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Editor: Ayham Aboeed Updated: 2/28/2024 1:45:08 PM


FDA-Approved Indications

Fluconazole is a member of the triazole family and a commonly used antifungal agent.[1] This antifungal agent is FDA-approved to treat vaginal candidiasis, oropharyngeal and esophageal candidiasis, peritonitis, and systemic Candida infections, including candidemia, disseminated candidiasis, pneumonia, and cryptococcal meningitis. Prophylaxis is also known to decrease candidiasis incidence in patients receiving bone marrow transplantation who receive radiation therapy or cytotoxic chemotherapy.[2]

Off-Label Uses

Non-FDA-approved uses for fluconazole include blastomycosis, histoplasmosis, and coccidioidomycosis. Recently, there has been an increase in fluconazole therapy to treat coccidioidomycosis-inflicted bone and joint infection, meningitis, pneumonia in immunocompromised patients, and pneumonia as a primary infection in HIV-positive or severely debilitated patients.[2]

Recent studies have proven that fluconazole is more effective at treating soft tissue and pulmonary infections than other azole antifungal treatments, mainly with infections caused by coccidioidomycosis.[2]

Invasive candidiasis has been reported in patients with severe COVID-19 infection. Fluconazole or other azoles can be used in combination with echinocandins and liposomal amphotericin B. Cryptococcal meningoencephalitis has been reported in immunocompromised patients, which requires aggressive treatment with the induction phase for amphotericin B and flucytosine, followed by fluconazole followed by consolidation and secondary prophylaxis with fluconazole.[3]

Mechanism of Action

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Mechanism of Action

Fluconazole interacts with 14-demethylase, a cytochrome P-450 enzyme responsible for catalyzing the conversion of lanosterol to ergosterol.[4] As ergosterol forms a critical part of the fungal cell membrane, fluconazole inhibits the synthesis of ergosterol to increase cellular permeability. Other functions of the medication are to prevent endogenous respiration and the formation of yeasts. Of note, the loss of sterols goes parallel with the accumulation of sterols found in fungi and is the primary cause of the perceived fungistatic activity of fluconazole.

Mammalian demethylation is less sensitive to fluconazole inhibition; using fluconazole helps the body counteract the causative agents of fungal infection. However, despite this mechanism of action, triazoles are considered fungistatic against Candida species.

Fluconazole's efficacy is limited to yeasts and the endemic fungi, Histoplasma, Blastomyces, and Coccidioides. In addition, fluconazole has excellent activity against Candida and Cryptococcus species but has less activity against C glabrata and no activity against C krusei.


Absorption: The pharmacokinetic properties are similar following administration by the intravenous or oral routes; intravenous administration is helpful in patients with impaired gastrointestinal absorption or motility. Fluconazole's absorption is unaffected by food or gastric pH.

Distribution: The bioavailability of oral fluconazole is over 90% compared with intravenous administration.[5] The daily dose of fluconazole does not change based on the mode of administration.

Metabolism: The serum half-life is approximately 24 hours, permitting for once-daily dosing; however, the daily dose of fluconazole for treating infections other than vaginal candidiasis should depend on the type of organism and the response to therapy. Treatment should continue until clinical parameters show that active fungal infection has subsided.

Elimination: Fluconazole clearance is primarily via renal excretion, with approximately 80% of the administered dose appearing as the unchanged drug in the urine. In comparison, it excretes about 11% of the medication in the urine as metabolites.

Mechanism of Resistance

Mutation in the ERG11 gene decreases the binding of the drug target enzyme, lanosterol C14-alpha demethylase, to fluconazole, leading to drug resistance. Efflux pumps coded by 2 carrier gene families include CDR-1 and CDR-2 genes belonging to the ATP-binding cassette superfamily (ABC) and MDR-1 genes. Efflux pumps encoded by CDR-1 can cause resistance to all azole drugs, while efflux pumps encoded by MDR are selective for fluconazole. Resistance in C. glabrata usually includes the upregulation of CDR genes.[6]


Available Dosage Forms

Fluconazole is available in oral (suspension and tablet form) and intravenous preparations.

