VERIFIED CONTENTAuthor: Roman Wodowski

Fluconazole belongs to the group of antifungal triazoles. It works mainly by inhibiting the cytochrome P-450-dependent demethylation of 14 alpha-lanosterol, which is an important element in the biosynthesis of ergosterol in the fungus. The accumulation of 14 alpha-methyl sterols correlates with the subsequent loss of ergosterol in the fungal cell membrane.

Indications for the use of fluconazole

Treatment of fungal infections (including acute and recurrent vaginal candidiasis, balanitis yeast, mucosal candidiasis, generalized candidiasis, dermatophytosis, onychomycosis, cryptococcal meningitis) and prevention of fungal infections (prevention of recurrence) cryptococcal meningitis in high-risk patients, prevention of recurrence of candidal mucositis of the oral cavity, pharynx and esophagus in HIV-infected patients, prevention of recurrence of vaginal candidiasis, prevention of mycoses in immunocompromised patients.

Contraindications to the use of fluconazole

Hypersensitivity to the active substance or related azole compounds is a counter-indication to the use of fluconazole. From repeated dose interaction studies, administration of terfenadine to patients receiving multiple doses of fluconazole of 400 mg / day or more is contraindicated.

The use of other drugs that prolong the QT interval and are metabolised by cytochrome P450 (CYP3A4 isoenzyme), such as cisapride, astemizole, pimozide, quinidine and erythromycin, is contraindicated in patients receiving fluconazole.

Available preparations

The drug is available only on prescription, in the form of:

  • oral capsules,
  • syrup
  • and infusion solution.

Dosage of Fluconazole

The dosage is determined by the doctor based on the diagnosis. The daily dose should be adapted to the type and severity of the fungal infection. Follow its recommendations. An insufficiently long treatment period may cause the recurrence of active infection.

Fluconazole side effects

The most frequently reported side effects are:

  • headache,
  • stomach ache,
  • diarrhea,
  • nausea,
  • vomiting,
  • blood levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase increased
  • and rash.

Interaction with other drugs and substances

Drugs with fluconazole interact with a number of other drugs. Therefore, tell your doctor about all medications you take, including over-the-counter medications.

  • Contraindicated is the use of fluconazole with cisapride, astemizole, pimozide, erythromycin, the use of terfenadine and fluconazole in a dose greater than or equal to 400 mg,
  • Fluconazole may increase the plasma concentration of halofantrine due to its inhibitory effect on CYP3A4. Concomitant use of fluconazole and halofantrine may increase the risk of cardiotoxicity (prolonged QT interval, torsades de pointes). Concomitant use of these medicinal products should be avoided,
  • Fluconazole may affect the pharmacokinetics of other drugs metabolised by CYP2D6, CYP3A4, and CYP2C9 isoenzymes. May potentiate the effects of alfentanil, amitriptyline and nortriptyline, celecoxib, fentanyl, methadone, NSAIDs (e.g. ibuprofen, flurbiprofen), saquinavir, rifabutin, theophylline and zidovudine
  • During concomitant use of fluconazole and warfarin, the prothrombin time increased 2-fold, possibly due to inhibition of the metabolism of warfarin by the CYP2C9 isoenzyme. You may need to adjust your warfarin dose,
  • After oral administration of midazolam, fluconazole increased the concentration of midazolam and the effect of the drug on psychomotor functions,
  • Potentiated and prolonged effects of triazolam have been observed with concomitant administration of fluconazole and triazolam. If the simultaneous use of benzodiazepines and fluconazole is necessary, it is recommended to reduce the doses of benzodiazepines and to monitor the patient properly,
  • Fluconazole inhibits the metabolism of carbamazepine. A 30% increase in serum carbamazepine levels was also observed. There is a risk of developing carbamazepine toxicity,
  • Concomitant treatment with cyclophosphamide and fluconazole causes an increase in serum bilirubin and creatinine. If these drugs are used concomitantly, special attention should be paid to the risk of increases in serum bilirubin and creatinine levels,
  • The risk of myopathy and rhabdomyolysis is increased when fluconazole is co-administered with HMG-CoA reductase inhibitors metabolised by CYP3A4, such as atorvastatin and simvastatin, or metabolised by CYP2C9 such as fluvastatin. Ifconcomitant treatment is necessary, patients should be monitored for signs of myopathy and rhabdomyolysis, and their creatinine kinase levels monitored,
  • Fluconazole significantly increases the concentration of cyclosporine. These drugs can be used simultaneously, reducing the dose of cyclosporine depending on its concentration,
  • Fluconazole may increase plasma concentrations of everolimus by inhibiting the enzyme CYP3A4,
  • Fluconazole increases the plasma concentration of sirolimus presumably by inhibiting its metabolism by CYP3A4 and P-glycoprotein. These drugs can be used in combination, if the dosage of sirolimus is adjusted depending on the concentration and / or effect of the drug,
  • Serum levels should be monitored when used concomitantly with phenytoin,
  • Patients on long-term treatment with fluconazole and corticosteroids should be monitored for symptoms of adrenal insufficiency after discontinuation of fluconazole,
  • It is expected that fluconazole may increase the plasma concentrations of the vinca alkaloids (e.g. vincristine and vinblastine) and lead to neurotoxicity.

Impact on driving and the use of machines

No studies on the effects of fluconazole on the ability to drive and use machines have been performed. The patient should be warned about the possibility of dizziness while using the product.

Pregnancy and breastfeeding

Fluconazole in standard doses and short-term doses should not be used during pregnancy unless clearly necessary. Fluconazole is excreted in human milk reaching concentrations lower than those in the serum. Breastfeeding is not recommended after taking multiple doses of fluconazole or after high doses.

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