LANSOPRAZOLE CRISTERS 30 mg Gastro-resistant Cap Bottle/28

Each capsule contains white or almost white spherical gastro-resistant microgranules; the cap and body of the capsule are white.

Lansoprazole................................................................................................................................................. 30 mg

For a gastro-resistant capsule.

Excipient with known effect: each capsule contains 200,949 mg of sucrose.

Excipients:

LANSOPRAZOLE CRISTERS is indicated in adults.

• Treatment of duodenal ulcer and gastric ulcer.

• Treatment of reflux oesophagitis.

• Prevention of reflux oesophagitis.

• Eradication of Helicobacter pylori (H. pylori) with concomitant administration of appropriate antibiotic therapy for the treatment of ulcers associated with H. pylori.

• Treatment of duodenal ulcer and benign gastric ulcer, induced by NSAIDs in patients requiring continuous NSAID treatment.

• Prevention of NSAID-induced duodenal ulcer and gastric ulcer in patients at risk (see section Dosage and administration) requiring continuous NSAID treatment.

• Symptomatic gastro-oesophageal reflux.

• Zollinger-Ellison syndrome.

Dosage

Treatment of duodenal ulcer

The recommended dose is 30 mg once daily for 2 weeks. In patients whose healing is not complete after this period, treatment will be continued, at the same dose, for an additional 2 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 whose healing is not complete after this period, treatment may be continued, at the same dose, for an additional 4 weeks.

Reflux esophagitis

The recommended dose is 30 mg once a day for 4 weeks. In patients whose healing is not complete after this period, treatment may be continued, at the same dose, for an additional 4 weeks.

Prevention of reflux esophagitis

15 mg once a day. The dose may be increased up to 30 mg per day if necessary.

 

Eradication of Helicobacter pylori

The choice of appropriate combination therapy should be made according to official local recommendations concerning bacterial resistance, the duration of treatment (usually 7 days, but sometimes up to 14 days), and the appropriate use of antibacterial agents.

The recommended dosage is 30 mg of LANSOPRAZOLE CRISTERS twice daily for 7 days in combination with one of the following combinations:

• 250-500 mg of clarithromycin twice daily + 1 g of amoxicillin twice daily,

• 250 mg of clarithromycin twice daily + 400-500 mg of metronidazole twice daily.

Eradication rates of H. pylori Up to 90 % are obtained when clarithromycin is combined with LANSOPRAZOLE CRISTERS and amoxicillin or metronidazole.

Six months after successful eradication therapy, the risk of reinfection is low and relapse is therefore unlikely.

A regimen comprising 30 mg of lansoprazole twice a day, 1 g of amoxicillin twice a day and 400-500 mg of metronidazole twice a day has also been studied. Using this combination, lower eradication rates were observed than for regimens involving clarithromycin. They may be suitable for patients who cannot take clarithromycin as part of eradication therapy, where local rates of metronidazole resistance are low.

Treatment of NSAID-induced duodenal ulcer and benign gastric ulcer in patients requiring continuous NSAID therapy

30 mg once daily for four weeks. In patients whose ulcer healing is not complete, treatment may be continued for an additional four weeks. In patients at risk or with difficult-to-heal ulcers, a longer treatment duration and/or a higher dose may be used.

Prevention of NSAID-induced duodenal ulcer and gastric ulcer in patients at risk (aged over 65 years or with a history of gastric or duodenal ulcer) requiring prolonged NSAID therapy

15 mg once a day. In case of treatment failure, the dose of 30 mg once a day should be used.

Symptomatic gastro-esophageal reflux

The recommended dose is 15 mg or 30 mg per day. Symptom relief is achieved rapidly. Individual dose adjustment should be considered. If symptoms are not relieved within 4 weeks with a daily dose of 30 mg, further investigations are recommended.

Zollinger-Ellison syndrome

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

Special populations

Renal impairment

No dose adjustment is necessary in patients with renal impairment.

Hepatic impairment

Patients with severe or moderate liver disease should be kept under regular monitoring and a 50 % reduction of the daily dose is recommended (see sections Warnings and precautions and Pharmacokinetics).

Elderly patients

Due to the reduced clearance of lansoprazole in elderly subjects, individual dose adjustment may be necessary. A daily dose of 30 mg should not be exceeded in elderly subjects, unless there are relevant clinical indications.

