Lansoprazole - instructions for use, dose, side effects, contraindications

Excipients: 161.5 mg or 323.0 mg (sugar pellets (sucrose) 14.94 or 29.88 mg, sugar syrup (sucrose) 35.60 mg or 71.20 mg, mannitol 44.82 mg or 89.64 mg, carmelose calcium 7.47 mg or 14.94 mg, magnesium carbonate 2.39 mg or 4.78 mg, sodium phosphate disubstituted 1.05 mg or 2.10 mg, sodium lauryl sulfate 0.04 mg or 0.08 mg, povidone K-30 0.18 mg or 0.36 mg, polysorbate-80 0.57 or 1.14 mg, hypromellose 10,99 mg or 21,98 mg, acrylic coating L30DA 33.22 mg or 66.44 mg, talc 4.30 mg or 8.60 mg, macrogol 4.30 mg or 8.60 mg, titanium dioxide 1.41 mg or 2.82 mg, sodium hydroxide 0.22 mg or 0.44 mg); capsules hard gelatinous "Coni Snape" No. 3 (for dosage of 15 mg): titanium dioxide 1.44 mg, indigocarmine 0.06 mg, gelatin up to 48 mg;

capsules hard gelatinous "Coni Snape" No. 1 (for dosage of 30 mg): titanium dioxide 2.28 mg, iron oxide dye yellow 1.3 mg, indigocarmine 0.23 mg, gelatin to 76 mg.

Description:Tgelatin capsules No. 3 (for a dosage of 15 mg) with a white body and a blue lid or No. 1 (for a dosage of 30 mg) with a white body and a lid of green color. The contents of the capsules are white or almost white spherical pellets.

Pharmacotherapeutic group:The iron of the stomach secretion is a reducing agent - a proton pump inhibitor

ATX: & nbsp

A.02.B.C Proton pump inhibitors

A.02.B.C.03 Lansoprazole

Pharmacodynamics:

Antiulcer. Specific proton pump inhibitor (H + K + ATPase); metabolized in parietal cells of the stomach to active sulfonamide derivatives, which inactivate the sulfhydryl groups of H + K + ATPase. It blocks the final stage of synthesis of hydrochloric acid, reducing basal and stimulated secretion, regardless of the nature of the stimulus. Possessing high lipophilicity, it easily penetrates into parietal cells of the stomach and concentrates in them.It has a cytoprotective effect, increasing oxygenation of the gastric mucosa, increasing the secretion of bicarbonate.

The rate and degree of inhibition of basal and stimulated secretion of hydrochloric acid are dose-dependent. After taking 30 mg of lansoprazole, the pH begins to rise after 2-3 hours. The inhibition of production of hydrochloric acid at a dose of 30 mg - 80-97%. Does not affect the motility of the gastrointestinal tract (GIT). Inhibitory effect increases in the first 4 days of admission. After stopping the intake, the acidity for 39 hours remains below 50% basal level, "ricochet" increase in secretion is not noted. Secretory activity is normalized 3-4 days after the end of the drug intake.

In patients with Zollinger-Ellison syndrome, it is more prolonged. Increases the concentration of pepsinogen in the blood serum and inhibits the production of pepsin.

Promotes the formation of gastric mucosa specific IgA Helicobacter pylori, suppressing their growth, increases the anti-Helicobacter activity of other drugs.

Reduces the blood flow in the antrum part of the stomach, the gatekeeper, the bulb of the duodenum by an average of 17%, inhibits the motor-evacuation function of the stomach.

Increases the concentration of gastrin in serum by 50-100% (the concentration of gastrin reaches the plateau after 2 months of treatment and returns to the initial values after the end of the course of treatment).

Effective in the treatment of peptic ulcer of stomach and duodenal, resistant to blocker H₂-gistaminovyh receptors. Provides faster healing of ulcerative defects in the duodenum (85% of duodenal ulcers heal after 4 weeks of treatment at a dose of 30 mg / day). With reflux esophagitis, complete cure of patients is noted by the end of 8 weeks. intake (30 mg / day) in 88.7%.

