Treatment of functional dyspepsia in Chinese adult patients with domperidone: A multicenter, randomized, double-blind, placebo-controlled pilot study.

OBJECTIVE: This pilot study aimed to evaluate the efficacy and safety of domperidone for the treatment of Chinese patients with functional dyspepsia (FD) who were diagnosed according to the Rome IV criteria and to identify the FD subtypes that potentially responded better to domperidone. METHODS: This multicenter prospective study was conducted in China from August 2018 to July 2020, consisting of a 1-week screening phase and a 2-week double-blind treatment phase. Participants were randomized to receive domperidone 10 mg or matching placebo tablets thrice daily for 14 days. The primary end-point was the overall treatment effect (OTE) response rate after 2-week therapy. RESULTS: Altogether 160 patients were included, with 80 patients in each group. The OTE response rate after 2-week therapy was significantly higher for domperidone compared with placebo (60.7% vs 46.0%; relative risk [RR] 1.318, 95% confidence interval [CI] 0.972-1.787). Moreover, the OTE response rate after 2-week domperidone or placebo treatment was 60.3% versus 54.9% for postprandial distress syndrome (PDS) (RR 1.098, 95% CI 0.750-1.607) and 60.6% versus 35.2% for overlapping PDS-epigastric pain syndrome (EPS) (RR 1.722, 95% CI 0.995-2.980). Adverse events were reported by seven patients in the domperidone group and 12 patients in the placebo group. None of the adverse events in the domperidone group were serious. CONCLUSION: Domperidone showed a positive pattern regarding OTE response rates after 2-week therapy compared to placebo in patients with FD, as well as in subtypes of PDS and overlapping PDS-EPS. No new safety issue was observed.

A blinded, randomized and controlled multicenter clinical trial to assess the efficacy and safety of Leisguard® as an immunotherapeutic treatment for healthy Leishmania infantum-seropositive dogs.

BACKGROUND: Domperidone (Leisguard®) is an immunomodulatory drug used as a preventive measure in healthy dogs. However, no studies have been published in healthy Leishmania infantum-seropositive dogs. The aim of this study was to evaluate the clinical efficacy and safety of domperidone as immunotherapy in Leishmania-seropositive healthy dogs. METHODS: Sixty-seven dogs were treated with domperidone at 0.5 mg/kg and 44 dogs received placebo, once daily for 4 consecutive weeks. Monthly treatments were repeated every 4 months until the end of the 1-year follow-up period. Veterinary examinations were performed on days 0, 30, 120, 150, 240, 270 and 360. Samples of blood and urine were collected on days 0, 120, 240 and 360 for routine laboratory tests and quantitative in-house ELISA for the detection of L. infantum-specific antibodies. Furthermore, Leishmania real-time PCR and IFN-γ ELISA were performed at day 0 and the end of the study. Dogs that developed disease were withdrawn from the study and classified as sick dogs. Adverse drug reactions were reported. RESULTS: Thirty dogs developed disease during the follow-up period: 13/67 (19.4%) in the group treated with domperidone and 17/44 (38.6%) in the placebo-treated group (P = 0.03). Low-seropositive dogs treated with domperidone (4/40, 9.1%) were significantly less likely to develop disease compared to low-seropositive dogs treated with placebo (7/24, 29.2%; P = 0.04), while no differences were found between domperidone (9/23, 39.1%) and placebo (10/20, 50%) in medium- to high-seropositive dogs. At the end of the study, a higher proportion of Leishmania PCR-positive dogs was observed in the placebo-treated group (16/33, 48.5%) compared to the domperidone group (13/51, 25.5%; P = 0.04). Furthermore, low-seropositive dogs treated with domperidone with an increase of IFN-γ concentration presented a higher increase than those treated with placebo at the end of the study. Four dogs treated with domperidone presented self-limiting diarrhea. CONCLUSIONS: Healthy dogs with low L. infantum antibody levels treated with domperidone were less likely to develop disease compared to placebo-treated dogs. Furthermore, domperidone presented a good safety profile.

Women's experiences with using domperidone as a galactagogue to increase breast milk supply: an australian cross-sectional survey.

