How do I choose between Perinorm (domperidone) and Lesuride for prokinetic therapy?

Choosing Between Perinorm (Metoclopramide) and Lesuride (Levosulpiride)

For most patients requiring prokinetic therapy, domperidone (not Perinorm/metoclopramide) should be the preferred first-line agent due to its significantly lower risk of extrapyramidal side effects, while levosulpiride offers a middle-ground option with both prokinetic and 5-HT4 agonist properties. 1

Primary Recommendation: Consider Domperidone First

The American Gastroenterological Association recommends domperidone over metoclopramide for extended therapy due to its superior neurological safety profile. 1 This is critical because:

• Metoclopramide carries a high risk of extrapyramidal side effects including dystonia, akathisia, and potentially irreversible tardive dyskinesia 1
• The FDA only approves metoclopramide for gastroparesis specifically due to safety concerns 1
• Domperidone does not readily cross the blood-brain barrier, resulting in fewer central nervous system side effects 2, 3

When Metoclopramide (Perinorm) May Be Appropriate

Use metoclopramide in these specific scenarios:

• Short-term therapy only (to minimize extrapyramidal risk) 1
• Acute nausea/vomiting requiring rapid onset: metoclopramide acts within 30-60 minutes orally and 10-15 minutes intramuscularly 1
• When domperidone is unavailable and cardiac monitoring for levosulpiride is not feasible 1
• Dose: 5-20 mg three to four times daily 1

Critical Metoclopramide Warnings:

• Patients must be regularly monitored for movement disorders 4
• Avoid in elderly patients and those requiring prolonged therapy 1
• Never use as first-line for chronic conditions like gastroparesis when alternatives exist 1

Levosulpiride (Lesuride) as Middle-Ground Option

Levosulpiride offers theoretical advantages:

• Dual mechanism: D2 receptor blockade plus 5-HT4 receptor agonism may enhance efficacy in functional dyspepsia and diabetic gastroparesis 3
• Lower extrapyramidal risk than metoclopramide due to looser binding to D2 receptors in the nigrostriatal pathway 3
• Still crosses blood-brain barrier, so extrapyramidal effects remain possible but less frequent 3

Levosulpiride Considerations:

• Hyperprolactinemia can occur (affects all antidopaminergic prokinetics) 3
• May be preferred when both prokinetic and 5-HT4 effects are desired 3
• Limited availability in some countries compared to metoclopramide 3

Cardiac Safety: The Domperidone Caveat

While domperidone is neurologically safer, cardiac monitoring is essential:

• QT prolongation risk exists, particularly with doses >30 mg/day and in patients >60 years old 1, 5
• Contraindications: pre-existing QT prolongation, concurrent CYP3A4 inhibitors, electrolyte abnormalities 5, 6
• Recommended dosing: Start 10 mg three times daily, maximum 20 mg three to four times daily 1
• ECG monitoring warranted in high-risk patients 1, 5

However, even at very high doses (80-120 mg/day), domperidone showed low cardiovascular event rates in clinical practice 7, and the cardiac risk is still considered acceptable compared to the neurological risks of metoclopramide for prolonged therapy 1

Clinical Decision Algorithm

Step 1: Assess treatment duration needed

• Short-term (<2 weeks): Metoclopramide acceptable if rapid onset needed 1
• Long-term/chronic: Domperidone strongly preferred 1

Step 2: Screen for contraindications

• Cardiac risk factors present (QT prolongation, age >60, electrolyte abnormalities): Consider levosulpiride or use domperidone with ECG monitoring 1, 5
• Parkinson's disease or high extrapyramidal risk: Domperidone mandatory (does not worsen extrapyramidal symptoms) 1
• Pediatric patients: Domperidone preferred due to lower extrapyramidal risk 1

Step 3: Consider clinical indication

• Functional dyspepsia: Levosulpiride may offer advantage via 5-HT4 mechanism 3
• Gastroparesis: Domperidone first-line per AGA guidelines 1
• Chemotherapy-induced nausea: Domperidone 20 mg 3-4 times daily effective 1
• Migraine-associated nausea: Either domperidone or metoclopramide acceptable as adjunct 8

Practical Prescribing

For domperidone:

• Start 10 mg three times daily before meals 1
• Duration of effect: 7-14 hours per dose 1
• Baseline ECG if cardiac risk factors present 5

For metoclopramide (if chosen):

• 5-10 mg three to four times daily 1
• Limit duration to shortest effective period 1
• Document informed consent regarding extrapyramidal risks 1

For levosulpiride:

• Similar dosing to metoclopramide 3
• Monitor for both cardiac and neurological effects 3

Common Pitfalls to Avoid

• Never use metoclopramide long-term without compelling reason - the extrapyramidal risk is cumulative and potentially irreversible 1
• Don't ignore cardiac screening for domperidone - while neurologically safer, QT prolongation is real 5, 6
• Avoid combining with other QT-prolonging drugs when using domperidone 5, 6
• Don't assume all prokinetics are interchangeable - their side effect profiles differ substantially 3