Pharmacokinetics:

Suction. Absorption - high, bioavailability more than 80 %. Eating lowers absorption and bioavailability (by 50%), but the inhibitory effect on gastric secretion does not change, regardless of food intake. Maximum concentration (FROM_mOh) in the blood plasma after oral administration of 30 mg of lansoprazole is 0.75-1.15 mg / l and is achieved after 1.5-2.2 hours.

Distribution. Connection with blood plasma proteins - 97,7-99,4%. Distribution in tissues, mainly in the gastric lining cells. The volume of distribution is 0.5 l / kg. Penetrates through the blood-brain barrier.It is determined in the milk of rats. The isolation in human milk of a person is unknown.

Metabolism. Actively metabolized by "primary passage" through the liver with the participation of isoenzyme CYP2C19 and (slightly) CYP3A4 with the formation of sulphinyl, sulphone and hydroxy derivatives. Is a substrate and an inhibitor CYP2C19, a substrate CYP3A4, as well as a substrate and an inhibitor of P-glycogen.

Excretion. It is excreted as metabolites through the kidneys (4-23%) and with bile (up to 75%). The half-life is about 1.5 hours, in elderly patients it is 1.9-2.9 hours, with a violation of liver function - 3.2-7.2 hours. Renal insufficiency does not significantly affect the rate and amount of excretion. Lansoprazole and its metabolites are poorly dialysed. Correction of the dose of the drug in patients on hemodialysis, or after a hemodialysis session, is not required.

Linearity. In the dose range of 15 to 60 mg, the pharmacokinetics of lansoprazole are linear - concentrations are proportional to the dose, the parameters are constant and no cumulation occurs. The effectiveness of the drug depends on genetic polymorphism CYP2C19 (inhibition of gastric secretion is most pronounced in "slow metabolizers").

Indications:

- Treatment and prevention of exacerbations of peptic ulcer of the stomach and duodenum;

- treatment and prevention of erosive and ulcerative lesions of the stomach and duodenum, associated with the use of non-steroidal anti-inflammatory drugs (NSAIDs), (NSAIDs-gastropathy);

- gastroesophageal reflux disease (GERD), including erosive-ulcerative reflux esophagitis and non-erosive forms of reflux disease (NERD);

- erosive and ulcerative lesions of the stomach and duodenum, associated with Helicobacter pylori (as part of combination therapy);

- Zollinger-Ellison syndrome and other pathological conditions, accompanied by increased acid secretion in the stomach.

Contraindications:

- Hypersensitivity to the components of the drug;

- pregnancy (I trimester);

- Children under 18 years of age (due to the lack of data on the use of the drug in children);

- deficiency of sucrose isomaltase, intolerance to fructose, glucose-galactose malabsorption.

Carefully:

With caution appoint patients with hepatic and / or renal failure, pregnancy (II-III trimesters), malignant neoplasms of the gastrointestinal tract, the elderly.

Concomitant clopidogrel therapy (except when absolutely indicated, after a full assessment of the risks and benefits of treatment).

Pregnancy and lactation:

The experience with lansoprazole in pregnant women is limited.

The drug is contraindicated in pregnancy (I trimester). Application in II-III trimester is permissible only in cases where the expected benefit of using the drug for the mother justifies the possible risk to the fetus.

It is not known whether lansoprazole in breast milk. If it is necessary to prescribe the drug during lactation, breastfeeding should be discontinued.

Dosing and Administration:

Inside. Capsules should be swallowed whole, not liquid. Preferably with a single admission per day, the drug should be taken in the morning, before breakfast, but perhaps in the evening, before supper. If necessary, twice taken before breakfast and dinner. If you can not swallow the whole capsule, its contents can be mixed with a small amount of apple juice (about 1 full tablespoon) and immediately swallowed without chewing. You can also enter through the probe.

The maximum daily dose - 60 mg, in the case of Zolinger-Ellison syndrome - may be higher.