Adult Dosing

Fluconazole administration requires multiple doses except in vaginal candidiasis, where the recommended dosage is 150 mg as a single oral dose. The doses range from 200 mg of fluconazole on the first day, followed by 100 mg once daily, as in oropharyngeal and esophageal candidiasis, to daily doses of 50 to 200 mg in treating Candida peritonitis and urinary tract infections. However, doses of up to 400 mg daily have been used in systemic candida infections and to prevent candidiasis in patients undergoing bone marrow transplantation.

In treating acute cryptococcal meningitis, the recommended dosage for fluconazole is 400 mg on the first day, and subsequent dosing is 200 mg once daily. The initial therapy should be continued for 10 to 12 weeks after the cerebrospinal fluid (CSF) shows negative cultures.[7] In addition, a suppression dose of 200 mg once daily is recommended in patients with AIDS. Higher daily doses of 600 to 1000 mg have been necessary for treating some endemic fungal infections like coccidioidomycosis, especially in disseminated diseases. The Infectious Disease Society of America endorses the use of fluconazole for coccidioidomycosis.[8]

Specific Patient Populations

Hepatic impairment: Given fluconazole's hepatotoxic potential, fluconazole use requires caution in patients with liver dysfunction. 

Renal impairment: The pharmacokinetics of fluconazole are affected by the reduction in renal function. Therefore, the dose of fluconazole needs to be reduced in patients with impaired renal function. If creatinine clearance is ≤50 mL/min, the clinician must reduce the dose to 50% of the recommended dose. Patients on hemodialysis should be given 100% of the recommended dose after each dialysis session. The clinician should administer the dose on non-dialysis days according to the patient's creatinine clearance.

Pregnancy considerations: According to the U.S. Food and Drug Administration, using fluconazole at chronic high doses (400 to 800 mg/d) during the first trimester of pregnancy has been associated with a rare and specific group of congenital disabilities in infants. However, this risk does not seem to be linked to a single low dose of the medication. Based on this information, fluconazole's current pregnancy category is former FDA Category D. 

There is a risk of cleft palate, bowed tibia and femur, brachycephaly, and increased risk of musculoskeletal malformations and congenital heart defects in patients exposed to high-dose fluconazole therapy during pregnancy. Hence, healthcare providers should avoid fluconazole in pregnant mothers except in patients with life-threatening fungal infections. However, fluconazole may be used if the expected benefit outweighs the risk to the fetus.[9]

Breastfeeding considerations: According to the manufacturer's labeling, clinicians should be cautious when prescribing fluconazole to a nursing woman. Fluconazole is acceptable in nursing mothers because doses excreted into breast milk are less than the neonatal fluconazole dosage. Therefore, clinicians frequently prescribe fluconazole to treat recurrent breast candidiasis in nursing mothers. The regimen for breast candidiasis is 400 mg once, followed by 200 mg daily for at least 2 weeks.[10]

Pediatric patients: The commonly used daily doses in adults (100, 200, and 400 mg) should be equivalent to the subsequent doses (3, 6, and 12 mg/kg), respectively, in pediatric patients, but doses exceeding 600 mg/d are not recommended.

Older patients: Fluconazole is primarily eliminated through renal excretion. Dosage adjustment based on creatinine clearance is necessary to ensure appropriate dosing in older patients.

Adverse Effects

Although most patients tolerate fluconazole, gastrointestinal symptoms are a frequently reported adverse event. These can include but are not limited to, nausea, abdominal pain, vomiting, and diarrhea, especially in children.[5] 

Other adverse effects may include anaphylaxis, hepatotoxicity, asthenia, myalgia, fatigue, fever, malaise, QT prolongation, torsade de pointes, seizures, dizziness, vertigo, insomnia, paresthesia, somnolence, tremor, leukopenia including neutropenia and agranulocytosis, thrombocytopenia, hypercholesterolemia, hypertriglyceridemia, hypokalemia, cholestasis, dry mouth, dyspepsia, taste perversion, acute exanthematous pustulosis, drug eruption, excessive sweating, alopecia, and chapped lips and exfoliative skin disorders such as Stevens-Johnson syndrome and toxic epidermal necrolysis.[11][12]

