Date of approval.
Date of revision.
Omeprazole Magnesium Enteric Dissolve Tablets Instructions
Please read the instructions carefully and use under the guidance of a physician
Drug Name]
Generic name: Omeprazole Magnesium Enteric Tablets
Trade name: Loxacol MUPS
English name: Omeprazole Magnesium Enteric-coated Tablets
Hanyu Pinyin: Aomeilazuomei Changrongpian
Ingredients
The main ingredient of this product is omeprazole magnesium.
Its chemical name: Bis-5-methoxy-2-{[(4-methoxy-3,5-dimethyl-2-pyridyl)methyl]sulfinyl}-1H-benzimidazole magnesium
The chemical structure formula is
Molecular formula: C34H36N6MgO6S2
Molecular weight: 713.21
【Properties】.
This product is light pink (10mg) or pink (20mg) film coated tablets.
Indications
Treatment of duodenal ulcer, gastric ulcer and reflux esophagitis; combined with antibiotics for the treatment of duodenal ulcer caused by Helicobacter pylori; treatment of peptic ulcer or gastroduodenal erosion associated with NSAIDs; prevention of peptic ulcer, gastroduodenal erosion or dyspeptic symptoms caused by NSAIDs; also used for the long-term treatment of chronic recurrent peptic ulcer and reflux esophagitis Used for symptomatic treatment of heartburn and reflux in gastroesophageal reflux disease; symptomatic treatment of ulcer-like symptoms and acid-related dyspepsia; used in the treatment of Dro-Ai syndrome.
Specification】
By C17H19N3O3S
(1) 10 mg; (2) 20 mg
Dosage
The tablet must be swallowed whole and served with at least half a glass of liquid. The tablets must not be chewed or crushed, they can be dispersed in water or slightly acidic liquid (e.g.: fruit juice), and the dispersion must be taken within 30 minutes.
Duodenal ulcer: The usual dose of 20 mg of this product once a day, usually the ulcer can be cured within two weeks. If the efficacy of the initial course of treatment is not certain, treatment should be given for another two weeks. For duodenal ulcers that have failed to respond to treatment with other drugs, 40 mg once a day is usually sufficient to cure the ulcer within four weeks. Treatment may be repeated in patients with recurrence.
Eradication of H. pylori.
Triple therapy: 20 mg of this product, 1000 mg of amoxicillin and 500 mg of clarithromycin, both twice a day for one week. Or 20 mg of this product, 250 mg of clarithromycin and 400 mg of metronidazole, all twice a day for one week.
Dual therapy: Benadryl 40 mg once a day and clarithromycin 500 mg 3 times a day for two weeks. Or 20 mg of this product and 750-1000 mg of amoxicillin, both twice a day for two weeks. To ensure cure, refer to the recommended dose for duodenal ulcers.
NSAID-associated duodenal ulcer or duodenal erosion with or without NSAIDs: the usual dose is 20 mg once a day. Cure is usually achieved within four weeks, and if the initial course of therapy is of uncertain efficacy, treatment should be given for another four weeks.
To prevent NSAID-associated duodenal ulcers, duodenal erosions, or dyspeptic symptoms: the normal dose is 20 mg once a day.
To prevent recurrence of recurrent duodenal ulcers where H. pylori eradication therapy has not been effective, the dose may be individually adjusted according to the severity of the disease. The efficacy is dose-dependent. The usual dose of this product is 20 mg once a day. In some patients 10 mg daily may be sufficient; if this dose is not effective, it may be increased to 40 mg.
Gastric ulcer: The usual dose of 20 mg once a day is usually curative within four weeks. If the initial course does not completely cure, treatment should be given for an additional four weeks. Patients with gastric ulcers for which other treatments have failed may be given 40 mg of this product once a day, which usually cures within eight weeks. In cases of recurrence, treatment may be repeated.
For long-term treatment of gastric ulcers, this product is given 20 mg once a day. If treatment fails, the dose may be increased to 40 mg once a day.
