Splitting tablets may affect dosage

“Splitting pills could lead to patients taking the wrong doses,” according to the Daily Express. The newspaper said that research into the practice showed it could be risky for drugs where the difference between a recommended and toxic dose is small.

The small study looked at typical drugs prescribed for diseases such as Parkinson’s disease, congestive heart failure, thrombosis and arthritis. Five academic volunteers split tablets into halves or quarters using three routinely used, accepted methods. The researchers found that the dose potentially given to patients when tablets were split could deviate from the recommended dose by at least 15%, and sometimes by more than 25%.

The researchers call for action to change the practice in nursing homes, where splitting drugs is routinely used. They also want drug firms to produce a range of options, including smaller or bigger dose tablets, so that splitting becomes unnecessary. Patients currently sometimes require a dose of medication that can only be provided through splitting a tablet. Increasing choice in tablet size sounds like a sensible proposal, and this research highlights the importance of taking pills according to the instructions.

Where did the story come from?

The study was carried out by researchers from the faculty of pharmaceutical sciences at Ghent University in Belgium. The study did not receive specific grants from any funding source. It was published in the peer-reviewed Journal of Advanced Nursing.

The BBC and Daily Express reported this research fairly.

What kind of research was this?

In this comparative study, the researchers aimed to report deviations from the expected weight of tablets following usual methods of splitting them into smaller pieces. They looked at whether the overall weight of the split tablet decreased compared to the unsplit weight. In other words, they calculated how much of the tablet was lost in the process of splitting.

The researchers explained that splitting tablets is a common practice in all sectors of healthcare. For example, a study in primary care in Germany showed that 24% of all drugs were split. It may be done for different reasons, such as to increase dose ﬂexibility, make tablet pieces easier to swallow or allow cost savings for both patients and healthcare providers as tablets of twice the strength are rarely twice the price.

The authors say that after a tablet is split, the parts are often not equal in size, and that a portion of a tablet can be lost during splitting if the tablet fragments.

So far, research has only looked at individual splitting methods and, according to the researchers, no one has compared the accuracy of a range of methods to see which is best.

What did the research involve?

The results of this small study, conducted in 2007, were analysed descriptively. Five volunteers were asked to split eight tablets of different sizes and shapes using three different routine methods. The methods were representative of those in usual practice in nursing homes. The volunteers included a pharmacy professor, a researcher, a student, an administrative worker and a lab technician. Only one had previous experience of splitting.

The methods used were:

method 1: a dedicated splitting device, called Pilomat
method 2: scissors for unscored tablets or manual splitting for scored tablets
method 3: a kitchen knife

They split tablets that were round or oblong, flat or not, scored or not. Half of the tablets were split into four segments and half into two. The tablets that were split were warfarin, digoxin, metformin, a combined levodopa and carbidopa tablet, phenprocoumon, spironolactone, methylprednisolone and lisinopril.

Warfarin and phenprocoumon were chosen because they are anticoagulants and, therefore, need meticulous dosage adjustment (titration) and frequent splitting. Methylprednisolone and lisinopril were selected because they are mainly split for economic reasons. The four remaining tablets were included because experienced nurses indicated that the tablets often cause problems during splitting (they are small tablets, big round tablets without scoring lines, coated tablets or fragment when split).

Tablets and tablet parts were weighed using an analytical balance before and after splitting.

What were the basic results?

For all tablets, the Pilomat device (method one) gave the lower average change from the unsplit weight. The deviations from the expected weight of the tablet parts were:

9.5% reduction with the splitting device (method one)
15.2% reduction with scissors and manual breaking (method two)
13.7% reduction with the kitchen knife (method three)

The differences between method one and methods two or three were statistically significant. The difference between method two and method three was not statistically signiﬁcant.

For individual tablets, methylprednisolone (a scored, oblong, non-flat tablet) seemed to be the hardest to split into four manually or using scissors, with an average change of 22.2% compared to the expected weight of the tablet parts.

How did the researchers interpret the results?

Large dose deviations or weight losses can occur while splitting tablets. The researchers say: “This could have serious clinical consequences for medications with a narrow therapeutic-toxic range,” in other words where the difference between an effective and a toxic dose is small. On the basis of their results, the researchers recommend that a splitting device is used when splitting cannot be avoided.

Conclusion

The authors acknowledge some drawbacks to their study:

Method two included two distinct techniques: using scissors for unscored tablets and manual breaking for scored tablets. This means that the researchers were unable to compare scissors as a technique on its own. However, they argue that this combination of methods is usual practice.
By using volunteers from their department rather than nurses, they are unable to say that nurses in a nursing home environment would have performed the splitting in the same way or with the same results.
They did not test the clinical importance of the differences in weight they discovered.

Overall, this study has been carefully conducted and analysed, adding some quantifiable data to the concerns about splitting tablets.

The researchers call for three changes that could improve practice in this area. They recommend the use of a splitting device as routine method when splitting cannot be avoided. They say that pharmacists should give clear messages about the risks related to splitting. Finally, they suggest that manufacturers could avoid the need for splitting by introducing a wider range of tablet doses or liquid formulations. These steps all seem like sensible advice.