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Name:Cefazolin
Manufacturer:Samson Medical Technologies, L.l.c.
Category:Prescription Marketed Drugs


CEFAZOLIN FOR INJECTION, USP

CEFAZOLIN - cefazolin sodium injection, powder, lyophilized, for solution 
Samson Medical Technologies, L.L.C.

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CEFAZOLIN FOR INJECTION, USP

Rx Only

PHARMACY BULK PACKAGE -
NOT FOR DIRECT INFUSION

To reduce the development of drug-resistant bacteria and maintain the effectiveness of cefazolin and other antibacterial drugs, cefazolin should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria.

DESCRIPTION

Cefazolin for Injection, USP, is a sterile, lyophilized, semisynthetic cephalosporin for intravenous administration. It is the sodium salt of 3-{[(5-methyl-1,3,4-thiadiazol-2-yl)thio]-methyl}-8-oxo-7- [2-(1H -tetrazol-1-yl)acetamido]-5-thia-1-azabicyclo [4.2.0]oct-2-ene-2-carboxylic acid. Each Pharmacy Bulk Package contains 48 mg (2.1 mEq) of sodium per 1 gram of cefazolin sodium. Cefazolin for Injection, USP, is supplied in 100 grams and 300 grams SmartPak® Pharmacy Bulk Packages equivalent to 100 grams or 300 grams of cefazolin. Each Pharmacy Bulk Package contains cefazolin sodium equivalent to 100 grams or 300 grams of cefazolin.

The molecular formula is C14H13N8NaO4S3. The molecular weight is 476.49.

The structural formula is as follows:

Structural Formula

The pH of the reconstituted solution is between 4 and 6.

BEFORE ADMINISTRATION, THIS PHARMACY BULK PACKAGE REQUIRES RECONSTITUTION TO A CONCENTRATION OF 100 mg per mL OR 200 mg per mL AND TRANSFER INTO STERILE SYRINGES. A Pharmacy Bulk Package is a container of a sterile preparation for intravenous use that contains many single doses. The contents are intended for use in a pharmacy admixture service and are restricted to the preparation of admixtures for intravenous infusion.

CLINICAL PHARMACOLOGY

Studies have shown that following intravenous administration of cefazolin to normal volunteers, mean serum concentrations peaked at approximately 185 mcg/mL and were approximately 4 mcg/mL at 8 hours for a 1 gram dose.

The serum half-life for cefazolin is approximately 1.8 hours following IV administration.

In a study (using normal volunteers) of constant intravenous infusion with dosages of 3.5 mg/kg for 1 hour (approximately 250 mg) and 1.5 mg/kg the next 2 hours (approximately 100 mg), cefazolin produced a steady serum concentration at the third hour of approximately 28 mcg/mL.

Studies in patients hospitalized with infections indicate that cefazolin produces mean peak serum concentrations approximately equivalent to those seen in normal volunteers.

Bile levels in patients without obstructive biliary disease can reach or exceed serum levels by up to five times; however, in patients with obstructive biliary disease, bile levels of cefazolin are considerably lower than serum levels (< 1 mcg/mL).

In synovial fluid, the cefazolin level becomes comparable to that reached in serum at about 4 hours after drug administration.

Studies of cord blood show prompt transfer of cefazolin across the placenta. Cefazolin is present in very low levels in the milk of nursing mothers.

Cefazolin is excreted unchanged in the urine. In the first 6 hours approximately 60% of the drug is excreted in the urine and this increases to 70% to 80% within 24 hours.

In patients undergoing peritoneal dialysis (2 L/hr.), cefazolin produced mean serum levels of approximately 10 and 30 mcg/mL after 24 hours' instillation of a dialyzing solution containing 50 mg/L and 150 mg/L, respectively. Mean peak levels were 29 mcg/mL (range 13 to 44 mcg/mL) with 50 mg/L (3 patients), and 72 mcg/mL (range 26 to 142 mcg/mL) with 150 mg/L (6 patients). Intraperitoneal administration of cefazolin is usually well tolerated.

Controlled studies on adult normal volunteers, receiving 1 gram 4 times a day for 10 days, monitoring CBC, SGOT, SGPT, bilirubin, alkaline phosphatase, BUN, creatinine, and urinalysis, indicated no clinically significant changes attributed to cefazolin.

Microbiology

In vitro tests demonstrate that the bactericidal action of cephalosporins results from inhibition of cell wall synthesis. Cefazolin has been shown to be active against most strains of the following microorganisms both in vitro and in clinical infections as described in INDICATIONS AND USAGE:

Gram-Positive Aerobes:

Staphylococcus aureus (including beta-lactamase-producing strains)

Staphylococcus epidermidis

Streptococcus pyogenes, Streptococcus agalactiae and other strains of streptococci

Streptococcus pneumoniae

Methicillin-resistant staphylococci are uniformly resistant to cefazolin, and many Enterococcus strains are resistant.

Gram-Negative Aerobes:

Escherichia coli

Proteus mirabilis

Most strains of indole positive Proteus (Proteus vulgaris), Enterobacter spp., Morganella morganii, Providencia rettgeri and Pseudomonas spp. are resistant to cefazolin.

Susceptibility Tests:

Diffusion Techniques:

Quantitative methods that require measurement of zone diameters provide reproducible estimates of the susceptibility of bacteria to antimicrobial compounds. One such standardized procedure1 that has been recommended for use with disks to test the susceptibility of microorganisms to cefazolin uses the 30-mcg cefazolin disk. Results of the standardized single-disk susceptibility test1 with a 30-mcg cefazolin disk should be interpreted according to the following criteria:

RECOMMENDED RANGES FOR CEFAZOLIN SUSCEPTIBILITY TESTING

Zone diameter (mm) Interpretation
≥ 18 Susceptible (S)
15 to 17 Intermediate (I)
≤ 14 Resistant (R)

Standardized single-disk susceptibility test should be performed ONLY with a 30-mcg cefazolin disk.