NSAID-related gastric ulcer or gastric mucosal erosion with or without NSAIDs: the usual dose is 20 mg once a day. Usually cured within four weeks, if the initial course of treatment is not efficacious, another four weeks of treatment should be given.
Prevention of NSAID-related gastric ulcers, gastric mucosal erosions or dyspeptic symptoms: the usual dose is 20 mg once a day.
Reflux esophagitis: The dose can be individually adjusted according to the severity of the disease. The usual dose of this product is 20 mg once a day. Cure is usually achieved within four weeks, and if the initial course of treatment is not effective, a further four weeks of treatment should be given. Patients with reflux esophagitis for whom other treatments have failed may be given 40 mg once a day, usually within eight weeks. In case of recurrence, treatment should be repeated.
Long-term treatment of chronic recurrent reflux esophagitis is individualized by dose depending on the severity of the disease. The efficacy is dose-dependent. The usual dose of this product is 20 mg once a day. In some patients, 10 mg daily may be sufficient; if this dose is not effective, it may be increased to 40 mg once a day.
Symptomatic treatment of gastroesophageal reflux disease: The usual dose of 20 mg once a day is used. In some patients, 10 mg daily may be sufficient; if 20 mg daily for two to four weeks does not control symptoms, further investigations are recommended.
Treatment of ulcer-like symptoms: The usual dose of 20 mg once a day is used. In some patients, 10 mg per day may be sufficient. If symptoms are not controlled after two to four weeks of treatment with 20 mg daily, further investigation is recommended.
Acid-related dyspepsia: The recommended dose of 20 mg of this product once a day is recommended for the relief of epigastric pain or discomfort with or without heartburn. In some patients 10 mg daily may be sufficient, so 10 mg may be used as a starting dose. If symptoms are not controlled after four weeks of treatment with 20 mg daily, further testing is recommended.
Zoe Ehrlich syndrome: The recommended starting dose is 60 mg of this product once a day. The dose should then be individually adjusted and the duration of treatment determined by clinical manifestations. 20-120 mg per day can control symptoms in more than 90% of patients, and if more than 80 mg per day is needed, it should be divided into two doses.
People with hepatic impairment: the daily dosage should not exceed 20 mg for those with severe hepatic impairment.
Patients with renal impairment: No dosage adjustment is required for patients with renal impairment.
For patients who cannot take the drug orally, a non-enteral delivery form of omeprazole is available, see instructions for Loxacol injection or powder 40 mg.
[Adverse Reactions].
In 3096 patients (2631 of which were from double-blind or open international multicenter studies) exposed to omeprazole in global clinical trials, adverse reactions with an incidence ≥ 2% included headache (6.9%), abdominal pain (5.2%), nausea (4.0%), diarrhea (3.7%), vomiting (3.2%), and gastrointestinal distention (2.7%). Adverse reactions with an incidence of ≥1% included acid reflux (1.9%), upper respiratory tract infection (1.9%), constipation (1.5%), dizziness (1.5%), rash (1.5%), malaise (1.3%), back pain (1.1%), and cough (1.1%).
The following adverse reactions have been identified during the use of this product after approval for marketing. Because these adverse reactions have been spontaneously reported by an unknown number of people, it is difficult to estimate their actual incidence or to determine their causal relationship with drug exposure. A breakdown by human organ system is listed below.
Systemic diseases: hypersensitivity reactions including tachyphylaxis, anaphylaxis, angioedema, bronchospasm, interstitial nephritis, urticaria, fever, pain, fatigue, malaise.
Cardiovascular system: chest pain, angina pectoris, tachycardia, bradycardia, palpitations, elevated blood pressure, peripheral edema.
Endocrine system: gynecomastia.
Gastrointestinal system: pancreatitis (some can be fatal), anorexia, irritable bowel, fecal discoloration, esophageal candidiasis, tongue mucosal atrophy, stomatitis, dry mouth, abdominal distention, microscopic colitis. Gastric fundic gland polyps have been observed very rarely in patients during omeprazole treatment. These polyps are benign and can be reversed after cessation of treatment.
