Lancap 15 Mg/30 Mg Capsules

• LANCAP 30 mg is indicated for the short-term treatment of gastric and duodenal ulcers and reflux oesophagitis.
• LANCAP 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.

LANCAP 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. Depending on the endoscopic results, a repeat course of 4 weeks may be necessary.

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 u2013 30 mg once a day for 2 to 4 weeks.

Special populations

Elderly: No dose adjustment is necessary. However, 30 mg per day is the maximum daily dose.

Renal impairment: No dose adjustment is necessary in renal failure -this also applies to patients on dialysis.

Method of administration

LANCAP should preferably be taken before a meal.

Missed dose: Doctors should advise patients who forget to take LANCAP to take a dose as soon as possible and then continue with the normal dose. Patients should not take a double dose to compensate for the missed dose.

• Hypersensitivity to lansoprazole or to any of the ingredients of LANCAP.
• Pregnancy and lactation (see section 4.6).
• Severe liver impairment.
• LANCAP is contraindicated with atazanavir or nelfinavir, as it substantially reduces exposure to the HIV-protease inhibitor (see section 4.5).

Diagnosis of reflux oesophagitis: Diagnosis of reflux oesophagitis should be confirmed by endoscopy.

Exclusion of malignant ulcers: Treatment with LANCAP 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 LANCAP.

Effect of prolonged use: Daily treatment with acid-suppressing medicines such as LANCAP 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.

Proton pump inhibitors such as LANCAP have also been reported to impair the bioavailability of dietary vitamin C. Fat malabsorption, secondary to increased deconjugation of bile acids caused by bacterial overgrowth in the jejunum, has also been reported with proton pump inhibitors such as LANCAP treatment. For the suggestion that proton pump inhibitors such as LANCAP can cause calcium malabsorption, (see section 4.8).

Subacute cutaneous lupus erythematosus (SCLE): Proton pump inhibitors such as LANCAP 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 LANCAP. SCLE after previous treatment with a proton pump inhibitor such as LANCAP may increase the risk of SCLE with other proton pump inhibitors.

Increased risk of Clostridium difficile associated diarrhoea: LANCAP may be associated with an increased risk of Clostridium difficile associated diarrhoea (CDAD). A diagnosis of CDAD should be considered for patients taking LANCAP who develop diarrhoea that does not stop. Patients should use the lowest dose and shortest duration of LANCAP therapy appropriate to the condition being treated.

Bone fracture: LANCAP therapy may be associated with an increased risk for osteoporosis-related fractures of the hip, wrist or spine. The risk of fracture was increased in patients who received high-dose, defined as multiple daily doses, and long-term therapy (a year or longer) mainly in the elderly or in the presence of other recognised risk factors. Patients should use the lowest dose and shortest duration of LANCAP therapy appropriate to the condition being treated. Patients at risk for osteoporosis-related fractures should be managed according to established treatment guidelines and should receive appropriate care (see section 4.8).

Occurrence of hypomagnesaemia: Severe hypomagnesaemia has been reported in patients treated with LANCAP for at least 3 months to one year. Hypomagnesemia also produces impaired parathyroid hormone secretion which may lead to hypocalcemia. Serious manifestations of hypomagnesaemia such as fatigue, tetany, delirium, convulsions, dizziness and ventricular dysrhythmia can occur, but may begin slowly and be overlooked. In most patients affected, symptoms improved after magnesium replacement and discontinuation of LANCAP. For patients expected to be on prolonged treatment or who take LANCAP with digoxin or medicines which may cause hypomagnesaemia (e.g. diuretics), health care professionals should consider measuring magnesium levels before starting and during treatment with LANCAP (see section 4.8).

Concomitant use with methotrexate: Concomitant use of LANCAP 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 LANCAP 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 gastro-intestinal tract. Treatment with LANCAP may lead to an increased risk of gastro-intestinal infections such as Salmonella, and Campylobacter, Shigella or Clostridium difficile.

Helicobacter pylori: In patients suffering from gastro-duodenal ulcers, the possibility of H. pylori infection as an etiological factor should be considered.

Effect on central nervous system: LANCAP 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 LANCAP, is possibly porphyrinogenic and should be used only when no safer alternative is available, and precautions should be considered in all patients.

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 LANCAP if acute interstitial nephritis develops (see section 4.8).

Long term use: Because of limited safety data for patients on maintenance treatment for longer than 1-year, regular review of the treatment should be regularly performed in these patients.

Effects of LANCAP on other medicines

Medicines with pH dependant absorption: LANCAP causes a profound and long-lasting inhibition of gastric acid secretion, therefore it is possible that LANCAP may interfere with the absorption of medicines where gastric pH is an important determinant of bioavailability (e.g. itraconazole, ketoconazole, posaconazole, ampicillin esters, iron salts, digoxin, atazanavir, dasatinib and erlotinib). If voriconazole is taken concomitantly with LANCAP the plasma concentration of both medicines may be increased.