A report of “Susceptible” indicates that the pathogen is likely to be inhibited by usually achievable concentrations of the antimicrobial compound in the blood. A report of “Intermediate” indicates that the result should be considered equivocal, and, if the microorganism is not fully susceptible to alternative, clinically feasible drugs, the test should be repeated. This category implies possible clinical applicability in body sites where the drug is physiologically concentrated or in situations where high dosage of the drug can be used. This category also provides a buffer zone that prevents small uncontrolled technical factors form causing major discrepancies in interpretation. A report of “Resistant” indicates that usually achievable concentrations of the antimicrobial compound in the blood are unlikely to be inhibitory and that other therapy should be selected.

Standardized susceptibility test procedures require the use of laboratory control microorganisms. The 30-mcg cefazolin disk should provide the following zone diameters in these laboratory test quality control strains:

Microorganism Zone diameter (mm)
E. coli ATCC 25922 21 to 27
S. aureus ATCC 25923 29 to 35

The cefazolin disk should not be used for testing susceptibility to other cephalosporins.

Dilution Techniques:

Quantitative methods that are used to determine minimum inhibitory concentrations provide reproducible estimates of the susceptibility of bacteria to antimicrobial compounds. One such standardized procedure uses a standardized dilution method2 (broth, agar or microdilution) or equivalent with cefazolin powder. The MIC values obtained should be interpreted according to the following criteria:

MIC (mcg/mL) Interpretation
≤ 16 Susceptible (S)
≥ 64 Resistant (R)

Interpretation should be as stated above for results using diffusion techniques.

As with standard diffusion techniques, dilution methods require the use of laboratory control microorganisms. Standard cefazolin powder should provide the following MIC values:

Microorganism MIC (mcg/mL)
S. aureus ATCC 25923 0.25 to 1
E. coli ATCC 25922 1 to 4

INDICATIONS AND USAGE

Cefazolin for Injection is indicated in the treatment of the following serious infections due to susceptible organisms:

Respiratory Tract Infections: Due to S. pneumoniae, S. aureus (including beta-lactamase-producing strains) and S. pyogenes. Injectable benzathine penicillin is considered to be the drug of choice in treatment and prevention of streptococcal infections, including the prophylaxis of rheumatic fever.

Cefazolin is effective in the eradication of streptococci from the nasopharynx; however, data establishing the efficacy of cefazolin in the subsequent prevention of rheumatic fever are not available.

Urinary Tract Infections: Due to E. coli, P. mirabilis.

Skin and Skin Structure Infections: Due to S. aureus (including beta-lactamase-producing strains), S. pyogenes, and other strains of streptococci.

Biliary Tract Infections: Due to E. coli, various strains of streptococci, P. mirabilis, and S. aureus.

Bone and Joint Infections: Due to S. aureus.

Genital Infections: (i.e., prostatitis, epididymitis) due to E. coli, P. mirabilis.

Septicemia: Due to S. pneumoniae, S. aureus (including beta-lactamase-producing strains), P. mirabilis, E. coli.

Endocarditis: Due to S. aureus (including beta-lactamase-producing strains) and S. pyogenes.

Appropriate culture and susceptibility studies should be performed to determine susceptibility of the causative organism to cefazolin.

Perioperative Prophylaxis: The prophylactic administration of cefazolin preoperatively, intraoperatively, and postoperatively may reduce the incidence of certain postoperative infections in patients undergoing surgical procedures which are classified as contaminated or potentially contaminated (e.g., vaginal hysterectomy, and cholecystectomy in high-risk patients such as those older than 70 years, with acute cholecystitis, obstructive jaundice, or common duct bile stones).

The perioperative use of cefazolin may also be effective in surgical patients in whom infection at the operative site would present a serious risk (e.g., during open-heart surgery and prosthetic arthroplasty).

The prophylactic administration of cefazolin should usually be discontinued within a 24-hour period after the surgical procedure. In surgery where the occurrence of infection may be particularly devastating (e.g., open-heart surgery and prosthetic arthroplasty), the prophylactic administration of cefazolin may be continued for 3 to 5 days following the completion of surgery.

If there are signs of infection, specimens for cultures should be obtained for the identification of the causative organism so that appropriate therapy may be instituted.

(See DOSAGE AND ADMINISTRATION.)

To reduce the development of drug-resistant bacteria and maintain the effectiveness of cefazolin and other antibacterial drugs, cefazolin should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

CONTRAINDICATIONS

CEFAZOLIN FOR INJECTION IS CONTRAINDICATED IN PATIENTS WITH KNOWN ALLERGY TO THE CEPHALOSPORIN GROUP OF ANTIBIOTICS.

WARNINGS

BEFORE THERAPY WITH CEFAZOLIN FOR INJECTION USP IS INSTITUTED, CAREFUL INQUIRY SHOULD BE MADE TO DETERMINE WHETHER THE PATIENT HAS HAD PREVIOUS HYPERSENSITIVITY REACTIONS TO CEFAZOLIN, CEPHALOSPORINS, PENICILLINS, OR OTHER DRUGS. IF THIS PRODUCT IS GIVEN TO PENICILLIN-SENSITIVE PATIENTS, CAUTION SHOULD BE EXERCISED BECAUSE CROSS- HYPERSENSITIVITY AMONG BETA-LACTAM ANTIBIOTICS HAS BEEN CLEARLY DOCUMENTED AND MAY OCCUR IN UP TO 10% OF PATIENTS WITH A HISTORY OF PENICILLIN ALLERGY.

IF AN ALLERGIC REACTION TO CEFAZOLIN OCCURS, DISCONTINUE TREATMENT WITH THE DRUG. SERIOUS ACUTE HYPERSENSITIVITY REACTIONS MAY REQUIRE TREATMENT WITH EPINEPHRINE AND OTHER EMERGENCY MEASURES, INCLUDING OXYGEN, IV FLUIDS, IV ANTIHISTAMINES, CORTICOSTEROIDS, PRESSOR AMINES, AND AIRWAY MANAGEMENT, AS CLINICALLY INDICATED.

