Date of approval.
Date of revision.
Cefdinir Capsules Instructions
Please read the instructions carefully and use under the guidance of a physician
Drug Name]
Generic name: Cefdinir Capsules
English name: Cefdinir Capsules
Hanyu Pinyin: Toubaodini Jiaonang
Ingredients
The main ingredient of this product is cefdinir.
Chemical name: (6R,7R)-7-[[(2-amino-4-thiazolyl)-(oxime)acetyl]amino]-3-vinyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid
Chemical structure formula.
Molecular formula: C14H13N5O5S2
Molecular weight: 395.42
Properties
The content of this product is light yellow or yellow powder or granule.
Indications】
The following infections caused by strains of Staphylococcus spp, Streptococcus spp, Pneumococcus spp, Streptococcus pneumoniae, Propionibacterium spp, Neisseria gonorrhoeae, Catamora spp, Escherichia coli, Klebsiella spp, Proteus mirabilis, Proteus mirabilis, Haemophilus influenzae, etc. that are sensitive to cefdinir.
– Pharyngitis, tonsillitis, acute bronchitis, pneumonia.
– Otitis media, sinusitis.
– pyelonephritis, cystitis, gonococcal urethritis.
– adnexitis, intrauterine infection, vestibular adenitis.
– mastitis, perianal abscesses, secondary infections of traumatic or surgical wounds.
– Folliculitis, boils, boils, carbuncles, infectious impetigo, dermatitis, cellulitis, lymphangitis, nail fungus, subcutaneous abscesses, powdery infection, chronic sepsis.
– Blepharitis, mydriasis, blepharitis
Specification
0.1g
Dosage and Administration
Take orally.
The usual dose for adults is 0.1g once, 3 times a day.
The dose can be increased or decreased according to age and symptoms, or according to medical advice.
Adverse Reactions
According to foreign clinical trial data, 354 cases (2.58%) of adverse reactions (including abnormal laboratory data) were reported in 13,715 patients treated with this product. The major adverse reactions were gastrointestinal symptoms (110 cases, 0.80%), such as diarrhea or abdominal pain, and skin symptoms (31 cases, 0.23%), such as rash or pruritus. Major laboratory data abnormalities included elevated glutathione (126 cases, 0.92%) and glutathione (89 cases, 0.65%); and eosinophilia (41 cases, 0.30%).
Clinical adverse reactions
0.1% ≤ incidence <5% incidence <0.1% incidence unknown allergy rash urticaria, pruritus, fever, edema erythema hematology eosinophilia neutropenia renal elevated blood urea nitrogen gastrointestinal diarrhea, abdominal pain, stomach upset nausea, vomiting, heartburn, loss of appetite, constipation microorganisms stomatitis candidiasis vitamin deficiency vitamin K deficiency symptoms (hypo prothrombinemia, bleeding tendency), B complex vitamin deficiency symptoms (tongue inflammation, stomatitis, lack of appetite, neuritis) Other Dizziness, headache, numbness with chest pressure Note: If the above symptoms occur, discontinue immediately and treat appropriately. Other adverse reactions
Dermatology: Shi-Jo syndrome (<0.1%) or toxic epidermolysis bullosa (<0.1%) may occur. Patients should be closely monitored and discontinued immediately and treated appropriately if fever, headache, arthralgia, erythema/blistering of the skin or mucous membranes, or skin sensation of tightness/burning/pain occur.
Allergic reactions: Allergic reactions such as dyspnea, erythema, angioedema, urticaria may occur with an incidence of <0.1%. Patients should be closely observed and if abnormalities occur, the drug should be discontinued immediately and treated appropriately.
Shock: Shock may occur, incidence<0.1%. Patients should be closely observed and if symptoms such as sensory discomfort, discomfort in the mouth, wheezing, dizziness, dysgeusia, tinnitus or sweating occur, the drug should be discontinued immediately and treated appropriately.
Hematology: Complete hematocrit (<0.1%), granulocyte deficiency (<0.1%, initial symptoms of fever, sore throat, headache, discomfort), thrombocytopenia (<0.1%, initial symptoms of petechiae, purpura) or hemolytic anemia (<0.1%, initial symptoms of fever, hemoglobinuria, anemia symptoms) may occur. Patients should be closely observed and if abnormalities occur, the drug should be discontinued immediately and treated appropriately.
Colitis: severe colitis (<0.1%) may occur, such as pseudomembranous colitis confirmed by blood and stool. Patients should be closely monitored and if symptoms such as abdominal pain or frequent diarrhea occur, the drug should be discontinued immediately and treated appropriately.
Interstitial pneumonia or PIE syndrome: Interstitial pneumonia or PIE syndrome confirmed by fever, cough, dyspnea, abnormal chest radiography or eosinophilia may occur (<0.1%). If such symptoms occur, the drug should be discontinued immediately and treated appropriately, such as with adrenocorticosteroid drugs.
