Generic Name

Domperidone

Mechanism

• Domperidone is a highly selective peripheral dopamine D₂‑receptor antagonist.
• By blocking D₂ receptors in the gastrointestinal tract, it diminishes dopaminergic inhibition of gut motility, leading to enhanced smooth‑muscle contraction and accelerated gastric emptying.
• It also reduces the activity of the chemoreceptor trigger zone in the area postrema, thereby decreasing nausea and vomiting.
• Because very little crosses the blood–brain barrier (<1 %), central adverse effects such as extrapyramidal symptoms are uncommon compared with other prokinetics.

Pharmacokinetics

• Bioavailability: ~38 % when given orally; dose‑dependent decline above 30 mg day⁻¹.
• Absorption: Rapid, peak plasma concentration (Tₘₐₓ) within 1–2 h.
• Distribution: Wide (Vᵈ ≈ 1.5 L/kg); highly protein‑bound (~86 %).
• Metabolism: Primarily hepatic via CYP3A4 (minor CYP2D6 involvement).
• Elimination half‑life: ~4–5 h; terminal phase 10–12 h.
• Excretion: Predominantly fecal (≈86 %); renal clearance <10 %.
• Drug interactions: Strong CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin) ↑ plasma concentrations; strong inducers (e.g., rifampin) ↓ levels.
• Renal impairment: No dose adjustment needed due to minimal renal excretion, but caution in severe hepatic dysfunction.

Indications

• Induced or functional nausea & vomiting (e.g., chemotherapy, postoperative).
• Delayed gastric emptying (gastroparesis) including diabetic and idiopathic forms.
• Peptic ulcer disease and gastroesophageal reflux when prokinetic benefit is desired.
• Lactation stimulation in breastfeeding mothers (off‑label, limited evidence).
• *Note:* Approved for pediatric use in certain jurisdictions; dosage based on weight (≤0.5 mg/kg/d).

Contraindications

• Absolute contraindications:
• Known hypersensitivity to domperidone or any excipient.
• Baseline QTc >440 ms (males) or >460 ms (females).
• Warnings:
• QT prolongation → risk of torsades de pointes, especially with other QT‑prolonging drugs.
• Severe hepatic impairment → markedly increased exposure.
• Pregnancy (Category D) → potential fetal harm; use only if benefits outweigh risks.
• Breastfeeding → drug passes into milk; avoid unless proven safe.
• Polypharmacy → significant interactions with CYP3A4 inhibitors/inducers.

Dosing

Special Considerations:
• Break‑glass technique for oral solutions (e.g., 1 mL = 10 mg).
• Taper is usually unnecessary; abrupt cessation may cause rebound nausea.

Adverse Effects

• Common (≥ 1 %):
• Headache, dizziness, abdominal cramps, diarrhea, constipation, nausea, dry mouth.
• Rare vestibular disturbances.
• Serious (≤ 1 %):
• QTc prolongation & torsades de Pointes (especially > 40 mg/day).
• Extrapyramidal syndrome (rare due to low CNS penetration).
• Severe diarrhea leading to electrolyte imbalance.
• Hypersensitivity reactions: rash, angioedema.

Monitoring

• Baseline and periodic ECG to measure QTc, particularly if supratherapeutic dosing or concurrent QT‑prolonging drugs.
• Liver function tests (LFTs): ALT/AST, bilirubin, especially in hepatic disease.
• Electrolytes: K⁺/Mg²⁺, especially in patients with diarrhea or on diuretics.
• Pregnancy test (if applicable) and fetal monitoring.
• Infant observation if mother is lactating.

Clinical Pearls

• QTc Watch: In the EU, the regulatory cap is 30 mg/day; exceeding this dose is associated with a significant jump in torsades incidence.
• Metoclopramide vs Domperidone:
• *Domperidone* preferred for prolonged treatment because of minimal central side‑effects.
• *Metoclopramide* has higher risk of tardive dyskinesia but can be used for acute antiemetic needs.
• CYP3A4 Interaction Strategy:
• When co‑administered with strong inhibitors (e.g., ketoconazole), dose reduction to 10 mg/day is advised.
• For strong inducers (e.g., rifampin), consider co‑therapy with another prokinetic or higher dosing (subject to safety data).
• Pediatric Use: Dosing often weight‑based (≤ 0.5 mg/kg/day). Monitor gastric motility via scintigraphy if life‑simulating symptoms persist.
• Breastfeeding Caution: Although excretion into milk is low, infants may develop hypotonia; consider alternative prokinetics if infant symptoms appear.
• Delaying Gastric Emptying: Short‑term, low‑dose domperidone can ameliorate postoperative ileus when combined with laxatives.
• Hormonal Influence: Estrogen therapy can increase domperidone clearance; check for menopausal status when prescribing.

These points help clinicians weigh benefits versus risks and optimize patient safety when using domperidone.