Cefazolin

454.51

454.51

247-362-8

IHS69L0Y4T

DTXSID2022753

C28913

Needles from aqueous acetone

J01DB04|J - Antiinfectives for systemic use

3004909090

235

-0.58

Needles from aq acetone.

2.0±0.1 g/cm3

198-200 °C (decomp)

1.961

4.87e-01 g/L

Cefazolin sodium and soln of the drug should be protected from light. Cefazolin sodium sterile powder should be stored @ a temp less than 40 deg C, preferable between 15-30 deg C. Cefazolin sodium powder tends to darken, depending on storage condition; however, such discoloration does not indicate loss of potency. /Cefazolin sodium/

1.5X10-18 mm Hg at 25 deg C (est)

Henry's Law constant = 2.0X10-23 atm-cu m/mol at 25 °C (est)

pKa = 3.6 (carboxylic acid) (est)

186.2 Ų [M+H]+ [CCS Type: TW, Method: calibrated with Waters Major Mix]|192.7 Ų [M+Na]+ [CCS Type: TW, Method: calibrated with Waters Major Mix]

NONH for all modes of transport

3

20/21/22-36/37/38

26-36

Xn

Commercially available frozen cefazolin sodium injections are stable for 24 mo when stored @ -20 deg C. Thawed soln of the commercially available frozen injections are stable for 48 hr @ room temp (25 deg C) or 10 days when refrigerated at 5 deg C. If the commercially available frozen cefazolin sodium injections are refrigerated immediately after removal from the freezer, the injections are stable for a total of 12 days (ie, 10 days @ 5 deg C followed by 48 hr @ room temp). Soln that have been

P261, P272, P280, P285, P302+P352, P304+P341, P321, P333+P313, P342+P311, P363, P501

H317

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl cefazolin sodium, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Cefazolin sodium/

|Danger|H317 (100%): May cause an allergic skin reaction [Warning Sensitization, Skin]|P261, P272, P280, P285, P302+P352, P304+P341, P321, P333+P313, P342+P311, P363, and P501|Aggregated GHS information provided by 56 companies from 1 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.|H317 (96.77%): May cause an allergic skin reaction [Warning Sensitization, Skin]|Aggregated GHS information provided by 62 companies from 3 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Parenteral administration of cephalosporins can be associated with minor elevations in serum aminotransferase and alkaline phosphatase values, but these are generally mild, transient and not associated with symptoms or development of more severe liver injury. The frequency of these elevations is reported to be as high as 11%, but varies depending upon the frequency of monitoring, duration of therapy, and nature and severity of the underlying illness. Clinically apparent liver injury from parenteral cephalosporin administration is rare, and not all of the formulations have been linked to cases of liver injury. Cefazolin has been most frequently linked to cholestatic jaundice, but it is also one of the most frequently used cephalosporins. The clinical pattern of injury suggests that hepatotoxicity is largely a class effect from the cephalosporins, even though it is idiosyncratic and rare. The typical latency period is 1 to 4 weeks with an abrupt onset of liver injury. Symptoms and jaundice can arise after the course of antibiotics and typically consist of nausea, abdominal pain, pruritus and jaundice. The pattern of serum enzyme elevations is usually described as cholestatic, but mixed and hepatocellular instances have been reported. Liver injury is often accompanied by fever, rash and eosinophilia or other signs and symptoms of hypersensitivity. A history of penicillin allergy is not common, but the liver injury resembles that associated with penicillin hepatotoxicity.

Hypoprothrombinemia induced by large doses of salicylates and/or cephalosporins, and the gastrointestinal ulcerative or hemorrhagic potential of nonsteroidal anti-inflammatory drugs (NSAIDs), salicylates, or sulfinpyrazone may increase the risk of hemorrhage. /Cephalosporins/|Probenecid decreases renal tubular secretion of those cephalosporins excreted by this mechanism, resulting in increased and prolonged cephalosporin serum concentrations, prolonged elimination half-life, and increased risk of toxicity; probenecid has no effect on the excretion of cefoperazone, ceftazidime, or ceftriaxone; however, other cephalosporins and probenecid might be used concurrently in the treatment of infections, such as sexually transmitted diseases (STDs) or other infections, in which high and/or prolonged antibiotic serum and tissue concentrations are required. /Cephalosporins/|Concomitant admin of oral probenecid competitively inhibits tubular secretion resulting in higher and more prolonged serum concn of most cephalosporins. /Cephalosporins/|Concurrent use of nephrotoxic agents such as aminoglycosides, colistin, polymyxin B, or vancomycin may increase the risk of nephrotoxicity with some cephalosporins ... . /Cephalosporins/|For more Interactions (Complete) data for CEFAZOLIN (6 total), please visit the HSDB record page.

