Excipients and patients

Last updated: Sunday, December 10, 2023

It can be difficult to find out about adverse reactions to excipients and how frequently they occur, although one of the reasons for a substance being selected as an excipient is that it should not commonly cause side effects. In addition, the amount of an individual excipient in a medicine is usually small.

However, occasionally, excipients can cause dose-related adverse reactions. Persistent administration of sugar-containing medicines might cause tooth decay, for example, and the popular sweetener sorbitol used in some liquid medicines can cause diarrhoea because it acts as an osmotic laxative. Another example is the sodium content of medicines. Sometimes this is high enough for a medicine not to be recommended for patients on a restricted salt diet (e.g. those with hypertension). Antacids and dispersible, effervescent and soluble tablets may contain quite high amounts of sodium.

In practice, the commonest side effects of excipients tend to be due to intolerance, which is often dose-related, and allergy, which is not dose-related. In these situations it is important to help patients to avoid further exposure.

Factors influencing risk

Some excipients are not absorbed from the gut, and so are particularly unlikely to cause systemic reactions after oral administration (e.g. talc). Certain other common excipients are natural to the human body and in the amounts used in pharmaceuticals are unlikely to cause side effects (e.g. citric acid). Many excipients also occur naturally in food and so may form part of a regular diet (e.g. starches).

Some excipients can potentially cause problems in both adults and children such as sorbitol, which is commonly found in liquid medicines. However, certain excipients can present special problems in children such as those in the table below. Exposure to these agents should be minimised as far as possible but occasionally a medicine containing a problem excipient may be indicated after a careful risk-benefit assessment (e.g. amiodarone injection containing benzyl alcohol).

Excipient	Linked with
Glucose and sucrose	Obesity, and tooth decay if taken orally
Benzyl alcohol	A gasping syndrome in neonates
Ethanol	CNS effects
Aspartame	A source of phenylalanine in patients with phenylketonuria
Polyoxyl castor oils	Severe anaphylactoid reactions
Propylene glycol	CNS effects especially in neonates and children under 4 yrs
Colourants (e.g. tartrazine)	Hypersensitivity and behavioural disturbances

A more detailed assessment of the risks posed by excipients to children is presented by the NPPG and the RCPCH.

As already noted, the commonest reason you may be asked about excipients is that a patient has a known allergy or intolerance to it. In this situation you need to find out the history and nature of the reaction in order to best help the patient. We examine this aspect in more detail on the next page.