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Sir, we read with great interest Professor Pemberton's article regarding the interactions of miconazole gel and warfarin.1
Another potentially underappreciated, although rarer, interaction which practitioners should be aware of is that of the antifungal agent fluconazole with those taking a statin. There has been documented evidence regarding the severe potential side-effect of rhabdomyolysis, ie muscle necrosis, in those taking statins who are co-incidentally prescribed fluconazole.2,3,4
Muscle necrosis may lead to myoglobinuria and acute renal failure as a result of impaired clearance of the statin.
We were alerted to this important interaction on reading a colleague's letter which appeared to demonstrate co-administration of fluconazole and atorvastatin5 without consideration of the side effect of rhabdomyolysis.
SDCEP drug prescribing guidance advises fluconazole not be prescribed to patients on statins.6 Pharmacy updates advise caution when co-administering fluconazole with atorvastatin, with consideration of reducing the statin dose7 and monitoring for muscle symptoms.
It is perhaps fortunate in this case that the atorvastatin was not stopped at the same time as administration of fluconazole, as this may have led to a false-positive result with the elimination of the patient's oral ulceration being mistakenly associated with the introduction of the anti-fungal agent. This would have delayed identification of the true cause of the ulceration, ie the statin.
Approximately seven million people in the UK are prescribed a statin8 making them the most commonly prescribed medication. With so many patients taking this medication, practitioner awareness of this potentially dangerous interaction needs to be raised.
Pemberton M N . Morbidity and mortality associated with the interaction of miconazole oral gel and warfarin. Br Dent J 2018; 225: 129–132.
Franz C C, Bruggisser M, Krähenbühl S, Rätz A B . Rhabdomyolysis associated with atorvastatin combined with amiodarone and fluconazole. Praxis 2011; 100: 273–284.
Kahri J, Valkonen M, Bäcklund T, Vuoristo M, Kivistö K T . Rhabdomyolysis in a patient receiving atorvastatin and fluconazole. Eur J Clin Pharmacol 2005; 60: 905–907.
Hsiao S H, Chang H J, Hsieh T H, Kao S M, Yeh P Y, Wu T J . Rhabdomyolysis caused by the moderate CYP3A4 inhibitor fluconazole in a patient on stable atorvastatin therapy: a case report and literature review. J Clin Pharm Ther 2016; 41: 575–578.
Smith D J, Dillon M, Russell J, Kanatas A . Statins and oral ulceration. Br Dent J 2016; 220: 45–46.
Scottish Dental Clinical Effectiveness Programme. Drug Prescribing for Dentistry: Dental Clinical Guidance (January 2016).
PL Detail-Document, Clinically Significant Statin Drug Interactions. Pharmacist's Letter/Prescriber's Letter. March 2016. Available at https://pharmacist.therapeuticresearch.com/Content/Segments/PRL/2016/Mar/Clinically-Significant-Statin-Drug-Interactions-9486 (accessed 6 November 2018).
NHS. NICE publishes new draft guidelines on statins use (17 February, 2014). Available at https://www.nhs.uk/news/medication/nice-publishes-new-draft-guidelines-on-statins-use. (accessed 6 November 2018).
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Tebbutt, J., Graham, R. Pharmacology: Dangerous interactions. Br Dent J 225, 907 (2018). https://doi.org/10.1038/sj.bdj.2018.1042