LD50 Mouse oral (acute) >11000 mg/kg bw|LD50 Mouse intravenous >2000 mg/kg bw|LD50 Rat intravenous >2000 mg/kg bw|LD50 Rat oral (acute) >11000 mg/kg bw

Patients who are allergic to one class of agents may manifest cross-reactivity when a member of the other class is admin. Immunological studies have demonstrated cross-reactivity in as many as 20% of patients who are allergic to penicillin, but clinical studies indicate a much lower frequency (about 1%) ... /Cephalosporins and penicillins/|Serious bleeding related either to ... thrombocytopenia, and/or platelet dysfunction has been reported with several beta-lactam antibiotics. This appears to be a particular problem with certain patients (elderly, poorly nourished, or those with renal insufficiency) who are receiving moxalactam. /Cephalosporins/

74-86%

Cefazolin's production and use as an actibacterial drug for both humans and animals(1-3) may result in its release to the environment through various waste streams(SRC).

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 12(SRC), determined from a log Kow of -0.58(2) and a regression derived equation(3), indicates that cefazolin is expected to have very high mobility in soil(SRC). An estimated pKa of 3.6 (caboxylic acid)(SRC), calculated using a method based on linear free energy relationships and perturbed molecular orbital theory(4), indicates that this compound will exist primarily as an anion in the environment and anions generally have higher mobility in soil than their neutral counterparts(5). Volatilization of cefazolin from moist soil surfaces is not expected to be an important fate process(SRC) because anions do not volatilize. Cefazolin is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.5X10-18 mm Hg(SRC), determined from a fragment constant method(6). Biodegradation data were not available(SRC, 2006).|AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 12(SRC), determined from a log Kow of -0.58(2) and a regression-derived equation(3), indicates that cefazolin is not expected to adsorb to suspended solids and sediment(SRC). An estimated pKa of 3.6 (caboxylic acid)(SRC), calculated using a method based on linear free energy relationships and perturbed molecular orbital theory(4), indicates that this compound will exist primarily as an anion in the environment. Volatilization from water surfaces is not expected(SRC) because anions do not volatilize. According to a classification scheme(5), an estimated BCF of 0.2(SRC), from its log Kow(2) and a regression-derived equation(6), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Biodegradation data were not available(SRC, 2006).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), cefazolin, which has an estimated vapor pressure of 1.5X10-18 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely in the particulate phase in the ambient atmosphere. Particulate-phase cefazolin may be removed from the air by wet or dry deposition(SRC). Cefazolin absorbs light at wavelengths >290 nm (UV max = 272 nm with a possible shoulder above 290 nm)(3) and therefore may be susceptible to direct photolysis by sunlight(4).

Cefazolin is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(1). Cefazolin absorbs light at wavelengths >290 nm (UV max = 272 nm with a possible shoulder above 290 nm)(2) and therefore may be susceptible to direct photolysis by sunlight(1).

An estimated BCF of 0.2 was calculated for cefazolin(SRC), using a log Kow of -0.58(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is low(SRC).

The Koc of cefazolin is estimated as 12(SRC), using a log Kow of -0.58(1) and a regression-derived equation(2). According to a classification scheme(3), this estimated Koc value suggests that cefazolin is expected to have very high mobility in soil. An estimated pKa of 3.6(SRC), calculated using a method based on linear free energy relationships and perturbed molecular orbital theory(4), indicates that this compound will exist primarily as an anion in the environment and anions generally have higher mobility in soils than their neutral counterparts(5).

The estimated pKa of cefazolin is 3.6 (carboxylic acid), calculated using a method based on linear free energy relationships and perturbed molecular orbital theory(1). Based on this pKa value, cefazolin is expected to exist primarily as an anion in the environment(SRC). Volatilization of cefazolin from moist soil or water surfaces is not expected to be an important fate process(SRC) because anions do not volatilize. Cefazolin is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.5X10-18 mm Hg(SRC), determined from a fragment constant method(2).

