Ran-Lansoprazole 15mg. 30mg Capsule

RAN-LANSOPRAZOLE 30 is indicated for the short-term treatment of gastric and duodenal ulcers and reflux oesophagitis. RAN-LANSOPRAZOLE 15 is indicated in the short-term management of mild functional dyspepsia and for the prevention of relapse of gastro-oesophageal reflux. RAN-LANSOPRAZOLE is indicated for Helicobacter pylori-positive duodenal ulcers in conjunction with appropriate antibiotics as part of an eradication programme.

Posology
Gastric ulcer: 30 mg once a day for up to eight weeks.
Duodenal ulcer: 30 mg once a day for up to four weeks.
RAN-LANSOPRAZOLE is indicated for Helicobacter pylori-positive ulcers, as part of an eradication program with appropriate antibiotics.
Oesophagitis due to gastro-oesophageal Reflux: 30 mg once a day for four weeks. If symptom control has not been achieved after four weeks of treatment with the prescribed daily dose, further investigation is recommended.
Maintenance treatment for the prevention of gastro-oesophageal reflux: 15 mg once a day for a maximum period of one year.
Functional dyspepsia: Adults: 15-30 mg once a day for 2 to 4 weeks.
Special populations
Elderly population: No dose adjustment is necessary. However, 30mg per day is the maximum daily dose.
Renal impairment: No dose adjustment is necessary in renal failure u2013 this also applies to patients on dialysis.
Paediatric population: Safety and efficacy in children has not been established.

Method of administration
Oral use. RAN-LANSOPRAZOLE should be preferably taken before a meal.

Hypersensitivity to lansoprazole or to any of the excipients of RAN-LANSOPRAZOLE.
Pregnancy and lactation (see section 4.6).
Severe liver impairment.
RAN-LANSOPRAZOLE should not be co-administered with atazanavir and nelfinavir due to significant reduction in atazanavir exposure (see section 4.5).
RAN-LANSOPRAZOLE is contraindicated with atazanavir and nelfinavir as it substantially reduces exposure to the HIV-protease inhibitor (see section 4.5).

