Drug & supplement interaction

Caffeine + Letrozole

Letrozole brand name: Femara.

No Known Interaction
Medically reviewed by · Updated July 2026 · Pair last verified Sep 13, 2026
The bottom line No known interaction

We found no known interaction between Caffeine and Letrozole in our sources. Absence of a documented interaction is not the same as proven safety, and does not guarantee one does not exist. Do not start, stop, or change a medication or supplement based on this page; confirm with your pharmacist or doctor first. Additionally, although there is no interaction, the two are separately associated with some of the same side effects, which would make a new symptom harder to attribute to one or the other.

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Interaction report

Caffeine and Letrozole

We checked these two against our interaction database. Here is what we found.

No Known Interaction Found

We did not find a documented interaction between Letrozole and Caffeine in our sources. This does not guarantee that the combination is completely free of risk — there is often limited research on supplements and herbal products, especially around drug interactions.

If you decide to take both, the practical routine is simple: add one new thing at a time and note the date you started it. If the combination is going to disagree with you, it usually shows in the first days to a couple of weeks — and a start date turns “I’ve been feeling off” into something a pharmacist can actually work with. Do not stop a prescribed medicine on your own.

Always talk with your pharmacist or doctor before making changes to your medications or supplements, particularly if you take several medications or have an ongoing health condition.

Caffeine safety at a glance

Caffeine overall Use caution Generally safe in moderate amounts for healthy adults, but high doses can cause serious side effects.
Pregnancy Possibly Safe When used orally in amounts commonly found in foods. Intakes of caffeine should be monitored during pregnancy. Caffeine crosses the human placenta, but is not c... Read the full pregnancy detail
Breastfeeding Possibly Safe When used orally in amounts commonly found in foods. Caffeine intake should be closely monitored while breast-feeding. During lactation, breast milk concentrati... Read the full breastfeeding detail

Pregnancy & breastfeeding ratings are from Natural Medicines (Therapeutic Research Center) — the full detail is in the Special populations card below. Safety guidance is general; always confirm with your pharmacist or doctor for your situation.

Still wondering about combining Letrozole and Caffeine? Ask Dr. Brian Staiger, PharmD, BCPS directly ›
How we checked

Why No Interaction Is Listed for Letrozole

Interactions in our licensed database are recorded against drug classes, not just single drug names. Letrozole is filed under 4 classifications — including aromatase inhibitors, cytochrome p450 2c19 (cyp2c19) inhibitors, cytochrome p450 3a4 (cyp3a4) substrates. Caffeine has documented interactions with 41 drug classes — the most serious being ephedrine (major), adenosine (adenocard) (moderate) and anticoagulant/antiplatelet drugs (moderate) — and none of Letrozole’s classifications are among them.

Classification data comes from our licensed Natural Medicines dataset. A medication can belong to classes beyond those recorded there, so this describes how the check was run — it is not a safety guarantee.

Keep it in perspective

Caffeine Does Interact With Other Medications

Caffeine has 8 major, 483 moderate, 164 minor known drug interactions in our database — Letrozole isn’t one of them. If you take anything else, check it against the full list below.

Major 8 Moderate 483 Minor 164 No known interaction 2,175 (incl. Letrozole)
Taking anything else?

Check Another of Your Medications Against Caffeine

Covers the 2,830 medications we’ve checked against Caffeine. Pick one to open its full report.

What to actually watch for

No Interaction Found — But Data Suggests Caffeine and Letrozole May Share Several of the Same Side Effects

This is not an interaction. Neither one changes how your body handles the other, and nothing here says they react together. What our sources do show is that each has separately been linked to the effects below — so taking both can make those effects more likely to turn up, and harder to pin on one or the other if they do.

  • Swelling Additional detail

    Caffeine

    “Some evidence shows caffeine is associated with fibrocystic breast disease or breast cancer in females; however, this is controversial since findings are conflicting. Restricting caffeine in females with fibrocystic breast conditions doesn't seem to affect breast nodularity, swelling, or pain.”

    Caffeine · Natural Medicines adverse-effect record, reported in breast cancer.

