Date of approval.
Date of revision.
Instructions for Argireline Benzoate Tablets
Please read the instructions carefully and use under the guidance of a physician
Drug Name]
Generic name: Alogliptin Benzoate Tablets
English name: Alogliptin Benzoate Tablets
Hanyu Pinyin: Benjiasuan Agelieting Pian
Ingredients
The active ingredient of this product is alogliptin benzoate.
Chemical name: 2-({6-[(3R)-3-aminopiperidin-1-yl]-3-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl}methyl)-benzonitrile monobenzoate
Chemical structure formula.
Molecular formula: C18H21N5O2-C7H6O2
Molecular weight: 461.51
Properties】This product is a yellow film-coated tablet, which appears white or off-white after removing the coating.
Indications】This product is suitable for the treatment of type 2 diabetes mellitus.
Monotherapy
This product is used as an adjunct to diet control and exercise to improve glycemic control in patients with type 2 diabetes.
Combination with Metformin Hydrochloride
When metformin hydrochloride alone still cannot effectively control blood glucose, this product can be used in combination with metformin hydrochloride to improve blood glucose control in patients with type 2 diabetes based on diet and exercise.
Important Use Restrictions
This product is not intended for use in patients with type 1 diabetes or diabetic ketoacidosis because its effectiveness in type 1 diabetes and diabetic ketoacidosis has not been established.
【Specifications】.
25mg (as Alogliptin).
Dosage]
Recommended Dose
The recommended dose of this product is 25mg once daily.
This product can be taken with or without food.
Patients with impaired renal function
No dose adjustment is required for the use of Alogliptin benzoate tablets in patients with mild renal impairment (creatinine clearance [CrCl] ≥ 60 mL/min).
In patients with moderate renal impairment (creatinine clearance [CrCl] ≥30mL/min to <60mL/min), the dose of Alogliptin benzoate tablets is 12.5mg once daily.
The dose of Alogliptin benzoate in patients with severe renal impairment (creatinine clearance [CrCl] ≥15mL/min to <30mL/min) or end-stage renal failure (ESRD) (CrCl <15mL/min or requiring hemodialysis) is 6.25mg once daily. Alogliptin benzoate tablets may be used regardless of the duration of dialysis. Agliptin benzoate Tablets have not been studied in patients on peritoneal dialysis ([pharmacokinetics]).
Because the dose of Alogliptin Benzoate Tablets needs to be adjusted according to renal function, it is recommended that renal function be evaluated and reviewed periodically prior to initiating therapy.
The approved size of this product is only 25mg, which is not suitable for people with CrCl <60mL/min.
Adverse reactions】According to foreign literature
(1) Foreign clinical trials.
Because clinical studies are conducted under a variety of different conditions, the incidence of adverse reactions observed in clinical studies of one drug cannot be directly compared with the incidence of adverse reactions in clinical studies of another drug and may not reflect the incidence observed in clinical practice.
Approximately 8,500 patients with type 2 diabetes were treated with alogliptin benzoate in 14 randomized, double-blind controlled clinical trials, with approximately 2,900 subjects randomly assigned to the placebo group and approximately 2,200 subjects assigned to the active control drug group. The mean duration of treatment with alogliptin benzoate tablets was 40 weeks, and more than 2400 subjects were treated for more than 1 year. Of these patients, 63% had a history of hypertension, 51% had a history of dyslipidemia, 25% had a history of myocardial infarction, 8% had a history of unstable angina, and 7% had a history of congestive heart failure. The mean duration of diabetes was 7 years, the mean body mass index (BMI) was 31 kg/m2 (51% of patients had a BMI ≥30 kg/m2), and the mean age was 57 years (24% of patients were ≥65 years old).
Two placebo-controlled monotherapy studies were conducted for 12 and 26 weeks, respectively, in which patients received alogliptin benzoate tablets 12.5 mg once daily, alogliptin benzoate tablets 25 mg once daily, and placebo. Four placebo-controlled combination studies were also completed for 26 weeks: combination of metformin, combination of sulfonylurea, combination of thiazolidinedione, and combination of insulin.
