In May of 2007, the Rocephin© package insert was updated to reflect a new interaction
between ceftriaxone and concurrently administered IV calcium products. Roche provided the FDA with
five post marking reports of neonatal deaths related to the interaction. Since, four additional
post-marketing reports of the interaction have occurred in patients up to 1 year of age. In
September of 2007, an FDA alert was distributed to healthcare professionals to update them on the
revisions in the package insert concerning the interaction. At this time the FDA provided a
recommendation to not mix or infuse calcium-containing products concurrently with ceftriaxone, along
with not administering either product in the same or different infusion lines or sites in any
patient within 48 hours of each product being given. A theoretical recommendation based on 5
elimination half-lives of the medications. Tuesday April 14, 2009, the FDA retracted their statement
on the ceftriaxone and calcium interaction after Roche provided results on two in vitro studies on
the interaction in neonatal and adult plasma. Based on the results of these studies the FDA has
recommended the following:
- "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
Despite the FDA's recommendations, the combination of these medications
should also be avoided in patients up to 1 year of age due to the documented post-marketing deaths.
Additionally, using ceftriaxone 28 days and under is already contraindicated due to bilirubin
displacement from its binding to serum albumin leading to bilirubin encephalopathy and eventually
Warning to Pharmacists: Do not dispense ceftriaxone to any patient = 28
days old or patients < 1 year of age currently receiving calcium containing products including
total parenteral nutrition containing calcium.
See the FDA alert for more information at http://www.fda.gov/cder/drug/InfoSheets/HCP/ceftriaxone042009HCP.htm and
dailymed at http://dailymed.nlm.nih.gov/dailymed/about.cfm for more information on
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