Estradiol with Tacrine Interaction Details

Brand Names Associated with Estradiol

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

Interaction Effect

An increased risk of tacrine adverse effects

Interaction Summary

Hormone replacement therapy (HRT) with estradiol valerate and levonorgestrel significantly increased tacrine concentrations in ten healthy female volunteers. HRT reduces the metabolic conversion of tacrine to its main metabolite, 1-hydroxytacrine, by inhibiting cytochrome P450 1A2 enzymes during the first-pass phase, which may increase the likelihood of enhanced tacrine efficacy and adverse effects.

Severity

Moderate

Onset

Delayed

Evidence

Probable

How To Manage Interaction

Monitor patients for enhanced tacrine adverse effects during long-term treatment in conjunction with estradiol. Smaller doses of tacrine may be appropriate.

Mechanism Of Interaction

Inhibition of cytochrome P450 1A2-mediated conversion of tacrine to 1-hydroxytacrine

Literature Reports

A) Ten healthy female volunteers participated in a randomized, double-blind crossover study which evaluated the effects of hormone replacement therapy (HRT) on the pharmacokinetics of tacrine. Each subject received HRT with estradiol valerate 2 mg and levonorgestrel 0.25 mg or matching placebo once daily for ten days. One hour after the last dose of HRT on day 10, a single dose of tacrine 40 mg was administered. HRT increased the area under the concentration-time curve (AUC) of tacrine by 60% and increased the mean maximum concentration (Cmax) by 46%. The mean apparent oral clearance of tacrine was reduced by 31% in the presence of HRT. No significant pharmacokinetic effects were seen on 1-hydroxytacrine during the HRT phase, indicating that HRT reduces the 1-hdyroxylation of tacrine by cytochrome P450 1A2. While this drug interaction may enhance the efficacy of tacrine in the treatment of Alzheimer's disease, the incidence and severity of adverse effects may also increase, which could contribute to decreased patient compliance .

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.

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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.