 

Paediatric population

In the absence of sufficient clinical data, the use of LANSOPRAZOLE CRISTERS is not recommended in children (see section Pharmacokinetics) and the relevance to humans of the results of studies in juvenile animals is unknown (see section Preclinical safety).

Treatment of infants under 1 year of age should be avoided, as the available clinical data have not demonstrated a beneficial effect of lansoprazole in the treatment of gastro-oesophageal reflux.

Method of administration

For optimal effect, LANSOPRAZOLE CRISTERS must be taken once daily in the morning, except in the case of H. pylori eradication, for which the treatment must be taken twice daily, once in the morning and once in the evening. LANSOPRAZOLE CRISTERS must be taken at least 30 minutes before meals (see section Pharmacokinetics). The capsules must be swallowed whole with a liquid.

For patients with swallowing difficulties, studies and clinical practice suggest that the capsules can be opened and the microgranules mixed with a small amount of water, apple juice or tomato juice, or sprinkled onto a small amount of non-solid food (example: yogurt, apple compote) to facilitate administration. The capsules can also be opened and the microgranules mixed with 40 ml of apple juice for administration via nasogastric tube (see section Pharmacokinetics). After preparation of the suspension or mixture, the medicinal product must be administered immediately.

Hypersensitivity to the active substance or to any of the excipients listed in section Composition.

Malignant gastric tumour

As with all other anti-ulcer treatments, the possibility of a malignant gastric tumour should be excluded when treating gastric ulcer with lansoprazole, as lansoprazole may mask symptoms and delay diagnosis.

Concomitant administration of HIV protease inhibitors

The combination of lansoprazole with HIV protease inhibitors with pH-dependent absorption, such as atazanavir and nelfinavir, is not recommended due to a very marked reduction in their bioavailability (see section Interactions).

Hypomagnesaemia

Cases of severe hypomagnesaemia have rarely been reported in patients treated with proton pump inhibitors (PPIs) such as lansoprazole for at least three months and, in most cases, for one year. Hypomagnesaemia may manifest with serious clinical signs such as fatigue, tetany, delirium, convulsions, dizziness, ventricular arrhythmia, but it may begin insidiously and go unnoticed. Hypomagnesaemia may lead to hypocalcaemia and / or hypokalaemia (see section Adverse effects). In most patients, hypomagnesaemia (and hypomagnesaemia associated with hypocalcaemia and / or hypokalaemia) improved after magnesium supplementation and discontinuation of the PPI.

In patients requiring prolonged treatment, or when PPIs are combined with digoxin or with medicines that may induce hypomagnesaemia (for example diuretics), healthcare professionals should consider measuring blood magnesium levels before starting PPI treatment and periodically thereafter during treatment.

Influence on the absorption of vitamin B12

Lansoprazole, like any gastric antisecretory agent, may decrease the absorption of vitamin B12 (cyanocobalamin) due to hypo- or achlorhydria. This should be taken into account in patients with reduced stores or with risk factors for decreased absorption of vitamin B12 during long-term treatment, or if clinical symptoms are observed.

Hepatic impairment

Lansoprazole should be used with caution in patients with severe or moderate hepatic impairment (see sections Dosage and administration and Pharmacokinetics).

Bacterial gastrointestinal infections

Lansoprazole, like other PPI treatments, may be associated with an increased risk of infection due to Clostridium difficile.

A decrease in gastric acidity due to lansoprazole may increase the levels of bacteria normally present in the gastrointestinal tract. Treatment with lansoprazole may lead to a slight increase in the risk of gastrointestinal infections, including those due to Salmonella and Campylobacter.

Eradication of Helicobacter pylori

In patients with gastroduodenal ulcers, the possibility of infection by H. pylori as an aetiological factor should be considered.

If lansoprazole is used in combination with antibiotics for eradication treatment of H. pylori, then the conditions of use of those antibiotics must also be followed.

Long-term treatment

Due to limited safety data in patients receiving maintenance treatment for more than one year, regular monitoring of treatment and a thorough reassessment of the benefit/risk ratio should be regularly performed in these patients.