Fluconazole therapy can cause transient mild-to-moderate serum aminotransferase elevations and is a known cause of drug-induced liver injury with a likelihood score of B (likely cause of clinically apparent liver injury). The drug-induced liver injury (DILI) pattern is usually hepatocellular and occurs within the initial few weeks of therapy. Hepatotoxicity can be associated with hypersensitivity reactions, including eosinophilia, fever, and rash. Most patients recover after discontinuing fluconazole, but clinical recovery may require 3 to 4 months. Rechallenge with the fluconazole may lead to the recurrence of hepatotoxicity, so the drug should be avoided.[13]

Drug-Drug Interactions

Fluconazole is a moderate inhibitor of CYP2C9 and CYP3A4 and a potent inhibitor of CYP2C19, which can result in significant drug-drug interactions.

Amiodarone: Caution must be exercised with concomitant administration of fluconazole and amiodarone, particularly with high-dose fluconazole (800 mg), which may increase QT prolongation.[14]

Antiepileptic drugs: The neurotoxicity increases in patients taking fluconazole with antiepileptic drugs such as phenytoin or carbamazepine. Fluconazole inhibits the cytochrome P4503AA4 isoenzyme, leading to toxicity symptoms like ataxia, hyperreflexia, nystagmus, and tremors.[15][16]

All-trans-retinoid acid (ATRA): Combination therapy with fluconazole and ATRA has been associated with pseudotumor cerebri. Pseudotumor cerebri is reversible upon discontinuation of drug therapy.[17]

Benzodiazepines: The blood concentration of benzodiazepines (eg, alprazolam, triazolam, midazolam) increases when coadministered with fluconazole, a weak or moderate CYP3A4 inhibitor resulting in symptoms of toxicity, including sedation and hypnosis.

Calcium channel blockers: Drugs such as felodipine, amlodipine, and nifedipine are substrates of CYP3A4; fluconazole inhibits their metabolism and increases the exposure of calcium channel blockers.[18]

Ibrutinib: Fluconazole can increase plasma ibrutinib concentrations. Reduced ibrutinib dosage and frequent monitoring for adverse reactions are recommended.[19]

Ivacaftor: Coadministration with fluconazole may increase ivacaftor exposure. Reduction in the dose of ivacaftor is recommended.[20]

Lemborexant: Avoid simultaneous use of fluconazole with lemborexant, as it can increase exposure to this drug, resulting in an increased risk of adverse reactions.[21]

Losartan: Fluconazole inhibits the metabolism of losartan. Blood pressure should be continuously monitored in patients receiving losartan.[22]

Methadone: Fluconazole may increase the serum concentration of methadone. Use with caution and monitor patients for CNS depression.[23]

NSAIDs: Fluconazole can potentially increase the systemic exposure of NSAIDs metabolized by CYP2C9. Monitoring for adverse events and toxicity is suggested. Adjustment of the dosage of NSAIDs may be required.[24]

Oral hypoglycemic agents (OHA): Concurrent use of fluconazole with glyburide, tolbutamide, and glipizide may increase the risk of hypoglycemic attacks.[25]

Rifabutin: Fluconazole can increase serum levels of rifabutin, leading to uveitis. Patients receiving both medications should be carefully monitored.[26]

Statins: Concurrent administration of fluconazole with statins metabolized via CYP3A4 (eg, atorvastatin, simvastatin) or CYP2C9 (eg, fluvastatin) increases the risk of myopathy and rhabdomyolysis.[27]

Saquinavir: Fluconazole increases saquinavir plasma concentrations by inhibiting its metabolism, requiring monitoring for potential toxicity.[28]

Tofacitinib: Coadministration of fluconazole with tofacitinib necessitates reducing tofacitinib due to increased systemic exposure.[29]

Theophylline: Coadministration of fluconazole with theophylline, a drug with a narrow therapeutic index, significantly increases theophylline concentration. Therapeutic drug monitoring and dosage adjustment are required.[30]

Tolvaptan: Fluconazole significantly increases plasma exposure to tolvaptan, increasing the risk of adverse drug reactions such as diuresis, dehydration, and acute renal failure. If coadministered, the tolvaptan dose should be reduced, and the patient should be closely monitored.[31]

