FDA - MedWatch - Rocephin (ceftriaxone sodium) - Dear Healthcare Provider Letter Clarifying Potential Risk Associated With Concomitant Use Of Rocephin With Calcium Containing Products

MedWatch - The FDA Safety Information and Adverse Event Reporting Program

ROCKVILLE, Md., Sept. 11, 2007--Roche informed healthcare professionals about revisions made to the prescribing information for Rocephin to clarify the potential risk associated with concomitant use of Rocephin with calcium or calcium-containing solutions or products.

Healthcare professionals are advised that Rocephin and calcium-containing solutions including continuous calcium-containing infusions such as parenteral nutrition, should not be mixed or co-administered to any patient irrespective of age, even via different infusion lines at different sites. Rocephin and IV calcium-containing solutions should not be administered within 48 hours of each other in any patient. No data are available on the potential interaction between ceftriaxone and oral calcium-containing products or interaction between intramuscular ceftriaxone and calcium-containing products (IV or oral).

Read the Healthcare Professional Sheet regarding this below.

Information for Healthcare Professionals
Ceftriaxone (marketed at Rocephin)


FDA ALERT [9/2007]: This Alert highlights important revisions to the CONTRAINDICATIONS, WARNINGS, and DOSAGE and ADMINISTRATION sections of the full prescribing information for Rocephin. This new information addresses the interaction of ceftriaxone with calcium-containing products based on reports of fatal cases in neonates. Although there are no reported cases of ceftriaxone-calcium precipitates in patients other than neonates, the potential for this interaction exists in patients of any age. Generally, fatalities have been associated with simultaneous administration of ceftriaxone and calcium-containing products. However, administration of the two products at different times and via different infusion lines has also been fatal. Therefore, ceftriaxone should not be mixed with calcium-containing products and not administered in the same or different infusion lines or sites in any patient within 48 hours of each other. The information in the August 2007 ceftriaxone label clarifies the ceftriaxone labeling revision in May 2007 that first included information on this interaction.

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.

The ceftriaxone full prescribing information includes new information in the CONTRAINDICATIONS, WARNINGS, and DOSAGE and ADMINISTRATION sections about the interaction of ceftriaxone with calcium-containing products and the resulting potential risk of life-threatening and fatal.

Recommendations and considerations for healthcare professionals:

  • 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.
  • Do not administer ceftriaxone and intravenous calcium-containing products including parenteral nutrition to any patient by the same or different infusion lines or sites within 48 hours of each other. Cases of fatal reactions with ceftriaxone-calcium precipitates in lungs and kidneys in neonates have been reported. Although most cases occurred with simultaneous administration of the two products, the interaction has also been reported when ceftriaxone and calcium-containing products were administered at different times and through different infusion lines. Based on 5 half-lives of ceftriaxone, there is a theoretical possibility that the interaction could occur up to 48 hours after ceftriaxone administration.
  • Although there are no cases of ceftriaxone-calcium precipitates in patients other than neonates, there is a potential for the interaction between ceftriaxone and calcium-containing products in patients of any age.
  • 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.
  • Before initiating therapy with ceftriaxone or calcium-containing products, carefully review patients’ medication history for concomitant therapies and those administered in the previous 48 hours.
  • Report patients who have adverse events following ceftriaxone administration to the FDA’s MedWatch program (see reporting information at the bottom of this page)

Information for the patient: Physicians who are prescribing ceftriaxone should discuss with their patients or their caregivers:

  • Ceftriaxone and calcium-containing products can interact with each other and cause life-threatening reactions.
  • Tell your healthcare provider about all medicines that have been given to you, especially those given to you through your veins in the past two days.

Background Information and Data

The Rocephin full prescribing information was updated in May 2007 to add new information about the interaction between ceftriaxone and calcium-containing products based on post-marketing reports in neonates. In August 2007, the full prescribing information was modified to further clarify this issue.

Roche, the manufacturer of ceftriaxone, had provided to FDA post-marketing reports of five neonatal deaths related to the interaction between ceftriaxone and calcium-containing products. According to the reports, the deaths occurred suddenly. In four neonates, ceftriaxone was co-administered with calcium-containing fluids using the same infusion line and in the fifth neonate ceftriaxone and calcium gluconate were administered by different routes and at different times (the exact time difference was not reported). Two autopsies found evidence of crystalline material in the renal and pulmonary vasculature. In a third neonate there was evidence of a precipitate in the intravenous tubing and the neonate’s death occurred soon after the crystalline material was injected.

In addition to the five post-marketing reports provided by Roche, FDA has received four additional post-marketing reports of interactions between ceftriaxone and calcium-containing products in patients up to one year of age since FDA first approved Rocephin in 1984. Three of the interactions resulted in death; in one instance the patient was receiving parenteral nutrition. An autopsy in one patient revealed evidence of crystals in the lungs.

Although FDA is not aware of any cases of ceftriaxone-calcium interactions in adults there is a theoretical possibility that this interaction may occur based on the physical incompatibility of ceftriaxone and calcium-containing solutions. Ceftriaxone-calcium incompatibilities have been reported in the literature.1,2Precipitates can be observed when ceftriaxone is reconstituted or mixed with a calcium-containing product.

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.

References

1. Burkiewicz JS. Incompatibility of ceftriaxone sodium with lactated Ringer’s injection. Am J Health-Syst Pharm 1999;56: 384.

2. Trissel L.A. Handbook on injectable drugs. 14th ed. Bethesda: American Society of Health-System Pharmacists; 2007.

Call 1-800-FDA-1088 (1-800-332-1088)

Posted: September 2007


View comments

Hide
(web3)