Products

Cefazolin Sodium for Injection

Instructions for Cefazolin Sodium for Injection
Please read the instructions carefully and use under the guidance of a physician
Warning: This product is contraindicated in individuals who are allergic to cephalosporins and those with a history of penicillin anaphylactic shock or immediate reactions

[Name of the drug]
Generic name: Cefazolin Sodium for Injection
Product name: Cefazolin Sodium for Injection
Hanyu Pinyin: Zhusheyong Toubaozuolinna
[Ingredients]
The main ingredient of this product is cefazolin sodium.
Chemical Name: (6 R R,7 R )-3-[[(5-methyl-1,3,4-thiadiazole-2-yl)thio]methyl]-7-[(1 H H-tetraazole-1-yl)acetylamino]-8-oxo-5-thio-1-zabicyclic [4.2.0] Sodium oct-2-en-2-carboxate salt anhydride.
Chemical structural formula:
 
Molecular formula:C ₁₄ H ₁₃ N ₈ NaO ₄ S ₃
Molecular weight: 476.48
[Characteristics]
This product is a white or white-like powder or crystalline powder; Odorless.
[Indications]
It is suitable for the treatment of the following infections caused by sensitive bacteria:
1. Respiratory tract infections: Respiratory tract infections caused by Streptococcus pneumoniae, Klebsiella spp., Haemophilus influenzae, Staphylococcus aureus (penicillin-sensitive and penicillin-resistant), and group A β-hemolytic streptococcus, including otitis media, bronchitis, pneumonia, etc.
2. Urinary tract infections: Urinary tract infections caused by Escherichia coli, Proteus mirabacterium, Klebsiella spp. and some bacteria of the genus Enterobacteriaceae and Enterococcus.
3. Skin and soft tissue infections: Skin and soft tissue infections caused by Staphylococcus aureus (penicillin sensitive and penicillin resistant), group A β-hemolytic streptococcus and other streptococci bacteria.
4. Bone and Joint Infections: Bone and joint infections caused by Staphylococcus aureus.
5. Sepsis: Sepsis caused by Streptococcus pneumoniae, Staphylococcus aureus (penicillin-sensitive and penicillin-resistant), Proteus mira, Escherichia coli and Klebsiella spp.
6. Infective endocarditis: Infective endocarditis caused by Staphylococcus aureus (penicillin-sensitive and penicillin-resistant) and group β-hemolytic streptococcus.
7. Hepatobiliary system infection: Hepatobiliary system infection caused by Escherichia coli, various streptococcus spp., Proteus mirabyl, Klebsiella spp. and Staphylococcus aureus.
8. Reproductive system infections: Reproductive system infections (such as prostatitis, epididymitis) caused by Escherichia coli, Proteus mirabacter, Klebsiella spp. and some enterococci.
9. Perioperative infection prevention: This product can also be used as a prophylactic drug before, during and after surgery. Reduces the incidence of certain postoperative infections in contaminated or potentially contaminated patients (e.g., vaginal hysterectomy and cholecystectomy surgery, over 70 years of age, with acute cholecystitis, obstructive jaundice, or high risk of common bile duct stones).
Perioperative use of this product may also be effective in preventing the risk of serious infection of the surgical site during surgery (e.g., during open-heart surgery and joint replacement).
Prophylactic administration of this product should usually be discontinued within 24 hours of surgical procedure. During surgery, if an infection may lead to serious consequences (e.g., open-heart surgery and joint replacement), this product can be continued prophylactically for 3 to 5 days after surgery is completed.
This product should not be used for central nervous system infections. It is less effective for chronic urinary tract infections, especially those with abnormal urinary tract anatomy. This product is not suitable for the treatment of gonorrhea and syphilis.
[Specifications]
As C ₂ p.m. _:14 N ₈ O ₄ S ₃ 计 1.0g
[Usage and dosage]
1. Adult medication
Intravenous slow bolus, intravenous infusion or intramuscular injection, 0.5g~1g at a time, 2~4 times a day, severe infection can be increased to 6g a day, divided into 2~4 intravenous injections. The recommended dose is shown in Table 1. Intravenous (IV) administration should be no less than 30 minutes.