Colitis

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

Concomitant administration of NSAIDs

The treatment for prevention of peptic ulceration in patients requiring continuous NSAID treatment must be limited to high-risk patients (for example: history of gastrointestinal haemorrhage, perforation or ulcer, advanced age, concomitant medication known to increase the likelihood of upper gastrointestinal adverse events [for example: corticosteroids or anticoagulants], presence of a serious comorbidity, or prolonged use of NSAIDs at the maximum recommended doses).

Risk of bone fracture

Proton pump inhibitors, particularly when used at high doses and over a prolonged period (> 1 year), may moderately increase the risk of hip, wrist and vertebral fracture, mainly in elderly subjects or in the presence of other identified risk factors. Observational studies suggest that proton pump inhibitors may increase the overall risk of fracture by 10 to 40 %. This increase may be partly due to other risk factors. Patients at risk of osteoporosis should be managed in accordance with current guidelines and receive adequate intake of vitamin D and calcium.

Severe cutaneous reactions

Severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (Lyell's syndrome), and drug reaction with eosinophilia and systemic symptoms (DRESS), which may be life-threatening or fatal, have been reported in association with lansoprazole at an unknown frequency (see section Adverse effects).

At the time of prescription, patients should be informed of these signs and symptoms and the occurrence of these skin reactions should be closely monitored. If signs and symptoms suggestive of these reactions appear, lansoprazole should be discontinued immediately and an alternative treatment should be considered.

Subacute cutaneous lupus erythematosus (SCLE)

Proton pump inhibitors are associated with very occasional cases of SCLE. If lesions develop, particularly on sun-exposed skin areas, and if they are accompanied by arthralgia, the patient should consult a physician promptly and the healthcare professional should consider discontinuing LANSOPRAZOLE CRISTERS. The occurrence of SCLE after 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) levels may interfere with tests performed for the investigation of neuroendocrine tumours. To avoid this interference, treatment with LANSOPRAZOLE CRISTERS should be interrupted at least 5 days before measuring CgA levels (see section Pharmacodynamics). If CgA and gastrin levels have not normalised after the initial measurement, measurements should be repeated 14 days after discontinuation of the proton pump inhibitor treatment.

Impairment of renal function

Acute tubulo-interstitial nephritis (TIN) has been observed in patients taking lansoprazole and may occur at any time during lansoprazole treatment (see section Adverse effects). Acute tubulointerstitial nephritis may progress to renal failure. In case of suspected TIN, lansoprazole should be discontinued and appropriate treatment promptly initiated.

Excipient with known effect

This medicine contains sucrose. Patients with fructose intolerance, glucose-galactose malabsorption syndrome or sucrase/isomaltase deficiency (rare hereditary diseases) must not take this medicine.

Effects of lansoprazole on other medicines

Medicines with pH-dependent absorption

Lansoprazole may interfere with the absorption of medicines for which bioavailability depends on gastric pH.

+ HIV protease inhibitors

Combination not recommended with HIV protease inhibitors whose absorption depends on gastric pH, such as atazanavir and nelfinavir, due to a very marked decrease in plasma concentrations of the protease inhibitor (see section Warnings and precautions).

A study showed that concomitant administration of lansoprazole (60 mg once daily) and atazanavir 400 mg to healthy volunteers markedly reduced exposure to atazanavir (decrease of approximately 90 % in AUC (area under the curve) and Cmax (maximum concentration).

+ Ketoconazole, itraconazole and posaconazole

Absorption of ketoconazole, itraconazole and posaconazole from the gastrointestinal tract is increased in the presence of gastric acid. Administration of lansoprazole may result in concentrations of ketoconazole, itraconazole and posaconazole below the therapeutic threshold, and the combination should be avoided.

+ Digoxin

The combination of lansoprazole and digoxin may lead to an increase in plasma concentration of digoxin. Plasma concentrations of digoxin should therefore be monitored and the digoxin dose adjusted if necessary at the start and end of lansoprazole treatment.

Medicines metabolised by cytochrome P450 enzymes

Lansoprazole may increase plasma concentrations of medicines metabolised by CYP3A4. Caution is recommended when combining lansoprazole with medicines metabolised by this enzyme that have a narrow therapeutic margin.

+ Theophylline

Lansoprazole reduces the plasma concentration of theophylline, which may decrease the expected clinical effect. Patient monitoring should be considered when these two medicines are combined.

