ZHENGMEI ZHENGMEIKANG Omeprazole Enteric-coated Capsules For Peptic Ulcer 20mg*7

[Drug Name]
Generic Name: Omeprazole Enteric-Coated Capsules
Trade Name: Zhengmeikang Omeprazole Enteric-Coated Capsules 20mg*7 capsules
Pinyin Full Code: ZhengMeiKang AoMeiLaZuoChangRongJiaoNang 20mg*7Li

[Main Ingredients]
The main ingredient of this product is omeprazole. Chemical name: 5-methoxy-2[(4-methoxy-3,5-dimethyl-2-pyridyl)-methyl]-sulfinyl]-1H-benzimidazole.

[Properties]
This product consists of white or off-white enteric-coated pellets or granules.

[Indications/Main Functions]
Omeprazole Enteric-Coated Capsules are indicated for gastric ulcers, duodenal ulcers, stress ulcers, reflux esophagitis, and Zollinger-Ellison syndrome (gastrinoma).

[Specifications]
20mg*7 capsules

[Dosage and Administration]
Take orally before meals. Do not chew. 1. Peptic ulcer: 20 mg (1 tablet) once or twice daily. Take orally in the morning or evening. The treatment course for gastric ulcers is usually 4 to 8 weeks, and for duodenal ulcers is usually 2 to 4 weeks. 2. Reflux esophagitis: 20 to 60 mg (1 to 3 tablets) once or twice daily. Take orally in the morning or evening. The treatment course is usually 4 to 8 weeks. 3. Zollinger-Ellison syndrome: The dosage should be adjusted individually. The recommended starting dose for adults is 60 mg (3 tablets) once daily. The total daily dose can be adjusted to 20 to 120 mg (1 to 6 tablets) depending on the condition. If the total daily dose exceeds 80 mg (4 tablets), it should be taken in two divided doses.

[Adverse Reactions]
This drug is well tolerated. Possible adverse reactions include: 1. Digestive System: Dry mouth, mild nausea, vomiting, abdominal distension, constipation, diarrhea, and abdominal pain may occur; elevated alanine aminotransferase (ALT), aspartate aminotransferase (AST), and bilirubin levels may occur. These reactions are generally mild and transient, and generally do not affect treatment. International data have also reported that gastric mucosal cell hyperplasia or atrophic gastritis may be observed in gastric corpus biopsy specimens of patients treated with long-term omeprazole therapy. 2. Neuropsychiatric System: Paresthesias, dizziness, headaches, drowsiness, insomnia, and peripheral neuritis may occur. 3. Metabolic/Endocrine System: Long-term use of omeprazole may lead to vitamin B12 deficiency. 4. Other possible side effects include rash, gynecomastia, and hemolytic anemia. According to literature reports, in 3096 patients worldwide who received omeprazole extended-release capsules in clinical trials, the most common adverse reactions (incidence ≥ 2%) included headache (6.9%), abdominal pain (5.2%), nausea (4%), diarrhea (3.7%), vomiting (3.2%), and flatulence (2.7%). Other adverse reactions occurring in ≥ 1% of patients included acid regurgitation (1.9%), upper respiratory tract infection (1.9%), constipation (1.5%), dizziness (1.5%), rash (1.5%), fatigue (1.3%), back pain (1.1%), and cough (1.1%). The safety profile in clinical trials was similar in patients aged 65 years and older compared to those aged 65 years or younger. Postmarketing Experience: The following adverse reactions were identified postmarketing with omeprazole extended-release capsules. Because these adverse reactions were reported voluntarily by patients, it is not possible to reliably estimate their actual incidence or establish a causal relationship to drug exposure. Systemic: Hypersensitivity reactions including anaphylaxis, anaphylactic shock, angioedema, bronchospasm, interstitial nephritis, urticaria, fever, pain, fatigue, and malaise. Cardiovascular: Chest pain or angina, tachycardia, bradycardia, palpitations, increased blood pressure, and peripheral edema. Endocrine: Gynecomastia. Gastrointestinal: Pancreatitis (some fatal), anorexia, irritable bowel, discolored stools, esophageal candidiasis, tongue mucosal atrophy, stomatitis, abdominal distension, and dry mouth. Fundic gland polyps have rarely developed during omeprazole treatment; these polyps are benign and reversible with discontinuation of treatment. Long-term omeprazole use in patients with Zollinger-Ellison syndrome has led to the development of gastroduodenal carcinoids. This finding is considered a clear sign of tumor association. Liver: Liver disorders, including hepatic failure (some fatal), hepatic necrosis (some fatal), hepatic encephalopathy, cholestasis, icteric hepatitis, and elevated liver function tests (alanine aminotransferase, aspartate aminotransferase, glutamyl transaminase, alkaline phosphatase, and bilirubin). Nutritional and metabolic disorders: Hypoglycemia, hypomagnesemia, hyponatremia, and weight gain. Musculoskeletal: Muscle weakness, myalgia, arthralgia, low back pain, and fractures. Neurological/Psychiatric: Psychiatric and sleep disorders, including depression, anxiety, aggression, hallucinations, confusion, insomnia, nervousness, anxiety, apathy, hypersomnia, and dream disturbances: tremor, paresthesia, and dizziness. Respiratory: Epistaxis and sore throat. Skin: Generalized skin reactions include severe toxic epidermolytic necrolysis (some fatal), Stevens-Jonhons syndrome and erythema multiforme, photosensitivity, urticaria, rash, skin inflammation, pruritus, ecchymosis, purpura, alopecia, dry skin, and hyperhidrosis. Sensory System: Tinnitus, taste perversion. Eye: Optic atrophy, anterior ischemic optic neuropathy, optic neuritis, dry eye syndrome, eye irritation, blurred vision, and diplopia. Genitourinary System: Interstitial nephritis, hematuria, proteinuria, elevated serum creatinine, microscopic pyuria, urinary tract infection, glycosuria, frequent urination, and testicular pain. Hematological System: Agranulocytosis (some fatal), hemolytic anemia, pancytopenia, neutropenia, anemia, thrombocytopenia, and leukocytopenia or leukocytosis.

