FDA Updates Recommendations for Use of Ceftriaxone

            On April 21, 2009, the FDA released revisions to their September 2007 recommendations concerning concomitant administration of ceftriaxone and intravenous calcium-containing products.  Roche, the manufacturer of ceftriaxone, carried out two in vitro studies to assess the interaction of ceftriaxone and calcium.  These studies were done to address previously reported cases of fatality in neonates due to a precipitation of ceftriaxone-calcium.  One study used adult plasma, and the second study used neonatal plasma from umbilical cord blood to establish the potential for a ceftriaxone-calcium precipitate using variable ceftriaxone and calcium concentrations.  The results arising from Roche’s studies encouraged the FDA to release the following updated recommendations concerning the use of ceftriaxone and intravenous calcium:
           
            Concomitant use of ceftriaxone and intravenous calcium-containing products is contraindicated in neonates (≤ 28 days of age).

            Ceftriaxone should not be used in neonates (≤ 28 days of age) if they are receiving (or expected to receive) calcium-containing intravenous products.

            In patients > 28 days of age, ceftriaxone and calcium-containing intravenous products may be administered sequentially, provided that the infusion lines are thoroughly flushed between infusions with a compatible fluid.

            Ceftriaxone must not be administered simultaneously with intravenous calcium-containing solutions by means of a Y-site in any age group.

            Ceftriaxone and calcium-containing intravenous products may be used concomitantly in patients > 28 days of age, as long as the above precautionary steps are taken.  Previously, it was recommended that ceftriaxone and calcium-containing intravenous products should not be administered within 48 hours of one another in all age groups.

            Examples of calcium-containing intravenous products include, but are not limited to, Ringer’s Solution, Hartmann’s solution, and parenteral nutrition containing calcium.

            Currently, no data exists in regard to interactions between intramuscular ceftriaxone and the intravenous or oral formulations of calcium-containing products.

References

1. Burkiewicz JS.  Incompatibility of ceftriaxone sodium with lactated Ringer’s injection.  American Journal of Health System Pharmacy. 1999;56:384
2. Ceftriaxone [package insert].  Dayton, NJ:  Aurobindo Pharma USA, Inc; 2008.
3. www.fda.gov

Bradley Evans, PharmD. Candidate