CEFTRIAXONE: Package Insert and Label Information (Page 5 of 6)

Compatibility and Stability

Do not use diluents containing calcium, such as Ringer’s solution or Hartmann’s solution, to reconstitute ceftriaxone for injection vials or to further dilute a reconstituted vial for IV administration. Particulate formation can result.

Ceftriaxone has been shown to be compatible with Flagyl^®* IV (metronidazole hydrochloride). The concentration should not exceed 5 to 7.5 mg/mL metronidazole hydrochloride with ceftriaxone 10 mg/mL as an admixture. The admixture is stable for 24 hours at room temperature only in 0.9% sodium chloride injection or 5% dextrose in water (D5W). No compatibility studies have been conducted with the Flagyl^®* IV RTU^® (metronidazole) formulation or using other diluents. Metronidazole at concentrations greater than 8 mg/mL will precipitate. Do not refrigerate the admixture as precipitation will occur.

Vancomycin, amsacrine, aminoglycosides, and fluconazole are incompatible with ceftriaxone in admixtures. When any of these drugs are to be administered concomitantly with ceftriaxone by intermittent intravenous infusion, it is recommended that they be given sequentially, with thorough flushing of the intravenous lines (with one of the compatible fluids) between the administrations.

Ceftriaxone for injection solutions should not be physically mixed with or piggybacked into solutions containing other antimicrobial drugs or into diluent solutions other than those listed above, due to possible incompatibility (see WARNINGS).

Ceftriaxone for injection sterile powder should be stored at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature] and protected from light. After reconstitution, protection from normal light is not necessary. The color of solutions ranges from light yellow to amber, depending on the length of storage, concentration and diluent used.

Ceftriaxone for injection intramuscular solutions remain stable (loss of potency less than 10%) for the following time periods:

		Storage
Diluent	Concentration mg / mL	Room Temp . ( 25 ° C )	Refrigerated ( 4 ° C )
Sterile Water for Injection	100250, 350	2 days24 hours	10 days3 days
0.9% Sodium Chloride Solution	100250, 350	2 days24 hours	10 days3 days
5% Dextrose Solution	100250, 350	2 days24 hours	10 days3 days
Bacteriostatic Water+ 0.9% Benzyl Alcohol	100250, 350	24 hours24 hours	10 days3 days
1% Lidocaine Solution(without epinephrine)	100250, 350	24 hours24 hours	10 days3 days

Ceftriaxone for injection intravenous solutions, at concentrations of 10, 20 and 40 mg/mL, remain stable (loss of potency less than 10%) for the following time periods stored in glass or PVC containers:

* Data available for 10 to 40 mg/mL concentrations in this diluent in PVC containers only.
	Storage
Diluent	Room Temp . ( 25 ° C )	Refrigerated ( 4 ° C )
Sterile Water	2 days	10 days
0.9% Sodium Chloride Solution	2 days	10 days
5% Dextrose Solution	2 days	10 days
10% Dextrose Solution	2 days	10 days
5% Dextrose + 0.9% Sodium Chloride Solution*	2 days	Incompatible
5% Dextrose + 0.45% Sodium Chloride Solution	2 days	Incompatible

The following intravenous ceftriaxone for injection solutions are stable at room temperature (25°C) for 24 hours, at concentrations between 10 mg/mL and 40 mg/mL: Sodium Lactate (PVC container), 10% Invert Sugar (glass container), 5% Sodium Bicarbonate (glass container), Freamine III (glass container), Normosol-M in 5% Dextrose (glass and PVC containers), Ionosol-B in 5% Dextrose (glass container), 5% Mannitol (glass container), 10% Mannitol (glass container).

After the indicated stability time periods, unused portions of solutions should be discarded.

NOTE: Parenteral drug products should be inspected visually for particulate matter before administration.

Ceftriaxone for injection reconstituted with 5% Dextrose or 0.9% Sodium Chloride solution at concentrations between 10 mg/mL and 40 mg/mL, and then stored in frozen state (-20°C) in PVC or polyolefin containers, remains stable for 26 weeks.

Frozen solutions of ceftriaxone for injection should be thawed at room temperature before use. After thawing, unused portions should be discarded. DO NOT REFREEZE.

ANIMAL PHARMACOLOGY

Concretions consisting of the precipitated calcium salt of ceftriaxone have been found in the gallbladder bile of dogs and baboons treated with ceftriaxone.

