Ezetimibe Tablets

Isoprenaline is an oral, potent lipid-lowering drug with a different mechanism of action from other lipid-lowering drugs (e.g., statins, bile acid chelators (resins), phenoxy acid derivatives, and plant sterol esters). Isoprenaline adheres to the brush border of the small intestine villi, inhibiting the absorption of cholesterol, thereby reducing the transport of cholesterol from the small intestine to the liver, reducing the liver's cholesterol storage and increasing the clearance of cholesterol from the blood. Isoprenaline does not increase bile secretion (like bile acid chelators) nor inhibit the synthesis of cholesterol in the liver (like statins). Compared with placebo, Isoprenaline inhibits the absorption of cholesterol in the small intestine by 54%. Statins reduce the synthesis of cholesterol in the liver. The combination of the two drugs can further lower cholesterol levels, which is better than the use of either drug alone. Isoprenaline selectively inhibits cholesterol absorption without affecting the absorption of triglycerides, fatty acids, bile acids, progesterone, ethinyl estradiol, and fat-soluble vitamins A and D in the small intestine. Compared with either drug alone, the combined use of ezetimibe and HMG-CoA reductase inhibitors can effectively improve serum TC, LDL-C, ApoB, TG and HDL-C levels. The effect of ezetimibe alone or in combination with HMG-CoA reductase inhibitors on cardiovascular disease morbidity and mortality has not yet been established.

The main ingredients of this product are: Ezetimibe Chemical name: 1-(4-fluorophenyl)-3(R)-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4(S)-(4-hydroxyphenyl)-2-azetidine (azetidine) ketone Chemical structure: Molecular formula: C24H21F2NO3 Molecular weight: 409.4

This product is white or off-white tablets.

Primary hypercholesterolemia: This product can be used alone or in combination with HMG-CoA reductase inhibitors (statins) as an adjunctive therapy in addition to dietary control to treat primary (heterozygous familial or non-familial) hypercholesterolemia, and can reduce total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and apolipoprotein B (ApoB). Homozygous familial hypercholesterolemia (HoFH): This product can be used in combination with statins as an adjunctive therapy to other lipid-lowering therapies (such as LDL-C plasmapheresis), or to reduce TC and LDL-C levels in HoFH patients when other lipid-lowering therapies are ineffective. Homozygous sitosterolemia (or phytosterolemia): This product is used as an adjunctive therapy in addition to dietary control to reduce the levels of sitosterol and phytosterols in patients with homozygous familial sitosterolemia.

Patients should adhere to a proper low-fat diet during treatment with this product. The recommended dose of this product is 10 mg once a day, which can be taken alone, in combination with statins, or in combination with fenofibrate. This product can be taken at any time of the day, on an empty stomach or with food. Use of the drug in elderly patients No dose adjustment is required for elderly patients. Use of the drug in pediatric patients Children and adolescents aged 10 years and older: No dose adjustment is required. Children under 10 years old: This product is not recommended. Use of the drug in patients with impaired liver function No dose adjustment is required for patients with mild liver impairment (Child-Pugh score of 5 or 6) (see [Pharmacokinetics]). Use of the drug in patients with impaired renal function No dose adjustment is required for patients with impaired renal function. This product should be taken more than 2 hours before or more than 4 hours after taking bile acid chelators when used in combination with bile acid chelators.