Safety and efficacy in children has not been established.
Diagnosis of reflux oesophagitis: Diagnosis of reflux oesophagitis should be confirmed by endoscopy.
Exclusion of malignant ulcers: Treatment with RAN-LANSOPRAZOLE may alleviate the symptoms of malignant ulcers and can delay diagnosis. Therefore, in the presence of symptoms such as, significant unintentional weight loss, recurrent vomiting, dysphagia, haematemesis, or melaena, and when gastric ulcer is suspected or present, the possibility of malignancy of gastric ulcer or a malignant disease of the oesophagus should be excluded prior to treatment with RAN-LANSOPRAZOLE.
Acute Interstitial Nephritis: Acute interstitial nephritis has been observed in patients taking proton pump inhibitors (PPIs) including LANCAP. Acute interstitial nephritis may occur at any point during PPI therapy and is generally attributed to an idiopathic hypersensitivity reaction and is associated with damage to the tubulointerstitium, leading to acute kidney injury. Patients may present with varying signs and symptoms from symptomatic hypersensitivity reactions to non-specific symptoms of decreased renal function (e.g. malaise, nausea, anorexia). In reported case series, some patients were diagnosed on biopsy and in the absence of extra-renal manifestations (e.g., fever, rash or arthralgia). Interstitial nephritis may lead to renal failure. Discontinue RAN-LANSOPRAZOLE if acute interstitial nephritis develops (see section 4.8).
Proton pump inhibitors, such as lansoprazole as in RAN-LANSOPRAZOLE, are associated with an increased risk of subclinical acute or chronic interstitial nephritis associated with proton pump inhibitors (PPIs) leading to chronic renal inflammation and reduced renal function. Interstitial nephritis may progress to renal failure as it is not necessarily reversed when treatment is discontinued.
RAN-LANSOPRAZOLE should be used with caution in patients with liver impairment (see section 4.3).
In patients suffering from gastro-duodenal ulcers, the possibility of H. pylori infection as a aetiological factor should be considered. If RAN-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.
Effect of prolonged use: Daily treatment with acid-suppressing medicines such as RAN-LANSOPRAZOLE over a long period of time (e.g., longer than 3 years) may lead to malabsorption of cyanocobalamin (vitamin B12) caused by hypo- or achlorhydria. Rare reports of cyanocobalamin deficiency occurring with acid-suppressing therapy have been reported. This diagnosis should be considered if clinical symptoms consistent with cyanocobalamin deficiency are observed. 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.
RAN-LANSOPRAZOLE is not indicated for mild gastrointestinal complaints such as nervous dyspepsia.
Occurrence of hypomagnesaemia: Severe hypomagnesaemia has been reported in patients treated with proton pump inhibitors (PPIs) like RAN-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 dysrhythmia can occur but they may begin insidiously and be overlooked. In most affected patients, hypomagnesaemia improved after magnesium replacement and discontinuation of RAN-LANSOPRAZOLE. For patients expected to be on prolonged treatment or who take RAN-LANSOPRAZOLE with digoxin or medicines that may cause hypomagnesaemia (e.g., diuretics), health care professionals should consider measuring magnesium levels before starting RAN-LANSOPRAZOLE treatment and periodically during treatment.
Bone fracture: Proton pump inhibitors, such as RAN-LANSOPRAZOLE, especially if used in high doses and over long durations (>1 year), may increase the risk of hip, wrist and spine fracture, predominantly in the elderly or in presence of other recognised risk factors. Patients should use the lowest dose and shortest duration of RAN-LANSOPRAZOLE therapy appropriate to the condition being treated. Patients at risk of osteoporosis should receive care according to current clinical guidelines.
Concomitant use with methotrexate: Concomitant use of RAN-LANSOPRAZOLE with methotrexate (primarily at high dose) may elevate and prolong serum levels of methotrexate and/or its metabolite, possibly leading to methotrexate toxicities. In high-dose methotrexate administration, a temporary withdrawal of RAN-LANSOPRAZOLE may be considered in some patients (see section 4.5).
Effects related to acid inhibition: During long-term treatment, gastric glandular cysts have been reported in increased frequency. These physiological changes result from pronounced inhibition of gastric acid secretion. Decreased gastric acidity increases gastric counts of bacteria normally present in the gastrointestinal tract. Treatment with RAN-LANSOPRAZOLE may lead to an increased risk of gastro-intestinal infections such as Salmonella and Campylobacter.
Increased risk of Clostridium difficile associated diarrhoea: Proton pump inhibitor (PPI) therapy like RAN-LANSOPRAZOLE may be associated with an increased risk of Clostridium difficile associated diarrhoea (CDAD). This diagnosis should be considered for diarrhoea that does not improve. Patients should use the lowest dose and shortest duration of RAN-LANSOPRAZOLE therapy appropriate to the condition being treated.
Proton pump inhibitors, such as lansoprazole as in RAN-LANSOPRAZOLE, are associated with subacute cutaneous lupus erythematosus (SCLE). If lesions occur, especially in sun-exposed areas of the skin, and if accompanied by arthralgia, the medical practitioner should consider stopping RAN-LANSOPRAZOLE.
Effect on central nervous system: RAN-LANSOPRAZOLE may lead to drowsiness and impaired concentration that may be aggravated by the simultaneous intake of alcohol or other central nervous system depressants.
Possible porphyrinogenicity: Lansoprazole, as in RAN-LANSOPRAZOLE, is possibly porphyrinogenic and should be used only when no safer alternative is available, and precautions should be considered in all patients.

