CONTRAINDICATION: Risk of fatal interaction – Ceftriaxone (Rocephine® Mesporin®) and Calcium-containing infusions (e.g. Ringer’s lactate)

Ringer’s lactate injection USP is an intravenous fluid used as an electrolyte replacement solution for restoring fluid-electrolyte balance as well as an alkalinizing agent. A 250ml product contains the following:

– Sodium chloride USP 6g/L

– Sodium lactate 3.1g/L

– Potassium Chloride (KCl) 0.3g/L

– Calcium Chloride USP 0.2g/L

 

Ceftriaxone is an intravenous antibiotic belonging to the class of 3rd generation cephalosporins. It is a broad-spectrum anti-bacterial agent and very stable against most ß-lactamases. It is effective against streptococci, Haemophilus influenzae, Neisseriae, penicillin resistant strains of Staphylococcus aureus, multiresistant enterobacters, as well as other bacteria. Its effect against Pseudonomas aeruginosa is limited and it is ineffective against methicillin resistant strains of Staphylococcus aureus, Enterococcus faecalis, Clostridium difficile, and Bacteroides fragilis.

 

MECHANISM OF ACTION: CEFTRIAXONE 

Ceftriaxone works by inhibiting the mucopeptide synthesis in the bacterial cell wall. The beta-lactam moiety of Ceftriaxone binds to carboxypeptidases, endopeptidases, and transpeptidases in the bacterial cytoplasmic membrane. These enzymes are involved in cell-wall synthesis and cell division. By binding to these enzymes, Ceftriaxone results in the formation of defective cell walls and ultimately leads to cell death.

 

THE INTERACTION:

Concomitant administration of ceftriaxone and Calcium containing intravenous infusions such as Lactated Ringer’s Injection, USP is contraindicated (must not be administered) in new-borns (≤ 28 days of age) because both drugs can interact to cause a fatal ceftriaxone-calcium salt precipitation in the bloodstream of the baby. This occurs even if separate infusion lines are used.

 However, for patients older than 28 days (including adults), ceftriaxone must not be administered at the same time with intravenous calcium-containing solutions, including Lactated Ringer’s Injection, USP, through the same infusion line (e.g., via Y-connector).

 

If the same infusion line is used for sequential administration, the line must be thoroughly flushed between infusions with a compatible fluid.

 

WHO PUBLISHED FDA RECOMMENDATIONS (As published from the 2nd Meeting of the Sub-committee of the Expert Committee on the Selection and Use of Essential Medicines):

1. Ceftriaxone should not be mixed with Calcium-containing products
2. Calcium-containing infusions should not be administered with ceftriaxone in the same or different infusion lines or sites in any patient within 48 hours of each other.
3. According to AFSSAPS, Ceftriaxone is contraindicated in pre-mature infants up to 41 weeks (Gestation age + weeks after birth) of age.
4. FDA Approved label & AFSSAPS state that it is contraindicated in neonates less than 28days, if they receive Calcium-containing preparation or if there is hyperbilirubinaemia.
5. It is important to add that this interaction is most evident in neonates but may also occur in older people hence the need for a chance of the interaction occurring be avoided.

 

* AFSSAPS is an acronym for Agence Francaise de Securite Sanitaire des Produits de Sante (French Health Products Safety Agency)

 

REFERENCES:

•http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2826919/

•http://www.drugbank.ca/drugs/DB01212

•http://www.infomed.ch/100drugs/cefphar.html

•http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=dad7735c-709b-40ea-ab7a-15577e24a966

•http://who.int