Gastroduodenal carcinoid tumors were reported in patients with Dro-Ai syndrome on long-term omeprazole treatment, a finding thought to be related to the underlying disease.
Hepatobiliary system: liver failure (some fatal), hepatic necrosis (some fatal), hepatic encephalopathy, hepatocellular disease, cholestasis, mixed hepatitis, jaundice, elevated liver function markers (ALT, AST, GGT, alkaline phosphatase and bilirubin).
Infections: Clostridium difficile diarrhea.
Metabolic diseases and malnutrition: hypoglycemia, hypomagnesemia, hypocalcemia, hypokalemia, hyponatremia, weight gain.
musculoskeletal system: muscle weakness, myalgia, myospasm, joint pain, leg pain, fractures
Neurological/psychiatric disorders: depression, agitation, aggression, hallucinations, confusion, insomnia, catatonia, apathy, drowsiness, anxiety, abnormal dreams, tremor, sensory abnormalities, vertigo, taste disturbances.
Respiratory system: epistaxis, sore throat.
Skin and subcutaneous tissues: toxic epidermal necrolysis relaxans (some can be fatal), Stevens-Johnson syndrome, erythema multiforme, photosensitivity, urticaria, rash, dermatitis, pruritus, petechiae, purpura, alopecia, dry skin, hyperhidrosis.
Ear and vagus system: tinnitus.
Diseases of the eye: optic nerve atrophy, anterior ischemic optic neuropathy, optic neuritis, dry eye syndrome, eye irritation, blurred vision, diplopia.
Genitourinary system: interstitial nephritis, hematuria, proteinuria, elevated blood creatinine, microscopic pyuria, urinary tract infections, diabetes, dysuria, testicular pain.
Blood and lymphatic system: granulocyte deficiency (some can be fatal), hemolytic anemia, pancytopenia, neutropenia, anemia, thrombocytopenia, leukopenia, leukocytosis.
【Contraindication】.
1, Known hypersensitivity to omeprazole, other benzimidazoles or any other component of this product is contraindicated. Hypersensitivity reactions may include tachyphylaxis, anaphylaxis, angioedema, bronchospasm, interstitial nephritis, and urticaria.
2. As with other proton pump inhibitors, omeprazole should not be used in combination with nelfinavir.
Precautions
1.Gastric malignancy
When gastric ulcer is suspected or confirmed and alarm symptoms (such as unconscious significant wasting, recurrent vomiting, dysphagia, vomiting blood or black stool) appear, malignancy should be excluded first because treatment may mask the symptoms and thus lead to delayed diagnosis.
2.Atrophic gastritis
Atrophic gastritis is occasionally seen on pathological biopsy of the gastric body in patients receiving long-term omeprazole therapy.
3. Acute interstitial nephritis
Acute interstitial nephritis has been observed in patients taking proton pump inhibitors (PPIs), including this product. Acute interstitial nephritis may occur at any time during PPI therapy and is usually caused by idiopathic hypersensitivity reactions. If acute interstitial nephritis occurs, the product should be discontinued (see [Contraindications]).
4. Cyanocobalamin (vitamin B12) deficiency
Long-term (e.g., more than 3 years) daily treatment with acid-suppressive drugs may result in hypogastric acidity or gastric acid deficiency followed by vitamin B12 malabsorption. There are rare reports in the literature of cyanocobalamin deficiency due to acid suppression therapy. This diagnosis should be considered if clinical signs corresponding to cyanocobalamin deficiency are observed.
5. Clostridium difficile diarrhea
Published observational studies suggest that PPI therapy may increase the risk of Clostridium difficile diarrhea, especially in hospitalized patients. This diagnosis should be considered if the diarrhea does not improve (see [Adverse Reactions]).
Patients should be treated with the lowest dose and shortest course of PPI based on medical therapy.
Cases of Clostridium difficile diarrhea have been reported with almost all antimicrobial agents in use. For more information on antibacterial drugs used in combination with this product (e.g. clarithromycin and amoxicillin), please refer to the relevant drug insert.
