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 of lansoprazole orally and up to 90 mg of lansoprazole 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.
Not applicable.
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).
| Common | Uncommon | Rare | Very rare | Not Known | |
| Blood and lymphatic system disorders | leucopenia, thrombocytopenia, eosinophilia | anaemia | pancytopenia , agranulocytosis | ||
| Immune system disorders | anaphylactic shock | ||||
| Metabolism and nutritional disorders | hypomagnesaemia | ||||
| Psychiatric disorders | depression | hallucination, insomnia, confusion | visual hallucinations | ||
| Nervous system disorders | headache, dizziness | paresthesia, vertigo, restlessness, somnolence, tremor | |||
| Eye disorders | visual disturbances. | ||||
| Gastrointestinal disorders | vomiting, nausea, diarrhoea, stomach ache, constipation, flatulence, dry mouth or throat, fundic gland polyps (benign) | pancreatitis, candidiasis of the oesophagus, glossitis, taste disturbances | colitis, stomatitis | ||
| Hepatobiliary disorders | increase in liver enzyme levels | hepatitis, jaundice | |||
| Skin and subcutaneous tissue disorders | urticaria, itching, rash | petechiae, purpura, erythema multiforme, photosensitivity, hair loss, | Stevens-Johnson syndrome, toxic epidermal necrolysis | subacute cutaneous lupus erythematosus | |
| Musculoskeletal and connective tissue disorders | fracture of the hip, wrist or spine , arthralgia, myalgia, | ||||
| Renal and urinary disorders | interstitial nephritis | ||||
| Reproductive system and breast disorders | gynaecomastia | ||||
| General disorders and administration site conditions | fatigue | oedema | angioedema, fever, hyperhidrosis, anorexia, impotence | ||
| Investigations | increase in cholesterol and triglyceride levels, hyponatremia |
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.
Non-clinical data reveal no special hazards for humans based 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 cell hyperplasia developed as well as liver tumours and adenoma of rete testis.
The clinical relevance of these findings is unknown.
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 cells 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 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 30 mg 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 oro-dispersible tablet (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 occur within 1.5 to 2.0 hours. Intake of food slows the absorption rate of lansoprazole and reduces the bioavailabilty by about 50%. The plasma protein binding is 97%.
Studies have shown that oro-dispersible tablets dispersed in a small amount of water and given via syringe directly into the mouth or administered via naso-gastric tube result in equivalent AUC compared to the usual mode of administration.
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.
A study with 14C labelled lansoprazole indicated that approximately one-third of the administered radiation was excreted in the urine and two-thirds 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 1 mg/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 and 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 hepatic 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).
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. 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, Lansoprazol-Teva FasTab 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.
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.
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.
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 Lansoprazol-Teva FasTab. SCLE after previous treatment with a proton pump inhibitor may increase the risk of SCLE with other proton pump inhibitors.
As Lansoprazol-Teva FasTab contains lactose, patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption 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.
No special requirements.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