BACKGROUND: Domperidone is one of the most commonly utilised pharmacological galactagogues, with evidence of increasing use in clinical practice. However, the use of domperidone as a galactagogue remains controversial, with mixed evidence on safety and efficacy, leading to variable clinical practice recommendations. We sought to evaluate contemporary patterns of domperidone use and examine maternal experiences related to perceived safety and effectiveness. METHODS: In 2019, we conducted an online, cross-sectional survey of Australian breastfeeding women to examine individual experiences related to domperidone use, in addition to perceptions of safety and effectiveness. RESULTS: Among 1876 survey responses, 19% (n = 355) reported using domperidone. Domperidone use was significantly higher in women who were primiparous, gave birth preterm, delivered by caesarean section, had self-perceived low milk supply, and saw a lactation consultant. Nearly 20% of women commenced domperidone use in the first week postpartum (19%, n = 67). The median duration of use was six weeks (interquartile range 3-16 weeks). Maximum reported doses of domperidone used ranged from 20 mg/day to 160 mg/day. Half (n = 178, 50%) of women reported using a dose of 30 mg/day or less, 44% (n = 155) reported using a dose between 31 and 60 mg/day, and 6% (n = 22) reported using a dose greater than 61 mg/day. Nearly half of the respondents reported domperidone as 'very' or 'extremely effective' (45%, n = 161), with only 8% (n = 27) reporting it was 'not at all effective'. Almost half (n = 172, 48%) of all women using domperidone reported side effects, including weight gain (25%), headaches (17%) and dry mouth (13%). Higher doses were associated with an increased likelihood of any side effects (≤ 30 mg/day, 38%; >31-≤60 mg/day, 48%, > 61 mg/day 73%; P < 0.004), with 31 (9%) stopping domperidone because of side effects. CONCLUSION: We identified widespread variation in domperidone utilisation patterns, with domperidone broadly perceived to be effective in increasing breast milk supply. Side effects associated with domperidone treatment were common, appeared to be dose-related, and were frequently associated with treatment cessation. These findings highlight the importance of improved clinical practice recommendations and generation of evidence from additional high-quality clinical trials evaluating the efficacy and safety of domperidone. More conclusive clinical trials are needed to determine the efficacy, as well as optimal dose and duration, of domperidone use.

Risk of Adverse Events Associated with Domperidone and Metoclopramide in Gastroparesis: Systematic Review and Meta-analysis.

BACKGROUND: Dopamine antagonists are the main pharmacological options to treat gastroparesis. The aim of this study was to conduct a systematic literature review (SLR) to evaluate the profile of adverse events (AEs) of dopamine antagonists used in the treatment of children and adults with gastroparesis. METHODS: We searched EMBASE and MEDLINE up to March 25, 2021, for relevant clinical trials and observational studies. We conducted a proportional meta-analysis to estimate the pooled occurrence of AEs (%), with 95% confidence interval (CI), from arm-level data across studies and the comparative occurrence of AEs from placebo-controlled clinical trials (odds ratio [OR] with 95% CI). RESULTS: We identified 28 studies assessing AEs experienced by patients treated for gastroparesis with domperidone and metoclopramide; 22 studies contributed data to the meta-analyses. Cardiovascular, neurological, and endocrine AEs were commonly observed, with point incidences varying from 1 to > 50%. Clinically important AEs, such as QTc prolongation, occurred in 5% of patients treated with domperidone (95% CI: 3.32-8.62). Restlessness, an extrapyramidal AE, occurred in 15% of patients (95% CI: 7.48-26.61) treated with metoclopramide, with a 7-fold increase compared with patients receiving placebo (OR: 7.72; 95% CI: 1.27-47.05). Variation in terminology to describe extrapyramidal events precluded further pooled analyses. Additional meta-analyses were not feasible due to discrepancies in the assessment and reporting of the AEs. CONCLUSIONS: The evidence confirms concerns of cardiovascular, extrapyramidal, and endocrine AEs in patients with gastroparesis treated with domperidone and metoclopramide. Imprecise AE reporting limits firm interpretation and conclusions. REGISTRATION: PROSPERO international prospective register of systematic reviews (registration number: CRD42021248888).