6. Interaction with Clopidogrel
The combination of this product with clopidogrel should be avoided. Clopidogrel is a precursor drug whose active metabolite inhibits platelet aggregation. When co-administered with drugs such as omeprazole, the latter inhibits CYP2C19 activity, which can affect the metabolism of clopidogrel to active metabolites. Co-administration of clopidogrel and 80 mg omeprazole can reduce the pharmacological activity of clopidogrel, even if the two are administered 12 hours apart. Antiplatelet therapy with other drugs should be considered when this product is used (see [Drug Interactions]).
7. Fractures
Several published observational studies suggest that PPI therapy may increase the risk of osteoporosis-related fractures (hip, wrist, or spine). Patients receiving high doses (defined as multiple daily doses) and long-term (1 year or longer) PPI therapy have an increased risk of fracture. Patients should be treated with the lowest dose and shortest course of PPI therapy, depending on the medical condition. For patients with osteoporosis-related fracture risk, should be treated according to the relevant treatment guidelines.
8. Hypomagnesemia
In patients who received PPI treatment for at least 3 months (the vast majority of treatment after 1 year), rare asymptomatic and symptomatic hypomagnesemia cases reported. Serious adverse events include hand and foot convulsions, cardiac arrhythmias and seizures. For most patients, correction of hypomagnesemia requires magnesium supplementation and discontinuation of the PPI.
Expected to need to extend PPI treatment or have a combination of drugs such as digoxin or drugs that may lead to hypomagnesemia (such as diuretics), need to consider regular monitoring of blood magnesium concentration.
9, combined with St. John’s wort or rifampin
Induction of CYP2C19 or CYP3A4 drugs (such as St. John’s wort or rifampin) can significantly reduce the blood concentration of omeprazole. Combination of this product with St. John’s wort or rifampin should be avoided.
10.Interaction with diagnostic tests for neuroendocrine tumors
Serum chromogranin A (CgA) levels may increase secondary to drug-induced decrease in gastric acid. elevated CgA levels may result in false positive diagnostic tests for neuroendocrine tumors. Healthcare professionals should suspend omeprazole use for at least 14 days before evaluating blood CgA levels and consider retesting this indicator if the initial test CgA level is elevated. Because normal reference values may vary between laboratories, if a series of tests (e.g., monitoring) are needed, they should be performed in the same laboratory.
11. Combined use of methotrexate
The literature suggests that the combined use of PPIs and methotrexate (mainly at high doses, see methotrexate instructions) may increase the blood levels and prolong the duration of methotrexate and/or its metabolites and may lead to methotrexate toxicity. Some patients need to consider suspending PPI when using high doses of methotrexate (see [Drug Interactions])
12. This product contains sucrose and should not be taken by patients with rare genetic disorders such as fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase deficiency.
13, Treatment with proton pump inhibitors may result in a slightly elevated risk of gastrointestinal infections, such as Salmonella and Campylobacter infections.
14, For patients taking this product for a long time, especially those who have been using it for more than 1 year, regular monitoring should be performed.
15.Patients with recurrent symptoms of indigestion and heartburn over a long period of time should be seen regularly.
16.Patients should consult a physician if they have
Have a previous history of gastric ulcer or gastrointestinal surgery
Have been treated continuously for indigestion or heartburn for more than 4 weeks
Have jaundice or severe liver disease
Age 55 years or older with new or recent symptomatic changes
Pregnant and lactating women]
Adequate and well-controlled studies have not been conducted in pregnant women. The available epidemiologic data do not demonstrate an increased risk of major congenital malformations or other adverse pregnancy outcomes when omeprazole is used in early pregnancy. Because of the effects of high doses of esomeprazole magnesium on the developing skeleton observed in rat studies, this product should be used during pregnancy only if the potential benefit to the fetus outweighs the potential risk.
Omeprazole may be secreted into breast milk and should be used with caution in lactating women.
Pediatric use]
There is no experience with the use of this product in children in China.
Geriatric use]
No dose adjustment is required for elderly patients.
Drug Interactions
Effect of omeprazole on the pharmacokinetics of other drugs
1. Drugs with pH-dependent absorption.
During treatment with omeprazole, the decrease of acidity in the stomach may promote or inhibit the absorption of other drugs.
