RAN-LANSOPRAZOLE 15

Indications

• Gastro-oesophageal reflux disease
• Duodenal ulcer
• Benign gastric ulcer
• NSAID-associated gastric or duodenal ulcer
• Zollinger-Ellison syndrome

Dosage

Adults: 30 mg once daily for 4 weeks for duodenal ulcers, 30 mg once daily for 8 weeks for gastric ulcers, and 15 mg once daily for maintenance treatment. For gastro-oesophageal reflux disease, the usual dose is 15 mg

Mechanism of action

Lansoprazole is a prodrug that becomes activated in an acidic environment. Once protonated, it forms stable disulfide bonds with cysteine residues on the H+,K+-ATPase enzyme in parietal cells. This covalent binding leads to prolonged inhibition of gastric acid secretion, affecting both basal and stimulated acid production regardless of the stimulus.

Pharmacodynamics

Lansoprazole decreases gastric acid secretion by specifically targeting the H+,K+-ATPase enzyme, which catalyzes the final step in gastric acid secretion. It effectively heals duodenal ulcers and alleviates symptoms associated with acid secretion, such as heartburn, while also reducing pepsin secretion. Its action is effective in both daytime and nocturnal acid secretion, making it useful in treating various acid-related disorders.

Pharmacokinetics

Lansoprazole is absorbed after oral administration, with peak plasma concentrations usually occurring within 1-2 hours. It is extensively metabolized in the liver primarily via cytochrome P450 enzymes, leading to various metabolites that are excreted in urine. The half-life of lansoprazole is approximately 1.5 hours, but its acid-suppressive effects last longer due to its mechanism of action. The presence of food can affect the absorption rate, so it is typically recommended to take lansoprazole before meals.

Contra-indications

• Hypersensitivity to lansoprazole or any of its excipients
• Concurrent use with rilpivirine-containing products

Adverse effects

• Headache
• Diarrhoea
• Nausea
• Abdominal pain
• Constipation
• Flatulence
• Dizziness
• Fatigue
• Skin rash
• Elevated liver enzymes
• Acute interstitial nephritis
• Clostridium difficile-associated diarrhoea
• Bone fractures
• Hypomagnesemia

Interactions

• Increased risk of gastrointestinal infections due to reduced gastric acidity
• Apalutamide may decrease exposure when used with lansoprazole
• May alter the absorption of drugs that require an acidic environment for optimal absorption

Precautions

• Use with caution in patients with hepatic impairment
• Monitor for signs of Clostridium difficile infection in patients with prolonged therapy
• Consider risk of hypomagnesemia and associated complications

Pregnancy

Manufacturer advises to avoid use during pregnancy due to lack of adequate human data.

Breast-feeding

Specialist sources indicate use with caution, as lansoprazole is likely to be present in human milk, but in small amounts probably too low to be harmful.

Storage

Store below 25°C in a dry place, protect from light.

Formulations

• Gastro-resistant capsules
• Oral suspension
• Gastro-resistant tablets
• Gastro-resistant granules

Mechanism of action

As a PPI, lansoprazole is a prodrug and requires protonation via an acidic environment to become activated. Once protonated, lansoprazole is able to react with cysteine residues, specifically Cys813 and Cys321, on parietal H+,K+-ATPase resulting in stable disulfides. PPI's in general are able to provide prolonged inhibition of acid secretion due to their ability to bind covalently to their targets. Lansoprazole is a selective and irreversible proton pump inhibitor. In the acidic environment of the gastric parietal cell, lansoprazole is converted to active sulphenamide derivatives that bind to the sulfhydryl group of (H+, K+)-adenosine triphosphatase ((H+,K+)-ATPase), also known as the proton pump (H+,K+)-ATPase catalyzes the final step in the gastric acid secretion pathway. Lansoprazole's inhibition of (H+,K+)-ATPase results in inhibition of both centrally and peripherally mediated gastric acid secretion. The inhibitory effect is dose-related. Lansoprazole inhibits both basal and stimulated gastric acid secretion regardless of the stimulus.

Pharmacodynamics

Lansoprazole decreases gastric acid secretion by targeting H+,K+-ATPase, which is the enzyme that catalyzes the final step in the acid secretion pathway in parietal cells. Conveniently, lansoprazole administered any time of day is able to inhibit both daytime and nocturnal acid secretion. The result is that lansoprazole is effective at healing duodenal ulcers, reduces ulcer-related pain, and offers relief from symptoms of heartburn Lansoprazole also reduces pepsin secretion, making it a useful treatment option for hypersecretory conditions such as Zollinger-Ellison syndrome.