Miconazole oral gel to treat oral thrush in adults taking statins

Treatment of oral thrush (candidiasis) with miconazole is complicated by concurrent HMG-CoA reductase (statin) use because of potential for drug interactions.

Complications of using miconazole with statins

Miconazole may increase blood levels of some statins, increasing risk of adverse effects such as rhabdomyolysis and myopathy.

Before prescribing miconazole to a person taking a statin consider (1):

• if an interaction is likely
• the clinical significance of any expected interaction
• licensing (i.e. does the SPC contraindicate use)
• risk mitigation measures
• alternative treatment options (e.g. use of a non-interacting treatment such as nystatin)

Interaction between miconazole and statins

• mechanism
  • according to the SPC for miconazole oral gel miconazole, an azole antifungal, is absorbed systemically. It inhibits CYP450 isoenzymes CYP2C9 and CYP3A4, and may increase blood levels of drugs metabolised by these isoenzymes.
  • some statins are metabolised, to a greater or lesser extent, by these isoenzymes. Extent of metabolism and associated clinical significance of the interaction varies from statin to statin (see below)
• potency of CYP3A4 and CYP2C9 inhibition
  • is not known how strongly miconazole inhibits CYP450 isoenzymes but it is expected to interact with statins in a similar way to fluconazole, a moderate inhibitor of CYP2C9 and CYP3A4 (1)
    • itraconazole and ketoconazole are potent inhibitors of CYP3A4

Advice for individual statins and miconazole

• Simvastatin
  • do not use miconazole in combination with simvastatin. Instead use a different antifungal, e.g. nystatin.
  • the SPC for simvastatin states that simvastatin is a substrate of CYP3A4; concomitant use of miconazole oral gel may increase simvastatin levels
    • due to risk of myopathy and rhabdomyolysis associated with combined use of miconazole and simvastatin the SPC for miconazole oral gel specifically contra-indicates use
    • Stockley's Drug Interactions (subscription required) highlights several cases of rhabdomyolysis and myopathy associated with fluconazole and simvastatin use
  • if essential to use miconazole, simvastatin must be temporarily stopped whilst the individual is using miconazole
  • consider involving the individual's GP in this decision
    
    
• Atorvastatin
  • do not use miconazole oral gel, if possible. Instead use a different antifungal, e.g. nystatin
  • SPC for atorvastatin states that atorvastatin is metabolised by CYP3A4
    • concomitant use with other inhibitors of CYP3A4, such as miconazole, can increase plasma concentrations of atorvastatin and increase risk of myopathy
    • combination use with azole antifungals is cautioned, but not contra-indicated.
    • Stockley's Drug Interactions (subscription required) highlights cases of rhabdomyolysis and myopathy associated with fluconazole and atorvastatin use
      • as miconazole has the potential to interact similarly, prescribers should consider benefits of treatment versus the risk of using this combination.
  • if miconazole oral gel must be used, it may be prudent to:
    • temporarily withhold atorvastatin, whilst the individual is using miconazole, to avoid possible adverse effects or,
    • use a lower dose of atorvastatin and monitor for toxicity
  • consider involving the individual's GP in this decision
    
    
• Fluvastatin
  • use miconazole oral gel with caution
    • counsel individual regarding possible risk of an interaction and monitor for adverse effects.
  • as fluvastatin is metabolised by multiple CYP450 pathways, the SPC for fluvastatin highlights its metabolism is relatively insensitive to CYP450 inhibition
    • although an interaction is unlikely, a theoretical risk cannot be excluded and the BNF interaction checker and Stockley's Drug Interactions (subscription required) suggest caution with this combination
      
      
• Rosuvastatin
  • use miconazole oral gel. A clinically significant interaction is not expected.
  • SPC for rosuvastatin states that drug interactions resulting from CYP450-mediated metabolism are not expected
    • rosuvastatin undergoes limited metabolism (about 10%, principally by CYP2C9, and by CYP2C19, CYP3A4 and CYP2D6 to a lesser extent).
  • there is a small theoretical risk of an increase in rosuvastatin levels, Stockley's Drug Interactions (subscription required) highlights this is unlikely to be clinically relevant
    
    
• Pravastatin
  • use miconazole oral gel. A clinically significant interaction is not expected
  • SPC for pravastatin states it is not metabolised, to a clinically significant extent, by the CYP450 isoenzyme system.
  • absence of a significant pharmacokinetic interaction with pravastatin has been demonstrated for several azole antifungals including fluconazole, itraconazole and ketoconazole

Counselling people using miconazole with an interacting statin (1):

if people on an interacting statin need to use miconazole they should be advised to report any possible signs or symptoms of myopathy and rhabdomyolysis, such as:

• unexplained muscle pain
• tenderness
• weakness
• dark coloured urine

if myopathy occurs, the statin should be stopped immediately

Report any adverse effects due to the combination to the MHRA via the Yellow Card Scheme.

Reference:

• NHS Specialist Pharmacy Service (November 2021). Using miconazole oral gel to treat oral thrush in adults taking a statin