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.

Download full-text


Available from: Emily Steadman
  • Source
    • "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). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Biological functions of antibiotics are not limited to killing. The most likely function of antibiotics in natural microbial ecosystems is signaling. Does this signaling function of antibiotics also extend to the eukaryotic - in particular mammalian - cells? In this review, the host modulating properties of three classes of antibiotics (macrolides, tetracyclines, and β-lactams) will be briefly discussed. Antibiotics can be effective in treatment of a broad spectrum of diseases and pathological conditions other than those of infectious etiology and, in this capacity, may find widespread applications beyond the intended antimicrobial use. This use, however, should not compromise the primary function antibiotics are used for. The biological background for this inter-kingdom signaling is also discussed.
    Full-text · Article · Aug 2013 · Frontiers in Microbiology
  • Source
    • "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. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Bacterial infections are common in the neonates and are a major cause of morbidity and mortality. Sixty percent of preterm infants admitted to neonatal intensive care units received at least one antibiotic during the first week of life. Penicillins, aminoglycosides and cephalosporins comprised 53, 43 and 16%, respectively. Kinetic parameters such as the half-life (t1/2), clearance (Cl), and volume of distribution (Vd) change with development, so the kinetics of penicillins, cephalosporins and aminoglycosides need to be studied in order to optimise therapy with these drugs. The aim of this study is to review the pharmacokinetics of penicillins, cephalosporins and aminoglycosides in the neonate in a single article in order to provide a critical analysis of the literature and thus provide a useful tool in the hands of physicians. The bibliographic search was performed electronically using PubMed, as the search engine, until February 2nd, 2010. Medline search terms were as follows: pharmacokinetics AND (penicillins OR cephalosporins OR aminoglycosides) AND infant, newborn, limiting to humans. Penicillins, cephalosporins and aminoglycosides are fairly water soluble and are mainly eliminated by the kidneys. The maturation of the kidneys governs the pharmacokinetics of penicillins, cephalosporins and aminoglycosides in the neonate. The renal excretory function is reduced in preterms compared to term infants and Cl of these drugs is reduced in premature infants. Gestational and postnatal ages are important factors in the maturation of the neonate and, as these ages proceed, Cl of penicillins, cephalosporins and aminoglycosides increases. Cl and t1/2 are influenced by development and this must be taken into consideration when planning a dosage regimen with these drugs. More pharmacokinetic studies are required to ensure that the dose recommended for the treatment of sepsis in the neonate is evidence based.
    Full-text · Article · Aug 2010 · Pharmaceuticals
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Based on case reports in infants, the safety of concomitant use of ceftriaxone and intravenous calcium in all ages has recently come under challenge. Systematic population-based data to guide clinicians with respect to this risk are, however, lacking. To determine whether concomitant administration of ceftriaxone and intravenous calcium was associated with the occurrence of severe cardiorespiratory events or death in critically ill adults. We performed a matched-cohort study from retrospective data of adults admitted to intensive care units (ICUs) in Calgary, Canada, who were provided continuous high-dose intravenous calcium. Those who received ceftriaxone while on continuous renal replacement therapy were considered exposed. Up to 3 unexposed patients were selected by matching on a number of prognostic factors from the remaining subjects not concurrently exposed to ceftriaxone and calcium. Univariate methods and multivariate conditional logistic regression were used for statistical analysis. We identified 142 patients exposed to the implicated combination who could be matched to at least one unexposed patient. Hospital mortality was 66% in the exposed versus 63% in unexposed patients (p = 0.442). ICU length of stay, ICU mortality, hospital length of stay, and the frequency of acute oxygenation events were all similar by univariate analysis. Multivariate conditional logistic regression modeling failed to find a significant association between exposure and hospital mortality (adjusted OR 1.15, 95% CI 0.65 to 2.04) or other relevant outcomes. In this high-risk group, administration of high concentrations of calcium and concurrent ceftriaxone was not significantly associated with greater mortality or adverse outcomes compared to matched unexposed patients. Although this was an underpowered study and rare adverse effects from the interaction of these 2 compounds cannot be completely excluded, these data provide overall reassurance of the safety of this combination in the majority of critically ill adults.
    Full-text · Article · Jun 2010 · Annals of Pharmacotherapy
Show more