Tamoxifen

Selective estrogen receptor modulator (SERM)

ATC code: L02BA01

Brand names: Nolvadex, Soltamox, Tamoxen

Updated 17 Jul 2026 · Methodology

Indications

ER-positive breast cancer

First line

Drug of choice for adjuvant endocrine therapy of hormone-receptor positive breast cancer in premenopausal women (ESMO, NCCN). Dose 20 mg once daily for 5–10 years (the ATLAS trial showed a 10-year benefit over 5 in high-risk patients). For risk reduction in women at high risk (BRCA carriers, LCIS, DCIS) efficacy is shown in the NSABP P-1 and IBIS-I trials; this use is outside the registered indication.

Drug of choice in premenopausal women and an alternative in postmenopausal patients.

Sources

ICD-10: C50 · ICD-11: 2C6Z

Marketing claims without evidence base

The drug is promoted for these uses outside international guidelines. Each entry below is analyzed against AEMPS, FDA, EMA, Cochrane and major RCTs.

Athletic endurance

Not recommended

Tamoxifen is used by amateur bodybuilders and AAS users in post-cycle therapy to block estrogen receptors and restore endogenous testosterone production. ASCO 2022 and the AEMPS Ficha Técnica confine tamoxifen to hormone-receptor-positive breast cancer and risk reduction in high-risk women. Approved indications in male athletes do not exist. Use carries venous thromboembolism, endometrial cancer ( boxed warning) and thromboembolic stroke risk.

Sources

How to read tiers A–F

AStrong evidence – first or second line in international guidelines
BRecommended in selected cases
CStudy data contradict each other
DBenefit not proven, no documented harm
FDocumented harm, or risk without benefit

Mechanism of action

A selective estrogen receptor modulator: antagonist in breast tissue, partial agonist in endometrium, bone, and liver. Competitively binds estrogen receptors in breast tumor cells, blocking proliferative signaling. CYP2D6-metabolized to active endoxifen with 30–100-fold higher estrogen receptor affinity. In CYP2D6 poor metabolizers (~7% of Caucasians), efficacy is reduced.

Safety

Boxed warning

FDA boxed warning: increased risk of endometrial cancer, stroke, and venous thromboembolism. In women with risk factors, decisions are individualized.

Contraindications

Tamoxifen hypersensitivity
Active thromboembolic disease
Pregnancy and lactation
Severe hepatic impairment
Concomitant strong CYP2D6 inhibitors (paroxetine, fluoxetine, bupropion)

Serious adverse effects

Venous thromboembolism (2–3× risk)
Endometrial cancer (2–3× risk, developing after 2–5 years of therapy)
Stroke
Cataract
Hepatotoxicity up to acute liver failure
Hepatic steatosis

Common adverse effects

Hot flashes and night sweats
Vaginal bleeding and discharge
Weight gain
Fatigue
Nausea
Reduced libido

Pregnancy: can you take Tamoxifen?

AEMPS summary of product characteristics (section 4.6): tamoxifen is contraindicated in pregnancy. Women who could become pregnant are advised to avoid pregnancy during treatment and to use barrier or other non-hormonal contraception, and premenopausal women are carefully examined before starting treatment to rule out pregnancy. Women are told about the potential risks to the fetus if they become pregnant during treatment or within two months after stopping it.

Breastfeeding: can you take Tamoxifen?

Contraindicated during lactation – suppresses milk production.

Calculate RID Full profile on NIH LactMed ↗

Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.

Practical notes

Timing and administration

Take once daily, with or without food. Standard adjuvant duration is 5 years; up to 10 years at high recurrence risk. In premenopausal patients use non-hormonal contraception (copper IUD, barrier methods); hormonal contraception is contraindicated. Pre-treatment and annual gynecologic exam – endometrial hyperplasia and endometrial cancer risk (1 case per 1000 patient-years). Monitor liver enzymes.

