Product Overview
【Drug Name】
Brand Name: Walker
English Name: Vonoprazan fumarate tablets
Pinyin: Fumasuan Funuolasheng Pian
【Main Ingredients】
The active ingredient of this product is vonoprazan fumarate.
【Appearance】 This product is a light red film-coated tablet, white after removing the coating.
【Indications】
Reflux esophagitis.
【Dosage and Administration】
Oral administration. Adults take 20 mg once daily. Most patients usually benefit within 4 weeks; if the effect is not satisfactory, the course of treatment may be extended to up to 8 weeks.
【Adverse Reactions】
Clinical Trials: The table below lists the adverse reactions reported during domestic and international clinical trials of this product. The frequency classification uses the following conventions and is based on the Committee on International Organizations of Medical Sciences (CIOMS) guidelines: Very common (≥1/10); Common (≥1/100 to <1/10); Occasional (≥1/1,000 to <1/100); Rare (≥1/10,000 to 1/1,000); Very rare (<1/10,000); Unknown (cannot be estimated based on available data). The following are adverse reactions observed post-marketing but not included above, with unknown frequencies: Immune system disorders: Drug hypersensitivity reactions (including anaphylactic shock), drug-induced dermatitis, urticaria. Hepatobiliary system disorders: Hepatotoxicity, jaundice. Skin and subcutaneous tissue disorders: Erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis.
【Contraindications】
1. This product is contraindicated in patients with known hypersensitivity to any component of this product.
2. This product is contraindicated in patients currently receiving atazanavir or rilpivirine (see [Drug Interactions]).
【Precautions】
1. Hepatotoxicity: Abnormal liver function (including liver injury) has been reported in clinical trials. Such reports have also been received post-marketing, many occurring shortly after treatment initiation. Close monitoring is necessary, and appropriate measures, including discontinuation of the drug, should be taken if evidence of abnormal liver function or signs or symptoms suggestive of hepatic insufficiency are present. 2. Vonoprazan can increase gastric pH; therefore, it is not recommended to take this product concurrently with drugs whose absorption depends on gastric pH (see [Contraindications], [Drug Interactions]). 3. Taking this product may mask symptoms of gastric malignancies; the possibility of malignancy should be ruled out before starting this product. 4. Several observational studies conducted abroad (mainly involving hospitalized patients) have reported an increased risk of gastrointestinal infections caused by Clostridium difficile in patients receiving proton pump inhibitor therapy. Pseudomembranous colitis may be due to concomitant use of antibiotics during Helicobacter pylori eradication. If unusual pain or frequent diarrhea occurs, appropriate measures, including discontinuation of the drug, should be taken. 5. Several observational studies conducted abroad have reported an increased risk of osteoporosis-related hip, wrist, or spinal fractures during proton pump inhibitor (PPI) treatment. The increased risk is more pronounced in patients receiving high-dose or long-term (≥1 year) treatment. 6. Disease progression should be closely monitored during treatment, and the lowest necessary therapeutic dose should be used based on the patient's condition. 7. Vonoprazan should be used with caution in patients with kidney or liver disease, as its metabolism and excretion may be delayed, leading to elevated blood concentrations. 8. Benign gastric polyps have been observed during long-term administration of this product.
【Special Populations】
Pediatric Precautions: No such studies have been conducted and there are no reliable references.
Pregnancy and Lactation Precautions:
Pregnancy: To date, no clinical studies evaluating vonoprazan have been conducted in pregnant subjects. In a rat toxicology study, embryo-fetal toxicity was observed at an exposure exceeding approximately 28 times the AUC of the maximum clinical dose (40 mg/day) of vonoprazan. Note that patients who are pregnant or may become pregnant should not take vonoprazan unless the expected therapeutic benefit is considered to outweigh any possible risks. Lactation: To date, no clinical studies have evaluated vonoprazan in lactating subjects. It is unknown whether vonoprazan is excreted into human breast milk. Animal studies have shown that vonoprazan is excreted into breast milk. It is recommended to avoid taking vonoprazan during lactation; if administration is necessary, breastfeeding should be discontinued first.
Precautions for the Elderly: Due to the decline in overall physiological function (e.g., liver and kidney function) in elderly patients, this product should be used with caution.
[Drug Interactions] Vonoprazan can increase gastric pH, suggesting that for drugs whose oral bioavailability is an important determinant of oral bioavailability, vonoprazan may affect its absorption. Vonoprazan should not be taken concurrently with atazanavir or rilpivirine, and caution should be exercised when taking it concurrently with nelfinavir, itraconazole, or tyrosine kinase inhibitors (gefitinib, nilotinib, erlotinib), as the effects of these drugs may be weakened. Vonoprazan should be taken with caution when co-administered with digoxin and methyldigoxin, as the effects of these drugs may be enhanced. Vonoprazan is primarily metabolized by the hepatic drug-metabolizing enzyme CYP3A4, and partially by CYP2B6, CYP2C19, and CYP2D6. Vonoprazan should be taken with caution when co-administered with the CYP3A4 inhibitor clarithromycin, as the blood concentration of vonoprazan may be increased.