    5 sources cited
    1. 8043. Ferrini RL, Barrett-Connor E. Caffeine intake and endogenous sex steroid levels in postmenopausal women. The Rancho Bernardo Study. Am J Epidemiol 1996:144:642-4. PubMed
    2. 108806. Zheng KH, Zhu K, Wactawski-Wende J, et al. Caffeine intake from coffee and tea and invasive breast cancer incidence among postmenopausal women in the Women's Health Initiative. Int J Cancer 2021;149(12):2032-2044. PubMed
    3. 8996. Horner NK, Lampe JW. Potential mechanisms of diet therapy for fibrocystic breast conditions show inadequate evidence of effectiveness. J Am Diet Assoc 2000;100:1368-80. PubMed
    4. 108807. Wang S, Li X, Yang Y, et al. Does coffee, tea and caffeine consumption reduce the risk of incident breast cancer? A systematic review and network meta-analysis. Public Health Nutr 2021;24(18):6377-6389. PubMed
    5. 91023. Beaudoin MS, Allen B, Mazzetti G, Sullivan PJ, Graham TE. Caffeine ingestion impairs insulin sensitivity in a dose-dependent manner in both men and women. Appl Physiol Nutr Metab. 2013;38(2):140-7. doi: 10.1139/apnm-2012-0201. Epub 2012 9. PubMed

    Letrozole

    Listed in the ADVERSE REACTIONS section of the FDA label for Letrozole. Read the label on DailyMed ›

  • Tiredness Additional detail

    Caffeine

    “Caffeine may lead to habituation and physical dependence, with amounts as low as 100 mg daily. An estimated 9% to 30% of caffeine consumers could be considered addicted to caffeine. Higher doses of caffeine have caused nervousness, agitation, anxiety, irritability, delirium, depression, sleep disturbances, impaired attention, manic behavior, psychosis and panic attacks.”

    Caffeine · Natural Medicines adverse-effect record, reported in anxiety.

    6 sources cited
    1. 36355. Griffiths, R. R. and Chausmer, A. L. Caffeine as a model drug of dependence: recent developments in understanding caffeine withdrawal, the caffeine dependence syndrome, and caffeine negative reinforcement. Nihon Shinkei Seishin Yakurigaku Zasshi 2000;20(
    2. 36453. Hughes, J. R., Higgins, S. T., Bickel, W. K., Hunt, W. K., Fenwick, J. W., Gulliver, S. B., and Mireault, G. C. Caffeine self-administration, withdrawal, and adverse effects among coffee drinkers. Arch.Gen.Psychiatry 1991;48(7):611-617. PubMed
    3. 36512. Levy, M. and Zylber-Katz, E. Caffeine metabolism and coffee-attributed sleep disturbances. Clin Pharmacol Ther 1983;33(6):770-775. PubMed
    4. 36599. Garrett, B. E. and Griffiths, R. R. Physical dependence increases the relative reinforcing effects of caffeine versus placebo. Psychopharmacology (Berl) 1998;139(3):195-202. PubMed
    5. 36505. Stillner, V., Popkin, M. K., and Pierce, C. M. Caffeine-induced delirium during prolonged competitive stress. Am.J.Psychiatry 1978;135(7):855-856. PubMed
    6. 37717. Whalen, D. J., Silk, J. S., Semel, M., Forbes, E. E., Ryan, N. D., Axelson, D. A., Birmaher, B., and Dahl, R. E. Caffeine consumption, sleep, and affect in the natural environments of depressed youth and healthy controls. J Pediatr.Psychol. 2008;33(4):35 PubMed

    Letrozole

    Listed in the ADVERSE REACTIONS section of the FDA label for Letrozole. Read the label on DailyMed ›

  • Headache Additional detail

    Caffeine

    “Caffeine can cause headaches, anxiety, jitteriness, restlessness, and nervousness. In adolescents, there is an inverse correlation between the consumption of caffeine and various measurements of cognitive function. Insomnia is a frequent adverse effect in children. Caffeine may result in insomnia and sleep disturbances in adults as well.”

    Caffeine · Natural Medicines adverse-effect record, reported in anxiety.

