Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2019 Publisher: Actavis Group PTC ehf, Reykjavikurvegur 76-78, 220 Hafnarfjordur, Iceland
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
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, like all proton pump inhibitors (PPIs), might increase the counts of bacteria normally present in the gastrointestinal tract. This may increase the risk of gastrointestinal infections caused by bacteria such as Salmonella, Campylobacter and, especially in hospitalized patients, Clostridium difficile.
Co-administration of lansoprazole is not recommended with HIV protease inhibitors for which absorption is dependent on acidic intragastric pH, such as atazanavir and nelfinavir, due to significant reduction in their bioavailability (see section 4.5). If co-administration of lansoprazole with HIV protease inhibitors is unavoidable, close clinical monitoring is recommended.
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 medicinal products that may cause hypomagnesaemia (e.g., diuretics), health care professionals should consider measuring magnesium levels before starting PPI treatment and periodically during treatment.
Increased Chromogranin A (CgA) level may interfere with investigations for neuroendocrine tumours. To avoid this interference, Lansoprazole capsules treatment should be stopped for at least 5 days before CgA measurements (see section 5.1). 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.
Daily treatment with any acid-suppressing medications over a prolonged period of time (several years) may lead to malabsorption of cyanocobalamin (vitamin B12) caused by hypo- or achlorhydria. Cyanocobalamin deficiency should be considered in patients with Zollinger-Ellison syndrome and other pathological hypersecretory conditions requiring long- term treatment, individuals with reduced body stores or risk factors for reduced vitamin B12 absorption (such as the elderly) on long-term therapy or if relevant clinical symptoms are observed.
Lansoprazole should be used with caution in patients with moderate and severe hepatic dysfunction (see sections 4.2 and 5.2).
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.
With the exception of patients treated for the eradication of H. pylori infection, if diarrhoea persists, administration of lansoprazole should be discontinued, due to the possibility of microscopic colitis with thickening of the collagen bundle or infiltration of inflammatory cells noted in the large intestine submucosa. In majority of cases, symptoms of microscopic colitis resolve on discontinuation of lansoprazole.
The treatment for the prevention of peptic ulceration of patients 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 the 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.
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 capsules. SCLE after previous treatment with a proton pump inhibitor may increase the risk of SCLE with other proton pump inhibitors (see section 4.8).
As lansoprazole contains sucrose, patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine.
This medicine contains less than 1 mmol sodium (23 mg) per capsule, that is to say essentially ‘sodium-free’.
Lansoprazole may interfere with the absorption of other medicinal products where gastric pH is an important determinant of oral bioavailability.
Co-administration of lansoprazole is not recommended with HIV protease inhibitors for which absorption is dependent on acidic intragastric pH, such as atazanavir and nelfinavir, due to significant reduction in their bioavailability (see section 4.4).
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 Cmax).
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.
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.
Lansoprazole may increase plasma concentrations of medicinal products that are metabolised by CYP3A4. Caution is advised when combining lansoprazole with medicinal products which are metabolised by this enzyme and have a narrow therapeutic window.
There have been reports of increased INR and prothrombin time in patients receiving PPIs and warfarin concomitantly. Increases in INR and prothrombin time may lead to abnormal bleeding and even death. Patients treated with lansoprazole and warfarin concomitantly may need to be monitored for increase in INR and prothrombin time.
Lansoprazole reduces the plasma concentration of theophylline, which may decrease the expected clinical effect at the dose. Patient monitoring should be taken in co-administration of lansoprazole with theophylline.
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.
Lansoprazole has been observed to inhibit the transport protein, P-glycoprotein (P-gp) in vitro. The clinical relevance of this is unknown.
A dose reduction may be considered when combining lansoprazole with the CYP2C19 inhibitor fluvoxamine. The plasma concentrations of lansoprazole increase up to 4-fold.
Enzyme inducers affecting CYP2C19 and CYP3A4 such as rifampicin, and St John´s wort (Hypericum perforatum) can markedly reduce the plasma concentrations of lansoprazole.
Concomitant use with high-dose methotrexate may elevate and prolong serum levels of methotrexate and/or its metabolite, possibly leading to methotrexate toxicities.
Sucralfate/Antacids may decrease the bioavailability of lansoprazole. Therefore lansoprazole should be taken at least 1 hour after taking these medicinal products.
No clinically significant interactions of lansoprazole with nonsteroidal anti-inflammatory medicinal products have been demonstrated, although no formal interactions studies have been performed.
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.
It is not known whether lansoprazole is excreted 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 for the child and the benefit of lansoprazole therapy for the woman.
No human data on the effect of lansoprazole on fertility are available. Reproductive studies in pregnant rats and rabbits revealed no lansoprazole-related impairment of fertility.
Adverse drug reactions such as dizziness, vertigo, visual disturbances and somnolence may occur (see section 4.8). Under these conditions the ability to react may be decreased.
Frequencies are defined as common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000), not known (cannot be estimated from the available data).
Uncommon: leucopenia, thrombocyto-penia, eosinophilia
Rare: anaemia
Very rare: pancytopenia, agranulocytosis
Very rare: anaphylactic shock
Not known: hypomagnesaemia (see section 4.4)
Uncommon: depression
Rare: hallucination, insomnia, confusion
Not known: visual hallucinations
Common: headache, dizziness
Rare: paresthesia, vertigo, restlessness, somnolence, tremor
Rare: visual disturbances.
Common: vomiting nausea, diarrhoea, stomach ache, constipation, flatulence, dry mouth or throat, fundic gland polyps (benign)
Rare: pancreatitis, candidiasis of the oesophagus, glossitis, taste disturbances
Very rare: colitis, stomatitis
Common: increase in liver enzyme levels
Rare: hepatitis, jaundice
Common: urticaria, itching, rash
Rare: petechiae, purpura, erythema multiforme, photosensitivity, hair loss
Very rare: Stevens-Johnson syndrome, toxic epidermal necrolysis
Not known: subacute cutaneous lupus erythematosus (see section 4.4)
Uncommon: fracture of the hip, wrist or spine (see section 4.4), arthralgia, myalgia
Rare: interstitial nephritis
Rare: gynaecomastia
Common: fatigue
Uncommon: oedema
Rare: angioedema, fever, hyperhidrosis, anorexia, impotence
Very rare: increase in cholesterol and triglyceride levels, hyponatremia
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; website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.
Not applicable.
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