EXPERIMENTAL MILK: In depletion studies carried out in lactating cows it was shown that after the recommended treatment with the commercial formulation intended for lactating cows (two treatments of all four quarters at two successive milkings), residues in composite milk samples were below 50 ug/L at the 7th milking and below 25 ug/L at the 8th milking after the last treatment.

NIOSH (NOES Survey 1981-1983) has statistically estimated that 16,111 workers (13,596 of these are female) are potentially exposed to cefazolin in the US(1). Occupational exposure to cefazolin may occur through dermal contact with this compound at workplaces where cefazolin is produced or used(SRC). Exposure to cefazolin among the general population may be limited to those administered this substance as a drug and to those who administer cefazolin to animals(SRC).

Mainly used to treat bacterial infections of the skin. It can also be used to treat moderately severe bacterial infections involving the lung, bone, joint, stomach, blood, heart valve, and urinary tract. It is clinically effective against infections caused by staphylococci and streptococci species of Gram positive bacteria. May be used for surgical prophylaxis; if required metronidazole may be added to cover B. fragilis.|FDA Label

The parenterally administered cephalosporins are widely used as broad spectrum antibiotics for moderate-to-severe infections with susceptible organisms. Despite their widescale use, cases of drug induced liver disease from the cephalosporins are very rare, with only isolated case reports having been published.

Mesh Heading: anti-bacterial agents|Cephalosporins|Cefazolin is indicated in the treatment of biliary tract infections caused by susceptible organisms. /Included in US product labeling/|THERAP CAT: Antibacterial.|For more Therapeutic Uses (Complete) data for CEFAZOLIN (17 total), please visit the HSDB record page.

Hypersensitivity reactions to cephalosporins are the most common side effects ... /and/ appear to be identical to those caused by the penicillins ... Patients who are allergic to one class of agents may manifest cross-reactivity when a member of the other class is admin. Immunological studies have demonstrated cross-reactivity in as many as 20% of patients who are allergic to penicillin, but clinical studies indicate a much lower frequency (about 1%) ... There are no skin tests that can reliably predict whether a patient will manifest an allergic reaction to the cephalosporins. /Cephalosporins/|Maternal Medication usually Compatible with Breast-Feeding: Cefazolin: Reported Sign or Symptom in Infant or Effect on Lactation: None. /From table 6/|Positive direct and indirect antiglobulin (Coombs') test results have been reported in 3% or more of patients receiving a cephalosporin. The mechanism of this reaction is usually nonimmunologic in nature; a cephalosporin-globulin complex coats the erythrocytes and reacts nonspecifically with Coombs' serum. Nonimmunologic positive Coombs' test results are most likely to occur in patients who have received large doses of a cephalosporin or who have impaired renal function or hypoalbuminemia. /Cephalosporins/|A positive Coombs reaction appears frequently in patients who receive large doses of a cephalosporin. Hemolysis is not usually associated with this phenomenon, although it has been reported. Cephalosporins have produced rare instances of bone-marrow depression, characterized by granulocytopenia ... Serious bleeding related either to ... thrombocytopenia, and/or platelet dysfunction has been reported with several beta-lactam antibiotics. This appears to be a particular problem with certain patients (elderly, poorly nourished, or those with renal insufficiency) who are receiving moxalactam. /Cephalosporins/|For more Drug Warnings (Complete) data for CEFAZOLIN (38 total), please visit the HSDB record page.

Resistance to the cephalosporins may be related to inability of the antibiotic to reach its sites of action; to alterations in the penicillin-binding proteins (PBPs) that are targets of the cephalosporins, such that the antibiotics bind with lower affinity; or to bacterial enzymes (beta-lactamases) that can hydrolyze the beta-lactam ring and inactivate the cephalosporin ... The most prevalent mechanism of resistance to cephalosporins is destruction of the cephalosporins by hydrolysis of the beta-lactam ring ...Cefazolin is more susceptible to hydrolysis by beta-lactamase from Staphylococcus aureus than is cephalothin ...

Cefazolin (also known as cefazoline or cephazolin) is a semi-synthetic first generation cephalosporin for parenteral administration. Cefazolin has broad-spectrum antibiotic action due to inhibition of bacterial cell wall synthesis. It attains high serum levels and is excreted quickly via the urine.

