Date of approval.
Date of revision.
Pantoprazole Sodium Enteric Dissolve Tablets Instructions
Please read the instructions carefully and use under the guidance of a physician
Drug Name]
Generic name: Pantoprazole Sodium Enteric-Coated Tablets
English name: Pantoprazole Sodium Enteric-Coated Tablets
Hanyu Pinyin: Pantuolazuona Changrongpian
Ingredients
The main ingredient of this product is pantoprazole sodium.
Chemical name: 5-difluoromethoxy-2-[[(3,4-dimethoxy-2-pyridyl)methyl]sulfinyl]-1H-benzimidazole sodium monohydrate
Chemical structure formula.
Molecular formula: C16H14F2N3NaO4S-H2O
Molecular weight: 423.38
Properties
This product is an enteric coated tablet, which appears white or off-white after removing the coating.
Indications
– Duodenal ulcer
– Gastric ulcer
– Moderate to severe reflux esophagitis
– Helicobacter pylori infection can be eradicated by combining with the following drugs.
-Clarithromycin and amoxicillin, or
-Clarithromycin and metronidazole, or
-Amoxicillin and metronidazole
(see dosing instructions) to reduce the recurrence of duodenal and gastric ulcers caused by this microbial infection.
Reminder
Pantoprazole is not indicated for the treatment of gastrointestinal disorders with mild lesions, such as neurologic dyspepsia.
Malignant lesions of the stomach and esophagus must be excluded before pantoprazole is applied to treat gastric ulcers to avoid delaying the diagnosis due to symptomatic relief.
The diagnosis of reflux esophagitis should be verified by endoscopy.
Specification
40mg (based on C16H15F2N3O4S)
Dosage]
This product should be taken as described below without a special prescription from a physician. Please follow these methods, otherwise it may not be effective.
Combination therapy is required to eradicate infection in duodenal ulcer or gastric ulcer with H. pylori infection. The combination of pantoprazole with antibacterial drugs may be administered in any of the following regimens.
1 pantoprazole sodium enteric tablet × 2 times/day + 1000 mg amoxicillin × 2 times/day + 500 mg clarithromycin × 2 times/day
1 pantoprazole sodium enteric coated tablet × 2 times/day + 500 mg metronidazole × 2 times/day + 500 mg clarithromycin × 2 times/day
1 pantoprazole sodium enteric coated tablet × 2 times/day + 1000 mg amoxicillin × 2 times/day + 500 mg metronidazole × 2 times/day
In combination therapy, regimens with metronidazole are used only if other regimens fail to eradicate H. pylori infection.
If the patient has no indication for combination therapy, pantoprazole may be used alone at the following doses unless otherwise prescribed by a physician, if tested negative for H. pylori.
Patients with duodenal ulcer, gastric ulcer, and reflux esophagitis generally take one pantoprazole sodium enteric-coated tablet daily. In individual cases, the dose may be doubled (i.e., 2 pantoprazole sodium enteric tablets daily), especially if other treatments are not effective.
Caution
The daily dose of pantoprazole should generally not exceed 40 mg in patients with impaired renal function and in elderly patients, with some exceptions, i.e. when using combination therapy for eradication of H. pylori infection, elderly patients are also treated with regular doses (40 mg´2 times/day) of pantoprazole during 1 week of therapy.
The dose should be reduced to 1 tablet (40 mg pantoprazole sodium enteric-coated tablets) every other day in patients with severe hepatic impairment.
Dosage pattern and duration of treatment
This product should not be chewed or bitten and should be taken complete with water 1 hour before breakfast. When using combination therapy for the eradication of H. pylori infection, the second daily dose should be taken before dinner. Combination therapy usually lasts 7 days, after which, if symptoms persist, pantoprazole should be continued to ensure complete healing of the ulcer, and the recommended dose for the treatment of gastric and duodenal ulcers should be observed.
Usually duodenal ulcers heal within 2 weeks, and if a 2-week course is not sufficient, treatment may be continued for an additional 2 weeks.
Gastric ulcers and reflux esophagitis require 4 weeks of treatment. If the course of treatment is not sufficient, treatment may be continued for an additional 4 weeks.
Due to limited experience with long-term medication, the course of treatment should not exceed 8 weeks.
[Adverse reactions].
Adverse drug reactions may occur in approximately 5% of patients. The most frequently reported adverse reactions are diarrhea and headache, which may occur in approximately 1% of patients.
