Estradiol with Efavirenz Interaction Details

Brand Names Associated with Estradiol

Brand Names Associated with Efavirenz

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Nov 13, 2023

Interaction Effect

Decreased hormonal contraceptive exposure and increased risk of breakthrough bleeding and/or contraceptive failure

Interaction Summary

Coadministered efavirenz may result in increased or reduced serum concentrations of hormonal contraceptives. In healthy women, coadministration of efavirenz and an oral contraceptive (ethinyl estradiol/norgestimate) did not increase ethinyl estradiol exposure; however, exposure to the progestin components (norgestimate and levonorgestrel) was significantly decreased . In a study, concomitant use of a CYP3A4 inducer disproportionally increased the rate of unplanned pregnancy with oral and implanted contraceptives; therefore, consider intrauterine or intravaginal routes if coadministration is required . Contraceptive failure with etonogestrel in patients receiving efavirenz has been reported. A reliable method of barrier contraception is indicated when efavirenz and a hormonal contraceptive are coadministered. Continue adequate contraceptive measures for 12 weeks upon discontinuation of efavirenz .

Severity

Major

Onset

Delayed

Evidence

Probable

How To Manage Interaction

Based on clinical studies, decreased progestin levels may be expected if efavirenz is coadministered with hormonal contraceptives including oral contraceptives, implants, and injections. Advise patients to use a reliable method of barrier contraception when efavirenz and a hormonal contraceptive are coadministered. Continue adequate contraceptive measures for 12 weeks upon discontinuation of efavirenz. Use of intrauterine or intravaginal contraceptives may be preferable during coadministration with a CYP3A inducer .

Mechanism Of Interaction

Induction of CYP3A4-mediated metabolism of hormonal contraceptives

Literature Reports

A) Concomitant use of a CYP3A4 inducer with oral or implantable contraceptive products containing levonorgestrel (684 events) or etonogestrel/desogestrel (864 events) was associated with a disproportionately higher rate of unintended pregnancy compared to all other event types reported to the FDA Adverse Event Reporting System (FAERS) between 1971 and 2020 [levonorgestrel (14,504 total events); etonogestrel/desogestrel (9348 total events)]. When compared between CYP3A4 inducer exposure vs no exposure, cases of unintended pregnancy made up a significantly higher proportion of total events when levonorgestrel was administered orally (32.8% vs 10.5%) or as an implant (51.9% vs 11.9%), and a similar association was identified with implanted etonogestrel products (42.5% vs 13.1%). However, when contraceptives were administered as an intrauterine device (levonorgestrel, 10.3% vs 11.5%) or intravaginal ring (etonogestrel, 10.9% vs 8.7%), no significant associations were identified. Oral desogestrel (pro-drug of etonogestrel) in combination with ethynyl estradiol also was not significantly affected (11.8% vs 17.4%). Intrauterine and vaginal ring products may be preferred in lieu of oral and implantable contraceptive products in women concomitantly receiving CYP3A4 inducers .

B) In a pharmacokinetic study in healthy HIV-negative women (n=28; mean age 26 years), coadministration of efavirenz (600 mg daily) and an oral contraceptive containing ethinyl estradiol (EE) and norgestimate (NGM) resulted in similar exposure for ethinyl estradiol to that seen when given alone; however, exposure to the progestin components (norgestimate and levonorgestrel) was significantly decreased. In this open-label, three-period, four-treatment study, participants received in period 1 (treatment A) Ortho Tri-Cyclen LO(R) (EE 0.025 mg plus NGM 0.18 mg on days 1 to 7 (phase 1); EE 0.025 mg plus NGM 0.215 mg on days 8 to 14 (phase 2); and EE 0.025 mg plus NGM 0.25 mg on days 15 to 21 (phase 3)). This was followed by period 2 (days 29 to 56) where participants with acceptable baseline safety assessments received a full cycle of Ortho-CyClen(R) (EE 0.035 mg plus NGM 0.25 mg (phases 1 to 3; treatment B)). Participants with satisfactory safety assessments began a second cycle of Ortho-CyClen(R) (days 57 to 77; period 3) coadministered with efavirenz 600 mg/day for 14 days (days 57 to 70; treatment C). Ethinyl estradiol pharmacokinetic parameters (Cmax, AUC, and Cmin) were not significantly different when efavirenz was given concurrently. However, norgestimate exposure was significantly decreased in the presence of efavirenz. The adjusted geometric means for Cmax, AUC, and Cmin were reduced by 46% (90% confidence interval (CI), 39% to 52%), 64% (90% CI, 62% to 67%), and 82% (90% CI, 79% to 85%), respectively. Post-hoc analysis also showed similar results with levonorgestrel exposure (adjusted geometric means for Cmax, AUC, and Cmin reduced by 80% to 86% in the presence of efavirenz) .

Estradiol Overview

• Estrogen is used to treat hot flushes ('hot flashes'; sudden strong feelings of heat and sweating) in women who are experiencing menopause ('change of life', the end of monthly menstrual periods). Some brands of estrogen are also used to treat vaginal dryness, itching, or burning, or to prevent osteoporosis (a condition in which the bones become thin and weak and break easily) in women who are experiencing or have experienced menopause. However, women who need a medication only to treat vaginal dryness or only to prevent osteoporosis should consider a different treatment. Some brands of estrogen are also to relieve symptoms of low estrogen in young women who do not produce enough estrogen naturally. Some brands of estrogen are also used to relieve the symptoms of certain types of breast and prostate (a male reproductive gland) cancer. Estrogen is in a class of medications called hormones. It works by replacing estrogen that is normally produced by the body.

Efavirenz Overview

• Efavirenz is used along with other medications to treat human immunodeficiency virus (HIV) infection. Efavirenz is in a class of medications called non-nucleoside reverse transcriptase inhibitors (NNRTIs). It works by decreasing the amount of HIV in the blood. Although efavirenz does not cure HIV, it may decrease your chance of developing acquired immunodeficiency syndrome (AIDS) and HIV-related illnesses such as serious infections or cancer. Taking these medications along with practicing safer sex and making other life-style changes may decrease the risk of transmitting (spreading) the HIV virus to other people.

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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.

Where Does Our Information Come From?

Information for our drug interactions is compiled from several drug compendia, including:

• Gold Standard Drug Database
• Micromedex
• Lexicomp
• DrugBank

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.

The information posted is fact-checked by HelloPharmacist clinicians and reviewed quarterly.