LIMZER

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

Indications

• Gastric ulcer
• Duodenal ulcer
• Gastro-oesophageal reflux disease (GERD)
• Severe oesophagitis
• Helicobacter pylori eradication (in combination therapy)
• Prevention of NSAID-associated gastric and duodenal ulcers
• Zollinger-Ellison syndrome

Dosage

Adults: The usual dose for adults is 20 mg once daily for 4 weeks for duodenal ulcer and GERD. For gastric ulcer, the dose may be 20 mg to 40 mg once daily

Mechanism of action

Omeprazole works by specifically binding to the proton pump (H+/K+ ATPase) in the gastric parietal cells, leading to irreversible inhibition of acid secretion. This binding prevents the exchange of hydrogen ions for potassium ions, effectively reducing the production of gastric acid and promoting healing of acid-related conditions.

Pharmacodynamics

The pharmacodynamic effects of omeprazole manifest as a significant decrease in gastric acidity, which improves symptoms related to excessive acid secretion. The onset of action typically occurs within an hour of administration, with maximum effect seen within 2 to 4 days of continuous use. The duration of action allows for once-daily dosing in most indications.

Pharmacokinetics

Omeprazole is rapidly absorbed from the gastrointestinal tract, reaching peak plasma concentrations within 0.5 to 3.5 hours after oral administration. It is extensively metabolized in the liver via the cytochrome P450 system, primarily CYP2C19 and CYP3A4, leading to the formation of inactive metabolites. The elimination half-life is approximately 0.5 to 1 hour, but the effects on gastric acid secretion last much longer due to the irreversible nature of proton pump inhibition. Omeprazole is excreted mainly in the urine as metabolites, with less than 1% of the drug excreted unchanged.

Contra-indications

• Hypersensitivity to omeprazole or any component of the formulation
• Use with caution in patients with severe liver impairment

Adverse effects

• Nausea
• Vomiting
• Diarrhea
• Headache
• Abdominal pain
• Flatulence
• Constipation
• Dizziness
• Fatigue
• Rash
• Muscle weakness
• Gastrointestinal candidiasis
• Aggression
• Agitation
• Bronchospasm
• Encephalopathy

Interactions

• Cenobamate may increase exposure to omeprazole
• Fedratinib may increase exposure to omeprazole
• Apalutamide may decrease exposure to omeprazole
• Cilostazol may increase exposure to omeprazole

Precautions

• Monitor patients for gastrointestinal symptoms
• Use caution in patients with a history of liver disease
• Consider potential for vitamin B12 deficiency with long-term use
• Monitor for signs of Clostridium difficile infection in the colon

Pregnancy

Not known to be harmful during pregnancy, but should be used only if clearly needed.

Breast-feeding

Excreted in breast milk, caution is advised when administered to nursing mothers.

Storage

Store below 25 degrees Celsius. Protect from moisture. Keep out of reach of children.

Formulations

• Orodispersible tablets
• Gastro-resistant capsules
• Intravenous injection
• Oral suspension

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.