Splitting tablets

Editor, – The recent article (Aust Prescr 2002;25:133-5) 'Splitting tablets' is very useful, but one point needs clarification.

I refer to the statement: 'Tablets that are scored are usually considered by the manufacturer to be suitable for division... ' and to the reference to azathioprine (Imuran) in Table 1.

It is correct that film-coated tablets should not usually be split, but the more important reason not to split Imuran tablets is that it is a cytotoxic drug. Splitting would be likely to release small particles into the air. Strangely though, Imuran tablets are scored. Apparently, the reason for this is that the tablets which are made in just one location are marketed in many countries, and at least one of them (Germany, I think) requires ALL tablets to be scored.

Jeff Lerner
Pharmacist
South bank, Vic.

Editor, – The article 'Splitting tablets' (Aust Prescr 2002;25:133-5) outlines practical issues on the splitting of tablets. However, it does contain one deficiency. It fails to mention the potential problem associated with the splitting of tablets containing antineoplastic drugs.

Antineoplastic drugs are potentially toxic medicines and it is essential that patients and other healthcare workers adequately understand their correct use. Many antineoplastic drugs have been found to be mutagenic, teratogenic and carcinogenic on the basis of cell DNA and chromosomal studies, animal models and, to a lesser degree, experience in treated patients. The risk associated with occupational low-level exposure has not been determined. Therefore, without evidence to the contrary, risk is assumed to be present.

Tablets and capsules of antineoplastic drugs must be handled in a manner which minimises exposure to healthy individuals. This includes avoiding skin contact and liberation of powdered drug into the air. Based on this premise, antineoplastic drugs in tablet form should not be split or crushed, and capsules should not be opened. Where required, antineoplastic mixtures should be prepared according to accepted standards.

With the increasing number of oral cytotoxic drugs available on the market, prescribers and consumers must be made aware of the potential dangers, albeit small, in splitting these tablets.

Jim Siderov
Senior Pharmacist, Cancer Services
Pharmacy Department
Austin & Repatriation Medical Centre
Heidelberg, Vic.

Dr J.L. Marriott and Professor R.L. Nation, the authors of the article, comment:

We thank the correspondents for their useful comments on our article. They are correct in suggesting that tablets containing antineoplastic drugs should not be split. To the best of our knowledge, all but one of the antineoplastic drugs available as tablets are marketed as unscored tablets; the one exception is the 50 mg strength of azathioprine tablet available under three brand names(Azuman, Imuran and Thioprine). In this case, it should not be necessary to even contemplate splitting a tablet as a 25 mg strength tablet is available from one of the manufacturers (Imuran). The 25 mg tablet is unscored and, as with other tablets of this type, should not be split.

Editor, - 'Splitting tablets'(Aust Prescr 2002;25:133-5) was a thought-provoking article on a subject that is not usually given much consideration by either practitioners or patients.

I would like to add the following few comments on this topic.

1. In circumstances where the splitting of tablets is permissible, cost benefit improves the patient's compliance. A tablet of double strength may offer a5-15% cost saving compared to half its strength (although this will vary between countries and products). This not only gives a psychological boost to the cost-conscious patient, but also gives a cumulative benefit for chronic diseases like hypertension and diabetes mellitus because of the increased compliance. Further, a patient when asked to take half of a tablet sometimes feels more secure than with a full tablet.

2. Digoxin has been cited as one of the examples for uneven breaking of a tablet that may lead to clinically significant fluctuations. Any fluctuation in the steady state plasma concentration usually requires nearly five half lives. Digoxin, despite being a drug with a narrow therapeutic index, is far less likely to fluctuate in a significant manner even if the splitting of the tablet is uneven (even if it happens on a daily basis), because of its long half-life.

3. The article could also have suggested that patients should be warned not to consume split tablets which are altered in colour, consistency and contour because of the risk of adverse effects or ineffectiveness.

G. Sivagnanam

Additional Professor of Pharmacology
Chengalpattu Medical College
Chengalpattu
Tamilnadu
India