How fluconazole works
Fluconazole is an antifungal agent (antimycotic) from the azole group. It blocks an enzyme that is vital for fungi.
Cholesterol is usually mentioned only in a negative context – as a blood fat that can “clog” the vessels. In certain quantities, however, cholesterol is essential for the human body. Among other things, it is an important building block of the cell membrane. Without cholesterol and thus without a functional membrane, the body’s cells would be unable to perform many tasks.
The membrane of fungal cells contains a building block that is structurally related to cholesterol but not identical to it: ergosterol (also called ergosterol). Without this substance, the fungal membrane loses its stability, and the fungus is no longer able to grow.
Azole antifungals such as fluconazole inhibit a specific fungal enzyme (lanosterol-14-alpha-demethylase) involved in the production of ergosterol. This selectively slows down the growth of the fungus. In this process, fluconazole has a growth-inhibiting effect on some fungi (fungistatic) and even a killing effect on others (fungicidal).
Absorption, degradation and excretion
It is broken down by the body only to a small extent and excreted largely unchanged in the urine. About 30 hours after ingestion, the blood level of fluconazole has decreased by half again.
When is fluconazole used?
The active ingredient fluconazole is used to treat fungal infections. Examples include infestation of the oral, nasal, and vaginal mucosa with the yeast Candida albicans (e.g., oral thrush, vaginal thrush), fungal skin infections (dermatomycoses), and infestation of the meninges with Coccidioides immitis (coccidioidomycosis, also known as valley or desert fever).
Fluconazole therapy can also be given as a precautionary measure to prevent (re)fungal infection in immunocompromised patients. These would be, for example, transplant patients, cancer patients and HIV patients.
Treatment is usually given for a limited period of time, as the development of resistance in the fungi cannot be ruled out. In individual cases, however, permanent treatment with fluconazole may be necessary.
How fluconazole is used
Usually, a double dose of fluconazole is taken on the first day of treatment to quickly achieve a high concentration of active substance in the body.
In some cases, the active ingredient is administered directly into a vein (intravenously). For children and people who have trouble swallowing, fluconazole is available in juice form.
What are the side effects of fluconazole?
One in ten to one hundred people treated experience side effects such as headache, abdominal pain, nausea, diarrhea, vomiting, skin rash, and an increase in liver enzymes in the blood.
One in one hundred to one thousand patients may experience anemia, decreased appetite, drowsiness, dizziness, cramps, sensory disturbances, constipation and other digestive problems, muscle pain, fever, skin rash, and itching.
What should be considered when taking fluconazole?
Contraindications
Fluconazole should not be taken by:
- concomitant use of terfenadine (anti-allergic drug), if Fluconazole daily dosage is 400 milligrams or more
- @ concomitant use of drugs that prolong the so-called QT interval in the ECG and are degraded via the CYP3A4 enzyme (e.g., erythromycin, cisapride, astemizole, pimozide, and quinidine)
Interactions
Examples include the anti-allergy drug terfenadine, pimozide (drug for psychosis), antibiotics such as erythromycin, and certain drugs for cardiac arrhythmias. Concurrent use must be avoided or requires dose adjustment.
Caution is also advised if ciclosporin, sirolimus, or tacrolimus (drugs used to prevent transplant rejection) are taken at the same time. These agents have a narrow therapeutic range (overdose occurs easily).
Dose adjustment may also be required in combination with other agents.
- Antidepressants such as amitriptyline and nortriptyline.
- Anticoagulants such as warfarin and phenprocoumon
- Anti-epileptic and anti-seizure agents such as carbamazepine and phenytoin
- Opioids such as methadone, fentanyl and alfentanil
- Asthma medications such as theophylline
- blood lipid-lowering drugs like atorvastatin and simvastatin
- pain medicines like celecoxib
- certain cancer medicines like olaparib
Age restriction
If indicated, fluconazole may be administered from birth.
Pregnancy and lactation
The active substance fluconazole passes into breast milk. If treatment is required in mothers, however, breastfeeding is still possible.
For both pregnancy and breastfeeding, local therapy with clotrimazole, miconazole, or nystatin is preferred for vaginal mycosis (vaginal fungus).
How to obtain medication with fluconazole
In Germany, Austria, and Switzerland, medications with the active ingredient fluconazole are available by prescription in any dosage form.
How long has fluconazole been known?
The newer antifungal agents of the azole group were developed starting around 1969. A major drawback of the first agents in this group, such as clotrimazole, was that they could only be administered orally and not by injection.
For this reason, ketoconazole was developed in 1978, which could be administered by injection but was very toxic to the liver. Based on its structure, a new antifungal drug was then developed – it was given the name fluconazole. It was very effective and well tolerated both orally and by injection. In 1990, fluconazole was finally granted regulatory approval.