Domperidone Safety in First Trimester Pregnancy
Domperidone is safe to use during the first trimester of pregnancy for severe nausea and vomiting, as it is explicitly listed as a second-line antiemetic compatible with all trimesters of pregnancy by the European Association for the Study of the Liver (EASL). 1
Guideline-Based Positioning
EASL 2023 guidelines explicitly classify domperidone as compatible with the 1st, 2nd, and 3rd trimesters of pregnancy, as well as with breastfeeding and paternal exposure. 1 This represents the most authoritative and recent guideline statement on domperidone safety in pregnancy.
Domperidone is positioned as a second-line treatment for hyperemesis gravidarum, after first-line agents like cyclizine, doxylamine/pyridoxine, prochlorperazine, and promethazine. 1
The American College of Obstetricians and Gynecologists (ACOG) recommends starting with vitamin B6 and doxylamine-pyridoxine combination as first-line therapy, escalating to metoclopramide for moderate symptoms, before considering other second-line agents. 2, 3
Supporting Safety Evidence
A large retrospective cohort study of 13,964 pregnancies (10.3% exposed to domperidone) found no increased risk of congenital malformations when domperidone was used during the first trimester (adjusted OR = 0.89,95% CI 0.77-1.03). 4 More than 75% of these exposures occurred in the first trimester. 4
A prospective cohort study of 120 first-trimester pregnant women taking domperidone showed no difference in malformation rates compared to unexposed controls (3 malformations in each group, OR = 0.6,95% CI 0.1-2.8). 5
Interestingly, women exposed to domperidone during pregnancy had a decreased risk of natural pregnancy termination (adjusted HR = 0.78,95% CI 0.71-0.87), likely due to effective symptom control. 4
Treatment Algorithm for First Trimester Nausea
Start with non-pharmacological interventions: Small, frequent, bland meals; BRAT diet; avoidance of triggers; separation of solid and liquid intake. 6, 3
First-line pharmacological: Vitamin B6 (pyridoxine) 10-25 mg every 8 hours, or doxylamine-pyridoxine combination (10 mg/10 mg delayed-release). 2, 6, 3
Second-line agents: Metoclopramide 5-10 mg orally every 6-8 hours (preferred due to extensive safety data with 33,000 first-trimester exposures showing no increased malformation risk, OR 1.14,99% CI 0.93-1.38) 2, 6 OR domperidone as an alternative second-line option. 1
Third-line for refractory cases: Ondansetron (with caution before 10 weeks due to small absolute risk increases of 0.03% for cleft palate and 0.3% for ventricular septal defects). 2, 6
Critical Clinical Considerations
Early intervention is crucial to prevent progression to hyperemesis gravidarum, which affects 0.3-2% of pregnancies. 2, 6
Use the PUQE score to quantify severity: mild (≤6), moderate (7-12), severe (≥13) to guide treatment intensity. 2, 6
Thiamine supplementation (100 mg daily for minimum 7 days) should be provided in cases of prolonged vomiting to prevent Wernicke encephalopathy. 2, 6
For severe cases requiring hospitalization, initiate IV hydration with normal saline plus potassium chloride, IV metoclopramide 10 mg every 6-8 hours, and thiamine before any dextrose administration. 2
Important Caveat About FDA Status
Domperidone is not FDA-approved for any indication in humans in the United States. 7 However, this does not negate its established safety profile in pregnancy as documented by European guidelines and large observational studies. The EASL guidelines represent current best evidence from international expert consensus. 1
Despite lack of FDA approval, domperidone has been used extensively worldwide for decades with a well-established safety profile, particularly regarding its lower propensity for extrapyramidal side effects compared to metoclopramide. 8