In a 112-week clinical study, patients took 10 mg of this product daily alone (n=2396) or in combination with statins (n=11,308) or fenofibrate (n=185). The results showed that patients generally tolerated this product well, adverse reactions were mild and transient, the overall incidence of side effects was similar to that of placebo, and the trial termination rate due to adverse reactions in the trial group was comparable to that in the placebo group. The incidence of common (≥1/100, 1/10) or uncommon (≥1/1000, 1/100) drug-related adverse reactions in patients taking this product alone (n=2396) was higher than that in the placebo group (n=1159), and the incidence of adverse reactions in patients taking it in combination with statins (n=11,308) was higher than that in patients taking statins alone (n=9361). When taking this product alone: Various examinations: Uncommon: ALT and/or AST increased; blood CPK increased; γ-glutamyl transferase increased; abnormal liver function tests. Respiratory, thoracic and mediastinal disorders; Uncommon: cough. Digestive disorders: Common: abdominal pain; diarrhea; flatulence. Uncommon: dyspepsia; gastroesophageal reflux; nausea. Musculoskeletal and connective tissue disorders: Uncommon: joint pain; muscle cramps; neck pain. Metabolic and nutritional disorders: Uncommon: loss of appetite. Vascular disorders: Uncommon: hot flashes; hypertension. General disorders and medication site abnormalities: Common: fatigue. Uncommon: chest pain; general pain. Combined use with statins: Various examinations: Common: ALT increased, AST increased. Nervous system disorders: Common: headache. Uncommon: paresthesia. Digestive disorders: Uncommon: dry mouth; gastritis. Skin and subcutaneous tissue disorders: Uncommon: pruritus; rash; urticaria. Musculoskeletal and connective tissue disorders: Common: myalgia. Uncommon: back pain; myasthenia; limb pain. General disorders and medication site abnormalities: Common: fatigue; peripheral edema. Combination of ezetimibe and fenofibrate: Digestive disorders: Common: Abdominal pain. In a multicenter, double-blind, placebo-controlled clinical study in patients with mixed hyperlipidemia, 625 patients were treated for up to 12 weeks and 576 patients were treated for an additional 48 weeks. The combination of ezetimibe and fenofibrate was well tolerated. The study was not designed to compare rare events between treatment groups. The incidence (95% confidence interval) of clinically significant elevations (sustained 3 times the upper limit of normal) of serum aminotransferases was 4.5% (1.9, 8.8) and 27% (1.2, 5.4) when fenofibrate was used alone and when ezetimibe was used in combination with fenofibrate, respectively (adjusted for treatment). The corresponding incidences of cholecystectomy were 0.6% (0.0, 3.1) and 1.7% (0.6, 4.0), respectively (see Precautions). The number of patients treated with ezetimibe or fenofibrate alone or in combination with fenofibrate in this study was insufficient to assess the risk of gallbladder disease. In this study, no CPK elevations above 10 times the upper limit of normal occurred in any treatment group. Laboratory indicators: In controlled clinical studies of ezetimibe alone, the incidence of transaminase elevations (ALT and/or AST ≥ 3 times the upper limit of normal) was similar in ezetimibe (0.5%) and placebo (0.3%). In studies of ezetimibe combined with statins, the incidence of transaminase elevations was 1.3% in patients taking ezetimibe and statins and 0.4% in patients taking statins alone. However, this transaminase elevation had no clinical manifestations and was not associated with cholestasis, and returned to normal values after interruption or continuation of treatment. The elevation of CPK (≥ 10 times the upper limit of normal) caused by ezetimibe alone or in combination with statins was similar to that of placebo or statins alone, respectively. Adverse reactions reported post-marketing for this product (ignoring causality evaluation): Abnormalities of the blood and lymphatic system: thrombocytopenia. Nervous System Disorders: Dizziness; Paresthesia. Digestive System Disorders: Pancreatitis; Constipation. Skin and Subcutaneous System Disorders: Erythema multiforme. Musculoskeletal and Connective Tissue Disorders: Myalgia; Myopathy/Rhabdomyolysis (see Precautions). Systemic and Application Site Disorders: Asthenia. Immune System Disorders: Hypersensitivity reactions, including anaphylaxis, angioedema, rash, and urticaria. Hepatic System Disorders: Hepatitis; Gallstones; Cholecystitis. Psychiatric Disorders: Depression.

Allergic to any component of this product. Active liver disease, or patients with unexplained persistent elevation of serum transaminases. All HMG-CoA reductase inhibitors are restricted for use in pregnant and lactating women. When this product is used in combination with such drugs in women with potential childbirth, the HMG-CoA reductase inhibitor product instructions should be referred to (see Use in Pregnant and Lactating Women).

