Lancerol®

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT LANCEROL® (LANCEROL®)

Composition:

Active substance: lansoprazole;

1 capsule contains lansoprazole in pellets, calculated as 100% substance 30 mg;

Excipients (in the pellet composition): sugar spheres (sucrose, corn starch, purified water) (0.85–1.0 mm), sodium lauryl sulfate, meglumine, mannitol (E 421), hypromellose (hydroxypropylmethylcellulose), polyethylene glycol 6000, talc, polysorbate 80, titanium dioxide (E 171), methacrylic acid copolymer (type A);

Capsule shell composition: gelatin.

Pharmaceutical form. Capsules.

Main physicochemical properties: hard gelatin capsules size №1, body and cap colorless and transparent. Capsule contents – white or almost white pellets.

Pharmacotherapeutic group. Drugs for treatment of peptic ulcer and gastroesophageal reflux disease. Proton pump inhibitors.

ATC code A02BC03.

Pharmacological properties.

Pharmacodynamics.

Lansoprazole inhibits the activity of H+/K+-ATPase (proton pump) in parietal cells of the gastric mucosa. Thus, Lanzerol® inhibits the final stage of gastric acid production, reduces the volume and acidity of gastric juice, thereby decreasing the harmful effect of gastric juice on the mucosa.

The degree of inhibition depends on the dose and duration of treatment. Even a single 30 mg dose of lansoprazole inhibits gastric acid secretion by 70–90%. The onset of action occurs within 1–2 hours and lasts for 24 hours.

Pharmacokinetics.

Lansoprazole is absorbed in the intestine. In healthy volunteers, after administration of 30 mg of lansoprazole, maximum plasma concentration ranges from 0.75 to 1.15 mg/L and is reached within 1.5–2 hours. Maximum plasma concentration and bioavailability depend on individual patient characteristics and do not change with the frequency of drug administration.

Protein binding of the drug in plasma is 98%.

Lansoprazole is excreted from the body via bile and urine (only in the form of metabolites – lansoprazole sulfone and hydroxylansoprazole), with 21% of the administered dose being excreted in urine within 24 hours. The elimination half-life is 1.5 hours.

The elimination half-life is prolonged in patients with severe hepatic impairment and in patients aged 69 years and older. Absorption of lansoprazole is practically unchanged in patients with renal impairment.

Clinical characteristics.

Indications.

• Benign peptic ulcer of the stomach and duodenum, including that associated with the use of nonsteroidal anti-inflammatory drugs;
• gastroesophageal reflux disease;
• Zollinger–Ellison syndrome;
• for eradication of Helicobacter pylori (in combination with antibiotics).

Contraindications.

• Hypersensitivity to lansoprazole or to any other component of the drug;
• concomitant use with atazanavir;
• malignant neoplasms of the gastrointestinal tract.

Interaction with other medicinal products and other forms of interaction.

Lansoprazole, like other proton pump inhibitors, reduces the concentration of atazanavir (an HIV protease inhibitor), the absorption of which depends on gastric acidity, and thus may affect the therapeutic efficacy of atazanavir and lead to the development of resistance to HIV infection. Concomitant use of atazanavir and lansoprazole is contraindicated.

Lansoprazole may increase plasma concentrations of drugs metabolized by CYP3A4 (warfarin, antipyrine, indometacin, ibuprofen, phenytoin, propranolol, prednisolone, diazepam, clarithromycin, or terfenadine).

Medicinal products that inhibit CYP2C19 (fluvoxamine) lead to a significant increase (4-fold) in lansoprazole plasma concentration. Dose adjustment of lansoprazole is required when used concomitantly.

Inducers of CYP2C19 and CYP3A4 (rifampicin, St. John's wort) may significantly reduce lansoprazole plasma concentrations. Dose adjustment of lansoprazole is required when used concomitantly.

Lansoprazole causes prolonged suppression of gastric secretion; therefore, a theoretical possibility exists for lansoprazole to affect the bioavailability of drugs whose absorption is pH-dependent (ketoconazole, itraconazole, ampicillin esters, iron salts, digoxin).

Concomitant use of lansoprazole and digoxin may lead to increased digoxin plasma levels. Therefore, careful monitoring of digoxin plasma levels and dose adjustment of digoxin, if necessary, is required at the beginning and after discontinuation of lansoprazole therapy.

No clinical manifestations of interactions between lansoprazole and amoxicillin have been observed.

