Cutting Fluconazole Dose In Half For Valley Fever

In our latest question and answer, the pharmacist discusses the use of fluconazole for the treatment of Valley Fever.

Cutting Fluconazole Dose In Half For Valley Fever
Nov 03, 2018

Nicole asked

My doctor has prescribed me 400mg of fluconazole daily for valley fever. I take one 200mg pill in the morning and another at night. However I noticed yesterday when I took the pull I got a bad headache, dizzy, and felt drowsy. Can I take 1/2 a pill twice a day until Monday day when I can call her?

At a glance

  • Several drugs can be used for the treatment of valley fever, including fluconazole.
  • You should not alter your prescribed dosage of fluconazole. Doing so may reduce the effectiveness of the drug.

Answer

Valley Fever Title

No, it is not advisable to split your prescribed dose of fluconazole in half for the treatment of your infection (Valley Fever). There are many reasons for this but simply put, evidence suggests that fluconazole doses below 400 mg are not effective.

What Is Valley Fever?

Valley fever (coccidioidomycosis) is an infection caused by a fungus known as coccidioides. The infection typically occurs in the lungs but can spread to other parts of the body (disseminated coccidioidomycosis).

Valley fever is transmitted by breathing in the microscopic fungal spores from the air but is not contagious from person to person.

Many individuals who are exposed to coccidioides don't get sick, and if they do, symptoms typically resolve on their own (without medication) within weeks to months. If symptoms do occur, they are generally classified as 'flu-like' symptoms, and can include:

  • Fatigue
  • Cough
  • Fever
  • Shortness of breath
  • Headache
  • Night sweats
  • Muscle aches
  • Rash

Some individuals are more susceptible than others to being symptomatic after being exposed to coccidioides. This includes those who are:

  • HIV positive
  • Have had an organ transplant
  • Are on immunosuppressants
  • Pregnant
  • Diagnosed with diabetes

After being evaluated by your doctor, they may or may not recommend treatment with anti-fungal medication (this will be based on a variety of factors). The most commonly recommended treatment is fluconazole.

What Is Fluconazole?

Fluconazole Tabs

Fluconazole is a synthetic antifungal agent with a broad spectrum of activity. It was approved by the FDA in January 1990.

Fluconazole is used for the treatment of a variety of infections, including:

  • Candida infections (e.g. vaginal candidiasis)
  • Cryptococcal meningitis
  • Coccidioides infections (e.g. Valley Fever)

Fluconazole is a fungistatic anti-fungal agent, meaning that it inhibits the growth of fungus but does not kill it directly. Specifically, it works by altering the fungal cell membrane, inhibiting ergosterol synthesis, which is an essential component of the membrane.

Fluconazole has a long-half life, allowing it to be dosed infrequently. Most indications only call for once-daily dosing. It may be administered without regard to meals.

In most cases, it is extremely important to choose and take the proper dose of an anti-infective agent, like fluconazole. Taking a dose that is too low, may not only lead to treatment failure but may increase the risk of infection worsening (3).

MIC Importance

A key term when it comes to the treatment of infections (e.g. bacterial or fungal) is MIC or minimum inhibitory concentration. The MIC is the lowest concentration of a drug that prevents visible growth of the microorganism in question.

Fluconazole is classified as a 'concentration-independent' drug, which is also known as a time-dependent drug. They are characterized by having maximum activity at drug concentrations at or slightly above the MIC.

A drug, fluconazole, in this case, needs to be dosed at a level in which the MIC will be reached for extended periods of time for proper treatment. Dosing too low, to a point where MIC isn't reached, will not properly eradicate an infection.

Cutting your fluconazole dose in half, from 400 mg per day to 200 mg per day, may not allow the drug to reach appropriate concentrations in the body. In fact, the few studies that have been done in regard to fluconazole treatment of Valley Fever have reported that doses under 400 mg are ineffective.

Treatment For Valley Fever

Fluconazole Tabs

Both the CDC (Centers for Disease Control) and the IDSA (Infectious Diseases Society of America) state that most infections will resolve without anti-fungal treatment.

However, as discussed above, some individuals will need anti-fungal therapy in an attempt to reduce the severity of symptoms or prevent the infection from getting worse. Treatment duration is usually 3 to 6 months of fluconazole or another type of anti-fungal medication.

The guidelines for the treatment of Valley Fever recommend the following:

"For CM [coccidioidomycosis], we recommend fluconazole 400–1200 mg orally daily as initial therapy for most patients with normal renal function. There is no role for a dose <400 mg daily in the adult patient without substantial renal impairment."

It goes on to say:

"Some experts prefer to use itraconazole 200 mg 2–4 times daily, but this requires closer monitoring to assure adequate absorption, and there are more drug–drug interactions than with fluconazole".

In addition to the two anti-fungal medications listed above, other possible agents include:

Final Words

You should not change or alter your prescribed fluconazole dose for the treatment of Valley Fever. Doing so may render it ineffective.

Be sure to speak with your doctor regarding how to potentially make fluconazole better tolerated or to discuss any alternative therapy options that may be available to you.

References
  1. 2016 Infectious Diseases Society of America (IDSA) Clinical Practice Guideline for the Treatment of Coccidioidomycosis. Oxford Academic
  2. Fluconazole therapy for coccidioidal meningitis. The NIAID-Mycoses Study Group. PubMed
  3. Antifungal Pharmacokinetics and Pharmacodynamics. PubMed
  4. Therapeutic drug monitoring (TDM) of antifungal agents: guidelines from the British Society for Medical Mycology. PubMed
  5. Fluconazole (Diflucan): a review. PubMed
  6. Diflucan Prescribing Information. AccessFDA
  7. About Valley Fever (Coccidioidomycosis). CDC
  8. Valley Fever Awareness. CDC

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