Precautions for children: In children and adolescents (10-18 years old), the absorption and metabolism of Ezetimibe are similar to those in adult patients. Based on the plasma concentration of total ezetimibe, there is no difference in the pharmacokinetics of adolescents and adults. There is no pharmacokinetic data for children under 10 years old. Clinical data for children and adolescents (9-17 years old) are limited to patients with HoFH and sitosterolemia. Precautions for pregnancy and lactation: There is no clinical data on drug use during pregnancy. Animal experiments have shown that Ezetimibe has no direct or indirect adverse effects on pregnancy, embryonic and fetal development, delivery, and postnatal neonatal development. However, pregnant women should still use Ezetimibe with caution. In studies on pregnant rodents, Ezetimibe combined with lovastatin, simvastatin, pravastatin, and atorvastatin did not cause embryonic or fetal teratogenic effects. In studies on pregnant rabbits, a small amount of skeletal malformations was observed. Studies on rats have found that ezetimibe can be excreted in rat breast milk. It is not yet clear whether ezetimibe is excreted in human breast milk. Therefore, unless it can be proven that its potential benefits outweigh the potential risks to the infant, Ezetimibe should not be used in breastfeeding women. Elderly precautions: The plasma concentration of total ezetimibe in elderly patients (over 65 years old) is twice that of young patients (18-45 years old). There is no significant difference in the amount of LDL-C reduction and safety after medication between elderly and young patients. Therefore, there is no need to adjust the dosage of medication for elderly patients.

Preclinical studies have shown that this product has no induction effect on cytochrome P450 drug metabolizing enzymes. No clinically significant pharmacokinetic interactions have been found between this product and known drugs that can be metabolized by cytochrome P450, 1A2, 2D6, 2C8, 2C9, 3A4 or transacetylase. When this product is used in combination with drugs such as dapsone, dextromethorphan, digoxin, oral contraceptives (ethinyl estradiol and levonorgestrel), glipizide, tolbutamide or midazolam, this product has not been found to affect the pharmacokinetics of the above drugs. When cimetidine is used in combination with this product, cimetidine does not affect the bioavailability of this product. Antacids: Taking antacids at the same time can reduce the absorption rate of this product but does not affect its bioavailability. Antacids: Taking antacids at the same time can reduce the absorption rate of this product but does not affect its bioavailability. This reduction in absorption rate has no clinical significance. Cholestyramine: Concomitant administration of cholestyramine decreased the mean AUC of total ezetimibe (ezetimibe ezetimibe glucuronide) by approximately 55%. When ezetimibe is added to cholestyramine to enhance the LDL-C lowering effect, the enhanced effect may be reduced due to the above interaction. Cyclosporine: In one study, eight renal transplant patients with creatinine clearance 50 ml/min and stable cyclosporine were given a single 10 mg dose of ezetimibe, and the mean AUC of total ezetimibe increased 3.4-fold (ranging from 2.3 to 7.9-fold) compared to healthy controls in another study (n=17). In another study, a renal transplant patient with severe renal insufficiency (creatinine clearance 13.2 ml/min/1.73m2) receiving multiple medications, including cyclosporine, had a 12-fold increase in total ezetimibe exposure compared to controls. In a two-stage crossover study of 12 healthy subjects, 20 mg of ezetimibe was taken daily for 8 days. After a single dose of 100 mg cyclosporine for 7 days, the mean AUC of cyclosporine increased by 15% (range -10%-51%) compared with cyclosporine alone. Fibrates: Combination therapy of ezetimibe with fibrates other than fenofibrate has not been studied. Fibrates can increase the concentration of cholesterol in bile and contribute to the development of cholelithiasis. In preclinical studies in dogs, ezetimibe was found to increase the amount of cholesterol in bile. Combination therapy of ezetimibe with fibrates other than fenofibrate is not recommended until relevant studies are conducted. Fenofibrate: In a pharmacokinetic study, fenofibrate increased total ezetimibe concentrations by approximately 1.5-fold when ezetimibe was co-administered with fenofibrate. If gallstones are suspected in a patient receiving ezetimibe in combination with fenofibrate, a gallbladder examination should be performed and alternative lipid-lowering therapies should be considered. Gemfibrozil: In pharmacokinetic studies, when this product is co-administered with gemfibrozil, gemfibrozil increases the total ezetimibe concentration by about 1.7 times. No clinical data are available at present. Statins: No clinically significant pharmacokinetic interactions were observed when this product was co-administered with atorvastatin, simvastatin, pravastatin, lovastatin, fluvastatin, and rosuvastatin. Anticoagulants: Studies in 12 healthy men showed that the co-administration of this product (10 mg/day) with warfarin or fluindione did not significantly affect the bioavailability and clotting time of warfarin. After this product was marketed, there were reports of an increase in the international normalized ratio in patients who used it in combination with warfarin. Most of these patients were also receiving other medications.

Keep away from light and store in sealed container (below 30℃).

10 mg

36 months