【Pharmacological Action】
Vonoprazan reversibly inhibits H+,K+-ATPase activity in a potassium-competitive manner, can remain in the gastric parietal cells for a prolonged period to inhibit gastric acid production, and can effectively inhibit the formation of upper gastrointestinal mucosal damage. Toxicological Studies: Genotoxicity: The Ames test, Chinese hamster lung fibroblast chromosome aberration test, and rat micronucleus test results for vonoprazan were all negative. Reproductive Toxicity: At doses of 30, 100, and 300 mg/kg/day, vonoprazan did not affect the fertility or early embryonic development of male or female rats. At doses ≥100 mg/kg/day, maternal toxicity was observed in parent animals, including death in 4 out of 20 male animals at a dose of 300 mg/kg/day, accompanied by symptoms such as dilated pupils, tremors, prone position, soiled vulvar hair, reduced activity, red nasal discharge and bloody tears, weight loss, and decreased food intake; at a dose of 100 mg/kg/day, pupils were dilated. The NOAEL for maternal toxicity in both male and female animals was 30 mg/kg/day, and the NOAEL for reproductive function and early embryonic development was ≥300 mg/kg/day. In rat embryo-fetal developmental toxicity studies, no developmental toxicity was observed at vonoprazan doses up to 100 mg/kg/day, but developmental toxicity was observed at a dose of 300 mg/kg/day, including decreased fetal weight and number of caudal vertebrae, tail deformities, anal stenosis, membranous ventricular septal defects, and an increased incidence of external and visceral abnormalities such as abnormal origin of the subclavian artery. Maternal toxicity was observed at doses ≥100 mg/kg/day, including death in 1/20 of animals at a dose of 300 mg/kg/day, dilated pupils, tremors, prone position, reduced fecal volume, soiled fur, and drooling; maternal weight gain was slowed and food intake was reduced at doses ≥100 mg/kg. In rabbit embryo-fetal developmental toxicity studies, vonoprazan doses of 3, 10, and 30 mg/kg/day had no effect on embryo-fetal development. Maternal toxicity was observed at doses ≥10 mg/kg/day, including reduced fecal volume, decreased body weight or weight gain, and reduced food intake; at a dose of 30 mg/kg/day, two female rabbits aborted, and one mother experienced the death of her entire litter. In rat perinatal toxicity studies, doses up to 10 mg/kg/day showed no significant effect on maternal or F1 offspring development. Maternal and fetal toxicity was observed at a dose of 100 mg/kg/day. Effects on fetuses included reduced weight and liver discoloration (white and black) on day 4 after birth. This product is a light red film-coated tablet, white after removing the coating. No abnormal effects were observed on the survival, development, or growth of F2 generation offspring at doses ≤100 mg/kg/day. Vonoprazan and its metabolites can be secreted in breast milk and cross the placental barrier. Carcinogenicity: In a 2-year carcinogenicity study in mice, vonoprazan was administered by gavage at doses of 0.6, 20, 60, and 200 mg/kg/day. Survival rates decreased at a vonoprazan dose of 200 mg/kg/day. Treatment was discontinued when fewer than 20 male animals survived (week 88), and premature necropsy was performed on all surviving animals when fewer than 15 survived (week 90). In male animals at doses ≥6 mg/kg/day and female animals at doses ≥60 mg/kg/day, gastric neuroendocrine cell tumors were observed; at a dose of 200 mg/kg/day, gastric adenomas were observed. In male animals at doses ≥20 mg/kg/day and female animals at doses ≥60 mg/kg/day, hepatocellular adenomas were observed; and in male animals at doses ≥60 mg/kg/day and female animals at doses ≥200 mg/kg/day, hepatocellular carcinoma was observed. In a 2-year carcinogenicity study in rats, gavage administration of vonoprazan at doses of 5, 15, 50, and 150 mg/kg/day resulted in gastric neuroendocrine cell tumors at doses ≥5 mg/kg/day, hepatocellular tumors at doses ≥50 mg/kg/day, and hepatocellular carcinoma in one male animal and three male animals, respectively, at doses of 50 and 150 mg/kg/day. The occurrence of gastric-related tumors is believed to be related to hypergastrinemia caused by inhibition of gastric acid secretion. Hepatocellular carcinoma may be a rodent-specific finding, associated with the induction of hepatic enzymes.
【Storage】
Store tightly closed below 30°C.
【Specifications】
20mg x 7 tablets
【Packaging】
Box
【Expiration Date】
36 months
【Approval Number】
National Medical Products Administration Approval No. J20200011
【Manufacturer】
Tianjin Takeda Pharmaceutical Co., Ltd.
