Cefazillin

White sterile powder for injection.
Each vial contains cefazolin sodium equivalent to cefazolin 1 g.

Pharmacology: Pharmacodynamics: Mechanism of Action: Inhibits bacterial cell wall synthesis by binding to one or more of the penicillin-binding proteins (PBPs) which in turn inhibits the final transpeptidation step of peptidoglycan synthesis in bacterial cell walls, thus inhibiting cell wall biosynthesis. Bacteria eventually lyse due to ongoing activity of cell wall autolytic enzymes (autolysins and murein hydrolases) while cell wall assembly is arrested.
Pharmacokinetics: Absorption: Cefazolin sodium is not appreciably absorbed from GI tract and must be administered parenterally.
Time to maximum plasma concentration (Tmax), IM: 0.5 to 2 hour.
Time to maximum plasma concentration (Tmax), IV: within 5 minutes.
Distribution: Widely into most body tissues and fluids including gallbladder, liver, kidneys, bone, sputum, bile, pleural, and synovial; CSF penetration is poor.
Protein binding: 74% to 86%.
Metabolism: Minimally hepatic.
Excretion: Renal: 80% to 100% unchanged in urine.
Elimination half-life: via IM or IV in neonates 3 to 5 hours, adult 90 to 150 minutes (prolonged with renal impairment).

Biliary tract infections: Due to Escherichia coli, various strains of streptococci, Proteus mirabilis, Klebsiella species, and Staphylococcus aureus.
Bone and joint infections: Due to S. aureus.
Perioperative prophylaxis: The prophylactic administration of cefazolin preoperatively, intraoperatively, and postoperatively may reduce the incidence of certain postoperative infections in patients undergoing surgical procedures.
Respiratory tract infections: Due to Streptococcus pneumoniae, Klebsiella species, Haemophilus influenzae, S. aureus (penicillin-sensitive and penicillin-resistant), and group A beta-hemolytic streptococci.
Septicemia: Due to S. aureus (penicillin-sensitive and penicillin-resistant).
Skin and skin structure infections: Due to S. pneumoniae, S. aureus (penicillin-sensitive and penicillin-resistant), group A beta-haemolytic streptococci, and other strains of streptococci.
Urinary tract infections: Due to E. coli, P. mirabilis, Klebsiella species.

Recommended Dose: Adult and Geriatric: Usual dosage: For a list of infections, refer to Indications/Uses.
Mild infections caused by susceptible gram-positive cocci: 250-500 mg IM or IV every 8 hours.
Moderate to severe infections: 500 mg to 1 g IM or IV every 6-8 hours.
Severe, life-threatening infections (eg, endocarditis, septicemia): 1-1.5 g IM or IV 6 hours. In rare instances, up to 12 g daily has been used.
Group B streptococcus (perinatal prophylaxis): 2 g IV at the time of onset of labor or rupture of membranes followed by 1 g IV every 8 hours until delivery.
Perioperative prophylaxis: 1-2 g IM or IV administered 30 minutes to 1 hour prior to the start of surgery. For procedures 2 hours or more, 500 mg to 1 g IM or IV during surgery. 500 mg to 1 g IM or IV every 6-8 hours for 24 hours postoperatively. In surgery where the occurrence of infection may be particularly devastating (eg, open-heart, prosthetic arthroplasty), the prophylactic administration of cefazolin injection may be continued for 3 to 5 days following the completion of surgery.
Pneumococcal pneumonia: 500 mg IM or IV every 12 hours.
Urinary tract infections (uncomplicated): 1 g IM or IV every 12 hours.
Pediatric: Usual dosage: For a list of infections, refer to Indications/Uses. Children >1 month: 25-50 mg/kg daily IM or IV divided in 3 or 4 doses. May increase to 100 mg/kg daily divided to 3 or 4 doses for severe infections. Maximum 6 g daily.
Renal Impairment: Adult: Creatinine clearance 35-54 mL/minute: Administer full dose in intervals of 8 hours or more.
Creatinine clearance 11-34 mL/minute: Administer 50% of usual dose every 12 hours.
Creatinine clearance ≤10 mL/minute: Administer 50% of usual dose every 18 to 24 hours.
Pediatric: Creatinine clearance >70 mL/minute: No dosage adjustment necessary.
Creatinine clearance 40-70 mL/minute: 60% of usual daily dose divided every 12 hours.
Creatinine clearance 20-40 mL/minute: 25% of usual daily dose divided every 12 hours.
Creatinine clearance 5-20 mL/minute: 10% of usual daily dose divided every 24 hours.
Mode of Administration: Cefazillin is a sterile powder for injection. Reconstituted solutions of cefazolin are light yellow to yellow. Before administer, visual examination should be performed to ensure that there are no visible particles and the color does not change.
Preparation: CEFAZILLIN vials should be reconstituted with sterile water for injection as shown in the table as follows. (See table.)