Clostridium difficile associated diarrhea (CDAD) has been reported with the use of nearly all antibacterial agents, including Cefazolin for Injection, USP and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.

C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy.

CDAD must be considered in all patients who present with diarrhea following antibiotic use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents.

If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.

PRECAUTIONS

General: Prolonged use of Cefazolin for Injection, USP may result in the overgrowth of nonsusceptible organisms. Careful clinical observation of the patient is essential.

When Cefazolin for Injection, USP is administered to patients with low urinary output because of impaired renal function, lower daily dosage is required (see DOSAGE AND ADMINISTRATION).

As with other beta-lactam antibiotics, seizures may occur if inappropriately high doses are administered to patients with impaired renal function (see DOSAGE AND ADMINISTRATION).

Cefazolin, as with all cephalosporins, should be prescribed with caution in individuals with a history of gastrointestinal disease, particularly colitis.

Cephalosporins may be associated with a fall in prothrombin activity. Those at risk include patients with renal or hepatic impairment or poor nutritional state, as well as patients receiving a protracted course of antimicrobial therapy, and patients previously stabilized on anticoagulant therapy. Prothrombin time should be monitored in patients at risk and exogenous vitamin K administered as indicated.

Prescribing Cefazolin for Injection, USP in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.

Drug Interactions: Probenecid may decrease renal tubular secretion of cephalosporins when used concurrently, resulting in increased and more prolonged cephalosporin blood levels.

Drug/Laboratory Test Interactions: A false positive reaction for glucose in the urine may occur with Benedict's solution, Fehling's solution or with Clinitest® tablets, but not with enzyme-based tests such as Clinistix®.

Positive direct and indirect antiglobulin (Coombs) tests have occurred; these may also occur in neonates whose mothers received cephalosporins before delivery.

Information for Patients: Diarrhea is a common problem caused by antibiotics which usually ends when the antibiotic is discontinued. Sometimes after starting treatment with antibiotics, patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as two or more months after having taken the last dose of the antibiotic. If this occurs, patients should contact their physician as soon as possible.

Patients should be counseled that antibacterial drugs including cefazolin, should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When cefazolin is prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may: (1) decrease the effectiveness of the immediate treatment, and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by cefazolin or other antibacterial drugs in the future.

Carcinogenesis/Mutagenesis: Mutagenicity studies and long-term studies in animals to determine the carcinogenic potential of Cefazolin for Injection, USP have not been performed.

Pregnancy: Teratogenic Effects: Pregnancy Category B. Reproduction studies have been performed in rats, mice, and rabbits at doses up to 25 times the human dose and have revealed no evidence of impaired fertility or harm to the fetus due to cefazolin. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

Labor and Delivery: When cefazolin has been administered prior to caesarean section, drug levels in cord blood have been approximately one quarter to one third of maternal drug levels. The drug appears to have no adverse effect on the fetus.

Nursing Mothers: Cefazolin is present in very low concentrations in the milk of nursing mothers. Caution should be exercised when cefazolin is administered to a nursing woman.

Pediatric Use: Safety and effectiveness for use in premature infants and neonates have not been established. See DOSAGE AND ADMINISTRATION for recommended dosage in pediatric patients older than 1 month.

Geriatric Use: Of the 920 subjects who received cefazolin in clinical studies, 313 (34%) were 65 years and over, while 138 (15%) were 75 years and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function (see PRECAUTIONS, General and DOSAGE AND ADMINISTRATION).

ADVERSE REACTIONS

The following reactions have been reported:

Gastrointestinal: Diarrhea, oral candidiasis (oral thrush), vomiting, nausea, stomach cramps, anorexia, and pseudomembranous colitis. Onset of pseudomembranous colitis symptoms may occur during or after antibiotic treatment (see WARNINGS). Nausea and vomiting have been reported rarely.

Allergic: Anaphylaxis, eosinophilia, itching, drug fever, skin rash, Stevens-Johnson syndrome.

Hematologic: Neutropenia, leukopenia, thrombocytopenia, thrombocythemia.

Hepatic: Transient rise in SGOT, SGPT, and alkaline phosphatase levels has been observed. As with other cephalosporins, reports of hepatitis have been received.

Renal: As with other cephalosporins, reports of increased BUN and creatinine levels, as well as renal failure, have been received.

Local Reactions: Rare instances of phlebitis have been reported at site of injection. Pain at the site of injection after intramuscular administration has occurred infrequently. Some induration has occurred.

Other Reactions: Genital and anal pruritus (including vulvar pruritus, genital moniliasis, and vaginitis).

DOSAGE AND ADMINISTRATION

BEFORE ADMINISTRATION, THIS PHARMACY BULK PACKAGE REQUIRES RECONSTITUTION TO A CONCENTRATION OF 100 mg per mL OR 200 mg per mL AND TRANSFER INTO STERILE SYRINGES.

THIS IS A PHARMACY BULK PACKAGE – NOT FOR DIRECT INJECTION

USUAL ADULT DOSAGE
Type of Infection Dose Frequency

*In rare instances, doses up to 12 grams of cefazolin per day have been used.

