of about 10-20 msec was seen for the combination of domperidone (10mg four times daily) and ketoconazole (200 mg twice daily) (slightly greater than the increase seen with ketoconazole alone), but not for domperidone monotherapy (10 mg four times a day). The QTc prolonging effect of this combination (i.e. with ketoconazole) is not completely understood and cannot be explained solely by domperidone pharmacokinetic data.

 

The risk of the interaction in patients with co-morbid cardiovascular disease is not known.

 

Domperidone is metabolised mainly by the CYP 3A4 enzyme. In vitro data indicate that the concomitant use of medicines that significantly inhibit this enzyme may interact with domperidone with resultant increased plasma levels of domperidone.  Examples of CYP 3A4 inhibitors include azole antifungals, macrolide antibiotics e.g. erythromycin, HIV protease inhibitors e.g. ritonavir, and grapefruit juice.

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