Ferric Ammonium Citrate 400 mg/5 ml Mixture

Introduction

Ferric ammonium citrate 400 mg/5 ml mixture (FAC syrup) is a commonly prescribed medication for prevention and treatment of iron-deficiency anaemia in premature infants at Malaysia.

• FAC mixture is commonly supplied for 3-4 months post discharge or until next review.

Extemporaneous Formulation (BPC 1973, page 742)

Ferric ammonium citrate BP 80 g

Compound orange spirit BP 2 ml

Syrup BP 100 ml

Double strength chloroform water BP 500 ml

Water q.s. to 1000 ml.

* This product would be recently prepared as double strength chloroform water BP acts as a preservative and therefore would attract a four-week discard date.

* The dose should be taken well diluted with water.

Dosage Calculation

Dosing of FAC syrup is based on elemental iron needed per day. As per Frank Shann Drug Doses, 2017, ferrous salts dosage is as below:

• Prophylaxis, 2 mg/kg/day elemental iron oral
• Treatment, 6 mg/kg/day elemental iron oral.

* In real practice, the dosing prescribed can be within the range of 2-6 mg/kg/day elemental iron.

To calculate the volume of FAC syrup needed, you should know the elemental iron content in Ferric Ammonium Citrate 400 mg/5 ml syrup.

• As written in page 97 of Paediatric Protocols for Malaysian Hospitals, 4th Edition, 2019), it contains 86 mg/5 ml of elemental iron.

The estimation of 86 mg elemental iron per 5 ml is probably based on ratio of molar mass.

• Ferric ammonium citrate(C6H8FeNO7), molar mass 261.98 g/mol
• Iron molar mass 55.845 g/mol
• Hence 400 * (55.845/261.98) = 85.266

NOTE: In Martindale, it is stated that Ferric Ammonium Citrate (USP 2023) contains between 16.5% and 18.5% iron. Based on this estimation, a FAC 400 mg/5 ml syrup likely contains less than 86 mg/5 ml of elemental iron. While ferric ammonium citrate has a general formula, it is a complex compound with variable composition. This variability arises from factors such as hydration, the manufacturing process and the presence of impurities. Therefore, to determine the specific elemental iron content of a particular batch, it is crucial to refer to the manufacturer's Certificate of Analysis (CoA).

Calculation Example

For a baby weighing 2.1 kg, having a target dose of 6 mg/kg/day of elemental iron,

Elemental iron needed = 2.1 kg * 6 mg/kg/day = 12.6 mg

Volume of Ferric Ammonium Citrate Mixture = 12.6 mg / 86 mg * 5 ml = 0.73 ml

The Alternative

On 19 November 2024, a directive was released, banning the use of chloroform or chloroform spirit as a preservative in pharmaceutical products, natural products and supplements. The official ban on chloroform in commercial pharmaceutical products has prompted a range of responses from hospital pharmacies too.

• Many questioned the sudden ban on chloroform.
• The potential risks associated with chloroform have been recognized for years, yet its use persisted till now.
• Some suggest seeking suitable alternative preservatives for ferric ammonium citrate mixture.
• This presents a significant challenge, as thorough testing and evaluation will be necessary to ensure the safety and efficacy of any replacement.
• Others have opted to supply the FAC powder to patients and instruct them on its preparation.
• This may potentially lead to preparation errors and be inconvenient for patients.
• Some pharmacies have continued to prepare the mixture temporarily, given that this has been the established practice for years.
• This is a temporary solution until a safer alternative can be implemented.

Given that safety and stability are the primary concerns, iron (III)-hydroxide polymaltose complex syrup (e.g. Maltofer syrup, Saferon syrup) is the preferred alternative commercial source of elemental iron.

• Maltofer syrup and Saferon syrup both contain 10 mg of elemental iron per ml of syrup.
• Iron polymaltose is absorbed best if taken during or immediately after a meal.

NOTE: Eurofer-iron syrup contains 0.1 g of sodium benzoate per 100 ml, making it unsuitable for neonates due to the risk of hyperbilirubinemia.