Ceftriaxone (rocephin): incompatible with solutions containing calcium

Updated advice for healthcare professionals not to mix or infuse ceftriaxone with solutions containing calcium.

Article date: October 2009

Ceftriaxone (rocephin) is a broad-spectrum cephalosporin antibiotic that is used to treat infections known or likely to be due to one or more susceptible micro-organisms and when parenteral therapy is needed. Ceftriaxone can be given by deep intramuscular injection, slow intravenous injection, or by slow intravenous infusion after reconstitution of the solution.

Ceftriaxone and calcium precipitation

We have previously reminded healthcare professionals that ceftriaxone should not be mixed or simultaneously infused with calcium-containing solutions such as Hartmann’s or Ringer’s because of a risk of precipitation. See our previous drug safety update.

We also advised that ceftriaxone is contraindicated in newborns who need calcium treatment because of a risk of precipitation of ceftriaxone–calcium salt.

Review of available data

A review of the available data suggests that newborns (up to age 28 days) are at greater risk of calcium–ceftriaxone precipitation than older patients, particularly if they are premature or have impaired bilirubin binding.

The risk of calcium–ceftriaxone precipitation in adults is likely to be low; however, as a precaution, ceftriaxone and calcium should not be administered simultaneously by the intravenous route. However, they may be given sequentially in patients age 28 days or older if the infusion line is rinsed or flushed between solutions, or the infusions are given via different infusion lines at different sites.

Some total parenteral nutrition (TPN) solutions contain similar levels of calcium to that in saline solutions such as Ringer’s or Hartmann’s, and may present a similar degree of risk.

Advice for healthcare professionals shows that:

  • ceftriaxone is contraindicated in:
    • premature newborns up to a corrected age of 41 weeks (weeks of gestation+weeks of life)
    • full-term newborns up to age 28 days who:
      • need treatment with calcium-containing solutions (including TPN solutions), because of a risk of precipitation of ceftriaxone–calcium salt
      • have jaundice or who are hypoalbuminaemic or acidotic, because these are conditions in which bilirubin binding is likely to be impaired
  • simultaneous infusion: for all patients, ceftriaxone must not be mixed with calcium-containing intravenous solutions, and must not be given simultaneously with calcium-containing solutions — even via different infusion lines
  • sequential infusion: calcium and ceftriaxone may be infused sequentially in patients aged 28 days or older provided that either the infusion line is rinsed or flushed between solutions, or the infusions are given via different infusion lines at different sites
  • in patients requiring continuous nutrition with calcium-containing TPN solutions, healthcare professionals may wish to consider using alternative antibacterial treatments which do not carry a similar risk of precipitation. If there is no alternative to giving ceftriaxone with TPN solutions, then administration can be simultaneous provided they are given via different infusion lines at different sites

  Article citation: Drug Safety Update Oct 2009, vol 3 issue 3: 2.

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