Nelfinavir, atazanavir
The blood levels of nelfinavir and atazanavir are reduced when combined with omeprazole.
Combined use of omeprazole and nelfinavir is prohibited. Combined omeprazole (40 mg once daily) reduces exposure to nelfinavir by approximately 40% and exposure to the pharmacologically active metabolite M8 by approximately 75-90%. Interactions may also include inhibition of CYP2C19.
Combined use of omeprazole and atazanavir is not recommended. In healthy volunteers, the combination of omeprazole (40 mg once daily) and atazanavir 300 mg/ritonavir 100 mg resulted in a 75% reduction in atazanavir exposure. An increase in atazanavir dose to 400 mg did not compensate for the effect of omeprazole on atazanavir exposure. In healthy volunteers, the combination of omeprazole (20 mg once daily) and atazanavir 400 mg/ritonavir 100 mg reduced atazanavir exposure by approximately 30% compared with atazanavir 300 mg/ritonavir 100 mg (once daily).
Digoxin
In healthy subjects, the combined use of omeprazole (20 mg once daily) and digoxin increased digoxin bioavailability by 10%. Higher doses of omeprazole should be used with caution in elderly patients. Patients should be monitored intensively for digoxin when combining omeprazole with digoxin.
Clopidogrel
In healthy subjects, the combination of clopidogrel (300 mg loading dose/75 mg daily maintenance dose) and omeprazole (80 mg daily dose) resulted in a 46% reduction in exposure to the active metabolite of clopidogrel and a 16% reduction in the maximal inhibition of platelet aggregation (ADP induction). When using this product, treatment with other antiplatelet agents should be considered.
Other
The absorption of posaconazole, erlotinib, ketoconazole, itraconazole, and mortezolomide (MMF) can be significantly reduced, which in turn can affect their clinical efficacy. Combinations with posaconazole and erlotinib should be avoided. Use this product with caution in transplant patients receiving MMF.
2. Active substances metabolized via CYP2C19.
Omeprazole is a moderately potent inhibitor of CYP2C19, the latter being the major metabolizing enzyme of omeprazole. Therefore, the combined use of active substances also metabolized by CYP2C19 will reduce their metabolism and thus increase the systemic exposure of these substances. Such drugs include warfarin and other vitamin K antagonists, cilostazol, diazepam, and phenytoin. Patients receiving these drugs should be monitored when initiating or discontinuing omeprazole and the dose should be adjusted if necessary.
Warfarin
Elevated INR and prothrombin time have been reported in patients on combined PPIs (including omeprazole) and warfarin. elevated INR and prothrombin time may lead to abnormal bleeding and even death. Monitoring of patients treated with proton pump inhibitors and warfarin may be required due to elevated INR and prothrombin time.
Cilostazol
In a crossover study, healthy subjects receiving a 40 mg dose of omeprazole increased the Cmax and AUC of cilostazol by 18% and 26%, respectively, and the Cmax and AUC of its active metabolite, 3,4-dihydrocilostazol, by 29% and 69%, respectively. A reduction in the dose of cilostazol should be considered when combined with this product.
3. Unknown mechanism
Saquinavir
Combined use of omeprazole and saquinavir/ritonavir can increase the blood concentration of saquinavir by approximately 70%. Clinical and laboratory monitoring of saquinavir toxicity is recommended when combining this product, and consideration of saquinavir dose reduction should be considered as appropriate.
Tacrolimus
Co-administration of omeprazole may increase the blood levels of tacrolimus. Monitoring of tacrolimus concentrations and renal function (creatinine clearance) should be intensified and tacrolimus dose adjusted if necessary.
Methotrexate
The combined administration of PPI and methotrexate (primarily at high doses) may elevate and prolong the blood levels of methotrexate and/or its metabolite hydroxymethotrexate. Temporary discontinuation of omeprazole may be considered when high doses of methotrexate are administered.