Moderate to severe infections 500 mg to 1 gram every 6 to 8 hours
Mild infections caused by susceptible gram-positive cocci 250 mg to 500 mg every 8 hours
Acute uncomplicated urinary tract infections 1 gram every 12 hours
Pneumococcal pneumonia 500 mg every 12 hours
Severe, life-threatening infections (e.g., endocarditis, septicemia)* 1 gram to 1.5 grams every 6 hours

Perioperative Prophylactic Use: To prevent postoperative infection in contaminated or potentially contaminated surgery, recommended doses are:

  1. 1 gram IV administered ½ hour to 1 hour prior to the start of surgery.
  2. For lengthy operative procedures (e.g., 2 hours or more), 500 mg to 1 gram IV during surgery (administration modified depending on the duration of the operative procedure).
  3. 500 mg to 1 gram IV every 6 to 8 hours for 24 hours postoperatively.
    It is important that (1) the preoperative dose be given just (½ to 1 hour) prior to the start of surgery so that adequate antibiotic levels are present in the serum and tissues at the time of initial surgical incision; and (2) cefazolin may be administered, if necessary, at appropriate intervals during surgery to provide sufficient levels of the antibiotic at the anticipated moments of greatest exposure to infective organisms.
    In surgery where the occurrence of infection may be particularly devastating (e.g., open-heart surgery and prosthetic arthroplasty), the prophylactic administration of Cefazolin for Injection may be continued for 3 to 5 days following the completion of surgery.

Dosage Adjustment for Patients with Reduced Renal Function

Cefazolin for Injection may be used in patients with reduced renal function with the following dosage adjustments: Patients with a creatinine clearance of 55 mL/min. or greater or a serum creatinine of 1.5 mg% or less can be given full doses. Patients with creatinine clearance rates of 35 to 54 mL/min. or serum creatinine of 1.6 to 3 mg% can also be given full doses, but dosage should be restricted to at least 8 hour intervals. Patients with creatinine clearance rates of 11 to 34 mL/min. or serum creatinine of 3.1 to 4.5 mg% should be given ½ the usual dose every 12 hours. Patients with creatinine clearance rates of 10 mL/min. or less or serum creatinine of 4.6 mg% or greater should be given ½ the usual dose every 18 to 24 hours. All reduced dosage recommendations apply after an initial loading dose appropriate to the severity of the infection. Patients undergoing peritoneal dialysis: See CLINICAL PHARMACOLOGY.

Pediatric Dosage In pediatric patients, a total daily dosage of 25 to 50 mg per kg (approximately 10 to 20 mg per pound) of body weight, divided into three or four equal doses, is effective for most mild to moderately severe infections. Total daily dosage may be increased to 100 mg per kg (45 mg per pound) of body weight for severe infections. Since safety for use in premature infants and in neonates has not been established, the use of Cefazolin for Injection in these patients is not recommended.

PEDIATRIC DOSAGE GUIDE
Weight 25 mg/kg/Day
Divided into 3 Doses
25 mg/kg/Day
Divided into 4 Doses
Approximate
Single Dose
Vol. (mL)
Needed with Dilution of
Approximate
Single Dose
Vol. (mL)
Needed with Dilution
of
lbs kg mg/q8h 100 mg/mL 200 mg/mL mg/q6h 100 mg/mL 200 mg/mL
10 4.5 40 mg 0.4 mL 0.2 mL 30 mg 0.3 mL 0.15 mL
20 9 75 mg 0.75 mL 0.38 mL 55 mg 0.55 mL 0.28 mL
30 13.6 115 mg 1.15 mL 0.58 mL 85 mg 0.85 mL 0.43 mL
40 18.1 150mg 1.5 mL 0.75 mL 115 mg 1.15 mL 0.58 mL
50 22.7 190 mg 1.9 mL 0.95 mL 140 mg 1.4 mL 0.7 mL
Weight 50 mg/kg/Day
Divided into 3 Doses
50 mg/kg/Day
Divided into 4 Doses
Approximate
Single Dose
Vol. (mL)
Needed with Dilution of
Approximate
Single Dose
Vol. (mL)
Needed with
Dilution of
lbs kg mg/q8h 100 mg/mL 200 mg/mL mg/q6h 100 mg/mL 200 mg/mL
10 4.5 75 mg 0.75 mL 0.38 mL 55 mg 0.55 mL 0.28 mL
20 9 150 mg 1.5 mL 0.75 mL 110 mg 1.1 mL 0.55 mL
30 13.6 225 mg 2.25 mL 1.13 mL 170 mg 1.7 mL 0.85 mL
40 18.1 300 mg 3 mL 1.5 mL 225 mg 2.25 mL 1.13 mL
50 22.7 375 mg 3.75 mL 1.88 mL 285 mg 2.85 mL 1.43 mL

In pediatric patients with mild to moderate renal impairment (creatinine clearance of 70 to 40 mL/min.), 60 percent of the normal daily dose given in equally divided doses every 12 hours should be sufficient. In patients with moderate impairment (creatinine clearance of 40 to 20 mL/min.), 25 percent of the normal daily dose given in equally divided doses every 12 hours should be adequate. Pediatric patients with severe renal impairment (creatinine clearance of 20 to 5 mL/min.), may be given 10 percent of the normal daily dose every 24 hours. All dosage recommendations apply after an initial loading dose.

Directions for Proper Use of a Pharmacy Bulk Package

Not for direct infusion. The Pharmacy Bulk Package is for use in the hospital pharmacy admixture service only in a suitable work area, such as a laminar flow hood. Using aseptic technique, the container closure may be penetrated only one time using a suitable sterile dispensing set or transfer device that allows measured dispensing of the contents. Use of a syringe and needle is not recommended as it may cause leakage. The withdrawal of container contents should be accomplished without delay. However, should this not be possible, a maximum time of 4 HOURS from initial port closure entries is permitted to complete fluid transfer operations. This time limit should begin with the introduction of the solvent or diluent into the Pharmacy Bulk Pack.