[Contraindications]
This product is contraindicated in patients with a known hypersensitivity to benzimidazole-containing drugs or any of its ingredients. It is contraindicated for patients with severe renal insufficiency and infants.

[Drug Interactions]
1. Interference with Antiretroviral Therapy: The use of atazanavir and nelfinavir with proton pump inhibitors is not recommended. The use of atazanavir with proton pump inhibitors can significantly reduce atazanavir plasma concentrations, potentially leading to drug ineffectiveness and drug resistance. The use of saquinavir with proton pump inhibitors can increase saquinavir concentrations, potentially increasing drug toxicity and requiring dose reduction. Omeprazole can interact with some antiretroviral drugs. The clinical significance and mechanisms of these interactions are uncertain. One possibility is that omeprazole treatment increases gastric mucosal pH, thereby impairing antiretroviral drug absorption. Another possible mechanism of action is through CYP2C19. Reduced Atazanavir and Nelfinavir Concentrations: The serum concentrations of some antiretroviral drugs, such as atazanavir and nelfinavir, can be reduced when used with omeprazole. Multiple doses of nelfinavir (1250 mg twice daily) and omeprazole (40 mg once daily) reduced nelfinavir and M8 AGU by 36% and 92%, Cmax by 37% and 89%, and Cmin by 39% and 75%, respectively. Multiple doses of atazanavir (400 mg daily) and omeprazole (40 mg once daily, taken 2 hours before atazanavir) reduced AGU by 96%, CamX by 96%, and Cmin by 95%. Therefore, the use of omeprazole with drugs such as atazanavir and nelfinavir is not recommended. Other retroviral drugs, such as saquinavir, can increase serum concentrations. Multiple doses of saquinavir/rituximab (100/100 mg twice daily for 15 days) and omeprazole 40 mg once daily for 1 day can increase serum concentrations. 1-15 days] when used together, ACU increased by 82%, Camx increased by 75%, and Cmin increased by 106%. Therefore, it is recommended that clinical laboratories monitor the toxicity of saquinavir when used simultaneously with omeprazole. From a safety perspective, individual patients should reduce the dose of saquinavir. There are also some antiretroviral drugs whose serum concentrations do not change when used with omeprazole. 2. Affecting gastric pH affects the bioavailability of drugs because omeprazole can permanently inhibit the secretion of gastric acid, and gastric acidity is an important factor in determining bioavailability. In theory, omeprazole can inhibit the secretion of gastric acid. Omeprazole may interfere with the absorption of drugs (such as ketoconazole, itraconazole, ampicillin esters and iron salts). The absorption of digoxin can be increased when taken with omeprazole. When healthy subjects took omeprazole (20 mg once daily) and digoxin together, the bioavailability of digoxin increased by 10% (two subjects increased by 30%). Therefore, patients taking omeprazole and digoxin at the same time may need to be monitored. In clinical trials, antacids are often used with omeprazole. Omeprazole can change the pH value in the stomach, thereby destroying the sustained-release and controlled-release preparations and accelerating the dissolution of the drug. 3. Impact Omeprazole can prolong the metabolism of drugs oxidized in the liver, such as diazepam, warfarin, and phenytoin. Patients taking proton pump inhibitors (e.g., omeprazole and warfarin) may experience an increase in the international normalized ratio (INR) and prothrombin time. Increased INR and prothrombin time may lead to abnormal bleeding or even death. Patients taking proton pump inhibitors and warfarin may require monitoring of INR and prothrombin time. Although no interaction has been observed with omeprazole and phenytoin or propranolol in normal human subjects, there are clinical studies that may be of concern. Omeprazole has been reported to interact with other drugs metabolized by the cytochrome P450 system (e.g., cyclosporine, disulfiram, benzyl alcohol). When these drugs are taken concomitantly with omeprazole, patients should be monitored to determine if dose adjustments of these drugs are necessary. The concomitant use of