What is the relationship between Fluconazole (an antifungal medication) and Factor VII (FVII) deficiency?

From the Guidelines

Fluconazole does not directly cause Factor VII deficiency, but it can increase the risk of bleeding in patients taking warfarin due to its inhibition of CYP2C9, which can lead to increased INR levels. The relationship between fluconazole and Factor VII deficiency is indirect, as fluconazole can interact with warfarin, a medication that antagonizes vitamin K and can exacerbate Factor VII deficiency 1. Fluconazole is an antifungal medication that works by inhibiting fungal cytochrome P450 enzymes, particularly 14-alpha-demethylase, which is necessary for ergosterol production in fungal cell membranes. While fluconazole can interact with human cytochrome P450 enzymes and affect the metabolism of certain medications, it does not directly impact Factor VII production or function.

Some key points to consider when using fluconazole in patients with pre-existing Factor VII deficiency include:

• Monitoring of INR levels is warranted due to the potential interaction between fluconazole and warfarin 1
• Standard fluconazole dosing can generally be used (typically 100-400 mg daily depending on the infection being treated)
• Liver function and coagulation parameters should be monitored, especially in severe Factor VII deficiency cases or if the patient is on anticoagulant therapy
• Alternative antifungal medications, such as nystatin oral solution, may be considered in patients with a high risk of bleeding or those taking warfarin 1

It is essential to note that the primary concern with fluconazole use in patients with Factor VII deficiency is the potential for increased bleeding risk due to interactions with warfarin, rather than a direct effect on Factor VII production or function 1.

From the Research

Relationship Between Fluconazole and Factor VII Deficiency

There is no direct relationship between Fluconazole, an antifungal medication, and Factor VII (FVII) deficiency, as the provided studies do not discuss this specific topic.

Factor VII Deficiency

• Factor VII deficiency is a rare bleeding disorder with autosomal recessive inheritance, affecting approximately 1 in 500,000 people 2, 3, 4, 5.
• The disorder has a highly variable spectrum of bleeding problems, and FVII levels correlate poorly with bleeding risk 2, 5.
• Treatment options include plasma-derived and recombinant FVII concentrates, as well as fresh frozen plasma and prothrombin complex concentrates in some cases 2, 4, 5.

Fluconazole

• Fluconazole is an antifungal medication used for prophylaxis and treatment of fungal infections, particularly in patients with neutropenia 6.
• It is effective against candidiasis, but its use is restricted by the existence of resistant strains, such as Candida krusei and C. glabrata 6.

Lack of Direct Relationship

• There are no research papers that directly discuss the relationship between Fluconazole and Factor VII deficiency, as the provided studies focus on either FVII deficiency or antifungal prophylaxis and treatment 2, 3, 4, 5, 6.