Dilution Cefoperazone

CEFOPERAZONE (CEFOBID ®)

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Usual Diluents

D5W, NS

Standard Dilutions [Amount of drug] [Infusion volume] [Infusion rate]

[0 to 1 gram] [50 ml] [30 min]
[ Over 1 gram] [100 ml] [30 min]

Stability / Miscellaneous

Label: Refrigerate

DOSAGE AND ADMINISTRATION
The usual adult daily dose of CEFOBID (sterile cefoperazone) is 2 to 4 grams per day administered in equally divided doses every 12 hours.

In severe infections or infections caused by less sensitive organisms, the total daily dose and/or frequency may be increased. Patients have been successfully treated with a total daily dosage of 6–12 grams divided into 2, 3 or 4 administrations ranging from 1.5 to 4 grams per dose.

In a pharmacokinetic study, a total daily dose of 16 grams was administered to severely immunocompromised patients by constant infusion without complications. Steady state serum concentrations were approximately 150 mcg/mL in these patients.

When treating infections caused by Streptococcus pyogenes, therapy should be continued for at least 10 days.

Solutions of CEFOBID and aminoglycoside should not be directly mixed, since there is a physical incompatibility between them. If combination therapy with CEFOBID and an aminoglycoside is contemplated this can be accomplished by sequential intermittent intravenous infusion provided that separate secondary intravenous tubing is used, and that the primary intravenous tubing is adequately irrigated with an approved diluent between doses. It is also suggested that CEFOBID be administered prior to the aminoglycoside. In vitro testing of the effectiveness of drug combination(s) is recommended.

RECONSTITUTION
The following solutions may be used for the initial reconstitution of CEFOBID (sterile cefoperazone). Solutions for Initial Reconstitution (table 1)

5% Dextrose Injection (USP)	0.9% Sodium Chloride Injection (USP)
5% Dextrose and 0.9% Sodium Chloride Injection (USP)	Normosol® M and 5% Dextrose Injection
5% Dextrose and 0.2% Sodium Chloride Injection (USP)	Normosol® R
10% Dextrose Injection (USP)

Bacteriostatic Water for Injection [Benzyl Alcohol or Parabens] (USP)*	Sterile Water for Injection*
*Not to be used as a vehicle for intravenous infusion. Preparations containing Benzyl Alcohol should not be used in neonates.

General Reconstitution Procedures
CEFOBID (sterile cefoperazone) for intravenous or intramuscular use may be initially reconstituted with any compatible solution mentioned above in Table 1. Solutions should be allowed to stand after reconstitution to allow any foaming to dissipate to permit visual inspection for complete solubilization. Vigorous and prolonged agitation may be necessary to solubilize CEFOBID in higher concentrations (above 333 mg cefoperazone/mL). The maximum solubility of CEFOBID (sterile cefoperazone) is approximately 475 mg cefoperazone/mL of compatible diluent.

Preparation for Intravenous Use
General

CEFOBID (sterile cefoperazone) concentrations between 2 mg/mL and 50 mg/mL are recommended for intravenous administration.

Preparation of Vials
Vials of CEFOBID (sterile cefoperazone) may be initially reconstituted with a minimum of 2.8 mL per gram of cefoperazone of any compatible reconstituting solution appropriate for intravenous administration listed in the above Table 1. For ease of reconstitution the use of 5 mL of compatible solution per gram of CEFOBID is recommended. The entire quantity of the resulting solution should then be withdrawn for further dilution and administration using any of the following vehicles for intravenous infusion:
Table 2. Vehicles for Intravenous Infusion

5% Dextrose Injection (USP)	Lactated Ringer's Injection (USP)
5% Dextrose and Lactated Ringer's Injection	0.9% Sodium Chloride Injection (USP)
5% Dextrose and 0.9% Sodium Chloride Injection (USP)	Normosol® M and 5% Dextrose Injection
5% Dextrose and 0.2% Sodium Chloride Injection (USP)	Normosol® R
10% Dextrose Injection (USP)

The resulting intravenous solution should be administered in one of the following manners:

Intermittent Infusion
Solutions of CEFOBID should be administered over a 15–30 minute time period.

Continuous Infusion
CEFOBID can be used for continuous infusion after dilution to a final concentration of between 2 and 25 mg cefoperazone per mL.

Preparation for Intramuscular Injection
Any suitable solution listed above may be used to prepare CEFOBID (sterile cefoperazone) for intramuscular injection. When concentrations of 250 mg/mL or more are to be administered, a lidocaine solution should be used. These solutions should be prepared using a combination of Sterile Water for Injection and 2% Lidocaine Hydrochloride Injection (USP) that approximates a 0.5% Lidocaine Hydrochloride Solution. A two-step dilution process as follows is recommended: First, add the required amount of Sterile Water for Injection and agitate until CEFOBID powder is completely dissolved. Second, add the required amount of 2% lidocaine and mix.