omeprazole with voriconazole (a combined inhibitor of CYP2C19 and CYP3A4) results in a more than doubling of omeprazole exposure. Omeprazole dose adjustment is generally not required, but should be considered in patients with Zollinger-Ellison syndrome who require doses up to 240 mg/day. Compared to omeprazole, when healthy subjects took voriconazole (400 mg q12h x 1 day, then 200 mg x 6 days) and omeprazole (40 mg once daily for 7 days) simultaneously, the Cam× and AUG0-24 of omeprazole were significantly increased by an average of 2 times (90% CI: 1.8, 2.6) and an average of 4 times (90% CI: 33, 44). Omeprazole is an inhibitor of CYP2C19. In a crossover study of 20 healthy subjects, daily administration of omeprazole 40 mg increased the Cmax and AUC of cilostazol by 18% and 28% respectively after one week of treatment. % and 26%. One of the active metabolites, 3,4-dihydro-cilostawi, is 4-7 times more active than cilostazol, with Cmax and AUC increased by 29% and 69%, respectively. The combined use of cilostazol and omeprazole is expected to increase the concentrations of cilostazol and other active metabolites mentioned above. Therefore, a reduction in the dose of cilostazol from 100 mg twice daily to 50 mg twice daily should be considered. Drugs that induce GYP2C19 or CYP3A4 (such as rifampicin) may lead to decreased serum concentrations of omeprazole. In a study of 12 healthy subjects, the use of cilostazol and omeprazole was associated with a decrease in serum concentrations of omeprazole. In a crossover study in healthy male subjects, St. John’s wort (00 mg three times daily for 14 days), an inducer of CYP3A4, reduced the systemic exposure of omeprazole in both CYP2C19 metabolizers (Cmax and AUC decreased by 37.5% and 37.9%, respectively) and normal metabolizers (Cmax and AUC decreased by 49.6% and 43.9%, respectively). Concomitant use of St. John’s wort or rifampin with omeprazole should be avoided. Clopidogrel and omeprazole are CYP2C19 inhibitors. Clopidogrel inhibits CYP2C19. 19 is metabolized into an active metabolite. The combined use of clopidogrel and omeprazole (80 mg) resulted in reduced plasma concentrations of the active metabolite of clopidogrel and reduced platelet inhibition. In a crossover clinical study, 72 healthy subjects took clopidogrel alone (300 mg loading dose followed by 75 mg daily) for 5 days and compared it with omeprazole (80 mg omeprazole, taken concurrently with clopidogrel) for 5 days. Co-administration of the two drugs reduced exposure to the active metabolite of clopidogrel by 46% (on day 1) and 42% (on day 5). The active metabolite of clopidogrel selectively and irreversibly inhibits the binding of adenosine diphosphate (ADP) to the platelet P2Y12 receptor, thereby inhibiting platelet aggregation. Clopidogrel When used concomitantly with omeprazole, platelet aggregation inhibition within 5 mC adenosine diphosphate was reduced by 39% (day 1) and 21% (day 5). In another study, 72 healthy subjects took the same dose of clopidogrel and 80 mg of omeprazole over a 12-hour period; similar results were obtained; taking clopidogrel and omeprazole at different times did not prevent their interaction. There are no adequate studies comparing the combination of low-dose omeprazole or higher-dose clopidogrel with standard-dose clopidogrel. 4. Tacrolimus: The concomitant use of omeprazole and tacrolimus may increase tacrolimus serum concentrations. 5. When omeprazole is coadministered with clarithromycin or erythromycin, their plasma concentrations may increase. 6. Omeprazole Drug interaction studies with omeprazole have shown that daily oral administration of omeprazole at a dose of 20-40 mS does not affect other related CYP isoenzymes and has no metabolic interactions with the following substrates: CYP1A2 (caffeine, phenacetin, theophylline), CYP2C9 (S-warfarin, piroxicam, dihydrofenac, and naproxen), CYP2D6 (metoprolol, propranolol), CYP2E1 (ethanol), and CYP3A (lidocaine, quinidine, estradiol, budesonide). 7. Interference in the Diagnosis of Neuroendocrine Tumors: Drug-induced reduction in gastric acid can cause enteroid cell hyperplasia and increase chromogranin A levels, potentially interfering with the diagnosis of neuroendocrine tumors.

