Lansoprazole

Lansoprazole is a substituted benzimidazole proton pump inhibitor that irreversibly inhibits the gastric H+/K+ ATPase. Its orodispersible formulation makes it useful for children, patients with dysphagia and enteral tube administration.

Classification. Proton pump inhibitor; gastric antisecretory agent.

Mechanism. Prodrug activated in the acidic secretory canaliculus to a sulphenamide that binds the pump covalently, blocking the final step of acid secretion until new pumps are synthesised.

Pharmacodynamics. Maximal suppression after 3 to 5 days of daily dosing; 30 mg lansoprazole is broadly equipotent to 20 mg omeprazole for healing.

Pharmacokinetics. Oral bioavailability about 80%; food reduces absorption by about half, so dosing before food matters. Protein binding 97%; half-life 1 to 2 hours, prolonged in liver impairment and older adults.

Metabolism. Hepatic via CYP2C19 and CYP3A4; metabolites excreted in bile and urine. Weak CYP2C19 inhibitor and weak CYP1A2 inducer.

Adult oral doses unless stated. Use the lowest effective dose for the shortest necessary duration.

GORD with erosive oesophagitis. 30 mg once daily for 4 weeks, continued for a further 4 weeks if not healed. Maintenance 15 to 30 mg once daily.

Nonerosive reflux and dyspepsia. 15 to 30 mg once daily for 4 weeks; thereafter 15 mg on demand.

Peptic ulcer disease.

• Duodenal ulcer: 30 mg once daily for 4 weeks.

• Gastric ulcer: 30 mg once daily for 8 weeks, with endoscopic confirmation of healing.

NSAID-associated ulcer. Healing 30 mg once daily for 4 to 8 weeks. Prophylaxis 15 to 30 mg once daily for as long as the NSAID continues in those at raised risk.

Helicobacter pylori eradication. Lansoprazole 30 mg twice daily for 14 days, combined with one of:

• Amoxicillin 1 g twice daily plus clarithromycin 500 mg twice daily.

• Penicillin allergy: clarithromycin 500 mg twice daily plus metronidazole 400 to 500 mg twice daily.

• Bismuth quadruple therapy where clarithromycin resistance is high or after a failed first attempt: bismuth subsalicylate 524 mg four times daily, tetracycline 500 mg four times daily and metronidazole 400 to 500 mg three times daily.

Clarithromycin resistance is reported to be high in several East African settings, so bismuth quadruple therapy or a 14-day course is advised where local susceptibility data are lacking.

Zollinger-Ellison syndrome. Start 60 mg once daily and titrate to acid output; give daily doses over 120 mg in two divided doses. Doses up to 180 mg daily have been used.

Upper gastrointestinal bleeding, oral phase after IV therapy. 30 mg twice daily to day 14, then 30 mg once daily to complete 6 to 8 weeks. No IV formulation is widely available.

Paediatric dosing (GORD, erosive oesophagitis).

• Body weight 30 kg or less: 15 mg once daily (or 0.5 to 1 mg/kg once daily, maximum 15 mg, in smaller children).

• Body weight over 30 kg: 15 to 30 mg once daily.

• Course up to 12 weeks, then review.

Contraindications. Hypersensitivity to any PPI; coadministration with rilpivirine. Avoid with atazanavir and nelfinavir.

Before starting. Endoscopy first for alarm features: new dyspepsia over age 55, weight loss, dysphagia, bleeding, iron deficiency anaemia, persistent vomiting or a mass.

Common adverse effects. Headache, diarrhoea, nausea, abdominal pain, constipation and dizziness.

Serious adverse effects.

• Microscopic colitis: the association is stronger for lansoprazole than for other PPIs. Consider it with chronic watery diarrhoea and stop or switch.

• Hypomagnesaemia, Clostridioides difficile infection and acute interstitial nephritis.

• Vitamin B12 deficiency, fracture, subacute cutaneous lupus erythematosus and rebound hypersecretion with long-term use.

Major interactions.

• Clopidogrel: possible reduction in activation, smaller than with omeprazole; pantoprazole is preferred.

• Tacrolimus: raised levels, particularly in CYP2C19 poor metabolisers; monitor levels.

• Theophylline: modest fall in levels from CYP1A2 induction; monitor levels when starting or stopping.

• Methotrexate at high dose: reduced clearance; withhold lansoprazole around high-dose courses.

• Reduced absorption of ketoconazole, itraconazole capsules, atazanavir, rilpivirine, erlotinib, dasatinib, oral iron and mycophenolate mofetil.

Special groups.

• Pregnancy: human data are reassuring though smaller than for omeprazole; use when clearly needed.

• Breastfeeding: limited data, low expected infant exposure; compatible.

• Children: orodispersible tablets suit young children and allow partial dosing when dispersed in water.

• Older adults: clearance falls; the usual maximum is 30 mg daily except for Helicobacter pylori eradication.

• Kidney impairment: no dose adjustment.

• Liver impairment: moderate to severe impairment, reduce the daily dose by 50% and monitor.

Formulations. Gastro-resistant capsules 15 mg and 30 mg; orodispersible tablets 15 mg and 30 mg.

Oral administration. Take at least 30 minutes before breakfast; a second daily dose goes before the evening meal. Swallow capsules whole or open and sprinkle the granules on soft acidic food without chewing. Orodispersible tablets dissolve on the tongue and are swallowed with saliva, or may be dispersed in a small volume of water.

Enteral tubes. Disperse an orodispersible tablet in 10 mL water and give through a tube of 8 French or larger, flushing after. Do not crush capsule granules.

Baseline. No routine tests. Magnesium before long-term use with digoxin or diuretics.

Monitoring.

• Review indication and continued need at 4 to 8 weeks, then at least annually.

• New chronic watery diarrhoea: consider microscopic colitis or C. difficile infection.

• Magnesium periodically on long-term therapy in those at risk; tacrolimus levels when coprescribed.

• Stop 2 weeks before H. pylori breath or stool antigen testing, and at least 5 days before chromogranin A measurement.

Therapeutic drug monitoring. Not applicable.

Stopping. After long-term use, step down or halve the dose for 2 to 4 weeks before stopping, using antacids for rebound symptoms. Stop at once if interstitial nephritis, microscopic colitis, C. difficile infection or cutaneous lupus is suspected.

Referral and escalation. Endoscopy for alarm features or failure of 8 weeks of twice daily therapy. Persistent diarrhoea after stopping needs colonoscopy with random biopsies.