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

1 the vial contains: active substance: omeprazole sodium monohydrate - 42.56 mg (equivalent to 40 mg omeprazole); Excipients: disodium edetate dihydrate - 1.5 mg, sodium hydroxide (used for conditioning pH up to the required value) q.s.

Description:

Lyophilized powder or white or almost white color.

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

ATX: & nbsp

A.02.B.C.01 Omeprazole

Pharmacodynamics:

Mechanism of action

Omeprazole is a racemic mixture of two enantiomers, reduces the secretion of gastric juice through a highly selective mechanism of action: specific inhibition of the proton pump of parietal cells of the stomach. Omeprazole is a weak base, accumulates in the acidic environment of the secretory tubules of the parietal cells of the gastric mucosa, is activated and inhibits the enzyme H⁺, K⁺ATPase. The effect of omeprazole on the last stage of the formation of hydrochloric acid in the stomach is dose-dependent and provides a highly effective inhibition of basal and stimulated secretion of hydrochloric acid,regardless of the stimulating factor. After intravenous administration of 40 mg of omeprazole, the action of omeprazole occurs quickly and lasts for 24 hours. The maximum effect is achieved after 2 hours. After discontinuation of the drug, the secretory activity is completely restored after 3-5 days.

Effect on the secretion of hydrochloric acid in the stomach

A single intravenous injection of omeprazole causes a dose-dependent inhibition of gastric juice secretion. Intravenous administration of 40 mg of omeprazole causes a rapid reduction in gastric acidity by an average of 90%, which is maintained for 24 hours both with intravenous injection and with intravenous infusion. The inhibition of acid secretion depends on the area under the concentration-time curve (AUC) omeprazole, and not from the plasma concentration of omeprazole at a given time.

During treatment with omeprazole tachyphylaxis is not observed.

Action on Helicobacter pylori

Omeprazole has a bactericidal effect against AND. pylori in vitro. Eradication H. pylori when omeprazole is used together with antibacterial drugs it is accompanied by a rapid elimination of symptoms, a high degree of healing of defects in the mucous membrane of the gastrointestinal tract and a prolonged remission of peptic ulcer.

Other effects associated with inhibition of acid secretion

There have been reports of a slight increase in the incidence of glandular cysts in the stomach in patients taking orally for a long time, drugs that reduce the secretion of the glands of the stomach. These phenomena are caused by physiological changes as a result of pronounced inhibition of acid secretion. Cysts are benign and undergo reverse development.

Reduced acid secretion in the stomach by proton pump inhibitors (PIH) or other acid-inhibiting agents may result in a slight increase in the risk of intestinal infections caused by pathogens such as Salmonella spp., Campylobacter spp., Clostridium difficile.

In children and adults with long-term use omeprazole, there was an increase in the number of enterochromafia-like cells, probably associated with an increase in the concentration of gastrin in the blood plasma. Clinical significance of this phenomenon is not.

Pharmacokinetics:

Possessing high lipophilicity, omeprazole easily penetrates the parietal cells of the gastric mucosa. In the blood plasma omeprazole intensively binds to plasma proteins - 95%, mainly with albumin and alpha-1-acid glycoprotein. The volume of distribution in healthy volunteers is 0.3 l / kg body weight. Omeprazole almost completely is metabolized in the liver with the help of cytochrome P450 isoenzymes (CYP) with the formation of 6 pharmacologically inactive metabolites. The main pathway of metabolism is through isoenzyme CYP2C19. Another way - with the participation of cytochrome isoenzyme CYP3A4. The result of the high affinity of omeprazole to the isofermet CYP2C19 is the possibility of competitive inhibition and metabolic interactions with other drugs that are metabolized by an isoenzyme CYP2C19. Due to low affinity to the isoenzyme CYP3A4 omeprazole does not inhibit the metabolism of other isoenzyme substrates CYP3A4. Omeprazole has no inhibitory effect on the main isoenzymes of the cytochrome system CYP. Approximately 3% of Caucasians and 15-20% of Asians reduced isoenzyme activity CYP2C19, those. they are "slow" metabolizers. In these individuals, the metabolism of omeprazole, in all probability, occurs primarily through isoenzyme CYP3A4. With the repeated use of 20 mg of omeprazole once a day, the mean AUC was 5 to 10 times higher in "slow" metabolizers compared to individuals with normal isoenzyme activity CYP2C19. The mean peak plasma concentrations were also 3 to 5 times higher. These data have no effect on the dosage regimen of omeprazole.

