ULTOP DSR 40/30MG 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)
• Benign gastric ulcers
• Duodenal ulcers
• NSAID-associated peptic ulcer disease
• Prophylaxis of NSAID-associated gastric ulcers

Mechanism of action

Pantoprazole, as a substituted benzimidazole derivative, accumulates in the acidic compartment of the parietal cells of the stomach. In this acidic environment, it is converted to its active form, a sulfenamide, which binds covalently to cysteine residues on the hydrogen-potassium ATPase (proton pump) enzyme. This binding inactivates the enzyme, thereby inhibiting the final step of gastric acid secretion. The inhibition is potent and lasts longer than that of H2 receptor antagonists, leading to a significant reduction in gastric acidity.

Pharmacodynamics

Pantoprazole effectively decreases gastric acid secretion, which alleviates symptoms associated with acid reflux, promotes healing of esophageal inflammation, and enhances patient quality of life. It has shown superiority in symptom relief and healing compared to H2 receptor antagonists. The drug has an excellent safety profile, with a low incidence of drug interactions, making it suitable for use in high-risk populations, including the elderly and those with renal or moderate hepatic impairment.

Pharmacokinetics

Pantoprazole is rapidly absorbed after oral administration, with peak plasma concentrations occurring within 1 to 2 hours. It is extensively metabolized in the liver via the cytochrome P450 system, particularly CYP2C19 and CYP3A4, resulting in various metabolites. The drug has a half-life of approximately 1 hour, but its effects last significantly longer due to its irreversible binding to the proton pump. Excretion occurs mainly via the urine, with a minor portion eliminated in feces.

Adverse effects

• Headache
• Diarrhea
• Nausea
• Vomiting
• Abdominal pain
• Constipation
• Flatulence
• Dizziness
• Rash
• Fatigue
• Hypomagnesemia

Interactions

• Increased exposure with alpelisib
• May affect the absorption of drugs requiring an acidic environment

Precautions

• Monitor for gastrointestinal infections
• Use with caution in patients with liver impairment
• Long-term use may lead to vitamin B12 deficiency
• Consider risk of bone fractures with prolonged PPI therapy

Pregnancy

Pantoprazole should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Limited data on its safety in pregnancy are available.

Breast-feeding

Pantoprazole is excreted in breast milk. A decision should be made whether to discontinue breastfeeding or to discontinue the drug, taking into account the importance of the drug to the mother.

Storage

Store at room temperature, away from moisture and heat. Protect from light.

Formulations

• 40 mg enteric-coated tablet
• 40 mg oral suspension
• 40 mg powder for solution for infusion

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

Hydrochloric acid (HCl) secretion into the gastric lumen is a process regulated mainly by the H(+)/K(+)-ATPase of the proton pump, expressed in high quantities by the parietal cells of the stomach. ATPase is an enzyme on the parietal cell membrane that facilitates hydrogen and potassium exchange through the cell, which normally results in the extrusion of potassium and formation of HCl (gastric acid). Proton pump inhibitors such as pantoprazole are substituted _benzimidazole_ derivatives, weak bases, which accumulate in the acidic space of the parietal cell before being converted in the _canaliculi_ (small canal) of the gastric parietal cell, an acidic environment, to active _sulfenamide_ derivatives. This active form then makes disulfide bonds with important cysteines on the gastric acid pump, inhibiting its function. Specifically, pantoprazole binds to the _sulfhydryl group_ of H+, K+-ATPase, which is an enzyme implicated in accelerating the final step in the acid secretion pathway. The enzyme is inactivated, inhibiting gastric acid secretion. The inhibition of gastric acid secretion is stronger with proton pump inhibitors such as pantoprazole and lasts longer than with the H(2) antagonists. Pantoprazole is a proton pump inhibitor. It accumulates in the acidic compartment of parietal cells and is converted to the active form, a sulfanilamide, which binds to hydrogen-potassium-ATP-ase at the secretory surface of gastric parietal cells. Inhibition of hydrogen-potassium-ATPase blocks the final step of gastric acid production, leading to inhibition of both basal and stimulated acid secretion. The duration of inhibition of acid secretion does not correlate with the much shorter elimination half-life of pantoprazole. /Pantoprazole sodium/

Pharmacodynamics

This drug acts to decrease gastric acid secretion, which reduces stomach acidity. Pantoprazole administration leads to long-lasting inhibition of gastric acid secretion. **General Effects** Pantoprazole has been shown to reduce acid reflux-related symptoms, heal inflammation of the esophagus, and improve patient quality of life more effectively than histamine-2 receptor antagonists (H2 blockers). This drug has an excellent safety profile and a low incidence of drug interactions. It can be used safely in various high-risk patient populations, including the elderly and those with renal failure or moderate hepatic dysfunction. 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 pantoprazole have 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. PPIs such as pantoprazole 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. **A note on laboratory testing abnormalities** During treatment with antisecretory medicinal products such as pantoprazole, serum gastrin (a peptide hormone that stimulates secretion of gastric acid) increases in response to the decreased acid secretion caused by proton pump inhibition. The increased gastrin level may interfere with investigations for neuroendocrine tumors. Published evidence suggests that proton pump inhibitors should be stopped 14 days before chromogranin A (CgA) measurements. This permits chromogranin A levels, that might be falsely elevated after proton pump inhibitor treatment, to return to the normal reference range. Reports have been made of false-positive results in urine screening tests for tetrahydrocannabinol (THC) in patients receiving the majority of proton pump inhibitors, including pantoprazole. A confirmatory method should be used.