Nexium (Lyophilisates for solution)
Active material: Esomeprazole
When ATH: A02BC05
CCF: Inhibitor N+-K+-ATPase
ICD-10 codes (testimony): K21, K21.0
When CSF: 11.01.03
Manufacturer: ASTRAZENECA AB (Sweden)
DOSAGE FORM, STRUCTURE AND PACKAGING
Valium for drug of a solution for / in in the form of a compressed mass of white or almost white.
| 1 fl. | |
| esomeprazole sodium | 42.5 mg, |
| that corresponds to the content of esomeprazole | 40 mg |
Excipients: ethylenediaminetetraacetic acid disodium salt, Sodium hydroxide, nitrogen, etc. and /, water d / and.
Bottles glass volume 5 ml (10) – Stands Paper (1) – packs cardboard.
Pharmacological action
Inhibitor N+-K+-ATPase. Esomeprazole is an S-isomer of omeprazole and reduces gastric acid secretion by specific inhibition of the acid pump in parietal cells. S- and R-isomer of omeprazole have similar pharmacodynamic activity.
Mechanism of action
Esomeprazole is a weak base, It accumulates and passes into the active form in the acidic environment of the secretory canaliculi of the parietal cells of the gastric mucosa, which inhibits the proton pump – фермент H+-K+-ATF canine. Esomeprazole inhibits both basal, and stimulated gastric secretion.
Effect on gastric acid secretion
After ingestion esomeprazole 20 mg or 40 mg in patients with symptomatic gastroesophageal disease gastric pH value was higher 4 average 13 and h 17 hr from 24 no. The effect was the same for / in the introduction and ingestion.
Analysis of pharmacokinetic data revealed a correlation between inhibition of acid secretion and the concentration of drug in plasma following oral administration (We were used to estimate the concentration of the parameter AUC).
Therapeutic effect, achieved as a result of inhibition of acid secretion
Healing of reflux esophagitis in applying esomeprazole 40 mg occurs in approximately 78% patients through 4 weeks of therapy and 93% patients through 8 weeks of therapy (ingestion).
Other effects, associated with the inhibition of acid secretion
During treatment antisecretory gastrin levels in plasma increased as a result of reduction of acid secretion.
Patients, antisecretory drugs taken orally for a long time, It noted an increase in the number of cells enterohromofinopodobnyh, probably due to an increase in plasma gastrin content.
Patients, taking antisecretory drugs inside for a long time, often mentioned the formation of cysts in the glandular stomach. These phenomena are caused by physiological changes as a result of inhibition of acid secretion. Cysts are benign and reversible.
Pharmacokinetics
Absorption and raspredelenie
In Кажущийсяd at equilibrium in healthy people is about 0.22 l / kg. Plasma protein binding – 97%.
Metabolism and excretion
Esomeprazole undergoes complete metabolism involving the cytochrome P450 system (CYP). The main part is metabolized with the participation of specific polymorphic isoform CYP2C19, thus formed hydroxy- and metabolites of esomeprazole desmetilirovannye. The metabolism of the remaining part is carried out another specific isoform CYP3A4; with the formation of esomeprazole sulfoderivatives, the major metabolite, determined in plasma.
Options, below, reflect, primarily, the nature of the pharmacokinetics in patients with active isoenzyme CYP2C19 (Patients with rapid metabolism).
The total plasma clearance is approximately 17 l / h after a single dosing and 9 l / – after multiple dose. T1/2 is 1.3 hours after preparation repeated receptions at intervals of one day. AUC is increased by repeated introduction. This increase is dose- and time-dependent, that is a consequence of decreased metabolism in the first passage through the liver, as well as lower systemic clearance, probably, caused by the, that esomeprazole and / or its metabolite sulfosoderzhaschy inhibit CYP2C19 isozyme.
With a single daily intake of Esomeprazole is completely eliminated from plasma in the interval between doses, and do not tend to accumulate.
Repeated on / in a dose of esomeprazole 40 mg, middle Cmax in plasma is approximately 13.6 mmol / l. If ingestion of similar doses of the average plasma concentration of 4.6 mmol / l. Several smaller increases overall exposure (approximately 30%) at / in the introduction of esomeprazole, compared with oral. None of the major metabolites of esomeprazole has no effect on gastric acid secretion. When administered to 80% dose excreted as metabolites in the urine, the rest of the – with feces. The urine is detected less 1% unchanged esomeprazole.
Pharmacokinetics in special clinical situations
Approximately 1-2% population reduced CYP2C19 isoenzyme (patients with slow metabolism). In such patients, the metabolism of esomeprazole is mainly carried out by the action of CYP3A4 and repeated ingestion 40 mg esomeprazole 1 time / day at the mean AUC 100% higher, than in patients with active enzyme CYP2C19 (Patients with rapid metabolism). Averages Cmax in the plasma of patients with slow metabolism increased approximately 60%. Similar differences were found in the / in the introduction of esomeprazole. These features do not affect the Dosage ezomerpazola.