- PIn duodenal ulcer in the phase of exacerbation - 30 mg / day for 2-4 weeks (in resistant cases to 60 mg / day);

- with gastric ulcer in the phase of exacerbation - 30 mg once a day for 4-8 weeks;

- erosive-ulcerative lesions of the stomach and duodenum associated with the administration of NSAIDs (NSAIDs) - 30 mg per day for 4-8 weeks;

- GERD, including reflux esophagitis and NERB - 30 mg per day for 4-8 weeks. In case of erosive esophagitis, if necessary, the duration of therapy can be doubled;

- for eradication Helicobacter pylori - 30 mg twice a day for 10-14 days in combination with antibacterial drugs;

- anti-relapse treatment of peptic ulcer of the stomach and duodenum - 15 mg / day. The efficacy and safety of 12-month therapy with lansoprazole has been proven;

- anti-relapse treatment of erosive esophagitis - 15 mg / day. The efficacy and safety of 12-month therapy with lansoprazole has been proven;

- anti-relapse treatment of erosive and ulcerative lesions of the stomach and duodenum, as well as dyspeptic symptoms when taking NSAIDs - 30 mg per day;

- With Zollinger-Ellison syndrome, the dose is selected individually, until basal acid production is less than 10 mmol / h. A starting dose of 60 mg once a day is recommended. If necessary, a daily dose of 120 mg is recommended to be used in two divided doses. The duration of therapy is determined by the doctor;

- with hepatic failure in elderly patients, treatment starts with half the doses, gradually increasing them to the recommended, but not more than 30 mg per day.

Side effects:

The frequency of side effects was estimated as follows: very often (> 1/10); often (> 1/100, <1/10); infrequently (> 1/1000, <1/100); rarely (> 1/10000, <1/1000); Very rarely (<1/10000), the frequency is unknown (the incidence of side effects can not be estimated based on available data).

Violations of the blood and lymphatic system: rarely - thrombocytopenia (with hemorrhagic manifestations), leukopenia, eosinophilia, pancytopenia, agranulocytosis; very rarely anemia.

Immune system disorders: rarely - hives, angioedema, very rarely - anaphylactic reactions, frequency unknown - multiforme exudative erythema;

Disorders from the metabolism and nutrition: rarely - anorexia, increased appetite;

Disorders from the psyche: infrequently - depression, anxiety;

Disturbances from the nervous system: often - headache; infrequently - dizziness, drowsiness, confusion;

Disturbances on the part of the organ of sight: often - pain in the eyes, impaired vision;

Hearing disorders and labyrinthine disturbances: frequency unknown - tinnitus;

Disturbances from the respiratory system, chest and mediastinal organs: rarely - cough, pharyngitis, rhinitis, upper respiratory tract infection;

Disorders from the digestive system: often constipation; infrequent - increased or decreased appetite, nausea, abdominal pain, diarrhea; frequency unknown - nonspecific ulcerative colitis, candidiasis of the gastrointestinal tract;

Disturbances from the skin and subcutaneous tissues: rarely - skin itching, purpura, petechiae; frequency unknown - toxic epidermal necrolysis, Stevens-Johnson syndrome; frequency unknown - skin rash, photosensitivity;

Disturbances from musculoskeletal and connective tissue: rarely - pain in the joints, muscles and bones;

Disorders from the kidneys and urinary tract: rarely - interstitial nephritis, renal insufficiency, creatininemia; frequency unknown - urogenital disorders;

Violations of the genitals and breast: frequency unknown - erectile dysfunction, gynecomastia.

General disorders and disorders at the site of administration: infrequently - malaise, rarely - alopecia, flu-like syndrome.

Laboratory and instrumental data: rarely - increased activity of "liver" transaminases (ALT, ACT, GGT, APF and LDH), hyperbilirubinemia.

Overdose:

Overdose Symptoms in humans are not described. Admission of 600 mg of lansoprazole did not cause the patient any adverse effects. In an animal experiment, the administration of lansoprazole at doses exceeding the daily recommended daily dose of up to 1600 times did not cause fatalities or any clinical abnormalities.

