Lansoprazol

Lansoprazole 15 mg gastro-resistant capsules

Each gastro-resistant capsule contains 15 mg of lansoprazole.

Gastro-resistant capsule.

Size 3 capsule with opaque yellow cap and body, containing white or off-white spherical microgranules.

- Treatment of duodenal and gastric ulcer

- Treatment of reflux oesophagitis

- Prophylaxis of reflux oesophagitis

- Eradication of Helicobacter pylori (H. pylori) concurrently given with appropriate antibiotic therapy treatment for H. pylori-associated ulcers

- Treatment of NSAID-associated benign gastric and duodenal ulcers in patients requiring continued NSAID treatment

- Prophylaxis of NSAID-associated gastric ulcers and duodenal ulcers in patients at risk requiring continued therapy

- Symptomatic gastroesophageal reflux disease

- Zollinger-Ellison syndrome.

For optimal effect, Lansoprazole should be taken once daily in the morning, except when used for H. pylori eradication when treatment should be twice a day, once in the morning and once in the evening. Lansoprazole should be taken at least 30 minutes before food. Capsules should be swallowed with liquid.

For patients with difficulty swallowing; studies and clinical practice suggest that the capsules may be opened and the granules mixed with a small amount of water, apple/tomato juice or sprinkled onto a small amount of soft food (e.g. yoghurt, apply puree) to ease administration. Capsules may also be opened and granules mixed with 40 ml apple juice for administration through a nasogastric tube. After preparing the suspension or mixture, the drug should be administered immediately.

Treatment of duodenal ulcer:

The recommended dose is 30 mg once daily for 2 weeks. In patients not fully healed within this time, the medication is continued at the same dose for another two weeks.

Treatment of gastric ulcer:

The recommended dose is 30 mg once daily for 4 weeks. The ulcer usually heals within 4 weeks, but in patients not fully healed within this time, the medication may be continued at the same dose for another 4 weeks.

Reflux oesophagitis:

The recommended dose is 30 mg once daily for 4 weeks. In patients not fully healed within this time, the treatment may be continued at the same dose for another 4 weeks.

Prophylaxis of reflux oesophagitis:

15 mg once daily. The dose may be increased up to 30 mg daily as necessary.

Eradication of Helicobacter pylori:

When selecting appropriate combination therapy consideration should be given to official local guidance regarding bacterial resistance, duration of treatment, (most commonly 7 days but sometimes up to 14 days), and appropriate use of antibacterial agents.

The recommended dose is 30 mg of lansoprazole twice daily for 7 days in combination with one of the following:

clarithromycin 250-500 mg twice daily + amoxicillin 1 g twice daily

clarithromycin 250 mg twice daily + metronidazole 400-500 mg twice daily

The H. pylori eradication results obtained when clarithromycin is combined with either amoxicillin or metronidazole gives rates of up to 90%, when used in combination with Lansoprazole.

Six months after successful eradication treatment, the risk of re-infection is low and relapse is therefore unlikely.

Use of a regimen including lansoprazole 30 mg twice daily, amoxicillin 1 g twice daily and metronidazole 400-500 mg twice daily has also been examined. Lower eradication rates were seen using this combination than in regimens involving clarithromycin. It may be suitable for those who are unable to take clarithromycin as part of an eradication therapy, when local resistance rates to metronidazole are low.

Treatment for NSAID associated benign gastric and duodenal ulcers in patients requiring continued NSAID treatment:

30 mg once daily for four weeks. In patients not fully healed the treatment may be continued for another four weeks. For patients at risk with ulcers that are difficult to heal, a longer course of treatment and/or a higher dose should probably be used.

Treatment for NSAID associated gastric and duodenal ulcers in patients at risk (such as age > 65 or history of gastric or duodenal ulcer) requiring prolonged NSAID treatment:

15 mg once daily. If the treatment fails the dose 30 mg once daily should be used.

