Hospital Pharmacist
Vol 10 No 2 p34
February 2003

Dilemmas in prescribing for paediatric patients

By V’Iain Fenton-May, BPharm, FRPharmS

Paediatric patients belong to one of the most vulnerable sections of our society. The pharmacodynamics of the young child are variable, and are dependent on the age and disease state of an individual patient. The medicinal needs of paediatric patients should, therefore, be handled by professionals within the pharmaceutical and medical fields. Anyone dealing with the prescribing or dispensing of medicines for paediatrics must have access to the most up-to-date information available.

Because of the altered pharmacodynamic handling and pharmacokinetic response to drugs in paediatric patients, the pharmaceutical industry has been reluctant to pursue the licensing of many pharmaceuticals for use in children. There are also a number of social, financial and ethical issues to be overcome before we will see widespread licensing of medicines for paediatric patients.

The difficulties faced are the ethical issues of experimentation in children, the need to obtain consent from parents, the population size in age ranges, and the uncertain profitability of the target market.

In the meantime, we are faced with the situation where some 40 per cent of prescribing for children concerns the use of unlicensed medicines (including "specials"), and the use of licensed medicines outside their licence restrictions ("off-label" use).

Recent papers in the British Medical Journal¹ have highlighted the potential problems inherent in the use of off-label medicines and specials. One of the main areas of concern is that adequate dosing regimens have not been fully assessed. However, it could be argued that it is the potential for adverse drug reactions in paediatric patients, and the difficulties in predicting an individual's response to a product, that reduces the desire of manufacturers to obtain licences for use in children.

It is morally unjust not to carry out clinical studies in children, where a medicinal product is expected to offer clinical benefits.

The United States is leading the world in permitting the Food and Drug Administration to mandate paediatric studies on pharmaceutical products, where it deems it to be appropriate.² Currently, the European Union is following suit, and has produced a discussion paper on the subject.³ We should give full support to such a movement.

There is nothing morally or legally wrong with the use of unlicensed medicines, and it would be unethical to deny the paediatric population medicinal care, provided that the products are appropriate to an individual patient's needs and are of a suitable quality. Part of a joint declaration from the Royal College of Paediatrics and Child Health, and the National Paediatric Pharmacists Group (NPPG), has captured the spirit of this concept in their statement:

"The informed use of unlicensed medicines, or of licensed medicines for unlicensed applications, is necessary in paediatric practice."

Pharmacists should, however, be aware of their ethical and professional responsibilities to ensure that a medicine (whether unlicensed or licensed) is of an appropriate quality, and is suitable for the patient.

Information on unlicensed medicines is available from a variety of sources. However, the information found on the internet should be treated with caution as, in some cases, its accuracy cannot be guaranteed. The first port of call for information should be to peer reviewed data, and a peer group. The information sources available in the pharmaceutical world include the National Health Service medicines information centres, the NPPG, and the National Quality Assurance Group.

The NHS has a duty to research its own activities. It is unfortunate that the number of NHS pharmaceutical laboratories performing stability testing of specials and extemporaneous products is diminishing. This is because of altering priorities within the pharmacy profession, and a move away from traditional, technical activities. However, hospital pharmacists in the United States are currently producing information on extemporaneously produced medicines, using stability indicating assays.

In general, the quality of licensed products is not in question. However, it should be noted that decisions regarding reformulation and acceptance of "out of specification" batches are taken by the manufacturer of that product and the competent authorities (Medicines Control Agency), having regard to the licensed indications only. For example, a batch of an injectable analgesic licensed for adults may be deemed to be acceptable, in circumstances of shortages, if it were to assay out at 112 per cent. In adults, this would not have a clinical significance, but such a change may affect the clinical response to the product if used outside the licensed indication for young children. However, the user would be unaware of the change in strength of the product.

The preparation of specials requires the application of good dispensing practice at the time of preparation (or the use of a licensed manufacturer) to ensure high quality.

With respect to extemporaneous preparation, a number of organisations have produced their own guidelines, each being appropriate to the level of specialisation and volume of work.

A pharmacist will satisfy their ethical responsibilities, when dealing with unlicensed products, if they can answer the following:

• Is the proposed product the most appropriate to provide for the patient's needs?

• Are there suitably trained operatives, under the supervision of a pharmacist, available to compound the product?

• Is the process adequately documented?

• Are the raw materials and facilities appropriate, and is the equipment valid?

• Are procedures in place to ensure that the products are not contaminated?

• Is there a regular audit on facilities, products, and staff?

• Is the preparation suitably formulated, and is the expiry date appropriate?

When working within such constraints, we can be assured that the patient receives the best available treatment at the time of need.