Drug–drug interactions

3 pairs found. Sorted from critical to minor.

MajorBupropionOther antidepressants (NDRI)

Mechanism

Bupropion is a strong CYP2D6 inhibitor. Endoxifen falls 60%.

Symptoms

Tumour progression.

Management

For smoking cessation – nicotine replacement or varenicline (not a CYP2D6 inhibitor).

Sources

Pair details →Bupropion →

MajorFluoxetineSelective serotonin reuptake inhibitors

Mechanism

Fluoxetine is a strong CYP2D6 inhibitor. Endoxifen falls 60%.

Symptoms

Tumour progression on long-term use.

Management

Alternative – sertraline, escitalopram or venlafaxine.

Sources

Pair details →Fluoxetine →

MajorParoxetineSelective serotonin reuptake inhibitor (SSRI)

Mechanism

Tamoxifen is a prodrug: CYP2D6 converts it to endoxifen, one of its most active forms. Paroxetine is a strong CYP2D6 inhibitor. The data cited in the Spanish SmPCs of both drugs show a 65–75% fall in endoxifen levels with CYP2D6 inhibitors. In some studies tamoxifen efficacy dropped with paroxetine, up to higher breast cancer relapse and mortality; other studies found no such effect, as the label notes.

Symptoms

Tumour progression on imaging after 6–12 months.

Management

Avoid paroxetine during tamoxifen therapy where possible, as the Spanish SmPCs of both drugs require. The label advises an antidepressant with little or no CYP2D6 inhibition. The Spanish SmPC describes venlafaxine as a relatively weak CYP2D6 inhibitor. Sertraline also inhibits CYP2D6 (mild to moderate), and escitalopram doubled desipramine and metoprolol levels in studies. Fluoxetine and bupropion are strong CYP2D6 inhibitors, like paroxetine. If depression does not respond to the switch, oncology and psychiatry agree the regimen together.