Efficacy and Safety of a Persian Medicine Formula on Functional Dyspepsia Symptoms: A Randomized Double-Blind Active-Control Clinical Trial.

INTRODUCTION: Functional dyspepsia (FD) is one of the most frequent gastrointestinal disorders with a high burden. Although FD is a heterogeneous disorder without any standard therapy (treatment/treatment - repetition), there is a wide history of using herbal remedies for its treatment. Two of these herbal remedies quoted in various Persian medicine resources are celery and ajwain. Their effects have been investigated in recent clinical trials in FD patients. We aimed to compare the effect of celery and ajwain to that of domperidone in patients with postprandial distress syndrome. METHODS: This is a randomized double-blind active-control clinical trial, conducted at Kerman, Iran in 2020. Participants of this study were 100 patients suffering from FD (postprandial distress syndrome subtype). The intervention group received 1 g of the combination of celery and ajwain (Apium graveolens L. and Trachyspermum copticum [L.] Link), while the control group received 30 mg of domperidone per day for 4 consecutive weeks. Primary outcomes were symptom severity and frequency, and secondary outcomes were quality of life (QoL) and safety. All outcomes were assessed at the end of the trial and also 4 weeks after the trial was finished. RESULTS: No significant differences in symptom frequency were found between groups. However, differences in symptom severity were found at the end of the follow-up (week 8) (p = 0.001). The intragroup analysis showed a significant decrease in the symptoms severity and frequency at the end of week 4 in both groups (p < 0.001). QoL in the intervention group was higher compared to the control group at the end of the study (p < 0.001) and at the point of the follow-up (week 8; p < 0.001). No serious adverse events occurred in either group. CONCLUSION: The herbal mixture of celery and ajwain could be considered a safe and effective remedy, decreasing the severity of symptoms and increasing QoL in patients with postprandial distress syndrome. It is further suggested to confirm these findings in high-quality multi-center clinical trials.

Drug-induced Sudden Death: A Scoping Review.

BACKGROUND: The risk of sudden cardiac death (SCD) can be increased with the use of drugs. However, it has been described heterogeneously in the literature. OBJECTIVE: This study aims to systematically review epidemiological studies dealing with druginduced sudden death, describe their methodologies, and summarize the results found. METHODS: A scoping review has been carried out using Medline electronic database. The search was limited up to 2020. Epidemiological studies were included, and case reports or case series were excluded. RESULTS: Out of 3,114 potential articles, 74 were included. Most studies originated from North America (40.5%) or Europe (39.2%). Case-control (47.3%) or cohort (40.5%) studies were the most common designs. The data for outcomes and exposure were retrieved mainly from administrative databases (37.8%) or medical charts/hospital discharge reports (32.4%), but most studies used several sources of information. A composite variable of sudden death or SCD, mainly with ventricular arrhythmia, was the most frequently used endpoint. Only 18.9% of the studies included autopsy results to confirm the death. Psychotropic drugs were the most frequently studied. An increased risk of different outcomes for typical antipsychotics, tricyclic antidepressants, domperidone, and antiepileptics is suggested. CONCLUSION: The methodologies used were highly heterogeneous, and the results were, in general, not conclusive. An improvement of the methodologies is needed to achieve a conclusion regarding the risk of SCD associated with drug use.

Psychiatric Manifestations of Withdrawal Following Domperidone Used as a Galactagogue.

Background: Domperidone is a dopamine-2 antagonist used off-label to increase breast milk production. Dosages commonly promoted for lactation are often far above those of studied on-label indications and might pose additional risks, especially upon discontinuation of the drug. Patients: Three U.S. patients are presented who used domperidone for lactation and experienced varying degrees of psychiatric withdrawal symptoms lasting months during dosage tapering and after cessation. Conclusion: Domperidone as a galactagogue may pose a significant psychiatric risk upon discontinuation. This presentation is commonly confused with, but clinically distinct from, postpartum depression. Lactating mothers who present with psychiatric symptoms should be explicitly probed about domperidone use, even in areas where domperidone is not authorized for use. Maternal hesitancy to disclose domperidone use may lead to suboptimal outcomes for the patient and delay management of withdrawal manifestations. The best course of treatment remains unknown, but a slow hyperbolic taper to gently discontinue domperidone may minimize withdrawal symptoms in these patients. Individuals exploring domperidone use should be informed of potential risks upon withdrawal, including psychiatric manifestations, requisite taper, and potential impacts of using unstudied high doses.

