Generic medicines

Editor, – The article, 'Frequently asked questions about generic medicines' (Aust Prescr 2007;30:41-3), provides a clear and useful precis of some of the key issues that can impact on the decision to substitute an equivalent generic medicine.

However, the question of whether or not to substitute a medicine with a narrow therapeutic index with a bioequivalent generic remains open to debate. Perhaps the prescriber and pharmacist could approach this decision with more confidence if we consider the criteria used to define the term narrow therapeutic index, or more correctly narrow therapeutic ratio, by regulatory agencies.

The US code of federal regulations (Part 320.33(c) - Bioavailability and bioequivalence requirements) defines a medicine displaying a narrow therapeutic ratio as follows:

There is less than a 2-fold difference between median lethal dose and median effective dose

OR

There is less than a 2-fold difference between minimum toxic concentrations and minimum effective concentrations in the blood

AND

Safe and effective use of the drug products requires careful dosage titration and patient monitoring.¹

The US Food and Drug Administration (FDA) specifically mentions only five medicines falling into this category, namely digoxin, lithium, phenytoin, theophylline and warfarin. However, the FDA recommends that even medicines with narrow therapeutic indices may be evaluated for bioequivalence using the conventional confidence interval limits of 0.80 to 1.25.²

In reality, the number of medicines matching the definition of narrow therapeutic ratio is very small indeed. In clinical practice, the dosage and plasma concentration of these medicines is usually carefully titrated and monitored.

Greg Pearce
Medical Advisor
Alphapharm Pty Ltd
Glebe, NSW

Professors AJ McLachlan, I Ramzan and RW Milne, authors of the article, comment:

We agree with the issues that Dr Pearce raises and add a further comment. We would suggest that the list of narrow safety margin medicines (and the criteria listed) also includes immunosuppressants (such as cyclosporin) and many anticancer medicines. A useful commentary on this issue makes the critical point that inter-subject (between people) variability in the pharmacokinetics of narrow safety margin medicines is considerably higher than intra-subject (within the same person on any given day) variability in pharmacokinetics.³This means that for many of these drugs careful monitoring of a patient's therapeutic response (or some surrogate of that response) can facilitate dose individualisation and that once that dose is selected, therapy can generally continue uneventfully with appropriate monitoring.

In our article we also highlighted the importance of separating the scientific (which remain unchallenged) from the clinical (which remain in the purview of clinical judgement) issues surrounding generic substitution of medicines. The latter point being that the potential for confusion around the issues of brand substitution can be managed by effective communication and clinical judgement. Obviously the potential for problems increases significantly when people are confused about their medicines and are taking medicines with a narrow safety margin.

In summary, Australian prescribers, pharmacists, other healthcare providers and patients should have full confidence in the Australian system used to establish and evaluate bioequivalence of drug products which applies to all medicines independent of their safety margin. Effective communication of all these issues is a central component of brand substitution.

Editor, – I note that the problem of generic medicines has been mentioned again in your April edition (Aust Prescr 2007;30:41-3).

I am a firm believer in not using generic names - not from habit, but from practicality. When a drug is marketed the makers go to a lot of trouble to find a name that is easily recognised and remembered and unlikely to be confused with other drugs. The same cannot be said about generic names which are often complicated chemical names and the possibility of confusion arises.

John B Walker
Ear, Nose and Throat Specialist
Edgecliff, NSW

Response:

The Editorial Executive Committee believes that the use of generic names in Australian Prescriber is appropriate. There are several reasons for this.

1. Medical students are not taught brand names, so it is appropriate that educational material uses generic names.

2. There are many different brand names for commonly prescribed drugs. It would be impractical to include all the brand names of each drug mentioned in Australian Prescriber.

3. The variety of brand names can cause confusion. There is a possibility of medication error with badly written prescriptions for drugs such as Losec and Lasix, Mobilis and Movalis, MS Contin and Oxycontin, Provera and Proviron.

4. The brand names are devised as part of a drug company's marketing strategy. As Australian Prescriber is independent of the pharmaceutical industry it avoids brand names.

5. Many thousands of people overseas visit the Australian Prescriber website. As brand names vary from country to country it is helpful if the articles use internationally approved names.

While the Editorial Executive Committee appreciates other views, generic names will continue to be used inAustralian Prescriber.