    6 sources cited
    1. 36466. Wrenn, K. D. and Oschner, I. Rhabdomyolysis induced by a caffeine overdose. Ann.Emerg.Med. 1989;18(1):94-97. PubMed
    2. 37694. Doan, B. K., Hickey, P. A., Lieberman, H. R., and Fischer, J. R. Caffeinated tube food effect on pilot performance during a 9-hour, simulated nighttime U-2 mission. Aviat.Space Environ Med 2006;77(10):1034-1040.
    3. 37755. Killgore, W. D., Rupp, T. L., Grugle, N. L., Reichardt, R. M., Lipizzi, E. L., and Balkin, T. J. Effects of dextroamphetamine, caffeine and modafinil on psychomotor vigilance test performance after 44 h of continuous wakefulness. J Sleep Res 2008;17(3):3 PubMed
    4. 37806. Killgore, W. D., Kahn-Greene, E. T., Grugle, N. L., Killgore, D. B., and Balkin, T. J. Sustaining executive functions during sleep deprivation: A comparison of caffeine, dextroamphetamine, and modafinil. Sleep 2-1-2009;32(2):205-216. PubMed
    5. 37865. Addicott, M. A. and Laurienti, P. J. A comparison of the effects of caffeine following abstinence and normal caffeine use. Psychopharmacology (Berl) 2009;207(3):423-431. PubMed
    6. 37830. Koran, L. M., Aboujaoude, E., and Gamel, N. N. Double-blind study of dextroamphetamine versus caffeine augmentation for treatment-resistant obsessive-compulsive disorder. J Clin Psychiatry 2009;70(11):1530-1535. PubMed

    Letrozole

    Listed in the ADVERSE REACTIONS section of the FDA label for Letrozole. Read the label on DailyMed ›

  • Nausea Additional detail

    Caffeine

    Recorded for Caffeine in the same Natural Medicines adverse-effect record shown under Headache above.

    Letrozole

    Listed in the ADVERSE REACTIONS section of the FDA label for Letrozole. Read the label on DailyMed ›

Reported for Caffeine but not commonly for Letrozole: raised blood pressure, stomach upset, fainting and dependence or withdrawal symptoms.

Effects for Letrozole come from the ADVERSE REACTIONS section of its FDA label; effects for Caffeine come from the Natural Medicines adverse-effect record, quoted above. Wording is matched across sources by our own clinical vocabulary, so treat this as a prompt to pay attention, not a diagnosis.

Special populations

Caffeine in Pregnancy & Breastfeeding

Pregnancy Possibly Safe

When used orally in amounts commonly found in foods. Intakes of caffeine should be monitored during pregnancy. Caffeine crosses the human placenta, but is not considered a teratogen. Fetal blood and tissue levels are similar to maternal concentrations. The use of caffeine during pregnancy is controversial; however, moderate consumption has not been associated with clinically important adverse fetal effects. In some studies consuming amounts over 200 mg daily is associated with a significantly increased risk of miscarriage. This increased risk seems to occur in those with genotypes that confer a slow rate of caffeine metabolism. According to a review by Health Canada, and a subsequent large meta-analysis conducted in the US, up to 300 mg daily can be consumed during pregnancy without an increased risk of spontaneous abortion, stillbirth, preterm birth, fetal growth retardation, or congenital malformations. However, observational research in a Norwegian cohort found that caffeine consumption is associated with a 16% increased odds of the baby being born small for gestational age when compared with no consumption. The same Norwegian cohort found that low to moderate caffeine consumption during pregnancy is not associated with changes in neurodevelopment in children up to 8 years of age. Advise patients to keep caffeine consumption below 300 mg daily during pregnancy. This is similar to the amount of caffeine in about 3 cups of coffee or tea.

