Cefazolin

Pharmaceuticals -> Antibiotics

Pharmaceuticals -> Antibiotics (Cefalosporins)

Pharmaceuticals -> Listed in ZINC15

Pharmaceuticals -> Used in Switzerland

log Kow = -0.58

-0.58

-0.24

Mol wt 476.50. White to yellowish-white, odorless crystalline powder with a bitter, salty taste. Crystallizes in alpha, beta, and gamma forms (Kariyone). Easily sol in water, slightly sol in methanol, ethanol. Practically insol in benzene, acetone, chloroform /Sodium salt/

Easily sol in DMF, pyridine; sol in aq acetone, aq dioxane, aq ethanol; slightly sol in methanol. Practically insol in chloroform, benzene, ether.

4.87e-01 g/L

Breast Feeding; Lactation; Milk, Human; Anti-Infective Agents; Antibacterial Agents; Cephalosporins

Access group antibiotics

Following reconstitution with sterile water for injection, bacteriostatic water for injection, or 0.9% sodium chloride injection, soln containing approx 225 or 330 mg of cefazolin per ml have a pH of approx 4.5-6 and are stable for 24 hr @ room temp or 96 hr @ 5 °C. Rapid hydrolysis of the drug occurs when pH exceeds 8.5, and precipitation of the insoluble free acid may occur when pH is below 4.5.

Soln containing 2.25-4.5 mg of cefazolin per ml are stable for 24 hr @ room temp or 96 hr @ 5 °C in the following infusion fluids: 0.9% sodium chloride; 5% or 10% dextrose; 5% dextrose and 0.2%, 0.45%, or 0.9% sodium chloride; 5% dextrose and lactated Ringer's; Ringer's; lactated Ringer's; 5% or 10% invert sugar in water; Normosol -M in D5-W; Ionosol B with 5% dextrose; Plasma-Lyte with 5% dextrose; and 5% sodium carbonate. The manufacturers of Ancef and Kefzol state that these cefazolin sodium soln are stable for 10 days when refrigerated.

Soln containing approx 225 or 330 mg of cefazolin per ml may be frozen in their original containers immediately after reconstitution with sterile water for injection, bacteriostatic water for injection, or 0.9% sodium chloride injection and are stable for 12 wk when stored at -20 °C. If the soln are warmed to facilitate thawing, care should be taken to avoid heating after thawing has been completed. Once thawed, solutions should not be refrozen.

Commercially available frozen cefazolin sodium injections are stable for 24 mo when stored @ -20 °C. ... Thawed soln of the commercially available frozen injections are stable for 48 hr @ room temp (25 °C) or 10 days when refrigerated at 5 °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 °C followed by 48 hr @ room temp). Soln that have been thawed and stored @ room temp for up to 24 hr may then be refrigerated @ 5 °C for up to 3 days and stored for an additional 24 hr @ room temp; this recycling procedure must be completed within 11 days from the time of thawing. /Cefazolin sodium/

186.2 Ų [M+H]+ [CCS Type: TW; Method: calibrated with Waters Major Mix]

189.18 Ų [M+Na]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]

Danger

H317 (100%): May cause an allergic skin reaction [Warning Sensitization, Skin]

P233, P260, P261, P271, P272, P280, P284, P302+P352, P304+P340, P321, P333+P317, P342+P316, P362+P364, P403, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 57 reports by companies from 1 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

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/

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

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.

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.

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).

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.

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).

/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.

Drug-Induced Liver Injury Severity and Toxicity (DILIst)

cefazolin

DILI Positive

Intravenous

DOI:10.1016/j.drudis.2019.09.022

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 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).