The following table lists the reported adverse reactions to pantoprazole, in order of frequency of occurrence in the following categories.
Very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000), unknown (could not be evaluated based on available data).
For all adverse reactions reported post-marketing, the frequency of adverse reactions could not be assessed and is therefore listed as “unknown”.
Within each frequency group, adverse reactions are listed in descending order of severity.
Table 1: List of adverse reactions to pantoprazole in clinical trials and post-marketing experience
Frequency
System
Organ Classification Uncommon Rare Very Rare Unknown Blood and lymphatic system disorders Granulocyte deficiency thrombocytopenia; leukopenia; holocytopenia Immune system disorders Allergies (including allergic reactions and anaphylaxis) Metabolism and malnutrition Hyperlipidemia and elevated lipids (triglycerides, cholesterol); weight changes Hyponatremia; hypomagnesemia; hypocalcemia (1); hypokalemia Psychiatric disorders Sleep disorders Depression (and exacerbations) Disorientation (and exacerbations) Hallucinations; confusion (especially in susceptible patients, and exacerbations of existing symptoms) Neurological disorders Headache; dizziness Taste disorders Sensory abnormalities Eye disorders Visual disturbances/blurred vision Gastrointestinal disorders Diarrhea; nausea/vomiting; bloating; constipation; dry mouth; abdominal pain and discomfort Hepatobiliary disorders Elevated liver enzymes (transaminases, gamma-glutamyl transferase) glutamyl transferase) Elevated bilirubin Hepatocellular injury; jaundice; liver failure Skin and subcutaneous tissue disorders Rash / rash / eruption; pruritic urticaria; angioedema Stevens-Johnson syndrome; Lyell syndrome; erythema multiforme; photosensitivity; subacute cutaneous lupus erythematosus Skeletal muscle and connective tissue disorders Hip, wrist, or spine fractures Arthralgia; myalgia Muscle spasms (2) Renal and urinary disorders Interstitial nephritis (may progress to renal failure) Reproductive and breast disorders Gynecomastia General condition and site of medication manifestations Weakness, fatigue, and malaise Elevated body temperature; peripheral edema Hypocalcemia (1): hypocalcemia associated with hypomagnesemia
Muscle spasm (2): muscle spasm caused by electrolyte disorders
[Contraindication
This product should not be used in patients with known hypersensitivity to a component of the drug.
In combination therapy for the eradication of H. pylori infection, this product is contraindicated in patients with moderate to severe hepatic or renal dysfunction because of the lack of clinical experience with the efficacy and safety of combination therapy in such patients.
Precautions]
When used in combination with other drugs, the dosing principles of each drug should be observed. Do not use expired pantoprazole.
Store the drug out of the reach of children.
1. Hepatic impairment
No dose adjustment is required in patients with mild to moderate hepatic impairment. For patients with severe hepatic impairment, the daily dose of pantoprazole should not exceed 20 mg. Liver enzyme monitoring should be performed periodically during treatment, especially with long-term use. If liver enzymes are elevated, the drug should be discontinued.
In combination therapy for eradication of H. pylori infection, this product is contraindicated in patients with moderate to severe hepatic impairment because clinical experience with the efficacy and safety of combination therapy in such patients is lacking.
2. Renal Impairment
No dose adjustment is required in patients with impaired renal function. It is contraindicated in patients with impaired renal function in combination therapy for the eradication of H. pylori infection because of the lack of clinical experience with the efficacy and safety of combination therapy in such patients.
3. Fractures
Proton pump inhibitor (PPI) therapy may mildly increase the risk of hip, wrist, and spine fractures, especially when receiving high doses and long-term dosing (> 1 year), primarily in elderly patients or in patients with other known risk factors. Observational studies have shown that PPIs may increase the overall risk of fracture by 10-40%. Some of this increased risk may also be due to other risk factors. Patients at risk for osteoporosis should be treated according to current clinical guidelines and should consume adequate amounts of vitamin D and calcium.
4. Gastrointestinal infections caused by bacteria
Treatment with proton pump inhibitors may result in a slightly increased risk of bacterial-induced gastrointestinal infections, such as Salmonella, Campylobacter or Clostridium difficile infections.
