Date of approval.
Date of revision.
Eprazole Enteric Dissolve Tablets Instructions
Please read the instructions carefully and use under the guidance of a physician.
Drug Name]
Generic name: Eprazole Enteric Tablets
Trade name: Ilaprazole
English Name: Ilaprazole Enteric-Coated Tablets
Hanyu Pinyin: Aipulazuo Changrong Pian
Ingredients
Main components: Iprazole
Chemical Name: 5-(1H-pyrrol-1-yl)-2-[[(4-methoxy-3-methyl ) -2-pyridinyl]-methyl]-sulfinyl-1H-benzimidazole
Chemical structure formula.
Molecular formula: C19H18N4O2S
Molecular weight: 366.43
Properties]: This product is an enteric tablet, which appears white or off-white after removing the coating.
Indications
This product is suitable for the treatment of duodenal ulcer and reflux esophagitis.
Specification
5mg
Dosage】This product is used for adults with duodenal ulcer and reflux esophagitis, swallowed daily in the morning on an empty stomach (do not chew).
Duodenal ulcer: 5-10mg per dose, once daily for 4 weeks, or as directed by physician.
Reflux esophagitis: 10mg once daily for 4 weeks. For patients who are not cured, another 4 weeks of medication is recommended; for patients who are cured but continue to have symptoms, 5mg daily for another 4 weeks, or as directed by a physician.
[Adverse Reactions].
The following adverse reactions have been reported in clinical trials of Eprazole Enteric Tablets for duodenal ulcer and reflux esophagitis. Adverse reactions are often mild to moderate and may recover on their own. The maximum duration of treatment for subjects in completed Phase III clinical trials of this product was 8 weeks, and safety data for longer duration of use are not yet available.
Duodenal ulcer (Phase II and III: a total of 507 subjects taking this product) Common adverse reactions (>1/100, <1/10) diarrhea (2.4%), headache and dizziness (2.4%), abnormal liver function (elevated ALT, AST) (1. 8%) Rare adverse reactions (>1/1,000, <1/100) skin rash, urticaria, lumbago, abdominal distension, dry mouth, palpitation, chest tightness, prolonged menstruation, abnormal urine routine (proteinuria), elevated urea nitrogen, abnormal electrocardiogram (ventricular asystole, degree I AV block), abnormal blood routine (leukopenia), etc. Reflux esophagitis (stages II and III: a total of 535 subjects taking this product) Common adverse reactions (>1/100, <1/10) abnormal liver function (elevated ALT, AST) (6.7%), gastrointestinal discomfort (2.6%), dizziness (2.1%), rash (1.1%) Rare adverse reactions (>1/1,000, < ;1/100) diarrhea, nausea/vomiting, dry mouth, bloating, constipation, fatigue and drowsiness, chest tightness, muscle and joint discomfort, abnormal blood count (leukopenia), allergic rhinitis, abnormal urine count (proteinuria) [Contraindication
Contraindicated if you are allergic to any of the ingredients of this product. It is prohibited for those who are allergic to Eprazole and other benzimidazole compounds.
Precautions】1. This product cannot be chewed or crushed, and should be swallowed whole. 2. This product has a strong inhibitory effect on gastric acid secretion, and should not be taken in large doses for a long time for general peptic ulcer and other diseases. 3. Malignant lesions of the stomach and esophagus should be ruled out before use to avoid delayed diagnosis due to symptom relief.
4, because the clinical study data of patients with hepatic and renal insufficiency is not sufficient, use with caution in patients with hepatic and renal insufficiency.
5, long-term use of proton pump inhibitors patients should pay attention to the possible risk of fracture, especially elderly patients, to regularly monitor blood magnesium levels to prevent the emergence of hypomagnesemia.
6, patients who are using clopidogrel drugs should pay attention to drug interactions with proton pump inhibitors, and communicate with the doctor on the safety of drug use before treatment to ensure drug safety.
There is no clinical trial data on the use of this product in pregnant and lactating women, and it is not recommended for pregnant and lactating women. If breastfeeding women must use the drug, they should suspend breastfeeding.
Use in Children】No clinical trial data are available for children. It is prohibited for infants and children.
Geriatric Use】In general, elderly patients have reduced gastric acid secretion capacity and other physiological functions, and should use the drug with caution. The results of clinical trials have shown that the safety and efficacy of this product in elderly patients are not significantly different from those in the general population.
Drug Interactions]
1. Since eprazole inhibits gastric acid secretion, it may affect the bioavailability of drugs that depend on gastric pH absorption (e.g. ketoconazole, itraconazole, etc.) and care should be taken to adjust the dose or avoid combining them.