Symptomatic gastro-oesophageal reflux disease:

The recommended dose is 15 mg or 30 mg daily. Relief of symptoms is obtained rapidly. Individual adjustment of dosage should be considered. If the symptoms are not relieved within 4 weeks with a daily dose of 30 mg, further examinations are recommended.

Zollinger-Ellison syndrome:

The recommended initial dose is 60 mg once daily. The dose should be individually adjusted and the treatment should be continued for as long as necessary. Daily doses of up to 180 mg have been used. If the required daily dose exceeds 120 mg, it should be given in two divided doses.

Impaired hepatic or renal function:

There is no need for a dose adjustment in patients with impaired renal function.

Patients with moderate or severe liver disease should be kept under regular supervision and a 50% reduction of the daily dose is recommended.

Elderly:

Due to reduced clearance of lansoprazole in the elderly an adjustment of dose may be necessary based on individual requirements. A daily dose of 30 mg should not be exceeded in the elderly unless there are compelling indications.

Children:

Hypersensitivity to the active substance or to any of the excipients. Lansoprazole should not be administered with atazanavir.

In common with other anti-ulcer therapies, the possibility of malignant gastric tumour should be excluded when treating a gastric ulcer with lansoprazole because lansoprazole can mask the symptoms and delay the diagnosis.

Lansoprazole should be used with caution in patients with moderate and severe hepatic dysfunction.

Decreased gastric acidity due to lansoprazole might be expected to increase gastric counts of bacteria normally present in the gastrointestinal tract. Treatment with lansoprazole may lead to a slightly increased risk of gastrointestinal infections such as Salmonella and Campylobacter.

In patients suffering from gastro-duodenal ulcers, the possibility of H. pylori infection as an etiological factor should be considered.

If lansoprazole is used in combination with antibiotics for eradication therapy of H. pylori, then the instructions for the use of these antibiotics should also be followed.

Because of limited safety data for patients on maintenance treatment for longer than 1 year, regular review of the treatment and a thorough risk/benefit assessment should regularly be performed in these patients.

Very rarely cases of colitis have been reported in patients taking lansoprazole. Therefore in the case of severe and/or persistent diarrhoea, discontinuation of therapy should be considered.

The treatment for the prevention of peptic ulceration of patient in need of continuous NSAID treatment should be restricted to high risk patients (e.g. previous gastrointestinal bleeding, perforation or ulcer, advanced age, concomitant use of medication known to increase the likelihood of upper GI adverse events [e.g. corticosteroids or anticoagulants], the presence of a serious co-morbidity factor or the prolonged use of NSAID maximum recommended doses).

Proton pump inhibitors, especially if used in high doses and over long durations (>1 year), may modestly increase the risk of hip, wrist and spine fracture, predominantly in the elderly or in presence of other recognised risk factors. Observational studies suggest that proton pump inhibitors may increase the overall risk of fracture by 10-40%. Some of this increase may be due to other risk factors. Patients at risk of osteoporosis should receive care according to current clinical guidelines and they should have an adequate intake of vitamin D and calcium.

Hypomagnesaemia

Severe hypomagnesaemia has been reported in patients treated with PPIs like lansoprazole for at least three months, and in most cases for a year. Serious manifestations of hypomagnesaemia such as fatigue, tetany, delirium, convulsions, dizziness and ventricular arrhythmia can occur but they may begin insidiously and be overlooked. In most affected patients, hypomagnesaemia improved after magnesium replacement and discontinuation of the PPI.

For patients expected to be on prolonged treatment or who take PPIs with digoxin or drugs that may cause hypomagnesaemia (e.g., diuretics), health care professionals should consider measuring magnesium levels before starting PPI treatment and periodically during treatment.

Subacute cutaneous lupus erythematosus (SCLE)

Proton pump inhibitors are associated with very infrequent cases of SCLE. If lesions occur, especially in sun-exposed areas of the skin, and if accompanied by arthralgia, the patient should seek medical help promptly and the health care professional should consider stopping Lansoprazole. SCLE after previous treatment with a proton pump inhibitor may increase the risk of SCLE with other proton pump inhibitors.

