Pharmacological properties
Lansoprazole inhibits the activity of the proton pump H+/K+-ATPase in the parietal cells of the gastric mucosa. Thus, lansoprazole inhibits the final stage of gastric acid formation, reduces the amount and acidity of gastric juice, as a result of which its harmful effects on the mucous membrane are reduced.
The degree of inhibition is determined by the dose and duration of treatment. Even a single dose of 30 mg of lansoprazole inhibits gastric acid secretion by 70-90%. The effect occurs within 1 or 2 hours and lasts for 24 hours.
Lansoprazole is absorbed in the intestine. In healthy patients, when taking 30 mg of lansoprazole, 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 taking the drug.
The binding of the drug to blood plasma proteins is 98%.
Lansoprazole is excreted from the body with bile and urine (only in the form of metabolites - lansoprazole sulfone and hydroxyl lansoprazole), with 21% of the dose of the drug excreted in the urine per day. T ½ is 1.5 hours.
T½ increases in patients with severe hepatic impairment and in patients over 69 years of age. In patients with renal impairment, the absorption of lansoprazole is practically unchanged.
Indication
Gastric and duodenal ulcers, including those associated with the use of nonsteroidal anti-inflammatory drugs, gastroesophageal reflux disease, Zollinger-Ellison syndrome, for the eradication of Helicobacter pylori (in combination with antibiotics).
Application
Adults take orally. Usually the dose is 30 mg once a day 30-40 minutes before meals, the capsules are taken whole without chewing, with 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 performed if the drug is administered through a nasogastric tube.
The dosage and duration of treatment are decided by the doctor depending on the clinical situation and the nature 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 and the second before dinner.
If the patient misses a dose, he should take it as soon as possible. If it is almost time for the next dose, the patient should not take a double dose.
Duodenal ulcer: The dose for the treatment of an active ulcer is 30 mg once daily for 2-4 weeks.
The dose for the treatment of ulcers caused by taking nonsteroidal anti-inflammatory drugs is 30 mg once a day. The duration of treatment is 4-8 weeks.
Peptic ulcer: The dose for the treatment of active ulcers is 30 mg once daily for 8 weeks. The dose for the treatment of ulcers caused by nonsteroidal anti-inflammatory drugs is 30 mg once daily for 4-8 weeks.
Gastroesophageal reflux disease: for moderate to severe esophagitis, the recommended dose is 30 mg once daily for 4 weeks. If erosive esophagitis does not resolve within 4 weeks, the duration of treatment may be doubled.
The dose for long-term prevention of relapse of erosive esophagitis is 30 mg once daily. The safety and efficacy of lansoprazole therapy have been confirmed for 12 months of treatment.
Zollinger-Ellison syndrome: the dose of the drug is selected so that the basal acid secretion does not exceed 10 mmol / h. The recommended initial dose is 60 mg 1 time per day 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 continues until the disappearance of clinical symptoms.
Eradication of Helicobacter pylori: the dose is 30 mg 2 times a day (before breakfast and dinner). The patient should take the drug together with antibiotics according to the approved regimen, for 1-2 weeks.
Renal and hepatic insufficiency. Patients with mild to moderate hepatic and renal impairment do not require dose adjustment. Patients with severe hepatic impairment should take the minimum effective dose, but not more than 30 mg/day.
Elderly patients: No dose adjustment is required when using the drug.
Contraindication
Hypersensitivity to lansoprazole or any other component of the drug. Pregnancy and breastfeeding. Children's age.
Side effects
During treatment, adverse reactions such as abdominal pain, diarrhea, nausea were commonly reported, most commonly diarrhea. Headache was also reported in more than 1% of cases. Additional adverse reactions observed in 1% of patients participating in internal clinical trials and in the post-marketing period are as follows.
Body as a whole: anaphylactoid reactions, asthenia, fatigue, candidiasis, chest pain (not always specific), edema, fever, flu-like syndrome, bad breath, infections (not always nonspecific), weakness.
Gastrointestinal: anorexia, cardiospasm, cholelithiasis, constipation, vomiting, hepatotoxicity, jaundice, hepatitis, candidiasis of the esophagus, gastrointestinal tract, dry mouth, thirst, dyspepsia, dysphagia, belching, esophageal stenosis, esophageal ulcer, esophagitis, stool discoloration, flatulence, gastric polyps, gastroenteritis, colitis, gastrointestinal hemorrhage, vomiting blood, increased or decreased appetite, increased salivation, melena, rectal hemorrhage, stomatitis, taste disorders, glossitis, pancreatitis, tenesmus, ulcerative colitis.
On the part of the endocrine system: diabetes mellitus, goiter, hyperglycemia/hypoglycemia.
From the blood and lymphatic system: anemia, hemolysis, agranulocytosis, aplastic anemia, hemolytic anemia, leukopenia, neutropenia, pancytopenia, thrombocytopenia, eosinophilia, thrombotic and thrombocytopenic purpura.
Musculoskeletal and connective tissue disorders: arthritis/arthralgia, musculoskeletal pain, muscle pain.
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.