+ Tacrolimus

Concomitant administration of lansoprazole increases plasma concentrations of tacrolimus (a substrate of CYP3A and P-gp). Taking lansoprazole increases the mean tacrolimus level by up to 81%. Monitoring of plasma tacrolimus concentrations is recommended at the start or end of lansoprazole treatment.

Measurement of tacrolimus blood concentrations, monitoring of renal function and dose adjustment during the combination and after its discontinuation.

Medicines transported by P-glycoprotein

Inhibition of P-glycoprotein (P-gp) by lansoprazole has been observed in vitro. Its clinical relevance is unknown.

Effects of other medicinal products on lansoprazole

Medicinal products inhibiting CYP2C19

+ Fluvoxamine

A dose reduction may be considered when lansoprazole is combined with fluvoxamine, an inhibitor of CYP2C19. Plasma concentrations of lansoprazole are increased up to 4 times normal.

Medicinal products inducing CYP2C19 and CYP3A4

Enzyme inducers affecting CYP2C19 and CYP3A4, such as rifampicin and St John's wort (Hypericum perforatum) may substantially reduce plasma concentrations of lansoprazole. Risk of reduced efficacy of the antisecretory treatment due to decreased metabolism by St John's wort must be taken into account.

Other

+ Sucralfate/Antacids

Sucralfate and antacids may reduce the bioavailability of lansoprazole. Therefore, lansoprazole should be taken at least 1 hour after these medicinal products.

No clinically significant interaction between lansoprazole and non-steroidal anti-inflammatory drugs has been demonstrated, although no formal interaction study has been performed.

Other interactions

Combinations not recommended

+ Methotrexate

Risk of increased methotrexate toxicity due to decreased elimination.

Combination not recommended with methotrexate at doses > 20 mg / week. Combination to be taken into account for lower doses.

Associations to be taken into account

+ Cyanocobalamin

Risk of cyanocobalamin deficiency after prolonged treatment (several years), as the reduction in gastric acidity caused by these medicines may decrease digestive absorption of vitamin B12.

+ Tyrosine kinase inhibitors

Risk of decreased bioavailability of the tyrosine kinase inhibitor, due to its pH-dependent absorption.

+ Mycophenolate mofetil

Decrease in mycophenolic acid concentrations by approximately one third, with potential risk of reduced efficacy.

+ Ulipristal

Risk of decreased effect of ulipristal, through decreased absorption.

+ Warfarin

Concomitant administration of lansoprazole 60 mg and warfarin did not modify the pharmacokinetics of warfarin or the INR. However, there have been cases of increased INR and prothrombin time when PPIs were combined with warfarin. Increases in INR and prothrombin time may lead to abnormal bleeding and possibly death. Monitoring of INR and prothrombin time is recommended in patients treated with lansoprazole and warfarin.

Pregnancy

There are limited data on the use of lansoprazole in pregnant women. Animal studies have not shown direct or indirect harmful effects on pregnancy, embryonic/foetal development, delivery or post-natal development.

As a precaution, it is preferable to avoid the use of lansoprazole during pregnancy.

Breast-feeding

It is not known whether lansoprazole is excreted in human milk. Studies performed in animals have shown excretion of lansoprazole in milk. A decision must be made whether to discontinue breastfeeding or to discontinue lansoprazole therapy, taking into account the benefit of breastfeeding for the child and the benefit of therapy for the woman.

Fertility

There are no data in humans on the effect of lansoprazole on fertility. Reproduction studies in pregnant female rats and rabbits did not reveal any effect of lansoprazole on fertility, nor any teratogenic or foetotoxic effect, nor any effect on nursing infants.

Undesirable effects such as dizziness, vertigo, visual disturbances and somnolence may occur (see section Adverse effects). In these circumstances, the ability to react may be reduced.

Tabulated list of undesirable effects.

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); frequency not known (cannot be estimated from the available data).

For all undesirable effects reported after marketing, it is not possible to apply any frequency of undesirable effects, so they are mentioned with a frequency of 'not known'. Within each frequency group, undesirable effects are presented in order of decreasing seriousness.