Instructions for Reconstitution: Visually examine outer (natural foil) bag for damage. IF THE SEAL IS BROKEN OR DAMAGE IS OBSERVED, DO NOT OPEN THE OUTER BAG. STERILITY OF THE INNER BAG SURFACE MAY BE COMPROMISED. DISCARD BOTH BAGS IMMEDIATELY. DO NOT USE THE INNER BAG IF PARTICULATE OR FOREIGN MATTER IS PRESENT, IF THE DRY POWDER IS DARK YELLOW OR BROWN, IF THE SEALS ARE NOT INTACT, OR IF THERE IS ANY OTHER DAMAGE TO THE BAG. IN SUCH CASES, DISCARD THE BAG IMMEDIATELY. Remove the translucent unthreaded cap from the reconstitution (smaller) port and discard it. Follow the above “Directions for Proper Use of a Pharmacy Bulk Package” and proceed to reconstitute the powder through the reconstitution (smaller) port, using Sterile Water for Injection. Mix gently by picking up the bag and gently moving from side to side until dissolution is complete. Once the powder is completely dissolved, approximately 15 minutes for 100 grams or 25 minutes for 300 grams, hang the bag from the eyelets support.

If a pump is used, the following general procedure is recommended:

  1. Attach a sterile spike to the outlet (unspiked) end of a new sterile transfer tube set, and insert spike into spike port of the bag of Sterile Water for Injection to be used to reconstitute the SmartPak® Pharmacy Bulk Package.
  2. Attach the inlet (attached spike) end of the tube set to the Transfer Port of the SmartPak® Pharmacy Bulk Package.
  3. Reverse the pump to transfer Sterile Water for Injection into the SmartPak® Pharmacy Bulk Package.
  4. After completing the transfer of Sterile Water for Injection, remove the spike from the bag of Sterile Water for Injection, and disconnect the spike from this end of the tube set.
  5. Replace this spike with a transfer needle, and insert this needle into the Reconstitution Port of the SmartPak® Pharmacy Bulk Package.
  6. Using the pump, circulate the reconstituted drug through the tube set and SmartPak® Pharmacy Bulk Package to thoroughly mix (about 15 minutes for the 100 gram container and 25 minutes for the 300 gram container).
  7. After solution is complete, remove the transfer needle from the Reconstitution Port of the SmartPak® Pharmacy Bulk Package, and replace it with a syringe filling adaptor.
  8. Hang the bag from the eyelets support. Reconstituted solution can now be transferred using a pump from the SmartPak® Pharmacy Bulk Package, through the tube set in the Transfer Port, into syringes via the syringe filling adaptor.

It should be noted that the spike placed into the SmartPak® Pharmacy Bulk Package in Step 2 is NEVER removed during this procedure and that the Reconstitution Port is self-sealing.

Solutions should be allowed to stand after dissolution to allow any foaming to dissipate in order to permit visual inspection for completed solubilization. CAUTION: TO AVOID POSSIBLE LEAKAGE CAUSED BY THE HEAVY WEIGHT OF THE ADDED WATER, DO NOT SHAKE VIGOROUSLY OR PULL STRONGLY ON THE BAG.

DILUTION TABLE
SmartPak® Bag Size Amount of Sterile Water Approximate Concentration
100 grams 960 mL 100 mg/mL (1 g/10 mL)
450 mL 200 mg/mL (1 g/5 mL)
300 grams 2880 mL 100 mg/mL (1 g/10 mL)
1350 mL 200 mg/mL (1 g/5 mL)

Dispensing Reconstituted Cefazolin/Instructions for Filling Empty Syringes: Unscrew the clear threaded cap from the Transfer (larger) Port and discard it. Using this Transfer Port, fill sterile empty syringes, using a new transfer device. Syringes may be filled using aseptic technique following the usual practice of the institution. Such practices may range from the use of a three-way stopcock to use of a calibrated peristaltic pump. If reconstituted to 100 mg/mL: dispense 5 mL for 500 mg or 10 mL for 1 g. If reconstituted to 200 mg/mL: dispense 2.5 mL for 500 mg or 5 mL for 1 g. For pediatric dosages, see PEDIATRIC DOSAGE GUIDE.

Figure
RECONSTITUTION PHASE MIXING PHASE DISPENSING PHASE
  1. Remove translucent Reconstitution Port cap by pulling
  2. Insert new transfer device for reconstitution
  3. Add appropriate volume of Sterile Water for Injection
  4. Disconnect transfer device from Sterile Water for Injection container, and replace the spike or needle with appropriate new transfer adaptor
  5. See Package Insert labeling for further details
  1. Mix gently: either recirculate via a tubing loop or by picking up the bag and gently moving it from side to side until dissolution is completed (15 to 25 minutes) and foam, if any, dissipates
  2. Check for particulate matter, leaks and discoloration (dark yellow or brown)
  3. If any of the above are found, discard bag immediately
  4. If satisfactory, hang bag, using the eyelets
  5. See Package Insert labeling for further details
  1. Unscrew clear Transfer Port cap
  2. Insert new transfer device
  3. Transfer dose into sterile empty syringe
  4. Properly label syringes
  5. See Package Insert labeling for further details

Administration

Cefazolin for Injection, USP, SmartPak® Pharmacy Bulk Packages are for intravenous use only following reconstitution and transfer into syringes.

Intravenous injection (After transfer of reconstituted solution to empty syringes as directed.): Reconstituted with Sterile Water for Injection as directed to 100 mg/mL, the contents of syringes containing 10 mL (1 gram) of Cefazolin for Injection, USP, may be injected slowly over 3 to 5 minutes, directly or through tubing for patients receiving parenteral fluids. Do not inject in less than 3 minutes. Injected solutions must not be more concentrated than 100 mg/mL. Therefore, if reconstituted as directed to 200 mg/mL, use 2.5 mL for 500 mg or 5 mL for 1 gram, but DILUTE TO 10 mL WITH WATER FOR INJECTION before injection.

Intermittent or continuous intravenous infusion: After transfer of the contents from the SmartPak® Pharmacy Bulk Packages into syringes, cefazolin can be administered in intermittent or continuous infusion via a syringe pump.