5. Hypomagnesemia
Severe hypomagnesemia has been reported in patients on PPIs such as pantoprazole who have been on treatment for at least 3 months, mostly for 1 year of treatment. Severe clinical manifestations of hypomagnesemia, such as fatigue, twitching of the hands and feet, confusion, convulsions, dizziness and ventricular arrhythmias, may occur, but these symptoms may appear insidiously and thus be overlooked. In most patients, hypomagnesemia improves after magnesium supplementation and discontinuation of PPI.
For patients who need to receive long-term treatment, or combined PPI and digoxin or hypomagnesemic drugs (such as diuretics), physicians should consider monitoring magnesium levels at the start of PPI therapy and periodically during treatment.
6. the effect on vitamin B12 absorption
As with all gastric acid inhibitors, pantoprazole may result in decreased absorption of vitamin B12 (cyanocobalamin) due to decreased gastric acid or gastric acid deficiency. These conditions should be considered in patients with reduced vitamin B12 stores in the body, or in patients at risk of reduced vitamin B12 absorption, when receiving long-term therapy or when appropriate clinical symptoms are observed.
7. Interference of laboratory tests
Elevated levels of chromogranin A (CgA) may interfere with the examination of neuroendocrine tumors. To avoid such interference, pantoprazole therapy should be suspended for at least 5 days before CgA level testing is performed. If CgA and gastrin levels do not return to normal after 5 days, the test should be repeated 14 days after discontinuation of PPI therapy.
8. Gastric malignancy
When there are any warning symptoms (e.g., spontaneous significant weight loss, recurrent vomiting, dysphagia, vomiting of blood or black stools) and a gastric ulcer is suspected or confirmed, the presence of a malignancy should be ruled out first, as treatment with pantoprazole may alleviate the symptoms and lead to a delay in diagnosis.
9. Carcinogenicity
Due to the characteristics of GERD, long-term use of pantoprazole may be required. In long-term studies in rodents, pantoprazole has been shown to be carcinogenic, causing rare gastrointestinal tumors. The relevance of these findings to the development of tumors in humans cannot yet be determined.
10. Acute interstitial nephritis
Acute interstitial nephritis has been observed in patients taking PPIs. 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.
11. Subacute cutaneous lupus erythematosus (SCLE)
Very rarely SCLE is associated with proton pump inhibitors. Physicians should consider discontinuing this product if skin lesions develop, especially in sun-exposed areas of the skin, and if they are associated with arthralgia. The risk of SCLE may be increased with the use of other proton pump inhibitors if SCLE has previously developed after treatment with a particular PPI.
12. Patients treated with this product for a long time, especially if used for more than 1 year, should be monitored regularly.
Pregnant women and nursing mothers
1. Pregnant women
There are insufficient data on the use of this product in pregnant women. Animal studies have shown reproductive toxicity. The potential risk to humans is unknown. Avoid using this product during pregnancy.
2. Lactating women
Animal studies have shown that pantoprazole is excreted in breast milk. There is insufficient information on the excretion of pantoprazole via human milk, but pantoprazole excretion via human milk has been reported. The risk to the newborn/infant cannot be excluded. Therefore, the benefit of breastfeeding to the infant should be weighed against the benefit of pantoprazole therapy to the mother to decide whether to discontinue breastfeeding or discontinue pantoprazole therapy.
[Pediatric Dosage].
There is no experience with its use in children.
Geriatric use]
See the precautions in [Dosage].
Drug Interactions】 1.
1. Drugs with pH-dependent drug absorption pharmacokinetic characteristics
Since pantoprazole has an acid-suppressive effect, it may affect the absorption of other drugs for which the pH in the stomach is an important determinant of oral bioavailability, such as ketoconazole, itraconazole, posaconazole and other azole antifungal drugs and other drugs such as erlotinib.
2. HIV protease inhibitors
Combining pantoprazole with HIV protease inhibitors is not recommended because the absorption of HIV protease inhibitors (e.g., atazanavir) is dependent on acidic intragastric pH and combining them significantly decreases the bioavailability of HIV protease inhibitors.
3. Methotrexate
Methotrexate levels have been reported to increase in some patients when PPIs are combined with high doses of methotrexate (e.g., 300 mg). Therefore, temporary discontinuation of pantoprazole may need to be considered in situations requiring high doses of methotrexate, such as cancer and psoriasis.