Pregnancy Possibly Unsafe

When used orally in amounts over 300 mg daily. Caffeine crosses the placenta, producing fetal blood concentrations similar to maternal levels. Consumption of caffeine in amounts over 300 mg daily is associated with a significantly increased risk of miscarriage in some studies. Advise patients to keep caffeine consumption below 300 mg daily during pregnancy. This is similar to the amount of caffeine in about 3 cups of coffee or tea. Additionally, high doses of caffeine throughout pregnancy have resulted in symptoms of caffeine withdrawal in newborn infants. High doses of caffeine have also been associated with spontaneous abortion, premature delivery, and low birth weight. In a cohort of mother/infant pairs with a median maternal plasma caffeine level of 168.5 ng/mL (range 29.5-650.5 ng/mL) during pregnancy, birth weights and lengths were lower in the 4th quartile of caffeine intake compared with the 1st. By age 7, heights and weights were lower by 1.5 cm and 1.1 kg respectively. In another cohort of mother/infant pairs with higher maternal pregnancy plasma caffeine levels, median 625.5 ng/mL (range 86.2 to 1994.7 ng/mL), heights at age 8 were 2.2 cm lower, but there was no difference in weights.

Lactation Possibly Safe

When used orally in amounts commonly found in foods. Caffeine intake should be closely monitored while breast-feeding. During lactation, breast milk concentrations of caffeine are thought to be approximately 50% of serum concentrations and caffeine peaks in breastmilk approximately 1-2 hours after consumption.

Lactation Possibly Unsafe

When used orally in large amounts. Caffeine is excreted slowly in infants and may accumulate. Caffeine can cause sleep disturbances, irritability, and increased bowel activity in breast-fed infants exposed to caffeine.

DISCLAIMER: This tool is intended for informational purposes only, and should not be interpreted as specific medical advice. Patients should consult with a qualified healthcare provider before making decisions about therapies and/or health conditions.© 2026 Therapeutic Research Center

From our Q&A

Questions About Caffeine or Letrozole

These are real questions from readers, answered by the pharmacists at HelloPharmacist — written by a person, not generated from a database. Each one covers Caffeine or Letrozole, not necessarily both, but if one is close to what you were about to ask it will usually go further than a database entry can:

Not quite your question? Ask our pharmacists directly — it is free, there is no account required, and answers usually come back within 24 hours.

Everything else you take

See Every Supplement That Interacts With Letrozole

This page covers Caffeine only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Letrozole page lists 142 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Grapefruit (major), St. John's Wort (major), 7-methoxyflavone (moderate) and Acacia Rigidula (moderate).

By severity: 3 major · 99 moderate · 40 minor.

From our pharmacist’s overview on the Letrozole page

“Letrozole (Femara) is prescribed to keep hormone-driven breast cancer from returning, so a supplement that shifts its blood level can quietly undercut treatment. Give this list of 142 ingredients genuine respect, and learn the three major entries first.”

Reviewed by 2 · Jul 18, 2026

Open the Letrozole interaction page

One more smart check

Taking Caffeine as Part of a Dietary Supplement Product? Check It for Interactions

We hold 6,775 real supplement products containing Caffeine, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Caffeine. Even though Caffeine itself has no known interaction with Letrozole, another ingredient on your label might. Find your product and we’ll check every ingredient on its label:

How much people look this up

Where Caffeine and Letrozole Sit Against Everything Else

Out of every supplement and medication people look up on HelloPharmacist, here is where these two land this week — and which way each has been moving.

Supplement Caffeine
Top 5%

#25 of 1,452 supplements looked up here in the last 7 days

29 days ago today
Medication Letrozole
Top 5%

#51 of 2,830 medications looked up here in the last 7 days

29 days ago today

Position among everything looked up on this site, not a measure of how commonly either one is used or how important it is. A supplement can climb this list because of a news story. It counts every request to the page, automated ones included, and nothing here identifies anyone.

Where does our data come from?
  • Source: the Natural Medicines (TRC Healthcare) clinical database — the evidence-graded professional reference for herb & supplement interactions.
  • Citation library: 103,510 references behind our interaction content, 65,311 of them resolved to verified PubMed/DOI sources. See every Caffeine reference on this page ↓
  • Freshness: we automatically re-check this combination every week — this pair was last verified September 13, 2026. The Caffeine and Letrozole records this page draws on were last updated July 11, 2026.
  • What “no known interaction” means: no documented interaction in the sources above — not a guarantee of safety. Supplements are studied far less than prescription drugs, so we say exactly what the evidence supports, and nothing more.
Data structure & sourcing designed and verified by .
Supplement

About Caffeine

What is Caffeine?