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 RAN-LANSOPRAZOLE and warfarin concomitantly may need to be monitored for increases in INR and prothrombin time.
Concomitant administration of PPIs such as RAN-LANSOPRAZOLE and methotrexate (primarily at high dose) may elevate and prolong serum levels of methotrexate and/or its metabolite hydroxymethotrexate, possibly leading to methotrexate toxicities. In high-dose methotrexate administration, a temporary withdrawal of RAN-LANSOPRAZOLE may be considered in some patients.
Medicines with pH dependent absorption
RAN-LANSOPRAZOLE causes a profound and long-lasting inhibition of gastric acid secretion; therefore it is possible that RAN-LANSOPRAZOLE may interfere with the absorption of medicines where gastric pH is critical to bioavailability (e.g. itraconazole, ketoconazole, posaconazole, ampicillin esters, iron salts, digoxin, atazanavir, dasatinib and erlotinib). If voriconazole is taken concomitantly with RAN-LANSOPRAZOLE the plasma concentration of both medicines may be increased.
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 max). RAN-LANSOPRAZOLE should not be co-administered with atazanavir and nelfinavir (see section 4.3).
Ketoconazole and itraconazole: The absorption of ketoconazole and itraconazole from the gastrointestinal tract is enhanced by the presence of gastric acid. Administration of RAN-LANSOPRAZOLE may result in sub-therapeutic concentrations of ketoconazole and itraconazole and the combination should be avoided.
Digoxin: Co-administration of RAN-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 RAN-LANSOPRAZOLE treatment.
Medicines metabolised by P450 enzymes: Since RAN-LANSOPRAZOLE is a weak inducer of the cytochrome P450 system, the possibility exists for interactions with medicines which are metabolised via this system, such as warfarin, antipyrine, indomethacin, ibuprofen, or other nonsteroidal anti-inflammatory drugs (NSAIDS); oral contraceptives, phenytoin, propranolol, prednisone, diazepam or clarithromycin. Lansoprazole may increase plasma concentrations of medicines that are metabolised by CYP3A4. Caution is advised when combining RAN-LANSOPRAZOLE with medicines which are metabolised by this enzyme and have a narrow therapeutic window.
Theophylline: Lansoprazole reduces the plasma concentration of theophylline, which may decrease the expected clinical effect at the dose. Patients may require additional titration of the theophylline dosage when treatment with RAN-LANSOPRAZOLE is commenced or discontinued, to ensure clinically effective blood levels. Caution is advised when combining the two medicines.
Tacrolimus: Co-administration of lansoprazole increases the plasma concentrations of tacrolimus (a CYP3A and P-gp substrate) and result in a decreased clearance. Lansoprazole exposure increased the mean exposure of tacrolimus by up to 81 %. Monitoring of tacrolimus plasma concentrations is advised when concomitant treatment with RAN-LANSOPRAZOLE is initiated or ended.
RAN-LANSOPRAZOLE has been shown to have no clinically significant interaction with amoxicillin.
Medicines which inhibit CYP2C19: 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.
Medicines which induce CYP2C19 and CYP3A4: Enzyme inducers affecting CYP2C19 and CYP3A4 such as rifampicin, and St Johnu00b4s wort (Hypericum perforatum) can markedly reduce the plasma concentrations of lansoprazole.
Others: Sucralfate/Antacids: Sucralfate/Antacids may decrease the bioavailability of lansoprazole. Therefore RAN-LANSOPRAZOLE should be taken at least 1 hour after taking these medicines.
Clopidogrel: Concomitant administration of lansoprazole and clopidogrel in healthy subjects had no clinically important effect on exposure to the active metabolite of clopidogrel or clopidogrel-induced platelet inhibition. No dose adjustment of clopidogrel is necessary when administered with an approved dose of RAN-LANSOPRAZOLE.
The decrease in gastric activity with RAN-LANSOPRAZOLE may give false positive results in diagnostic investigations for neuroendocrine tumours and treatment should be stopped before such investigations. Treatment with RAN-LANSOPRAZOLE may cause false-negative results in the urea breath test for Helicobacter pylori infection. It is recommended that a urea breath test should not be performed for at least 2 weeks after stopping treatment with RAN-LANSOPRAZOLE.

Pregnancy
RAN-LANSOPRAZOLE is contraindicated in pregnancy. Adequate and well-controlled studies in humans have not been done.
Breastfeeding
RAN-LANSOPRAZOLE is contraindicated in lactation. It is not known whether lansoprazole is distributed into breast milk. However, lansoprazole or its metabolites are distributed into the milk of rats. Because lansoprazole has been shown to cause tumorigenic effects in animals, a decision should be made as to whether nursing should be discontinued or the medicine withdrawn, taking into account the importance of lansoprazole to the mother (see section 4.3).

Adverse 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. Patients should be advised, particularly at the initiation of therapy, against taking charge of vehicles or machines or performing potentially hazardous tasks where loss of concentration could lead to accidents.