Interference with laboratory tests

Increased Chromogranin A (CgA) level may interfere with investigations for neuroendocrine tumours. To avoid this interference, lansoprazole treatment should be stopped for at least 5 days before CgA measurements. If CgA and gastrin levels have not returned to reference range after initial measurement, measurements should be repeated 14 days after cessation of proton pump inhibitor treatment.

This medicine contains sucrose. Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine.

Adverse drug reactions such as dizziness, vertigo, visual disturbances and somnolence may occur. Under these conditions the ability to react may be decreased.

Frequencies are defined as common (>1/100, <1/10); uncommon (>1/1,000, <1/100); rare (>1/10,000, <1/1,000); very rare (<1/10,000), not known (cannot be estimated from the available data).

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

The effects of overdose on lansoprazole in humans are not known (although the acute toxicity is likely to be low) and, consequently, instruction for treatment cannot be given. However, daily doses of up to 180 mg lansoprazole orally and up to 90 mg intravenously have been administered in trials without significant undesirable effects.

In the case of suspected overdose the patient should be monitored. Lansoprazole is not significantly eliminated by haemodialysis. If necessary, gastric emptying, charcoal and symptomatic therapy is recommended.

Pharmacotherapeutic group: Proton pump inhibitors, ATC code: A02BC03

Lansoprazole is a gastric proton pump inhibitor. It inhibits the final stage of gastric acid formation by inhibiting the activity of H⁺/K⁺ ATPase of the parietal cell in the stomach. The inhibition is dose- dependent and reversible, and the effect applies to both basal and stimulated secretion of gastric acid. Lansoprazole is concentrated in the parietal cells and becomes active in their acidic environment, whereupon it reacts with the sulphydryl group of the H⁺/K⁺ ATPase causing inhibition of the enzyme activity.

Effect on gastric acid secretion:

Lansoprazole is a specific inhibitor of the parietal cell proton pump. A single oral dose of lansoprazole inhibits pentagastrin-stimulated gastric acid secretion by about 80%. After repeated daily administration for seven days, about 90% inhibition of gastric acid secretion is achieved. It has a corresponding effect on the basal secretion of gastric acid. A single oral dose of 30 mg reduces basal secretion by about 70%, and the patients' symptoms are consequently relieved starting from the very first dose. After eight days of repeated administration the reduction is about 85%. A rapid relief of symptoms is obtained by one capsule (30 mg) daily, and most patients with duodenal ulcer recover within 2 weeks, patients with gastric ulcer and reflux oesophagitis within 4 weeks. By reducing gastric acidity, lansoprazole creates an environment in which appropriate antibiotics can be effective against H. pylori.

During treatment with antisecretory medicinal products, serum gastrin increases in response to the decreased acid secretion. Also CgA increases due to decreased gastric acidity. The increased CgA level may interfere with investigations for neuroendocrine tumours.

Available published evidence suggests that proton pump inhibitors should be discontinued between 5 days and 2 weeks prior to CgA measurements. This is to allow CgA levels that might be spuriously elevated following PPI treatment to return to reference range.

Lansoprazole is a racemate of two active enantiomers that are biotransformed into the active form in the acidic environment of the parietal cells. As lansoprazole is rapidly inactivated by gastric acid, it is administered orally in enteric-coated form(s) for systemic absorption.

Absorption and distribution

Lansoprazole exhibits high (80-90%) bioavailability with a single dose. Peak plasma levels occurred within 1.5 to 2.0 hours. Intake of food slows the absorption rate of lansoprazole and reduces the bioavailability by about 50%. The plasma protein binding is 97%.

Studies have shown that granules from opened capsules gives equivalent AUC as the intact capsule if the granules are suspended in a small amount of orange juice, apple juice, or tomato juice mixed with a tablespoon of apple or pear puree or sprinkled on a tablespoon of yoghurt, pudding or cottage cheese. Equivalent AUC has also been shown for granules suspended in apply juice administered through a naso-gastric tube.