In case of taking high doses of the drug at the prehospital stage shown observation, gastric lavage, cleansing enema, reception of activated charcoal. There is no specific antidote. The patient should be under medical supervision.Hemodialysis is ineffective.

Interaction:

Lansoprazole causes a prolonged severe inhibition of the acidity of gastric juice, so it can reduce the absorption of drugs with pH-dependent absorption and bioavailability - azole antifungal agents (ketoconazole, intraconazole, posaconazole), oral cephalosporins (cefpodoxime, cefuroxime), ampicillin, antiretroviral drugs (indinavir, nelfinavir, atazanavir). When combined with lansoprazole, one should keep in mind the potential decrease in their effectiveness and the appearance of resistance.

Against the background of an increase in the pH of the gastric contents, the release rate of the active components from the enteric-coated dosage forms may increase due to premature degradation of the coating, which increases the risk of side effects of drugs taken with lansoprazole.

Lansoprazole reduces absorption salts of iron, digoxin.

Slows absorption cyanocobalamin.

Sucralfate reduces the absorption and bioavailability of lansoprazole. It should be taken 30-40 minutes after taking lansoprazole.

Antacids slow down and reduce the absorption of lansoprazole, should be taken 1 hour before admission or 1-2 hours after taking lansoprazole.

Lansoprazole is metabolized with the participation of isozymes of the system cytochrome P450 CYP2C19 and CYP3A4; when combined, strong inducers CYP2C19 and CYP3A4 can increase the metabolism of lansoprazole, inhibitors CYP2C9 - reduce the metabolism of lansoprazole.

Lansoprazole in vivo slows down the elimination of drugs metabolized in the liver by microsomal oxidation (diazepam, ibuprofen, indomethacin, clarithromycin, prednisone, propranolol, phenytoin, terfenadine, indirect anticoagulants, phenytoin). There are no clinically significant interactions with diazepam, ibuprofen, indomethacin, prednisone, propranolol, phenytoin, oral contraceptives.

Joint application with clopidogrel can reduce its antiplatelet activity (possible mechanism - inhibition of mediated CYP2C9 metabolic activation of clopidogrel).

Ritonavir (substrate and inhibitor CYP2C9) can have a variable effect on the area under the "concentration-time" curve (AUC) lansoprazole (increase or decrease). If necessary, concomitant therapy is recommended to control the therapeutic and possible side effects, as well as dose adjustment of lansoprazole.

Repeated administration of lansoprazole induces metabolism and increases (up to 19%) clearance theophylline (CYP1A2, CYP3A4). When initiating or reversing therapy with lansoprazole, additional dose titration may be required theophylline to provide clinically meaningful concentrations in the blood.

When combined with clarithromycin (CYP3A4) in the blood plasma, concentrations of lansoprazole and 14-hydroxy-clarithromycin increase (increased anti-Helicobacter activity).

Lansoprazole has no clinically significant interaction with amoxicillin.

When combined with warfarin (CYP2C9, CYP1A2, CYP3A4) there may be an increased risk of bleeding.

Voriconazole. When combined, a significant increase in the maximum concentration of lansoprazole is possible, which may require a reduction in its dose by half.

It is not excluded interaction with a number of drugs that are substrates, inhibitors or inducers of P-glycoprotein (cimetidine, tacrolimus, nifedipine, ketoconazole, amitriptyline).

When combined, an increase in bioavailability and suppression of P-gipoprotein-mediated elimination digoxin, it is necessary to monitor the concentration of digoxin. When combined with inhibitors of HMG-CoA reductase (lovastatin, simvastatin, atorvastatin) may increase the bioavailability of statin (mechanism - competitive inhibition of intestinal P-glycoprotein with a decrease in secretion of statin in the lumen of the intestine, as well as competitive inhibition of metabolism CYP3A4) - the risk of myotoxicity.