Excretion

The total plasma clearance is 0.3-0.6 l / min after a single injection of omeprazole.

The average half-life period in the terminal phase is 40 minutes. It is excreted as metabolites by the kidneys (80%) and with bile (20%).

Have patients with impaired liver function there is an increase AUC omeprazole and a significant decrease in plasma clearance.

Have patients with impaired renal function There were no significant changes in the pharmacokinetics of omeprazole. In chronic renal failure, excretion decreases in proportion to a decrease in creatinine clearance.

Have elderly patients (over 75 years old) slightly decreases the metabolic rate of omeprazole.

Indications:

- LTreatment of duodenal ulcer;

- prevention of recurrence of duodenal ulcer;

- treatment of gastric ulcer;

- prevention of recurrence of gastric ulcer;

- prevention and treatment of erosive and ulcerative lesions of the stomach and duodenum caused by the use of non-steroidal anti-inflammatory drugs (NSAIDs);

- reflux esophagitis;

- maintenance therapy of reflux-esophagitis in the phase of remission;

- symptomatic treatment of gastroesophageal reflux;

- Zollinger-Ellison syndrome.

Contraindications:

- Hypersensitivity to omeprazole, substituted benzimidazoles and other components of the drug;

- simultaneous use with atazanavir, nelfinavir, erlotinib and posaconazole;

- the period of breastfeeding;

- age under 18 years (efficiency and safety are not established for this form of release).

Carefully:

With caution should be used in patients with severe hepatic insufficiency, with osteoporosis, with the presence of "anxious" symptoms: significant weight loss, recurrent vomiting, vomiting with blood (hematemesis), swallowing, color change of stool (tarry stool - melena), vitamin deficiency AT₁₂ (cyanocobalamin); simultaneously accepting clopidogrel, itraconazole, warfarin, cilostazol, diazepam, phenytoin, saquinavir, tacrolimus, clarithromycin, voriconazole, rifampicin, preparations of St. John's wort perfumed, during pregnancy.

Pregnancy and lactation:

Data on the use of omeprazole during pregnancy and breastfeeding are limited. Sporadic reports on the development of congenital anomalies in newborns were obtained. The use of Ortanol® during pregnancy is only possible if the intended benefit to the mother exceeds the potential risk to the fetus.

Omeprazole penetrates into breast milk in trace concentrations. If it is necessary to administer Ortanol® to a nursing mother, the question of stopping breastfeeding should be addressed.

Dosing and Administration:

The drug is administered intravenously drip for 20-30 minutes.

If it is not possible to perform oral therapy for patients with peptic ulcer and duodenal ulcer or reflux esophagitis, intraperitoneal administration of preperate 40 mg once daily is recommended.

With Zollingsra-Ellison syndrome, an initial intravenous injection of 60 mg per day is recommended.If necessary, increase the dose to 80-120 mg per day, dividing it into two injections.

Have patients with impaired liver function the daily dose should not exceed 20 mg.

Have patients with impaired renal function correction of the dose is not required.

Have elderly patients (over 65 years) correction of the dose is not required.

Preparation of the infusion solution before use >

Solution for infusion is prepared by dissolving the contents of one vial with lyophilizate in 100 ml of 0.9% sodium chloride solution or 5% glucose solution.

1. Collect 5 ml infusion solution from a vial with a solvent or infusion bag into the syringe.

2. Introduce the infusion solution into a vial of omeprazole lyophilizate, mix thoroughly until the drug dissolves completely.

