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Patients taking the antifungal drug voriconazole (VFEND), which is marketed in both oral and injectable forms, should be aware that it has clinically important interactions with many other prescription medications.
Voriconazole was initially marketed in the U.S. in 2002 and is approved by the Food and Drug Administration to treat several types of serious fungal infections.[1] Notably, the product labeling for voriconazole lists more than a dozen drugs that should never be taken...
Patients taking the antifungal drug voriconazole (VFEND), which is marketed in both oral and injectable forms, should be aware that it has clinically important interactions with many other prescription medications.
Voriconazole was initially marketed in the U.S. in 2002 and is approved by the Food and Drug Administration to treat several types of serious fungal infections.[1] Notably, the product labeling for voriconazole lists more than a dozen drugs that should never be taken concomitantly (at the same time) with voriconazole because the risk of dangerous drug interactions is so great.
Increased risk of fatal heart rhythm abnormalities[2],[3]
Like some other drugs in the azole family of antifungal drugs, voriconazole 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.
Numerous oral drugs, when used concomitantly with voriconazole, further increase the risk of QT prolongation (see Table 1, below, for examples). The list of such drugs includes certain medications for treating abnormal heart rhythms, Alzheimer’s disease, bacterial infections, depression, heart failure, HIV infection, opioid withdrawal and psychosis, among other conditions.
In most cases, these interacting drugs themselves also cause QT prolongation beyond that caused by voriconazole alone. In addition, voriconazole can inhibit substances in the liver called enzymes that metabolize (break down or chemically modify) many of these same interacting drugs, thus increasing the blood levels of the interacting drugs and further exacerbating the risk of QT prolongation.
For several of these drugs, the risk of QT prolongation and potentially fatal abnormal heart rhythms is so high that they should not be taken concomitantly with voriconazole.
Table 1: Examples of Oral Drugs That May Increase the Risk of QT Prolongation and Potentially Fatal Heart Rhythm Abnormalities
| Generic Name | Brand Name(s)† | Drug Class |
|---|---|---|
| azithromycin* | ZITHROMAX | Antibiotic |
| chloroquine* | generic only | Drug for malaria |
| chlorpromazine* | generic only | Antipsychotic |
| ciprofloxacin* | CIPRO | Antibiotic |
| citalopram* | CELEXA | Antidepressant |
| clarithromycin* | BIAXIN XL | Antibiotic |
| disopyramide* | NORPACE | Abnormal heart rhythm drug |
| dofetilide | TIKOSYN | Abnormal heart rhythm drug |
| donepezil** | ARICEPT | Alzheimer’s disease drug |
| dronedarone** | MULTAQ | Abnormal heart rhythm drug |
| efavirenz | SUSTIVA | Antiviral drug for HIV infection |
| erythromycin | E.E.S., E.E.S. 400, ERY-TAB, ERYC, ERYPED, ERYTHROCIN | Antibiotic |
| escitalopram* | LEXAPRO | Antidepressant |
| haloperidol* | generic only | Antipsychotic |
| hydroxychloroquine | PLAQUENIL | Drug for malaria, rheumatoid arthritis and lupus erythematosus |
| imipramine** | TOFRANIL | Antidepressant |
| ivabradine | CORLANOR | Heart failure drug |
| levofloxacin* | generic only | Antibiotic |
| lofexidine | LUCEMYRA | Opioid withdrawal syndrome drug |
| methadone* | METHADOSE | Opioid for pain, opioid-use disorder |
| moxifloxacin** | generic only | Antibiotic |
| nortriptyline* | PAMELOR | Antidepressant |
| ofloxacin* | generic only | Antibiotic |
| pimozide | generic only | Tourette’s syndrome drug |
| quinidine* | generic only | Abnormal heart rhythm drug |
| sertraline* | ZOLOFT | Antidepressant |
| sotalol | BETAPACE, SORINE, SOTYLIZE | Abnormal heart rhythm drug |
| tacrolimus | ASTAGRAF XL, ENVARSUS XR, PROGRAF | Immunosuppressant/organ transplant drug |
| thioridazine** | generic only | Antipsychotic |
| trazodone** | generic only | Antidepressant |
| vardenafil* | generic only | Erectile dysfunction drug |
| ziprasidone** | GEODON | Antipsychotic |
†Brand-name combination products containing other active ingredients not listed
*Designated as Limited Use by Worst Pills, Best Pills News
**Designated as Do Not Use by Worst Pills, Best Pills News
Other important drug interactions[4],[5]
Voriconazole can inhibit liver enzymes involved in the breakdown of many other drugs. As a result, concomitant use of voriconazole with these other drugs can increase the blood levels of the other drugs to potentially toxic levels (see Table 2, below, for examples). The list of such drugs includes certain widely used medications for treating gout, high cholesterol, hypertension (high blood pressure), infections, inflammation, pain, psychosis and seizures, among other conditions.