/LABORATORY ANIMALS: Acute Exposure/ An antibacterial, has been tested in rabbit eyes; 25 mg subconjunctivally or 2.25 mg injected into the vitreous humor appeared to be non-toxic by ophthalmoscopy, ERG, and histology. /Cefazolin sodium/[Grant, W.M. Toxicology of the Eye. 3rd ed. Springfield, IL: Charles C. Thomas Publisher, 1986., p. 196]

/LABORATORY ANIMALS: Acute Exposure/ In a guinea pig maximization test cefazolin did not cause sensitization.[European Medicines Agency (EMEA), The European Agency for the Evaluation of Medicinal Products, Veterinary Medicines Evaluation Unit, Committee for Veterinary Medicinal Products; Cefazolin, Summary Report. EMEA/MRL/0126/96-Final (July 1996). Available from, as of July 21, 2006: http://www.ema.europa.eu/ema/index.jsp?curl=pages/document_library/landing/document_library_search.jsp&murl=menus/document_library/document_library.jsp&mid]

/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ Repeated-dose toxicity studies of up to six months duration were carried out in rats and dogs in most cases using subcutaneous administration. Apart from local toxicity at the injection site most effects occurred in the intestinal tract resulting in diarrhea and enlargement of the cecum. In a 90 day subcutaneous study in rat 250 mg/kg bw only caused reaction at the injection site and cecal enlargement (2/20 animals). In a 3 and 6 month subcutaneous study in dogs, 250 mg/kg and 125 mg/kg, respectively, were without effect. An oral 90 day study was performed in rats. Diarrhea and abdominal swelling was observed together with cecal enlargement. The NOEL in this study was 20 mg/kg bw.[European Medicines Agency (EMEA), The European Agency for the Evaluation of Medicinal Products, Veterinary Medicines Evaluation Unit, Committee for Veterinary Medicinal Products; Cefazolin, Summary Report. EMEA/MRL/0126/96-Final (July 1996). Available from, as of July 21, 2006: http://www.ema.europa.eu/ema/index.jsp?curl=pages/document_library/landing/document_library_search.jsp&murl=menus/document_library/document_library.jsp&mid]

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ The effect of cefazolin on reproduction was investigated in segment I, II and III studies in rats, mice and rabbits. Cefazolin administered subcutaneously did not affect male or female fertility, or the post natal development of the offspring in rats. Cefazolin was not teratogenic in mice and rabbits after subcutaneous dosing. Oral administration of cefazolin to pregnant rats caused maternal toxicity (diarrhea and cecal enlargement) and reduction in litter size and fetal weight, but showed no specific effects on the fetuses. The NOEL for dams (and fetuses) was 10 mg/kg bw.[European Medicines Agency (EMEA), The European Agency for the Evaluation of Medicinal Products, Veterinary Medicines Evaluation Unit, Committee for Veterinary Medicinal Products; Cefazolin, Summary Report. EMEA/MRL/0126/96-Final (July 1996). Available from, as of July 21, 2006: http://www.ema.europa.eu/ema/index.jsp?curl=pages/document_library/landing/document_library_search.jsp&murl=menus/document_library/document_library.jsp&mid]

For more Non-Human Toxicity Excerpts (Complete) data for CEFAZOLIN (6 total), please visit the HSDB record page.

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/

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).

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/

J01DB04

J - Antiinfectives for systemic use

QJ - Antiinfectives for systemic use

QJ - Antiinfectives for systemic use

J01DB04

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.

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/

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.

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.

IHS69L0Y4T

CEFAZOLIN

Established Pharmacologic Class [EPC] - Cephalosporin Antibacterial

Chemical Structure [CS] - Cephalosporins

Cefazolin is a Cephalosporin Antibacterial.

CEFAZOLIN

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.

Vet: Antibacterial ... usually quite active against many gram-positive bacteria ... moderately active against gram-negative bacteria ... relatively susceptible to beta-lactamases ... not as effective against anaerobes as ... penicillins. /First-generation cephalosporins/

Mesh Heading: anti-bacterial agents

MEDICATION

Use (kg; approx.) in Germany (2009): >10000

7-AMINOCEPHALOSPORANIC ACID IS CONVERTED TO ITS SODIUM SALT & ACETYLATED WITH 1H-TETRAZOLE-1-ACETYL CHLORIDE & ACETOXY GROUP IS THEN DISPLACED BY REACTION WITH 5-METHYL-1,3,4-THIADIAZOLE-2-THIOL IN BUFFER SOLN. ...IS ISOLATED AS CEFAZOLIN (ACID) & CONVERTED TO SODIUM SALT WITH SODIUM BICARBONATE. /CEFAZOLIN SODIUM SALT/

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/