Metoclopramide Dosing for Intractable Hiccups
For intractable hiccups, metoclopramide should be dosed at 10 mg orally three times daily, which can be titrated up to 10-20 mg every 6 hours (maximum 3-4 doses per day) based on response. 1, 2
Evidence-Based Dosing Regimen
The most robust evidence comes from a randomized controlled trial demonstrating efficacy with 10 mg orally three times daily for 15 days, which showed significantly higher total efficacy compared to placebo (relative risk 2.75, P = 0.03). 2 This represents the only adequately powered RCT specifically for hiccups and should guide initial dosing.
For breakthrough therapy or more severe cases, guidelines support 5-20 mg orally or intravenously every 6 hours, with a maximum of 3-4 administrations daily. 1 The American Society of Clinical Oncology specifically endorses this dosing range for hiccups associated with cancer treatment. 1
Route of Administration
- Oral route is preferred for most patients at 10 mg three times daily 2
- Intravenous administration at 10-20 mg every 6 hours can be used when oral intake is not feasible or rapid relief is needed 1, 3
- Both routes demonstrate similar efficacy when gastrointestinal absorption is intact 3
Duration of Therapy
Continue treatment for 15 days based on the trial protocol that demonstrated efficacy. 2 If hiccups resolve earlier, therapy can be discontinued without tapering.
Important Safety Considerations
Extrapyramidal symptoms and dystonic reactions are the most concerning adverse effects, particularly with prolonged use. 1 The trial documented mild adverse events including fatigue, upset mood, and dizziness, but no serious treatment-related events. 2
Avoid in patients with:
- Pheochromocytoma, seizure disorders, GI bleeding, or GI obstruction 3
- Severe renal or hepatic impairment (requires dose adjustment) 3
QT prolongation can occur with repeated doses, potentially precipitating torsades de pointes. 1 Avoid concurrent use with other QT-prolonging agents.
Comparative Context
While chlorpromazine remains the only FDA-approved drug for hiccups, systematic reviews indicate that baclofen and metoclopramide are the only agents studied in randomized controlled trials. 4, 5 Metoclopramide offers advantages over neuroleptics like chlorpromazine due to a more favorable side effect profile during long-term therapy. 5
The evidence quality for metoclopramide is moderate—supported by one well-designed RCT 2 and multiple observational studies 4, 5—making it a reasonable first-line or second-line option alongside baclofen and gabapentin. 5