ZINACEF- cefuroxime sodium injection, powder, for solution
ZINACEF- cefuroxime sodium injection, solution
Covis Pharmaceuticals Inc
To reduce the development of drug-resistant bacteria and maintain the effectiveness of ZINACEF and other antibacterial drugs, ZINACEF should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria.
Cefuroxime is a semisynthetic, broad-spectrum, cephalosporin antibiotic for parenteral administration. It is the sodium salt of (6R,7R)-3-carbamoyloxymethyl-7-[Z-2-methoxyimino-2-(fur-2-yl)acetamido]ceph-3-em-4-carboxylate
After intramuscular (IM) injection of a 750-mg dose of cefuroxime to normal volunteers, the mean peak serum concentration was 27 mcg/mL. The peak occurred at approximately 45 minutes (range, 15 to 60 minutes). Following IV doses of 750 mg and 1.5 g, serum concentrations were approximately 50 and 100 mcg/mL, respectively, at 15 minutes. Therapeutic serum concentrations of approximately 2 mcg/mL or more were maintained for 5.3 hours and 8 hours or more, respectively. There was no evidence of accumulation of cefuroxime in the serum following IV administration of 1.5-g doses every 8 hours to normal volunteers. The serum half-life after either IM or IV injections is approximately 80 minutes.
Approximately 89% of a dose of cefuroxime is excreted by the kidneys over an 8-hour period, resulting in high urinary concentrations.
Following the IM administration of a 750-mg single dose, urinary concentrations averaged 1,300 mcg/mL during the first 8 hours. Intravenous doses of 750 mg and 1.5 g produced urinary levels averaging 1,150 and 2,500 mcg/mL, respectively, during the first 8-hour period.
The concomitant oral administration of probenecid with cefuroxime slows tubular secretion, decreases renal clearance by approximately 40%, increases the peak serum level by approximately 30%, and increases the serum half-life by approximately 30%. Cefuroxime is detectable in therapeutic concentrations in pleural fluid, joint fluid, bile, sputum, bone, and aqueous humor.
Cefuroxime is detectable in therapeutic concentrations in cerebrospinal fluid (CSF) of adults and pediatric patients with meningitis. The following table shows the concentrations of cefuroxime achieved in cerebrospinal fluid during multiple dosing of patients with meningitis.
INDICATIONS AND USAGE
ZINACEF is indicated for the treatment of patients with infections caused by susceptible strains of the designated organisms in the following diseases:
Lower Respiratory Tract Infections , including pneumonia, caused by Streptococcus pneumoniae , Haemophilus influenzae (including ampicillin-resistant strains), Klebsiella spp., Staphylococcus aureus(penicillinase- and non–penicillinase-producing strains), Streptococcus pyogenes , and Escherichia coli.
Urinary Tract Infections caused by Escherichia coli and Klebsiella spp.
Skin and Skin?Structure Infections caused by Staphylococcus aureus (penicillinase- and non–penicillinase-producing strains), Streptococcus pyogenes , Escherichia coli , Klebsiella spp., and Enterobacter spp.
Septicemia caused by Staphylococcus aureus (penicillinase- and non–penicillinase-producing strains), Streptococcus pneumoniae , Escherichia coli , Haemophilus influenzae (including ampicillin-resistant strains), and Klebsiella spp.
Meningitis caused by Streptococcus pneumoniae , Haemophilus influenzae (including ampicillin-resistant strains),Neisseria meningitidis , and Staphylococcus aureus (penicillinase- and non–penicillinase-producing strains).
Gonorrhea: Uncomplicated and disseminated gonococcal infections due to Neisseria gonorrhoeae(penicillinase- and non–penicillinase-producing strains) in both males and females.
Bone and Joint Infections caused by Staphylococcus aureus (penicillinase- and non–penicillinase-producing strains).
Clinical microbiological studies in skin and skin?structure infections frequently reveal the growth of susceptible strains of both aerobic and anaerobic organisms. ZINACEF has been used successfully in these mixed infections in which several organisms have been isolated.
DOSAGE AND ADMINISTRATION
The usual adult dosage range for ZINACEF is 750 mg to 1.5 grams every 8 hours, usually for 5 to 10 days. In uncomplicated urinary tract infections, skin and skin?structure infections, disseminated gonococcal infections, and uncomplicated pneumonia, a 750-mg dose every 8 hours is recommended. In severe or complicated infections, a 1.5-gram dose every 8 hours is recommended.
