Fluconazole

Source: Wikipedia, the free encyclopedia.

Fluconazole
Clinical data
Trade namesDiflucan, others
AHFS/Drugs.comMonograph
MedlinePlusa690002
License data
Pregnancy
category
  • AU: D
Routes of
administration		By mouth, intravenous, topical
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability>90% (oral)
Protein binding11–12%
MetabolismLiver 11%
Elimination half-life30 hours (range 20–50 hours)
ExcretionKidney 61–88%
Identifiers
  • 2-(2,4-Difluorophenyl)-1,3-bis(1H-1,2,4-triazol-1-yl)propan-2-ol
JSmol)
Melting point139[4] °C (282 °F)
  • OC(Cn1cncn1)(Cn1cncn1)c1ccc(F)cc1F
  • InChI=1S/C13H12F2N6O/c14-10-1-2-11(12(15)3-10)13(22,4-20-8-16-6-18-20)5-21-9-17-7-19-21/h1-3,6-9,22H,4-5H2 checkY
  • Key:RFHAOTPXVQNOHP-UHFFFAOYSA-N checkY
  (verify)

Fluconazole is an

injection into a vein.[5]

Common side effects include vomiting, diarrhea, rash, and

cellular membrane.[5]

Fluconazole was patented in 1981 and came into commercial use in 1988.

generic medication.[5] In 2021, it was the 165th most commonly prescribed medication in the United States, with more than 3 million prescriptions.[9][10]

Medical uses

Fluconazole is a first-generation

azole antifungals (such as ketoconazole) in that its structure contains a triazole ring instead of an imidazole ring. While the imidazole antifungals are mainly used topically, fluconazole and certain other triazole antifungals are preferred when systemic treatment is required because of their improved safety and predictable absorption when administered orally.[11]

Fluconazole's spectrum of activity includes most

dermatophytes, among others.[medical citation needed] Common uses include:[2][11][12][13][14]

  • The treatment of non-systemic Candida infections of the vagina ("yeast infections"), throat, and mouth.
  • Certain systemic Candida infections in people with healthy immune systems, including infections of the bloodstream, kidney, or joints. Other antifungals are usually preferred when the infection is in the heart or central nervous system, and for the treatment of active infections in people with weak immune systems.
  • The prevention of Candida infections in people with weak immune systems, such as those neutropenic due to cancer chemotherapy, those with advanced HIV infections, transplant patients, and premature infants.
  • As a second-line agent for the treatment of cryptococcal meningoencephalitis, a fungal infection of the central nervous system.

Resistance

Antifungal resistance to drugs in the azole class tends to occur gradually over the course of prolonged drug therapy, resulting in clinical failure in immunocompromised patients (e.g., patients with advanced HIV receiving treatment for thrush or esophageal Candida infection).[15]

In

ATP-binding cassette and major facilitator superfamily transporters. Other gene mutations are also known to contribute to development of resistance.[15] C. glabrata develops resistance by up regulating CDR genes, and resistance in C. krusei is mediated by reduced sensitivity of the target enzyme to inhibition by the agent.[2]

The full spectrum of fungal susceptibility and resistance to fluconazole can be found in the product data sheet.[16] According to the US Centers for Disease Control and Prevention, fluconazole resistance among Candida strains in the US is about 7%.[17]

Contraindications

Fluconazole is contraindicated in patients who:[14]

  • Drink alcohol
  • have known hypersensitivity to other azole medicines such as ketoconazole;[2]
  • are taking terfenadine, if 400 mg per day multidose of fluconazole is administered;[2]
  • concomitant administration of fluconazole and quinidine, especially when fluconazole is administered in high dosages;
  • take
    SSRIs such as fluoxetine or sertraline
    .

Side effects

Adverse drug reactions associated with fluconazole therapy include:[14]

If taken during

first trimester.[19]

Fluconazole is secreted in human milk at concentrations similar to plasma.[2]

Fluconazole therapy has been associated with

cardiac arrhythmias. Thus, it is used with caution in patients with risk factors for prolonged QT interval, such as electrolyte imbalance or use of other drugs that may prolong the QT interval (particularly cisapride and pimozide).[21]

Some people are allergic to azoles, so those allergic to other azole drugs might be allergic to fluconazole.[22] That is, some azole drugs have adverse side-effects. Some azole drugs may disrupt estrogen production in pregnancy, affecting pregnancy outcome. [23]

Oral fluconazole is not associated with a significantly increased risk of birth defects overall, although it does increase the odds ratio of tetralogy of Fallot, but the absolute risk is still low.[24] Women using fluconazole during pregnancy have a 50% higher risk of spontaneous abortion.[25]

Fluconazole should not be taken with cisapride (Propulsid) due to the possibility of serious, even fatal, heart problems.[21] In rare cases, severe allergic reactions including anaphylaxis may occur.[26]

Powder for oral suspension contains sucrose and should not be used in patients with hereditary fructose, glucose/galactose malabsorption or sucrase-isomaltase deficiency. Capsules contain lactose and should not be given to patients with rare hereditary problems of galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption [27]

Interactions

Fluconazole is an inhibitor of the human

cardiac arrhythmia if used concurrently with other drugs that prolong the QT interval. Berberine has been shown to exert synergistic effects with fluconazole even in drug-resistant Candida albicans infections.[29] Fluconazole may increase the serum concentration of Erythromycin (Risk X: avoid combination).[28]