3. Draw a syringe solution of omeprazole and transfer it to a vial of a solvent or infusion bag.

4. Repeat steps 1-3 until all omeprazole will not be transferred to a vial of a solvent or an infusion bag.

Alternative method of preparing solutions for ipfuzii in soft containers

1. To prepare the solution, use a two-sided needle-adapter. Insert one end of the needle into the vial with lyophilizate, and connect the other end to the infusion bag containing the infusion solution.

2. Dissolve the omeprazole lyophilizate by pumping the infusion solution between the infusion bag and the vial.

3. Make sure that the lyophilizate is completely dissolved, then disconnect the empty vial and remove the needle from the infusion bag. The resulting solution can not be reused, the chemical and physical stability of the prepared solution of omeprazole is observed for 4 hours at a temperature of no higher than 25 ° C in a dark place.

From the microbiological point of view, diluted solution is recommended to be used immediately.

Side effects:

According to the World Health Organization (WHO), unwanted effects are classified according to their frequency of development as follows: very often (≥ 1/10), often (≥1 / 100, <1/10), infrequently (≥1 / 1000, < 1/100), rarely (≥1 / 10000, <1/1000) and very rarely (<1/10000); frequency is unknown (the frequency of occurrence of phenomena can not be determined on the basis of available data).

On the part of the blood and lymphatic system

rarely: leukopenia, thrombocytopenia; rarely: agranulocytosis, pancytopenia.

From the immune system

rarely: hypersensitivity reactions (fever, angioedema, anaphylactic reactions / anaphylactic shock).

From the side of metabolism and nutrition

rarely: hyponatremia;

frequency is unknown: hypomagnesemia (see section "Special instructions"). Severe hypomagnesemia can lead to the development of hypokalemia and hypokalemia.

Disorders of the psyche

infrequently: insomnia;

rarely: agitation, confusion, depression, aggression, hallucinations.

From the nervous system

often: headache;

infrequently: dizziness, paresthesia, drowsiness; rarely: a violation of taste sensations.

From the side of the organ of vision

rarely: blurred vision.

From the side of the hearing organ and labyrinthine disorders

infrequently: vertigo.

From the respiratory system

rarely: bronchospasm.

From the gastrointestinal tract

often: pain in the abdomen, constipation, diarrhea, flatulence, nausea, vomiting; rarely: dryness of the oral mucosa, stomatitis, candidiasis of the gastrointestinal tract; rarely: dyspepsia;

frequency is unknown: microscopic colitis.

From the liver and biliary tract

infrequently: increased activity of "hepatic" enzymes;

rarely: hepatitis (with jaundice or without);

rarely: hepatic insufficiency, encephalopathy in patients with previous liver diseases.

From the skin and subcutaneous tissues

infrequently: dermatitis, itching, skin rash, hives;

rarely: photosensitivity, alopecia;

rarely: erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell's syndrome).

From the musculoskeletal and connective tissue

infrequently: fracture of the thigh, bones of the wrist, vertebrae; rarely: myalgia, arthralgia; rarely: muscle weakness.

From the side of the kidneys and urinary tract

rarely: interstitial nephritis.

From the genitals and breast

rarely: gynecomastia.

Other

infrequently: malaise, peripheral edema; rarely: increased sweating.

There were isolated reports of the occurrence of an irreversible visual impairment in patients with severe concomitant diseases with intravenous injection of omeprazole in high doses, but a causal relationship between omeprazole therapy and visual impairment was not established.

Overdose:

Symptoms: nausea, vomiting, dizziness, abdominal pain, diarrhea, headache. In some cases, there was apathy, depression, confusion.

Treatment: symptomatic therapy.Hemodialysis is not effective enough.

Interaction:

Effect of omeprazole on the pharmacokinetics of other drugs

Decreased secretion of hydrochloric acid in the stomach during treatment with omeprazole may result in a decrease or increase in absorption of other medicines, the bioavailability of which is largely determined by the acidity of the gastric juice (incl. posaconazole, erlotinib, ketoconazole, itraconazole, digoxin, iron preparations and cyanocobalamin).

It should avoid the simultaneous use of omeprazole with posaconazole and erlotinib.