Respiratory system: asthma, bronchitis, increased cough, shortness of breath, nosebleed, pulmonary hemorrhage, hiccups, pneumonia, inflammation/infection of the upper respiratory tract, pharyngitis, rhinitis.
Skin and subcutaneous tissue disorders: angioedema, erythema multiforme, toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme, acne, facial flushing, alopecia, pruritus, rash, urticaria, purpura, petechiae, hyperhidrosis, photosensitivity.
From the sensory organs: blurred vision, deafness, eye pain, change in taste, tinnitus, visual field defects, speech disorders, otitis media.
From the genitourinary system: menstrual disorders, albuminuria, breast enlargement/gynecomastia, breast tenderness, glycosuria, hematuria, impotence, kidney stones, urinary retention.
Combination therapy with amoxicillin and clarithromycin. In clinical studies, there were no specific adverse reactions characteristic of combination therapy when lansoprazole was administered with amoxicillin and clarithromycin. The adverse reactions that occurred with combination therapy were characteristic of lansoprazole, amoxicillin and clarithromycin.
The most common adverse reactions in patients receiving triple therapy (lansoprazole/clarithromycin/amoxicillin) for 14 days were diarrhea, headache, and taste perversion. There were no differences in the incidence of adverse reactions between triple therapy for 10 and 14 days. There were no differences in the incidence of adverse reactions between triple and dual therapy. The most common adverse reactions with dual therapy of lansoprazole and amoxicillin were diarrhea and headache.
Adverse reactions were not prolonged and did not require discontinuation of treatment.
Laboratory changes. Liver function tests, increased ALT, AST, LF, creatinine, globulins, gammaglutamyl transpeptidase, increased/decreased leukocyte count, albumin/globulin ratio, change in erythrocyte count, hyperbilirubinemia, eosinophilia, hyperlipidemia, increased/decreased electrolytes, increased/decreased cholesterol, increased glucocorticoids, increased LDL, increased/decreased platelets, increased gastrin, positive occult blood test. Urine - albuminuria, glucosuria, hematuria.
In patients receiving lansoprazole, elevations of liver enzymes to more than 3 times the upper limit of normal have been reported at the end of treatment. One of these patients did not develop jaundice during treatment. There were no laboratory changes specific to the combination therapy (lansoprazole with clarithromycin and amoxicillin) and lansoprazole with amoxicillin.
Special instructions
Before prescribing Lansoprazole, the possibility of malignant neoplasms in the stomach and esophagus should be excluded.
When carrying out combination therapy with clarithromycin and amoxicillin, it is necessary to familiarize yourself with the precautions regarding the use of these drugs in 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 when patients have diarrhea. Also, before starting the use of amoxicillin and clarithromycin, attention should be paid to the presence of a history of hypersensitivity reactions to penicillins, cephalosporins and other allergens.
In patients with renal failure, binding to blood proteins decreases 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 liver failure, the dose of the drug should be reduced.
Pregnancy and breastfeeding. The drug is not used during pregnancy and breastfeeding. If necessary, use of the drug should be discontinued.
Interactions
Lansoprazole is metabolized by the cytochrome P450 system, particularly CYP 3A and CYP 2C19. Studies with lansoprazole do not indicate sufficient clinical interaction with other drugs that are metabolized by the cytochrome P450 system (warfarin, antipyrine, indomethacin, ibuprofen, phenytoin, propranolol, prednisolone, diazepam, clarithromycin, or terfenadine). These drugs are metabolized by the cytochrome P450 system, including CYP 1A2, CYP 2C9, CYP 2C19, CYP 2D6, and CYP 3A. When lansoprazole is used simultaneously 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 maintain clinically effective theophylline concentrations in individual patients, theophylline dose adjustment is required at the beginning or termination of treatment with lansoprazole.
There are no clinical manifestations of interactions with amoxicillin.
In a cross-over study conducted with lansoprazole 30 mg, omeprazole 20 mg and concomitant sucralfate 1 g, the absorption of proton pump inhibitors and the bioavailability of lansoprazole and omeprazole were reduced by 17 and 16%, respectively, when sucralfate was administered concomitantly. Therefore, proton pump inhibitors should be taken 30 minutes before sucralfate. In a clinical study, the simultaneous use of antacids and lansoprazole had no effect on their action. Lansoprazole causes prolonged inhibition of gastric secretion, so it is theoretically possible that lansoprazole may affect the bioavailability of drugs for which pH is important for absorption (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 may affect the therapeutic effect of atazanavir and the development of resistance to HIV infection.
In clinical studies in healthy volunteers, lansoprazole has been shown to have no effect on the pharmacokinetics of warfarin and prothrombin time. An increase in INR and prothrombin time may lead to bleeding and even death.
Tacrolimus: Concomitant use of lansoprazole and tacrolimus may increase the concentration of tacrolimus in the blood, especially in transplant patients.
Overdose
There are no reports of cases of overdose with lansoprazole. A single dose of 600 mg was not accompanied by clinical manifestations of overdose. However, in case of overdose, increased adverse reactions are 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 overdose, symptomatic and supportive therapy is performed.
Storage conditions
Store at a temperature not exceeding 25 °C.