Tricyclic antidepressants: The use of fluconazole in patients taking tricyclic antidepressants like amitriptyline, protriptyline, and nortriptyline leads to an increased risk of cardiotoxicity characterized by QT prolongation, torsade de pointes, and cardiac arrest. These effects are also observed when fluconazole is concurrently used with class I antiarrhythmic agents and amiodarone.[32]

Vinca alkaloids: Fluconazole may increase plasma levels of vinca alkaloids such as vincristine and vinblastine, increasing the risk of neurotoxicity.[33]

Voriconazole: Concomitant administration of voriconazole and fluconazole should be avoided. Monitoring for adverse drug reactions and toxicity related to voriconazole is recommended, especially if voriconazole is initiated within 24 hours after the last dose of fluconazole.[34]

Warfarin: The risk of bleeding characterized by signs of bruising, epistaxis, gastrointestinal bleeding, hematuria, and melena increases when fluconazole is concurrently used with warfarin.[35]

Zidovudine: Fluconazole increases zidovudine levels, prolongs its half-life, and may lead to zidovudine-related adverse reactions. Dosage reduction and close monitoring may be necessary when administering these drugs together.[36]


Fluconazole is contraindicated if the patient has hypersensitivity to the drug or any formulation components. Caution is recommended when administering fluconazole to patients with proarrhythmic conditions. Patients taking fluconazole should avoid medications metabolized by CYP3A4, which have the potential to significantly increase the QT interval, such as erythromycin, pimozide, and quinidine.[32] Avoid coadministration of abrocitinib with fluconazole due to increased systemic exposure to abrocitinib and its active metabolites.[37]

Warning and Precautions: 

The oral suspension of fluconazole powder contains sucrose; caution is essential for patients with hereditary fructose, glucose/galactose malabsorption, and sucrase-isomaltase deficiency.[5] Fluconazole may cause dizziness and seizures; patients are advised to avoid driving vehicles or operating machinery.[38] Fluconazole inhibits human adrenocortical steroidogenesis, and reversible adrenal insufficiency has been observed with fluconazole use.[39]


In rare cases, hepatic toxicity has correlated with the use of fluconazole. Hepatic reactions range from mild transient elevations in transaminases to clinical hepatitis. Fatalities have occurred, primarily in patients with severe underlying medical conditions, predominantly AIDS, malignancy, or chronic liver disease, and often while taking multiple concomitant medications. There is no apparent relationship between the total daily dose, duration of therapy, sex, or the patient's age.

In most cases, hepatotoxicity caused by fluconazole is reversible upon discontinuation of the medication. However, the clinical team must closely monitor patients who experience abnormal liver function tests while taking fluconazole to assess the potential progression of more severe liver injury. Clinicians should discontinue fluconazole if clinical signs and symptoms are consistent with liver disease. The risk of bleeding characterized by signs of bruising, epistaxis, gastrointestinal bleeding, hematuria, and melena increases when fluconazole is concurrently used with warfarin. Patients on warfarin therapy who have been prescribed fluconazole need monitoring of PT/INR.[35][40]

Concomitant use of fluconazole and fentanyl/alfentanil may result in elevated fentanyl concentrations, which can result in profound sedation. Monitor for potential respiratory depression.[41] Fluconazole increases plasma levels of cyclosporine and tacrolimus, requiring monitoring of serum concentrations of cyclosporine and tacrolimus and serum creatinine to decrease the risk of nephrotoxicity. Dose adjustment of tacrolimus and cyclosporine is recommended when used concomitantly with fluconazole.[42]


In a case report, acute toxicity of fluconazole has been described with peripheral nervous system involvement. In addition, the patient developed polyneuropathy, a confusional state, acute kidney injury, and thrombotic thrombocytopenic purpura.[43] 

Hallucinations and paranoid behavior accompanying fluconazole overdose have been reported. In the event of an overdose, providing symptomatic treatment and supportive measures, including gastric lavage if necessary, is recommended. There is no antidote for fluconazole toxicity. Due to the renal excretion of fluconazole, a 3-hour hemodialysis session can effectively lower plasma levels by approximately 50%, facilitating the elimination of the fluconazole.[5]

Enhancing Healthcare Team Outcomes

Healthcare professionals prescribing fluconazole should know the drug's indications, contraindications, and interactions. While fluconazole is generally well tolerated, its use requires caution in patients with QTc prolongation. An EKG is a strong recommendation before initiating drug therapy in these patients. Additionally, liver and renal function monitoring is essential to adjust dosages.