Click on icon to see table/diagram/image

Administration: IM: Inject deep IM into large muscle mass.
IV: Inject direct IV over 3 to 5 minutes or may infuse as an intermittent infusion over 30 to 60 minutes.
Admixture compatibility: Stable in D5W, D5LR, D5¼NS, D5½NS, D5NS, D10W, LR, NS.
Compatible: Acyclovir, allopurinol, alprostadil, amifostine, anidulafungin, atracurium, aztreonam, bivalirudin, calcium gluconate, cyclophosphamide, cyclosporine, dexmedetomidine, diltiazem, docetaxel, doxorubicin liposome, enalaprilat, esmolol, etoposide phosphate, famotidine, fenoldopam, fentanyl, filgrastim, fluconazole, fludarabine, foscarnet, gallium nitrate, gemcitabine, granisetron, heparin, hetastarch in lactate electrolyte injection (Hextend), insulin (regular), labetalol, lidocaine, linezolid, magnesium sulfate, melphalan, meperidine, midazolam, milrinone, morphine, multivitamins, nicardipine, ondansetron, oxytocin, palonosetron, pancuronium, propofol, ranitidine, remifentanil, sargramostim, tacrolimus, teniposide, theophylline, thiotepa, vecuronium, vitamin B complex with C, warfarin.
Incompatible: Amphotericin B cholesteryl sulfate complex, caspofungin, idarubicin, pemetrexed, pentamidine, vinorelbine.

Overdose: Symptoms are headache, vertigo, paresthesia, central nervous states of agitation, myoclonia, and convulsions.
Treatment: In case of poisoning, elimination accelerating measures are indicated. A specific antidote does not exist. Cefazolin can be hemodialyzed.

CEFAZILLIN is contraindicated in patients who have hypersensitivity to cephalosporins.

Cross-allergenicity with penicillin: Administer cautiously with penicillin-sensitive patients. There is evidence of partial cross-allergenicity; cephalosporins cannot be assumed to be an absolutely safe alternative to penicillin in the penicillin-allergic patient. The estimated incidence of cross-sensitivity is 5% to 16%; however, it is possibly as low as 3% to 7%.
Serum sickness-like reactions: Erythema multiforme of skin rashes accompanied by polyarthritis, arthralgia, and, frequently, fever have been reported; these reactions usually occurred following a second course of therapy. Signs and symptoms occur after a few days of therapy and resolve a few days after drug discontinuation with no serious sequelae. Antihistamines and corticosteroids may be of benefit in managing symptoms.
CNS effects: Severe neurological reactions (some fetal) have been reported with some cephalosporins, including encephalopathy, myoclonus, seizures, and nonconvulsive status epilepticus. Risk may be increased in the present of renal impairment; ensure dose adjusted for renal function or discontinue therapy if patient develops neuro-toxicity; effects are often reversible upon discontinuation.
Coagulation abnormalities: Cephalosporins may be associated with increased international normalized ratio, especially in nutritionally-deficient patients, prolonged treatment, or hepatic or renal disease.
Clostridium difficile-associated diarrhea: C. difficile-associated diarrhea (CDAD) has been reported for nearly all antibacterial agents and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon and may permit overgrowth of C. difficile. Careful medical history is necessary because CDAD has been reported to occur more than 2 months after the administration of antibacterial agents.
Hemolytic anemia: Hemolytic anemia has been observed in patients receiving cephalosporin class antibiotics. Rare cases of severe hemolytic anemia, including fatalities, have been reported in association with cephalosporins. If a patient develops anemia any time within 2 to 3 weeks subsequent to the start of therapy, consider the diagnosis of cephalosporin-associated anemia and stop the drug until etiology is determined with certainty. Blood transfusions may be administered as needed. Periodically monitor patients who receive prolonged courses of cephalosporins for treatment of infections for signs and symptoms of hemolytic anemia, including measurement of hematological parameters when appropriate.
Granulocytopenia: Granulocytopenia and more rarely agranulocytosis may develop during prolonged treatment (more than 10 days) with cephalosporins.
Renal function impairment: Cephalosporins may be nephrotoxic, use with caution in the presence of markedly impaired renal function. In elderly patients and in patients with known or suspected renal impairment, monitor carefully prior to and during therapy.

