Login
Subscribe
Patients taking the commonly prescribed antifungal drug fluconazole (DIFLUCAN) should be aware that it has clinically important interactions with many other prescription medications.
Fluconazole was approved by the Food and Drug Administration in 1990 and is used to treat vaginal yeast (Candida) infections; yeast infections of the mouth, throat and esophagus; a type of fungal meningitis; and certain other serious fungal infections.[1] It also is approved for prevention of Candida fungal ...
Patients taking the commonly prescribed antifungal drug fluconazole (DIFLUCAN) should be aware that it has clinically important interactions with many other prescription medications.
Fluconazole was approved by the Food and Drug Administration in 1990 and is used to treat vaginal yeast (Candida) infections; yeast infections of the mouth, throat and esophagus; a type of fungal meningitis; and certain other serious fungal infections.[1] It also is approved for prevention of Candida fungal infections in patients undergoing bone marrow transplantation who receive high-dose chemotherapy or radiation therapy.
Increased risk of fatal heart rhythm abnormalities[2],[3]
Like some other drugs in the azole family of antifungal drugs, fluconazole can cause prolongation of the QT interval. QT prolongation is a change in the electrical activity of the heart that can lead to a fatal heart rhythm disturbance called torsades de pointes, which can cause cardiac arrest and sudden death. During postmarketing surveillance of fluconazole, there have been rare cases of QT prolongation and torsades de pointes in patients using the drug. Patients with low blood potassium levels and severe heart failure are at greatest risk of these adverse effects.
In addition, fluconazole can inhibit substances in the liver called enzymes that metabolize (break down or chemically modify) other drugs, including some that themselves can cause QT prolongation. The product labeling for fluconazole therefore warns that it should never be used together with other drugs that can cause QT prolongation and that are metabolized by liver enzymes inhibited by fluconazole (see Table 1, below, for examples of such drugs). The list includes certain antibiotics, antidepressants, antipsychotics, drugs for abnormal heart rhythms and other antifungal drugs, among others.
Importantly, the liver enzyme inhibiting effects of fluconazole can persist for up to five days after stopping the drug because it takes a long time for the drug to be cleared from the body.
Table 1: Examples of Oral Drugs That Should Never Be Taken with Fluconazole Because of Risk of Fatal Heart Rhythm Abnormalities
| Generic Name | Brand Name(s)† | Drug Class |
|---|---|---|
| amiodarone* | PACERONE | Abnormal heart rhythm drug |
| aripiprazole* | ABILIFY | Antipsychotic |
| citalopram* | CELEXA | Antidepressant |
| clarithromycin* | BIAXIN XL | Antibiotic |
| clozapine* | CLOZARIL, FAZACLO ODT, VERSACLOZ | Antipsychotic drug |
| dronedarone** | MULTAQ | Abnormal heart rhythm drug |
| erythromycin | E.E.S., ERY-TAB, ERYC, ERYPED, ERYTHROCIN | Antibiotic |
| escitalopram* | LEXAPRO | Antidepressant |
| haloperidol* | generic only | Antipsychotic |
| itraconazole*** | ONMEL, SPORANOX, TOLSURA | Antifungal drug |
| ketoconazole** | generic only | Antifungal drug |
| methadone* | DOLOPHINE, METHADOSE | Opioid |
| pimozide | ORAP | Tourette syndrome drug |
| quinidine* | generic only | Abnormal heart rhythm drug |
| quinine | QUALAQUIN | Antimalaria drug |
| tacrolimus | ASTRAGRAF XL, ENVARSUS XR, PROGRAF | Immunosuppressant/organ transplant drug |
| trazodone** | generic only | Antidepressant |
| vardenafil* | LEVITRA, STAXYN | Erectile dysfunction drug |
†Brand-name combination products were excluded.
*Designated as Limited Use
**Designated as Do Not Use
***Designated as Do Not Use except for serious fungal infections
Other important drug interactions[4],[5]
Fluconazole also can inhibit liver enzymes involved in the breakdown of many other drugs. As a result, concomitant (simultaneous) use of fluconazole and these drugs can increase the blood levels of the other drugs, potentially leading to drug toxicity (see Table 2, below, for examples).
For example, concomitant use of fluconazole and the anticoagulant (blood thinner) warfarin (COUMADIN, JANTOVEN) can increase blood levels of warfarin. This can increase the risk of bleeding complications. Ideally, concomitant use of these two drugs should be avoided. If such use is unavoidable, more frequent monitoring of warfarin levels should occur during initiation and discontinuation of fluconazole.
Table 2: Examples of Oral Drugs That May Reach Toxic Levels When Taken Concomitantly with Fluconazole
| Generic Name | Brand Name(s)† | Drug Class |
|---|---|---|
| amlodipine* | KATERZIA, NORVASC | Calcium channel blocker, hypertension drug |
| celecoxib** | CELEBREX | Nonsteroidal anti-inflammatory drug |
| cyclosporine | GENGRAF, NEORAL, SANDIMMUNE | Immunosuppressant/organ transplant drug |
| felodipine | generic only | Calcium channel blocker, hypertension drug |
| fentanyl* | ABSTRAL, ACTIQ, DURAGESIC, FENTORA, SUBSYS | Opioid |
| glyburide* | DIABETA, GLYNASE | Diabetes drug |
| phenytoin | DILANTIN, PHENYTEK | Seizure drug |
| theophylline* | ELIXOPHYLLIN, THEO-24, THEOCHRON | Asthma drug |
| tofacitinib** | XELJANZ | Immunosuppressant for rheumatoid arthritis, other diseases |
| verapamil | CALAN, VERELAN | Calcium channel blocker, hypertension drug |
| warfarin | COUMADIN, JANTOVEN | Anticoagulant |
†Brand-name combination products were excluded.
*Designated as Limited Use
**Designated as Do Not Use
What You Can Do
If you need treatment with fluconazole, review all your other medications with your doctor to assess for potentially significant drug interactions. Be aware that other drugs not listed in this article also may have dangerous interactions with fluconazole.
References
[1] Pfizer. Label: fluconazole (DIFLUCAN). February 2019. https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/019949s065,020090s047lbl.pdf. Accessed October 1, 2019.
[2] Ibid.
[3] IBM Micromedex. Drug interactions. http://www.micromedexsolutions.com/home/dispatch. Search term: “fluconazole.” Accessed October 1, 2019.
[4] Pfizer. Label: fluconazole (DIFLUCAN). February 2019. https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/019949s065,020090s047lbl.pdf. Accessed October 1, 2019.
[5] IBM Micromedex. Drug interactions. http://www.micromedexsolutions.com/home/dispatch. Search term: “fluconazole.” Accessed October 1, 2019.