2. The results of in vitro tests and metabolic studies suggest that hepatic CYP3A4 enzymes are involved in the metabolism of this product, but it is not yet possible to identify CYP3A4 enzymes as the main metabolizing enzymes of this product. The results of foreign studies showed that oral administration of 40 mg/dose of eprazole once a day for 5 days in 24 healthy subjects increased the plasma concentration of midazolam, a specific substrate of CYP3A4 enzyme, by 31-41%, suggesting that eprazole is a weak inhibitor of CYP3A4 enzyme and presumably its effect on drugs metabolized by CYP2C19 enzyme (such as diazepam, citalopram, promethazine, phenytoin sodium It is assumed that it has little effect on the metabolism of drugs metabolized by CYP2C19 enzyme (such as diazepam, citalopram, promethazine, phenytoin sodium, clomipramine, etc). There are no definitive data on whether this product is metabolized by the hepatic CYP2C19 enzyme, but available clinical trial data suggest that genetic polymorphisms of the CYP2C19 enzyme in humans do not affect the efficacy of this product.3. Pharmacokinetics of the combination of eprazole (5 mg/dose, twice daily), clarithromycin (500 mg/dose, twice daily) and amoxicillin (1 g/dose, twice daily) parameters were compared with single administration, the AUC0-¥ of eprazole decreased by approximately 8.2% (90% CI: 70.7% to 100.1%) and Cmax decreased by approximately 29.4% (90% CI: 58.3% to 80.5%), while the AUC0-¥ of clarithromycin was unchanged (90% CI: 80.1% to 120.9%) and Cmax increased by approximately 24.4% (90% CI (90% CI: 100.7%～149.2%).
[Drug Overdose] There is no experience with overdose of this product to date. No abnormalities have been observed in clinical studies with oral administration of 40 mg of this product (single dose) in healthy subjects. If accidentally taken in large quantities should be immediately symptomatic and supportive treatment.
Clinical trials】1. Gastric acid secretion inhibition study 12 healthy subjects participated in the gastric acid secretion inhibition test, the results showed that the product inhibited gastric acid secretion in a dose-dependent manner, the specific results are shown in Table 1.
Table 1 The results of 24-hour gastric pH monitoring in healthy subjects on the first day of drug administration
pH≥4 total time percentage of nighttime pH≥4 total time percentage of population in which pH≥4 was maintained for at least 16 hours Eprazole 5mg 80.36% 79.10% 25.00% Eprazole 10mg 88.11% 95.16% 41.67% Eprazole 20mg 91.02% 94.46% 75.00% Omeprazole 20mg76.61%68.06%8.33% The 24-hour gastric pH monitoring results of duodenal ulcer patients on day 5 showed that the percentage of time the 5mg dose had pH ≥ 3 was 93.8%, which met the acid suppression requirement for the treatment of peptic ulcer. The specific results are shown in Table 2.
Table 2 Results of 24-hour gastric pH monitoring (median) of duodenal ulcer patients on the 5th day of dosing
pH ≥ 3 time percentage pH ≥ 4 time percentage pH ≥ 5 time percentage 24 hours pH night pH Eprazole 5 mg (n=11) 93.80% 86.60% 76.20% 6.005.60 Eprazole 10 mg (n=10) 98.70% 97.75% 93.25% 6.406.60 Omeprazole 20 mg (n=10) 95.10%92.65%81.45%6.305.80 Clinical trial 2.1 A phase III multicenter, randomized, double-blind, double-model, positive drug parallel-controlled confirmatory clinical trial for the treatment of duodenal ulcer was conducted for this product. The enrolled population was divided into an eprazole 10 mg test group and an omeprazole 20 mg control group, and subjects swallowed the drug once daily in the morning on an empty stomach for 4 weeks. Gastroscopic ulcer healing was observed at the end of the 2nd and 4th week of the trial. The results are shown in Table 3.
Table 3 Phase III clinical healing of duodenal ulcers
2-week healing rate 4-week healing rate 4-week healing rate Eprazole 10 mg (n = 330) 77.88% 93.03% 84.55% Omeprazole 20 mg (n = 164) 75.00% 90.85% 82.32% 2.2 A randomized, double-blind, double-model, multicenter, positive drug parallel trial of different doses of Eprazole enteric-coated tablets for the treatment of duodenal ulcers was conducted. controlled trial. The enrolled population was divided into an eprazole 5 mg test group, an eprazole 10 mg test group, and a rabeprazole 10 mg control group, and subjects swallowed the drug once daily on an empty stomach in the morning for 4 weeks. Gastroscopic ulcer healing was observed at the end of the 2nd and 4th week of the trial. The results are shown in Table 4.