4. Coumarin-based anticoagulants (phenylpropyl coumarin or warfarin)
Post-marketing reports of increased INR, prothrombin time in patients taking concomitant PPI with warfarin or phenprocoumarin. increased INR, prothrombin time may lead to abnormal bleeding and even death. Monitoring of INR, prothrombin time is required for patients treated with both pantoprazole and warfarin or phenprocoumarin.
5. Clopidogrel
In healthy subjects, concomitant use of pantoprazole with clopidogrel had no clinically significant effect on exposure to the active metabolites of clopidogrel or on clopidogrel-induced platelet inhibition. No clopidogrel dose adjustment was required when approved doses of pantoprazole were administered.
6. Other Interaction Studies.
Pantoprazole is metabolized in the liver by the cytochrome P450 enzyme system, so any other drug that is metabolized by this enzyme system cannot be excluded from the possibility of interaction with it . However, no clinically significant interactions were observed with pantoprazole in drug interaction studies, such as carbamazepine, caffeine, valium, diclofenac, digoxin, ethanol, glibenclamide, metoprolol, nifedipine, phenprocoumon, phenytoin, theophylline, warfarin, and oral contraceptives.
There were also no interactions between pantoprazole and concomitant antacids.
No clinically significant interactions were observed between pantoprazole and concomitant antibiotics (clarithromycin, metronidazole, amoxicillin) in human kinetic studies.
[Drug Overdose].
Since pantoprazole is extensively bound to protein, it is not easily dialyzed.
In case of overdose with clinical signs of toxicity, no specific treatment is recommended except for symptomatic and supportive treatment.
Pharmacology and Toxicology
Mechanism of action
Pantoprazole is a benzimidazole derivative that inhibits gastric acid secretion by specifically binding to the proton pump on the cells of the gastric wall.
Pantoprazole is activated in the acid-secreting tubules of gastric lining cells and then specifically binds to the final link of gastric acid secretion, the proton pump (i.e. H+,K+-ATPase), to inhibit gastric acid secretion. The acid inhibitory effect is dose-dependent and can effectively inhibit basal and nocturnal gastric acid secretion. Like other proton pump inhibitors and H2 receptor antagonists, pantoprazole decreases gastric acid secretion and stimulates a corresponding increase in gastrin levels, an effect that is reversible.
Toxicological effects
Acute toxicological studies showed that the LD50 was 390 mg/kg in rats and 250 mg/kg in mice after intravenous application. chronic toxicological studies showed that pantoprazole caused an increase in gastrin levels in the blood of animals (rats and mice) and led to morphological changes in the gastric mucosa and an increase in gastric weight, an effect that was reversible and disappeared spontaneously with termination of administration. This product does not affect fertility and there is no evidence of teratogenicity.
Pharmacokinetics]
It can effectively inhibit basal, nocturnal and 24-hour gastric acid secretion, and the acid-suppressive effect is dose-related.
The pharmacokinetics of this product is linear, with the AUC (area under the concentration time curve) and Cmax (peak blood concentration) increasing proportionally with increasing dose after intravenous or oral administration of 10-80 mg. The apparent volume of distribution is 0.15 L/kg, the clearance rate is 0.1 L/h/kg, the clearance half-life (t1/2) is about 1 hour, and the plasma protein binding rate is 98%.
Drug metabolism The product is almost always metabolized in the liver by the cytochrome P450 enzyme system, with an additional pathway of phase II metabolism. The main metabolite is pantoprazole desmethyl sulfate, most of which (about 80%) is excreted by the kidney, and the rest is excreted from the feces by bile secretion.
Storage】Storage below 30℃.
Package】Polyamide/aluminum/polyvinyl chloride cold pressed solid pharmaceutical compound hard tablets and pharmaceutical aluminum foil; 7 tablets/plate×1 plate/box, 7 tablets/plate×2 plates/box.
【Effective period】24 months
【Execution standard
【Approval number】State Drug Administration H20143100
Drug marketing license holder
Name: Hangzhou Kangenbei Pharmaceutical Co.
Registered Address: No. 568, Binkang Road, Changhe Street, Binjiang District, Hangzhou, China
Manufacturer
Company Name: Hangzhou Kang’enbei Pharmaceutical Co.
Address: No. 568, Binkang Road, Changhe Street, Binjiang District, Hangzhou
Postal code: 310052
Telephone number: 0571-86622535
Fax number: 0571-87774127
Web address: www.hzconba.conbagroup.com