Effect of other active substances on omeprazole pharmacokinetics
1. CYP2C19 and/or CYP3A4 inhibitors
Since omeprazole is known to be metabolized by CYP2C19 and CYP3A4, drugs known to inhibit CYP2C19 or CYP3A4 (e.g., clarithromycin and voriconazole) may increase the blood concentration of omeprazole by inhibiting the metabolic rate of omeprazole. The combination of voriconazole may at least double the exposure to omeprazole. Dose adjustment of omeprazole is not usually necessary. However, in patients with severe hepatic impairment or when long-term treatment is required, dosage adjustment of omeprazole should be considered.
2. CYP2C19 and/or CYP3A4 inducers
Drugs known to induce CYP2C19 and/or CYP3A4 (e.g., rifampin and St. John’s wort) can reduce the blood concentration of omeprazole by accelerating the metabolic rate of omeprazole. Combining omeprazole with St. John’s wort or rifampin should be avoided.
[Drug overdose].
Information on omeprazole overdose is limited, with reports of single oral doses up to 2400 mg (a dose 120 times the clinically recommended dosage). Clinical manifestations include nausea, vomiting, dizziness, abdominal pain, diarrhea, headache, apathy, depression, confusion, blurred vision, tachycardia, sweating, flushing, and dry mouth; symptoms are transient and no cases of serious clinical outcome have been reported.
Omeprazole is extensively bound to proteins and therefore cannot be readily cleared by dialysis. In case of overdose, symptomatic treatment and supportive therapy should be administered.
Pharmacology and Toxicology
Pharmacological effects
Omeprazole is a benzimidazole compound that blocks the final step of gastric acid secretion by specifically inhibiting the H+-K+ ATPase system of gastric lining cells. The effect is dose-dependent and inhibits both basal gastric acid secretion and gastric acid secretion in the stimulated state. Results from animal studies show that omeprazole is present in the gastric mucosa for at least 24 hours after rapid elimination in the plasma. Omeprazole has no antagonistic effect on choline and histamine H2 receptors.
Microbiology
Omeprazole in diphasic combination with clarithromycin or triple combination of omeprazole, clarithromycin and amoxicillin is effective against most strains of H. pylori in in vitro trials as well as in clinical practice.
Toxicological studies
Genotoxicity.
Negative results in the omeprazole Ames test, mouse lymphoma cell test and rat liver DNA damage test, positive results in the in vitro human lymphocyte chromosome aberration test, 1 of 2 mouse micronucleus tests and in vivo mouse bone marrow cell chromosome test.
Reproductive toxicity.
No significant abnormalities in fertility or reproductive behavior were observed in rats given orally 138 mg/kg/day of omeprazole (approximately 34 times the human oral dose of 40 mg based on body surface area).
No potential teratogenic effects of omeprazole were found in pregnant rats given orally 138 mg/kg/day (approximately 34 times the human oral dose of 40 mg based on body surface area) and pregnant rabbits given orally 69 mg/kg/day (approximately 34 times the human oral dose of 40 mg based on body surface area).
In rabbits given omeprazole 6.9-69.1 mg/kg/day (approximately 3.4-34 times the human oral dose of 40 mg based on body surface area), dose-dependent increases in embryonic mortality, fetal resorption and abortion rates were seen.
Dose-dependent embryo/fetus toxicity and postnatal developmental toxicity were seen in offspring of parental rats given omeprazole at 13.8-138.0 mg/kg/day (approximately 3.4-34 times the human oral dose of 40 mg on a body surface area basis).
Carcinogenicity.
In two 2-year carcinogenicity tests in rats, omeprazole doses of 1.7, 3.4, 13.8, 44.0, and 140.8 mg/kg/day (approximately 0.4-34 times the human oral dose of 40 mg based on body surface area) resulted in dose-dependent gastrointestinal chromophobic (ECL) cell carcinoids in both males and females; the incidence was significantly higher in females than in males, and The blood concentration of omeprazole was higher in females than in males. Gastric carcinoid tumors were rarely seen in unadministered animals, whereas ECL cell hyperplasia was seen in both female and male administered groups.
