COMPOSITION AND EXCIPIENTS
Each capsule of Lansostom 15 contains 15 mg lansoprazole (as Delayed Release Pellets).
Each capsule of Lansostom 30 contains 30 mg lansoprazole (as Delayed Release Pellets).
PHARMACODYNAMIC PROPERTIES
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.
PHARMACOKINETIC PROPERTIES
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 occur 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%.
Biotransformation 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. There is no evidence of accumulation following multiple doses in healthy subjects. Sulphone, sulphide and 5-hydroxyl derivatives of lansoprazole have been identified in plasma. These metabolites have very little or no antisecretory activity.
INDICATIONS
• 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. pyloriassociated 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.
CONTRAINDICATIONS
Hypersensitivity to the active substance or to any of the excipients.
Lansoprazole should not be administered with atazanavir.
WARNINGS AND PRECAUTIONS
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 maybe 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 the treatment.
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.
DRUGS INTERACTIONS
Medicinal products with pH dependent absorption:
Lansoprazole may interfere with the absorption of drugs where gastric pH is critical to bioavailability.
Atazanavir:
A study has shown that co-administration of lansoprazole (60 mg once daily) with atazanavir 400 mg to healthy volunteers resulted in a substantial reduction in atazanavir exposure (approximately 90% decrease in AUC and C). Lansoprazole should not be co-administered with atazanavir .
Ketoconazole and itraconazole:
The absorption of ketoconazole and itraconazole from the gastrointestinal tract is enhanced by the presence of gastric acid. Administration of lansoprazole may result in sub-therapeutic concentrations of ketoconazole and itraconazole and the combination should be avoided.
Digoxin:
Co-administration of lansoprazole and digoxin may lead to increased digoxin plasma levels. The plasma levels of digoxin should therefore be monitored and the dose of digoxin adjusted if necessary when initiating and ending lansoprazole treatment.
Medicinal products metabolised by P450 enzymes
Lansoprazole may increase plasma concentrations of drugs metabolised by CYP3A4. Caution is advised when combining lansoprazole with drugs which are metabolised by this enzyme and have narrow therapeutic window.
Theophylline:
Lansoprazole reduces the plasma concentration of theophylline, which may decrease the expected clinical effect at the dose. Caution is advised when combining the two drugs.
Tacrolimus:
Co-administration of lansoprazole increases the plasma concentrations of tacrolimus (a CYP3A and P- gp substrate). Lansoprazole exposure increased the mean exposure of tacrolimus by up to 81%. Monitoring of tacrolimus plasma concentrations is advised when concomitant treatment with lansoprazole is initiated or ended.
Medicinal products transported by P-glycoprotein
Lansoprazole has been observed to inhibit the transport protein, P-glycoprotein (P-gp) in vitro. The clinical relevance of this is unknown.
Effects of other drugs on lansoprazole
Fluvoxamine:
A dose reduction may be considered when combining lansoprazole with the CYP2C19 inhibitor fluvoxamine. A study shows that the plasma concentrations of lansoprazole increase up to 4-fold.
Drugs which induce CYP2C19 and CYP3A4
Enzyme inducers affecting CYP2C19 and CYP3A4 such as rifampicin, and St John’s wort (Hypericum perforatum) can markedly reduce the plasma concentrations of lansoprazole.
Sucralfate/Antacids:
Sucralfate/Antacids may decrease the bioavailability of lansoprazole. Therefore lansoprazole should be taken at least 1 hour after taking these drugs.
No clinically significant interactions of lansoprazole with nonsteroidal anti-inflammatory drugs have been demonstrated, although no formal interactions studies have been performed.
Pregnancy:
For lansoprazole no clinical data on exposed pregnancies are available. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/foetal development, parturition or postnatal development. Therefore, the use of lansoprazole during pregnancy is not recommended.
Lactation:
It is not known whether lansoprazole is secreted in human breast milk. Animal studies have shown excretion of lansoprazole in milk. A decision on whether to continue/discontinue breast-feeding or to continue/discontinue therapy with lansoprazole should be made taking into account the benefit of breastfeeding to the child and the benefit of lansoprazole therapy to the woman.
Effects on ability to drive and use machines :
Adverse drug reactions such as dizziness, vertigo, visual disturbances and somnolence may occur. Under these conditions the ability to react may be decreased .
UNDESIRABLE EFFECTS
Common: Nausea, diarrhoea, stomach ache, constipation, vomiting, flatulence, dry mouth or throat, fundic gland polyps (benign), increase in liver enzyme levels, Urticaria, itching, rash, Fatigue.
Uncommon: Thrombocytopenia, eosinophilia, leucopenia, Depression, Arthralgia, myalgia, fracture of the hip, wrist or spine, Oedema.
POSOLOGY AND METHOD OF ADMINISTRATION
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 (see section 5.2). 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:
The use of lansoprazole is not recommended in children as clinical data are limited.
OVERDOSE
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.
STORAGE CONDITIONS
Store at temperature between 15° to 30°.
PACKAGING
Lansostom (15 – 30) mg is supplied as blister strips (Aluminum – Clear P.V.D.C),each strip contains 10 capsules and each pack contains 2 or 3 strips with enclosed leaflet ( 20 or 30 capsules per pack).