Table 4 Ulcer healing in the duodenal ulcer dose-effect relationship test
2-week healing rate 4-week healing rate 4-week healing rate Eprazole 5 mg (n = 131) 67.18% 90.08% 77.86% Eprazole 10 mg (n = 129) 75.97% 91.47% 83.72% Rabeprazole 10 mg (n = 130) 68.46% 90.77% 75.38% 2.3 This product was subjected to a phase III multicenter, randomized, double-blind, double-modeled, positive parallel-controlled confirmatory clinical trial for the treatment of reflux esophagitis. The subjects swallowed the drug once daily with warm water half an hour before breakfast for 4 weeks and continued to take the drug at half the dose for 4 weeks if the esophagitis healed after 4 weeks; those whose esophagitis did not heal after 4 weeks continued to take the drug at the same dose for 4 weeks. The healing of esophageal mucosa under gastroscopy was observed at the end of the 4th and 8th week of the trial. The specific results are shown in Table 5.
Table 5 Phase III clinical reflux esophagitis healing status
4-week healing rate 8-week healing rate Eprazole 10 mg (n=322) 76.09% 83.54% Esomeprazole 40 mg (n=215) 77.67% 82.79% The 4-week healing rate in patients with LA-C and LA-D grade at baseline in the phase III clinical trial was 40% (7/18) and 60% (9/15) for the Eprazole 10 mg and Esomeprazole 40 mg groups, respectively. 60% (9/15); 8-week healing rates were 50% (9/18) and 80% (12/15) for the eprazole 10 mg and esomeprazole 40 mg groups, respectively. Due to the small sample size, the results should be interpreted with caution.
[Pharmacology and Toxicology] Pharmacology: Eprazole is an irreversible proton pump inhibitor, and its structure belongs to benzimidazole class. Eprazole selectively enters the gastric lining cells after oral administration and is converted into hyposulfamide active metabolite, which interacts with the sulfhydryl group on H+/K+-ATPase to form a covalent bond of disulfide bond, irreversibly inhibiting H+/K+-ATPase and producing the effect of inhibiting gastric acid secretion. Toxicity study genotoxicity: Eprazole CHL cell chromosome aberration test and Salmonella typhimurium revertant mutation test results were positive. The results of the micronucleus test in mice were negative. Reproductive toxicity: In rats given 20, 80, 160 and 320 mg/kg orally from day 6 to day 17 of gestation, there was a slight increase in loss of animals prior to implantation, but otherwise no abnormalities were observed. In male rats given orally 63 days before mating, during mating and 2 weeks after mating, and in female rats given orally 14 days before mating, during mating and up to day 17 of gestation, at doses up to 320 mg/kg, there was an increased incidence of physical and visceral abnormalities in the fetuses, including: small eyes, enlarged subpyramidal gaps, abdominal cleft deformities, external genital deformities, short body size, generalized edema, gapless anus, and upper and lower extremity anomalies, incomplete ossification of the occipital bone, one or more of the thoracic centers, and failure to ossify the fifth metacarpal. It was administered orally to F1 rats from the 6th day of gestation to the 21st day of postpartum, and the F1 rats in the 1000 mg/kg group showed coarse body hair and hair loss, and delayed ossification. 200 and 1000 mg/kg groups showed a significant reduction in liver weight, and post-pregnancy examination of F1 female rats showed a decrease in the number of corpus luteum, the number of implantations and the number of live fetuses. Carcinogenicity: In P53(+/-) mice given orally for 26 weeks, the animals showed increased gastric weight at doses of 16 and 64 mg/kg/d, and basal mucosal hyperplasia was seen on pathological examination. endocrine tumors. The results were similar to those of other proton pump inhibitors.
Pharmacokinetics】The results of human pharmacokinetics showed that the Cmax and AUC increased with increasing dose in a single oral dose (morning fasting) of 5mg, 10mg and 20mg of this product in subjects. No prodrug was detected in the urine of the subjects. Subjects received the product orally for 7 consecutive days at a dose of 10 mg/day. Pharmacokinetic tests showed no significant changes in the pharmacokinetic parameters of eprazole compared to single doses with no accumulation in the body. Steady-state concentrations of eprazole in plasma were achieved after more than 4 days of continuous oral administration. Compared with fasting, eating can delay the peak time of blood concentration, but it has little effect on other pharmacokinetic parameters.
Storage】Store in a cool place (not more than 20℃) under shade and seal.
Package】1.Double aluminum-plastic composite film bubble package: (1) 6 tablets per box; (2) 14 tablets per box 2.Solid oral medicine in polypropylene bottles: (1) 6 tablets per bottle; (2) 10 tablets per bottle; (3) 14 tablets per bottle; (4) 20 tablets per bottle; (5) 28 tablets per bottle
Expiration date】36 months
【Execution standard
State Food and Drug Administration Standard YBH04672007
Approval number
State Drug Administration Standard H20070256
Manufacturer
Company Name: Lizhu Group Lizhu Pharmaceutical Factory
Production Address: No. 38, North Venture Road, Jinwan District, Zhuhai, Guangdong Province
Postal code: 519045 Phone number: 8008301238 (free) Fax number: 0756-8870128
Web address: www.livzon.com.cn