Approval Date.
Benzosuberastine Tablets Instructions
Please read the instructions carefully and use under the guidance of a physician.
Drug Name]
Generic Name: Bepotastine Besilate Tablets
English name: Bepotastine Besilate Tablets
Hanyu Pinyin: Benhuang Beitasiting Pian
Ingredients
Main ingredients: Benhuang Beitasiting
Chemical name: (S)-4-[4-[(4-chlorophenyl)(2-pyridyl)methoxy]piperidine]butanoic acid benzenesulfonate
Chemical structure formula.
Molecular formula: C21H25ClN2O3・C6H6O3S
Molecular weight: 547.07
Properties
This product is a white film-coated tablet, which appears white to off-white after removing the coating.
Indications
Allergic rhinitis.
Urticaria.
Itching caused by skin diseases (eczema – dermatitis, itchy rash, pruritus).
Specification
10mg
Dosage
Adults: Take orally, 10mg each time, twice daily. Increase or decrease the dose according to age and symptoms, or as prescribed by the doctor.
Children: For children over 7 years old, take 10mg orally twice daily.
[Adverse Reactions].
<Adults>
Clinical trials: Of the total number of 1446 cases, 137 cases (9.5%) reported adverse reactions, mainly sleepiness 83 cases (5.7%), thirst 16 cases (1.1%), nausea 12 cases (0.8%), stomach pain 7 cases (0.5%), diarrhea 7 cases (0.5%), upset stomach 6 cases (0.4%), fatigue 4 cases (0.3%), vomiting 4 cases ( 0.3%), etc. In addition, the abnormal clinical examination values were suspected to be related to this product in 64 cases (5.2%) out of 1225 total cases, mainly an increase in ALT (GPT) in 25 cases (2.1%) in 1209 cases, urinary occult blood in 11 cases (1.1%) in 1020 cases, γ-GTP in 10 cases (0.9%) in 1130 cases, and AST (GOT) in 8 cases (0.7%) in 1210 cases. 0.7%), etc.
Investigation of use status: Of the total 4453 cases, 89 cases (2.0%) reported adverse reactions, which mainly included 59 cases (1.3%) of sleepiness, etc.
<Children>
Investigation of special use status in children: Among 1316 cases of pediatric patients (over 5 years old, under 15 years old), 14 cases (1.1%) reported adverse reactions, mainly 5 cases (0.4%) of drowsiness, 2 cases (0.2%) of thirst, 2 cases (0.2%) of urticaria, etc.
Clinical trials: Among the 615 pediatric patients (7 years old and above and under 15 years old) in phase III clinical trials, 14 cases (2.3%) reported adverse reactions. The main ones were drowsiness in 5 cases (0.8%), abnormal liver function in 2 cases (0.3%), and increase in AST (GOT) in 2 cases (0.3%), etc.
In case of adverse reactions, appropriate treatment such as discontinuation of the drug should be taken.
Frequency
Type 0.1~＜5%＜0.1% Frequency unknown Blood Increased white blood cell count, decreased white blood cell count, increased eosinophilia Mental nervous system Sleepiness, fatigue Headache, head heavy feeling, dizziness Digestive system Thirst, nausea, stomach pain, stomach upset feeling, diarrhea Dry mouth, tongue inflammation, vomiting, abdominal pain Constipation Allergic reactions Rash swelling, urticaria Liver AST (GOT), ALT (GPT), γ- GTP rise LDH, total bilirubin rise Kidney urine occult blood urine protein, urine sugar, urine bile original urine volume reduction, urinary difficulty, urinary shutdown other menstrual abnormalities swelling, palpitations, dyspnea, numbness, abnormal taste [Contraindication
Patients with a history of hypersensitivity to the components of this product.
Precautions】
Patients with renal dysfunction should be administered with caution. The blood concentration of this product may increase and may continue to maintain high blood concentrations, so it should be administered with caution starting with a low dose (e.g., 1 dose of 5 mg), and appropriate measures should be taken in case of abnormalities, such as dose reduction, discontinuation, etc.
Important basic precautions
Due to the possibility of drowsiness, patients taking this product should be careful when performing mechanical operations with hazards such as driving a car.
Patients who have been receiving steroid therapy for a long time and want to reduce the steroid dose by the use of this product should be strictly managed slowly.
For seasonal patients, consideration should be given to the factor of multiple seasons, and it is best to start administration before the onset of the season and continue until the end of the multiple seasons.
When no effect is seen with this product, care should be taken not to take it blindly for a long time.
Pregnant women and nursing mothers
Use with caution in pregnant women or women at risk of pregnancy. If the drug must be used, it should be used only when its therapeutic significance is judged to outweigh the therapeutic risks. The safety of administration during pregnancy is not known. In addition, animal studies (rats) have found a transfer of the drug to fetal rats.
Use with caution in lactating women. When the drug must be administered, breast-feeding must be avoided. Transfer to breast milk has been reported in animal studies (rats).
For children]
The safety of this drug has not been established in low birth weight infants, newborns, lactating infants or young children.
Geriatric use]
The product is mainly excreted by the kidneys. The elderly tend to have reduced physiological functions and therefore may continue to have high blood levels, which requires attention.
Drug Interactions]
No such studies have been conducted and no reliable references are available.
Drug overdose
No studies have been conducted and no reliable references are available.
