www.fda.gov/medwatch/safety/2007/safety07.htm#Rocephinwww.fda.gov/medwatch
Fatal cases of calcium-ceftriaxone precipitates in the lungs and kidneys of both term and premature newborns have prompted a warning and a new contraindication regarding concomitant use of the intravenous antibiotic ceftriaxone with calcium or calcium-containing solutions or products.
Last month, the Food and Drug Administration posted an alert on its MedWatch Web site informing health care professionals that ceftriaxone sodium for injection (Rocephin), “must not be mixed or administered simultaneously with calcium-containing solutions or products, even via different infusion lines.”
In addition, calcium-containing solutions or products should not be administered within 48 hours of the last administration of ceftriaxone, according to the FDA. This information is included in a “dear healthcare professional” letter issued by the manufacturer, Roche.
The FDA alert and Roche letter also emphasized that IV ceftriaxone should not be used to treat hyperbilirubinemic neonates, especially those who are premature. The letter cites in vitro studies that have shown that ceftriaxone “can displace bilirubin from its binding to serum albumin,” which can result in bilirubin encephalopathy in this population. Related information had been included in the pediatric use section of the prescribing information, but is now included in the contraindications section to “more prominently reinforce” this information, according to the letter.
The contraindications section also includes the statement that ceftriaxone “should not be administered concurrently with calcium-containing solutions or products in newborns because of the risk of precipitation of ceftriaxone-calcium salts.”
The Roche letter describes postmarketing reports of “isolated neonatal deaths” that were associated with calcium-ceftriaxone precipitates in the lungs and kidneys. In some of the cases, ceftriaxone and the calcium-containing solutions or medications had been administered by different routes and at different times.
Particulates also can form when diluents that contain calcium, such as Ringer's solution or Hartmann's solution, are used to reconstitute ceftriaxone for injection, according to the letter.
The contraindications, warnings, precautions, adverse reactions, and dosage and administration sections of the Rocephin label have been updated to reflect these revised recommendations. For more information, Roche can be contacted at 800-526-6367.
The approved indications for ceftriaxone include treatment of lower respiratory tract infections, skin and skin structure infections, urinary tract infections, intra-abdominal infections, acute bacterial otitis media when caused by susceptible organisms, and surgical prophylaxis.