Tacrine and Estradiol Topical: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Estradiol Topical
Tacrine
No brand names on record
How we grade severity & evidence
Severity levels
- Contraindicated: These should generally not be used together.
- Major: Potentially serious — often needs a change or close monitoring.
- Moderate: Can be significant — usually manageable with monitoring.
- Minor: Usually limited clinical impact.
Evidence grades
- Established: Well documented — supported by controlled studies or strong clinical data.
- Probable: Good supporting evidence, though not definitively proven.
- Suspected: Some evidence suggests this interaction, but it is not well established.
- Possible: Limited or conflicting evidence; the interaction may occur.
- Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.
Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.
What happens
An increased risk of tacrine adverse effects
Interaction Deep Dive
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 effects1.
Why it happens (mechanism)
Inhibition of cytochrome P450 1A2-mediated conversion of tacrine to 1-hydroxytacrine
Literature reports
1 report — tap to read
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 1.
Common questions
Can I take Tacrine and Estradiol Topical together?
An increased risk of tacrine adverse effects Always confirm with your pharmacist or prescriber before making any change.
How serious is the Tacrine and Estradiol Topical interaction?
It is rated moderate. Can be significant — usually manageable with monitoring.
How quickly could this interaction happen?
The documented onset is "delayed". Effects tend to build up gradually over days to weeks.
How strong is the evidence for this interaction?
The evidence is graded "probable". Good supporting evidence, though not definitively proven.
Questions for your pharmacist
- Does my dose of Tacrine or Estradiol Topical need adjusting while I take them together?
- What symptoms should prompt me to call you or my prescriber right away?
- Does the timing of my doses matter for this combination?
- Is there anything you'd monitor while I'm on both?
References (1)
- Laine K, Palovaara S, Tapanainen P, et al: Plasma tacrine concentrations are significantly increased by concomitant hormone replacement therapy. Clin Pharmacol Ther 1999; 66:602-608. DOI
Keep reading about Estradiol Topical
Keep reading about Tacrine
These medications also interact with supplements
Prescription drugs aren't the whole picture — herbal and dietary supplements can interact with them too. From the evidence-graded Natural Medicines database:
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