The risk of liver damage with oral terbinafine – putting it into context.

Over the years, I have written blogs discussing the issue of terbinafine toxicity as frequently when I speak to patients about oral antifungal treatments they often say “Isn’t terbinafine dangerous to take because of liver damage?” In this short piece, I am not going to disagree there is always potential risk with taking any drug but the important thing when discussing risk to patients is putting it into a context which is simple, clear, understandable and allow them to make decisions which are fully informed.

All drugs hold a risk of side effects - conveying the risk to patients can be difficult

The Risk of Terbinafine induced liver injury

I have previously written blogs on terbinafine safety (which you can find here and here)  but I recently came across a statistic which made me think about how we convey risk to our patients. As podiatrists in the UK we have a level of understanding of pharmacology, with many of us able to supply or prescribe antibiotics such as erythromycin, amoxicillin and flucloxacillin under our existing certification through a written order. For conditions such as foot infections, we may supply amoxicillin, erythromycin or flucloxacillin. Do we think about toxicities associated with these common drugs? Probably not regularly.

Comparing flucloxacillin with terbinafine, which holds the greater risk for liver injury? It’s tempting to say terbinafine given the public knowledge and general perception but in fact it’s not, by some considerable margin. Flucloxacillin is five to seven times more likely to cause liver damage than oral terbinafine [Flucloxacillin: 8.5 per 100 000 prescriptions v Terbinafine: 1 per 50 000–120 000 prescriptions] [1, 2].

"Flucloxacillin is five to seven times more likely to cause liver damage than oral terbinafine"

Putting it in that way may make a headline and make practitioners stop and think. However, presenting data as relative risk, in this way i.e. “Flucloxacillin is five times more likely to cause liver toxicity compared to terbinafine” whilst correct, may not be the best way to help patients understand risk.

Communicating risk forms the basis of good consent in healthcare practice but perhaps clinicians are not always aware how to do this effectively and in a way which conveys risks effectively.

Communicating the Risk

As research has shown patients perceptions of risk are often driven by emotion more than facts. Consequently, just supplying raw numbers can be unhelpful as emotions can override this and ultimately affect the decision. In addition, this relies on the numeracy skills of the practitioner and the patient.

The key perhaps is to present it in a form patients can understand which is competent and cognisant of patient’s emotion [3].

1.      Standardisation of words can help to convey risk: (“very common,” “common,” “uncommon,” “rare,” and “very rare”) but are open to differing interpretations by individuals. Descriptions like “low risk” also may have very different interpretations.

2.      Visualising risk for many is easier to comprehend. Several scales have been suggested such as visual depictions of proportions as charts. Paling [3] suggested a visual form (see the Paling Palette below) but pie charts are another way to visually depict risk and benefit. Visualisation of risk can improves patients comprehension [4].

3.      Using a consistent denominator. For example, “the chances of a person of developing liver damage by taking drug A is 1 in 100 000”.

4.      Where possible frame the risk as benefit not harm, or even better as both, as this reflects more honesty and builds practitioner trust. For example, “99 999 out of 100 000 people who take terbinafine have no liver injury.”

5.      Relative risk statements are likely to be less effective at conveying risk to patients and should be avoided. For example, as above - “Flucloxacillin is five times more likely to cause liver toxicity compared to terbinafine” is not the best way to convey specific risks.

The Paling Palette - An example of a way for patients to visualise risk. Image from PROTECT Website Source here

Implications for practice

Like all healthcare professionals, as part of the consent process, we are required to ensure the patient has an understanding of any procedure before the consent can be deemed valid. Particularly relevant here is ensuring the patient knows the materials risks of treatment, whilst ensuring we have taken reasonable care to ensure the patient knows this [5].

Whilst this may not apply to all aspects of podiatry care, certainly this will apply to nail surgery procedures and prescriptions of medications (including oral antifungals). On that basis, looking at how risk is conveyed and ensuring it is accessible and understandable to patients is important. For example, “3 in 100 patients undergoing nail surgery at our practice will have a recurrence” or conversely 97 out of 100 patients at our practice have a successful procedure with no recurrence of the ingrowing nail”.  A visual depiction using a perception chart or palette may help patients to contextualise the risk.

 

References

1.           Wing K, Bhaskaran K, Pealing L, Root A, Smeeth L, van Staa TP, Klungel OH, Reynolds RF, Douglas I: Quantification of the risk of liver injury associated with flucloxacillin: a UK population-based cohort study. J Antimicrob Chemother 2017, 72:2636–2646.

2.           Nibell O, Björk J, Nilsson A, Jacobsson G, Inghammar M: The risk of drug-induced liver injury associated with flucloxacillin: a nationwide, entropy-balanced cohort study. Clin Microbiol Infect 2025, 31:600–606.

3.           Paling J: Strategies to help patients understand risks. BMJ 2003, 327:745.

4.           Zikmund-Fisher BJ, Fagerlin A, Ubel PA: Improving understanding of adjuvant therapy options by using simpler risk graphics. Cancer 2008, 113:3382–3390.

5.           Sokol DK: Update on the UK law on consent. BMJ 2015, 350:h1481.