Cefazolin

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]

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/

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/