Sucralfate and antacid agents may reduce the bioavailability of lansoprazole; therefore, lansoprazole should be taken at least 1 hour after administration of these agents.

No clinically significant interaction between lansoprazole and nonsteroidal anti-inflammatory drugs has been identified.

When lansoprazole is used concomitantly with theophylline (CYP1A2, CYP3A), a moderate increase (up to 10%) in theophylline clearance is observed, but the clinical significance of this interaction is unlikely. However, to maintain therapeutically effective theophylline concentrations, some patients may require dose adjustment of theophylline at the initiation or after discontinuation of lansoprazole therapy.

Lansoprazole does not affect the pharmacokinetics of warfarin or prothrombin time.

Elevated INR and prothrombin time may lead to bleeding and even fatal outcomes.

When lansoprazole is used concomitantly with tacrolimus, tacrolimus plasma concentrations may increase, particularly in transplant patients. Therefore, tacrolimus plasma levels should be monitored at the initiation and after discontinuation of combined therapy with lansoprazole.

Special precautions for use.

Before prescribing Lancerol®, it is necessary to exclude the possibility of malignant tumors in the stomach and esophagus, as the drug may mask symptoms and thus delay the establishment of a correct diagnosis. Therefore, endoscopic monitoring with biopsy should be performed both before starting and after completing a course of treatment with lansoprazole.

When using combination therapy with clarithromycin and amoxicillin, precautions regarding the use of these medicinal products should be considered according to the instructions for medical use of clarithromycin and amoxicillin. Additionally, prior to initiating amoxicillin and clarithromycin, the presence of a history of hypersensitivity reactions to penicillins, cephalosporins, or other allergens should be taken into account.

Pseudomembranous colitis, sometimes life-threatening, may occur during the use of antibacterial agents. Therefore, this possibility must be considered when patients develop diarrhea.

In patients with renal impairment, protein binding in blood decreases by 1–1.5%.

Renal function disorders

Acute tubulointerstitial nephritis has been observed in patients taking lansoprazole and may occur at any time during lansoprazole therapy (see section "Adverse reactions"). Acute tubulointerstitial nephritis may progress to renal failure.

Lansoprazole therapy should be discontinued if acute tubulointerstitial nephritis is suspected, and appropriate treatment should be initiated immediately.

In patients with chronic hepatic insufficiency, the plasma elimination half-life increases from 1.5 hours to 3.2–7.2 hours, depending on the degree of hepatic dysfunction. Patients with severe liver impairment should receive reduced doses. Treatment should begin with half the indicated dose, gradually increasing to recommended doses, but not exceeding 30 mg per day.

Lansoprazole reduces gastric acidity, thereby increasing the risk of gastrointestinal infections caused by opportunistic pathogens such as Salmonella and Campylobacter.

Patients with gastric and duodenal ulcers should consider H. pylori infection as a possible etiological factor. If lansoprazole is used in combination with antibiotics for H. pylori eradication therapy, the instructions for medical use of these antibiotics should be followed.

Treatment and prevention of peptic ulcers should be limited to patients requiring long-term nonsteroidal anti-inflammatory drugs (NSAIDs) or those at risk, such as patients with a history of gastrointestinal bleeding, perforation, or ulcers; elderly patients; patients receiving concomitant medications that increase the risk of upper gastrointestinal disorders (e.g., corticosteroids or anticoagulants); patients with severe comorbid conditions; or those receiving prolonged treatment with maximum recommended NSAID doses.

Severe hypomagnesemia has been observed in patients treated with proton pump inhibitors (PPIs), such as lansoprazole, for at least three months and, in most cases, after one year of treatment. Severe manifestations of hypomagnesemia may include fatigue, muscle spasms, confusion, seizures, dizziness, and ventricular arrhythmias, which may develop suddenly. In most patients, symptoms of hypomagnesemia resolved after magnesium replacement therapy and discontinuation of the proton pump inhibitor.

For patients receiving long-term therapy or those taking PPIs concurrently with digoxin or medications that may cause hypomagnesemia (e.g., diuretics), monitoring of magnesium levels before starting PPI therapy and periodically during treatment may be necessary.

Proton pump inhibitors, particularly when used at high doses and for prolonged periods (more than 1 year), may slightly increase the risk of fractures of the hip, wrist, or spine, especially in elderly patients or those with other risk factors. Experimental study results suggest that proton pump inhibitors may increase the overall fracture risk by 10–40%. Some of these cases may be attributable to other risk factors. Patients at risk of osteoporosis should be monitored according to current clinical guidelines and should receive adequate calcium and vitamin D supplementation.

