Pharmacology · patient case question
Why should the plan to prescribe systemic fluconazole for Patient A be reconsidered?
Patient case: Five medication lists in one session
Patient: Four separate patients
Chief Complaint: A: denture soreness. B: needs an antibiotic before an extraction. C: routine review. D: brought in obtunded by her daughter.
Background: A, 68-year-old male: benign prostatic hyperplasia on terazosin, hyperlipidaemia on simvastatin. Denture stomatitis diagnosed today and systemic fluconazole considered. B, 90-year-old female: frail, on no regular medication. C, 71-year-old female: rheumatoid arthritis on methotrexate, osteoporosis on oral alendronate for six years. D, 79-year-old female: long-standing hypothyroidism, ran out of levothyroxine some weeks ago.
Vital Signs: D: T 94.6°F · HR 48 bpm · RR 8 · BP 96/58 mmHg · drowsy and confused
Findings: A: erythematous denture-bearing palatal mucosa. C: panoramic radiograph taken for pre-operative assessment.
Show answer and explanation
Correct answer: D. It inhibits CYP3A4, raising simvastatin levels and risking rhabdomyolysis
- A. There is no clinically significant absorption interaction between fluconazole and terazosin.
- B. Nystatin and fluconazole are not antagonistic; they simply work by related mechanisms on ergosterol and its synthesis.
- C. Fluconazole is active against Candida albicans and is a standard systemic agent for oral candidiasis. The problem here is the interaction, not the spectrum.
- D. CORRECT. The azole antifungals are potent inhibitors of CYP3A4, and simvastatin, lovastatin and atorvastatin are CYP3A4 SUBSTRATES. Inhibiting the enzyme causes statin plasma levels to rise sharply, and the consequence is MYOPATHY progressing to RHABDOMYOLYSIS — muscle pain and weakness, dark urine from myoglobinuria, and acute kidney injury. The safer routes are a TOPICAL antifungal, or liaison with the physician about briefly holding the statin. Note that pravastatin and rosuvastatin are not CYP3A4-dependent and are far less affected.
Note: The same CYP3A4 mechanism makes ERYTHROMYCIN and CLARITHROMYCIN dangerous with these statins — and grapefruit juice does it too. Fluconazole additionally potentiates WARFARIN, raising the INR, and even topical MICONAZOLE gel is absorbed sufficiently to do this. Miconazole is not the safe topical alternative in an anticoagulated patient; nystatin is.