Elderly patients (71-80 years) metabolism does not vary significantly esomeprazole.
After a single oral 40 mg esomeprazole the mean AUC of women on 30% exceeded the value of this parameter in men. Further, the systematic daily administration 1 time / day differences in the pharmacokinetics in patients of both sexes were observed. Similar differences were found in the / in the introduction of esomeprazole. The data do not affect the dosage.
The metabolism of esomeprazole in patients with impaired liver function mild to moderate severity may be violated. In patients with severe hepatic impairment metabolic rate decreased, which leads to a doubling of the AUC for esomeprazole. Therefore, the dose should not be exceeded 20 mg / day in patients with severe hepatic impairment. Esomeprazole and its major metabolites do not show a tendency to accumulate at reception 1 time / day.
A study of the pharmacokinetics in patients with impaired renal function has not been. Since the removal is carried out through the kidneys not of esomeprazole, and its metabolites, it can be assumed, that the metabolism of esomeprazole in patients with impaired renal function is not changed.
Testimony
- Gastroesophageal reflux disease (GERD) in patients with esophagitis and / or severe symptoms of reflux disease (as an alternative to oral therapy).
Dosage regimen
At impossibility of oral therapy can be recommended to patients in / introduction esomeprazole 20-40 mg 1 time / day.
Patients with reflux esophagitis recommended esomeprazole 40 mg 1 time / day.
To treat the symptoms of GERD the drug is prescribed in a dose 20 mg 1 time / day.
Usually, during parenteral administration of Nexium® short duration, the patient should be translated as quickly as possible to the reception of the drug inside.
No dose adjustment of the drug in patients with impaired renal function. Due to the limited experience of the use of Nexium® in patients with severe renal insufficiency, Caution should be exercised when treating such patients.
No dose adjustment of the drug in patients with impaired liver function mild to moderate severity. In Patients with severe hepatic impairment The maximum daily dose is 20 mg.
No dose adjustment from prearata elderly patients.
Regulations preparation and use of the drug
Preparation and use of the solution for I / injection
Solution w / injection is prepared by adding 5 ml 0.9% sodium chloride solution for / in the introduction to the vial with esomeprazole. Dilution of esomeprazole is a clear fluid pale yellow. The degradation of the prepared solution, mainly, pH-dependent, in connection with which to dissolve the drug should be used only 0.9% sodium chloride solution for the on / in the.
The prepared solution should not be mixed or co-administered with other drugs.
Before use, the solution should be evaluated visually for the absence of visible mechanical impurities and discoloration. Only the clear solution can be used.
The prepared solution is recommended to be administered immediately after preparation (from the microbiological point of view,).
Esomeprazole prepared solution for injection is injected in / for at least 3 m.
In appointing 20 mg esomeprazole administered half of the prepared solution. Unused remaining solution must be discarded.
Preparation and use of a solution for / infusion
The infusion solution is prepared by dissolving contents of one vial with esomeprazole in 100 ml 0.9% sodium chloride solution for the on / in the. Dilution of esomeprazole is a clear fluid pale yellow. Degradation of this solution is mainly dependent on the pH, in connection with which to dissolve the drug should be used only 0.9% sodium chloride solution for i / v administration.
The prepared solution should not be mixed or co-administered with other drugs.
Before use, the solution should be evaluated visually for the absence of visible mechanical impurities and discoloration. Only the clear solution can be used.
The mixed solution was introduced in the form of esomeprazole / in infusion for 10-30 m.
In appointing 20 mg esomeprazole administered half of the prepared solution for 10-30 m. Unused remaining solution must be discarded.
Side effect
Below are the side effects, marked with a / in and oral administration of Nexium® in the course of clinical trials. None of these effects were dependent on the dose.
Often (>1/100, <1/10): headache, abdominal pain, diarrhea, flatulence, nausea, vomiting, constipation.
Infrequently (>1/1000, <1/100): dermatitis, itch, hives, dizziness, dry mouth, blurred vision.
Rarely (>1/10 000, <1/1000): hypersensitivity reactions (angioedema, anaphylactic reaction), increase in liver enzymes, Stevens-Johnson syndrome, erythema multiforme, myalgia, leukopenia, thrombocytopenia, depression.
Very rare (<1/10 000): agranulocytosis, pancytopenia.
The following adverse effects were observed only when using a racemic mixture of the drug (omeprazole) and can also be expected in the application of esomeprazole.
From the central and peripheral nervous system: paraesthesia, drowsiness, insomnia, dizziness, reversible confusion, anxiety, excitation, depression, hallucinations (predominantly in severely ill patients).
On the part of the endocrine system: gynecomastia.
From the digestive system: stomatitis, gastrointestinal candidiasis, elevated liver enzymes, encephalopathy in patients with long-term severe liver disease, hepatitis C (or without) jaundice, hepatic failure.