  • Mental alertness and reducing fatigue
  • Improving athletic performance
  • Headache and migraine relief
  • Boosting focus and concentration
  • Weight loss aid

Caffeine is a natural stimulant found in coffee, tea, and many other plants and products. In moderate amounts it can boost alertness and reduce tiredness for most healthy adults, but too much can cause jitteriness, a racing heart, and sleep problems. Pregnant women and people with heart conditions or anxiety should be especially careful and check with a doctor or pharmacist.

Seeds, leaves, and beans of various plants (e.g., coffee, tea, cacao, guarana, kola) · Coffee, tea, energy drinks, sodas, tablets, capsules, pre-workout powders, gum

An interaction check asks whether these two react with each other — it does not ask whether Caffeine is a good idea for someone in your situation. Here is what our Caffeine record says about it on its own.

Caffeine: dosing

There is no single "correct" dose of caffeine, and the right amount depends on your age, health, and how sensitive you are. Many health authorities suggest that moderate daily intake is reasonable for most healthy adults, but individual limits vary widely.If you use a caffeine supplement, energy drink, or pre-workout powder, follow the directions on the product label and do not take more than recommended. Concentrated caffeine powders are especially dangerous because a small mistake can lead to a harmful overdose.Remember that caffeine adds up across coffee, tea, sodas, energy drinks, chocolate, and any supplements or medicines that contain it.

From our Caffeine monograph — the full record covers uses, side effects and every documented interaction.

Read the full Caffeine monograph & all interactions
Medication

About Letrozole

What Is Letrozole Used For?

Brand name: Femara

Letrozole (brand name Femara) is used to treat breast cancer in postmenopausal women whose tumors are driven by estrogen. It is used in three settings: as adjuvant (after-surgery) treatment for hormone receptor positive early breast cancer; as extended adjuvant treatment for women who have already completed about five years of tamoxifen therapy; and as first- or second-line treatment for locally advanced or metastatic (spread) breast cancer.

Femara is specifically indicated for first-line treatment of hormone receptor positive or receptor-unknown locally advanced or metastatic breast cancer, and for advanced breast cancer in women whose disease has progressed after antiestrogen therapy.

See full Letrozole drug information
Keep checking

Other Drugs & Caffeine

Browse every other medication we’ve checked against Caffeine — both the ones with a known interaction and the ones without. Select any drug for the full detail.

8Major
483Moderate
164Minor
2,174No known interaction
8 Major 483 Moderate 164 Minor 2,174 No interaction
Major

8 interactions

Moderate

483 interactions

Showing 60 of 483 moderate interactions — see all 483 on the Caffeine page.

Minor

164 interactions

Showing 60 of 164 minor interactions — see all 164 on the Caffeine page.

No interaction 2,174 drugs checked — show the list

We also checked Caffeine against these medications and found no known interaction in our sources. Open any page to confirm.

Showing the 60 most looked-up of 2,174 medications checked with no known interaction — see the full Caffeine list.

See the full Caffeine interactions page
See every supplement checked against Letrozole, ranked by severity
Evidence & sources

Caffeine References

The 236 references that drive our Caffeine monograph and interaction data, from the evidence-graded Natural Medicines (TRC Healthcare) database. Citations with a link open the study on PubMed or the publisher’s site.

