ESOFAG D CAPSULES

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

• Gastroesophageal reflux disease (GERD)
• Erosive esophagitis
• Peptic ulcers
• Helicobacter pylori eradication
• Zollinger-Ellison syndrome

Dosage

Adults: The usual oral dose

Mechanism of action

Esomeprazole exerts its stomach acid-suppressing effects by covalently binding to cysteine residues on the H+/K+-ATPase enzyme at the secretory surface of gastric parietal cells. This action inhibits both basal and stimulated gastric acid secretion irreversibly, requiring the synthesis of new enzyme to restore acid production. By blocking the final step of gastric acid production, esomeprazole reduces gastric acidity in a dose-dependent manner.

Pharmacodynamics

Esomeprazole is a substituted benzimidazole that inhibits gastric acid secretion without exhibiting anticholinergic or H2 receptor antagonistic properties. It is indicated for the treatment of GERD, healing of erosive esophagitis, and eradication of H. pylori to reduce duodenal ulcer recurrence. The suppression of gastric acid secretion is dose-related and effective against various stimuli that promote acid secretion.

Pharmacokinetics

Esomeprazole is rapidly absorbed after oral administration, with peak plasma concentrations typically occurring within 1-2 hours. It undergoes extensive hepatic metabolism primarily by the cytochrome P450 system, especially CYP2C19, resulting in several metabolites. The elimination half-life is approximately 1-2 hours, though its antisecretory effects last longer. It is excreted predominantly in the urine. Dose adjustments may be necessary in patients with hepatic impairment.

Contra-indications

• Hypersensitivity to esomeprazole or any of its components
• Concomitant use with rilpivirine-containing products

Adverse effects

• Abdominal pain
• Constipation
• Diarrhea
• Dizziness
• Dry mouth
• Headache
• Insomnia
• Nausea
• Skin reactions
• Vomiting
• Bone fractures
• Confusion
• Depression
• Drowsiness
• Leucopenia
• Malaise
• Myalgia
• Paraesthesia
• Peripheral edema
• Thrombocytopenia
• Vertigo
• Vision disorders
• Agranulocytosis
• Alopecia
• Gynaecomastia
• Hallucination
• Hepatic disorders
• Hyperhidrosis
• Hyponatraemia
• Nephritis
• Tubulointerstitial nephritis
• Pancytopenia
• Photosensitivity reaction
• Severe cutaneous adverse reactions (SCARs)
• Stomatitis
• Taste altered
• Hypomagnesaemia

Interactions

• Esomeprazole may increase the exposure to cannabidiol
• Esomeprazole may increase the exposure to cilostazol

Precautions

• Increased risk of fractures, particularly in the elderly and when used at high doses for over a year
• Caution in patients at risk of osteoporosis; adequate intake of calcium and vitamin D is recommended
• May increase the risk of gastrointestinal infections, including Clostridioides difficile
• Symptoms of gastric cancer should be ruled out before treatment
• Use with caution in patients with hepatic impairment

Pregnancy

Use with caution. The manufacturer advises avoiding use unless necessary since the effects on the fetus are not fully known.

Breast-feeding

Manufacturer advises avoiding use as esomeprazole is present in breast milk and may cause diarrhea in nursing infants. However, amounts are probably too small to be harmful.

Storage

Store in a cool, dry place below 25°C. Keep out of

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.

Mechanism of action

Esomeprazole exerts its stomach acid-suppressing effects by preventing the final step in gastric acid production by covalently binding to sulfhydryl groups of cysteines found on the (H+, K+)-ATPase enzyme at the secretory surface of gastric parietal cells. This effect leads to inhibition of both basal and stimulated gastric acid secretion, irrespective of the stimulus. As the binding of esomeprazole to the (H+, K+)-ATPase enzyme is irreversible and new enzyme needs to be expressed in order to resume acid secretion, esomeprazole's duration of antisecretory effect that persists longer than 24 hours. Esomeprazole is a proton pump inhibitor that suppresses gastric acid secretion by specific inhibition of the H+/K+-ATPase in the gastric parietal cell. The S- and R-isomers of omeprazole are protonated and converted in the acidic compartment of the parietal cell forming the active inhibitor, the achiral sulphenamide. By acting specifically on the proton pump, esomeprazole blocks the final step in acid production, thus reducing gastric acidity. This effect is dose-related up to a daily dose of 20 to 40 mg and leads to inhibition of gastric acid secretion.

Pharmacodynamics

Esomeprazole is a compound that inhibits gastric acid secretion and is indicated in the treatment of gastroesophageal reflux disease (GERD), the healing of erosive esophagitis, and <i>H. pylori</i> eradication to reduce the risk of duodenal ulcer recurrence. Esomeprazole belongs to a new class of antisecretory compounds, the substituted benzimidazoles, that do not exhibit anticholinergic or H2 histamine antagonistic properties, but that suppress gastric acid secretion by specific inhibition of the H⁺/K⁺ ATPase at the secretory surface of the gastric parietal cell. By doing so, it inhibits acid secretion into the gsatric lumen. This effect is dose-related and leads to inhibition of both basal and stimulated acid secretion irrespective of the stimulus. Esomeprazole is the s-isomer of [DB00338], which is a racemate of the S- and R-enantiomer. Esomeprazole has been shown to inhibit acid secretion to a similar extent as [DB00338], without any significant differences between the two compounds _in vitro_. PPIs such as esomeprazole have also been shown to inhibit the activity of dimethylarginine dimethylaminohydrolase (DDAH), an enzyme necessary for cardiovascular health. DDAH inhibition causes a consequent accumulation of the nitric oxide synthase inhibitor asymmetric dimethylarginie (ADMA), which is thought to cause the association of PPIs with increased risk of cardiovascular events in patients with unstable coronary syndromes. Due to their good safety profile and as several PPIs are available over the counter without a prescription, their current use in North America is widespread. Long term use of PPIs such as esomeprazole has been associated with possible adverse effects, however, including increased susceptibility to bacterial infections (including gastrointestinal _C. difficile_), reduced absorption of micronutrients including iron and B12, and an increased risk of developing hypomagnesemia and hypocalcemia which may contribute to osteoporosis and bone fractures later in life.