Again, for many of these interacting drugs, the risk of drug toxicity is so great that they should not be taken concomitantly with voriconazole.
Table 2: Examples of Oral Drugs That May Reach Toxic Levels When Taken Concomitantly With Voriconazole
| Generic Name | Brand Name(s)† | Drug Class |
|---|---|---|
| amlodipine* | KATERZIA, NORLIQVA, NORVASC | Dihydropyridine calcium channel blocker, hypertension drug |
| colchicine | COLCRYS, GLOPERBA, MITIGARE | Gout drug |
| cyclosporine | GENGRAF, NEORAL, SANDIMMUNE | Immunosuppressant/organ-transplant drug |
| diclofenac** | CAMBIA, CATAFLAM, ZIPSOR | Nonsteroidal anti-inflammatory drug |
| fentanyl* | ACTIQ, FENTORA | Opioid |
| ibuprofen | ADVIL, JUNIOR STRENGTH MOTRIN, MIDOL LIQUID GELS, MOTRIN IB, TAB-PROFEN | Nonsteroidal anti-inflammatory drug |
| lovastatin | ALTOPREV | Cholesterol-lowering statin |
| lurasidone | LATUDA | Antipsychotic |
| methadone* | METHADOSE | Opioid for pain, opioid-use disorder |
| nifedipine* | PROCARDIA XL | Dihydropyridine calcium channel blocker, hypertension drug |
| oxycodone* | OXAYDO, OXYCONTIN, ROXICODONE, ROXYBOND, XTAMPZA ER | Opioid |
| phenytoin | DILANTIN, PHENYTEK | Seizure drug |
| rifabutin | MYCOBUTIN | Antibiotic |
| simvastatin | FLOLIPID, ZOCOR | Cholesterol-lowering statin |
| sirolimus | RAPAMUNE | Immunosuppressant/organ-transplant drug |
| tamsulosin* | FLOMAX | Alpha blocker for benign prostate enlargement |
| warfarin | JANTOVEN | Anticoagulant |
†Brand-name combination products containing other active ingredients not listed
*Designated as Limited Use by Worst Pills, Best Pills News
**Designated as Do Not Use by Worst Pills, Best Pills News
The following are some particularly notable examples of such drug interactions.
Calcium channel blockers
Concomitant use of voriconazole with certain dihydropyridine calcium channel blockers, such as amlodipine (KATERZIA, NORLIQVA, NORVASC) and nifedipine (PROCARDIA XL) may increase the blood levels of these calcium channel blockers, thereby increasing the risk of dangerous decreases in blood pressure and pulse, as well as kidney damage.
Cholesterol-lowering statins
Concomitant use of voriconazole with certain statin drugs, such as lovastatin (ALTOPREV) and simvastatin (FLOLIPID, ZOCOR), can increase the blood levels of these statin drugs, thereby increasing the risk of statin-induced myopathy (muscle damage). In severe cases, this condition can progress to rhabdomyolysis, a life-threatening, muscle-destroying condition that can lead to sudden kidney failure and death. Patients taking certain statin drugs who are prescribed voriconazole may need to temporarily discontinue the statin, take a lower statin dose or switch to a different cholesterol-lowering treatment until after completion of the voriconazole treatment.
Warfarin (JANTOVEN)
Concomitant use of voriconazole and the anticoagulant (blood thinner) warfarin can increase blood levels of warfarin, which 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 voriconazole.
What You Can Do
If you need treatment with voriconazole, review all your other medications with your doctor to assess for potentially significant drug interactions. If you are taking a medication that interacts with voriconazole, you may be advised to adjust the dosage of the interacting drug, undergo more frequent monitoring of the blood levels of the interacting drug or stop the interacting drug, or your doctor may advise you to take a different drug for your fungal infection. Be aware that many other drugs not listed in this article also may have dangerous interactions with voriconazole.
References
[1] Pfizer. Label: voriconazole (VFEND). October 2022. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/021266s053,021267s063,021630s042lbl.pdf. Accessed March 6, 2023.
[2] IBM Micromedex. Drug interactions. http://www.micromedexsolutions.com/home/dispatch. Search term: “voriconazole.” Accessed March 6, 2023.
[3] Pfizer. Label: voriconazole (VFEND). October 2022. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/021266s053,021267s063,021630s042lbl.pdf. Accessed March 6, 2023.
[4] IBM Micromedex. Drug interactions. http://www.micromedexsolutions.com/home/dispatch. Search term: “voriconazole.” Accessed March 6, 2023.
[5] Pfizer. Label: voriconazole (VFEND). October 2022. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/021266s053,021267s063,021630s042lbl.pdf. Accessed March 6, 2023.
