RABICOR PLUS CAPSULE

Indications

• Gastric ulcer
• Duodenal ulcer
• Gastro-oesophageal reflux disease (GERD)
• Functional dyspepsia
• NSAID-associated peptic ulcer disease
• Zollinger-Ellison syndrome

Dosage

Adults: Initially 20 mg once daily for 4 to 8 weeks for GERD. For gastric and duodenal ulcers, the initial dose is 20 mg daily for 4 to 8 weeks. For NSAID-associated peptic ulcer disease, the recommended dose is 20 mg once daily for 4 to 8 weeks. Dose adjustments may be necessary in hepatic impairment, with a maximum dose of 20 mg daily

Mechanism of action

Rabeprazole sodium acts by irreversibly binding to and inhibiting the H+/K+ ATPase enzyme system (proton pump) in the gastric epithelium. This action leads to a decrease in gastric acid secretion, both basal and stimulated. The inhibition is dose-dependent and can last for 24 hours or longer, which helps in healing peptic ulcers and alleviating symptoms of acid-related disorders.

Pharmacodynamics

Rabeprazole sodium effectively suppresses gastric acid secretion, providing symptomatic relief and promoting mucosal healing in conditions associated with excessive gastric acidity. It demonstrates a rapid onset of action, with peak plasma concentrations occurring approximately 3-4 hours after administration. The drug's effects on gastric acid secretion can lead to increased gastric pH and improved healing of ulcerative lesions.

Pharmacokinetics

Rabeprazole sodium is rapidly absorbed after oral administration, with bioavailability of approximately 52% due to first-pass metabolism. The drug is extensively metabolized in the liver, primarily via the cytochrome P450 system. Its elimination half-life ranges from 1 to 2 hours, and it is excreted primarily through urine as metabolites. Food does not significantly affect its absorption.

Adverse effects

• Asthenia
• Angioedema
• Electrolyte imbalance
• Muscle spasms
• Hyperlipidaemia
• Weight change

Precautions

• Manufacturer advises caution in severe hepatic impairment, monitor liver function and discontinue if deterioration occurs.

Pregnancy

Manufacturer advises to avoid unless potential benefit outweighs risk-fetotoxic in animals.

Breast-feeding

Specialist sources indicate that the amount in milk is small and not known to be harmful.

Storage

Store below 25 degrees Celsius. Protect from light and moisture.

Formulations

• Gastro-resistant tablet
• Powder for solution for injection

Indications

• Functional dyspepsia
• Gastroesophageal reflux disease (GERD)
• Gastroparesis
• Postoperative ileus

Dosage

Children: For children, itopride should be used with caution, and specific dosing should be referred to in the BNF for Children due to the need for careful consideration of age, weight, and clinical condition.

Adults: The usual adult dose for itopride is 150 mg per day, divided into three doses of 50 mg each, taken before meals.

Mechanism of action

Itopride has anticholinesterase activity, which prevents the breakdown of acetylcholine (ACh) in the gastrointestinal tract. It also acts as a dopamine D2 receptor antagonist. By inhibiting AChE, it increases ACh levels, stimulating gastric smooth muscle contraction via M3 receptors. Additionally, by antagonizing D2 receptors, it diminishes the inhibitory effects of dopamine on ACh release, further promoting gastric motility and enhancing lower esophageal sphincter pressure.

Pharmacodynamics

The pharmacodynamic profile of itopride involves increased gastric motility and improved coordination between the stomach and duodenum. The inhibition of AChE leads to elevated ACh concentrations, which enhances smooth muscle contraction. The antagonism of D2 receptors supports this effect by removing the suppression on ACh release, leading to enhanced gastrointestinal activity, which is particularly beneficial in treating symptoms associated with dyspepsia and other motility disorders.

Pharmacokinetics

Itopride is well absorbed from the gastrointestinal tract, with a bioavailability that allows for effective therapeutic concentrations. It undergoes hepatic metabolism, primarily through conjugation and may have variable half-life depending on individual patient factors. The elimination route is primarily through urine, with metabolites being excreted. Its pharmacokinetic properties support its use as a prokinetic agent in managing gastric motility disorders.

Contra-indications

• Hypersensitivity to itopride or any of its components
• Gastrointestinal bleeding
• Mechanical obstruction of the gastrointestinal tract
• Severe renal impairment

Adverse effects

• Nausea
• Diarrhea
• Abdominal pain
• Dizziness
• Headache
• Somnolence
• Extrapyramidal symptoms

Interactions

• May enhance the effects of other prokinetic agents
• Anticholinergic drugs may reduce its efficacy
• May interact with dopaminergic agents

Precautions

• Use with caution in patients with a history of extrapyramidal symptoms
• Caution in patients with hepatic impairment
• Should be used cautiously in elderly patients

Pregnancy

There is insufficient data on the use of itopride during pregnancy. It should only be used if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Itopride is excreted in breast milk. Caution should be exercised when administering it to breastfeeding mothers.

Storage

Store at room temperature, away from moisture and heat. Keep out of reach of children.

Formulations

• Tablets (50 mg, 150 mg)
• Oral suspension

Indications

• Gastroesophageal reflux disease (GERD)
• Peptic ulcers
• Zollinger-Ellison syndrome
• Prevention of gastric ulcers associated with NSAID use

Dosage

Adults: Refer to BNF for specific dosing recommendations based on condition being treated.

Mechanism of action

Rabeprazole inhibits gastric acid secretion by irreversibly binding to the hydrogen-potassium ATPase enzyme system (H+, K+-ATPase) located at the parietal cell surface. This action blocks the final step in the gastric acid secretion process, leading to a reduction in hydrogen ion transport into the gastric lumen. Rabeprazole is activated in the acidic environment of the stomach, transforming into an active sulfenamide which exerts its inhibitory effects.

