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
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.
Impaired Renal Function
A reduced dosage must be employed when renal function is
impaired. Dosage should be determined by the degree of renal impairment and the
susceptibility of the causative organism (see Table 4).
Table 4: Dosage of ZINACEF in Adults With Reduced
|Creatinine Clearance (mL/min)
| > 20
||750 mg-1.5 grams
| < 10
|aSince ZINACEF is dialyzable, patients on
hemodialysis should be given a further dose at the end of the dialysis.
When only serum creatinine is available, the following
formula4 (based on sex, weight, and age of the patient) may be used
to convert this value into creatinine clearance. The serum creatinine should
represent a steady state of renal function.
|| (weight in kg) x (140 – age)
|(72) x serum creatinine (mg/100 mL)
|| (0.85) x (above value)
Note: As with antibiotic therapy in general,
administration of ZINACEF should be continued for a minimum of 48 to 72 hours
after the patient becomes asymptomatic or after evidence of bacterial
eradication has been obtained; a minimum of 10 days of treatment is recommended
in infections caused by Streptococcus pyogenes in order to guard against
the risk of rheumatic fever or glomerulonephritis; frequent bacteriologic and
clinical appraisal is necessary during therapy of chronic urinary tract
infection and may be required for several months after therapy has been completed;
persistent infections may require treatment for several weeks; and doses
smaller than those indicated above should not be used. In staphylococcal and
other infections involving a collection of pus, surgical drainage should be
carried out where indicated.
Pediatric Patients Above 3 Months of Age
Administration of 50 to 100 mg/kg/day in equally divided
doses every 6 to 8 hours has been successful for most infections susceptible to
cefuroxime. The higher dosage of 100 mg/kg/day (not to exceed the maximum adult
dosage) should be used for the more severe or serious infections.
In bone and joint infections, 150 mg/kg/day (not to
exceed the maximum adult dosage) is recommended in equally divided doses every
8 hours. In clinical trials, a course of oral antibiotics was administered to
pediatric patients following the completion of parenteral administration of
In cases of bacterial meningitis, a larger dosage of
ZINACEF is recommended, 200 to 240 mg/kg/day intravenously in divided doses
every 6 to 8 hours.
In pediatric patients with renal insufficiency, the
frequency of dosing should be modified consistent with the recommendations for
Preparation of Solution and Suspension
The directions for preparing ZINACEF for both IV and IM
use are summarized in Table 5.
For Intramuscular Use
Each 750-mg vial of ZINACEF should be constituted with
3.0 mL of Sterile Water for Injection. Shake gently to disperse and withdraw
completely the resulting suspension for injection.
For Intravenous Use
Each 750-mg vial should be constituted with 8.3 mL of
Sterile Water for Injection. Withdraw completely the resulting solution for
Each 1.5-gram vial should be constituted with 16.0 mL of
Sterile Water for Injection, and the solution should be completely withdrawn
The 7.5-gram pharmacy bulk vial should be constituted
with 77 mL of Sterile Water for Injection; each 8 mL of the resulting solution
contains 750 mg of cefuroxime.
Table 5: Preparation of Solution and Suspension
||Amount of Diluent to Be Added (mL)
||Volume to Be Withdrawn
||Approximate Cefuroxime Concentration (mg/mL)
|7.5-gram Pharmacy bulk package
|aNote: ZINACEF is a suspension at IM
b8 mL of solution contains 750 mg of cefuroxime; 16 mL of solution
contains 1.5 grams of cefuroxime.
After constitution, ZINACEF may be given intravenously or
by deep IM injection into a large muscle mass (such as the gluteus or lateral
part of the thigh). Before injecting intramuscularly, aspiration is necessary
to avoid inadvertent injection into a blood vessel.
The IV route may be preferable for patients with
bacterial septicemia or other severe or life-threatening infections or for
patients who may be poor risks because of lowered resistance, particularly if
shock is present or impending.