Renal disease: Severe renal disease (<0.1%), such as acute renal failure, may occur. Patients should be closely observed and if abnormalities occur, the drug should be discontinued immediately and treated appropriately.
Fulminant hepatitis, abnormal liver function or jaundice: Serious hepatitis may occur (<0.1%), such as fulminant hepatitis with markedly elevated glutamic aminotransferase, glutamic oxalacetic aminotransferase or alkaline phosphatase, abnormal liver function (<0.1%) or jaundice (<0.1%). Patients should be closely observed and if abnormalities occur, the drug should be discontinued immediately and treated appropriately.
[Contraindications].
It is contraindicated for those who have a history of shock to this product. Use with caution in patients with a history of hypersensitivity to penicillin or cephalosporins.
Precautions】
– By convention, the course of this product should be limited to the shortest cycle required to treat the patient after the susceptibility of the microorganism to this product has been determined to prevent the development of drug-resistant bacteria.
– It is recommended to avoid co-administration with iron preparations. If combination cannot be avoided, iron preparations should be administered after 3 hours of administration of this product.
– Because of the possibility of allergic reactions such as shock, a detailed allergy history should be obtained.
– It should be used with caution in the following patients
– Those with a history of allergy to penicillin antibiotics.
– Persons who have a body type prone to allergic symptoms such as bronchial asthma, rash, urticaria, etc. in themselves or their relatives.
– Patients with severe renal dysfunction: Since cefdinir is present in the serum of patients with severe renal dysfunction for a longer period of time, the dose should be reduced and the dosing interval extended according to the severity of renal dysfunction. For patients undergoing hemodialysis, the recommended dose is 100 mg once a day.
– Patients with severe underlying disease, those who cannot eat well or take nutrition non-orally, those of advanced age, and those with cachexia (as vitamin K deficiency can occur, close clinical observation is required).
– Effect on clinical test values
– In addition to the test paper urine glucose test, false positives may occur during urine glucose testing with Benedict’s reagent, Fehling’s reagent and Clinitest test, and should be noted.
– A positive direct serum antiglobulin test may occur and should be noted.
– Other precautions
Red feces may appear when combined with iron-added products (such as milk powder or enteral nutrition). Red urine may appear.
Pregnant women and nursing mothers
The safety of the drug during pregnancy has not been established. For pregnant women or women suspected of having pregnancy, the advantages and disadvantages of using the drug should be weighed and should only be used if the advantages outweigh the disadvantages.
For women who are breastfeeding, the advantages and disadvantages should be weighed and used only when the advantages outweigh the disadvantages.
For children]
For the use in children, please refer to the instruction of Cefdinir Granules.
Medication for Elderly Patients
When using this product in elderly patients, special attention should be paid to the following aspects and the dose and dosing interval should be adjusted according to clinical observation of the patients.
1. Elderly patients may be prone to adverse reactions due to decreased physical function.
2. Due to vitamin K deficiency, elderly patients may have a tendency to bleed.
[Drug Interactions].
Caution is required when combining this product with the following drugs.
Drug signs, symptoms and therapeutic mechanism and risk factors Iron preparation is recommended to be avoided in combination with cefdinir because it may cause a decrease in absorption of cefdinir by about 10%. If combination cannot be avoided, the dosing interval between the two should be greater than 3 hours. This product may bind to iron ions in the intestine, forming a complex that is difficult to absorb. The effect of warfarin potassium may be enhanced by warfarin potassium, but no interaction between the two has been reported. Antacids (containing aluminum or magnesium) should not be administered until 2 hours after administration of this product because their effects may be diminished by reduced absorption of cefdinir. The mechanism is not clear. [Drug overdose].
It is not clear.
Pharmacology and Toxicology
Pharmacological effects
Mechanism of action
Like other cephalosporin antibacterial drugs, cefdinir acts by inhibiting the synthesis of bacterial cell wall. Cefdinir is stable to some β-lactamases, therefore, many penicillin and cephalosporin resistant bacteria are sensitive to cefdinir.
Mechanisms of resistance
The mechanisms of resistance to cefdinir are mainly: hydrolysis of β-lactamases, altered penicillin-binding proteins (PBPs) and reduced membrane permeability. Cefdinir is inactive against most Enterobacter spp., Pseudomonas, Enterococcus, penicillin-resistant Streptococcus and methicillin-resistant Staphylococcus. β-lactamase-negative ampicillin-resistant Haemophilus influenzae is not susceptible to cefdinir.