Metabolism and elimination

Lansoprazole is extensively metabolised by the liver and the metabolites are excreted by both the renal and biliary route. The metabolism of lansoprazole is mainly catalysed by the enzyme CYP2C19. The enzyme CYP3A4 also contributes to the metabolism. The plasma elimination half-life ranges from 1 to 2 hours following single or multiple doses in healthy subjects. Suphone, sulphide and 5-hydroxyl derivatives of lansoprazole have been identified in plasma. These metabolites have very little or no antisecretory activity.

A study with ¹⁴C labelled lansoprazole indicated that approximately one-third of the administered radiation was excreted in the urine and two-third was recovered in the faeces.

Pharmacokinetics in elderly patients

The clearance of lansoprazole is decreased in the elderly, with elimination half-life increased approximately 50% to 100%. Peak plasma levels were not increased in the elderly.

Pharmacokinetics in paediatric patients

The evaluation of the pharmacokinetics in children aged 1-17 years of age showed a similar exposure as compared to adults with doses of 15 mg for those below 30 kg of weight and 30 mg for those above. The investigation of a dose of 17 mg/m² body surface or 1mg/kg body weight also resulted in comparable exposure of lansoprazole in children aged 2-3 months up to one year of age compared to adults.

Higher exposure to lansoprazole in comparison to adults has been seen in infants below the age of 2-3 months with doses of both 1.0 mg/kg or 0.5 mg/kg body weight given as a single dose.

Pharmacokinetics in hepatic insufficiency

The exposure of lansoprazole is doubled in patients with mild impairment and much more increased in patients with moderate and severe hepatic impairment.

CYP2C19 poor metabolisers

CYP2C19 is subject to genetic polymorphism and 2-6% of the population, called poor metabolisers (PMs), are homozygote for a mutant CYP2C19 allele and therefore lacks a functional CYP2C19 enzyme. The exposure of lansoprazole is several-fold higher in PMs than in extensive metabolisers (EMs).

Preclinical data reveal no special hazards for humans on conventional studies of safety pharmacology, repeated dose toxicity, toxicity to reproduction or genotoxicity.

In two rat carcinogenicity studies, lansoprazole produced dose-related gastric ECL cell hyperplasia and ECL cell carcinoids associated with hypergastrinaemia due to inhibition of acid secretion.

Intestinal metaplasia was also observed, as were Leydig cell hyperplasia and benign Leydig cell tumours. After 18 months of treatment retinal atrophy was observed. This was not seen in monkeys, dogs or mice.

In mouse carcinogenicity studies dose-related gastric ECL hyperplasia developed as well as liver tumours and adenoma of rete testis.

The clinical relevance of these findings is unknown.

Gastro-resistant microgranules:

Sugar spheres (sucrose and maize starch)

Sodium laurilsulphate

Meglumine

Mannitol (E421)

Hypromellose

Macrogol 6000

TalcPolysorbate 80

Titanium dioxide (E171)

Eudragit^® L30-D55 (methacrylic acid-ethyl acrylate copolymer, 1:1, dispersion 30%)

Capsule Shells:

Gelatin

Titanium dioxide (E171)

Quinoline yellow (E104)

Purified water

Not applicable.

3 years.

Do not store above 25°C.

Store in the original package in order to protect from moisture.

Non-peelable blister: Aluminium/OPA/PVC sealed with PVC/ Aluminium /PVDC laquer

Peelable blister: Aluminium /OPA/PVC sealed with PETP/ Aluminium /PVC laquer

7, 14, 15, 28, 30, 35, 56, 60 and 98 capsules.

28 and 98 capsule calendar pack.

Not all pack sizes may be marketed.

No special requirements.

Any unused product or waste material should be disposed of in accordance with local requirements.

Generics [UK] Limited t/a Mylan

Potters Bar

Hertfordshire

EN6 1TL

UK

PL 04569/0297

Date of first authorisation: 02/12/2005

Date of1atestrenewa1: 07/04/2009

08/12/2017