FDA Update [04/21/09]:  This Alert highlights important revisions to the Warnings, Dosage and Administration, Contraindications, and Clinical Pharmacology sections of the full prescribing information for ceftriaxone (Rocephin and its generics).  This information updates a previous Alert and addresses the interaction of ceftriaxone with calcium-containing products, based on previously reported fatal cases in neonates.   The manufacturer of ceftriaxone (Roche) conducted two in vitro studies to assess the potential for precipitation of ceftriaxone-calcium when ceftriaxone and calcium-containing products are mixed in vials and in infusion lines.  These two in vitro studies were conducted in neonatal  and adult plasma to assess the potential for precipitation of ceftriaxone-calcium using varying ceftriaxone and calcium concentrations, including concentrations in excess of those achieved in vivo.*  Based on the results from these studies, FDA has the following updated recommendations:

• 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 are expected to receive) calcium-containing intravenous products.

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

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

• FDA now recommends that ceftriaxone and calcium-containing products may be used concomitantly in patients >28 days of age, using the precautionary steps above because the risk of precipitation is low in this population.  FDA had previously recommended, but no longer recommends, that in all age groups ceftriaxone and calcium-containing products should not be administered within 48 hours of one another. 

In addition, FDA is reiterating three of the previous recommendations or considerations from September 2007:

• Do not reconstitute or mix ceftriaxone with a calcium-containing product, such as Ringer’s or Hartmann’s solution or parenteral nutrition containing calcium, because particulate formation can result.
• There are no data on interactions between intravenous ceftriaxone and oral calcium-containing products or between intramuscular ceftriaxone and intravenous or oral calcium-containing products.
• Report patients who have adverse events following ceftriaxone administration to the FDA’s MedWatch program (see reporting information at the bottom of this page).

* Two in vitro studies, one using adult plasma and the other neonatal plasma from umbilical cord blood have been carried out to assess interaction of ceftriaxone and calcium. Ceftriaxone concentrations up to 1 mM (in excess of concentrations achieved in vivo following administration of 2 grams ceftriaxone infused over 30 minutes) were used in combination with calcium concentrations up to 12 mM (48 mg/dL). Recovery of ceftriaxone from plasma was reduced with calcium concentrations of 6 mM (24 mg/dL) or higher in adult plasma or 4 mM (16 mg/dL) or higher in neonatal plasma. This may be reflective of ceftriaxone-calcium precipitation.

This information reflects FDA's current analysis of data available to FDA concerning this drug. FDA intends to update this when additional information or analyses become available.

To report any unexpected adverse or serious events associated with the use of this drug, please contact the FDA MedWatch program and complete a form on line at http://www.fda.gov/medwatch/report/hcp.htm or report by fax to 1-800-FDA-0178, by mail using the postage-paid address form provided on line, or by telephone to 1-800-FDA-1088.