Sources

Pair details →Paroxetine →

Label mentions29 mentions

Verbatim lines from the interaction sections, in the language of the label

From this drug’s label

MajorBupropion
«Inhibidores del CYP2D6: En publicaciones científicas se han descrito interacciones farmacocinéticas con inhibidores del CYP2D6, mostrando una reducción del 65-75% en los niveles plasmáticos de una de…»
AEMPS, section 4.5 · Open on CIMA
MajorFluoxetine
«Inhibidores del CYP2D6: En publicaciones científicas se han descrito interacciones farmacocinéticas con inhibidores del CYP2D6, mostrando una reducción del 65-75% en los niveles plasmáticos de una de…»
AEMPS, section 4.5 · Open on CIMA
Majorinhibidores del CYP2D6class named in the label
«Inhibidores del CYP2D6: En publicaciones científicas se han descrito interacciones farmacocinéticas con inhibidores del CYP2D6, mostrando una reducción del 65-75% en los niveles plasmáticos de una de…»
AEMPS, section 4.5 · Open on CIMA
MajorParoxetine
«Inhibidores del CYP2D6: En publicaciones científicas se han descrito interacciones farmacocinéticas con inhibidores del CYP2D6, mostrando una reducción del 65-75% en los niveles plasmáticos de una de…»
AEMPS, section 4.5 · Open on CIMA
MajorQuinidine
«Inhibidores del CYP2D6: En publicaciones científicas se han descrito interacciones farmacocinéticas con inhibidores del CYP2D6, mostrando una reducción del 65-75% en los niveles plasmáticos de una de…»
AEMPS, section 4.5 · Open on CIMA
Moderateanticoagulantesclass named in the label
«Anticoagulantes tipo cumarínicos: Cuando se administra tamoxifeno en combinación con anticoagulantes tipo cumarínicos, puede presentarse un incremento significativo del efecto anticoagulante, por lo…»
AEMPS, section 4.5 · Open on CIMA
Moderateanticoagulantsclass named in the label
«Drug Interactions:: When tamoxifen citrate is used in combination with coumarin-type anticoagulants, a significant increase in anticoagulant effect may occur. Where such coadministration exists…»
FDA, section 7 · Open on DailyMed
ModerateISRSclass named in the label
«Inhibidores del CYP2D6: En publicaciones científicas se han descrito interacciones farmacocinéticas con inhibidores del CYP2D6, mostrando una reducción del 65-75% en los niveles plasmáticos de una de…»
AEMPS, section 4.5 · Open on CIMA
ModerateLetrozole
«Drug Interactions:: Tamoxifen reduced letrozole plasma concentrations by 37%. The effect of tamoxifen on metabolism and excretion of other antineoplastic drugs, such as cyclophosphamide and other…»
FDA, section 7 · Open on DailyMed
Moderatemedicamentos que prolongan el QTclass named in the label
«Medicamentos que prolongan el intervalo QT: Tamoxifeno a la dosis recomendada puede prolongar el intervalo QTc en el electrocardiograma (ECG), y el uso concomitante de tamoxifeno con otros…»
AEMPS, section 4.5 · Open on CIMA
ModerateRifampicin
«Citocromo P4503A4: La principal ruta para el metabolismo de tamoxifeno es mediante el citocromo P4503A4. Se requiere precaución cuando se administra en combinación con medicamentos como la…»
AEMPS, section 4.5 · Open on CIMA
Anastrozole
«Drug Interactions:: Based on clinical and pharmacokinetic results from the anastrozole adjuvant trial, tamoxifen citrate should not be administered with anastrozole (see CLINICAL PHARMACOLOGY – Drug-…»
FDA, section 7 · Open on DailyMed
antineoplásicosclass named in the label
«Agentes citotóxicos: Cuando se emplea tamoxifeno en combinación con agentes citotóxicos para el tratamiento de cáncer de mama existe un mayor riesgo de aparición de efectos adversos tromboembólicos…»
AEMPS, section 4.5 · Open on CIMA
Bromocriptine
«Drug Interactions:: Concomitant bromocriptine therapy has been shown to elevate serum tamoxifen and N-desmethyl tamoxifen.»
FDA, section 7 · Open on DailyMed
Phenobarbital
«Drug Interactions:: One patient receiving tamoxifen citrate with concomitant phenobarbital exhibited a steady state serum level of tamoxifen lower than that observed for other patients (i.e., 26…»
FDA, section 7 · Open on DailyMed