HIV protease inhibitors: It has been shown that co-administration of atazanavir with proton-pump inhibitors such as LANCAP results in a substantial reduction in the bioavailability of atazanavir. Therefore, LANCAP must 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 lansoprazole, as in LANCAP, may result in sub-therapeutic concentrations of ketoconazole and itraconazole and the combination should be avoided.

Methotrexate: Concomitant administration of methotrexate (particularly in high doses) with LANCAP may elevate and prolong serum concentrations of methotrexate and/or its metabolite hydromethotrexate. However, no formal interaction studies of high dose methotrexate with PPIs such as LANCAP have been conducted (see section 4.4).

Digoxin: The absorption of digoxin may be enhanced if taken with LANCAP, resulting in increased plasma concentrations. Plasma levels of digoxin should thus be monitored and if necessary, the dosage adjusted upon initiating and ending LANCAP treatment.

Warfarin: The response to anticoagulants such as warfarin may be affected by any concomitant medicine. It is therefore good practice to monitor the patient with additional PT (prothrombin time)/INR (international normalised ratio) determinations when LANCAP is initiated, discontinued or taken irregularly, since a minor reduction in the concentration of warfarin may occur.

Medicines metabolised by P450 enzymes: LANCAP may increase plasma concentrations of medicines that are metabolised by CYP3A4. Caution is advised when combining LANCAP with medicines which are metabolised by this enzyme and have a narrow therapeutic window.

Theophylline: LANCAP reduces the plasma concentration of theophylline potentially decreasing the expected clinical effect at the required dose. Patients may require additional titration of the theophylline dosage when treatment with LANCAP is commenced or discontinued, to ensure clinically effective blood levels. Caution is thus advised when used in combination.

Tacrolimus: Co-administration of LANCAP may cause an increase in tacrolimus plasma concentrations and result in a decreased clearance. Monitoring of tacrolimus plasma concentrations is advised when concomitant treatment with LANCAP is initiated or ended.

Medicines transported by P-glycoprotein: Lansoprazole, as in LANCAP, has been observed to inhibit the transport protein, P-glycoprotein (P-gp) in vitro. The clinical relevance of this is unknown.

Effects of other medicines on LANCAP

Medicines which inhibit CYP2C19: Fluvoxamine may increase the plasma concentration of lansoprazole, therefore a dose reduction may need to be considered in patients taking these medicines concomitantly.

Medicines which induce CYP2C19 and CYP3A4: Enzyme inducers affecting CYP2C19 and CYP3A4, such as rifampicin and St Johnu2019s Wort, can reduce the plasma concentrations of lansoprazole.

Others: Sucralfate/Antacids: Administration of LANCAP concomitantly with sucralfate delays absorption of the proton pump inhibitor and reduces bioavailability by approximately 17 %. Therefore, LANCAP should be taken at least 30 minutes prior to sucralfate. The administration of antacids and LANCAP does not interfere with its effect. Non-steroidal anti-inflammatory medicines: No clinically significant interactions of LANCAP with non-steroidal anti-inflammatory medicines have been demonstrated, although no formal interaction studies have been performed.

Since LANCAP is a weak inducer of the cytochrome P450 system, the possibility exists for interactions with medicines which are metabolized via this system, such as warfarin, antipyrine, indomethacin, ibuprofen, or other nonsteroidal anti-inflammatory medicines (NSAIDs); oral contraceptives, phenytoin, propranolol, prednisone, diazepam or clarithromycin.

The decrease in gastric activity with LANCAP may give false positive results in diagnostic investigations for neuroendocrine tumours and treatment should be stopped before such investigations. Treatment with LANCAP 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 LANCAP. LANCAP has been shown to have no clinically significant interaction with amoxicillin. Concomitant administration of LANCAP with clopidogrel in healthy patients has 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 LANCAP.

Pregnancy: Adequate and well-controlled studies in humans have not been done (see section 4.3).

Breastfeeding: It is not known whether lansoprazole is distributed into breast milk. However, lansoprazole or its metabolites are distributed into the milk of rats. Lansoprazole has been shown to cause tumourigenic effects in animals.

Caution is advised since LANCAP can influence the ability to drive and use machines (see section 4.8). Patients should be advised, particularly at the initiation of therapy, against taking charge of vehicles or machinery or performing potentially hazardous tasks where loss of concentration could lead to accidents.