	Common	Uncommon	Rare	Very rare	Not known
Blood and lymphatic system disorders		Thrombocytopenia*, eosinophilia, leucopenia*	Anaemia	Agranulocytosis*, pancytopenia*
Immune system disorders				Anaphylactic shock*
Metabolism and nutrition disorders					Hyponatraemia*, Hypomagnesaemia*, Hypocalcaemia*ϯ and Hypokalaemia*ϯ
Psychiatric disorders		Depression	Insomnia, hallucination, confusion		Visual hallucinations
Nervous system disorders	Headache, dizzy sensation		Restlessness, vertigo, paresthesia, somnolence, tremors
Eye disorders			Visual disorders
Gastrointestinal disorders	Nausea, diarrhoea, abdominal pain, constipation, vomiting, flatulence, dryness of the mouth or throat, fundic gland polyps (benign)		Glossitis, oesophageal candidiasis, pancreatitis, taste disturbances	Colitis*, stomatitis
Hepatobiliary disorders	Increase in liver enzyme levels		Hepatitis, jaundice
Skin and subcutaneous tissue disorders	Urticaria, itching, rash		Petechiae, purpura, hair loss, erythema multiforme, photosensitivity	Stevens-Johnson syndrome*, toxic epidermal necrolysis (Lyell's syndrome)*	Subacute cutaneous lupus erythematosus* (see section Warnings and precautions), Drug reaction with eosinophilia and systemic symptoms (DRESS syndrome) (see section Warnings and precautions)
Musculoskeletal and connective tissue disorders		Arthralgia, myalgia, fracture of the hip, wrist or vertebrae (see section Warnings and precautions)
Renal and urinary disorders			Tubulo-interstitial nephritis (with possible progression to renal failure)
Disorders of the reproductive system and breast			Gynaecomastia
General disorders and administration site conditions	Fatigue	Oedema	Fever, hyperhidrosis, angioedema, anorexia, impotence
Investigations				Increased cholesterol and triglyceride levels, hyponatraemia

* adverse effects observed after the approval of dexlansoprazole (these effects being reported voluntarily by a population of uncertain size, their frequency cannot be estimated on the basis of available data).

ϯ Hypocalcaemia and/or hypokalaemia may be linked to the occurrence of hypomagnesaemia (see section Warnings and precautions)

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 reaction via the national reporting system: National Agency for the Safety of Medicines and Health Products (ANSM) and the network of Regional Centres of Pharmacovigilance - Website: https://signalement.social-sante.gouv.fr/.

The effects of an overdose of lansoprazole in humans are not known (although acute toxicity is likely to be low), and therefore no treatment recommendations can be specified. However, daily doses of up to 180 mg of lansoprazole orally and up to 90 mg of lansoprazole intravenously have been administered during clinical trials without causing significant adverse effects.

Please refer to section Adverse effects regarding possible symptoms of an overdose of lansoprazole.

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

Pharmacotherapeutic class: 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 the H+/K+ ATPase proton pump at the parietal cells of the stomach. The inhibition is reversible and dose-dependent. Its effects are exerted on both basal and stimulated gastric acid secretion. Lansoprazole concentrates in the parietal cells, becomes active in their acidic environment and reacts with the sulfhydryl group of the H+/K+ ATPase proton pump, resulting in inhibition of the enzyme's 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 approximately 80%.

After repeated daily administration over a period of seven days, approximately 90% of gastric secretion is inhibited. It has a similar effect on basal gastric acid secretion. A single oral administration of 30 mg reduces basal secretion by approximately 70%; patients' symptoms are therefore improved from the first dose. After 8 days of repeated administration, the reduction is approximately 85%. Rapid symptom relief is obtained with one capsule (30 mg) per day, and most patients with duodenal ulcer heal within 2 weeks, and patients with gastric ulcer or 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 concentration increases in response to decreased acid secretion. Similarly, CgA levels increase due to decreased gastric acidity. The increase in CgA levels may interfere with tests performed to investigate neuroendocrine tumours.

According to published data, intake of proton pump inhibitors should be interrupted between 5 days and 2 weeks before measuring CgA levels. The aim is to allow CgA levels, which would have been artificially increased by PPI intake, to return to normal.

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 acidity, it is administered orally in gastro-resistant form for systemic absorption.

Absorption and distribution

The single-dose bioavailability of lansoprazole is high (80-90%). Maximum plasma concentrations are reached in 1,5 to 2,0 hours. Food intake slows the rate of absorption of lansoprazole and reduces its bioavailability by about 50%. Plasma protein binding is 97%.