From other drugs’ labels

CriticalAnastrozole
«DRUG INTERACTIONS: Tamoxifen: Do not use in combination with anastrozole tablets. No additional benefit seen over tamoxifen monotherapy ( 7.1 , 14.1 )»
FDA, section 7 · Open on DailyMed
MajorAnastrozole
«Debe evitarse la co-administración de tamoxifeno o terapias que incluyan estrógeno con anastrozol, ya que esto puede disminuir su acción farmacológica (ver sección 4.4 y 5.1).»
AEMPS, section 4.5 · Open on CIMA
MajorBupropion
«Interacciones (ver sección 4.5): Datos de la literatura indican que los medicamentos que inhiben el CYP2D6 pueden producir una concentración reducida de endoxifeno que es el metabolito activo de…»
AEMPS, section 4.4 · Open on CIMA
MajorBupropion
«Potential for Bupropion Hydrochloride Extended-Release Tablets (SR) to Affect Other Drugs: Drugs Metabolized by CYP2D6 Bupropion and its metabolites (erythrohydrobupropion, threohydrobupropion…»
FDA, section 7 · Open on DailyMed
MajorFluoxetine
«Tamoxifeno : Existen publicaciones que documentan la interacción farmacocinética entre inhibidores de CYP2D6 y tamoxifeno, mostrando una reducción del 65-75% en los niveles plasmáticos de uno de los…»
AEMPS, section 4.5 · Open on CIMA
MajorLetrozole
«No existe experiencia clínica hasta la fecha sobre el uso de letrozol en combinación con estrógenos u otros agentes anticancerosos, aparte de tamoxifeno. El tamoxifeno, otros antiestrógenos o…»
AEMPS, section 4.5 · Open on CIMA
MajorParoxetine
«Inhibición del isoenzima CYP2D6: En la literatura se ha notificado una interacción farmacocinética entre inhibidores de CYP2D6 y tamoxifeno que muestra una reducción del 65-75% en los niveles…»
AEMPS, section 4.5 · Open on CIMA
MajorParoxetine
«DRUG INTERACTIONS: Concomitant use with tamoxifen: Consider use of an alternative antidepressant with little or no CYP2D6 inhibition. ( 5.11 , 7 )»
FDA, section 7 · Open on DailyMed
ModerateHydroxyzine
«Sustratos de CYP2D6: codeína, dextrometorfano, flecainida, mexiletina, ondansetron, tamoxifeno, el tramadol.»
AEMPS, section 4.5 · Open on CIMA
Letrozole
«DRUG INTERACTIONS: Tamoxifen»
FDA, section 7 · Open on DailyMed
Levothyroxine sodium
«Drugs Known to Affect Thyroid Hormone Pharmacokinetics: Clofibrate Estrogen-containing oral contraceptives Estrogens (oral) Heroin / Methadone 5-Fluorouracil Mitotane Tamoxifen These drugs may…»
FDA, section 7 · Open on DailyMed
Rifampicin
«antagonistas hormonales (antiestrógenos, p. ej., tamoxifeno, toremifeno, gestinona),»
AEMPS, section 4.5 · Open on CIMA
Tacrolimus
«Recomendaciones relativas a la a dministración simultánea: In vitro , se ha demostrado que las siguientes sustancias son potenciales inhibidores del metabolismo de tacrólimus: bromocriptina…»
AEMPS, section 4.5 · Open on CIMA
Warfarin
«Inhibidores enzimáticos: pueden potenciar el efecto anticoagulante, con riesgo de hemorragias, debido a una inhibición de su metabolismo hepático, cuando se administra conjuntamente con: alopurinol…»
AEMPS, section 4.5 · Open on CIMA

Check interaction with another drug

Opens the checker prefilled with this drug. Pick the second one from your regimen.

Open checker

Summary of a multi-drug list →

Medicine list: everything you take in one place →

Frequently asked

What is Tamoxifen used for?

Tamoxifen is evaluated for the following indications with varying evidence strength: ER-positive breast cancer (evidence tier A), Athletic endurance (evidence tier F). See the full indication matrix with dosing and citations above on this page.

What are the side effects of Tamoxifen?

Common side effects of Tamoxifen (≥ 1 in 100): Hot flashes and night sweats, Vaginal bleeding and discharge, Weight gain, Fatigue, Nausea, Reduced libido. See the Safety section for uncommon and serious reactions.

Is Tamoxifen safe during pregnancy?

Is Tamoxifen compatible with breastfeeding?

Contraindicated during lactation – suppresses milk production.

Who should not take Tamoxifen?

Tamoxifen is contraindicated in: Tamoxifen hypersensitivity; Active thromboembolic disease; Pregnancy and lactation; Severe hepatic impairment; Concomitant strong CYP2D6 inhibitors (paroxetine, fluoxetine, bupropion). Full list in the Safety section.

Does Tamoxifen carry an FDA boxed warning?

FDA boxed warning: increased risk of endometrial cancer, stroke, and venous thromboembolism. In women with risk factors, decisions are individualized.

Official sources

Direct links to regulator labels. Open in a new tab.

AEMPS / CIMALabel dated 05/18/2026
FDA / DailyMedLabel dated 04/30/2026

Other drugs in this group

Abiraterone, Anastrozole, Bicalutamide, Exemestane, Letrozole