In bone and joint infections, a 1.5-gram dose every 8 hours is recommended. In clinical trials, surgical intervention was performed when indicated as an adjunct to therapy with ZINACEF. A course of oral antibiotics was administered when appropriate following the completion of parenteral administration of ZINACEF.
In life-threatening infections or infections due to less susceptible organisms, 1.5 grams every 6 hours may be required. In bacterial meningitis, the dosage should not exceed 3 grams every 8 hours. The recommended dosage for uncomplicated gonococcal infection is 1.5 grams given intramuscularly as a single dose at 2 different sites together with 1 gram of oral probenecid. For preventive use for clean-contaminated or potentially contaminated surgical procedures, a 1.5-gram dose administered intravenously just before surgery (approximately one-half to 1 hour before the initial incision) is recommended. Thereafter, give 750 mg intravenously or intramuscularly every 8 hours when the procedure is prolonged.
For preventive use during open heart surgery, a 1.5-gram dose administered intravenously at the induction of anesthesia and every 12 hours thereafter for a total of 6 grams is recommended.
COMPATIBILITY AND STABILITY
When constituted as directed with Sterile Water for Injection, suspensions of ZINACEF for IM injection maintain satisfactory potency for 24 hours at room temperature and for 48 hours under refrigeration (5°C).
After the periods mentioned above any unused suspensions should be discarded.
When the 750-mg, 1.5-g, and 7.5-g pharmacy bulk vials are constituted as directed with Sterile Water for Injection, the solutions of ZINACEF for IV administration maintain satisfactory potency for 24 hours at room temperature and for 48 hours (750-mg and 1.5-g vials) or for 7 days (7.5-g pharmacy bulk vial) under refrigeration (5°C). More dilute solutions, such as 750 mg or 1.5 g plus 100 mL of Sterile Water for Injection, 5% Dextrose Injection, or 0.9% Sodium Chloride Injection, also maintain satisfactory potency for 24 hours at room temperature and for 7 days under refrigeration.
These solutions may be further diluted to concentrations of between 1 and 30 mg/mL in the following solutions and will lose not more than 10% activity for 24 hours at room temperature or for at least 7 days under refrigeration: 0.9% Sodium Chloride Injection; 1/6 M Sodium Lactate Injection; Ringer’s Injection, USP; Lactated Ringer’s Injection, USP; 5% Dextrose and 0.9% Sodium Chloride Injection; 5% Dextrose Injection; 5% Dextrose and 0.45% Sodium Chloride Injection; 5% Dextrose and 0.225% Sodium Chloride Injection; 10% Dextrose Injection; and 10% Invert Sugar in Water for Injection.
Unused solutions should be discarded after the time periods mentioned above.
ZINACEF has also been found compatible for 24 hours at room temperature when admixed in IV infusion with heparin (10 and 50 U/mL) in 0.9% Sodium Chloride Injection and Potassium Chloride (10 and 40 mEq/L) in 0.9% Sodium Chloride Injection. Sodium Bicarbonate Injection, USP is not recommended for the dilution of ZINACEF.
The 750-mg and 1.5-g ZINACEF TwistVialTM vials, when diluted in 50 or 100 mL of 5% Dextrose Injection, 0.9% Sodium Chloride Injection, or 0.45% Sodium Chloride Injection, may be stored for up to 24 hours at room temperature or for 7 days under refrigeration.
Constitute the 750-mg, 1.5-g, or 7.5-g vial as directed for IV administration in Table 5. Immediately withdraw the total contents of the 750-mg or 1.5-g vial or 8 or 16 mL from the 7.5-g bulk vial and add to a compatible container containing 50 or 100 mL of 0.9% Sodium Chloride Injection or 5% Dextrose Injection and freeze. Frozen solutions are stable for 6 months when stored at -20°C. Frozen solutions should be thawed at room temperature and not refrozen. Do not force thaw by immersion in water baths or by microwave irradiation. Thawed solutions may be stored for up to 24 hours at room temperature or for 7 days in a refrigerator.
Note: Parenteral drug products should be inspected visually for particulate matter and discoloration before administration whenever solution and container permit.
As with other cephalosporins, ZINACEF powder as well as solutions and suspensions tend to darken, depending on storage conditions, without adversely affecting product potency.