Evaluation of a Potential Clinical Interaction between Ceftriaxone and Calcium

Midwestern University Chicago College of Pharmacy, Downers Grove, Illinois 60515, USA.
Antimicrobial Agents and Chemotherapy (Impact Factor: 4.48). 04/2010; 54(4):1534-40. DOI: 10.1128/AAC.01111-09
Source: PubMed


In April 2009, the FDA retracted a warning asserting that ceftriaxone and intravenous calcium products should not be coadministered to any patient to prevent precipitation events leading to end-organ damage. Following that announcement, we sought to evaluate if the retraction was justified. A search of the FDA Adverse Event Reporting System was conducted to identify any ceftriaxone-calcium interactions that resulted in serious adverse drug events. Ceftazidime-calcium was used as a comparator agent. One hundred four events with ceftriaxone-calcium and 99 events with ceftazidime-calcium were identified. Adverse drug events were recorded according to the listed description of drug involvement (primary or secondary suspect) and were interpreted as probable, possible, unlikely, or unrelated. For ceftriaxone-calcium-related adverse events, 7.7% and 20.2% of the events were classified as probable and possible for embolism, respectively. Ceftazidime-calcium resulted in fewer probable embolic events (4%) but more possible embolic events (30.3%). Among cases that considered ceftriaxone or ceftazidime and calcium as the primary or secondary drug, one case was classified as a probable embolic event. That patient received ceftriaxone-calcium and died, although an attribution of causality was not possible. Our analysis suggests a lack of support for the occurrence of ceftriaxone-calcium precipitation events in adults. The results of the current analysis reinforce the revised FDA recommendations suggesting that patients >28 days old may receive ceftriaxone and calcium sequentially and provide a transparent and reproducible methodology for such evaluations.

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    • "In general even the higher doses of ceftriaxone are tolerated well but care should be taken in neonates, especially those with hyperbilirubinemia and those receiving intravenous calcium solutions (Monte et al., 2008). There is no support for such restrictions in patients >28 days old (Steadman et al., 2010). The adverse reactions to ceftriaxone are caused by rapid intravenous injection, unlabeled use, and past history of allergic reactions to cephalosporins or penicillins (Shalviri et al., 2012). "
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    • "Even more dangerous is the interaction of ceftriaxone with calcium. Such an interaction yields precipitation of calcium which resulted in serious adverse effect [54,55]. A particular serious effect is the precipitation of calcium in the lungs and death. "
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