Chloramphenicol eye drops containing borax or boric acid buffers (boron): use in children younger than 2 years

Chloramphenicol eye drops containing borax or boric acid buffers (boron): use in children younger than 2 years

Following a review of the available toxicological data and a calculation of daily exposure to boron from a typical dosing regimen, it was concluded that the balance between the benefits and risks of chloramphenicol eye drops containing borax or boric acid remains positive for children aged 0 to 2 years

• chloramphenicol eye drops can be safely administered to children aged 0 to 2 years where antibiotic eye drop treatment is indicated

In the UK the Medicines and Healthcare products Regulatory Agency (MHRA) has produced advice stating (1):

Advice for healthcare professionals:

• some licences for chloramphenicol eye drop products containing borax or boric acid buffers were recently updated to restrict use in children younger than 2 years of age to reflect warnings on maximum daily limits for boron exposure

• we have reviewed the available evidence and sought independent expert advice to understand whether there is a risk for children aged 0 to 2 years when using these products within the licensed indication, for what is likely to be a short period of time

• our review has concluded that the benefits of chloramphenicol eye drops containing borax or boric acid outweigh the potential risks for children, including those aged 0 to 2 years

• a typical regimen of one drop, applied typically 3 to 4 times a day, to both eyes, would result in a daily exposure well below the safety limit for children aged 0 to 2 years (see notes on dosing schedule in section on Findings of review)

• advise parents and caregivers that chloramphenicol eye drops remain an important medicine for children when antibiotic eye treatment is indicated and that they have been used safely for many years – see Advice to provide to parents and carers below

• the product information for affected chloramphenicol products is being updated to reflect the revised advice and remove restrictions for use in infants – in the meantime we ask healthcare professionals to reassure parents and carers that these products can be safely given to children aged 0 to 2 years as prescribed

Advice for healthcare professionals to provide to parents and carers

• eye infections (conjunctivitis) are very common in babies and infants and it is important they are treated properly

• chloramphenicol eye drops are an important medicine for treating bacterial eye infections in children and have been used safely for many years

• some eye drops contain borax or boric acid, which are sources of boron – these ingredients are included as buffers to make sure the medicine is not too acidic or alkaline and is comfortable when administered to the eye

• although concerns have been raised about boron and a possible effect on future fertility, these products can be safely given to children younger than 2 years as advised by a doctor or other prescriber

• experts have advised that the amount of liquid that can be absorbed through the eyes of young children and the way these products are prescribed mean that the daily exposure to children would be well below the calculated safety limits

Following a thorough review, we have concluded that the benefits outweigh the risks of using chloramphenicol eye drops containing borax and boric acid when indicated for children aged 0 to 2 years (2)

• if exposure is calculated using maximum doses and full drop sizes, the 1mg boron per day threshold would be exceeded. This has led to the contraindication of use in infants aged 0 to 2-year olds. However, expert opinion estimates that the maximum volume that can be accommodated in the conjunctival sac of a child younger than 2 years to be between 10µL and 20µL and dosage regimes typically lower than the maximum. Taking into consideration these practice-based factors, boron exposures would not be expected to exceed the European guidance threshold of 1mg boron per day for infants 0 to 2 years of age
  
  
• in addition, as discussed in this report, the European guidance threshold for boron is based on a pregnancy-related effect (reduced fetal weights) following oral exposure in adult rats. The uncertainty factors used in the derivation of this PDE (permitted daily exposure) are based on toxicokinetic data and bodyweight data from pregnant rats and humans. Therefore, the current PDE is not relevant to infants aged 0 to 2 years.

Reference:

1. Drug Safety Update volume 14, issue 12: July 2021: 1.Chloramphenicol eye drops containing borax or boric acid buffers: use in children younger than 2 years
2. MHRA (January 2022). Chloramphenicol eye drops containing borax and boric acid buffers: review of the use in children under 2 years