Fluconazole

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Contents

[edit] BRAND NAMES

[edit] STRUCTURE

Fluconazole.jpg

[edit] MECHANISM OF ACTION

Fluconazole is a triazole antifungal. It inhibits lanosterol 14α-demethylase, a cytochrome P-450 enzyme that converts lanosterol to ergosterol.

Ergosterol is an essential component of the fungal cell membrane. The inhibition of its synthesis results in accumulation of toxic 14α-methylated sterols and the production of a defective cell membrane with altered permeability and leakage of cellular contents.

Fluconazole is well absorbed and its absorption is not affected by food. It is capable of crossing the BBB and of reaching the ocular fluid at high concentration, therefore, useful for treating deep fungal keratitis.

It binds plasma proteins with a high extent and is essentially eliminated by the kidney in an unchanged form.

[edit] INDICATIONS

  • Vaginal candidiasis
  • Oropharyngeal and esophageal candidiasis
  • Meningitis in AIDS patients, due to its ability to cross the BBB, especially coccidioidal meningitis or cryptococcal meningitis. However, it is not active against Aspergillus.
  • Prophylaxis, to decrease the incidence of candidiasis in patients undergoing bone marrow transplantation who receive cytotoxic chemotherapy and/or radiation therapy.
  • Treatment of deep fungal keratitis.

[edit] DOSAGE

  • Oropharyngeal candidiasis: 50 mg daily for 7-14 days.
  • Vaginal candidiasis: 150 mg as a single dose.
  • Cryptococcal meningitis: Initially 400 mg then 200 mg once daily for 6-8 weeks.
  • Dermal infection (tinea corporis, cruris and dermal candidal infection) 150 mg once weekly or 50 mg daily for 2-4 weeks, tinea pedis 150 mg once weekly or 50 mg daily for 2-6 weeks; tinea versicolor 50 mg once daily for 2-4 weeks.
  • Prevention of fungal infection in patients with AIDS 100-200 mg daily.

[edit] CONTRAINDICATIONS

  • Patients who have shown hypersensitivity to fluconazole or to any of its excipients.
  • Coadministration of other drugs known to prolong the QT interval and which are metabolized via the enzyme CYP3A4 such as cisapride, astemizole, erythromycin, pimozide, and quinidine

[edit] PRECAUTIONS

[edit] INTERACTIONS

  • Fluconazole is a potent inhibitor of CYP2C19 and a moderate inhibitor of CYP3A4 and CYP2C9: there is a risk of increased plasma concentration of other compounds metabolized by these enzymes when coadministered with fluconazole (e.g. cyclosporine, phenytoin, theophylline, sulfonyureas, warfarin, zidovudine, zolpidem, vinca alkaloids, tacrolimus, nisoldipine, benzodiazepines, corticosteroids, TCA's, losartan, cisapride, terfinadine). Many patients that develop fungal infections are AIDS patients and since Fluconazole is able to affect the metabolism of anti-retroviral agents, it is extremely important to consider its interaction.

[edit] PREGNANCY AND LACTATION

  • Pregnancy Category C (US): Single 150 mg tablet use for Vaginal Candidiasis
    . There are no adequate and well-controlled studies of Diflucan in pregnant women. Available human data do not suggest an increased risk of congenital anomalies following a single maternal dose of 150 mg.
  • Pregnancy Category D (US): All other indications.
    A few published case reports describe a rare pattern of distinct congenital anomalies in infants exposed in utero to high dose maternal fluconazole (400-800 mg/day) during most or all of the first trimester. These reported anomalies are similar to those seen in animal studies. If this drug is used during pregnancy, or if the patient becomes pregnant while taking the drug, the patient should be informed of the potential hazard to the fetus.
  • Nursing Mothers: Fluconazole is secreted in human milk at concentrations similar to maternal plasma concentrations. Caution should be exercised when Fluconazole is administered to a nursing woman.

[edit] SIDE EFFECTS

Common (≥1% of patients): Nausea, abdominal pain, diarrhea and rash.

[edit] RELATED LINKS

Azoles mechanism of action

[edit] BIBLIOGRAPHY

[edit] REFERENCES

Antifungals
Ergosterol target : Cell membrane target Azoles (lanosterol 14 alpha-demethylase inhibitors) : Ergosterol inhibitors Imidazoles Topical: Bifonazole   Clotrimazole   Econazole   Fenticonazole   Ketoconazole   Isoconazole   Miconazole   Sertaconazole   Tioconazole
Triazoles Topical: Fluconazole   Terconazole
Systemic: Fluconazole   Itraconazole   Posaconazole   Voriconazole
Polyene antimycotics (ergosterol binding; they form pores in the membrane) Topical: Nystatin
Systemic: Amphotericin B
Allylamines (squalene epoxidase inhibitors) : Ergosterol inhibitors Topical: Amorolfine   Naftifine   Terbinafine
Systemic: Terbinafine
Echinocandins (β-glucan synthase inhibitors) : Cell wall target Anidulafungin   Caspofungin   Micafungin
Pyrimidine analogues / Thymidylate synthase inhibitors : Nucleic acid inhibitors Flucytosine
Mitotic inhibitors Griseofulvin
Others Ciclopirox