Domperidone Use as a Galactagogue and Infanticide Ideation: A Case Report.

Objectives: Domperidone is an antiemetic that is commonly used as an off-label prescription to induce lactation. Neuropsychiatric adverse effects of domperidone such as akathisia and depression are previously described. It has never been reported to be associated with infanticide ideation. The aim of this article is to discuss the occurrence of infanticide ideation following domperidone usage in an adoptive mother and the potential mechanisms by which these may occur. Methods: With Institutional Review Board approval, we herein report a nulliparous adoptive mother who developed infanticide ideation after 3 months of exposure to domperidone. The infanticide ideation was intrusive, recurrent, ego-dystonic, causing significant depressive symptoms and affecting the patient's functions. Physical examination and relevant biological investigations were unremarkable. Results: The patient is treated as domperidone-induced obsessional thought with adjustment disorder. The domperidone was stopped immediately. Serotonin and norepinephrine reuptake inhibitors was started. The infanticide ideation gradually resolved and patient achieved complete remission after 10 months of treatment. Conclusion: The infanticide ideation following consumption of domperidone is a potential neuropsychiatric adverse event that warrants further examination into the safety of domperidone as an "off-labeled" galactagogue. Comprehensive psychological assessment of mother who wishes to use domperidone as galactagogue is recommended.

Four-Way Crossover Phase 1 Thorough QT Study to Assess Cardiac Safety of Domperidone and Consideration for Design and Conduct of QT/QTc Study in China.

This study aimed to evaluate the QT prolongation potential of domperidone in healthy Chinese participants and explore the possibility of a thorough QT (TQT) study in China with a smaller sample size using concentration-QT (C-QT) modeling. Part 1 was a randomized, placebo- and positive-controlled, multiple-dose, 4-way crossover TQT study in healthy Chinese participants; 44 participants were randomized to either domperidone 10/20 mg or placebo 3 times daily, on days 1 to 3, followed by a single dose of either 10/20 mg domperidone/domperidone-placebo/domperidone-placebo plus 400 mg of moxifloxacin, on day 4. Twelve-lead electrocardiograms were recorded in triplicate at predefined time points with pharmacokinetic sampling. The results were that change from baseline in QT interval corrected for heart rate (QTc) using the Fridericia formula (QTcF) between domperidone and placebo was 1.3 milliseconds and 2.7 milliseconds for 10 and 20 mg 3 times daily, and upper limits of 2-sided 90%CI for all time points were below regulatory threshold of 10 milliseconds. In part 2, resampling analysis using C-QT modeling for moxifloxacin showed false-negative rates of <5% with sample sizes ≥6. We could conclude that no clinically relevant effect on corrected QT interval or new safety signals was observed with domperidone. A dedicated TQT study with C-QT modeling could assess drug effects on QT/corrected QT intervals for novel drug development in China.

Cardiac safety and clinical efficacy of high-dose domperidone for long-term treatment of gastroparesis symptoms.

Domperidone is an effective antiemetic used worldwide, but there have been reports of possible cardiotoxicity. Our goal was to explore the cardiac safety and clinical efficacy of long-term domperidone, titrated as high as 120 mg/day, in patients not responding or unable to tolerate other therapies for gastroparesis (GP).This retrospective cohort study was conducted at a single tertiary care academic center. We objectively assessed the safety and efficacy of domperidone through questionnaires, clinical follow-up and frequent ECGs as mandated by the Food and Drug Administration. We excluded patients with a history of dangerous arrhythmias, prolonged QTc, clinically significant electrolyte disturbances, gastrointestinal hemorrhage or obstruction, presence of a prolactinoma, pregnant or breastfeeding females, or allergy to domperidone. A total of 21 patients met the inclusion criteria for eligibility in this study (52.4% white, 42.9% Hispanic; mean age 50.1 years; 90.5% female). The mean duration of domperidone therapy was 52.3 (range 16-97) months with a mean highest dose of 80 mg/day (range 40-120 mg). Two patients (9.5%) taking 120 mg/day experienced asymptomatic meaningful QTc prolongation (>450 ms in males, >470 ms in females). One-third of patients had asymptomatic non-meaningful QTc prolongation. Palpitations or chest pain was reported in 19% of patients without ECG abnormalities or adverse cardiac events. The mean severity of vomiting and nausea was improved by 82% and 55%, respectively.Long-term treatment with high doses of domperidone (40-120 mg/day) improved GP symptoms in patients previously refractory to other medical therapies and with a satisfactory cardiovascular risk profile.