Tabulated list of Adverse events:
MedDRA system organ class Frequency Adverse reactions
Infections and Infestations Unknown frequency Clostridium difficile associated diarrhoea.
Blood and lymphatic system disorders Less frequent Thrombocytopenia, anaemia, leucopenia, neutropenia, eosinophilia, a granulocytosis, pancytopenia, haemolysis, lymphadenopathy. Unknown frequency Aplastic anaemia, haemolytic anaemia, thrombotic thrombocytopenic purpura.
Immune system disorders Less frequent Allergic reaction, bronchospasm, anaphylactic shock, angioedema, acute interstitial nephritis.
Endocrine disorders Less frequent Diabetes mellitus, goiter, hypothyroidism.
Metabolism and nutrition disorders Less frequent Avitaminosis, gout, dehydration, hyperglycaemia/hypoglycaemia, peripheral oedema, weight gain/loss. Unknown frequency Hypomagnesaemia (see section 4.4).
Psychiatric disorders Less frequent Depression, insomnia, hallucination, confusion, abnormal dreams, agitation, aggression, amnesia, anxiety, apathy, dementia, depersonalisation, emotional lability, hostility aggravated, libido decreased/increased, nervousness, neurosis, sleep disorder.
Nervous system disorders Frequent Headache, dizziness. Less frequent Somnolence, tremor, convulsion, restlessness, vertigo, paraesthesia, increased sweating, hemiplegia, hyperkinesia, hypertonia, hypesthesia, parosmia, thinking abnormality; speech disorder.
Eye disorders Less frequent Blurred vision, visual disturbances, abnormal vision, diplopia, amblyopia, blepharitis, cataract, conjunctivitis, dry eyes, eye disorder, eye pain, glaucoma, photophobia, retinal degeneration/disorder, visual field defect.
Ear and labyrinth disorders Less frequent Deafness, ear disorder, otitis media, tinnitus.
Cardiac disorders Less frequent Angina, dysrhythmia, bradycardia, myocardial infarction, palpitations, shock (circulatory failure), tachycardia, cardiospasm.
Vascular disorders Less frequent Migraine, cerebrovascular accident/cerebral infarction, hypertension/hypotension, syncope, vasodilation.
Respiratory, thoracic and mediastinal disorders Less frequent Asthma, bronchitis, increased cough, dyspnoea, epistaxis, haemoptysis, hiccup, laryngeal neoplasia, lung fibrosis, pharyngitis, pleural disorder, pneumonia, respiratory disorder, upper respiratory inflammation/infection, rhinitis, sinusitis, stridor.
Gastrointestinal disorders Frequent Diarrhoea, nausea, vomiting, constipation and abdominal pain, flatulence, dry mouth or throat. Less frequent Glossitis, taste abnormalities, taste loss, colitis, candidiasis of the oesophagus, pancreatitis, stomatitis, anorexia, abdomen enlarged, abnormal stools, bezoar, cholelithiasis, dyspepsia, dysphagia, enteritis, eructation, oesophageal stenosis, oesophageal ulcer, oesophagitis, faecal discolouration, gastric nodules/fundic gland polyps, gastritis, gastroenteritis, gastrointestinal anomaly, gastrointestinal disorder, gastrointestinal haemorrhage, gum haemorrhage, haematemesis, increased appetite, increased salivation, melaena, mouth ulceration, gastrointestinal moniliasis, rectal disorder, rectal haemorrhage, tenesmus, thirst, tongue disorder, ulcerative stomatitis.
Hepatobiliary disorders Frequent Increase in liver enzyme levels. Less frequent Hepatitis, jaundice, hyperbilirubinaemia. Unknown frequency Hepatotoxicity, hepatic failure or necrosis.
Skin and subcutaneous tissue disorders Frequent Skin rash, pruritus, urticaria. Less frequent Alopecia, petechiae, purpura, erythema multiforme, photosensitivity, Stevens-Johnson syndrome, toxic epidermal necrolysis, acne, contact dermatitis, dry skin, fixed eruption, hair disorder, maculopapular rash, nail disorder, skin carcinoma, skin disorder, peripheral oedema, subacute cutaneous lupus erythematosus.
Musculoskeletal, and connective tissue disorders Less frequent Arthralgia, myalgia, fracture of the hip, wrist or spine (see section 4.4), arthritis, bone disorder, joint disorder, leg cramps, musculoskeletal pain, myasthenia, ptosis, synovitis, back pain, neck pain, neck rigidity, pelvic pain.
Renal and urinary disorders Less frequent Dysuria, interstitial nephritis, kidney calculus, kidney pain, polyuria, urethral pain, urinary frequency, urinary tract infection, urinary urgency, urination impaired, urinary retention, in some patients renal failure has been reported concomitantly (see section 4.4).
Reproductive system and breast disorders Less frequent Gynaecomastia, galactorrhoea, abnormal menses, menorrhagia, menstrual disorder, breast enlargement, breast pain, breast tenderness, dysmenorrhoea, impotence, penis disorder, testis disorder, leucorrhoea, vaginitis.
General disorders and administration site conditions Frequent Fatigue. Less frequent Asthenia, fever, oedema, hyperhidrosis, carcinoma, chills, flu syndrome, infection, malaise, pain, chest pain, halitosis.
Investigations Less frequent Increase in cholesterol and triglyceride levels, hyponatraemia. Unknown frequency Increased creatinine, increased alkaline phosphatase, increased globulins, increased GGTP, increased/decreased/abnormal WBC, abnormal AG ratio, abnormal RBC, bilirubinaemia, increased blood potassium, increased blood urea, crystal urine present, decreased haemoglobin, increased/decreased/abnormal platelets, increased gastrin levels and positive faecal occult blood. Urine abnormalities such as albuminuria, glycosuria, and haematuria were also reported.

See section 4.8. The effects of overdose on lansoprazole in humans are not known. 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. Treatment is symptomatic and supportive.