	Final Cefoperazone Concentration	Step 1 Volume of Sterile Water	Step 2 Volume of 2% Lidocaine	Withdrawable Volume*
*There is sufficient excess present to allow for withdrawal of the stated volume. Final lidocaine concentration will approximate that obtained if a 0.5% Lidocaine Hydrochloride Solution is used as diluent.
1 g vial	333 mg/mL	2.0 mL	0.6 mL	3 mL
	250 mg/mL	2.8 mL	1.0 mL	4 mL
2 g vial	333 mg/mL	3.8 mL	1.2 mL	6 mL
	250 mg/mL	5.4 mL	1.8 mL	8 mL

When a diluent other than Lidocaine HCl Injection (USP) is used reconstitute as follows:

	Cefoperazone Concentration	Volume of Diluent to be Added	Withdrawable Volume*
*There is sufficient excess present to allow for withdrawal of the stated volume.
1 g vial	333 mg/mL	2.6 mL	3 mL
	250 mg/mL	3.8 mL	4 mL
2 g vial	333 mg/mL	5.0 mL	6 mL
	250 mg/mL	7.2 mL	8 mL

STORAGE AND STABILITY
CEFOBID (sterile cefoperazone) is to be stored at or below 25°C (77°F) and protected from light prior to reconstitution. After reconstitution, protection from light is not necessary.

The following parenteral diluents and approximate concentrations of CEFOBID provide stable solutions under the following conditions for the indicated time periods. (After the indicated time periods, unused portions of solutions should be discarded.)

Room Temperature (15°–25°C/59°–77°F)
24 Hours	Approximate Concentrations
Bacteriostatic Water for Injection [Benzyl Alcohol or Parabens] (USP)	300 mg/mL
5% Dextrose Injection (USP)	2 mg to 50 mg/mL
5% Dextrose and Lactated Ringer's Injection	2 mg to 50 mg/mL
5% Dextrose and 0.9% Sodium Chloride Injection (USP)	2 mg to 50 mg/mL
5% Dextrose and 0.2% Sodium Chloride Injection (USP)	2 mg to 50 mg/mL
10% Dextrose Injection (USP)	2 mg to 50 mg/mL
Lactated Ringer's Injection (USP)	2 mg/mL
0.5% Lidocaine Hydrochloride Injection (USP)	300 mg/mL
0.9% Sodium Chloride Injection (USP)	2 mg to 300 mg/mL
Normosol® M and 5% Dextrose Injection	2 mg to 50 mg/mL
Normosol® R	2 mg to 50 mg/mL
Sterile Water for Injection	300 mg/mL
Reconstituted CEFOBID solutions may be stored in glass or plastic syringes, or in glass or flexible plastic parenteral solution containers.

Refrigerator Temperature (2°–8°C/36°–46°F)
5 Days	Approximate Concentrations
Bacteriostatic Water for Injection [Benzyl Alcohol or Parabens] (USP)	300 mg/mL
5% Dextrose Injection (USP)	2 mg to 50 mg/mL
5% Dextrose and 0.9% Sodium Chloride Injection (USP)	2 mg to 50 mg/mL
5% Dextrose and 0.2% Sodium Chloride Injection (USP)	2 mg to 50 mg/mL
Lactated Ringer's Injection (USP)	2 mg/mL
0.5% Lidocaine Hydrochloride Injection (USP)	300 mg/mL
0.9% Sodium Chloride Injection (USP)	2 mg to 300 mg/mL
Normosol® M and 5% Dextrose Injection	2 mg to 50 mg/mL
Normosol® R	2 mg to 50 mg/mL
Sterile Water for Injection	300 mg/mL
Reconstituted CEFOBID solutions may be stored in glass or plastic syringes, or in glass or flexible plastic parenteral solution containers.

Freezer Temperature –20° to –10°C/–4°to 14°F)
3 Weeks	Approximate Concentrations
5% Dextrose Injection (USP)	50 mg/mL
5% Dextrose and 0.9% Sodium Chloride Injection (USP)	2 mg/mL
5% Dextrose and 0.2% Sodium Chloride Injection (USP)	2 mg/mL
5 Weeks
0.9% Sodium Chloride Injection (USP)	300 mg/mL
Sterile Water for Injection	300 mg/mL
Reconstituted CEFOBID solutions may be stored in plastic syringes, or in flexible plastic parenteral solution containers. Frozen samples should be thawed at room temperature before use. After thawing, unused portions should be discarded. Do not refreeze.

HOW SUPPLIED
CEFOBID (sterile cefoperazone) is available in vials containing cefoperazone sodium equivalent to 1 g cefoperazone × 10 (NDC 0049-1201-83) and 2 g cefoperazone × 10 (NDC 0049-1202-83) for intramuscular and intravenous administration.

CEFOBID (sterile cefoperazone) is available in 10 g (NDC 0049-1219-28) Pharmacy Bulk Package for intravenous administration.