Lansoprazole

Pharmacological properties

Lansoprazole inhibits the activity of the n + / k + -atase of the proton pump in the parietal cells of the gastric mucosa. thus, lansoprazole inhibits the final stage of the formation of acid of gastric juice, reduces the amount and acidity of gastric juice, as a result of which its harmful effect on the mucous membrane is reduced.

The degree of inhibition is determined by the dose and duration of treatment. Even a single dose of 30 mg of lanzoprazole inhibits the secretion of gastric acid by 70–90%. The action occurs within 1 or 2 hours and lasts throughout the day.

Lansoprazole is absorbed in the intestines. In healthy patients, 30 mg of lanzoprazole C_max in blood plasma is 0.75–1.15 mg / l and is achieved within 1.5–2 hours. C_max in blood plasma and bioavailability depend on the individual characteristics of the patient and do not change depending on the frequency of administration of the drug.

The binding of the drug to plasma proteins is 98%.

Lansoprazole is excreted from the body with bile and urine (only in the form of metabolites - lansoprazolsulfone and hydroxylanzoprazole), while 21% of the drug is excreted in the urine per day. T_½ 1.5 hours

T_½ increases in patients with severe impaired liver function and in patients over the age of 69 years. In patients with impaired renal function, the absorption of lanzoprazole is virtually unchanged.

Indications

Peptic ulcer of the stomach and duodenum, including those associated with NSAIDs, gastroesophageal reflux disease, Zollinger-Ellison syndrome, for eradication of helicobacter pylori (in combination with antibiotics).

Application

Adults are taken orally. usually the dose is 30 mg once a day 30–40 minutes before meals, the capsules are taken whole without chewing, drinking 15–200 mg of water. if this is not possible, the capsule can be opened and its contents dissolved in a small amount of apple juice (approximately 1 full spoon) and swallowed immediately without chewing. the same procedure must be carried out if the drug is administered through a nasogastric tube.

The question of dosage and duration of treatment is decided by the doctor, depending on the clinical situation and the nature of the course of the disease.

The maximum daily dose is 60 mg; for patients with impaired liver function - 30 mg. In patients with Zollinger-Ellison syndrome, doses may be increased.

If it is necessary to take 2 daily doses, the patient should take one before breakfast, the second before dinner.

If the patient did not take the drug at the appointed time, he should take it as soon as possible. If there is little time left before taking the next dose, the patient should not take a double dose.

Duodenal ulcer: the dose of the drug for the treatment of active ulcers is 30 mg once a day for 2–4 weeks.

The dose for the treatment of ulcers caused by NSAIDs is 30 mg 1 time per day. The duration of treatment is 4-8 weeks.

Peptic ulcer of the stomach: the dose of the drug for the treatment of active ulcers is 30 mg once a day for 8 weeks. The dose for the treatment of ulcers caused by NSAIDs is 30 mg 1 time per day for 4-8 weeks.

Gastroesophageal reflux disease: for moderate and severe forms of esophagitis, the recommended dose is 30 mg once a day for 4 weeks. If erosive esophagitis is not cured for 4 weeks, the duration of treatment can be increased by 2 times.

The dose for long-term prophylaxis of recurrence of erosive esophagitis is 30 mg 1 time per day. The safety and effectiveness of lansoprazole therapy has been confirmed for a 12-month administration.

Zollinger-Ellison syndrome: the dose of the drug is selected so that the basal acid secretion does not exceed 10 mmol / h. The recommended starting dose is 60 mg once daily before breakfast.If the patient takes doses higher than 120 mg, then he should take the first half of the daily dose before breakfast, and the second before dinner. Treatment lasts until the clinical symptoms disappear.

Eradication of Helicobacter pylori: the dose is 30 mg 2 times a day (before breakfast and dinner). The patient should take the drug along with antibiotics according to the approved scheme for 1-2 weeks.

Renal and liver failure. Patients with impaired liver and kidney function of mild to moderate degree do not require dose adjustment. Patients with severely impaired liver function should take the minimum effective dose, but not more than 30 mg / day.

Elderly patients. When using the drug, dose adjustment is not required.