An interprofessional healthcare team, including clinicians, infectious disease specialists, and pharmacists, operating as a cohesive unit and using open communication can optimize patient outcomes with fluconazole therapy and minimize adverse events and interactions. Given the potential adverse events and drug-drug interactions of fluconazole, it is incumbent on all interprofessional team members to monitor the patient and document any changes in status, including signs of therapy failure, and report these to other team members as appropriate.



Rex JH, Rinaldi MG, Pfaller MA. Resistance of Candida species to fluconazole. Antimicrobial agents and chemotherapy. 1995 Jan:39(1):1-8     [PubMed PMID: 7695288]


Galgiani JN, Ampel NM, Blair JE, Catanzaro A, Geertsma F, Hoover SE, Johnson RH, Kusne S, Lisse J, MacDonald JD, Meyerson SL, Raksin PB, Siever J, Stevens DA, Sunenshine R, Theodore N. 2016 Infectious Diseases Society of America (IDSA) Clinical Practice Guideline for the Treatment of Coccidioidomycosis. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2016 Sep 15:63(6):e112-46. doi: 10.1093/cid/ciw360. Epub 2016 Jul 27     [PubMed PMID: 27470238]

Level 1 (high-level) evidence


Song G, Liang G, Liu W. Fungal Co-infections Associated with Global COVID-19 Pandemic: A Clinical and Diagnostic Perspective from China. Mycopathologia. 2020 Aug:185(4):599-606. doi: 10.1007/s11046-020-00462-9. Epub 2020 Jul 31     [PubMed PMID: 32737747]

Level 3 (low-level) evidence


Spampinato C, Leonardi D. Candida infections, causes, targets, and resistance mechanisms: traditional and alternative antifungal agents. BioMed research international. 2013:2013():204237. doi: 10.1155/2013/204237. Epub 2013 Jun 26     [PubMed PMID: 23878798]


Amichai B, Grunwald MH. Adverse drug reactions of the new oral antifungal agents--terbinafine, fluconazole, and itraconazole. International journal of dermatology. 1998 Jun:37(6):410-5     [PubMed PMID: 9646122]


Khosravi Rad K, Falahati M, Roudbary M, Farahyar S, Nami S. Overexpression of MDR-1 and CDR-2 genes in fluconazole resistance of Candida albicans isolated from patients with vulvovaginal candidiasis. Current medical mycology. 2016 Dec:2(4):24-29. doi: 10.18869/acadpub.cmm.2.4.24. Epub     [PubMed PMID: 28959792]


Perfect JR, Dismukes WE, Dromer F, Goldman DL, Graybill JR, Hamill RJ, Harrison TS, Larsen RA, Lortholary O, Nguyen MH, Pappas PG, Powderly WG, Singh N, Sobel JD, Sorrell TC. Clinical practice guidelines for the management of cryptococcal disease: 2010 update by the infectious diseases society of america. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2010 Feb 1:50(3):291-322. doi: 10.1086/649858. Epub     [PubMed PMID: 20047480]

Level 1 (high-level) evidence


Galgiani JN, Ampel NM, Blair JE, Catanzaro A, Geertsma F, Hoover SE, Johnson RH, Kusne S, Lisse J, MacDonald JD, Meyerson SL, Raksin PB, Siever J, Stevens DA, Sunenshine R, Theodore N. Executive Summary: 2016 Infectious Diseases Society of America (IDSA) Clinical Practice Guideline for the Treatment of Coccidioidomycosis. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2016 Sep 15:63(6):717-22. doi: 10.1093/cid/ciw538. Epub     [PubMed PMID: 27559032]

Level 1 (high-level) evidence


Budani MC, Fensore S, Di Marzio M, Tiboni GM. Maternal use of fluconazole and congenital malformations in the progeny: A meta-analysis of the literature. Reproductive toxicology (Elmsford, N.Y.). 2021 Mar:100():42-51. doi: 10.1016/j.reprotox.2020.12.018. Epub 2020 Dec 28     [PubMed PMID: 33383164]