Due to limited safety data on the use of lansoprazole as maintenance therapy for longer than 1 year, a regular risk-benefit assessment should be conducted for this patient group.

Elderly patients.

Ulcer treatment in elderly patients does not differ significantly from that in younger patients. Adverse reactions and laboratory changes in elderly patients are similar to those in younger patients.

The product contains sucrose. This medicinal product is contraindicated in patients with rare hereditary fructose intolerance, glucose-galactose malabsorption syndrome, or sucrase-isomaltase deficiency.

Use during pregnancy or breastfeeding. The product must not be used during pregnancy or breastfeeding.

If treatment with this medicinal product is necessary, breastfeeding should be discontinued.

Ability to affect reaction speed when driving or operating machinery. When driving vehicles or operating machinery, the possibility of adverse reactions affecting the nervous system and visual organs, such as dizziness, vertigo, visual disturbances, and somnolence, should be considered, as these may impair reaction speed.

Method of Administration and Dosage

For oral use in adults. The usual dose is 30 mg once daily, taken 30–40 minutes before a meal. Capsules should be swallowed whole with 150–200 ml of water. If this is not possible, the capsule may be opened and its contents mixed with a small amount of apple juice (approximately 1 tablespoon), then swallowed immediately without chewing. The same procedure should be followed if the drug is administered via a nasogastric tube.

Dosage and duration of treatment are determined individually by a physician, depending on the clinical situation and course of the disease.

The maximum daily dose of the drug is 60 mg; for patients with impaired liver function – 30 mg. Dosages may be increased for patients with Zollinger–Ellison syndrome.

If two daily doses are required, the patient should take one before breakfast and the other before dinner.

If a dose is missed, the patient should take it as soon as possible. However, if the next dose is due soon, the missed dose should be skipped.

Peptic ulcer of the duodenum

The dose for treatment of active ulcer is 30 mg once daily for 2–4 weeks. The dose for ulcers caused by nonsteroidal anti-inflammatory drugs (NSAIDs) is 30 mg once daily. Treatment lasts 4–8 weeks.

Benign gastric ulcer

The dose for treatment of active ulcer is 30 mg once daily for 8 weeks. The dose for ulcers caused by NSAIDs is 30 mg once daily for 4–8 weeks.

Gastroesophageal reflux disease, reflux esophagitis

The recommended dose for treatment of gastroesophageal reflux disease is 30 mg daily. Symptom improvement occurs rapidly. Individual dose adjustment should be considered. If symptoms do not improve within 4 weeks of treatment with 30 mg daily, additional diagnostic testing is recommended.

For moderate to severe esophagitis, the recommended dose is 30 mg once daily for 4 weeks. If erosive esophagitis does not heal within 4 weeks, treatment duration may be doubled.

The dose for long-term prevention of recurrent erosive esophagitis is 30 mg once daily. The safety and efficacy of maintenance therapy with lansoprazole have been established for up to 12 months of treatment.

Helicobacter pylori eradication

The dose is 30 mg of the drug twice daily (before breakfast and before dinner). The patient must take the drug in combination with antibiotics according to approved regimens for 1–2 weeks.

Zollinger–Ellison syndrome

The drug dosage should be individually adjusted to maintain basal acid secretion below 10 mmol/h. The recommended initial dose is 60 mg once daily before breakfast. If the daily dose exceeds 120 mg, the patient should take the first half before breakfast and the second half before dinner. Treatment continues until clinical indications resolve.

Renal and hepatic impairment

Patients with mild to moderate hepatic or renal impairment do not require dose adjustment.

Patients with severe hepatic impairment should receive the lowest effective dose, not exceeding 30 mg daily.

Elderly patients

No dose adjustment is necessary when using the drug in elderly patients.

Children. Lansoprazole should not be used in children.

Overdose.

There are no reported cases of lansoprazole overdose.

Data indicate that a single 600 mg dose of the drug does not cause clinical symptoms of overdose; however, overdose may intensify adverse reactions.

Treatment. There is no specific antidote. Hemodialysis is ineffective. Activated charcoal should be administered to reduce drug absorption. In case of overdose, symptomatic and supportive treatment should be provided.

Side effects.

During treatment, the following adverse reactions are frequently reported: abdominal pain, diarrhea, nausea; diarrhea being the most common. Headache has also been reported in more than 1% of cases.

