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Ceftriaxone Injection (Rocephin) Interaction with Calcium Products and New Contraindication in Hyperbilirubinemic Neonates - Updated

04/14/2009

The FDA and Roche have updated their 2007 alert concerning an interaction between ceftriaxone (Rocephin) and calcium-containing products. Calcium-containing solutions may be incompatible with ceftriaxone, depending on the concentrations used. Precipitates may form if the solutions are mixed or used concomitantly, even when administered via different infusion lines at different sites. Several neonatal deaths have been attributed to formation of these precipitates in the kidneys or lungs.

The 2007 alert also informed healthcare professionals that ceftriaxone is now contraindicated in hyperbilirubinemic neonates, especially premature infants. Ceftriaxone displaces bilirubin from serum albumin binding sites, which increases serum bilirubin concentrations and may cause bilirubin encephalopathy. Avoid ceftriaxone use in hyperbilirubinemic infants.

Based on the 2007 alert, the FDA and manufacturer recommended waiting at least 48 hours after ceftriaxone administration before administering any calcium-containing solution or product. Since that time, the manufacturer has conducted 2 in vitro studies evaluating the compatibility of ceftriaxone and calcium-containing solutions in neonatal and adult plasma. The studies evaluated ceftriaxone concentrations above those normally achieved after infusing ceftriaxone 2 g over 30 minutes, combined with calcium concentrations up to 48 mg/dL (12 mM). Ceftriaxone-calcium precipitation was suspected in neonatal plasma at calcium concentrations above 16 mg/dL (4 mM) and in adult plasma at calcium concentrations above 24 mg/dL (6 mM).

Based on these studies, the FDA no longer recommends waiting at least 48 hours after ceftriaxone administration before administering any calcium-containing solution or product. In addition, concomitant use of ceftriaxone and calcium products is contraindicated only in neonates up to 28 days old, and is not contraindicated in patients older than 28 days. Do not reconstitute, dilute, or administer ceftriaxone with calcium-containing solutions, including Lactated Ringer’s, Ringer’s, Hartmann’s solution, or parenteral nutrition. Flush infusion lines thoroughly between sequential administration of ceftriaxone and any calcium-containing product.

The ceftriaxone prescribing information has been updated to reflect these changes. Additional information is available at the following links:

Updated
April 14, 2009; September 14, 2007; July 10, 2007; University of Utah, Drug Information Service. Copyright 2009, Drug Information Service, University of Utah, Salt Lake City, UT.