Risk of major congenital malformations associated with first-trimester exposure to propulsives: A health administrative database study in Japan.

PURPOSE: To evaluate the risk of major congenital malformations (MCMs) associated with first-trimester exposure to propulsives with a special focus on domperidone using a large administrative database in Japan. METHODS: A large claims database was used from January 2005 to August 2016. The dates of pregnancy onset and delivery were estimated using the developed algorithms. MCMs were defined according to the International Classification of Diseases, 10th revision codes. We compared the infants' risk of overall MCMs between women with or without first-trimester prescriptions of propulsives and estimated the odds ratios (ORs) with unadjusted and adjusted analyses. We also compared the risk of overall MCMs between women with domperidone prescriptions and those with other propulsive prescriptions during the first trimester. RESULTS: Among 38 270 women, propulsives were prescribed to 3197 women (8.4%) in the first trimester, including domperidone to 371 women (1.0%). Propulsive prescriptions in the first trimester were not significantly associated with an increased risk of overall MCMs (adjusted OR [aOR] 1.030, 95% confidence interval [CI] 0.843-1.257). Compared to the prescription of other propulsives in the first trimester, the prescription of domperidone in the first trimester was not associated with an increased risk of overall MCMs (aOR 0.724, 95% CI 0.363-1.447). CONCLUSIONS: The first-trimester prescription of propulsives, including domperidone, was not associated with an increased risk of overall MCMs.

Domperidone Withdrawal in a Nursing Female with Pre-existing Psychiatric Illness: A Case Report.

BACKGROUND: In this report, we describe a case of domperidone withdrawal in a woman with a history of major depressive disorder and obsessive-compulsive disorder (OCD), who experienced a recurrence of these disorders after stopping domperidone. CASE PRESENTATION: The symptoms improved after the restarting of domperidone and disappeared gradually as the drug was tapered and discontinued. Clinicians should consider domperidone withdrawal a differential diagnosis in women with a history of depression or anxiety who present with an acute onset of these symptoms following the abrupt discontinuation of domperidone. CONCLUSION: A gradual taper off of the drug may be effective in minimizing withdrawal symptoms and obviate the need for psychotropic drug use.

Thromboelastography with platelet mapping: Limited predictive ability in detecting preinjury antiplatelet agent use.

BACKGROUND: Preinjury antiplatelet agent (APA) use in trauma patients can increase traumatic hemorrhage and worsen outcomes. Thromboelastography with platelet mapping (TEGPM) has characterized platelet function via arachidonic acid (AA) and adenosine diphosphate (ADP) inhibition in nontrauma settings, but limited data exist in the acute trauma population. METHODS: A prospective observational study of adult trauma patients with suspected preinjury APA use who received TEGPM testing from 2017 to 2020 was performed. Patients on anticoagulants were excluded. Patients were grouped according to preinjury APA regimen: 81 mg or 325 mg of aspirin daily, 81 mg of aspirin and 75 mg of clopidrogrel daily, 75 mg of clopidrogrel daily, or no antiplatelet. Ability of TEGPM to detect APA use was assessed using predictive statistics and area under receiver operating characteristic curves (AUROCs). RESULTS: A total of 824 patients were included with most patients taking 81 mg of aspirin (n = 558). Patients on no antiplatelet were younger and had higher baseline platelet counts, while patients on 75 mg of clopidrogrel were more likely to be admitted after ground level fall. All other baseline characteristics were balanced. Admission TEG values were similar between groups. Median AA inhibition was higher in patients on aspirin containing regimens (p < 0.0001). Median ADP inhibition was higher in patients on clopidogrel containing regimens and those taking 325 mg of aspirin (p < 0.0001). Arachidonic acid inhibition accurately detected preinjury APA use and aspirin use (AUROC, 0.89 and 0.84, respectively); however, ADP inhibition performed poorly (AUROC, 0.58). Neither AA nor ADP inhibition was able to discern specific APA regimens or rule out APA use entirely. CONCLUSION: High AA inhibition accurately detects preinjury APA use in trauma patients. High ADP inhibition after trauma is common, limiting its utility to accurately identify preinjury APA use. Further study is needed to identify assays that can reliably detect and further characterize preinjury APA use in trauma populations. LEVEL OF EVIDENCE: Diagnostic test, level II.