Stability of Filled Syringes

In those situations in which the drug has been reconstituted with water and transferred to empty syringes, but not immediately administered to the patient, the syringes may be stored under the following conditions:

  1. 24 hours at room temperature
  2. 10 days under refrigeration, 2° to 8° C (36° to 46° F), if immediately refrigerated after transfer.
  3. 12 weeks at –20° C, if immediately frozen after transfer.
    THAW FROZEN SYRINGES CONTAINING CEFAZOLIN AT ROOM TEMPERATURE OR UNDER REFRIGERATION. DO NOT FORCE THAW BY IMMERSION IN WATER BATHS OR BY MICROWAVE IRRADIATION. IF, AFTER VISUAL INSPECTION, THE SOLUTION IS CLOUDY, CONTAINS PARTICULATE MATTER OR LEAKS ARE DETECTED, DISCARD THE SYRINGE AS STERILITY MAY BE IMPAIRED. DO NOT REFREEZE THAWED SYRINGES.

AFTER INITIAL ENTRY USE ENTIRE CONTENTS OF THE PHARMACY BULK PACKAGE PROMPTLY; ANY UNUSED PORTION MUST BE DISCARDED WITHIN 4 HOURS.

Prior to administration, parenteral drug products should be inspected visually for particulate matter and discoloration whenever solution and container permit.

HOW SUPPLIED

Cefazolin for Injection, USP, is available in the following SmartPak® Pharmacy Bulk Packages:

 
100 grams* (1 Pharmacy Bulk Package) Product No. 1100 NDC 66288-1100-1
 
300 grams** (1 Pharmacy Bulk Package) Product No. 1300 NDC 66288-1300-1
 
*Each 100 gram Pharmacy Bulk Package contains sterile cefazolin sodium equivalent to100 grams of cefazolin.
 
**Each 300 gram Pharmacy Bulk Package contains sterile cefazolin sodium equivalent to 300 grams of cefazolin.

No component of the SmartPak® system contains natural rubber latex.

As with other cephalosporins, cefazolin tends to darken depending on storage conditions within the stated recommendations; however, product potency is not adversely affected. Prior to reconstitution, store dry powder at 20° to 25° C (68° to77° F). [See USP Controlled Room Temperature]. Protect From Light.

REFERENCES:

1 National Committee for Clinical Laboratory Standards (NCCLS). January 2003. Performance Standards for Antimicrobial Disk Susceptibility Tests;– Approved Standard - Eighth Edition. NCCLS Document M2-A8 and Disk Diffusion Supplemental Tables M100-S-13. NCCLS, Wayne, PA, USA.

2 National Committee for Clinical Laboratory Standards (NCCLS). January 2003. Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically; Approved Standard – Sixth Edition. NCCLS M7-A6 and MIC Testing Supplemental Tables, M100-S13. NCCLS, Wayne, PA, USA.

Literature revised January 2009
C1100f

Manufactured for
SAMSON
MEDICAL TECHNOLOGIES. L.L.C.
Cherry Hill, NJ 08003

by
ACS Dobfar S.p.A.
20067 Tribiano (Milano) Italy

CEFAZOLIN
FOR INJECTION, USP

Manufactured for

SAMSON
MEDICAL TECHNOLOGIES. L.L.C.

Principal Display Panel – Inner Bag Label – 100 grams

NDC 66288-1100-1 SMARTPAK®

CEFAZOLIN FOR INJECTION, USP

PHARMACY BULK PACKAGE

NOT FOR DIRECT INFUSION

100 grams* [ONE HUNDRED GRAMS]

FOR INTRAVENOUS USE ONLY**

*Each 100 gram Pharmacy Bulk Package contains sterile cefazolin sodium equivalent to 100 grams of cefazolin. The sodium content is 48 mg (2.1 mEq) per gram of cefazolin sodium.

**THIS PHARMACY BULK PACKAGE IS INTENDED FOR PREPARING MANY SINGLE DOSES IN A PHARMACY ADMIXTURE PROGRAM. RECONSTITUTION TO A CONCENTRATION OF 100 MG/ML [1 G/10ML] OR 200 MG/ML [1 G/5ML] IS REQUIRED BEFORE ADMINISTRATION. SEE INSERT FOR FURTHER INFORMATION. THIS PACKAGE IS NOT INTENDED TO BE DISPENSED AS A UNIT.

Usual Dosage: Pharmacy Bulk Package Not Intended For Direct Intravenous Administration. See package insert for full prescribing information.

DIRECTIONS FOR PROPER USE OF PHARMACY BULK PACKAGE INNER (CLEAR) BAG: If the outer bag is opened outside the laminar flow hood, sterility may be compromised. Discard the inner bag. DISCARD THE BAG IMMEDIATELY IF FOREIGN MATTER IS PRESENT, IF THE DRY POWDER IS DARK YELLOW OR BROWN, IF THE SEALS ARE NOT INTACT, OR IF THERE IS ANY OTHER DAMAGE TO THE BAG. Lay inner bag flat in a laminar flow hood. Using aseptic technique, remove the unthreaded translucent cap from the reconstitution (smaller) port. Using a new sterile transfer device, proceed to reconstitute the powder through this port using Sterile Water for Injection. To achieve a final concentration of 100 mg/mL, use 960 mL; for 200 mg/mL, use 450 mL. Mix gently for at least 15 minutes by picking up the bag and gently moving from side to side or with pump, recirculate until dissolution is complete.

CAUTION: To avoid possible leakage caused by the heavy weight of the added water, do not shake vigorously or pull strongly on the bag. Solution should be allowed to stand after dissolution to allow any foaming to dissipate in order to permit visual inspection for complete solubilization. After reconstitution, gently squeeze the bag to check for minute leaks and use only if solution is clear and free from particulate or foreign matter. Hang the bag from the eyelets support. Remove the threaded clear cap from transfer (larger) port. Using this transfer port, a new sterile transfer device and aseptic technique, fill sterile empty syringes. For volume per syringe see Package Insert. DISCARD BAG WITHIN 4 HOURS AFTER INITIAL ENTRY. FOR FULL RECONSTITUTION AND DISPENSING INSTRUCTIONS, SEE DOSAGE AND ADMINISTRATION AND DIAGRAM.