Level 1 (high-level) evidence


. Fluconazole. Drugs and Lactation Database (LactMed®). 2006:():     [PubMed PMID: 30000282]


Pappas PG, Kauffman CA, Perfect J, Johnson PC, McKinsey DS, Bamberger DM, Hamill R, Sharkey PK, Chapman SW, Sobel JD. Alopecia associated with fluconazole therapy. Annals of internal medicine. 1995 Sep 1:123(5):354-7     [PubMed PMID: 7625624]

Level 2 (mid-level) evidence


Ünal Yüksekgönül A, Ertuğrul İ, Karagöz T. Fluconazole-associated QT interval prolongation and Torsades de Pointes in a paediatric patient. Cardiology in the young. 2021 Dec:31(12):2035-2037. doi: 10.1017/S1047951121001992. Epub 2021 May 24     [PubMed PMID: 34024302]


. Fluconazole. LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. 2012:():     [PubMed PMID: 31643623]


Buch T, Andersen SE. [Combination therapy with fluconazole and other QTc-prolonging drugs increase the QTc interval]. Ugeskrift for laeger. 2015 Oct 5:177(41):V04150371     [PubMed PMID: 26471025]


Nair DR, Morris HH. Potential fluconazole-induced carbamazepine toxicity. The Annals of pharmacotherapy. 1999 Jul-Aug:33(7-8):790-2     [PubMed PMID: 10466905]

Level 3 (low-level) evidence


Cadle RM, Zenon GJ 3rd, Rodriguez-Barradas MC, Hamill RJ. Fluconazole-induced symptomatic phenytoin toxicity. The Annals of pharmacotherapy. 1994 Feb:28(2):191-5     [PubMed PMID: 8173131]

Level 3 (low-level) evidence


Atas U, Aydin Ersoy M, Iltar U, Yucel OK, Turkoglu EB, Salim O. Papilledema and idiopathic intracranial hypertension due to the possible potentiation of ATRA by posaconazole in a case of acute promyelocytic leukemia. Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners. 2022 Sep:28(6):1474-1477. doi: 10.1177/10781552221076756. Epub 2022 Jan 28     [PubMed PMID: 35088649]

Level 3 (low-level) evidence


Galatti L, Mazzaglia G, Greco A, Sessa E, Cricelli C, Schito GC, Nicoletti G, Spina E, Caputi AP. Co-prescriptions with itraconazole and fluconazole as a signal for possible risk of drug-drug interactions: a four-year analysis from Italian general practice. Pharmacoepidemiology and drug safety. 2007 Apr:16(4):422-8     [PubMed PMID: 17323404]


Yasu T, Momo K, Kuroda S, Kawamata T. Fluconazole Increases Ibrutinib Concentration. American journal of therapeutics. 2020 Nov/Dec:27(6):e620-e621. doi: 10.1097/MJT.0000000000000993. Epub     [PubMed PMID: 32721144]


Goldenberg MM. Pharmaceutical approval update. P & T : a peer-reviewed journal for formulary management. 2012 Apr:37(4):209-11     [PubMed PMID: 22593632]


Landry I, Aluri J, Nakai K, Hall N, Miyajima Y, Ueno T, Dayal S, Filippov G, Lalovic B, Moline M, Reyderman L. Evaluation of the CYP3A and CYP2B6 Drug-Drug Interaction Potential of Lemborexant. Clinical pharmacology in drug development. 2021 Jun:10(6):681-690. doi: 10.1002/cpdd.915. Epub 2021 Jan 17     [PubMed PMID: 33455055]


Venkatakrishnan K, von Moltke LL, Greenblatt DJ. Effects of the antifungal agents on oxidative drug metabolism: clinical relevance. Clinical pharmacokinetics. 2000 Feb:38(2):111-80     [PubMed PMID: 10709776]

Level 3 (low-level) evidence


McCance-Katz EF, Sullivan LE, Nallani S. Drug interactions of clinical importance among the opioids, methadone and buprenorphine, and other frequently prescribed medications: a review. The American journal on addictions. 2010 Jan-Feb:19(1):4-16. doi: 10.1111/j.1521-0391.2009.00005.x. Epub     [PubMed PMID: 20132117]