With simultaneous application atazanavir and nelfinavir with omeprazole, a significant decrease in their plasma concentration can be observed, therefore simultaneous use of these drugs is not recommended.

Bioavailability digoxin with simultaneous application with omeprazole increases by 10%. Special care should be taken when using these drugs at the same time in elderly patients.

In a cross-sectional clinical trial clopidogrel (loading dose 300 mg, maintaining a dose of 75 mg per day) in the form of monotherapy and in combination with omeprazole (80 mg inday at the same time as clopidogrel) was used for 5 days. In this case, the bioavailability of the active metabolite clopidogrel decreased by 46% (day 1) and 42% (day 5), the level of inhibition of ADP-induced platelet aggregation decreased by 47% (day 1) and by 30% (day 5) with simultaneous application of omeprazole and clopidogrel. Another study found that the use of clopidogrel and omeprazole at different times does not exclude their interaction, which is probably due to the inhibitory effect of omeprazole on enzyme activity CYP2C19. Observations and clinical studies have produced conflicting data on the presence or absence of an increased risk of developing cardiovascular complications with simultaneous use of omeprazole and clopidogrel.

With simultaneous application with omeprazole, an increase in plasma concentration and an increase in the half-life warfarin (II- warfarin) and other antagonists of vitamin K, cilostazol, diazepam, phenytoin, and other drugs metabolized in the liver by isoenzyme CYP2C19 (a reduction in the doses of these drugs may be required).

When using omeprazole by patients receiving warfarin or other antagonists of vitamin K, careful monitoring of the international normalized relationship (INR) is necessary. In some cases, it may be necessary to reduce the dose of warfarin or another vitamin K antagonist. At the same time, in patients taking long-term warfarin, the joint use of omeprazole at a dose of 20 mg once a day did not cause a change in the coagulation time.

The use of omeprazole at a dose of 40 mg once a day in healthy volunteers led to an increase in C_max and AUC cilostasopa by 18% and 26%, respectively; for one of the active metabolites thyrostasol the increase was 29% and 69%, respectively.

With simultaneous application phenytoin It is recommended to measure the concentration of phenytoin in the blood plasma during the first two weeks after the start of treatment with omeprazole. In some cases, a dose adjustment of phenytoin may be required. At the same time, patients with long-term phenytoin, simultaneous use with omeprazole at a dose of 20 mg once a day did not cause a change in the concentration of phenytoin in the blood plasma. Omeprazole with simultaneous application increases the plasma concentration tacrolimus, which may require dose adjustment. It is necessary to monitor the concentration tacrolimus in blood plasma, and also to measure the clearance of creatinine.

With simultaneous application with omeprazole there is an increase in plasma concentration saquinavir / ritonavir up to 70%, while the tolerability of treatment for patients with HIV infection does not deteriorate.

Some patients reported increased concentrations methotrexate against a background of joint application with the IPN. When assigning high doses methotrexate should consider the possibility of a temporary withdrawal of omeprazole.

Omeprazole does not affect the metabolism of drugs that are metabolized by isoenzyme CYP3A4, such as cyclosporine, lidocaine, quinidine, estradiol, erythromycin and budesonide.

The effect of drugs on the pharmacokinetics of omeprazole

Simultaneous application with inhibitors of isoenzymes CYP2C19 and CYP3A4 (such as clarithromycin, voriconazole) can lead to an increase in the plasma concentration of omeprazole due to a slowing of its metabolism.The simultaneous use of omeprazole and voriconazole may lead to an increase AUC omeprazole more than 2 times. As a rule, in such cases, there is no need for correction of the dose of omeprazole, however, this may be required in patients with severe impairment of liver function and with long-term use of omeprazole.

Inductors of isoenzymes CYP2C19 and CYP3A4 (eg, rifampicin, preparations of St. John's wort penetrated {Hypericum perforatum) can accelerate the metabolism of omeprazole, thereby reducing its concentration in the blood plasma.

