Estradiol with Ritonavir Interaction Details

Brand Names Associated with Estradiol

Brand Names Associated with Ritonavir

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

Interaction Effect

Reduced estrogen/progestin exposure and reduced efficacy of contraceptive

Interaction Summary

COCs have shown significant decrease in plasma concentrations of estrogen and/or progestin during coadministration with ritonavir. Concomitant use of ritonavir and combination hormonal contraceptives may decrease efficacy of the contraceptive. The AUC of a single 50 mcg dose of ethinyl estradiol declined by 40% on average when given concomitantly with ritonavir 500 mg twice daily. Cmax of ethinyl estradiol also decreased by 32% . In a study, the AUC of ethinyl estradiol decreased from 1670 pg/mL/hr to 993 pg/mL/hr when coadministered with ritonavir . If concomitant use is necessary, alternate methods of contraception should be considered .

Severity

Major

Onset

Delayed

Evidence

Probable

How To Manage Interaction

Combination oral contraceptives (COCs) have shown significant decrease in plasma concentrations of estrogen and/or progestin during coadministration with ritonavir. Concomitant use of ritonavir and combination hormonal contraceptives may decrease efficacy of the contraceptive. Alternative methods of contraception should be considered .

Mechanism Of Interaction

Unknown

Literature Reports

A) Twenty-three female study participants received a single oral dose of an oral contraceptive containing ethinyl estradiol 50 mcg and ethynodiol diacetate 1 mg on study days 1 and 29. From days 15 through 30, ritonavir was administered twice daily. Cmax of ethinyl estradiol was 104 picograms (pg)/mL when administered alone, and decreased to 70.7 pg/mL in the presence of ritonavir. Likewise, the AUC of ethinyl estradiol decreased from 1670 pg/mL/hr to 993 pg/mL/hr when coadministered with ritonavir. These results are consistent with an increase in ethinyl estradiol clearance from hepatic enzyme induction of glucuronidation and/or cytochrome P450 hydroxylation caused by ritonavir .

B) Ritonavir is an inhibitor of CYP3A4, which is involved in the metabolism of both estrogens and levonorgestrel. As such, inhibition of metabolism may result in increase plasma concentrations of estrogen and/or levonorgestrel and risk of related side effects .

C) The AUC of a single 50 mcg dose of ethinyl estradiol declined by 40% on average when given concomitantly with ritonavir 500 mg twice daily. Cmax of ethinyl estradiol also decreased by 32% .

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.

Ritonavir Overview

• Ritonavir is used along with other medications to treat human immunodeficiency virus (HIV) infection. Ritonavir is in a class of medications called protease inhibitors. It works by decreasing the amount of HIV in the blood. Although ritonavir 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 lifestyle changes may decrease the risk of transmitting 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.