Contraindications

Hypersensitivity to lansoprazole or any other component of the drug. During pregnancy and breastfeeding. childhood.

Side effects

During treatment, adverse reactions such as abdominal pain, diarrhea, nausea, and most often diarrhea were often reported. also in more than 1% of cases, headache was reported. additional adverse reactions that were detected in 1% of patients who participated in internal clinical trials and in the post-marketing period are as follows.

The body as a whole: anaphylactoid reactions, asthenia, fatigue, candidiasis, chest pain (not always specific), swelling, fever, flu-like syndrome, bad breath, infections (not always non-specific), weakness.

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

From the gastrointestinal tract: anorexia, cardiospasm, cholelithiasis, constipation, vomiting, hepatotoxicity, jaundice, hepatitis, candidiasis of the esophagus, gastrointestinal tract, dry mouth, thirst, dyspepsia, dysphagia, belching, esophageal stenosis, esophageal ulcer, ezor, color , polyps of the stomach, gastroenteritis, colitis, gastrointestinal hemorrhages, vomiting of blood, increased or decreased appetite, increased salivation, melena, rectal hemorrhages, stomatitis, taste disorders, glossitis, pancreatitis, tenesmus, ulcerative colitis.

From the endocrine system: diabetes mellitus, goiter, hyperglycemia / hypoglycemia.

On the part of the blood and lymphatic systems: anemia, hemolysis, agranulocytosis, aplastic anemia, hemolytic anemia, leukopenia, neutropenia, pancytopenia, thrombocytopenia, eosinophilia, thrombotic and thrombocytopenic purpura.

From the musculoskeletal system and connective tissue: arthritis / arthralgia, musculoskeletal pain, myalgia.

From the nervous system: agitation, amnesia, agitation, apathy, depression, impaired consciousness, vertigo, hallucinations, hemiplegia, hostility, fear, decreased / increased libido, nervousness, insomnia, drowsiness, tremor, paresthesia, impaired thinking, confusion.

From the respiratory system: asthma, bronchitis, increased cough, shortness of breath, nosebleeds, pulmonary hemorrhage, hiccups, pneumonia, inflammation / infection of the upper respiratory tract, pharyngitis, rhinitis.

From the skin and subcutaneous tissue: angioedema, erythema multiforme, toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema polyforma, acne, facial flushing, alopecia, pruritus, rash, urticaria, purpura, petechiae, hyperhidrosis, photosensitivity.

From the sensory organs: blurred vision, deafness, eye pain, taste change, tinnitus, visual field defects, speech disorders, otitis media.

From the genitourinary system: menstruation, albuminuria, breast enlargement / gynecomastia, breast tenderness, glucosuria, hematuria, impotence, kidney stones, urinary retention.

Combination therapy with amoxicillin and clarithromycin. In clinical trials during the combination therapy of lanzoprazole with amoxicillin and clarithromycin, there are no specific adverse reactions characteristic of combination therapy. Adverse reactions that occur during combination therapy are characteristic of lanzoprazole, amoxicillin and clarithromycin.

The most common adverse reactions in patients receiving triple therapy (lanzoprazole / clarithromycin / amoxicillin) for 14 days were diarrhea, headache, and a change in taste. There were no differences in the frequency of adverse reactions during triple therapy for 10 and 14 days. Differences in the manifestations of adverse reactions during triple and double therapy were not noted. The most common adverse reactions when conducting dual therapy of lanzoprazole with amoxicillin are diarrhea and headache.

Adverse reactions were not prolonged and did not require discontinuation of treatment.

Laboratory changes. Indicators of impaired liver function, increased levels of AlAT, AsAT, alkaline phosphatase, creatinine, globulins, gamma-glutamyl transpeptidases, increased / decreased leukocyte levels, violation of the albumin / globulin ratio, changes in the number of red blood cells, hyperbilirubinemia, eosinophilia, hyperlipidemia, increased / decreased electrolytes, increased / decreased electrolytes Cholesterol, increased levels of glucocorticoids, increased LDL levels, increased / decreased platelets, increased gastrin levels, a positive test for occult blood. In the urine - albuminuria, glucosuria, hematuria.