Substances that inhibit the growth or reproduction of BACTERIA. (See all compounds classified as Anti-Bacterial Agents.)

Not absorbed from GI tract. Must be administered parenterally. Peak serum concentrations attained 1-2 hours post intramuscular injection.|Cefazolin is present in very low concentrations in the milk of nursing mothers. Cefazolin is excreted unchanged in the urine. In the first six hours approximately 60% of the drug is excreted in the urine and this increases to 70%-80% within 24 hours.|CEFAZOLIN CROSSES INFLAMED SYNOVIAL MEMBRANES, YIELDING SYNOVIAL FLUID ANTIBIOTIC CONCN GREATER THAN THOSE IN SERUM WITHIN 2 HR OF IM DOSE... CLEARANCE OF CEFAZOLIN BY KIDNEY IS PREDOMINANTLY BY GLOMERULAR FILTRATION, & CLEARANCE RATES ARE LINEARLY RELATED TO CREATININE CLEARANCE...|CEFAZOLIN RAPIDLY PENETRATES BODY TISSUES IN RATS, & DECLINE OF TISSUE ANTIBIOTIC LEVELS AFTER DOSING IS FIRST-ORDER. VERY SMALL AMT OF DRUG CROSS BLOOD-BRAIN BARRIER & PLACENTAL TRANSFER APPEARS NEGLIGIBLE...|...DURING STUDIES OF CEFAZOLIN TRANSFERENCE IN MAN, 92-100% OF ADMIN DOSE WAS ACCOUNTED FOR BY URINARY EXCRETION...|... About 80% of cefazolin is reversibly bound to plasma protein ... is excreted in bile even when there is gallbladder disease ... concn may normally exceed that in plasma by 3 times.|For more Absorption, Distribution and Excretion (Complete) data for CEFAZOLIN (13 total), please visit the HSDB record page.

Not metabolized.|Metabolism of cefazolin is very limited in most of the animal species tested and in /humans/. After parenteral administration of cefazolin nearly 100% is excreted unchanged in urine with 24 hours in /humans/, dog and horse. No major metabolites seem to occur.

The serum half-life is approximately 1.8 hours following IV administration and approximately 2.0 hours following IM administration.|The serum half-life of cefazolin is 1.2-2.2 hr in adults with normal renal function. In one study, half-life was 6.8 hr in 1 adult with a creatinine clearance of 26 ml/min, 12 hr in 3 adults with creatinine clearances of 12-17 ml/min, and 57 hr in 3 adults with creatinine clearances less than 5 ml/min.

In vitro tests demonstrate that the bactericidal action of cephalosporins results from inhibition of cell wall synthesis. By binding to specific penicillin-binding proteins (PBPs) located inside the bacterial cell wall, it inhibits the third and last stage of bacterial cell wall synthesis. Cell lysis is then mediated by bacterial cell wall autolytic enzymes such as autolysins.|Bactericidal; action depends on ability to reach and bind penicillin-binding proteins located in bacterial cytoplasmic membranes; cephalosporins inhibit bacterial septum and cell wall synthesis, probably by acylation of membrane-bound transpeptidase enzymes. This prevents cross-linkage of peptidoglycan chains, which is necessary for bacterial cell wall strength and rigidity. Also, cell division and growth are inhibited, and lysis and elongation of susceptible bacteria frequently occur. Rapidly dividing bacteria are those most susceptible to the action of cephalosporins. /Cephalosporins/

/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 ml/kg up to 200 ml of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/|/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