Five placebo-controlled trials were conducted, with study duration ranging from 16 weeks to 2 years, combining metformin, combining pioglitazone, and combining metformin background therapy plus pioglitazone therapy.
Three active-controlled studies were completed with a study duration of 52 weeks in which patients were treated with pioglitazone and metformin, combined metformin therapy, and monotherapy with glipizide for comparison.
In a combined analysis of the 14 controlled clinical studies, the overall incidence of adverse events was 66% in patients treated with 25 mg of alogliptin benzoate compared with 62% in placebo-treated patients and 70% in patients treated with the active control drug. compared to 4.5% in the placebo group and 6.2% in the active control group.
Adverse reactions that were reported to occur in ≥4% of patients in the alogliptin benzoate 25 mg treatment group and were reported more frequently than in patients in the placebo group are summarized in Table 1 below.
Table 1: Adverse reactions reported in ≥4% of patients treated with alogliptin benzoate tablets 25 mg and occurring more frequently than those given placebo (summary study) Number of patients (%) Alogliptin benzoate tablets 25 mg placebo active control N=5902 N=2926 N=2257 Rhinopharyngitis 257 (4.4) 89 (3.0) 113 (5.0) Headache 247 (4.2) 72 (2.5) 121 (5.4) Upper respiratory tract infections 247 (4.2) 61 (2.1) 113 (5.0) Pancreatitis
In the clinical research program, 5902 patients were treated with alogliptin benzoate tablets 25 mg once daily, of whom 11 (0.2%) reported pancreatitis, compared with 5183 patients treated with various control drugs, of whom 5 (<0.1%) reported pancreatitis.
Allergic reactions
In the combined analysis, the overall incidence of allergic reactions in the alogliptin benzoate 25 mg group was 0.6%, compared with an overall incidence of 0.8% in the various control drug groups. 1 patient treated with alogliptin benzoate 25 mg reported 1 serum sickness event.
Hypoglycemia
Hypoglycemic events were recorded based on blood glucose values and/or clinical signs and symptoms of hypoglycemia.
In the monotherapy study, the incidence of hypoglycemia was 1.5% in alogliptin benzoate tablet-treated patients compared to 1.6% in placebo-treated patients. The use of alogliptin benzoate tablets as a combination therapy with glibenclamide or insulin did not increase the incidence of hypoglycemia compared to placebo. In a monotherapy study comparing alogliptin benzoate tablets with sulfonylureas in elderly patients, the incidence of hypoglycemia was 5.4% in the alogliptin benzoate group and 26% in the glipizide group (see Table 2 below).
Table 2: Number and rate of incidence of hypoglycemia* in placebo and active control studies when alogliptin benzoate tablets were used as combination therapy with gliphenylurea, insulin, metformin, pioglitazone, or compared with glipizide as combination therapy with gliphenylurea (26 weeks) Alogliptin benzoate tablets 25 mg + gliphenylurea placebo + gliphenylurea N=198 N=99 Overall (%) 19 ( 9.6) 11 (11.1) Severe (%) †
0 1 (1) Combination therapy as insulin (+/- metformin) (26 weeks) Alogliptin benzoate tablets 25 mg + insulin (+/- metformin) Placebo + insulin (+/- metformin) N=129 N=129 Overall (%) 35 (27) 31 (24) Severe (%) †
1 (0.8) 2 (1.6) Combination therapy as metformin (26 weeks) Alogliptin benzoate tablets 25 mg + metformin Placebo + metformin N=207 N=104 Overall (%) 0 3 (2.9) Severe (%) †
0 0 As combination therapy with pioglitazone (metformin or sulfonylurea) (26 weeks) Alogliptin benzoate tablets 25 mg + pioglitazone placebo + pioglitazone N=199 N=97 Overall (%) 14 (7.0) 5 (5.2) Severe (%) †
0 1 (1) Comparison with Glipizide (52 weeks) Alogliptin benzoate tablets 25 mg Glipizide N=222 N=219 Overall (%) 12 (5.4) 57 (26) Severe (%) †
0 3 (1.4) Compared with metformin (26 weeks) Alogliptin benzoate tablets 25 mg Metformin 500 mg twice daily N=112 N=109 Overall (%) 2 (1.8) 2 (1.8) Severe (%) † 0 0 0 Compared with glipizide as combination therapy with metformin (52 weeks) Alogliptin benzoate tablets 25 mg + metformin Glipizide + metformin N= 877 N=869 Overall (%) 12 (1.4) 207 (23.8) Severe (%) †
0 (0.5) * Adverse events of hypoglycemia based on all reports of symptomatic and asymptomatic hypoglycemia; concomitant glucose testing not required; intention-to-treat population.