Preparations of St. John's wort (inductor CYP3A4) can increase metabolism and reduce the effectiveness of lansoprazole. You should avoid sharing.

Special instructions:

Before and after treatment, endoscopic control is necessary to exclude malignant neoplasm, because treatment can mask symptoms and make diagnosis difficult. To display a noticeable effect of therapy, it may take from 1 to 4 days.

Consult a physician if necessary with the concomitant use of other drugs.

It is recommended to avoid joint use of proton pump inhibitors and clopidogrel. When combined, the risk of repeated myocardial infarction, hospitalization for a heart attack or unstable angina, stroke, repeated revascularization increases. With the unconditional need for co-administration, patients should be carefully observed.

It is recommended to avoid joint use of proton pump inhibitors and antiretroviral drugs in HIV-infected patients. If it is necessary to use together with atazanavir / ritonavir, it is recommended to observe a 12-hour interval between taking lansoprazole and these drugs, as well as not to exceed the dose of lansoprazole 30 mg.

When combined with antiretroviral drugs (indinavir, nelfinavir, atazanavir), as well as ketoconazole, intraconazole, posaconazole, cefpodoxime, cefuroxime and ampicillin, it is necessary to monitor their effectiveness and the appearance of resistance.

Co-administration with imatinib may increase the risk of adverse reactions (potential interaction through CYP3A4), especially in persons with severe allergic reactions in the history.

In connection with an increased risk of myotoxicity, patients taking atorvastatin, lovastatin or simvastatinshould be carefully observed during the concomitant use of lansoprazole.

In patients who simultaneously take warfarin, it is necessary to monitor prothrombin time and INR (international normalized ratio).

Prolonged use of proton pump inhibitors increases the risk of infection (incl. Salmonella, Campylobacter, Clostridium difficile).

The use of bleeding prevention from the upper gastrointestinal tract should be correlated with the potential development of a ventilator-associated pneumonia.

Prolonged use of proton pump inhibitors increases the risk of fractures in women during menopause.

During the treatment should be avoided the use of alcoholic beverages.

The pharmacogenetic factor. The effectiveness of the drug depends on genetic polymorphism CYP2C19. In patients belonging to the "slow metabolizers" (PM-type), the efficacy is higher, eradication is achieved more reliably Helicobacter pylori compared with "fast metabolizers" (homEMtype), even against a background of resistance to clarithromycin.

The "withdrawal syndrome" or "acid rebound", while observing the recommendations for the duration of lansoprazole, is not typical.

Effect on the ability to drive transp. cf. and fur:

Due to the fact that in individuals, taking the drug may be accompanied by drowsiness and dizziness, care should be taken to establish an individual response to the drug. As a rule, in recommended doses the drug does not affect the speed of psychomotor reactions and concentration of attention.

Form release / dosage:

Capsules enteric, 15 mg and 30 mg.

Packaging:

For 7 or 10 capsules in a contour mesh box made of polyvinylchloride film and aluminum foil printed lacquered.

For 30, 50 or 100 capsules in cans of polymer from polyethylene, or in cans of polymeric polyethylene or polypropylene with a screw neck and a cap screwed from polyethylene for vitamins and medicines or in cans of polymeric polyethylene or polypropylene with a shock absorber and a lid stretched from polyethylene for vitamins and medicines, or polymeric banks of polyethylene terephthalate for drugs with means of capping of polyethylene or polypropylene.

Each jar or 1, 2 or 4 contour cell packs of 7 capsules, or 1, 2, 3 or 5 contour cell packs of 10 capsules together with instructions for use are placed in a pack of cardboard box.

Storage conditions:

In a dry, the dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use the product after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-003626

Date of registration:13.05.2016

Expiration Date:13.05.2021

The owner of the registration certificate:MEDISORB, CJSC MEDISORB, CJSC Russia

Manufacturer: & nbsp

MEDISORB, CJSC Russia

Information update date: & nbsp15.02.2018

Illustrated instructions

Instructions

Lansoprazole (Lansoprazole)