Antibacterial activity
In vitro and in clinical infections, cefdinir has antibacterial activity against most strains of the following microorganisms (see [Indications])
Gram-positive bacteria
Staphylococcus aureus (methicillin-susceptible strains only)
Streptococcus pneumoniae (penicillin-susceptible strains only)
Streptococcus pyogenes
Gram-negative bacteria
Haemophilus influenzae
Haemophilus parainfluenzae
Cataplasma
The following in vitro test data are available, but their clinical significance is not known. The in vitro minimum inhibitory concentration (MIC) of cefdinir is less than or equal to 1 μg/ml for at least 90% of the following microorganisms; however, data on the efficacy of cefdinir in the treatment of clinical infections caused by these microorganisms have not been obtained in adequately and well-controlled clinical trials.
Gram-positive bacteria
Staphylococcus epidermidis (methicillin-susceptible strains only)
Streptococcus lactis-free
Streptococcus straw green
Gram-negative bacteria
Citrobacter coxiella
Escherichia coli
Klebsiella pneumoniae
Proteus mirabilis
Susceptibility Testing Methods
Whenever possible, clinical microbiology laboratories should regularly report and provide physicians with the results of relevant in vitro susceptibility tests for antimicrobial drugs used in their hospitals that reflect the susceptibility characteristics of hospital- and community-acquired pathogens. These reports may assist physicians in the selection of antimicrobial drugs for treatment.
Dilution method
A quantitative method is used to determine the minimum inhibitory concentration (MIC), and these MIC values can be used to assess the susceptibility of bacteria to antimicrobial drugs. A standard test method (broth method or agar method) should be used to determine the MIC, and the measured MIC values can be interpreted according to the criteria in Table 1.
Diffusion method
The quantitative method using the determination of the diameter of the inhibition circle provides the same reproducible estimate of bacterial susceptibility to antimicrobial drugs. The size of the inhibition circle represents the degree of bacterial susceptibility to the antimicrobial drug and should be determined using a standard test method. This method uses paper sheets impregnated with 5 μg of cefdinir to determine the susceptibility of bacteria to antimicrobial drugs, and the spread of the sheets is determined according to the criteria in Table 1.
Table 1: Cefdinir susceptibility test determination criteria
Pathogena minimum inhibitory concentration (mcg/ml) inhibition diameter (mm) sensitive (S) intermediary (I) resistant (R) sensitive (S) intermediary (I) resistant (R) Haemophilus influenzae ≤ 1 – ≥ 20 – Haemophilus parainfluenzae ≤ 1 – ≥ 20 – Catamorax ≤ 12 ≥ 4 ≥ 2017-19 ≤ 16 Streptococcus pneumoniae b ≤ 0.51 ≥ 2 – Streptococcus pseudomallei ≤ 12≥4≥2017-19≤16a Except for Streptococcus pneumoniae, other streptococci are sensitive to penicillin (MIC≤0.12μg/ml) and can be considered sensitive to cefdinir.
b Streptococcus pneumoniae is sensitive to penicillin (MIC≤0.06μg/ml) and can be considered as sensitive to cefdinir. Susceptibility testing of Streptococcus pneumoniae isolates detecting 1 μg of benzocillin with an inhibition diameter of ≥20 mm is considered sensitive to penicillin and can be considered sensitive to cefdinir. Cefdinir susceptibility testing is not recommended for penicillin-mediated and resistant isolates, and reliable criteria for determining cefdinir susceptibility testing have not been obtained.
The susceptibility of staphylococci to cefdinir can be inferred by testing penicillin and cefoxitin or methicillin. Staphylococci that are sensitive to methicillin or cefoxitin are considered to be sensitive to cefdinir.
A “sensitive” drug sensitivity report indicates that the pathogenic bacteria will be largely inhibited from growing if the antimicrobial drug reaches an effective concentration at the site of infection. The report “intermediary” indicates that the result is inconclusive and that the test should be repeated if the microorganism is not fully susceptible to a clinically feasible alternative drug. This classification implies a possible clinical applicability at body sites where the drug is physiologically aggregated or where high doses can be used. This classification also provides a buffer to prevent interpretation differences due to small, uncontrolled technical factors. Reporting “drug resistance” indicates that if an antimicrobial drug is effective at the site of infection and largely fails to inhibit the growth of the pathogen, then other therapeutic approaches should be used.
Quality control
The standardized drug sensitivity testing process requires the use of laboratory monitoring and ensures the accuracy and precision of the test article and analytical reagents during the assay, as well as the skill level of the individual performing the experiment. Cefdinir powder standards with the MIC values in Table 2 should be provided. For 5 μg of cefdinir paper tablets using the diffusion method the inhibition diameter standard should conform to the values in Table 2.