Zuo CZ, Gong Y, Hou XY, Zhang YF, Peng WX, Zhu RH, Zhong DF, Chen XY. Effect of Fluconazole on the Pharmacokinetic Properties of Imrecoxib, a Novel NSAID: A Single-center, Open-label, Self-controlled Study in Healthy Chinese Male Volunteers. Clinical therapeutics. 2018 Aug:40(8):1347-1356. doi: 10.1016/j.clinthera.2018.06.009. Epub     [PubMed PMID: 30017171]


Schelleman H, Bilker WB, Brensinger CM, Wan F, Hennessy S. Anti-infectives and the risk of severe hypoglycemia in users of glipizide or glyburide. Clinical pharmacology and therapeutics. 2010 Aug:88(2):214-22. doi: 10.1038/clpt.2010.74. Epub 2010 Jun 30     [PubMed PMID: 20592722]

Level 2 (mid-level) evidence


Cheng WH, Chang CH, Lu PL, Lin HC. Bilateral uveitis associated with concurrent administration of rifabutin and nelfinavir. Taiwan journal of ophthalmology. 2015 Oct-Dec:5(4):187-188. doi: 10.1016/j.tjo.2014.08.004. Epub 2014 Oct 7     [PubMed PMID: 29018696]


Shaukat A, Benekli M, Vladutiu GD, Slack JL, Wetzler M, Baer MR. Simvastatin-fluconazole causing rhabdomyolysis. The Annals of pharmacotherapy. 2003 Jul-Aug:37(7-8):1032-5     [PubMed PMID: 12841814]

Level 3 (low-level) evidence


Vadlapatla RK, Patel M, Paturi DK, Pal D, Mitra AK. Clinically relevant drug-drug interactions between antiretrovirals and antifungals. Expert opinion on drug metabolism & toxicology. 2014 Apr:10(4):561-80. doi: 10.1517/17425255.2014.883379. Epub 2014 Feb 12     [PubMed PMID: 24521092]

Level 3 (low-level) evidence


Gupta P, Chow V, Wang R, Kaplan I, Chan G, Alvey C, Ni G, Ndongo MN, LaBadie RR, Krishnaswami S. Evaluation of the effect of fluconazole and ketoconazole on the pharmacokinetics of tofacitinib in healthy adult subjects. Clinical pharmacology in drug development. 2014 Jan:3(1):72-7. doi: 10.1002/cpdd.71. Epub 2013 Oct 8     [PubMed PMID: 27128233]


Niwa T, Inoue-Yamamoto S, Shiraga T, Takagi A. Effect of antifungal drugs on cytochrome P450 (CYP) 1A2, CYP2D6, and CYP2E1 activities in human liver microsomes. Biological & pharmaceutical bulletin. 2005 Sep:28(9):1813-6     [PubMed PMID: 16141569]


Chebib FT, Perrone RD, Chapman AB, Dahl NK, Harris PC, Mrug M, Mustafa RA, Rastogi A, Watnick T, Yu ASL, Torres VE. A Practical Guide for Treatment of Rapidly Progressive ADPKD with Tolvaptan. Journal of the American Society of Nephrology : JASN. 2018 Oct:29(10):2458-2470. doi: 10.1681/ASN.2018060590. Epub 2018 Sep 18     [PubMed PMID: 30228150]


Li M, Ramos LG. Drug-Induced QT Prolongation And Torsades de Pointes. P & T : a peer-reviewed journal for formulary management. 2017 Jul:42(7):473-477     [PubMed PMID: 28674475]


Teusink AC, Ragucci D, Shatat IF, Kalpatthi R. Potentiation of vincristine toxicity with concomitant fluconazole prophylaxis in children with acute lymphoblastic leukemia. Pediatric hematology and oncology. 2012 Feb:29(1):62-7. doi: 10.3109/08880018.2011.624163. Epub     [PubMed PMID: 22304011]