*In rare cases, patients should be treated with cefazolin up to 12 g per day.
2. Perioperative infection prevention medication
To prevent postoperative infection after contaminated or potentially contaminated surgery, the recommended dose is:
 . 1g~2g intravenously administered 0.5~1 hour before surgery.
 . For prolonged surgical procedures (e.g., 2 hours or more), intraoperative intravenous administration of 500 mg to 1 g (adjust the dosage according to the duration of the surgical procedure).
 . Within 24 hours after surgery, 500mg~1g was administered intravenously every 6~8 hours.
Important:
(1) Preoperative dose is given before the start of surgery (0.5~1 hour) so that the concentration of antibiotics in serum and tissue reaches sufficient when the surgical incision is started;
(2) If necessary, cefazolin is given at appropriate intervals during surgery to ensure adequate antibiotic concentrations at the expected moment of maximum exposure to the source of infection.
Prophylactic administration of cefazolin should usually be stopped within 24 hours after surgery. If an infection that may lead to serious consequences occurs during surgery (eg, open-heart surgery and joint replacement), cefazolin may be continued prophylactically for 3~5 days after surgery.
3. Medication for patients with renal insufficiency
When cefazolin is used in patients with renal insufficiency, the dose needs to be adjusted, see table 2. The recommended dose reduction should be given after the first dose (depending on the severity of the infection).

If the creatinine clearance rate of patients with renal dysfunction is greater than or equal to 55 ml/min, the normal dose can still be administered. When the creatinine clearance rate is 35~54ml/min, the full dose can be given, but the dosing interval should be at least 8 hours; When the creatinine clearance rate is 11~34ml/min, give 1/2 of the regular dose every 12 hours; When the creatinine clearance rate is less than or equal to 10ml/min, give 1/2 of the regular dose every 18~24 hours. All patients with varying degrees of renal impairment should have their starting loading dose adjusted according to the severity of infection. Patients undergoing peritoneal dialysis; See Pharmacokinetics.
4. Medication for children
For infants and children over 1 month old, for the vast majority of children with mild and moderate infection, according to their body weight of 25~50mg/kg every day, 3~4 intravenous slow bolus, intravenous drip or intramuscular injection; For children with severe infections, the daily dose can be increased to 100 mg/kg.
The safety of this product in premature infants and neonates has not been established, so this product is not recommended for premature infants and neonates. In children with mild to moderate renal insufficiency (creatinine clearance rate of 70~40ml/min), 60% of the normal dose is given every 12 hours.
In pediatric patients with moderate renal insufficiency (creatinine clearance of 40~20ml/min), 25% of the normal dose is given every 12 hours. In pediatric patients with severe renal insufficiency (creatinine clearance rate of 20~5ml/min), 10% of the normal dose is given every 24 hours. The recommended dose reduction should be given after the first dose.
[Adverse reaction]
The following adverse reactions have been reported:
Skin and subcutaneous tissue: rash, itching, hyperhidrosis, flushing, angioedema, allergic purpura, urticaria, erythema multiforme, exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis, acute generalized eruptive pustular dermatosis.
Digestive system: oral candidiasis (oral thrush), dry mouth, bitter mouth, mouth ulcers, nausea, vomiting, stomach cramps, abdominal pain, bloating, diarrhea, constipation, hepatitis, jaundice, anorexia and pseudomembranous colitis. Pseudomembranous colitis may occur during or after antibiotic therapy. Transient elevations in serum aminotransferase (SGOT, SGPT) and alkaline phosphatase levels are seen. Rarely, nausea and vomiting.
Systemic and administration site reactions: drug fever (occasionally), chest discomfort, fatigue, rarely thrombophlebitis occurring intravenously, rash, itching and swelling at the injection site. Occasional pain at the injection site after intramuscular injection administration, and some induration occurred. They are less and lighter than cefothiophene.
Immune system: anaphylaxis (incidence 1.1%), hypersensitivity reaction, anaphylactic shock.