Table 2. Acceptable quality control range for cefdinir
Quality control strains minimum inhibitory concentration (μg/ml) inhibition diameter (mm) Escherichia coli ATCC 259220.12-0.524-28 Haemophilus influenzae ATCC 497660.12-0.524-31 Staphylococcus aureus ATCC 25923–25-32 Staphylococcus aureus ATCC 292130.12-1–Pneumonia Streptococcus ATCC 496190.03-0.2526-31 Toxicological studies
Genotoxicity
Cefdinir showed negative results in the Ames test and the HGPRT point mutation test in Chinese hamster V79 cells; the test results were negative in the in vitro Chinese hamster V79 cell chromosome aberration test and the mouse bone marrow cell micronucleus test.
Reproductive toxicity
Oral administration of cefdinir 1000 mg/kg/day (70 times the human dose at mg/kg/day; 11 times the human dose at mg/m2/day) to rats did not show any impairment of fertility or reproductive behavior.
No teratogenic effects were observed in pregnant rats given cefdinir 1000 mg/kg/day orally (70 times the human dose at mg/kg/day; 11 times the human dose at mg/m2/day) and in pregnant rabbits given cefdinir 10 mg/kg/day orally (0.7 times the human dose at mg/kg/day; 0.23 times the human dose at mg/m2/day). Maternal toxicity (reduced body weight) was seen in pregnant rabbits in the mg/kg/day group, with no effect on fetuses. In the perinatal toxicity test, the body weight of the litter was reduced in the ≥100 mg/kg/day group and that of the rat offspring was reduced in the ≥32 mg/kg/day group. However, maternal reproductive parameters and offspring survival, development, behavior and reproductive function were not abnormal.
Pharmacokinetics
1. Blood concentration
When 50, 100 and 200 mg (potency) of cefdinir were administered orally to 6 healthy adults on an empty stomach, peak blood concentrations of 0.64, 1.11 and 1.74 μg/ml were reached after about 4 hours, and the plasma half-life was 1.6-1.8 hours.
Duration
Plasma drug concentration profiles after a single oral dose of cefdinir in male healthy adults
Six healthy adults who received 100 mg (potency) of cefdinir orally in one dose on an empty stomach and after eating could reach the peak blood concentration of 1.25 and 0.79 μg/ml after about 4 hours, respectively, and its absorption was slightly reduced when administered after eating.
In patients with impaired renal function, a single oral dose of 100 mg (potency) of cefdinir had a prolonged plasma half-life proportional to the degree of renal impairment.
Creatinine clearance
(ml/min) No. Half-life T1/2
(hr) Area under the curve AUC
(μg-hr/ml) ≥10031.662.7651～7012.4110.7431～5032.927.48≤3024.0616.946The plasma half-life of this product was prolonged nearly 11 times after a single oral dose of 100 mg (potency) after meal in hemodialysis patients. A single oral dose of 100 mg (potency) of cefdinir after a meal in the same patients hemodialysed for 4 hours at peak blood levels. The shortened half-life in those undergoing hemodialysis was approximately 1/6 of that in those not undergoing hemodialysis, with a clearance rate of 61%.
Peak concentration Cmax (μg/ml) 2.362.03 peak time to peak Tmax (hr) 9.00 – half-life T1/2 (hr) 16.952.76 area under the curve AUC0→∞ (μg-hr/ml) 69.0530.18 Clearance (%) – 612.Distribution
Distribution in patient’s sputum, tonsils, mucosal tissue of maxillary sinus, middle ear secretion, skin tissue and oral tissue, it is not known whether there is distribution in breast milk.
3. Metabolism
No metabolites with antibacterial activity have been found in human blood, urine and feces.
4. Excretion
Cefdinir is mainly excreted through the kidney
In healthy adults (fasting), the urinary excretion rate (0-24 hours) is about 26-33% when 50, 100 and 200mg (potency) are taken orally, and the peak urinary concentrations are 44.3, 81.5 and 132μg/ml in 4-6 hours respectively.
When 100mg (potency) of cefdinir was given orally at one time to patients with impaired renal function, the excretion was slow and proportional to the degree of renal impairment.
Storage】 Store in a cool (not more than 20℃) place under shade and seal.
Package】 Polyvinyl chloride solid pharmaceutical tablet with aluminum foil blister package; 10 capsules/plate Í1 plate/box, 6 capsules/plate Í2 plate/box.
Expiration date】 12 months
【Execution standard
【Approval number】
【Marketing license holder and manufacturer
Marketing license holder: Chengdu Bite Pharmaceutical Co.
Registered address: No. 15 Gaopeng Avenue, High-tech Zone, Chengdu
Manufacturer: Chengdu BITE Pharmaceutical Co.
Production Address: No. 1166, Airport Road 4, Southwest Airport Economic Development Zone, Shuangliu, Chengdu, China
Postal Code: 610207
Telephone number: 400-800-6276
Fax number: 028-85919027
Web address: http://www.btyy.com