DEFLUX TABLET

Indications

• Nausea
• Vomiting
• Gastroesophageal reflux disease
• Delayed gastric emptying
• Management of nausea associated with chemotherapy

Dosage

Children: For children under 35 kg, the recommended dose is 250 micrograms/kg up to 3 times daily. Oral liquid formulations should be administered using an appropriately designed graduated oral syringe to ensure accurate dosing.

Adults: The recommended dose in adults and adolescents over 12 years and over 35 kg is 10 mg up to 3 times daily, with a maximum daily dose of 30 mg. Treatment duration should not usually exceed 1 week.

Mechanism of action

Domperidone acts as a gastrointestinal emptying adjunct and peristaltic stimulant. Its gastroprokinetic properties are attributed to its peripheral dopamine receptor blocking properties, which facilitate gastric emptying and decrease small bowel transit time by increasing esophageal and gastric peristalsis and lowering esophageal sphincter pressure. Its antiemetic effects are due to dopamine receptor blockade at the chemoreceptor trigger zone and gastric level, particularly affecting the D2 and D3 dopamine receptors.

Pharmacodynamics

Domperidone selectively blocks dopamine receptors, leading to enhanced gastrointestinal peristalsis and causing an increase in prolactin release. It serves a dual purpose as an antiemetic and a tool for examining dopaminergic mechanisms, effectively accelerating gastric emptying and reducing nausea.

Pharmacokinetics

Domperidone is absorbed from the gastrointestinal tract, although its bioavailability is limited due to extensive first-pass metabolism. It has a relatively long half-life, allowing for multiple daily dosing. The drug is primarily excreted through the faeces, and caution is advised in patients with hepatic impairment due to potential accumulation.

Contra-indications

• Cardiac conduction impairment
• Underlying cardiac disease
• Severe hepatic impairment
• Concomitant use with drugs that prolong the QT interval
• Hypersensitivity to domperidone or any of its components

Adverse effects

• Drowsiness
• Dizziness
• Dry mouth
• Anxiety
• Asthenia
• Headache
• Diarrhoea
• Breast abnormalities
• Ventricular arrhythmia

Interactions

• Dronedarone - Severe (increases exposure)
• Cobicistat - Severe (increases exposure)
• Crizotinib - Severe (increases exposure)
• Idelalisib - Severe (increases exposure)
• Letermovir - Severe (increases exposure)
• Imatinib - Unknown (increases exposure)
• Nilotinib - Unknown (increases exposure)

Precautions

• Elderly patients may be at increased risk of side effects
• Monitor for changes in mood and other behavioral effects
• Caution in patients with a history of psychiatric disorders
• Caution in patients with a history of hypertension
• Use with caution in patients with renal impairment

Pregnancy

Use only if potential benefit outweighs risk.

Breast-feeding

Avoid - no information available.

Storage

Store at room temperature, away from moisture and heat.

Formulations

• Capsule
• Oral liquid formulation

Mechanism of action

Domperidone acts as a gastrointestinal emptying (delayed) adjunct and peristaltic stimulant. The gastroprokinetic properties of domperidone are related to its peripheral dopamine receptor blocking properties. Domperidone facilitates gastric emptying and decreases small bowel transit time by increasing esophageal and gastric peristalsis and by lowering esophageal sphincter pressure. Antiemetic: The antiemetic properties of domperidone are related to its dopamine receptor blocking activity at both the chemoreceptor trigger zone and at the gastric level. It has strong affinities for the D2 and D3 dopamine receptors, which are found in the chemoreceptor trigger zone, located just outside the blood brain barrier, which - among others - regulates nausea and vomiting

Pharmacodynamics

Domperidone is a specific blocker of dopamine receptors. It speeds gastrointestinal peristalsis, causes prolactin release, and is used as antiemetic and tool in the study of dopaminergic mechanisms.