Tabulated summary of adverse reactions

System Organ Class Frequency Side effects

Blood and lymphatic system disorders Less frequent Thrombocytopenia, anaemia, leukopenia, neutropenia, eosinophilia, agranulocytosis, pancytopenia, haemolysis, lymphadenopathy

Immune system disorders Less frequent Allergic reaction, bronchospasm, angioedema, anaphylaxis, anaphylactic shock, acute interstitial nephritis

Endocrine disorders Less frequent Diabetes mellitus, goitre, hypothyroidism

Metabolism and nutrition disorders Less frequent Hypomagnesaemia, severe hypomagnesaemia can correlate with hypocalcaemia and may result in hypokalaemia, hypocalcaemia, hypokalaemia

Psychiatric disorders Less frequent Abnormal dreams, agitation, amnesia, anxiety, apathy, confusion, depersonalisation, depression, emotional lability, hallucinations, hostility aggravated, libido decreased/increased, nervousness, sleep disorder, dementia, neurosis, insomnia

Nervous system disorders Frequent Less frequent Headache, dizziness Convulsion, diplopia, hemiplegia, hypoesthesia, hyperkinesia, hypertonia, paraesthesia, restlessness, thinking abnormality, somnolence, parosmia, tremor, vertigo

Eye disorders Less frequent Abnormal vision, amblyopia, blepharitis, blurred vision, cataract, conjunctivitis, dry eyes, eye pain, photophobia, retinal degeneration, visual field defect, visual disturbances

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

Vascular disorders Less frequent Vasodilation, cerebrovascular accident/cerebral infarction, hypertension/hypotension, migraine, syncope

Respiratory, thoracic and mediastinal disorders Less frequent Asthma, bronchitis, cough increased, dyspnoea, epistaxis, haemoptysis, hiccough, laryngeal neoplasia, pharyngitis, pleural disorder, pneumonia, respiratory disorder, upper respiratory inflammation/infection, rhinitis, sinusitis, stridor

Gastrointestinal disorders Frequent Less frequent Diarrhoea, dry mouth or throat, nausea, vomiting, constipation, abdominal pain, flatulence Abnormal stools, anorexia, bezoar, cardiospasm, cholelithiasis, colitis, dyspepsia, dysphagia, enteritis, eructation, faecal discolouration, gastric nodules/fundic gland polyps, gastritis, gastroenteritis, gastrointestinal anomaly, abdomen enlarged, gastrointestinal disorder, gastrointestinal haemorrhage, glossitis, gum haemorrhage, haematemesis, increased appetite, increased salivation, melena, mouth ulceration, oesophageal candidiasis, oesophageal stenosis, oesophageal ulcer, oesophagitis, oral moniliasis, rectal disorder, rectal haemorrhage, stomatitis, taste abnormalities, tenesmus

Gastrointestinal disorders continued Less frequent Thirst, tongue disorder, ulcerative colitis, ulcerative stomatitis, pancreatitis (sometimes fatal)

Hepato-biliary disorders Frequent Less frequent Elevation in hepatic enzymes Hepatitis, jaundice, hyperbilirubinaemia

Skin and subcutaneous tissue disorders Frequent Less frequent Skin rash, pruritus, urticaria Acne, alopecia, contact dermatitis, dry skin, erythema multiforme, fixed eruption, nail disorder, skin carcinoma, skin disorder, sweating, Steven-Johnson syndrome or toxic-epidermal necrolysis, photosensitivity, petechiae, purpura

Musculoskeletal, connective tissue and bone disorders Less frequent Asthenia, arthralgia, arthritis, back pain, myalgia, fracture of the hip, wrist or spine, joint disorder, leg cramps, musculoskeletal pain, myasthenia, neck pain, neck rigidity, pelvic pain, ptosis, synovitis

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, interstitial nephritis; in some patients, renal failure has been reported concomitantly (see section 4.4)

Reproductive system and breast disorders Less frequent Abnormal menses, breast enlargement, breast pain, breast tenderness, dysmenorrhoea, gynaecomastia, impotence, leucorrhoea, menorrhagia, menstrual disorder, penis disorder, vaginitis

General disorders and administrative site conditions Frequent Less frequent Fatigue Asthenia, carcinoma, chest pain, chills, fever, flu syndrome, halitosis, infection, malaise, oedema, pain

Investigations Less frequent Hyponatraemia, increase in cholesterol and triglyceride levels

Reporting of suspected adverse reactions: Reporting suspected adverse reactions after authorisation of the medicine is important. It allows continued monitoring of the benefit/risk balance of the medicine. Healthcare professionals are asked to report any suspected adverse reactions to SAHPRA via the Med Safety APP (Medsafety X SAHPRA) and eReporting platform (who-umc.org) found on SAHPRA website. An email can be sent directly to the company, [email protected] to ensure safety of the product.

Signs and symptoms: The effects of overdose on lansoprazole, as in LANCAP, in humans are not known (although the acute toxicity is likely to be low) and, consequently, instructions 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. See section 4.8 for possible symptoms of lansoprazole overdose.

Management of overdose: Treatment is symptomatic and supportive. In the case of suspected overdose, the patient should be monitored. Lansoprazole, as contained in LANCAP, is not significantly eliminated by haemodialysis.