These appeared as a gritty sediment in dogs that received 100 mg/kg/day for 4 weeks. A similar phenomenon has been observed in baboons but only after a protracted dosing period (6 months) at higher dose levels (335 mg/kg/day or more). The likelihood of this occurrence in humans is considered to be low, since ceftriaxone has a greater plasma half-life in humans, the calcium salt of ceftriaxone is more soluble in human gallbladder bile and the calcium content of human gallbladder bile is relatively low.

HOW SUPPLIED

Ceftriaxone for injection USP is supplied as a sterile crystalline powder in glass vials. The following packages are available:

Vials containing 250 mg equivalent of ceftriaxone. Box of 1 (NDC 68180-611-01) and box of 10 (NDC 68180-611-10).

Vials containing 500 mg equivalent of ceftriaxone. Box of 1 (NDC 68180-622-01) and box of 10 (NDC 68180-622-10).

Vials containing 1 g equivalent of ceftriaxone. Box of 1 (NDC 68180-633-01) and box of 10 (NDC 68180-633-10).

Vials containing 2 g equivalent of ceftriaxone. Box of 10 (NDC 68180-644-10).

NOTE: Ceftriaxone for injection USP sterile powder should be stored at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature] and protected from light.

CLINICAL STUDIES

Clinical Trials in Pediatric Patients With Acute Bacterial Otitis Media

In two adequate and well controlled US clinical trials a single IM dose of ceftriaxone was compared with a 10 day course of oral antibiotic in pediatric patients between the ages of 3 months and 6 years. The clinical cure rates and statistical outcome appear in the table below:

Clinical Efficacy in Evaluable Population
Study Day	Ceftriaxone Single Dose	Comparator – 10 days of Oral Therapy	95 % Confidence Interval	Statistical Outcome
Study 1 — US		amoxicillin/ clavulanate
14	74% (220/ 296)	82% (247/302)	(-14.4%, -0.5%)	Ceftriaxone is lower than control at study day 14 and 28.
28	58% (167/ 288)	67% (200/ 297)	(-17.5%, -1.2%)
Study 2 — US5		TMP-SMZ
14	54% (113/ 210)	60% (124/ 206)	(-16.4%, 3.6%)	Ceftriaxone is equivalent to control at study day 14 and 28.
28	35% (73/ 206)	45% (93/ 205)	(-19.9%, 0.0%)

An open-label bacteriologic study of ceftriaxone without a comparator enrolled 108 pediatric patients, 79 of whom had positive baseline cultures for one or more of the common pathogens. The results of this study are tabulated as follows:

Week 2 and 4 Bacteriologic Eradication Rates in the Per Protocol Analysis in the Roche Bacteriologic Study by pathogen

	Study Day 13 – to 15		Study Day 30 + 2
Organism	No . Analyzed	No . Erad . (%)	No . Analyzed	No . Erad . (%)
Streptococcus pneumoniae	38	32 (84)	35	25 (71)
Haemophilus influenzae	33	28 (85)	31	22 (71)
Moraxella catarrhalis	15	12 (80)	15	9 (60)

REFERENCES

1. Clinical and Laboratory Standards Institute (CLSI). Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically; Approved Standard -Tenth Edition. CLSI document M07-A10, Clinical and Laboratory Standards Institute, 950 West Valley Road, Suite 2500, Wayne, Pennsylvania 19087, USA, 2015.
2. Clinical and Laboratory Standards Institute (CLSI). Performance Standards for Antimicrobial Susceptibility Testing; Twenty-fifth Informational Supplement. CLSI document M100-S25, Clinical and Laboratory Standards Institute, 950 West Valley Road, Suite 2500, Wayne, Pennsylvania 19087, USA, 2015.
3. Clinical and Laboratory Standards Institute (CLSI). Performance Standards for Antimicrobial Disk Diffusion Susceptibility Tests; Approved Standard – Twelfth Edition. CLSI document M02-A12, Clinical and Laboratory Standards Institute, 950 West Valley Road, Suite 2500, Wayne, Pennsylvania 19087, USA, 2015.
4. Clinical and Laboratory Standards Institute (CLSI). Methods for Antimicrobial Susceptibility Testing of Anaerobic Bacteria; Approved Standard — Eight Edition. CLSI document M11-A8, Clinical and Laboratory Standards Institute, 950 West Valley Road, Suite 2500, Wayne, PA 19087 USA, 2012

Manufactured for:

Lupin Pharmaceuticals, Inc.

111 South Calvert Street

Baltimore, Maryland 21202

United States

Manufactured by:

Lupin Limited

Mandideep 462 046

INDIA

Revised: April 2016 ID#: 245115