Classification of drugs by potential risk to patient health

Most drugs are known to have potential adverse effects in patients, usually identified during the drug development and clinical trial stage, or in the UK, through the Yellow Card reporting system monitored by the Medicines and Healthcare Products Regulatory Agency (MHRA) (BNF, 2016b). These may include observed adverse effects, interactions with other drugs, vaccines or even complementary and herbal medicines. Adverse effects can be relatively minor or very severe. Furthermore, some drugs can themselves cause severe illness such as cardiac dysfunction. It is important that these risks are understood by prescribers, and a careful analysis should be undertaken of the potential cost to the patient of taking the drug in comparison with the potential benefits. If the patient is fully informed of the risks, and the healthcare team feel that the drug is still in the patient’s best interest, then informed consent can be taken from the patient and the drug prescribed. A common example of this is the cytotoxic anticancer drug trastuzumab, which is associated with a significant risk of congestive heart failure (Popat and Smith, 2008, p.325). However, as trastuzumab has been shown to be an effective treatment for HER2 positive breast cancer, its use is still recommended, although careful patient monitoring and cessation of treatment in the event of cardiac toxicity is recommended by NICE (NICE, 2010). In order to manage the risk of cytotoxic drugs to patients, drugs classified as cytotoxic (i.e. that may cause harm to some systems as well as treating tumours) require special handling. For example, they should only be prepared by trained personnel in designated pharmacy areas. Healthcare professionals handling these drugs should wear protective clothing (gloves, masks and gowns), and local procedures for the control of spillages and disposal of waste should be followed (BNF, 2016a).

Drugs may also be classified by the potential risk they pose when administered during pregnancy. Some drugs, such as diethylstilboestrol (thalidomide), have the potential to cause congenital malformation (teratogenesis) when administered in the first trimester. Similarly, some can affect the development of the foetus or its growth, particularly when administered in the second and third trimesters, which may be linked with congenital abnormalities such as cleft palate, heart defects or low birth weight, although evidence for this link is mixed (Nezvalová-Henriksen et al., 2013). Although many drugs are considered to not be harmful in pregnancy, it is difficult to classify these medications as “safe”, as ethical considerations prevent the use of clinical trials in pregnant women, therefore evidence tends to be based on reports of complications following usage. In general, prescribers are advised to only prescribe drugs when the benefits to the mother outweigh the potential risk to the foetus. This risk can be evaluated from evidence obtained from animal studies of teratogenicity, or evidence from studies or reported examples of teratogenicity in humans. Prescribers may also have similar concerns when prescribing to breastfeeding women, as there is a possibility that the drug may enter the breast milk and therefore be passed to the infant, however the potential risk of this is dependent on the pharmacokinetics of the drug (how it acts and is metabolised in the body), the rate of absorption and elimination of the drug by both mother and infant, and the potential effects of any drug (or drug metabolites) on the infant. In the UK, previously the BNF contained a table classifying the potential harmfulness of drugs during pregnancy, however in recent editions this has been replaced with recommendations for use in pregnant or breastfeeding women under each individual drug entry, with the general recommendation that drugs should only be prescribed to pregnant women if the benefit to the mother outweighs any potential risk. Institutions may have local recommendations for drug choices in pregnant women, or have produced their own formularies