Level 2 (mid-level) evidence


Damle B, Varma MV, Wood N. Pharmacokinetics of voriconazole administered concomitantly with fluconazole and population-based simulation for sequential use. Antimicrobial agents and chemotherapy. 2011 Nov:55(11):5172-7. doi: 10.1128/AAC.00423-11. Epub 2011 Aug 29     [PubMed PMID: 21876043]

Level 1 (high-level) evidence


Akamatsu H, Nakagawa H, Matsumaru I, Hashizume J, Harasawa H, Kodama Y, Miura T, Ohyama K. Effects of changing the timing of warfarin administration in combination with fluconazole on prolongation of the PT-INR: a case report. Journal of pharmaceutical health care and sciences. 2023 Apr 1:9(1):11. doi: 10.1186/s40780-023-00279-w. Epub 2023 Apr 1     [PubMed PMID: 37004089]

Level 3 (low-level) evidence


Oshikoya KA, Oreagba IA, Lawal S, Awodele O, Ogunleye OO, Senbanjo IO, Olayemi SO, Ezeaka VC, Temiye EO, Adeyemo TA, Opanuga O, Lesi OA, Akanmu SA. Potential drug-drug interactions in HIV-infected children on antiretroviral therapy in Lagos, Nigeria. HIV/AIDS (Auckland, N.Z.). 2014:6():49-59. doi: 10.2147/HIV.S52266. Epub 2014 Apr 5     [PubMed PMID: 24741328]


Wang X, Dowty ME, Wouters A, Tatulych S, Connell CA, Le VH, Tripathy S, O'Gorman MT, Winton JA, Yin N, Valdez H, Malhotra BK. Assessment of the Effects of Inhibition or Induction of CYP2C19 and CYP2C9 Enzymes, or Inhibition of OAT3, on the Pharmacokinetics of Abrocitinib and Its Metabolites in Healthy Individuals. European journal of drug metabolism and pharmacokinetics. 2022 May:47(3):419-429. doi: 10.1007/s13318-021-00745-6. Epub 2022 Feb 28     [PubMed PMID: 35226304]


Matsumoto K, Ueno K, Yoshimura H, Morii M, Takada M, Sawai T, Mitsutake K, Shibakawa M. Fluconazole-induced convulsions at serum trough concentrations of approximately 80 microg/mL. Therapeutic drug monitoring. 2000 Oct:22(5):635-6     [PubMed PMID: 11034273]

Level 3 (low-level) evidence


van der Pas R, Hofland LJ, Hofland J, Taylor AE, Arlt W, Steenbergen J, van Koetsveld PM, de Herder WW, de Jong FH, Feelders RA. Fluconazole inhibits human adrenocortical steroidogenesis in vitro. The Journal of endocrinology. 2012 Dec:215(3):403-12. doi: 10.1530/JOE-12-0310. Epub 2012 Oct 4     [PubMed PMID: 23038793]


de Filette J, Michiels V. Bleeding interaction between fluconazole and warfarin. Lancet (London, England). 2018 Sep 29:392(10153):e9. doi: 10.1016/S0140-6736(18)32217-7. Epub     [PubMed PMID: 30303086]


Costa HT, Leopoldino RWD, da Costa TX, Oliveira AG, Martins RR. Drug-drug interactions in neonatal intensive care: A prospective cohort study. Pediatrics and neonatology. 2021 Mar:62(2):151-157. doi: 10.1016/j.pedneo.2020.10.006. Epub 2020 Oct 23     [PubMed PMID: 33158761]


Gu TM, Lewis JS 2nd, Le H, Bubalo JS. Comparative effects of fluconazole, posaconazole, and isavuconazole upon tacrolimus and cyclosporine serum concentrations. Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners. 2022 Sep:28(6):1357-1362. doi: 10.1177/10781552211029046. Epub 2021 Jul 1     [PubMed PMID: 34192963]

Level 2 (mid-level) evidence


Eşkut N, Gedizlioğlu M, Ünal O, Özlü C, Ergene U. Acute fluconazole toxicity: a case presenting with protean manifestations including systemic and neurologic symptoms. Postgraduate medicine. 2021 Mar:133(2):250-252. doi: 10.1080/00325481.2020.1840830. Epub 2020 Nov 12     [PubMed PMID: 33176551]

Level 3 (low-level) evidence