† A serious event of hypoglycemia is defined as an event requiring medical assistance or showing lower levels or loss of consciousness or seizures.
In the Cardiovascular Safety (EXAMINE) study, the investigator-reported incidence of hypoglycemia was 6.7% in alogliptin benzoate treated patients and 6.5% in placebo treated patients. Serious hypoglycemic adverse reactions were reported in 0.8% and 0.6% of alogliptin benzoate and placebo-treated patients, respectively.
Vital Signs
No clinically significant changes in vital signs or electrocardiograms were observed in patients treated with alogliptin benzoate tablets.
Laboratory Tests
No clinically significant changes in hematology, serum chemistry, or urinalysis were observed in patients treated with Alogliptin benzoate tablets.
Impaired renal function
In the Glycemic Control in Patients with Type 2 Diabetes study, 3.4% and 1.3% of patients treated with alogliptin benzoate and placebo, respectively, had adverse reactions to renal function. The most common adverse reactions were renal impairment (0.5% in the alogliptin benzoate group and 0.1% in the positive control or placebo groups), decreased creatinine clearance (1.6% in the alogliptin benzoate group and 0.5% in the positive control or placebo groups), and increased blood creatinine (0.5% in the alogliptin benzoate group and 0.3% in the positive control or placebo groups).
In the EXAMINE study in patients at high risk of combined CV with type 2 diabetes, 23% of the alogliptin benzoate group and 21% of the placebo group reported adverse reactions of renal impairment. The most commonly reported adverse events were renal impairment (7.7% in the alogliptin benzoate group versus 6.7% in the placebo group), decreased glomerular filtration rate (4.9% in the alogliptin benzoate group versus 4.3% in the placebo group), and decreased renal clearance (2.2% in the alogliptin benzoate group versus 1.8% in the placebo group). Laboratory test results for renal function were evaluated, and eGFR was reduced by 25% or more in 21.1% and 18.7% of patients in the alogliptin benzoate and placebo groups, respectively. A period of worsening chronic kidney disease was observed in 16.8% and 15.5% of patients in the alogliptin benzoate and placebo groups, respectively.
Postmarketing Experience.
The following adverse reactions were identified in post-marketing use of alogliptin benzoate tablets outside the United States. These reactions were spontaneously reported from populations of unknown size, and therefore it is not possible to accurately estimate their frequency or determine a causal relationship with drug administration.
Hypersensitivity reactions included anaphylaxis, angioedema, rash, urticaria, and severe cutaneous adverse reactions (including Stevens-Johnson syndrome); elevated liver enzymes; fulminant hepatic failure and acute pancreatitis; severe disabling arthralgia; herpetic aspergillosis; diarrhea; constipation; nausea and intestinal obstruction.
Contraindications
Patients with a history of severe allergic reactions to Alogliptin products, including those who have experienced anaphylactic reactions, angioedema or severe skin adverse reactions.