From the hematopoietic system: leukopenia, thrombocytopenia, agranulocytosis, pancytopenia.
On the part of the musculoskeletal system: arthralgia, muscular weakness.
Dermatological reactions: rash, photosensitivity, toxic epidermal necrosis, alopecia.
Other: generalized weakness, hypersensitivity reactions (fever, bronchospasm), interstitial nephritis, increased perspiration, peripheral edema, changes in taste, giponatriemiya.
It reported some cases of irreversible visual impairment in the / in the introduction of omeprazole in patients in critical condition, particularly when administered at high doses, a causal relationship to drug intake is not installed.
Contraindications
- Children's age (due to the lack of data on drug use in this group of patients);
- Hypersensitivity to esomeprazole, substituted benzimidazoles or other ingredients of the formulation.
FROM caution should be prescribed to patients with severe renal insufficiency.
Pregnancy and lactation
Currently, data on the use of esomeprazole during pregnancy limited.
IN experimental studies animals did not reveal any direct or indirect negative impact of Nexium® on the development of an embryo or fetus. Introduction of a racemic mixture of the drug also did not have any adverse effect on animals at gestation, childbirth, and during postnatal development.
Prescribed the drug during pregnancy should only be, the expected benefit to the mother outweighs the potential risk to the fetus.
There are no data on the use of the drug in women during lactation. It is not known whether esomeprazole is released in breast milk, therefore, should not be given Nexium® during breastfeeding.
Cautions
In the presence of any alarm symptoms (eg, such as a significant spontaneous loss of body weight, frequent vomiting, dysphagia, vomiting of blood or melena), and in the presence of gastric ulcers (or suspected stomach ulcer), should rule out the presence of cancer, as treatment Nexium® It can lead to a smoothing of the symptoms and delay diagnosis.
Effects on ability to drive vehicles and management mechanisms
Nexium® It does not affect the ability to drive a car or operate machinery.
Overdose
At the moment, it describes very rare cases of intentional overdose. Symptoms, Orally described esomeprazole 280 mg, accompanied by general weakness and symptoms of the gastrointestinal tract. Single unit 80 mg esomeprazole inwardly and 100 mg / O did not induce any adverse effects.
Treatment: Specific antidotes are not known. Esomeprazole is well bound to plasma proteins, poetomu dialysis maloeffyektivyen. In case of overdose should be carried out symptomatic and general supportive treatment.
Drug Interactions
The reduced acidity in the stomach in the treatment of esomeprazole can reduce or enhance absorption of other drugs, suction mechanism which depends on the acidity of the medium. As with other drugs, suppress acid secretion or antacids, esomeprazole treatment may result in decreased absorption of ketoconazole or itraconazole.
Эзомепразол ингибирует CYP2C19 – the main enzyme, involved in its metabolism. The combined use with other drugs esomeprazole, in the metabolism of which involved CYP2C19, such as diazepam, citalopram, imipramine, klopiramin, phenytoin, may lead to increased concentrations of these drugs in the blood plasma and require dose reduction.
When combined ingestion esomeprazole 30 mg 45% decreased clearance of diazepam, which is a substrate of CYP2C19.
When combined ingestion esomeprazole 40 mg of phenytoin in epileptic patients on 13% increased residual concentration of phenytoin plasma. In this regard, it is recommended to control the concentration of phenytoin in plasma at the start of treatment with esomeprazole and its abolition.
When combined ingestion of warfarin and esomeprazole 40 mg did not change coagulation time observed in patients, long-term taking warfarin. But, reported several cases of clinically significant increase in the index MHO the joint application of warfarin and esomeprazole. In this connection it is recommended to monitor the beginning and at the end of the joint use of these drugs. In healthy volunteers, co-administration of esomeprazole inside 40 mg cisapride on 32% increased the AUC value and 31% увеличивал T1/2 cisapride, Cmax cisapride plasma while not significantly changed. When cisapride alone, it showed a slight lengthening of the QT interval. When adding esomeprazole further increase the QT interval were observed.
Proved, that esomeprazole does not cause clinically significant changes in the pharmacokinetics of amoxicillin and quinidine.
В метаболизме эзомепразола участвуют CYP2C19 и CYP3A4. The combined use of the inside of esomeprazole and clarithromycin 500 mg 2 times / day (CYP3A4 inhibitor) It leads to a twofold increase in the AUC of esomeprazole. Dose adjustment of esomeprazole is not required.
Conditions of supply of pharmacies
The drug is released under the prescription.
Conditions and terms
The drug should be stored in its original packaging away from children, dark place at a temperature no higher than 30 ° C. Bottle without carton packs under indoor lighting can be stored no more than 24 no. Shelf life – 2 year.
The prepared solution (for in / or injection / infusion) should be kept at a temperature no higher than 25 ° C and use within 12 no.