For direct intermittent IV administration, slowly
inject the solution into a vein over a period of 3 to 5 minutes or give it
through the tubing system by which the patient is also receiving other IV
For intermittent IV infusion with a Y-type
administration set, dosing can be accomplished through the tubing system by
which the patient may be receiving other IV solutions. However, during infusion
of the solution containing ZINACEF, it is advisable to temporarily discontinue
administration of any other solutions at the same site.
TwistVial™ vials are to be constituted only
with 50 or 100 mL of 5% Dextrose Injection, 0.9% Sodium Chloride Injection, or
0.45% Sodium Chloride Injection in compatible flexible diluent containers (see Instructions
for Constitution). TwistVial™ vials that have been joined to
compatible diluent containers and activated to dissolve the drug are stable for
24 hours at room temperature or for 7 days under refrigeration. Joined vials
that have not been activated may be used within a 14-day period; this period
corresponds to that for use of compatible containers following removal of the
outer packaging (overwrap).
Freezing solutions of ZINACEF is not recommended.
For continuous IV infusion, a solution of ZINACEF
may be added to an IV infusion pack containing one of the following fluids:
0.9% Sodium Chloride Injection; 5% Dextrose Injection; 10% Dextrose Injection;
5% Dextrose and 0.9% Sodium Chloride Injection; 5% Dextrose and 0.45% Sodium
Chloride Injection; or 1/6 M Sodium Lactate Injection.
Solutions of ZINACEF, like those of most beta-lactam
antibiotics, should not be added to solutions of aminoglycoside antibiotics
because of potential interaction.
However, if concurrent therapy with ZINACEF and an
aminoglycoside is indicated, each of these antibiotics can be administered
separately to the same patient.
Directions For Use Of ZINACEF Frozen In Galaxy® Plastic
ZINACEF supplied as a frozen, sterile, iso-osmotic,
nonpyrogenic solution in plastic containers is to be administered after thawing
either as a continuous or intermittent IV infusion. The thawed solution of the
premixed product is stable for 28 days if stored under refrigeration (5°C) or
for 24 hours if stored at room temperature (25°C). Do not refreeze.
Thaw container at room temperature (25°C) or under
refrigeration (5°C). Do not force thaw by immersion in water baths or by
microwave irradiation. Components of the solution may precipitate in the frozen
state and will dissolve upon reaching room temperature with little or no
agitation. Potency is not affected. Mix after solution has reached room
temperature. Check for minute leaks by squeezing bag firmly. Discard bag if
leaks are found as sterility may be impaired. Do not add supplementary
medication. Do not use unless solution is clear and seal is intact.
Use sterile equipment.
Do not use plastic containers in series connections. Such
use could result in air embolism due to residual air being drawn from the
primary container before administration of the fluid from the secondary
container is complete.
Preparation for Administration
Suspend container from eyelet support.
Remove protector from outlet port at bottom of container.
Attach administration set. Refer to complete directions
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
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 TwistVial™ 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.
Directions For Dispensing
Pharmacy Bulk Package—Not for Direct Infusion
The pharmacy bulk package is for use in a pharmacy admixture
service only under a laminar flow hood. Entry into the vial must be made with a
sterile transfer set or other sterile dispensing device, and the contents
dispensed in aliquots using aseptic technique. The use of syringe and needle is
not recommended as it may cause leakage.
AFTER INITIAL WITHDRAWAL USE ENTIRE CONTENTS OF VIAL PROMPTLY. ANY UNUSED
PORTION MUST BE DISCARDED WITHIN 24 HOURS.
4. Cockcroft DW, Gault MH. Prediction of creatinine
clearance from serum creatinine. Nephron. 1976;16:31-41.