Precautions]
(1) Pancreatitis
There have been post-marketing reports of acute pancreatitis in patients treated with Alogliptin benzoate tablets. In a trial of glycemic control in patients with type 2 diabetes, 6 cases (0.2%) of acute pancreatitis were reported in the alogliptin benzoate 25 mg group and 2 cases (<0.1%) in the positive control or placebo group. In the EXAMINE (a trial of cardiovascular outcomes in patients with type 2 diabetes combined with a high risk of CV) study, 10 cases (0.4%) were reported in the acute pancreatitis alogliptin benzoate group and 7 cases (0.3%) in the placebo group.
After initiation of alogliptin benzoate tablets, patients should be carefully observed for signs and symptoms of pancreatitis. If acute pancreatitis is suspected, immediately discontinue the use of Alogliptin benzoate tablets and take appropriate therapeutic measures. It is not known whether patients with a history of pancreatitis are at increased risk of pancreatitis with the use of Alogliptin benzoate tablets.
(2)
Allergic reactions
There have been post-marketing reports of serious allergic reactions in patients treated with Alogliptin benzoate tablets. These reactions include anaphylactic reactions, angioedema, and severe cutaneous adverse reactions (including Stevens-Johnson syndrome). If a serious allergic reaction is suspected, discontinue Alogliptin Benzoate Tablets, evaluate other possible causes of allergy, and initiate an alternative approach to the treatment of diabetes (see [Adverse Reactions] Postmarketing Experience). Caution should be exercised in patients who have experienced angioedema with other DPP-4 inhibitors; it is unclear whether angioedema is induced in these patients with the use of Alogliptin benzoate Tablets.
(3)
Liver function
There have been postmarketing reports of fatal and nonfatal liver failure in patients treated with allegretin benzoate tablets, some of which contain insufficient information to determine the likely cause (see [Adverse Reactions] Postmarketing Experience). In randomized controlled studies, elevations in serum alanine aminotransferase (ALT) above 3 times the upper limit of normal (ULN) were observed in: 1.3% of alogliptin-treated patients and 1.5% of all control-treated patients. In the EXAMINE study, 2.4% and 1.8% of patients in the alogliptin benzoate and placebo groups, respectively, had elevations of serum alanine aminotransferase above 3 times the upper limit of normal.
Patients with type 2 diabetes may have fatty liver, which can cause abnormal liver function test results, and patients may also have other types of liver disease, most of which can be treated and managed. Therefore, it is recommended to assess the patient’s liver function profile before starting treatment with Alogliptin benzoate tablets. Patients with abnormal liver function test results should be cautious about starting treatment with Alogliptin benzoate tablets.
Promptly perform liver function tests if patients report the onset of symptoms that may suggest liver injury (including fatigue, loss of appetite, right upper abdominal discomfort, deepening urine color, or jaundice). In the above clinical situation, if the patient develops clinically significant elevations in liver enzymes, and if abnormal liver function test results persist or worsen, discontinue Alogliptin benzoate tablets and look for possible causes. If no other cause of abnormal liver function tests is found, do not reintroduce Alogliptin benzoate tablets in the above mentioned patients.
(4)
Combine with other drugs that are known to cause hypoglycemia
Insulin and insulin stimulants (e.g., sulfonylureas) are known to cause hypoglycemia. Therefore, when used in combination with Alogliptin benzoate Tablets, it may be necessary to reduce the dose of insulin or insulinotropic agents to minimize the risk of hypoglycemia.
(5) Macrovascular events
There is no conclusive evidence from clinical studies that alogliptin benzoate tablets or any other hypoglycemic agents reduce the risk of macrovascular events.
(6) Heart Failure
In the EXAMINE study, which enrolled type 2 diabetic patients with recent coronary syndrome, 106 (3.9%) and 89 (3.3%) in the alogliptin benzoate and placebo groups, respectively, were hospitalized for congestive heart failure.
Patients at risk for heart failure should be considered for risk-benefit before starting treatment with alogliptin benzoate, such as a history of heart failure, a history of renal impairment, and observation of patients for signs and symptoms during treatment. Patients should be informed of the clinical features of heart failure and instructed to report these symptoms immediately. If heart failure continues to worsen, assess and take appropriate therapeutic measures according to the prevailing conditions and consider discontinuing Alogliptin benzoate tablets.