Mental and nervous system: dizziness, headache, general or local numbness, tremors, tingling sensations in the skin, syncope, increased intracranial pressure, convulsions, convulsions, drowsiness, restlessness, insomnia, hallucinations, nightmares, vertigo, hot flashes.
Respiratory system: dyspnea, pleural effusion, laryngeal edema, cough, rhinitis, bronchospasm, interstitial pneumonia, eosinophilic pneumonia.
Cardiovascular system: palpitations, cyanosis, tachycardia, atrial fibrillation and other arrhythmias, decreased blood pressure, increased blood pressure.
Hematological system: coagulation dysfunction, neutropenia, leukopenia, thrombocytopenia, thrombocytosis, pancytopenia, basophilia, eosinophilia, agranulocytosis, eosinophilia (incidence of 1.7%), leukocytosis, granulocytosis, mononucleosis, anemia, aplastic anemia, hemolytic anemia.
Kidney and urinary system: hematuria, urinary incontinence, elevated BUN value, elevated serum creatinine, interstitial nephritis, renal failure. Patients with renal insufficiency may experience encephalopathic reactions such as confusion and seizures when using high doses (12g per day) of this product.
Other: eyelid edema, dry eyes, blurred vision, arthralgia, muscle weakness, myalgia, tinnitus. Itching of the genitals and anus (including vulvar itching, genital tumors, and vaginitis). Candida albicans double infection is occasional.
[Contraindication]
1. Contraindicated for those who are allergic to cefazolin.
2. It is prohibited for those who are allergic to other cephalosporins.
3. It is contraindicated in patients with a history of severe allergy to penicillin or other β-lactams.
[Precautions]
1. Cross-allergic reaction: Patients who are allergic to one cephalosporin or cephamycin may also be allergic to other cephalosporins or cephalomycins; Patients who are allergic to penicillin, penicillin derivatives, or penicillamine may also be allergic to cephalosporins or cephalomycin.
Before using this product, patients must be asked in detail whether they have a history of prior allergy to cefazolin, other cephalosporins, penicillins, or other drugs. This product should not be used if there is a history of anaphylactic shock with penicillins. If an allergic reaction occurs during the course of treatment, the drug should be stopped immediately. In the event of anaphylactic shock, emergency measures such as epinephrine, glucocorticoids and antihistamines should be kept open, oxygen inhaled, and administered.
2. Interference with diagnosis: 1% of patients treated with cefazolin may have a positive direct or indirect antiglobulin Coombs test and false positive urine glucose (copper sulfate method). A small number of patients may have elevated alkaline phosphatase and serum aminotransferase.
3. For patients with renal insufficiency:
Patients with low urine output due to impaired or renal insufficiency should use this product with caution, and the amount must be reduced when applying. As with other β-lactam antibiotics, seizures can occur if inappropriately high doses are given to patients with impaired renal function (creatinine clearance less than 55 mL/min).
4. Patients with hepatic impairment, renal impairment, or malnutrition, patients with a longer course of treatment, and patients who have been stable on anticoagulation therapy may be at risk of cefazolin-related decreased prothrombin activity.
5. Long-term use can lead to the overgrowth of bacteria resistant to this product, and appropriate measures should be taken in time once a second infection occurs during treatment.
6. As with all cephalosporins, this product should be used with caution in patients with gastrointestinal disorders, especially those with a history of colitis.
7. Clostridium difficile associated diarrhea (CDAD) has been reported in almost all antimicrobials, including cefazolin, ranging in severity from mild diarrhea to fatal colitis. Antimicrobial therapy alters the normal flora in the patient's colon, leading to an overgrowth of C. difficile.
Toxins A and B produced by Clostridium difficile are responsible for the occurrence of CDAD. Strains of Clostridium difficile that produce high levels of toxins can cause increased morbidity and mortality of CDAD, and because these infections are antimicrobial-refractory, colectomy may be necessary in such patients. Anyone who develops diarrhea after antibiotics must consider the possibility of developing CDAD. CDAD has been reported to occur 2 months after the end of antimicrobial therapy, so it is necessary to carefully understand the patient's medical history when performing CDAD differentiation.