Domperidone increases harmful cardiac events in Parkinson's disease: A Bayesian re-analysis of an observational study.

OBJECTIVES: To assess the risks of ventricular tachyarrhythmia/sudden cardiac death (VT/SCD) with domperidone use in Parkinson's disease (PD). STUDY DESIGNS AND SETTINGS: Using Bayesian methods, results from an observationalstudy were combined with prior beliefs to calculate posterior probabilities of increasedrelative risk (RR)) of VT/SCD with use of domperidone compared to non-use and ofharm, defined as risk exceeding 15%. The analyses were carried with normallydistributed priors (log (RR)): uninformative (N(0,10)) or informative (N(0.53,179)),derived from a meta-analysis (OR (95%CI):1.70 (1.47-1.97)). Sensitivity analyses used:different priors' strengths, different priors, and Bayesian meta-analysis RESULTS: The uninformative prior yielded a RR: 1.23 (95% credible interval (CrI):0.94-1.62), like the published frequentist RR: 1.22 (95% CI:0.99-1.50), with 69% probabilityof harm. With an informative prior weighted at 100%, 50% and 10%, the RR were 1.63(1.41-1.88), 1.57 (1.31-1.91) and 1.39 (1.10-1.93), respectively. The correspondingprobabilities of harm were 100%, 99%, and 94%, respectively. CONCLUSION: While both the frequentist and Bayesian approaches with anuninformative prior were unable to reach a definitive conclusion concerning thearrhythmic risk of domperidone in PD patients, the Bayesian analysis with informativepriors showed a high probability of increased risk that was robust to multiple priorsensitivity analyses.

Randomised clinical trial: safety, pharmacokinetics and pharmacodynamics of trazpiroben (TAK-906), a dopamine D2 /D3 receptor antagonist, in patients with gastroparesis.

BACKGROUND: Gastroparesis is a chronic gastric motility disorder. Dopamine D2 /D3 receptor antagonists metoclopramide and domperidone are current treatment options but are associated with central nervous system and cardiovascular safety concerns, respectively, precluding chronic use. Trazpiroben (TAK-906), a dopamine D2 /D3 receptor antagonist, is under development for chronic treatment of moderate-to-severe gastroparesis. Nonclinical data suggest trazpiroben will have D2 /D3 receptor antagonism comparable with metoclopramide or domperidone. AIMS: To evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics (effect on prolactin and gastric function) of twice-daily trazpiroben (5, 25 and 100 mg) in participants with gastroparesis. METHODS: This phase 2a pilot study evaluated gastric emptying using the gastric emptying breath test, with metoclopramide as an internal control. Gastric accommodation and gastroparesis symptoms were assessed using the nutrient drink test and American Neurogastroenterology and Motility Society Gastroparesis Cardinal Symptom Index-Daily Diary, respectively. RESULTS: Overall, 51 participants were enrolled. Trazpiroben was well tolerated, demonstrating a favourable safety profile without cardiovascular or central nervous system adverse events. All trazpiroben doses were rapidly absorbed and eliminated (t1/2z 4-5 hours), and D2 /D3 receptor target engagement confirmed by increased serum prolactin (peaking at trazpiroben 25 mg). No effect on gastric emptying was demonstrated with trazpiroben or metoclopramide (P > 0.05), although benefits in volume-to-fullness were seen at trazpiroben 5 mg (P > 0.05) and 25 mg (88.5 vs -26.3 mL; P = 0.019), and nonsignificant numerical aggregate symptom score improvements were observed with trazpiroben 25 mg vs placebo (P = 0.182). CONCLUSIONS: Trazpiroben was well tolerated with a favourable safety profile, supporting its further development for the treatment of gastroparesis. ClinicalTrials.gov identifier: NCT03268941.