(7) Severe disabling arthralgia
There have been post-marketing reports of severe disabling arthralgia in patients treated with DPP-4 inhibitors. Symptoms become progressively apparent with increasing duration of treatment with this drug. Symptoms decreased after discontinuation of drug therapy. In a small percentage of patients, the symptoms reoccur when the same drug or other DPP-4 inhibitors are used again. Considering that DPP-4 inhibitors may cause severe arthralgia, the drug should be discontinued if appropriate.
(8) Herpetiform aspergillosis
There have been post-marketing reports of hospitalization for herpetiform aspergillosis in patients treated with DPP-4 inhibitors. Patients in the reports usually recovered by discontinuation of DPP-4 inhibitors and local or systemic immunosuppressive therapy. When taking treatment with Alogliptin benzoate tablets, tell the patient to report the development of blisters or vesicles and, if herpetiform aspergillosis is suspected, to discontinue Alogliptin benzoate tablets, seek dermatologic examination and take appropriate treatment measures.
[For Pregnant and Lactating Women].
Pregnancy classification B
Adequate or rigorous controlled studies of Alogliptin benzoate Tablets have not been conducted in pregnant women. Based on animal data, it is not expected that Alogliptin Benzoate Tablets will increase the risk of developmental abnormalities. Because animal reproduction studies are not always predictive of human risk and exposure, as with other glucose-lowering agents, alogliptin benzoate tablets should not be used during pregnancy except when clearly necessary.
No teratogenicity was observed when alogliptin was administered to pregnant rabbits or pregnant rats at doses up to 200 and 500 mg/kg (149 and 180 times the clinical dose, respectively, based on plasma drug exposure (AUC)) during the organogenesis period.
The administration of alogliptin at doses up to 250 mg/kg (approximately 95 times the clinical exposure based on AUC) to pregnant rats from the 6th day of gestation to the 20th day of lactation did not cause harm to embryonic development or adverse effects on offspring growth and development.
After oral administration of alogliptin to pregnant rats, drug transfer into the fetus via the placenta was observed.
Pediatric Dosage]
This study has not been conducted and no reliable references are available.
Geriatric Use]
In the clinical safety and efficacy study, a total of 8507 patients were treated with alogliptin benzoate tablets, of whom 2064 (24.3%) were 65 years of age or older and 341 (4%) were 75 years of age or older. No differences in overall safety or efficacy were observed between patients 65 years of age or older and younger patients. Clinical experience has not established a difference in response between older and younger patients, but it cannot be ruled out that some older patients may have a higher sensitivity.
[Drug Interactions].
Alogliptin benzoate tablets are excreted primarily by the kidneys in prototype form, with active renal tubular secretion presumed to be involved in this excretion (see [Pharmacokinetics]).
Precautions for Combined Use (Caution should be exercised when combining medications)
Drug signs, symptoms, treatment, mechanisms and other hypoglycemic drugs
Sulfonylureas.
Glimepiride.
Glibenclamide.
Gliclazide.
Methanesulfonylurea, etc.
Fast-acting insulin stimulantsNote 1).
Naglinide
Miglinide calcium
Alpha-glucosidase inhibitors.
Voglibose.
Acarbose.
Miglitol.
Biguanides.
Metformin hydrochloride.
Butylbiguanide hydrochloride
Thiazolidinediones.
Pioglitazone hydrochloride.
GLP-1 analogues.
Liraglutide.
Exenatide
Insulin preparationsNote 1) Since hypoglycemic symptoms may occur when Alogliptin benzoate Tablets are combined with the hypoglycemic agents in the left column, the drug should be used with caution. In particular, the risk of hypoglycemia may be increased when combining the application of Alogliptin benzoate Tablets with sulfonylureas. Consideration should be given to reducing the dose of sulfonylurea to reduce the risk of hypoglycemia produced by sulfonylurea.