Prior to reconstitution, store dry powder at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature] PROTECT FROM LIGHT. THE INNER BAG SHOULD BE RETAINED IN THE OUTER BAG UNTIL TIME OF USE.

Manufactured in Italy for:     Rx Only     Product No. 1100

A1100d

SAMSON

MEDICAL TECHNOLOGIES, L.L.C.

Cherry Hill, NJ 08003

Lot:

Exp:

Date entered _______

Time of entry _______

Discard within 4 hours

6628811001

Principal Display Panel – Inner Bag Label – 100 grams

Principal Display Panel – Outer Bag Label – 100 grams

NDC 66288-1100-1 SMARTPAK®

CEFAZOLIN FOR INJECTION, USP

PHARMACY BULK PACKAGE

NOT FOR DIRECT INFUSION

100 grams* [ONE HUNDRED GRAMS]

FOR INTRAVENOUS USE ONLY**

100 grams* [ONE HUNDRED GRAMS]

FOR INTRAVENOUS USE ONLY**

*Each 100 gram Pharmacy Bulk Package contains sterile cefazolin sodium equivalent to 100 grams of cefazolin. The sodium content is 48 mg (2.1 mEq) per gram of cefazolin sodium.

**THIS PHARMACY BULK PACKAGE IS INTENDED FOR PREPARING MANY SINGLE DOSES IN A PHARMACY ADMIXTURE PROGRAM. RECONSTITUTION TO A CONCENTRATION OF100 MG PER ML OR 200 MG PER ML IS REQUIRED BEFORE ADMINISTRATION. SEE INSERT FOR FURTHER INFORMATION. THIS PACKAGE IS NOT INTENDED TO BE DISPENSED AS A UNIT.

Usual Dosage: See package insert for full prescribing information.

DIRECTIONS FOR PROPER USE OF A PHARMACY BULK PACKAGE: Not for direct infusion. The Pharmacy Bulk Package is for use in the hospital pharmacy admixture service only in a suitable work area, such as a laminar flow hood. Using aseptic technique, the container closure may be penetrated only one time using a suitable sterile dispensing set or transfer device that allows measured dispensing of the contents. Use of a syringe and needle is not recommended as it may cause leakage. The withdrawal of container contents should be accomplished without delay. However, should this not be possible, a maximum time of 4 HOURS from initial port closure entries is permitted to complete fluid transfer operations. FOR FULL RECONSTITUTION AND DISPENSING INSTRUCTIONS SEE DOSAGE AND ADMINISTRATION AND DIAGRAM.

DIRECTIONS FOR PROPER USE OF PHARMACY BULK PACKAGE OUTER (NATURAL FOIL) BAG: Visually examine for damage. IF THE SEAL IS BROKEN OR DAMAGE IS OBSERVED, DO NOT OPEN THE OUTER BAG. STERILITY OF THE INNER BAG SURFACE MAY BE COMPROMISED. DISCARD BOTH BAGS IMMEDIATELY.

Do not open outer bag until ready for use. If outer bag is inadvertently opened outside the laminar flow hood, discard the inner bag. Open outer bag at tear notch. Promptly remove, unfold and lay inner (clear) bag flat on working surface of laminar flow hood.

Prior to reconstitution, store Pharmacy Bulk Package at 20° to 25°C (68° to 77° F). [See USP Controlled Room Temperature] PROTECT FROM LIGHT. RETAIN IN OUTER BAG UNTIL TIME OF USE.

Manufactured in Italy for:     Rx Only     Product No. 1100

B1100d

SAMSON

MEDICAL TECHNOLOGIES, L.L.C.

Cherry Hill, NJ 08003

Lot:

Exp:

6628811001

SmartPak® Patent Pending

Principal Display Panel – Outer Bag Label – 100 grams

Principal Display Panel – Inner Bag Label – 300 grams

NDC 66288-1300-1 SMARTPAK®

CEFAZOLIN FOR INJECTION, USP

PHARMACY BULK PACKAGE

NOT FOR DIRECT INFUSION

300 grams* [THREE HUNDRED GRAMS]

FOR INTRAVENOUS USE ONLY**

*Each 300 gram Pharmacy Bulk Package contains sterile cefazolin sodium equivalent to 300 grams of cefazolin. The sodium content is 48 mg (2.1 mEq) per gram of cefazolin sodium.

**THIS PHARMACY BULK PACKAGE IS INTENDED FOR PREPARING MANY SINGLE DOSES IN A PHARMACY ADMIXTURE PROGRAM. RECONSTITUTION TO A CONCENTRATION OF 100 MG/ML [1 G/10ML] OR 200 MG/ML [1 G/5 ML] IS REQUIRED BEFORE ADMINISTRATION. SEE INSERT FOR FURTHER INFORMATION. THIS PACKAGE IS NOT INTENDED TO BE DISPENSED AS A UNIT.

Usual Dosage: Pharmacy Bulk Package Not Intended For Direct Intravenous Administration. See package insert for full prescribing information.

DIRECTIONS FOR PROPER USE OF PHARMACY BULK PACKAGE INNER (CLEAR) BAG: If the outer bag is opened outside the laminar flow hood, sterility may be compromised. Discard the inner bag. DISCARD THE BAG IMMEDIATELY IF FOREIGN MATTER IS PRESENT, IF THE DRY POWDER IS DARK YELLOW OR BROWN, IF THE SEALS ARE NOT INTACT, OR IF THERE IS ANY OTHER DAMAGE TO THE BAG. Lay inner bag flat in a laminar flow hood. Using aseptic technique, remove the unthreaded translucent cap from the reconstitution (smaller) port. Using a new sterile transfer device, proceed to reconstitute the powder through this port using Sterile Water for Injection. To achieve a final concentration of 100 mg/mL, use 2880 mL; for 200 mg/mL, use 1350 mL. Mix gently for at least 25 minutes by picking up the bag and gently moving from side to side or with pump, recirculate until dissolution is complete.