Pharmacodynamics

By preventing the production of gastric acid, rabeprazole alleviates symptoms associated with excessive acid secretion, such as heartburn and esophagitis. It is particularly effective in treating gastroesophageal reflux disease (GERD) and peptic ulcers, as well as in combination with antibiotics for the eradication of Helicobacter pylori. Furthermore, rabeprazole is utilized in managing conditions like Zollinger-Ellison syndrome, where there is an overproduction of gastric acid.

Pharmacokinetics

Rabeprazole is rapidly absorbed following oral administration, with peak plasma concentrations occurring within 1 to 2 hours. It is extensively metabolized in the liver through the cytochrome P450 system, primarily via CYP2C19 and CYP3A4 isoenzymes. The elimination half-life of rabeprazole ranges from 1 to 2 hours. The drug is excreted mainly in the urine as metabolites, with minimal unchanged drug present. Food intake can affect the absorption but not the overall efficacy of the drug.

Adverse effects

• Headache
• Nausea
• Diarrhea
• Constipation
• Abdominal pain
• Rash
• Dizziness

Interactions

• apalutamide+rabeprazole: Unknown (decreases exposure)

Precautions

• Use with caution in patients with hepatic impairment
• Monitor for potential vitamin B12 deficiency with long-term use
• Consider risk of Clostridium difficile infection in patients with diarrhea

Pregnancy

Rabeprazole is classified as category B. Animal studies have shown no harm, but there are no well-controlled studies in pregnant women. Use only if clearly needed.

Breast-feeding

Rabeprazole is excreted in breast milk. Caution should be exercised when administered to a nursing mother.

Storage

Store at room temperature, away from moisture and heat. Keep out of reach of children.

Formulations

• Tablets: 20 mg

Mechanism of action

Itopride has anticholinesterase (AchE) activity as well as dopamine D2 receptor antagonistic activity. It is well established that M3 receptors exist on the smooth muscle layer throughout the gut and acetylcholine (ACh) released from enteric nerve endings stimulates the contraction of smooth muscle through M3 receptors. The enzyme AChE hydrolyses the released ACh, inactivates it and thus inhibits the gastric motility leading to various digestive disorders. Besides ACh, dopamine is present in significant amounts in the gastrointestinal tract and has several inhibitory effects on gastrointestinal motility, including reduction of lower esophageal sphincter and intragastric pressure. These effects appear to result from suppression of ACh release from the myenteric motor neurons and are mediated by the D2 subtype of dopamine receptors. Itopride, by virtue of its dopamine D2 receptor antagonism, removes the inhibitory effects on Ach release. It also inhibits the enzyme AchE which prevents the degradation of ACh. The net effect is an increase in ACh concentration, which in turn, promotes gastric motility, increases the lower esophageal sphincter pressure, accelerates gastric emptying and improves gastro-duodenal coordination. This dual mode of action of Itopride is unique and different from the actions of other prokinetic agents available in the market.

Mechanism of action

Rabeprazole belongs to a class of antisecretory compounds (substituted benzimidazole proton-pump inhibitors) that do not exhibit anticholinergic or histamine H2-receptor antagonist properties, but suppress gastric acid secretion by inhibiting the gastric H⁺/K⁺ATPase (hydrogen-potassium adenosine triphosphatase) at the secretory surface of the gastric parietal cell. Because this enzyme is regarded as the acid (proton) pump within the parietal cell, rabeprazole has been characterized as a gastric proton-pump inhibitor. Rabeprazole blocks the final step of gastric acid secretion. In gastric parietal cells, rabeprazole is protonated, accumulates, and is transformed to an active sulfenamide. When studied in vitro, rabeprazole is chemically activated at pH 1.2 with a half-life of 78 seconds. Rabeprazole is a selective and irreversible proton pump inhibitor. Rabeprazole suppresses gastric acid secretion by specific inhibition of the hydrogen-potassium adenosine triphosphatase (H+, K+-ATPase) enzyme system found at the secretory surface of parietal cells. It inhibits the final transport of hydrogen ions (via exchange with potassium ions) into the gastric lumen. Since the H+, K+-ATPase enzyme system is regarded as the acid (proton) pump of the gastric mucosa, rabeprazole is known as a gastric acid pump inhibitor. Rabeprazole does not have anticholinergic or histamine H2-receptor antagonist properties. Rabeprazole binds to hydrogen-potassium ATPase in gastric parietal cells; inactivation of this enzyme system (also known as the proton, hydrogen, or acid pump) blocks the final step in the secretion of hydrochloric acid secretion. The antisecretory effect is apparent within 1 hour following oral administration with the median inhibitory effect on 24-hour gastric acidity being 88% of maximal after the first dose.

Pharmacodynamics

Rabeprazole prevents the production of acid in the stomach. It reduces symptoms and prevents injury to the esophagus or stomach in patients with gastroesophageal reflux disease (GERD) or ulcers. Rabeprazole is also useful in conditions that produce too much stomach acid such as Zollinger-Ellison syndrome. Rabeprazole may also be used with antibiotics to get rid of bacteria that are associated with some ulcers. Rabeprazole is a selective and irreversible proton pump inhibitor, suppresses gastric acid secretion by specific inhibition of the H⁺, K⁺ -ATPase, which is found at the secretory surface of parietal cells. In doing so, it inhibits the final transport of hydrogen ions (via exchange with potassium ions) into the gastric lumen.