Risk of Pregnancy Termination and Congenital Anomalies After Domperidone Exposure: A Study in the EFEMERIS Database.

INTRODUCTION: Domperidone is widely used during pregnancy, although the risks associated with pregnant women have not been adequately evaluated. OBJECTIVE: The objective of this study was to compare the rate of pregnancy outcomes and congenital anomalies between pregnant women exposed and unexposed to domperidone during pregnancy. METHODS: We conducted a retrospective cohort study comparing pregnant women exposed and unexposed to domperidone during pregnancy. We used the EFEMERIS database containing the prescriptions and dispensing of drugs to pregnant women in Haute-Garonne, who had a pregnancy outcome between July 2004 and December 2017. We compared pregnant women who were exposed to domperidone at least once during pregnancy to unexposed pregnant women. Logistic regression and Cox proportional risk models were applied. RESULTS: Overall, 13,964 pregnancies (10.3% of pregnancies) were given domperidone. A reduction in the number of pregnant women exposed to domperidone (2004: 17.1% to 2017: 1.2%) was noted. More than 75% of pregnancies were exposed to domperidone in the first trimester of pregnancy. The rate of natural pregnancy termination in pregnant women exposed to domperidone was lower than that in unexposed pregnant women (adjusted hazard ratio = 0.78 [0.71-0.87]). The malformation rate in fetuses/newborns exposed in utero (first trimester) to domperidone is comparable to that of unexposed fetuses/newborns (adjusted odd ratio = 0.89 [0.77-1.03]). CONCLUSIONS: This is the first comparative study to enrol a large number of pregnant women exposed to domperidone. Data regarding the malformation rate following exposure to domperidone during the first trimester of pregnancy are reassuring. Women exposed to domperidone during pregnancy have a decreased risk for natural pregnancy termination, probably owing to an indication bias.

Off-label postpartum use of domperidone in Canada: a multidatabase cohort study.

BACKGROUND: Trends in off-label postpartum use of domperidone and the impact of safety advisories on its use remain unknown. Our objectives were to describe postpartum use of domperidone in Canada, to evaluate the impact of Health Canada advisories on prescribing patterns, and to describe the association between domperidone use and a composite end point of sudden cardiac death or ventricular tachycardia (VT) among postpartum patients. METHODS: We conducted a multidatabase cohort study involving pregnant patients with live births between 2004 and 2017 using administrative health databases from 5 Canadian provinces (British Columbia, Alberta, Saskatchewan, Manitoba and Ontario). We excluded patients with less than 1 year of prepregnancy database history and with approved indications for domperidone. We assessed domperidone use in the 6 months postpartum and the impact of the 2012 and 2015 Health Canada advisories on prescribing via interrupted time series analysis. We estimated crude rates of VT and sudden cardiac death. RESULTS: We included 1 190 987 live births. Mean maternal age was 28.6 (standard error 0.6) years. Domperidone use increased over time, from 7% in 2003-2005 to 12% in 2009-2011, when it plateaued. The 2012 advisory was followed by a drop in use and a reduction in slope, and the 2015 advisory had a more modest impact. Crude analysis suggests that domperidone may be associated with increased VT or sudden cardiac death (0.74 v. 0.37 per 10 000 person-years; difference per 10 000 person-years: 0.37, 95% confidence interval -0.67 to 1.41). INTERPRETATION: Postpartum domperidone use increased between 2004 and 2017, with prescribing attenuated after Health Canada advisories and a very low absolute rate of VT or sudden cardiac death. These findings suggest that Health Canada advisories affected prescribing; any potential increase in VT or sudden cardiac death with use of domperidone is small and could not be confirmed in this large study STUDY REGISTRATION: ClinicalTrials.gov, no. NCT04024865.