CAUTION: To avoid possible leakage caused by the heavy weight of the added water, do not shake vigorously or pull strongly on the bag. Solution should be allowed to stand after dissolution to allow any foaming to dissipate in order to permit visual inspection for complete solubilization. After reconstitution, gently squeeze the bag to check for minute leaks and use only if solution is clear and free from particulate or foreign matter. Hang the bag from the eyelets support. Remove the threaded clear cap from transfer (larger) port. Using this transfer port, a new sterile transfer device and aseptic technique, fill sterile empty syringes. For volume per syringe see Package Insert. DISCARD BAG WITHIN 4 HOURS AFTER INITIAL ENTRY. FOR FULL RECONSTITUTION AND DISPENSING INSTRUCTIONS SEE DOSAGE AND ADMINISTRATION AND DIAGRAM.

Prior to reconstitution, store dry powder at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature] PROTECT FROM LIGHT. THE INNER BAG SHOULD BE RETAINED IN THE OUTER BAG UNTIL TIME OF USE.

Manufactured in Italy for:     Rx Only     Product No. 1300

A1300d

SAMSON

MEDICAL TECHNOLOGIES, L.L.C.

Cherry Hill, NJ 08003

Lot:

Exp:

Date entered _______

Time of entry _______

Discard within 4 hours

6628813001

Principal Display Panel – Inner Bag Label – 300 grams

Principal Display Panel – Outer Bag Label – 300 grams

NDC 66288-1300-1 SMARTPAK®

CEFAZOLIN FOR INJECTION, USP

PHARMACY BULK PACKAGE

NOT FOR DIRECT INFUSION

300 grams* [THREE HUNDRED GRAMS]

FOR INTRAVENOUS USE ONLY**

*Each 300 gram Pharmacy Bulk Package contains sterile cefazolin sodium equivalent to 300 grams of cefazolin. The sodium content is 48 mg (2.1 mEq) per gram of cefazolin sodium.

**THIS PHARMACY BULK PACKAGE IS INTENDED FOR PREPARING MANY SINGLE DOSES IN A PHARMACY ADMIXTURE PROGRAM. RECONSTITUTION TO A CONCENTRATION OF 100 MG PER ML OR 200 MG PER ML IS REQUIRED BEFORE ADMINISTRATION. SEE INSERT FOR FURTHER INFORMATION. THIS PACKAGE IS NOT INTENDED TO BE DISPENSED AS A UNIT.

Usual Dosage: See package insert for full prescribing information.

DIRECTIONS FOR PROPER USE OF A PHARMACY BULK PACKAGE: Not for direct infusion. The Pharmacy Bulk Package is for use in the hospital pharmacy admixture service only in a suitable work area, such as a laminar flow hood. Using aseptic technique, the container closure may be penetrated only one time using a suitable sterile dispensing set or transfer device that allows measured dispensing of the contents. Use of a syringe and needle is not recommended as it may cause leakage. The withdrawal of container contents should be accomplished without delay. However, should this not be possible, a maximum time of 4 HOURS from initial port closure entries is permitted to complete fluid transfer operations. FOR FULL RECONSTITUTION AND DISPENSING INSTRUCTIONS SEE DOSAGE AND ADMINISTRATION AND DIAGRAM.

DIRECTIONS FOR PROPER USE OF PHARMACY BULK PACKAGE OUTER (NATURAL FOIL) BAG: Visually examine for damage. IF THE SEAL IS BROKEN OR DAMAGE IS OBSERVED, DO NOT OPEN THE OUTER BAG. STERILITY OF THE INNER BAG SURFACE MAY BE COMPROMISED. DISCARD BOTH BAGS IMMEDIATELY.

Do not open outer bag until ready for use. If outer bag is inadvertently opened outside the laminar flow hood, discard the inner bag. Open outer bag at tear notch. Promptly remove, unfold and lay inner (clear) bag flat on working surface of laminar flow hood.

Prior to reconstitution, store Pharmacy Bulk Package at 20° to 25°C (68° to 77° F). [See USP Controlled Room Temperature] PROTECT FROM LIGHT. RETAIN IN OUTER BAG UNTIL TIME OF USE.

Manufactured in Italy for:     Rx Only     Product No. 1300

B1300d

SAMSON

MEDICAL TECHNOLOGIES, L.L.C.

Cherry Hill, NJ 08003

Lot:

Exp:

6628813001*

Smartpak® Patent Pending

Principal Display Panel – Outer Bag Label – 300 grams

CEFAZOLIN 
cefazolin sodium injection, powder, lyophilized, for solution
Product Information
Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:66288-1100
Route of Administration INTRAVENOUS DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
Cefazolin Sodium (Cefazolin) Cefazolin 100 g
Product Characteristics
Color      Score     
Shape Size
Flavor Imprint Code
Contains     
Packaging
# Item Code Package Description Multilevel Packaging
1 NDC:66288-1100-1 1 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION (1 BAG) in 1 BAG None

Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
ANDA ANDA065141 01/01/2007

CEFAZOLIN 
cefazolin sodium injection, powder, lyophilized, for solution
Product Information
Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:66288-1300
Route of Administration INTRAVENOUS DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
Cefazolin Sodium (Cefazolin) Cefazolin 300 g
Product Characteristics
Color      Score     
Shape Size
Flavor Imprint Code
Contains     
Packaging
# Item Code Package Description Multilevel Packaging
1 NDC:66288-1300-1 1 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION (1 BAG) in 1 BAG None

Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
ANDA ANDA065141 01/01/2007

Labeler - Samson Medical Technologies, L.L.C. (102837429)
Establishment
Name Address ID/FEI Operations
ACS Dobfar S.p.A. 429243025 MANUFACTURE, API MANUFACTURE, ANALYSIS

Revised: 08/2010 Samson Medical Technologies, L.L.C.



Source: http://dailymed.nlm.nih.gov
Reproduced with permission of U.S. National Library of Medicine


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