Once CDAD is suspected or confirmed, the antibiotic the patient is receiving may need to be discontinued (except for antibiotics that have a direct inhibitory effect on Clostridium difficile). Patients should also be evaluated surgically for appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment for C. difficile infection, and surgical evaluation as clinically indicated.
8. This product is compatible with the following drugs and is contraindicated and cannot be dripped in the same bottle: amikacin sulfate, kanamycin sulfate, chlortetracycline hydrochloride, oxytetracycline hydrochloride, erythromycin gluconate, polymyxin sulfate B, colistin sodium mesylate sodium, calcium gluconate.
[Medication for pregnant and lactating women]
Pregnant women
Animal reproduction studies have been conducted in rats, mice, and rabbits, and there is no evidence of impairment of fetal or fetal fertility due to cefazolin when given up to 25 times the human dose. However, there have been no adequate and well-controlled studies in pregnant women. Because animal reproductive testing does not always predict human response, this product should only be used when clearly needed.
Cefazolin is used before cesarean section, and the drug concentration in the umbilical cord blood is about 1/4~1/3 of the maternal drug concentration. This product does not appear to have adverse effects on the fetus.
Lactating women
The content in the milk of this product is low, but breastfeeding women should still suspend breastfeeding when taking the drug.
[Children's medication]
The safety and efficacy of this product in preterm infants and neonates have not been determined, and the use of this product is not recommended for premature infants and newborns under 1 month of age. For pediatric patients over 1 month of age, see the recommended dosage under "Dosage".
[Medication for the elderly]
In a clinical trial of 920 patients treated with cefazolin, 313 participants (34%) were aged 65 years and older, and 138 participants (15%) were aged 75 years and older. There was no overall difference in the safety and efficacy of this product in these elderly subjects compared to younger subjects. Other clinical reports have not shown significant differences between older and younger patients, but the possibility that a small number of older patients are more sensitive to this product cannot be ruled out.
This product is excreted by the kidneys, so patients with renal insufficiency may be at greater risk of toxic reactions. Elderly patients usually have reduced kidney function, so the T1/2 of this product is significantly longer than that of young people in the elderly, and the dosage should be appropriately reduced or extended according to the changes in kidney function.
[Drug Interactions]
1. This product is combined with gentamicin or amikacin to enhance the antibacterial effect in vitro.
2. The combination of cefazolin and warfarin increases the risk of bleeding due to reduced synthesis of vitamin K-dependent coagulation factors.
3. Cefazolin is combined with live typhoid vaccine, and the immune effect of the latter is reduced.
4. This product may increase nephrotoxicity when used with anti-infective drugs (such as aminoglycosides, polymyxin E, polymyxin B), iodine-containing contrast agents, organoplatinum compounds, high-dose methotrexate, certain antiviral drugs (such as acyclovir, sodium phoscarnate), cyclosporine, tacrolimus and diuretics (such as furosemide), and it is recommended to monitor renal function.
5. When cefazolin is combined with probenecid, probenecid may reduce the renal tubular secretion of cephalosporins, and probenecid can lead to an increase in the blood concentration of this product and a prolonged blood half-life.
6. Cefazolin contains methiontetrazezole side chains, and alcohol-containing beverages or intravenous injection of ethanol-containing drugs can cause alcohol-withdrawal sulfur-like reactions (also known as disulfiram-like reactions) during medication.
[Drug overdose]
This product has no specific antagonists, and is mainly given symptomatic treatment and a large amount of water and rehydration in case of drug overdose.
[Pharmacology and Toxicology]
Pharmacological effects
Mechanism of action
Cefazolin is a fungicide that works by inhibiting the synthesis of bacterial cell walls.
Drug resistance
The main mechanisms of bacterial resistance to cephalosporins include the presence of ultra-broad-spectrum β-lactamase (ESBL) and enzymatic hydrolysis.