Pharmacology

Pharmacodynamics

Like other

fungicidal against certain organisms in a dose-dependent manner, specifically Cryptococcus.[31]

Pharmacokinetics

Following oral dosing, fluconazole is almost completely absorbed within two hours.

elimination half-life of fluconazole follows zero order, and only 10% of elimination is due to metabolism, the remainder being excreted in urine and sweat. Patients with impaired renal function will be at risk of overdose.[21]

In a bulk powder form, it appears as a white crystalline powder, and it is very slightly soluble in water and soluble in alcohol.[34]

History

Fluconazole was patented by Pfizer in 1981 in the United Kingdom and came into commercial use in 1988.[7] Patent expirations occurred in 2004 and 2005.[35]

References

  1. ^ "Product monograph brand safety updates". Health Canada. 7 July 2016. Retrieved 3 April 2024.
  2. ^ a b c d e f "Diflucan- fluconazole tablet; Diflucan- fluconazole powder, for suspension". DailyMed. 21 September 2023. Archived from the original on 22 February 2024. Retrieved 22 February 2024.
  3. ^ "Active substance: Fluconazole" (PDF). List of nationally authorised medicinal products. European Medicines Agency. 12 November 2020. Archived (PDF) from the original on 24 February 2024. Retrieved 22 December 2020.
  4. S2CID 213008181
    .
  5. ^ a b c d e f g h i j "Fluconazole". The American Society of Health-System Pharmacists. Archived from the original on 20 December 2016. Retrieved 8 December 2016.
  6. ^ "Fluconazole (Diflucan): Drug Safety Communication - FDA Evaluating Study Examining Use of Oral Fluconazole (Diflucan) in Pregnancy". U.S. Food and Drug Administration (FDA). 26 April 2016. Archived from the original on 29 April 2016. Retrieved 29 April 2016.
  7. ^
    ISBN 978-3-527-60749-5. Archived
    from the original on 10 September 2017.
  8. hdl:10665/325771
    . WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
  9. ^ "The Top 300 of 2021". ClinCalc. Archived from the original on 15 January 2024. Retrieved 14 January 2024.
  10. ^ "Fluconazole - Drug Usage Statistics". ClinCalc. Archived from the original on 8 July 2020. Retrieved 14 January 2024.
  11. ^ a b "US Pharmacist". Archived from the original on 10 February 2015. Retrieved 28 January 2015.
  12. ^ "IDSA Guidelines: Candida Infections". Archived from the original on 3 February 2015. Retrieved 28 January 2015.
  13. ^ "IDSA Guidelines: Cryptococcal Infections". Archived from the original on 3 February 2015. Retrieved 28 January 2015.
  14. ^
    ISBN 0-9757919-2-3
  15. ^ a b Bennett JE (2011). "Chapter 57: Antifungal Agents". In Brunton LL, Chabner BA, Knollmann BC (eds.). Goodman & Gilman's The Pharmacological Basis of Therapeutics (12th ed.). Archived from the original on 31 December 2013. Retrieved 22 May 2012.
  16. ^ "Spectrum of fungal susptibility and resistance to fluconazole" (PDF). Archived from the original (PDF) on 14 March 2016.
  17. ^ "Antifungal Resistance | Fungal Disease | CDC". 25 January 2019. Archived from the original on 19 May 2017.
  18. ^ "FDA Alert: Diflucan (fluconazole): Drug Safety Communication - Long-term, High-dose Use During Pregnancy May be Associated with Birth Defects". Archived from the original on 28 September 2011. Retrieved 4 August 2011.
  19. ^ a b "Fluconazole". Monograph. The American Society of Health-System Pharmacists. Archived from the original on 27 September 2014. Retrieved 27 September 2014.
  20. ^ "Prescribing medicines in pregnancy database". Australian Government. 3 March 2014. Archived from the original on 8 April 2014. Retrieved 22 April 2014.
  21. ^
    OCLC 1075550900
    .
  22. PMID 19164151. Archived
    (PDF) from the original on 11 June 2011. Retrieved 20 October 2009.
  23. S2CID 8282678
    .
  24. PMID 23984730
    .
  25. PMID 26746458
    .
  26. OCLC 942814866
    .
  27. ^ "Diflucan (Fluconazole) dosing, indications, interactions, adverse effects, and more". reference.medscape.com. Archived from the original on 23 April 2014.
  28. ^ a b "Login". Archived from the original on 21 December 2016. Retrieved 21 December 2016.
  29. PMID 19754040
    .
  30. ^ Pfizer Australia Pty Ltd. Diflucan (Australian Approved Product Information). West Ryde (NSW): Pfizer Australia; 2004.
  31. PMID 18990067
    .
  32. OCLC 1035129378
    .
  33. OCLC 1114483879
    .
  34. ^ "Fluconazole". MP Biomedicals. Archived from the original on 16 January 2009.
  35. ^ "Pfizer to Expand Fluconazole Donation Program to More than 50 Developing Nations". Kaiser Health News. 7 June 2001. Archived from the original on 30 October 2020. Retrieved 18 June 2019.

Further reading
Retrieved from "https://en.wikipedia.org/w/index.php?title=Fluconazole&oldid=1216993466"