[Precautions]
1. Concomitant Gastric Malignancy : Response to omeprazole treatment does not rule out the presence of gastric malignancy. This drug should be used only after the possibility of cancer has been ruled out, because treatment with this drug can alleviate its symptoms, thereby delaying diagnosis. 2. Atrophic gastritis: Patients taking omeprazole for a long time occasionally have atrophic gastritis found during gastric biopsy. 3. Fractures: Some observational studies have shown that proton pump inhibitor therapy may increase the risk of hip, wrist and spinal fractures caused by osteoporosis. Patients with high doses, multiple daily doses and long-term treatment (one year or longer) are at higher risk. Patients treated with proton pump inhibitors should use the lowest dose and shortest course of treatment. Patients at risk of fractures caused by osteoporosis should be treated according to established treatment guidelines. 4. Omeprazole can cause Impaired function of CYP2C19 reduces the antiplatelet activity of clopidogrel. Clopidogrel is a prodrug. Clopidogrel inhibits platelet aggregation entirely due to active metabolites. The metabolism of clopidogrel's active metabolites will be impaired by the use of concomitant drugs, such as omeprazole, which interferes with the activity of CYP2C19. The simultaneous use of clopidogrel and omeprazole should be avoided. Since proton pump inhibitors (including omeprazole) are inhibitors of GYP2C19, the pharmacological activity of clopidogrel will be reduced when clopidogrel and 80 mg of omeprazole are used together or separately within 12 hours. 5. Hypomagnesemia: Symptoms of hypomagnesemia rarely occur in patients who have used proton pump inhibitors for three months, and most of them have been treated for more than one year. Patients may experience symptoms. Serious adverse events include convulsions and epilepsy, and arrhythmias. For most patients, treatment of hypomagnesemia requires magnesium supplementation and discontinuation of proton pump inhibitors. For patients who require long-term treatment and patients taking proton pump inhibitors such as digoxin or taking drugs that may cause hypomagnesemia (for example, diuretics), consider testing the patient's magnesium level at the beginning of treatment and performing periodic tests. 6. Interference with the diagnosis of neuroendocrine tumors When the drug reduces the acidity of gastric juice, the concentration of chromogranin A (CgA) will increase. Increased chromogranin A concentration may lead to a false-positive diagnosis of neuroendocrine tumors. Omeprazole treatment should be temporarily stopped before evaluating the chromogranin A concentration level. If the initial chromogranin A concentration is If protein A concentration is elevated, retesting should be considered. 7. Use with caution in patients with renal or severe hepatic impairment. 8. Effects of medication on diagnosis: ① Omeprazole can inhibit gastric acid secretion, increasing gastric pH. This feedback loop causes G cells in the gastric mucosa to secrete gastrin, thereby increasing blood gastrin levels. Omeprazole can also cause false-negative results in the 13C-urea breath test (UBT), possibly due to omeprazole's direct or indirect inhibitory effect on Helicobacter pylori (Hp). Clinically, the 13G-urea breath test should be performed at least 4 weeks after omeprazole treatment. 9. Items to be examined or monitored before, during, and after medication use: Efficacy monitoring. When treating peptic ulcers, endoscopic examinations should be performed to determine if the ulcer has healed. When treating H. pylori-related peptic ulcers, a UBT test can be performed 4 to 6 weeks after treatment completion to determine whether H. pylori has been eradicated. When treating Zollinger-Ellison syndrome, basal gastric acid secretion should be monitored to ensure it is less than 10 mEq/h (i.e., the treatment target). ② Toxicity Monitoring: Liver function should be checked regularly. Long-term users should regularly examine the gastric mucosa for tumor-like hyperplasia. Serum vitamin B12 levels should also be monitored for users taking the drug for more than 3 years. 10. To prevent excessive acid suppression, long-term, high-dose use of this drug is not recommended for the treatment of general peptic ulcers (except for Zollinger-Ellison syndrome).

[Pediatric Use]
See the package insert for details.

[Elderly Use]
Generally, no dosage adjustment is required for this drug in the elderly, but caution should be used.