Antimicrobial profile
Cefazolin has antimicrobial activity against most strains of the following microorganisms in vitro and clinical infection:
Gram-positive bacteria
Staphylococcus aureus
Staphylococcus epidermidis
Streptococcus lactate
Streptococcus pneumoniae
Streptococcus pyogenes
Methicillin-resistant staphylococci are resistant to cefazolin.
Gram-negative bacteria
Escherichia coli
Proteus miraculous
Most indole-positive Proteus strains, Enterobacteriaceae, Morganella, Providence resii, Serratia, and Pseudomonas are resistant to cefazolin.
Sensitivity test method
Where possible, clinical microbiology laboratories should regularly report to physicians and provide the results of in vitro susceptibility tests of antimicrobials used in their hospitals, which reflect the susceptibility characteristics of hospital- and community-acquired pathogens. These reports help doctors choose antimicrobials when treating.
Dilution method
Dilution is a quantitative method for determining the MIC value of antimicrobials. These MICs are used to assess bacterial sensitivity to antimicrobials. MIC should be determined using standard test methods (if feasible, broth and/or agar). The MIC values obtained should be interpreted according to the criteria provided in Table 4.
Diffusion method
Paper diffusion is a quantitative method for measuring the diameter of the inhibition zone and can also provide reproducible assessment of bacterial sensitivity to antimicrobials. The size of the inhibition zone can be used to evaluate the sensitivity of bacteria to antimicrobials. Standard test methods should be used to determine the size of the inhibition zone. This method tests microbial sensitivity to cefazolin by using a paper piece impregnated with 30 μg cefazolin. Table 3 provides the criteria for the paper diffusion method.

注: S: 敏感（Susceptible）；I: 中介（Intermediate）；R: 耐药（Resistant）
aThe judgment criterion is based on 1 g every 8 hours.
B cefazolin sheets should not be used to determine sensitivity to other cephalosporins.
Note : Penicillin MIC ≤0.12 μg/mL for Streptococcus pyogenes and Streptococcus agalactiacus, or a paper diffusion zone containing 10 μg penicillin ≥ 24 mm in diameter, may be interpreted as sensitivity to cefazolin.
Note : Staphylococcal sensitivity to cefazolin can be inferred by testing for cefoxitin or oxacillin.
The report as "sensitive" means that if the antimicrobial reaches a concentration that inhibits the growth of pathogens at the site of infection, it is likely to inhibit pathogen growth. Reporting as "mediated" means that the results are ambiguous and that the trial should be repeated if the microorganism is not completely sensitive to the alternative clinically viable drug. This means that the possible clinical application is for use in body parts where the drug is physiologically aggregated or in the case of high doses. It also provides a buffer interval to prevent uncontrolled technical factors from causing significant differences in judgment. Reporting "drug resistance" means that antimicrobials cannot inhibit the growth of pathogens at the site of infection, and other treatments should be chosen.
Quality control
Standard sensitivity test methods enable the use of test controls, quality control and guarantee the accuracy and precision of test materials and reagents, as well as the individual techniques used to conduct the test. Standard cefazolin powders should provide the MIC value range in Table 4 below. The diffusion method uses 30 μg sheets of paper and should meet the criteria in Table 4.

Toxicology Research
Reproductive toxicity: No impairment of fertility or damage to the fetus due to cefazolin was found in reproductive toxicity studies in rats, mice, and rabbits (at doses up to 25 times the human dose).
[Pharmacokinetics]
Clinically, Cefazolin Sodium for Injection is used for intramuscular, intravenous or intravenous infusion.