Cardiovascular system: angina pectoris, cerebrovascular changes, arterial hypertension, arterial hypotension, myocardial infarction, palpitations, shock (circulatory failure), vasodilation.

Gastrointestinal tract: anorexia, cardiospasm, cholelithiasis, constipation, vomiting, hepatotoxicity, jaundice, hepatitis, candidiasis of gastrointestinal mucous membranes, dry mouth/thirst, dyspepsia, dysphagia, eructation, esophageal stricture, esophageal ulcer, esophagitis, change in stool color, flatulence, gastric polyps, gastroenteritis, colitis, gastrointestinal hemorrhage, vomiting with blood, increased or decreased appetite, increased salivation, melena, rectal bleeding, stomatitis, taste disturbances, glossitis, pancreatitis, tenesmus, ulcerative colitis.

Metabolism: hypomagnesemia.

Endocrine system: diabetes mellitus, goiter, hyperglycemia/hypoglycemia.

Blood and lymphatic system: anemia (including aplastic and hemolytic anemia), hemolysis, agranulocytosis, leukopenia, neutropenia, pancytopenia, thrombocytopenia, eosinophilia, thrombotic and thrombocytopenic purpura.

Musculoskeletal system: arthritis/arthralgia, musculoskeletal pain, myalgia.

Nervous system: agitation, amnesia, increased excitability, apathy, depression, dizziness/syncope, vertigo, hallucinations, hemiplegia, hostility, fear, decreased libido, nervousness, insomnia, somnolence, tremor, paresthesia, thinking disturbances, confusion.

Respiratory system: dyspnea, cough, pharyngitis, rhinitis, infections of upper and lower respiratory tract (bronchitis, pneumonia), asthma, epistaxis, pulmonary hemorrhage, hiccup.

Skin and subcutaneous tissue: angioneurotic edema, erythema multiforme, toxic epidermal necrolysis, Stevens-Johnson syndrome, polymorphic erythema, acne, facial hyperemia, alopecia, pruritus, rash, urticaria, purpura, petechiae, hyperhidrosis, photosensitivity.

Sensory organs: blurred vision, eye pain, visual field defects, tinnitus, deafness, otitis media, taste changes, speech disorders.

Urinary and reproductive system: tubulointerstitial nephritis (with possible progression to renal failure), kidney stone formation, urinary retention, glucosuria, hematuria, albuminuria, menstrual cycle disturbances, breast enlargement/gynecomastia, breast tenderness, impotence.

Combination therapy with amoxicillin and clarithromycin: when using combination therapy with lansoprazole, amoxicillin, and clarithromycin, there are no specific adverse reactions characteristic of combination therapy. The adverse reactions that may occur are typical for lansoprazole, amoxicillin, and clarithromycin.

The most common adverse reactions in patients receiving triple therapy (lansoprazole/clarithromycin/amoxicillin) for 14 days are diarrhea, headache, and taste disturbances. The most common adverse reactions during dual therapy with lansoprazole and amoxicillin are diarrhea and headache. Adverse reactions are transient and do not require discontinuation of treatment.

Laboratory findings: increased levels of AST, ALT, alkaline phosphatase, creatinine, globulins, gamma-glutamyl transferase, altered albumin/globulin ratio.

Also observed are increased/decreased leukocyte count, changes in erythrocyte count, bilirubinemia, eosinophilia, hyperlipidemia, increased/decreased electrolyte levels, increased/decreased cholesterol, decreased hemoglobin, increased potassium and urea levels, increased glucocorticoid levels, increased low-density lipoprotein levels, increased/decreased platelet count, increased gastrin levels, positive occult blood test. In urine: albuminuria, glucosuria, hematuria, presence of salts.

There are data on increased liver enzyme levels more than 3 times above the upper normal limit at the end of lansoprazole treatment, although jaundice was not observed.

Other: anaphylactoid reactions, anaphylactic shock, asthenia, increased fatigue, candidiasis, chest pain (not always specific), edema, fever, flu-like syndrome, bad breath, infections (not always specific), weakness.

Shelf life. 2 years.

Storage conditions.

Store in original packaging at a temperature not exceeding 25 °C. Keep out of reach of children.

Packaging. 10 capsules in a blister, 1 blister per carton.

Prescription status. Prescription only.

Manufacturer: JSC "Kyivmedpreparat".

Manufacturer's address and location of business activity.

139 Saksaganskogo St., Kyiv, 01032, Ukraine.