When hypoglycemic symptoms are observed with the combined application of alpha-glucosidase inhibitors, glucose should be given instead of sucrose.
When thiazolidinediones are applied in combination, close attention should be paid, especially to the development of edema.
Drugs that may enhance or diminish the hypoglycemic effect of glucose-lowering drugs
Drugs that enhance the hypoglycemic effect of glucose-lowering drugs.
beta-blockers.
Salicylic acid preparations.
monoamine oxidase inhibitors.
fibrates for hyperlipidemia.
Warfarin, etc.
Drugs that weaken the hypoglycemic effect of hypoglycemic agents.
adrenaline.
adrenocorticotropic hormone.
Thyroid hormones, etc. When combining Alogliptin benzoate tablets, in addition to the drugs listed on the left, attention should be paid to their interaction with the glucose-lowering drugs listed in the precautions, and further attention should be paid to the potentiating effect of the combination on the insulin-producing effect of the glucose-lowering drug. Note 1) See Precautions (4)
Drug overdose]
In foreign clinical studies, the highest dose of Alogliptin benzoate tablets administered was 800 mg for a single dose in healthy subjects and 400 mg once daily for 14 days in patients with type 2 diabetes (equivalent to 32 and 16 times the maximum recommended clinical dose of 25 mg, respectively). At these dose levels, no serious adverse events were observed.
If an overdose event occurs, the necessary clinical monitoring and supportive therapy should be instituted based on the patient’s clinical status. Depending on clinical judgment, it may be necessary to remove unabsorbed drug from the gastrointestinal tract.
Very small amounts of alogliptin can be cleared by dialysis, with approximately 7% cleared after 3 hours of hemodialysis. Therefore, hemodialysis at the time of overdose is unlikely to be beneficial. It is not known whether alogliptin benzoate tablets are cleared by peritoneal dialysis.
Pharmacology and Toxicology]
……
Pharmacokinetics]
According to foreign literature.
The pharmacokinetics of Alogliptin benzoate tablets were studied in healthy subjects and type 2 diabetic patients. In healthy subjects, peak plasma concentrations (median Tmax) were reached 1 to 2 hours after a single oral dose of up to 800 mg of alogliptin. When the maximum recommended clinical dose of 25 mg was administered, the mean terminal half-life (T1/2) for elimination of alogliptin benzoate tablets was approximately 21 hours.
After 14 days of repeated administration of the highest dose of 400 mg to patients with type 2 diabetes, the accumulation of alogliptin was small, with total alogliptin exposure (AUC) and peak (Cmax) elevated by 34% and 9%, respectively. When alogliptin was administered as a single or repeated dose in the dose range 25 to 400 mg, total exposure and peak elevation were proportional to the increase in dose. The interindividual coefficient of variation for alogliptin AUC was 17%. The pharmacokinetic profile of alogliptin benzoate tablets was similar between healthy volunteers and patients with type 2 diabetes.
Absorption
The absolute bioavailability of Alogliptin benzoate tablets was approximately 100%. Total and peak exposure to alogliptin benzoate is not significantly altered when alogliptin benzoate tablets are taken concomitantly with a high-fat meal. Therefore, alogliptin may be taken with or separately from food.
DISTRIBUTION
After a single 12.5 mg intravenous infusion of alogliptin in healthy subjects, the end-stage volume of distribution was 417 L, indicating broad distribution of the drug into the tissues.
The plasma protein binding rate of alogliptin was 20%.
Metabolism
Alogliptin is not extensively metabolized and 60 to 71% of the administered dose is excreted in the urine as a prototype.
After oral administration of [14C]alogliptin, 2 minor metabolites were detected, the N-demethylation metabolite M-I (<1% parent compound) and the N-acetylation metabolite M-II (<6% parent compound).M-I is the active metabolite and has similar inhibitory activity to the parent compound against DPP-4; M-II has no inhibitory activity against either DPP-4 or other DPP-related M-II had no inhibitory activity against DPP-4 or other DPP-related enzymes. In vitro data show that CYP2D6 and CYP3A4 are involved in the limited metabolic effects of alogliptin.