Absorb
After intramuscular injection of 500mg of this product, the peak time (tmax) of blood concentration is 1~2 hours, the peak blood concentration (Cmax) reaches 38mg/L (32~42mg/L), the blood concentration can still be measured at 7mg/L at 6 hours, and 3mg/L after 8 hours; After intramuscular injection of 14.9 mg/kg, the Cmax reached at 2 hours was 52.2 mg/L. Intravenous infusion of 0.5g of this product within 20 minutes, the peak blood concentration (Cmax) is 118mg/L, and the effective concentration is maintained for 8 hours; The same dose was added to 100ml of glucose injection and intravenous infusion was given within 30 minutes, and the Cmax could reach 143.6mg/L.
distribution
The distribution volume of cefazolin is 0.12L/kg, which is smaller than other cephalosporins, and it is difficult for this product to penetrate the blood-cerebrospinal fluid barrier, and the drug concentration cannot be measured in the inflamed cerebrospinal fluid. Cefazolin can reach higher concentrations in pleural effusion, ascites, pericardial fluid, and bursal fluid. The average concentrations at 30 minutes, 60 minutes, and 120 minutes after intravenous administration were 37mg/L, 15mg/L, and 12mg/L, respectively. The average concentrations were 9 mg/L, 15 mg/L and 33 mg/L at 60 minutes, 120 minutes and 240 minutes after intramuscular injection of 0.5 g, respectively. The concentration in ascites was 90% of the blood concentration in the same period. The concentration of the drug in the inflammatory exudate is basically equal to the serum concentration; The concentration in bile is equal to or slightly exceeds the plasma concentration in the same period, and after the general therapeutic dose is given, the concentration of cefazolin in bile is 17~31 mg/L, and the maintenance time is longer than that of cefothiophene.
Protein binding
The protein binding rate of this product is 74%~86%.
Metabolism
This product is not metabolized in the body; The original drug is filtered through the glomeruli and partially excreted in the urine through the renal tubules.
Clear
The half-life of blood elimination (t1/2β) in normal healthy adults is 1.5~2 hours.
80%~90% of the administered dose can be excreted within 24 hours, and the peak concentration of urine drug after intramuscular injection of 0.5g reaches 2400mg/L. Only a small amount (0.13%) of the drug is excreted from the bile, but the concentration of the drug in the bile remains high. Probenecid can increase the blood concentration by about 30% and prolong the effective blood concentration time.
Hemodialysis clears cefazolin slowly, and the blood concentration decreases by 40%~50% after 6 hours of hemodialysis. Peritoneal dialysis generally cannot remove this product.
Pharmacokinetics in special populations
children
For the distribution of cefazolin, after intravenous administration of 50mg/kg per day, the concentration in pus was 5.5~13.3mg/L and the intraosseous concentration was 3.2~5.5mg/kg. The fetal blood concentration is 70%~90% of the maternal blood concentration, and the content in milk is low. The half-life of blood elimination (t1/2β) of newborns within 1 week of birth is 4.5 ~ 5 hours.
Elderly
The half-life of blood elimination (t1/2β) in the elderly can be extended to 2.5 hours.
Patients with renal insufficiency
In patients with renal impairment, the serum half-life is prolonged, and the duration of serum concentrations depends on the degree of renal impairment. For example, the half-life of blood elimination (T1/2β) in patients with renal failure can be prolonged, and the clearance rate of endogenous creatinine is 12~17ml/min and less than 5ml/min is 12 hours and 57 hours, respectively.
[Storage]
Keep away from light, airtight, and store no more than 25°C.
[Packaging]
Medium borosilicate glass injection bottles, sterile powders for injection, tetrafluoroethylene copolymer film co-cloride butyl rubber stoppers and antibiotic bottles are packaged with aluminum-plastic combination caps, (1) 1 bottle per box, (2) 10 bottles per box.
[Validity period]
30 months
[Implementation standards]
The National Medical Products Administration has YBH08912021 standards
[Approval number]
Sinopharm standard word H20204005 (1.0g).
[Drug marketing authorization holder]
Company name: Guangdong Jincheng Jinsu Pharmaceutical Co., Ltd
Registered address: No. 10, Shennong Road, Torch Development Zone, Zhongshan City, Guangdong Province
[Manufacturer]
Company name: Guangdong Jincheng Jinsu Pharmaceutical Co., Ltd
Production address: No. 10 Shennong Road, Torch Development Zone, Zhongshan City, Guangdong Province
Postal code: 528437
Service hotline: 400-9988-970
Telephone number: (0760) 22830525 (switchboard).
Fax number: (0760) 22578279
Website: http://www.gdjcjs.com