/SIGNS AND SYMPTOMS/ Anaphylaxis presents clinically as the acute onset of peripheral vascular collapse and shock. This may begin minutes after contact with the precipitating allergen. It is the most feared and serious of the allergic reactions and carries with it a significant risk of death. Skin and mucosal lesions, including urticaria and angioedema, may immediately precede the onset of anaphylaxis. Nausea, vomiting, diarrhea, and bronchospasm may occur as part of the acute reaction to the drug. These end-organ responses are initiated by the release of histamine, serotonin, bradykinin and other vasoactive substances released by the basophils and mast cells. ... Penicillins, cephalosporins, and sulfonamides are the antimicrobials most often associated with anaphylactic reactions. /Penicillins and cephalosporins/|/SIGNS AND SYMPTOMS/ Rarely, Clostridium difficile-associated diarrhea and colitis (also known as antibiotic-associated pseudomembranous colitis) has occurred during or following discontinuance of cephalosporins, including following single doses of certain cephalosporins; fatalities have been reported rarely. /Cephalosporins/|/SIGNS AND SYMPTOMS/ A positive Coombs reaction appears frequently in patients who receive large doses of a cephalosporin. Hemolysis is not usually associated with this phenomenon, although it has been reported. Cephalosporins have produced rare instances of bone-marrow depression, characterized by granulocytopenia ... Serious bleeding related either to ... thrombocytopenia, and/or platelet dysfunction has been reported with several beta-lactam antibiotics. This appears to be a particular problem with certain patients (elderly, poorly nourished, or those with renal insufficiency) who are receiving moxalactam. /Cephalosporins/|/SIGNS AND SYMPTOMS/ Hypersensitivity reactions have been reported to occur in approx 5% or less of patients receiving a cephalosporin. These reactions include urticaria, pruritus, rash (maculopapular, erythematous, or morbilliform), fever and chills, reactions resembling serum sickness, eosinophilia, joint pain or inflammation, edema, erythema, genital and anal pruritus, angioedema, shock, hypotension, vasodilatation, Stevens-Johnson syndrome, erythema multiforme, toxic epidermal necrolysis, and exfoliative dermatitis. Anaphylaxis, including a few fatalities, has occurred rarely. /Cephalosporins/|For more Human Toxicity Excerpts (Complete) data for CEFAZOLIN (10 total), please visit the HSDB record page.

Ancef

Trade Name ... Kefzol, Zolicef /From table/|Parenteral: For injection: 500 mg (of cefazolin) Ancef, (GlaxoSmithKline), Cefazolin Sodium for Injection, (American Pharmaceutical Partners), Cefazolin Sodium for Injection, (Sandoz); 1 g (of cefazolin) Ancef, (GlaxoSmithKline), Cefazolin Sodium for Injection, (American Pharmaceutical Partners), Cefazolin Sodium for Injection, (Sandoz); 10 g (of cefazolin) pharmacy bulk package Ancef, (GlaxoSmithKline), Cefazolin Sodium for Injection, (American Pharmaceutical Partners), Cefazolin Sodium for Injection, (Sandoz); 20 g (of cefazolin) pharmacy bulk package Cefazolin Sodium for Injection, (American Pharmaceutical Partners). For injection,.for IV infusion: 1 g (of cefazolin) Ancef Piggyback, (Abbott), Cefazolin Sodium ADD-Vantage ( with 0.04% polysorbate 80), (Abbott), Cefazolin Sodium for Injection Piggyback, (American Pharmaceutical Partners), Cefazolin Sodium for Injection Piggyback, (Sandoz). /Cefazolin sodium/

Semi-synthetic antibiotic derived from 7-aminocephalosporanic acid, ... South African patent 6804513 corresponds to US patent 3516997 (1969, 1970 to Fujisawa).

Analyte: cefazolin; matrix: chemical identification; procedure: retention time of liquid chromatogram with comparison to standards|Analyte: cefazolin; matrix: chemical purity; procedure: liquid chromatography with detection at 254 nm and comparison to standards|Analyte: cefazolin; matrix: pharmaceutical preparation (injection solution; contains sodium bicarbonate); procedure: retention time of liquid chromatogram with comparison to standards (chemical identification)|Analyte: cefazolin; matrix: pharmaceutical preparation (injection solution; contains sodium bicarbonate); procedure: liquid chromatography with detection at 254 nm and comparison to standards (chemical purity)|For more Analytic Laboratory Methods (Complete) data for CEFAZOLIN (19 total), please visit the HSDB record page.

Analyte: cefazolin; matrix: tissue (liver, spleen, lung); procedure: high-performance liquid chromatography with ultraviolet detection at 270 nm|Analyte: cefazolin; matrix: blood (serum); procedure: high-performance liquid chromatography with ultraviolet detection at 310 nm; limit of detection: 250 ng/mL|Analyte: cefazolin; matrix: blood (serum); procedure: high-performance liquid chromatography with ultraviolet detection at 254 nm; limit of detection: 3 ug/mL|Analyte: cefazolin; matrix: blood (plasma); procedure: high-performance liquid chromatography with ultraviolet detection at 252 nm|For more Clinical Laboratory Methods (Complete) data for CEFAZOLIN (13 total), please visit the HSDB record page.

Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients