0827 Hazards of co-administration of IV ceftriaxone and IV calcium-containing products

Registered doctors in South Africa recently received a medicine safety notice distributed by a number of local drug manufacturers. This notice advised of “new information” regarding the potential risks of concomitant use of ceftriaxone with calcium-containing solutions or products. The gist of the notice is that package inserts will henceforth warn of dangers that predominantly affect neonates but might also apply to older patients. The problems in neonates as covered in the notice include possible displacement of bilirubin from albumin and potential development of bilirubin encephalopathy in jaundiced newborns (a concern that is based on in vitro work and is certainly not new to this drug that has been around for decades), but the main point of the notice is to warn of fatal reactions that have been reported in term and preterm neonates as a result of calcium-ceftriaxone precipitates in lungs and/or kidneys. This does not only apply to the use of calcium-containing diluents, but also to the use of a common line for infusion of drug plus any calcium-containing products and/or solutions, or even the use of different lines at intervals of up to 48 hours. Actually, reports of precipitates have been around for years, showing sludge and/or stone formation in the organs of excretion of the drug (gall bladder and kidneys); however, while incidence of this kind of precipitation might be up to ~15%, the reports mostly showed that stones were small and that sludge and stones would disappear within relatively short time periods. The reports of sudden death as a result of intravascular precipitation are more recent, involving neonates (and some older infants as well); however details are difficult to come by since they appear to be based on adverse reactions reported to the manufacturer or adverse drug event monitoring agencies rather than on published case reports. Clinicians should certainly take note and ensure that ceftriaxone is not co-administered with calcium-containing maintenance or nutritional solutions, or with any calcium-containing products that might be administered intermittently. One might wonder though why this warning has taken so long to reach South Africa because FDA warnings already appeared almost a year ago.

Read more:
Pediatr Nephrol 2007; 22: 690-4
Arch Trop Paediatr 2004; 24: 25-31
FDA Alert 9/2007