Ethinyl Estradiol; Norethindrone with Voriconazole Interaction Details
Brand Names Associated with Voriconazole
- Vfend®
- Voriconazole
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Nov 12, 2023
Interaction Effect
Increased voriconazole exposure, increased ethinyl estradiol and norethindrone exposure
Interaction Summary
Coadministration of voriconazole with an oral combination contraceptive containing ethinyl estradiol and norethindrone has resulted in increased plasma concentrations of voriconazole, ethinyl estradiol, and norethindrone. When these agents are coadministered, monitor patients for adverse events related to voriconazole (peripheral edema, visual disturbance) and ethinyl estradiol/norethindrone (abnormal menstruation, breast tenderness, edema) .
Severity
Moderate
Onset
Delayed
Evidence
Established
How To Manage Interaction
Use caution when prescribing voriconazole to patients who are using oral contraceptives, as concomitant use may cause elevated plasma concentrations of voriconazole, ethinyl estradiol, and norethindrone. Monitor patients for increased adverse effects related to voriconazole (peripheral edema, visual disturbance) and ethinyl estradiol/norethindrone (abnormal menstruation, breast tenderness, edema) .
Mechanism Of Interaction
Altered CYP450-mediated metabolism of voriconazole, ethinyl estradiol, and norethindrone
Literature Reports
A) Concomitant administration of voriconazole and an oral contraceptive in 16 healthy women resulted in increased systemic exposure to all analytes relative to monotherapy, according to an open-label, fixed-sequence, three-period study. In period 1, women (mean age, 25.9 years; range, 19 to 36 years) received voriconazole 400 mg every 12 hours on day 1 and 200 mg every 12 hours on days 2 through 4. During period 2, women were given an oral contraceptive containing ethinyl estradiol 0.035 mg/norethindrone 1 mg every 24 hours on days 12 through 32. In period 3, subjects received combination voriconazole 400 mg every 12 hours on day 57, 200 mg every 12 hours on days 58 through 60, and an oral contraceptive every 24 hours on days 40 through 60. With concurrent administration, there were mean increases in voriconazole AUC and Cmax of 46% (90% confidence interval (CI), 32% to 61%) and 14% (90% CI, 3% to 27%), respectively, compared with monotherapy. Ethinyl estradiol AUC and Cmax increased 61% (90% CI, 50% to 72%) and 36% (90% CI, 28% to 45%), respectively. Norethindrone AUC and Cmax increased 53% (90% CI, 44% to 64%) and 15% (90% CI, 3% to 28%), respectively. Regardless of causality, the most commonly-reported adverse events during combination therapy were headache, abnormal vision, dizziness, nausea, and chromatopsia .
Voriconazole Overview
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Voriconazole is used in adults and children 2 years of age and older to treat serious fungal infections such as invasive aspergillosis (a fungal infection that begins in the lungs and spreads through the bloodstream to other organs), esophageal candidiasis (a yeast [a type of fungus] infection that may cause white patching in the mouth and throat), and candidemia (a fungal infection in the blood). It is also used to treat certain other fungal infections when other medications will not work for certain patients. Voriconazole is in a class of antifungal medications called triazoles. It works by slowing the growth of the fungi that cause infection.
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Definitions
Severity Categories
Contraindicated
These drugs, generally, should not be used together simultaneously due to the high risk of severe adverse effects. Combining these medications can lead to dangerous health outcomes and should be strictly avoided unless otherwise instructed by your provider.
Major
This interaction could result in very serious and potentially life-threatening consequences. If you are taking this drug combination, it is very important to be under close medical supervision to minimize severe side effects and ensure your safety. It may be necessary to change a medication or dosage to prevent harm.
Moderate
This interaction has the potential to worsen your medical condition or alter the effectiveness of your treatment. It's important that you are monitored closely and you potentially may need to make adjustments in your treatment plan or drug dosage to maintain optimal health.
Minor
While this interaction is unlikely to cause significant problems, it could intensify side effects or reduce the effectiveness of one or both medications. Monitoring for changes in symptoms and your condition is recommended, and adjustments may be made if needed to manage any increased or more pronounced side effects.
Onset
Rapid: Onset of drug interaction typically occurs within 24 hours of co-administration.
Delayed: Onset of drug interaction typically occurs more than 24 hours after co-administration.
Evidence
Level of documentation of the interaction.
Established: The interaction is documented and substantiated in peer-reviewed medical literature.
Theoretical: This interaction is not fully supported by current medical evidence or well-documented sources, but it is based on known drug mechanisms, drug effects, and other relevant information.
How To Manage The Interaction
Provides a detailed discussion on how patients and clinicians can approach the identified drug interaction as well as offers guidance on what to expect and strategies to potentially mitigate the effects of the interaction. This may include recommendations on adjusting medication dosages, altering the timing of drug administration, or closely monitoring for specific symptoms.
It's important to note that all medical situations are unique, and management approaches should be tailored to individual circumstances. Patients should always consult their healthcare provider for personalized advice and guidance on managing drug interactions effectively.
Mechanism Of Interaction
The theorized or clinically determined reason (i.e., mechanism) why the drug-drug interaction occurs.
Disclaimer: The information provided on this page is for informational purposes only and should not be considered medical advice. Always consult with a qualified healthcare professional regarding your specific circumstances and medical conditions.
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Information for our drug interactions is compiled from several drug compendia, including:
The prescribing information for each drug, as published on DailyMED, is also used.
Individual drug-drug interaction detail pages contain references specific to that interaction. You can click on the reference number within brackets '[]' to see what reference was utilized.
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