In patients receiving lansoprazole, at the end of treatment, an increase in the level of liver enzymes was more than 3 times higher than the upper limit of normal. During treatment, one of these patients did not experience jaundice. When conducting combination therapy (lansoprazole with clarithromycin and amoxicillin) and lansoprazole with amoxicillin, there are no changes in laboratory parameters specific to combination therapy.

special instructions

Before prescribing the drug lansoprol, the possibility of malignant neoplasms in the stomach and esophagus should be excluded.

When conducting combination therapy with clarithromycin and amoxicillin with warnings regarding the use of these drugs, you must read the instructions for use of these drugs. When using antibacterial agents, pseudomembranous colitis may occur, sometimes life-threatening. Therefore, it is important to consider this if patients have diarrhea. You should also pay attention to the beginning of the use of amoxicillin and clarithromycin for a history of hypersensitivity reactions to penicillins, cephalosporins and other allergens.

In patients with renal failure, binding to blood proteins is reduced by 1–1.5%. In patients with varying degrees of chronic liver failure T_½ from blood plasma increases from 1.5 to 3.2–7.2 hours. In patients with severe hepatic insufficiency, the dose of the drug should be reduced.

Elderly patients. The treatment of ulcers in elderly patients is practically no different from that in younger patients. Adverse reactions and laboratory changes in the elderly are the same as in younger patients.

During pregnancy and breastfeeding. During pregnancy and lactation, the drug is not used. If necessary, the use of the drug should stop breast-feeding.

Interactions

Lansoprazole is metabolized using the cytochrome p450 system, especially cyp 3a and cyp 2c19. studies conducted with lansoprazole do not show sufficient clinical interaction with other drugs metabolized by the cytochrome p450 system (warfarin, antipyrine, indomethacin, ibuprofen, phenytoin, propranolol, prednisolone, diazepam, clarithromycin or terfenadine). these drugs are metabolized using the p450 cytochrome system, including cyp 1a2, cyp 2c 9, cyp 2c19, cyp 2d6 and cyp 3a.with the simultaneous use of lansoprazole with theophylline (cyp 1a2, cyp 3a), a moderate increase (10%) in theophylline clearance is noted, but the clinical significance of their interactions is unlikely, however, to support clinically effective theophylline concentrations in individual patients, dose adjustment of theophylline is required at the beginning or upon termination of treatment lansoprazole.

There are no clinical manifestations of interactions with amoxicillin.

In a cross-sectional study with lanzoprazole 30 mg, omeprazole 20 mg and the simultaneous use of sucralfate 1 g, with the simultaneous use of sucralfate, the absorption of proton pump inhibitors and the bioavailability of lansoprazole and omeprazole are reduced by 17 and 16%, respectively. Therefore, proton pump inhibitors should be taken 30 minutes before taking sucralfate. With the simultaneous use of antacids and lansoprazole in a clinical trial, there is no effect on their effect. Lansoprazole causes prolonged suppression of gastric secretion, so it is theoretically possible that lansoprazole can affect the bioavailability of drugs for which pH is important when absorbed (ketoconazole, ampicillin esters, iron salts, digoxin).

Lansoprazole, like other proton pump inhibitors, reduces the concentration of atazanavir (an HIV protease inhibitor), the absorption of which depends on gastric acidity, and therefore can affect the therapeutic effect of atazanavir and the development of resistance to HIV infection.

In clinical studies in healthy volunteers, it has been shown that lansoprazole does not affect the pharmacokinetics of warfarin and prothrombin time. An increase in INR and prothrombin time can lead to bleeding and even death.

Tacrolimus. With the simultaneous use of lansoprazole and tacrolimus, the concentration of tacrolimus in the blood may increase, especially in patients who underwent transplantation.

Overdose

There are no reports of cases of overdose of lansoprazole. a single dose of 600 mg was not accompanied by clinical manifestations of an overdose. however, with an overdose, an increase in the severity of adverse reactions is possible.

Treatment. There is no specific antidote. Hemodialysis is ineffective. To reduce the absorption of the drug, it is necessary to take activated charcoal. In case of taking an excessive dose, symptomatic and supportive therapy is performed.

Storage conditions

Store at a temperature not exceeding 25 ° c.