Antiemetics During Pregnancy

Antiemetic prescribing in pregnancy treats nausea and vomiting of pregnancy (up to 80% of pregnancies) and hyperemesis gravidarum (about 1%), defined as persistent vomiting with weight loss over 5% of pre-pregnancy weight, dehydration and ketonuria. Untreated hyperemesis causes electrolyte derangement, Wernicke encephalopathy, venous thromboembolism and poor foetal growth.

Severity. A score such as the Pregnancy-Unique Quantification of Emesis guides treatment: mild 6 or less, moderate 7 to 12, severe 13 or more.

Diagnosis first. Exclude urinary tract infection, gastroenteritis, hyperthyroidism, hepatitis, molar pregnancy, multiple pregnancy, diabetic ketoacidosis, raised intracranial pressure and, in endemic areas, malaria.

Mild. Small frequent meals, ginger 250 mg orally 4 times daily, pyridoxine 10 to 25 mg orally 3 times daily.

Moderate, first line.

• Doxylamine 10 mg with pyridoxine 10 mg delayed release: 2 tablets at bedtime, adding 1 tablet in the morning and 1 mid-afternoon if needed; maximum 4 tablets daily.
• Cyclizine 50 mg orally or IM up to 3 times daily; maximum 150 mg daily.
• Promethazine 12.5 to 25 mg orally every 4 to 6 hours; maximum 100 mg daily.
• Prochlorperazine 5 to 10 mg orally 3 times daily, or 12.5 mg IM.

Second line.

• Metoclopramide 10 mg orally, IM or IV 3 times daily; maximum 30 mg daily, for 5 days at most.
• Ondansetron 4 to 8 mg orally or IV every 8 hours; single IV dose maximum 16 mg.
• Chlorpromazine 10 to 25 mg orally every 6 to 8 hours, or 25 mg IM every 6 to 8 hours.

Third line (specialist). Mirtazapine 15 to 30 mg at night; gabapentin 300 mg at night, titrated to 900 to 1200 mg daily; prednisolone 40 to 50 mg orally daily (or hydrocortisone 100 mg IV twice daily) for 3 days, then taper to the lowest effective dose over 2 weeks; avoid before 10 weeks if possible (small rise in oral clefts).

Hyperemesis, admission care.

• Sodium chloride 0.9% 1 litre with potassium chloride 20 to 40 mmol/L, given over 4 to 6 hours and repeated to correct deficit and urinary ketones; avoid rapid sodium correction.
• Thiamine 100 mg IV daily before any glucose infusion; for suspected Wernicke encephalopathy, 500 mg IV 3 times daily for 3 days, then 250 mg IV daily for 3 to 5 days.
• Antiemetic combination (for example cyclizine plus metoclopramide, then ondansetron); correct magnesium, phosphate and glucose.
• Enoxaparin 40 mg subcutaneously daily (dose by weight) while admitted or with persistent immobility; continue if risk factors.
• Enteral feeding by nasogastric tube, or parenteral nutrition with specialist input, for persistent weight loss over 5% despite treatment.

Heartburn. Alginate and antacid; omeprazole 20 mg daily if needed.

Adverse effects. Sedation and dry mouth (cyclizine, promethazine); dystonia and akathisia (metoclopramide, prochlorperazine, chlorpromazine); QT prolongation (ondansetron, domperidone, chlorpromazine); constipation (ondansetron).

Avoid. Domperidone in cardiac disease or with QT-prolonging drugs; metoclopramide over 5 days; repeated high-dose ondansetron with other QT-prolonging drugs; ginger over 1 g daily.

Interactions. Ondansetron with macrolides, antipsychotics, quinolones, artemether-lumefantrine and methadone: QT prolongation, so check ECG and electrolytes. Metoclopramide with antipsychotics: dystonia. Promethazine with other sedatives: respiratory depression.

Special groups.

• Kidney impairment: halve metoclopramide when creatinine clearance is under 40 mL/min.
• Liver impairment: reduce ondansetron to a maximum of 8 mg daily in severe impairment.
• Breastfeeding: doxylamine, metoclopramide and ondansetron are acceptable for short courses.
• Regional: in malaria-endemic areas test for malaria in any vomiting patient with fever; vomiting within 30 minutes of an oral antimalarial dose needs the dose repeated.

Monitoring. Weight, urinary ketones, urea and electrolytes (sodium, potassium, magnesium, phosphate), glucose, liver tests and thyroid function at diagnosis and every 1 to 2 days when admitted. Repeat electrolytes before and after potassium replacement.

Adjustment. Step up each 24 to 48 hours without response. Switch to the IV or IM route when oral intake fails. Stop corticosteroid when symptoms settle.

Stopping rules. Stop metoclopramide at 5 days or at the first extrapyramidal sign. Stop ondansetron if QTc is over 480 ms.

Referral and escalation. Refer to obstetrics for weight loss over 5%, ketonuria, electrolyte disturbance, failure of oral antiemetics or inability to keep fluids down; urgent senior review for confusion, ataxia or nystagmus (Wernicke), persistent tachycardia or haematemesis.