Comment: Clinical Pharmaceutics and Calcium Ceftriaxone

Abstract

Weread with interest the letterby Rappand Kuhn' and the commentby Gin et aU on the warninglenersfrom the manufacturer and the Food and Drug Administration relatedto the ceftriaxone-calciurn precipitation issue.Given the huge differences betweenneonatal and adult patient dosages and pharmacokinetics,the recommendation that adults should not receive calcium-containing products or ceftriaxone within 48 hoursof each other is, in our opinion,somewhat exaggerated. The usual adult dosage of ceftriaxone is 1-2 g administered once a day. Only in severe infectionsshould the daily dosage be raised to 4 g. Thus, for a patientweighing 70 kg, we calculatethe following dosages: 1000 mg/70 kg =14mg/kg/day,2000 mg170 kg = 29 mg/kg/day,and 4000 mg/70 kg = 57 mg/kg/day. In contrast,infantsand young children

Evaluation of a Potential Clinical Interaction between Ceftriaxone and Calcium

“…As CRO is widely used in the United States to treat numerous invasive bacterial infections, several authors took interest in the initial FDA safety warning (10,22,23). Since recent changes have been implemented in the United States on the basis of data from in vitro studies, vigilant safety monitoring and clinical analysis can provide the best guidance for the use of these agents.…”

In Vitro Assessment of the Formation of Ceftriaxone–Calcium Precipitates in Human Plasma

“…Although ceftriaxone seems to be compatible with some parenteral nutrition for adults, even with higher calcium concentrations, 57 precipitates are formed in parenteral nutrition for neonates. 25,58 This observation can be explained by a higher amount of calcium in parenteral nutrition of neonates, 58 and may be related to the fact that no fatal cases of calciumceftriaxone interactions in adults have been reported. There may have been some administration errors in the past decades in adults as well, but in contrast to newborns, review of cumulative data did not suggest clinically relevant consequences.…”

“…With the objective of further evaluating the interaction of ceftriaxone with calcium-containing products and in view of ongoing discussions around these issues, 14,15,[23][24][25][26][27][28][29] we therefore decided to assess the risk of precipitations using an alternative strategy to quantitatively analyze the formation of calciumceftriaxone precipitates in plasma from adults. For these experiments, we used fresh human plasma from adults, supplemented with exogenous calcium and ceftriaxone, using upper clinically relevant concentrations, while respecting a reasonable safety margin.…”

Impact of the FDA warning of potential ceftriaxone and calcium interactions on drug use policy in clinical practice

“…. Clinicians and researchers expressed concern that the warning issued by the FDA was premature given the relative paucity of supportive safety data, particularly in light of the proven efficacy profile for ceftriaxone [6,7].…”