Lansoprazole 30 mg gastro-resistant capsules. (Arrow)
- 1. Name of the medicinal product
- 2. Qualitative and quantitative composition
- 3. Pharmaceutical form
- 4. Clinical particulars
- 4.1 Therapeutic indications
- 4.2 Posology and method of administration
- 4.3 Contraindications
- 4.4 Special warnings and precautions for use
- 4.5 Interaction with other medicinal products and other forms of interaction
- 4.6 Pregnancy and lactation
- 4.7 Effects on ability to drive and use machines
- 4.8 Undesirable effects
- 4.9 Overdose
- 5. Pharmacological properties
- 5.1 Pharmacodynamic properties
- 5.2 Pharmacokinetic properties
- 5.3 Preclinical safety data
- 6. Pharmaceutical particulars
- 6.1 List of excipients
- 6.2 Incompatibilities
- 6.3 Shelf life
- 6.4 Special precautions for storage
- 6.5 Nature and contents of container
- 6.6 Special precautions for disposal and other handling
- 7. Marketing authorisation holder
- 8. Marketing authorisation number(s)
- 9. Date of first authorisation/renewal of the authorisation
- 10. Date of revision of the text
- Company information
- More information about this medicine
Treatment of duodenal ulcer:The recommended dose is 30 mg once daily for 2 weeks. In patients not fully healed within this time, the medicinal product should be 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 medicinal product should be continued at the same dose for another 4 weeks.
Treatment of reflux oesophagitis:The recommended dose of lansoprazole 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 lansoprazol 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 dailyH. pylori eradication rates of up to 90%, are obtained when clarithromycin is combined with lansoprazol and amoxicillin or metronidazole.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 of 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 or with ulcers that are difficult to heal, a longer course of treatment and/or a higher dose should be considered. Prophylaxis of 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 to change the dose 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 (see section 4.4 and 5.2).
Elderly:Due to reduced clearance of Lansoprazole in the elderly an adjustment of the 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 clinical indications.
Children:The use of Lansoprazole is not recommended in children as clinical data are limited. Treatment of small children below one year of age should be avoided as available data have not shown beneficial effects in the treatment of gastro-oesophageal reflux disease.
HypomagnesaemiaSevere 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. As Lansoprazole contains sucrose, patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine.
The effects of lansoprazole on other drugs
Medicinal products with pH dependent absorptionLansoprazole 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 Cmax). Lansoprazole should not be co-administered with atazanavir (see section 4.3).
Ketoconazole and itraconazoleThe absorption of ketoconazole and itraconazole from the gastrointestinal tract is enhanced by the presence of gastric acid. Administration of lansoprazole may result in subtherapeutic concentrations of ketoconazole and itraconazole and the combination should be avoided.
DigoxinCo-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 enzymesLansoprazole may increase plasma concentrations of drugs that are metabolised by CYP3A4. Caution is advised when combining lansoprazole with drugs which are metabolised by this enzyme and have a narrow therapeutic window.
TheophyllineLansoprazole reduces the plasma concentration of theophylline, which may decrease the expected clinical effect at the dose. Caution is advised when combining the two medicinal products.
TacrolimusCo-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-glycoproteinLansoprazole 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
Drugs which inhibit CYP2C19Fluvoxamine:A dose reduction may be considered when combining Lansoprazole with the CYP2C19 inhibitor fluvoxamine. The plasma concentrations of Lansoprazole increase up to 4-fold.
Drugs which induce CYP2C19 and CYP3A4Enzyme inducers affecting CYP2C19 and CYP3A4 such as rifampicin, and St John´s wort (Hypericum perforatum) can markedly reduce the plasma concentrations of Lansoprazole.
OthersSucralfate / AntacidsSucralfate / antacids may decrease the bioavailability of lansoprazole. Therefore Lansoprazole should be taken at least one hour after taking these drugs.No clinically significant interactions of lansoprazole with non-steroidal anti-inflammatory drugs have been demonstrated, although no formal interactions studies have been performed.
PregnancyFor 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.The use of lansoprazole during pregnancy is not recommended.
LactationIt 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 breast-feeding to the child and the benefit of lansoprazole therapy to the woman.
|Common||Uncommon||Rare||Very Rare||Not known|
|Blood and lymphatic system disorders||Thrombocytopenia, eosinophilia, leucopenia.||Anaemia.||Agranulocytosis, pancytopenia|
|Metabolism and nutritional disorders||Hypomagnesaemia (see section 4.4)|
|Psychiatric disorders||Depression||Insomnia, hallucination, confusion|
|Nervous system disorders||Headache, dizziness||Restlessness, vertigo and paraesthesia, somnolence, tremor.|
|Eye disorders||visual disturbances|
|Gastrointestinal disorders||Nausea, diarrhoea, stomach ache, constipation, vomiting, flatulence and dry mouth or throat.||Glossitis, candidiasis of the oesophagus, pancreatitis, taste disturbances||Colitis, stomatitis.|
|Hepatobiliary disorders||Increase in liver enzyme levels.||Hepatitis and jaundice.|
|Skin and subcutaneous tissue disorders||Urticaria, itching, rash.||Petechia, purpura, hair loss, erythema multiforme, photosensitivity.||Stevens-Johnson syndrome and toxic epidermal necrolysis|
|Musculoskeletal and connective tissue disorders||Athralgia, myalgia, fracture of the hip, wrist or spine (see section 4.4)|
|Renal and urinary disorders||Interstitial nephritis.|
|Reproductive system and breast disorders||Gynaecomastia.|
|General disorders and administration site conditions||Fatigue.||Oedema.||Fever, hyperhidrosis, anorexia, impotence and angioedema.||Anaphylactic shock.|
|Investigations||Increase in cholesterol and triglyceride levels, hyponatremia|
Absorption and distributionLansoprazole 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 granules from opened capsules give 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 apple juice administered through a naso-gastric tube.
Metabolism and eliminationLansoprazole is extensively metabolised by the liver and the metabolites are excreted by both 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 patientsThe 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 patientsThe 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 insufficiencyThe 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 metabolisersCYP2C19 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).
Capsule content:Sugar spheres (containing sucrose and maize starch)Sodium starch glycolate (type A)Sodium laurilsulfate (type A)Povidone (K30)Potassium oleateOleic acidHypromelloseMethacrylic acid - ethyl acrylate copolymer 1:1 dispersion 30 per cent (containing polysorbitol 80 and sodium lauril sulphate)TriethylcitrateTitanium dioxide (E-171)Talc.
Capsule shell:HypromelloseCarrageenanPotassium chlorideCarnauba waxTitanium dioxide (E 171)
Printing inkShellac Propylene glycolAmmonium hydroxidePotassium hydroxide Black iron oxide (E172)
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