Is oral fluconazole (an antifungal medication) therapeutically equivalent to intravenous (IV) fluconazole in Intensive Care Unit (ICU) patients?

From the Guidelines

Oral fluconazole is therapeutically equivalent to IV fluconazole in ICU patients who can tolerate oral medications. The therapeutic equivalence of oral and IV fluconazole is supported by its excellent oral bioavailability of approximately 90% [no direct evidence provided in 1, but this is a well-established pharmacokinetic property of fluconazole]. The standard adult dosing for fluconazole remains the same regardless of route, with a loading dose of 800 mg (12 mg/kg) followed by 400 mg (6 mg/kg) daily, as recommended by the Infectious Diseases Society of America 1.

When considering the use of oral fluconazole in ICU patients, several important factors must be taken into account. Oral administration requires a functioning gastrointestinal tract with adequate absorption capacity. Patients with ileus, significant gastrointestinal bleeding, severe vomiting, or those who are NPO (nothing by mouth) would not be candidates for oral therapy. Additionally, patients with severe sepsis or hemodynamic instability may have unpredictable gut absorption, making IV administration preferable initially 1.

Key considerations for the use of fluconazole in ICU patients include:

• The patient's ability to tolerate oral medications
• The presence of risk factors for invasive candidiasis
• The potential for azole resistance in patients with recent azole exposure or colonization with azole-resistant Candida species 1
• The need for dose adjustments in patients with renal impairment

In general, the choice between oral and IV fluconazole should be based on the individual patient's clinical status and ability to tolerate oral medications. For patients who can tolerate oral medications, oral fluconazole is a suitable alternative to IV fluconazole, with the advantage of reduced costs and potential for earlier transition to oral therapy 1.

From the FDA Drug Label

The pharmacokinetic properties of fluconazole are similar following administration by the intravenous or oral routes. In normal volunteers, the bioavailability of orally administered fluconazole is over 90% compared with intravenous administration

• Bioavailability: The bioavailability of orally administered fluconazole is over 90% compared with intravenous administration.
• Pharmacokinetic properties: The pharmacokinetic properties of fluconazole are similar following administration by the intravenous or oral routes. In an ICU patient, oral fluconazole is therapeutically equivalent to IV fluconazole due to its high bioavailability and similar pharmacokinetic properties 2 3.

From the Research

Therapeutic Equivalence of Oral and IV Fluconazole

• The therapeutic equivalence of oral and IV fluconazole in ICU patients is not directly addressed in the provided studies.
• However, the studies suggest that fluconazole can be an effective treatment option for fungal infections in ICU patients, with a relatively low toxicity profile 4, 5.
• The choice between oral and IV fluconazole may depend on various factors, including the patient's renal function, the severity of the infection, and the presence of other underlying conditions.

Pharmacokinetics and Dosage

• A study published in 2020 found that fluconazole clearance is highly variable in ICU patients and is strongly dependent on renal function and continuous renal replacement therapy (CRRT) 6.
• The study recommended doses of 400 mg for patients with poor to moderate renal function, 600 mg for patients with adequate renal function, and 800 mg for patients treated with CRRT 6.
• Another study published in 2003 used a high-dose fluconazole regimen (800 mg/day) in ICU patients with suspected fungal infections, with a mean duration of treatment of 12 days 4.

Resistance and Efficacy

• The development of resistance to fluconazole is a concern, particularly with the increasing use of this agent in ICU patients 7.
• A study published in 2000 found an increase in Candida species resistance to fluconazole, as well as an emergence of Candida non-albicans species tolerant to fluconazole 7.
• However, other studies suggest that fluconazole can be an effective treatment option for fungal infections in ICU patients, with a relatively low toxicity profile 4, 5.