(cefuroxime for injection)
Instructions for Constitution of TwistVial™ vials
To Open Diluent Container
Peel the corner of the diluent overwrap and remove
flexible diluent container. Some opacity of the plastic flexible container due
to moisture absorption during the sterilization process may be observed. This
is normal and does not affect the solution quality or safety. The opacity will
To Assemble Vial and Flexible Diluent Container (Use
1. Remove the protective covers from the top of the vial
and the vial port on the diluent container as follows:
a. To remove the breakaway vial cap, swing the pull ring
over the top of the vial and pull down far enough to start the opening (see
Figure 1), then pull straight up to remove the cap (see Figure 2).
Note: Once the breakaway cap has been removed, do
not access vial with syringe.
b. To remove the vial port cover, grasp the tab on the
pull ring, pull up to break the 3 tie strings, then pull back to remove the
cover (see Figure 3).
2. Screw the vial into the vial port until it will go no
further. THE VIAL MUST BE SCREWED IN TIGHTLY TO ASSURE A SEAL. This occurs
approximately one-half turn (180°) after the first audible click (see Figure
4). The clicking sound does not assure a seal; the vial must be turned as far
as it will go.
Note: Once vial is seated, do not attempt to
remove (see Figure 4).
3. Recheck the vial to assure that it is tight by trying
to turn it further in the direction of assembly.
4. Label appropriately.
To Prepare Admixture
1. Squeeze the bottom of the diluent container gently to
inflate the portion of the container surrounding the end of the drug vial.
2. With the other hand, push the drug vial down into the
container, telescoping the walls of the container. Grasp the inner cap of the
vial through the walls of the container (see Figure 5).
3. Pull the inner cap from the drug vial (see Figure 6).
Verify that the rubber stopper has been pulled out, allowing the drug and
diluent to mix.
4. Mix container contents thoroughly and use within the
Preparation for Administration (Use Aseptic Technique)
Confirm the activation and admixture of vial contents.
Check for leaks by squeezing container firmly. If leaks
are found, discard unit as sterility may be impaired.
Close flow control clamp of administration set.
Remove cover from outlet port at bottom of container.
Insert piercing pin of administration set into port with
a twisting motion until the pin is firmly seated. Note: See full directions on
administration set carton.
Lift the free end of the hanger loop on the bottom of the
vial, breaking the 2 tie strings. Bend the loop outward to lock it in the
upright position, then suspend container from hanger.
Squeeze and release drip chamber to establish proper
fluid level in chamber.
Open flow control clamp and clear air from set. Close
Attach set to venipuncture device. If device is not
indwelling, prime and make venipuncture.
Regulate rate of administration with flow control clamp.
WARNING: Do not use flexible container in series
ZINACEF in the dry state should be stored between 15° and
30°C (59° and 86°F) and protected from light. ZINACEF is a dry, white to
off-white powder supplied in vials as follows:
NDC 24987-352-10 750-mg* Vial (Tray of 10)
NDC 24987-354-10 1.5-g* Vial (Tray of 10)
NDC 24987-400-00 7.5-g* Pharmacy Bulk Package
(Tray of 6)
NDC 24987-436-00 750-mg TwistVial™ Vial (Tray
NDC 24987-437-00 1.5-g TwistVial™ Vial (Tray
(The above TwistVial™ vials are to be used
only with compatible diluent containers.)
ZINACEF frozen as a premixed solution of cefuroxime
injection should not be stored above -20°C. ZINACEF is supplied frozen in
50-mL, single-dose, plastic containers as follows:
NDC 24987-425-00 1.5-g* Plastic Container
(Carton of 24)
*Equivalent to cefuroxime.
ZINACEF® (cefuroxime for injection):
Distributed by Covis Pharmaceuticals, Inc. Cary, NC 27511 Manufactured by
GlaxoSmithKline, Verona, Italy 37135 ZINACEF® (cefuroxime
injection): Distributed by Covis Pharmaceuticals, Inc. Cary, NC 27511
Manufactured by Baxter Healthcare Corporation, Deerfield, IL 60015. Covis
Pharmaceuticals, Inc. Cary, NC 27511