  1. McEvoy GK, ed. AHFS Drug Information. Bethesda, MD: American Society of Health-System Pharmacists, 1998.
  2. Harder S, Fuhr U, Staib AH, Wolff T. Ciprofloxacin-caffeine: a drug interaction established using in vivo and in vitro investigations. Am J Med 1989;87:89S-91S. PubMed
  3. Carbo M, Segura J, De la Torre R, et al. Effect of quinolones on caffeine disposition. Clin Pharmacol Ther 1989;45:234-40. PubMed
  4. Healy DP, Polk RE, Kanawati L, et al. Interaction between oral ciprofloxacin and caffeine in normal volunteers. Antimicrob Agents Chemother 1989;33:474-8. PubMed
  5. Mester R, Toren P, Mizrachi I, et al. Caffeine withdrawal increases lithium blood levels. Biol Psychiatry 1995;37:348-50. PubMed
  6. Jefferson JW. Lithium tremor and caffeine intake: two cases of drinking less and shaking more. J Clin Psychiatry 1988;49:72-3.
  7. Joeres R, Klinker H, Heusler H, et al. Influence of mexiletine on caffeine elimination. Pharmacol Ther 1987;33:163-9. PubMed
  8. Vahedi K, Domingo V, Amarenco P, Bousser MG. Ischemic stroke in a sportsman who consumed MaHuang extract and creatine monohydrate for bodybuilding. J Neurol Neurosurg Psychiatr 2000;68:112-3.
  9. Wakabayashi K, Kono S, Shinchi K, et al. Habitual coffee consumption and blood pressure: A study of self-defense officials in Japan. Eur J Epidemiol 1998;14:669-73. PubMed
  10. Hodgson JM, Puddey IB, Burke V, et al. Effects on blood pressure of drinking green and black tea. J Hypertens 1999;17:457-63. PubMed
  11. Rapuri PB, Gallagher JC, Kinyamu HK, Ryschon KL. Caffeine intake increases the rate of bone loss in elderly women and interacts with vitamin D receptor genotypes. Am J Clin Nutr 2001;74:694-700. PubMed
  12. The National Toxicology Program (NTP). Caffeine. Center for the Evaluation of Risks to Human Reproduction (CERHR). Available at: http://cerhr.niehs.nih.gov/common/caffeine.html.
  13. Klebanoff MA, Levine RJ, DerSimonian R, et al. Maternal serum paraxanthine, a caffeine metabolite, and the risk of spontaneous abortion. N Engl J Med 1999;341:1639-44. PubMed
  14. Eskenazi B. Caffeine—filtering the facts. N Engl J Med 1999;341:1688-9. PubMed
  15. Fernandes O, Sabharwal M, Smiley T, et al. Moderate to heavy caffeine consumption during pregnancy and relationship to spontaneous abortion and abnormal fetal growth: a meta-analysis. Reprod Toxicol 1998;12:435-44. PubMed

Medication overviews come from MedlinePlus (NIH); supplement label data from the NIH Dietary Supplement Label Database. Content is written and reviewed by licensed HelloPharmacist pharmacists — see our data sources and editorial standards.

Pharmacist Counseling Corner

Taking Caffeine and Letrozole Together: Common Questions

Is it safe to take Caffeine with Letrozole?
We do not list a known interaction between Caffeine and Letrozole. That does not guarantee the combination is risk-free, so confirm with your pharmacist or doctor — especially if you take other medications or have a health condition.
Do Caffeine and Letrozole have any of the same side effects?
Yes — our sources link each of them separately to 4 of the same effects. That is not an interaction: neither changes how your body handles the other. It does mean that if one of those effects turns up, it can be harder to tell which one is behind it. They are listed on this page with the source behind each.
How was the Caffeine and Letrozole combination checked?
Interactions in our licensed database are recorded against drug classes. Letrozole is filed under 4 classifications, and Caffeine has documented interactions with 41 drug classes — none of Letrozole's classifications are among them. A medication can belong to classes beyond those recorded in our dataset, so this describes how the check was run rather than guaranteeing safety.
Does Caffeine interact with any other medications?
Yes. Caffeine has 655 documented drug interactions in our database — Letrozole is simply not one of them. If you take anything else, it is worth checking each one; they are all listed on this page.
Does Letrozole interact with any supplements?
Yes. Letrozole has documented interactions with 142 supplements in our database — Caffeine is not one of them. The Letrozole interaction page linked on this page lists every one, ranked by severity.

Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy

Where next

Keep Exploring

Caffeine monograph Uses, safety profile, and every drug interaction in one place Letrozole drug information The full plain-English guide to this medication Letrozole supplement interactions Every supplement checked against Letrozole, ranked by severity Supplement interaction checker Check any supplement or product against your medications Browse medications A–Z Every drug we’ve checked against herbs & supplements References The 236 citations behind this page Ask a pharmacist Free, personal answer from our licensed team

Still Have a Question About Letrozole and Caffeine?

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This information is for education only and is not a substitute for professional medical advice. Always check with your pharmacist or doctor before starting, stopping, or combining supplements and medications.