Ceftriaxone

Cases of fatal outcomes in which a crystalline material was observed in the lungs and kidneys at autopsy have been reported in neonates receiving ceftriaxone for injection and calcium-containing fluids. In some of these cases, the same intravenous infusion line was used for both ceftriaxone for injection and calcium-containing fluids and in some a precipitate was observed in the intravenous infusion line.

Some cases occurred in patients with severe renal impairment who did not receive appropriate dosage adjustment. However, in other cases, neurological adverse reactions occurred in patients receiving an appropriate dosage adjustment. The neurological adverse reactions were reversible and resolved after discontinuation. If neurological adverse reactions associated with Ceftriaxone for Injection therapy occur, discontinue Ceftriaxone for Injection and institute appropriate supportive measures.

Make appropriate dosage adjustments in patients with severe renal impairment (see DOSAGE AND ADMINISTRATION ). Clostridium difficile -Associated Diarrhea Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including ceftriaxone for injection, and may range in severity from mild diarrhea to fatal colitis.

DOSAGE AND ADMINISTRATION Ceftriaxone for injection may be administered intravenously or intramuscularly. However, the intent of this Pharmacy Bulk Package is for the preparation of solutions for intravenous infusion only. Ceftriaxone for injection should be administered intravenously by infusion over a period of 30 minutes.

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 because a precipitate can form. Precipitation of ceftriaxone-calcium can also occur when ceftriaxone for injection is mixed with calcium-containing solutions in the same IV administration line.

Ceftriaxone for injection must not be administered simultaneously with calcium-containing IV solutions, including continuous calcium-containing infusions such as parenteral nutrition via a Y-site. However, in patients other than neonates, ceftriaxone for injection and calcium-containing solutions may be administered sequentially of one another if the infusion lines are thoroughly flushed between infusions with a compatible fluid (see WARNINGS).

Ceftriaxone for injection is contraindicated in neonates (≤ 28 days) if they require (or are expected to require) treatment with calcium-containing IV solutions, including continuous calcium-containing infusions such as parenteral nutrition because of the risk of precipitation of ceftriaxone-calcium (see CONTRAINDICATIONS).

No dosage adjustment is necessary for patients with impairment of renal or hepatic function (see PRECAUTIONS). The dosages recommended for adults require no modification in elderly patients, up to 2 g per day, provided there is no severe renal and hepatic impairment (see PRECAUTIONS ). DIRECTIONS FOR PROPER USE OF PHARMACY BULK PAC KAGE: The 10 gram bottle should be reconstituted with 95 mL of an appropriate IV diluent in a suitable work area such as a laminar flow hood.

The resulting solution will contain approximately 100 mg/mL of ceftriaxone. This closure may be penetrated only one time after reconstitution, using a suitable sterile transfer device or dispensing set which allows measured dispensing of the contents. The withdrawal of container contents should be accomplished without delay.

However, should this not be possible, a maximum time of 4 HOURS from initial closure entry is permitted to complete fluid transfer operations. Unused portions of solution held longer than the recommended time periods should be discarded. Reconstituted Bulk Solutions Should Not Be Used For Direct Infusion. Transfer individual dose to appropriate intravenous solutions as soon as possible following reconstitution of the bulk package.

The stability of the solution that has been transferred into a container varies according to diluent, concentration and temperature (see COMPATIBILITY AND STABILITY ). Concentrations between 10 mg/mL and 40 mg/mL are recommended; however, lower concentrations may be used if desired. 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 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: [See table below.] 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.