Studies have shown that the microgranules obtained from opening a capsule give an area under the curve (AUC) equivalent to the intact capsule if the microgranules are mixed in a small amount of orange juice, apple juice, or tomato juice, or mixed with a tablespoon of apple or pear sauce, or sprinkled on a tablespoon of yoghurt, dessert cream or fresh cheese. An equivalent AUC was also found for microgranules mixed with apple juice administered via nasogastric tube.

Biotransformation and elimination

Lansoprazole is mainly metabolised by the liver and the metabolites are excreted via the renal and biliary routes. Metabolism of lansoprazole is mainly catalysed by the enzyme CYP2C19. The enzyme CYP3A4 also contributes to its metabolism. The plasma elimination half-life of lansoprazole is between 1,0 and 2,0 hours depending on single or multiple doses administered to healthy subjects. There is no evidence of accumulation after multiple doses in healthy subjects. The sulfone, sulfide and 5-hydroxy derivatives of lansoprazole have been identified in plasma. These metabolites have weak or no antisecretory activity.

A study with lansoprazole labelled with 14C indicated that about one third of the administered amount was excreted in urine and two thirds in faeces.

Special populations

Elderly patients

The clearance of lansoprazole is reduced in elderly subjects, with an elimination half-life increased by approximately 50% to 100%. Peak plasma concentrations are not increased in elderly people.

Paediatric population

Evaluation of pharmacokinetics in children aged 1 to 17 years showed exposure similar to that of adults with doses of 15 mg for those weighing less than 30 kg and 30 mg for those above. Study of a dose of 17 mg/m2 body surface area or 1 mg/kg body weight showed comparable exposure to lansoprazole in children aged 2-3 months to one year compared with adults.

Higher exposure to lansoprazole compared with adults has been reported in children under 2-3 months with single doses of 1,0 mg/kg and 0,5 mg/kg body weight.

Hepatic impairment

Exposure to lansoprazole is doubled in patients with mild hepatic impairment and even higher in patients with moderate to severe hepatic impairment.

Slow metabolisers of CYP2C19

CYP2C19 is subject to genetic polymorphism, and 2 to 6% of the population, called slow metabolisers (SM), are homozygous for the allelic mutation of CYP2C19 and therefore have a deficiency of functional CYP2C19 enzyme. Exposure to lansoprazole is increased several-fold in SMs compared with rapid metabolisers (RM).

Preclinical data from conventional safety pharmacology, repeated-dose toxicology, reproductive toxicity or genotoxicity studies did not reveal any particular risk for humans.

In two carcinogenicity studies conducted in rats, lansoprazole caused dose-related gastric enterochromaffin-like (ECL) cell hyperplasia and ECL cell carcinoids associated with hypergastrinaemia in relation to inhibition of acid secretion. Intestinal metaplasia was also observed, as well as 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 mice, during carcinogenicity studies, dose-related gastric enterochromaffin-like (ECL) cell hyperplasia, hepatic tumours and adenomas of the rete testis.

The clinical relevance of this finding is not known.

Studies in juvenile animals

Studies in juvenile rats (a 8-week study, a 6-week toxicokinetic dose-titration study, a developmental sensitivity study) covering the paediatric population aged under 12 years showed an increased incidence of heart valve thickening. The findings were reversible, or tended towards reversibility, after a drug-free recovery period of 4 weeks. Juvenile rats aged under 21 days (an age equivalent to approximately 2 years in humans) were more susceptible to developing heart valve thickening. The safety margin relative to the exposure to lansoprazole expected in humans is of the order of 3 to 6 times the exposure in the juvenile animal studies, based on AUC at the no observed effect level (NOEL) (a 8-week study, a 6-week toxicokinetic dose-titration study) or lowest observed effect level (LOEL) (developmental sensitivity study). The relevance of these findings for paediatric patients aged under 12 years is unknown.

 

3 years.

To be stored at a temperature not exceeding 30°C.

Store the bottle tightly closed, protected from moisture.

Store the blister packs in the original outer packaging, protected from moisture.

No special requirements.

List II

Marketing authorisation (AMM)

CIP 3400941788413 (Fl/14). CIP 3400941788642 (Fl/28).

Price:

2,23 euros (Fl/14). 4,10 euros (Fl/28).

Social security reimbursement at 65% (Fl/14, Fl/28) in the indications:

• Indication(s) listed in the marketing authorisation at the date of publication of this order (Fl/14, Fl/28)

Collection.