Roche Clarifies Ceftriaxone Warnings

[Updates and replaces report from 6 July 2007]

Kate Traynor

BETHESDA, MD, 12 July 2007 — A July 5 MedWatch alert describing cases of deadly calcium–ceftriaxone precipitates in patients' lungs and kidneys was based solely on reports in neonates, and adults do not appear to be at risk for these adverse events, according to a Roche spokesman.

"There are no indications for a similar risk in adults receiving ceftriaxone and calcium," stated the company's public affairs director, Terrence Hurley, in an e-mail communication today.

"In the available scientific data, there are no reports of precipitations in adults treated with ceftriaxone and calcium, apart from case reports of the already well-known precipitates in gallbladder and kidney which are explicitly mentioned in the [labeling]," Hurley stated. "In particular, no case reports of pulmonary precipitations in adults could be retrieved."

The MedWatch announcement stated that Roche has received reports of neonatal deaths associated with calcium–ceftriaxone precipitates in the lungs and kidneys. The company had noted that in some cases, ceftriaxone and the calcium-containing product had been administered by different routes and at different times.

In response to these reports, Roche revised the labeling (PDF) for its ceftriaxone product, Rocephin, to state that ceftriaxone and calcium-containing solutions or products should not be concurrently administered to newborns.

The revised labeling also emphasizes that ceftriaxone is contraindicated in hyperbilirubinic newborns—and premature infants, in particular—because the drug can displace albumin-bound bilirubin and increase the risk of bilirubin encephalopathy. This information was previously provided in the "pediatric use" section of the labeling.

Of concern to pharmacists is a new warning in the labeling that at least 48 hours must lapse between the last administration of a dose of ceftriaxone and the use of any calcium-containing product.

But Hurley stated that the 48-hour window does not apply to orally administered calcium-containing products.

According to Hurley, Roche has not received any case reports of calcium–ceftriaxone precipitates forming in patients who concurrently received ceftriaxone and an oral calcium-containing product. He also stated that there are "no indications" of a precipitate risk among patients given intramuscular injections of Rocephin.

The new warnings in Rocephin's labeling were originally made at the behest of European regulatory bodies, Hurley stated. He noted that Switzerland-based Roche revised the U.S. labeling to harmonize the information and to "minimize any risk for the pediatric population."

He stated that the warnings were based on five reports of deaths in neonates that occurred between 1992 and 2002.

Hurley was not immediately able to determine whether the company plans to update the labeling for Rocephin to clarify the concerns he addressed today.