domperidone

INTRODUCTION

Domperidone, a prokinetic and antiemetic agent, is a peripheral dopamine2-receptor antagonist with effects in the upper gastrointestinal tract and the chemoreceptor trigger zone. Domperidone antagonizes the effect of dopamine on the smooth muscle, including the gastric and esophageal sphincters, which results in increased smooth-muscle contraction in the stomach and duodenum and hence increased gastrointestinal motility. Antagonism of dopamine action at the chemoreceptor trigger zone results in antiemesis. At the pituitary level, antagonism of dopamine leads to prolactin release, and as such, domperidone has been reported to cause gynecomastia, galactorrhea, oligomenorrhea, amenorrhea, infertility, decreased libido, hirsutism, and acne, all of which are manifestations of hyperprolactinemia.

Pediatric patients with cystic fibrosis account for a large proportion of domperidone users because of the high incidence of gastroesophageal reflux disease (GERD) in this population (estimated at between 25% and 81%). Prokinetic agents such as domperidone are frequently prescribed to alleviate GERD- related symptoms and to target the delay in gastric emptying that has been noted in this population. buy female viagra

At the Children’s and Women’s Health Centre of British Columbia, GERD therapy for children with cystic fibrosis typically involves a histamine2-antagonist (e.g., ranitidine) or a proton pump inhibitor (e.g., omeprazole). Domperidone is prescribed if these therapies are ineffective or not tolerated. At the time of writing, domperidone was prescribed for the alleviation of GERD symptoms for about 40% of patients with cystic fibrosis at this institution. As of late 2005, use of the drug exceeded 83 600 tablets per year, an increase from 14 600 tablets per year in 2001. This increase was related to withdrawal of the prokinetic agent cisapride from the Canadian market in August of 2000.

In March 2003, the cystic fibrosis medical team was involved in caring for a 15-year-old female with cystic fibrosis who presented with amenorrhea and in whom prolactinoma was subsequently diagnosed. At the time, she was receiving multiple drug therapies, including domperidone 0.9 mg/kg daily, for the management of her cystic fibrosis. The physicians involved in her care, including the cystic fibrosis and endocrinology medical teams, suspected that the prolactinoma might be associated with the use of domperidone. Domperi- done therapy was therefore discontinued, and serial samples were drawn for determination of serum prolactin levels to mon­itor her progress. At the time of diagnosis of the prolactinoma, the patient’s prolactin level was elevated, at 83.6 Hg/L (normal range 3.3—26.7 Hg/L); it decreased to a normal value of 11.6 Hg/L within 2 days of discontinuation of domperidone therapy. Suspecting a direct, clinically significant relationship between the elevated prolactin level and domperidone, the cystic fibrosis team began to routinely monitor prolactin levels in all children with cystic fibrosis who were receiving this drug.
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No specific guidelines are in place at this institution for monitoring prolactin or interpreting prolactin values in patients receiving domperidone therapy. A thorough literature search (using MEDLINE, EMBASE, PubMed, the Cochrane Database of Systematic Reviews, and Google databases) revealed no published guidelines for interpreting prolactin values in this population nor any evidence supporting this practice. In view of this lack of evidence and apparent incon­sistency in the timing, frequency, and clinical interpretation of prolactin levels in relation to domperidone dosing, as well as the associated costs ($30.76 for a single prolactin determina­tion), a review of this practice was undertaken.

The purpose of this chart review was to assess the use of prolactin monitoring in children with cystic fibrosis who were receiving domperidone therapy. The specific objectives were to characterize how prolactin values were used in monitoring these patients, to evaluate the appropriateness of this practice, and to formulate recommendations accordingly. suhagra 100