Splitting Tablets – Is It Safe?

The question of whether a solid dose form can be divided, or split in half, requires careful consideration. Patients and healthcare professionals may be required to split tablets for a variety of reasons; it may be necessary to administer a lower dose than what is available, the dose may need to be titrated carefully according to response or side effects, or the patient may have difficulty swallowing an intact tablet. After checking with their doctor or pharmacist to ensure that it is safe, some patients also split higher dose tablets to reduce their prescription costs, as a single prescription may then last for 60 days rather than 30 days. However, some important issues need to be considered.

A number of problems may arise which could either be related to the tablet formulation, or the patient. Elderly patients may find splitting tablets difficult due to vision or dexterity problems. There is also the issue that not all tablets can be safely split in half.

Tablets that should not be split include:

• Unscored tablets
• Irregularly shaped, or small sized tablets
• Film or sugar coated tablets
• Enteric coated tablets
• Modified release tablets; and
• Antineoplastics (chemotherapy or cytotoxic tablets).

Unscored, irregularly shaped, or small tablets

A tablet that is pre-scored by the manufacturer, indicated by a groove or indentation on the surface of the tablet, may be considered suitable to be split in half. The chance of getting equal doses between the two halves is better, provided the tablet has been broken exactly in the scored indentation. There are, however, some scored tablets that are not recommended to be split (e.g. Imuran^® due to its cytotoxicity).

Splitting tablets that are unscored, small, or irregularly shaped will result in an uneven break, and therefore cause dose variations. This may result in either getting too much of a medication, leading to enhanced adverse effects or getting less of a medication and therefore reduced therapeutic effects. This is more clinically significant for medicines with a narrow therapeutic index (e.g. warfarin, digoxin, phenytoin) where a small change in dose can lead to a large effect. Medicines with longer half-lives or wider therapeutic ranges tend to be less sensitive to small variations in dose.

Film, or sugar, coated tablets

A film coating is a thin polymer-based coat that is applied to tablets. Sugar coatings are much thicker and more time consuming to manufacture, therefore film coatings tend to be preferred. These coatings may be used to protect the medicine from light and moisture, mask objectionable tastes or odours, or to simply provide an easily identifiable appearance.

Nifedipine is an example of a highly light-sensitive medicine that is film coated. Splitting these tablets exposes the medication to light and moisture and leads to rapid degradation of the active ingredient. Breaking the film or sugar coating on medicines such as hydroxychloroquine may also expose the patient to its unpleasant taste and lead to reduced future compliance.

Many patients prepare their dose administration aids in advance for the week, which increases the risk of degradation of the active ingredient. This is particularly problematic for a medicine like aspirin, which is rapidly hydrolysed upon exposure to moisture.

Stability of the medicine and patient tolerability are therefore important factors to consider when splitting tablets.

Enteric coated tablets

An enteric coating is a polymer barrier applied to oral tablets to protect the medicine from the acidity of the stomach. It is designed to allow release later in the more alkaline environment of the intestine.
The enteric coating on tablets helps to:

• Delay the release of medicines that may be degraded by the acidity of the stomach (e.g. omeprazole)
• Reduce stomach irritation and gastrointestinal (GI) side effects; or
• Release the medication at a particular site in the GI tract for it to work.

Splitting a tablet which is enteric coated may result in the drug being degraded by the stomach acid and thereby reducing its bioavailabilty. It could also result in an increase in GI side effects, or simply failure of the medicine to reach its specific site of action.

Slow release tablets

Several tablets have been formulated using different release mechanisms to allow the medicine to enter the bloodstream at a slower and steadier rate (usually over 12-24 hours). Some slow release (SR) tablets can be safely split in half without affecting their extended release properties. For instance, some formulations of isosorbide mononitrate SR have been designed to be split in half, and are presented as scored tablets. Splitting other unscored slow release tablets will alter the release and absorption of the medicine. This may result in a large bolus dose, high peaks, and the potential for increased side effects and toxicity.

Antineoplastics and hazardous medications

Splitting cytotoxic and other hazardous medications may expose patients or carers to health risks through the inhalation of fine particles resulting from the split tablets. For example, finasteride presents a risk of birth defects in male foetuses, and broken tablets should therefore not be handled by pregnant women, or women of childbearing age.

Conclusion

Although splitting tablets may seem cost effective and safe in some situations, it is important to remember that not all tablets are safe to be split in half. Splitting of some tablets can cause unwanted wastage of medication, alter the efficacy of the medicine through degradation, or increase the potential for side effects. Apart from these tablet-related issues, there are also patient-related problems that need to be considered to ensure the safe administration of medications. Tablet splitting can be challenging for the elderly and the frail due to dexterity, visual, and cognitive issues. This difficulty in splitting tablets may have a negative effect on patient compliance. Where tablet splitting is permissible, the use of suitable devices such as a pill cutter should be employed to improve accuracy. Pharmacists play an integral role in ensuring that correct advice is provided for the safe administration of medications for better health outcomes.