The Medicines and Healthcare products Regulatory Agency (MHRA) has concluded that the benefits of chloramphenicol eye drops containing borax or boric acid outweigh the potential risks for children, including those under two years.
Parents or carers should be advised that conjunctivitis is very common in babies and infants, and it is important that bacterial eye infections are treated properly.
Pharmacists should reassure parents or carers that these products can be given to children under the age of two years when prescribed.
The administration of one drop three to four times a day, in both eyes, would result in “daily exposure well below the safety limit”, the MHRA concluded.
The European Medicines Agency (EMA) published an update last month (April 29) to The European Commission guideline on ‘Excipients in the labelling and package leaflet of medicinal products for human use’, which advised that any product that would result in exposure to more than 1mg daily of boron should not be used in children under two years, due to an associated future risk of impaired fertility.
Chloramphenicol eye ointment preparations do not contain boric acid or borates and so can be prescribed for children less than two years old, however, they are not licensed for sale or supply to children under two years as pharmacy-only preparations, according to the Specialist Pharmacy Service (SPS) alert.
As a result of the EMA guideline, the Midlands regional NHS England and NHS Improvement (NHSE&I) team has removed the service for the treatment of antibacterial conjunctivitis in children under two years “with immediate effect”, Leicestershire and Rutland local pharmaceutical committee (LPC) told contractors.
RCOphth: Benefits outweigh possible risks
Following the EMA update, the Royal College of Ophthalmologists (RCOphth) published a safety alert stating: “Chloramphenicol eye preparations have been widely used in children of all ages for nearly 70 years in ophthalmic practice with no documented adverse effects on fertility. To our knowledge, there is no new scientific data from human studies to support this change to the product licence.”
It suggested the “daily exposure would be well below 1mg/day, even if 100% absorption is assumed” and “it is unlikely that formulations of boron-containing eye drops will be changed to remove boron in the near future”.
The RCOphth is concerned that avoiding all use of antibiotic eye drops with boron-containing excipients in children will result in increased prescribing of second or third-line antibiotics and encourage the development of microbial resistance, it said.
“The benefits of chloramphenicol eye drops in paediatric ophthalmic practice for appropriate indications and with courses of appropriate duration outweigh the possible risks posed by boron ingestion,” the RCOphth advised.
MHRA “urgently” seeking advice
The MHRA told C+D last Friday (May 7) that it is aware that implementation of the EMA’s guideline “has led to a situation where paediatric use below the age of two years has been restricted and this has clinical implications”.
“As a result, the MHRA is reviewing the evidence available and seeking independent expert advice to understand the risk for paediatric patients when using these products within the licenced indication and for what is likely to be a short period of time,” the watchdog added.
“We will consider chloramphenicol eye drop product information to ensure that appropriate and proportionate warnings are implemented as appropriate.”
The MHRA is considering the best way to communicate the information to healthcare professionals, it added.
“We understand the urgency of this issue for patients and clinicians and we are working urgently to reach a prompt resolution,” the MHRA concluded.
The RCOphth also told C+D it is seeking to work with the MHRA and the Department of Health and Social Care senior pharmacist medicine supply team “to ensure the advice given by all national bodies and suppliers is proportionate and supports clinical requirements”.
In its update to the European Commission guideline, the EMA advised that all preparations containing boric acid or borates above a threshold level must include a warning in their package leaflet.
Boron, an essential trace element, is often used in medicines for its antimicrobial and buffering properties. Rat toxicity studies have identified testicular toxicity, leading to reduced fertility. As a result, the EMA recommends upper limits on the daily exposure to boron-containing excipients of 1mg per day for children under two years and 3mg per day for children aged 2-12 years.
Most UK manufacturers have now updated product information for chloramphenicol eye drops, which contain boric acid, to include a warning contraindicating use in children less than two years old, due to boron content.
Source: SPS alert, Using chloramphenicol eye products in children under 2 years, updated May 6, 2021