Alogliptin is predominantly present as the (R)-isomer (>99%), with little or no in vivo conversion to the (S)-isomer. At the 25 mg dose level, the (S)-isomer was not detected.
Excretion
The major route of elimination of [14C]alogliptin-derived radioactivity was via renal excretion (76%) and 13% was recovered via feces, with an overall recovery of 89% for the administered radioactive dose. The renal clearance of alogliptin was 9.6 L/hr, indicating the involvement of active renal tubular secretion in this process, and the systemic clearance was 14.0 L/hr. Special populations
Impaired renal function
A single-dose open-label study was conducted to compare the pharmacokinetics of alogliptin 50 mg in patients with chronic impaired renal function and in healthy subjects.
In patients with mildly impaired renal function (60 ≤ CrCl< 90 mL/min), an approximately 1.2-fold increase in plasma AUC was observed with alogliptin. This degree of elevation is not clinically relevant and therefore dose adjustment is not recommended for patients with mild renal impairment.
In patients with moderately impaired renal function (30 ≤ CrCl< 60 mL/min), an approximately 2-fold increase in plasma AUC was observed with alogliptin. To maintain similar systemic exposure to alogliptin benzoate tablets as patients with normal renal function, the recommended dose for patients with moderate renal impairment is 12.5 mg once daily.
In patients with severe renal impairment (15 ≤ CrCl< 30 mL/min) and end-stage renal failure (CrCl< 15 mL/min or requiring dialysis), an approximately 3-fold and 4-fold increase in plasma AUC of alogliptin was observed, respectively. Approximately 7% of the drug was cleared by dialysis over 3 hours. Alogliptin benzoate tablets may be administered without regard to the duration of dialysis. The recommended dose for patients with severe renal impairment and end-stage renal failure requiring dialysis is 6.25 mg once daily in order to maintain similar systemic exposure to alogliptin benzoate in patients with normal renal function.
Impaired liver function
Compared to healthy subjects, patients with moderate hepatic insufficiency (Child-Pugh classification B) had approximately 10% lower total and 8% lower peak exposure to alogliptin. This reduction was not clinically significant. Alogliptin benzoate tablets have not been studied in patients with severe hepatic impairment (Child-Pugh Classification C). Alogliptin benzoate tablets should be used with caution in patients with liver disease (see [Precautions]).
Gender
No adjustment of the dose of Alogliptin benzoate Tablets based on gender is required. Gender does not have any clinically meaningful effect on the pharmacokinetics of alogliptin.
Aging
No dose adjustment of Alogliptin Benzoate Tablets based on age is required. Age does not have any clinically meaningful effect on the pharmacokinetics of alogliptin.
Children
This study has not been conducted and no reliable references are available.
Race
No adjustment of the dose of Alogliptin benzoate Tablets based on race is required. Race (Caucasian, Black, and Asian) does not have any clinically meaningful effect on the pharmacokinetics of alogliptin.
Specification】25mg (as Alogliptin)
Storage】Sealed and stored at room temperature.
Package】Packaged in aluminum foil/polyvinyl chloride solid pharmaceutical rigid tablets, 6 tablets/box.
Expiration date】24 months
Execution Standard
Approval number
[Drug Marketing License Holder
Holder’s name: Jiangsu Huashi Tong Bio-pharmaceutical Technology Co.
Address of the holder: Room 1006, Science and Technology Building, No. 1, Yucheng Avenue, Taizhou City, Jiangsu Province
Postal Code: 223516
Telephone number: 027-87531661
Fax number: 027-87531746
【Manufacturer
Company name: Jiangsu Zhongtian Pharmaceutical Co.
Production Address: Taizhou City, Jiangsu Province – No. 10 Xinglin Road, Building 4 (Drug City)
Postal Code: 223516
Telephone number: 0523-86227406
Fax number: 0523-86227406
Web address: http://www.jsztpharm.com/