Pregnancy: Cefazolin is in US Pregnancy Category B which means animal reproduction studies have failed to demonstrate a risk to the fetus and there are no adequate and well-controlled studies in pregnant women or animal studies have shown an adverse effect but adequate and well-controlled studies in pregnant women have failed to demonstrate a risk to the fetus in any trimester.
Adverse effects were not observed in animal reproduction studies. Adverse events have not been reported in the fetus following administration of cefazolin prior to cesarean section. Cefazolin crosses the placenta. Drug levels in cord blood after administration of cefazolin are approximately one-fourth to one-third maternal drug levels.
Cefazolin is recommended for group B streptococcus prophylaxis in pregnant patients with a nonanaphylactic penicillin allergy. It is also one of the antibiotics recommended for prophylactic use prior to cesarean delivery in women at high risk for endocarditis.
In addition, the pharmacokinetics of cefazolin are altered in pregnant women. The half-life is shorter, the AUC is smaller, and the clearance and volume of distribution are increased.
Labor and Delivery: No information.
Lactation: Small amounts of cefazolin are excreted in breast milk. Caution should be exercised when administering cefazolin to nursing women. Non dose-related effects could include modification of bowel flora.

Cardiovascular: Localized phlebitis.
Central nervous system: Seizure.
Dermatologic: Pruritus, skin rash, Stevens-Johnson syndrome.
Gastrointestinal: Abdominal cramps, anorexia, diarrhea, nausea, oral candidiasis, pseudomembranous colitis, vomiting.
Genitourinary: Vaginitis.
Hepatic: Hepatitis, increased serum transaminases.
Hematologic: Eosinophilia, leucopenia, neutropenia, thrombocytopenia.
Hypersensitivity: Anaphylaxis.
Local: Pain at injection site.
Renal: Increased blood urea nitrogen, increased serum creatinine, renal failure.
Miscellaneous: Fever.

Metabolism: None known.
Vaccine, live: Cephalosporins may decrease the effectiveness of live vaccine. Concurrent use is not recommended.
Ethanol: Alcoholic beverages consumed concurrently with or 72 hours or less after cefazolin may produce acute alcohol intolerance (disulfiram-like reaction). This antibiotic posses a methyltetrazolethiol side chain that may inhibit aldehyde dehydrogenase. The reaction begins within 30 minutes after alcohol ingestion and may subside 30 minutes to several hours afterward; the reaction may occur 3 days or less after the last dose of the antibiotic.
Sodium picosulfate: Antibiotics may diminish the therapeutic effect of sodium picosulfate. Consider using an alternative product for bowel cleansing prior to a colonoscopy in patients who have recently used or are concurrently using an antibiotic.
Vitamin K antagonists: Cephalosporins may enhance the anticoagulant effect of Vitamin K Antagonists. Monitor therapy.
Loop diuretics: Use cephalosporins with caution in patients receiving potent diuretics (eg. Loop diuretics). The risk of nephrotoxicity may be increased. Monitor renal function.
Probenecid: Probenecid may increase and prolong cephalosporin plasma levels by competitive inhibiting renal tubular secretion. This is the most significant for cephalosporins primarily by tubular secretion.

Store intact vials below 30°C. Reconstituted solutions of cefazolin are light yellow to yellow. Protection from light is recommended for the powder and for the reconstituted solutions. Reconstituted solutions with WFI are stable for 8 hours at 15-30°C and for 7 days at 2-8°C. Reconstituted solutions with NSS are stable for 8 hours at 15-30°C.
Shelf life: 3 years.

Cephalosporins

J01DB04 - cefazolin ; Belongs to the class of first-generation cephalosporins. Used in the systemic treatment of infections.

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