In another trial, female rats were given omeprazole 13.8 mg/kg/day (approximately 3.4 times the human oral dose of 40 mg based on body surface area) for 1 year, after which the drug was discontinued for 1 year, and no carcinoid tumors were seen to develop. However, drug-related ECL cell hyperplasia occurred in rats at 1 year of administration (94% in the dosed group and 10% in the control group), and the difference between the dosed and control groups narrowed by the second year, although the incidence of ECL cell hyperplasia was still higher in the dosed group (46%/26%). gastric adenocarcinoma developed in one rat (2%) and was not seen in either male or female rats at 2 years of dosing. Historically, no similar tumors have been documented in rats of this species, and since only one case occurred, its significance is difficult to judge. In a 52-week toxicity test in SD rats, omeprazole doses of 0.4, 2, and 16 mg/kg/day (approximately 0.1-3.9 times the human oral dose of 40 mg based on body surface area) resulted in a small number of brain astrocytomas in males, but not in females. In a 2-year carcinogenicity test in SD rats, astrocytomas were not observed in males and females at the highest dose of 140.8 mg/kg/day (approximately 34 times the human oral dose of 40 mg on a body surface area basis).
No increase in tumor incidence was seen in the 78-week oncogenicity test in omeprazole mice, but the results of this test were inconclusive. p53 (+/-) transgenic mice had negative results in the 26-week oncogenicity test.
Juvenile animal test.
Juvenile rats were given esomeprazole magnesium at doses of 70-280 mg/kg/day (approximately 17-68 times the human oral dose of 40 mg based on body surface area) for 28 consecutive days from postnatal day 7 to day 35, with a recovery period of 14 days. The results showed an increase in the number of dead animals in the highest dose group. In addition, at 140 mg/kg/day (approximately 34 times the human oral dose of 40 mg based on body surface area) and higher doses, a decrease in body weight and weight gain, reduction in femur weight and length, and an effect on overall growth were seen.
Similar results were seen when esomeprazole strontium was tested at equimolar doses as described above.
Pharmacokinetics]
Absorption
Omeprazole is absorbed in the small intestine and is usually completely absorbed within 3 to 6 hours. The bioavailability after repeated administration is about 60%. Simultaneous ingestion of food has no effect on its bioavailability. The plasma protein binding rate of omeprazole is about 95%, and the apparent volume of distribution is 0.3L/kg.
Metabolism
Omeprazole is mainly metabolized completely in the liver, mainly by CYP2C19 and CYP3A4 enzyme catalysis. The metabolites are sulfone, sulfide and hydroxy omeprazole, which have no significant effect on gastric acid secretion. Total plasma clearance is 0.3-0.6 L/min. Omeprazole inhibits its own catalytic metabolism by CYP2C19; therefore, the bioavailability of omeprazole increases by approximately 50% with multiple doses compared to a single dose.
Excretion
The plasma elimination half-life of omeprazole after multi-dose administration is approximately 40 minutes (30-90 minutes). Approximately 80% of the metabolites are excreted in the urine and the remainder in the feces.
Patient Factors
The bioavailability of omeprazole is not significantly altered in elderly patients or in patients with renal hypofunction and is elevated in patients with hepatic impairment, but clearance is significantly decreased in all of these patients.
[Storage].
Seal and store below 25℃.
Package】
Double aluminum-plastic composite film bubble package.
(1) 10mg: 7 tablets/plate/box; 14 tablets/box.
(2) 20mg: 7 tablets/plate/box; 14 tablets/box.
Expiration date
36 months
Execution Standard
JX20030008
Approval number
(1) 10mg: H20130286
(2) 20mg: H20130288
Manufacturer
Company name: AstraZeneca AB
Address: SE-151 85, Södertälje, Sweden
China Liaison Office: No. 2, Huangshan Road, Wuxi New District, Jiangsu Province (please provide the basis)
Zip code: 214028
Quality complaint phone number: 0510-85220000, 800 828 1755
Product information free consultation phone number: 800 820 8116, 400 820 8116
Fax number: 021-38723255
Website: www.astrazeneca.com.cn