No clinically significant interaction of omeprazole with antacids, theophylline, caffeine, S-warfarin, piroxicam, diclofenac, naproxen, quinidine, lidocaine, propranol, metoprolol, ethanol.

Special instructions:

If you suspect a stomach ulcer in the early stages, you need to undergo an X-ray or endoscopy examination to establish the correct diagnosis and the appointment of an adequate treatment.

In the presence of "anxious" symptoms (significant weight loss, recurrent vomiting, dysphagia, vomiting of blood, melena), as well as with the presence of a stomach ulcer or if it is suspected, before starting therapy, it is necessary to exclude the presence of a malignant process,as treatment with omeprazole can mask the symptoms and thus delay the setting of the correct diagnosis.

Patients taking the drug for a long period (especially more than 1 year) should be under regular medical supervision. Omeprazole can reduce the absorption of vitamin B₁₂ due to hypo- or achlorhydria. This should be taken into account when using Ortanol in patients with a deficiency or a risk of developing vitamin B deficiency₁₂ with prolonged therapy.

Hypomagnesemia. A severe form of hypomagnesemia was observed in patients undergoing IPI treatment, including omeprazole, for at least three months and in most cases during treatment during the year. There were serious manifestations of hypomagnesemia, such as chronic fatigue, tetany, convulsions, delirium, dizziness and ventricular arrhythmias, but they can start gradually and remain unnoticed. In most patients, hypomagnesemia disappeared after additional intake of magnesium preparations and discontinuation of PID.

For patients who may require long-term treatment with omeprazole and / or taking IPN in conjunction with digoxin or drugs that can cause hypomagnesemia (eg, diuretics),should consider the possibility of measuring the content of magnesium before initiating PID therapy and periodic monitoring during treatment.

The use of PPIs, especially when used in high doses and for prolonged periods (> 1 year), may lead to a moderate increase in the risk of hip fracture, wrist and vertebral bodies, especially in the elderly or in the presence of other known risk factors. The carried out researches allow to assume, that reception of the given preparations can raise the general risk of fractures on 10-40%. To some extent, this increase in risk may be a consequence of other factors. Patients at risk for developing osteoporosis should undergo treatment in accordance with applicable clinical guidelines and take in the required amount of vitamin preparations D and calcium.

During the use of drugs that reduce the secretion of the glands of the stomach, the concentration of gastrin in the blood plasma increases. Due to a decrease in the secretion of hydrochloric acid, the concentration of chromogranin A (CgA) in the blood plasma, which can lead to false positive results in the diagnosis of patients with suspected neuroendocrine tumors.To prevent this effect, therapy with proton pump inhibitors should be stopped at least 5-14 days before the study concentration CgA. If during this time the concentration CgA did not return to the normal value, the study should be repeated.

Special precautions when destroying an unused preparation

There is no need for special precautions when destroying an unused preparation.

Effect on the ability to drive transp. cf. and fur:When taking Orthanol®, dizziness, drowsiness, and visual impairment may occur, therefore, care should be taken when driving vehicles and engaging in potentially dangerous activities that require an increased concentration of attention and speed of psychomotor reactions.

Form release / dosage:

Liofilizate for the preparation of a solution for infusions 40 mg.

Packaging:40 mg of omeprazole in bottles of clear glass, sealed with brombugyl rubber stoppers with aluminum rolling and plastic caps with an inscription in English "FLIP OFF". 1 bottle with instruction for use in a cardboard box or 5 or 10 bottles with instructions for use in a cardboard box with a cardboard holder inside.

Storage conditions:

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

Ready solution: in the dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

2 of the year.

Finished solution: 4 h.

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

Terms of leave from pharmacies:On prescription

Registration number:LP-003011

Date of registration:01.06.2015

Expiration Date:01.06.2020

The owner of the registration certificate:Sandoz d.Sandoz d. Slovenia

Manufacturer: & nbsp

LEK d.d. Slovenia

Representation: & nbspSANDOZ SANDOZ Switzerland

Information update date: & nbsp12.06.2017

Illustrated instructions

Instructions

Ortanol® (Ortanol®)