Pharmacology and Toxicology
Pharmacological effects
Benzbetastine has selective inhibition of histamine H1 receptors, no affinity for 5-HT2, α1, α2, and can inhibit the infiltration of eosinophils into inflammatory sites during allergic inflammation, and inhibit the production of activated eosinophil IL-5.
Pharmacodynamic tests showed that it inhibits histamine-induced skin reactions; in vitro tests inhibited histamine-induced contraction of guinea pig isolated smooth muscle, inhibited passive intradermal allergic reactions (PCA) in a type I allergic reaction model, inhibited the rise in nasal resistance and antigen-induced hyperpermeability of nasal mucosa vessels in an experimental allergic rhinitis model, inhibited platelet activating factor and antigen-induced eosinophil infiltration Inhibits antigen-induced eosinophilia in peripheral blood.
Toxicological studies
The non-toxic dose was 100 mg/kg/d in rats and 60 mg/kg/d in dogs when administered for 4 weeks, and 20 mg/kg/d in rats and 30 mg/kg/d in dogs when administered for 26 weeks.
Benzbetostine was negative for mutagenicity and carcinogenicity. The safe dose for reproductive function and fetuses is 100 mg/kg. There was transfer in the milk of rats after oral administration, and some transfer to fetuses.
Pharmacokinetics
Plasma drug concentration
<Adult>
The pharmacokinetic parameters of betahistine when administered orally as a single dose of 2.5 to 40 mg in healthy adult men were as follows.
Dose administered (mg) Tmax (hr) Cmax (ng/mL) AUC0-∞ (ng-hr/mL) t1/2 (hr) 2.50.8 ± 0.122.4 ± 2.1113.7 ± 7.03.3 ± 0.351.2 ± 0.246.2 ± 4.0203.6 ± 6.72.5 ± 0.1101.2 ± 0.2101.3 ±3.5438.6±29.12.4±0.1201.5±0.3199.5±13.1879.7±60.62.3±0.1401.6±0.3393.6±23.71916.4±81.12.9±0.2 (mean±standard error, n=6)
No accumulation was observed with 20 mg administered twice daily for 7 days multiple times, and the change in plasma drug concentration basically reached steady state on the second day of dosing initiation (Cmax=138.4±9.6 ng/mL after the last dose, mean±standard error, n=6). Meals essentially had no effect on plasma betahistine concentrations.
<Children>
In children aged 7 to 15 years with perennial allergic rhinitis and pediatric atopic dermatitis, when benzbetastine 10 mg was administered twice daily for 2 weeks in multiple doses, the blood concentrations of benzbetastine 1 to 3 hours after administration and 9 to 11 hours after administration were as follows.
Perennial allergic rhinitis patients atopic dermatitis patients C1-3hrC9-11hrC9-11hr mean±standard deviation
(Number of cases) 92.0±56.1
(62) 8.2±4.0
(43) 8.3±4.1
(106) (ng/mL)
Metabolism and excretion
Few metabolites were observed in plasma and urine, and 75-90% were excreted from urine in the original form of the drug (betahistine) within 24 hours after dosing.
Plasma protein binding rate
The plasma protein binding rate after 1 and 2 hours of a single dose of 10 mg in healthy adult men was 55.9% and 55.0%, respectively.
Plasma drug concentrations in patients with renal dysfunction
In patients with renal dysfunction (creatinine clearance 6 to 70 mL/min), the maximum blood concentration was increased and the AUC was significantly higher in patients with renal dysfunction (creatinine clearance 6 to 70 mL/min) when administered as a single oral dose of 5 mg of benzbetostine compared to those with normal renal function due to low renal function. When administered orally multiple times to patients with renal dysfunction, the maximum blood concentration to reach steady state is expected to increase to 1.2 to 1.8 times compared to those with normal renal function.
Classification of patients with renal dysfunction
(creatinine clearance) Tmax (hr) Cmax (ng/mL) t1/2 (hr) AUC0-∞ (ng-hr/mL) Those with normal renal function (n=5)
(>70mL/min) 1.2±0.455.1±16.82.9±0.5241.1±50.6 Patients with mild renal dysfunction (n=5)
(51-70mL/min) 1.0±0.061.0±10.83.1±0.6304.0±61.7 Patients with moderate or severe renal dysfunction (n=6)
(6 to 50 mL/min) 3.3±1.066.3±7.78.5±3.6969.1±398.3 (mean±standard deviation)
Plasma drug concentrations in the elderly
In the elderly (creatinine clearance 61.7-126.7mL/min) at a dose of benzbetostine 10mg administered orally twice a day for 3 days, the highest blood concentration after the last dose was 103.8±13.2ng/mL (mean±standard deviation, n=10).
Storage
Keep sealed.
Package】
Aluminum-plastic blister (pharmaceutical aluminum foil and polyvinyl chloride solid pharmaceutical hard tablets), plus polyester/aluminum/polyethylene pharmaceutical composite film bag packaging, 14 tablets/plate/box, 14 tablets/plate x 2 plates/box.
[Effective period
24 months.
Execution Standard
【Approval number】
【Manufacturing enterprise
Enterprise name: Chongqing Huabang Pharmaceutical Co.
Production Address: No. 69, Renhe Xingguang Avenue, Yubei District, Chongqing
Postal Code: 401121
Telephone number: 023-67034120 800-8070618 (need to use a landline to call)
Fax number: 023-67886970
Http: //www.huapont.cn