Progression of risk

A consideration of the risks associated with extemporaneous preparation.

Formulation failure

Any formulae used in extemporaneous preparation should be validated and have supporting stability data – ideally sourced from pharmacopoeial formulations, industry expert reports and published papers. In reality however, such standardised formulae are of limited availability resulting in a multitude of different formulations being used. This in turn may result in formulation failure leading to under- and/or overdosing which may cause toxicity or therapeutic failure. As the complexity of the formulation increases so does the risk of problems occurring. There are many potential causes of formulation failure including physical incompatibilities, drug/excipients binding issues and drug degradation.

Microbial contamination

Microbial contamination can lead to both physical and chemical changes in the preparation, and be a significant risk to immunocompromised patients. Thus the choice of preservative, storage/refrigeration and shelf-life are all key considerations.

Calculation errors

Calculation errors pose the greatest risk of causing serious harm to patients. If possible, formulations should be as simple as possible and independently verified and documented. Most commonly, errors arise when converting units (eg. milligrams to micrograms), when doses can be prescribed as free base or salt, when diluting concentrates or through simple decimal points errors.

Clinical consequences

The clinical consequences of dosing inaccuracy with medicines that have a narrow therapeutic index are potentially more significant than drugs with a wider therapeutic index. Likewise, patients with certain conditions or from particularly vulnerable patient groups may be at greater risk of morbidity than others. Therefore, the clinical consequences of a formulation failure or calculation error will vary depending on the inherent properties of the drug and the patient’s clinical condition. This should form part of the risk assessment in each instance, and where there is a significant risk of morbidity associated with a non-standard or complex formulation, extemporaneous preparation should be a last resort.

As the majority of patients receiving extemporaneously prepared products are from vulnerable patient groups, pharmacists should regard them as being at increased risk and regularly review their condition.

Starting materials

Whilst certain ingredients are now unsuitable (eg. chloroform is now a recognised as a potential carcinogen) or considered inappropriate for children or certain religious groups, they may still be used in some historical formulae.

Patient acceptability

Palatability and presentation is an important consideration, especially with regards to compliance in children.

Health and safety risks

As it may involve the handling of hazardous materials, extemporaneous preparation has the potential to put the respective pharmacist at risk. These risks should be identified and evaluated – through A Control of Substances Hazardous to Health (COSHH) risk assessment – prior to preparation.

Standards for Extemporaneous Preparation or Compounding (adapted from RPS Professional Standards and Guidance for the Sale and Supply of Medicines94:

Patients are entitled to expect that products extemporaneously prepared in a pharmacy are prepared accurately and are suitable for use.

You must ensure that:

  • a product is extemporaneously prepared only when there is no product with a marketing authorisation available* and where you are able to prepare the product in compliance with accepted standards.
  • you and any other staff involved are competent to undertake the tasks.
  • the requisite facilities and equipment are available. Equipment must be maintained in good order to ensure that performance is unimpaired, and must be fit for the intended purpose.
  • you are satisfied as to the safety and appropriateness of the formula of the product.
  • ingredients are sourced from recognised pharmaceutical manufacturers and are of a quality accepted for use in the preparation and manufacture of pharmaceutical products. Where appropriate, relevant legislation must be complied with.
  • particular attention and care is paid to substances which may be hazardous and require special handling techniques.
  • the product is labelled with the necessary particulars, including an expiry date and any special requirements for the safe handling or storage of the product.
  • if you are undertaking large scale preparation of medicinal products, all relevant standards and guidance are adhered to.
  • records are kept for a minimum of two years. The records must include:
    - formula, ingredients, quantities used, their source,
    - batch number, expiry date,
    - patient's details, prescription details, date of dispensing (where appropriate)
    - personnel involved, including the identity of the pharmacist taking overall responsibility.

* except where methadone mixture is prepared extemporaneously in accordance with guidance.