Published: 2 December 2021

Publications

Paediatric recommendations for chloramphenicol eye drops

Published: 2 December 2021
Prescriber Update 42(4): 49–50
December 2021

The paediatric dosing recommendations in the chloramphenicol eye drops data sheets are being updated to include dosing recommendations for children aged under two years. However, the updated dosing recommendations reflect conventional clinical practice.

Boric acid and borates

Boric acid and borates are excipients that are mainly used as pH buffers and antimicrobial preservatives in eye drops. These excipients contain boron. There has been concern that boron exposure may be associated with reproductive toxicity.¹

Advice for healthcare professionals

Eye infections are common in young children and require prompt treatment to prevent ocular complications. Chloramphenicol eye drops and ointment are a first-line treatment for superficial eye infections in children².

The recommended dosage regimen for children aged under two years is one drop in the affected eye(s) four times daily for five days³. This dose is associated with boron exposure that is below the threshold of concern for reproductive toxicity. In Europe, 1 mg of boron per day is the threshold for a safety warning for use in children aged under two years¹.

Chloramphenicol eye ointment is an alternative or additive to treatment with eye drops that does not contain boric acid or borates³.

New Zealand regulatory action

The Medicines Adverse Reactions Committee discussed the risk of reproductive toxicity with boron-containing excipients at the 186^th meeting on 10 June 2021.⁴

The Committee noted that the data is limited to animal studies, which have shown toxicities such as effects on sperm parameters and decreased birth weight with high doses of boric acid.¹ The Committee considered that the relevance of the animal data to humans is uncertain. Although human studies have not shown reproductive toxicity, they were not sufficiently robust to rule out this risk.

Chloramphenicol eye drop products may contain more than 1 mg boron in the maximum daily dose. The Committee recommended that the data sheets for chloramphenicol eye drop products should reflect the conventional dosing regimen for children aged under two years: one drop in the affected eye(s) four times daily for five days. This paediatric dose is associated with a boron exposure below the threshold of concern for reproductive toxicity.

International regulatory action

The European Medicines Agency (EMA) reviewed the reproductive toxicity of boric acid and borates in 2017. The EMA requires consumer warnings about boron and fertility concerns for medicinal products that exceed certain thresholds for boron content.¹

In July 2021, the United Kingdom Medicines and Healthcare products Regulatory Agency (MHRA) reviewed the risk of reproductive toxicity with the use of chloramphenicol eye drops containing boric acid and borates in children aged under two years. The MHRA concluded that benefits of chloramphenicol eye drops outweigh the risks in this age group.⁵

More information

• See the MARC meeting minutes and the report presented to the MARC.
• Search for a data sheet.

References

1. European Medicines Agency Committee for Medicinal Products for Human Use. 2017. Boric acid and borate used as excipients (EMA/CHMP/765436/2012) 9 October 2017. URL: ema.europa.eu/en/boric-acid-borates (accessed 15 October 2021).
2. New Zealand Formulary for Children (NZFC). 2021. NZFC v112: Anti-infective eye preparations 1 October 2021. URL: nzfchildren.org.nz/nzfc_5783 (accessed 15 October 2021).
3. Pharmacy Retailing (NZ) Limited Trading as Healthcare Logistics. 2021. Chlorsig New Zealand Data Sheet 5 October 2021. URL: medsafe.govt.nz/profs/Datasheet/c/Chlorsigeyedropeyeoint.pdf (accessed 15 October 2021).
4. Medsafe. 2021. Minutes of the 186th Medicines Adverse Reactions Committee Meeting. URL: medsafe.govt.nz/profs/adverse/Minutes186.htm (accessed 18 October 2021).
5. Medicines and Healthcare products Regulatory Agency. 2021. Chloramphenicol eye drops containing borax or boric acid buffers: Use in children younger than 2 years. Drug Safety Update 14(12): 1. URL: gov.uk/drug-safety-update/chloramphenicol-eye-drops-containing-borax-or-boric-acid-buffers-use-in-children-younger-than-2-years (accessed 15 October 2021).