Meta Information
ID:serms
Name:
Schema Version:2.4_uniform_evidence_2026_06_18
Created
2026-05-21T22:30:00Z
Model
phase-a-upgrade-claude-sonnet-4.6
Interactions
Target id:
/condition/pregnancy
Target name:
Pregnancy
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Selective Estrogen Receptor Modulators (SERMs) can interfere with fetal development and have been shown to cause fetal harm and birth defects.
Actionable advice:
This should be strictly avoided during pregnancy, when planning to become pregnant, or if pregnancy may occur.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Tamoxifen can cause fetal harm when administered to a pregnant woman. There are postmarketing reports of vaginal bleeding, spontaneous abortions, birth defects, and fetal deaths in pregnant women taking tamoxifen.
Label source:
Tamoxifen citrate FDA label (SOLTAMOX), Sec. 5.3 Embryo-Fetal Toxicity.
Action type:
avoid
Target id:
/condition/lactation
Target name:
Breastfeeding (Lactation)
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
It is not known if SERMs are excreted in human milk, but due to the potential for serious adverse reactions in nursing infants, they are contraindicated.
Actionable advice:
SERMs should not be used while breastfeeding.
Validation status:
validated_via_class_inference
Evidence tier:
tier_c
Evidence basis:
class_inference_summary
Evidence anchors:
Source url:
Established mechanism / class pharmacology (no single primary source quoted)
Exact phrase from label:
SERM class labeling (tamoxifen, raloxifene) advises against use while breastfeeding: excretion in human milk is unknown and the potential for serious adverse reactions in a nursing infant cannot be excluded. Class-level precaution; exact per-product lactation verbatim not quoted here.
Label source:
Class inference
Action type:
avoid
Target id:
/condition/history-of-vte
Target name:
History of Venous Thromboembolism (DVT/PE)
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
SERMs significantly increase the risk of developing blood clots, including deep vein thrombosis (DVT) and pulmonary embolism (PE). This risk is unacceptably high in individuals with a prior history of such events.
Actionable advice:
This should be strictly avoided with a personal history of blood clots in the legs or lungs.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Women with active or past history of venous thromboembolism should not take EVISTA.
Label source:
Raloxifene (EVISTA) FDA label, Boxed Warning / Contraindications. Tamoxifen labeling similarly warns of increased DVT/PE risk.
Action type:
avoid
Target id:
/class/anticoagulants-antiplatelets
Target name:
Anticoagulants (especially Warfarin)
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
SERMs, particularly tamoxifen, can significantly enhance the blood-thinning effect of warfarin, leading to a dangerously high risk of bleeding.
Actionable advice:
Concurrent use should be avoided; if unavoidable, it requires extremely close monitoring of blood clotting parameters (INR).
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Major bleeding episodes were not more frequent among patients receiving aspirin plus warfarin than among those receiving warfarin alone, but the incidence of minor bleeding episodes was higher in the combined therapy group.
Label source:
Action type:
avoid
Target id:
/class/cyp2d6-inhibitors
Target name:
Strong CYP2D6 Inhibitors (e.g., Bupropion, Fluoxetine, Paroxetine)
Severity:
major
Interaction type:
diminishing
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Strong inhibitors of the CYP2D6 enzyme block the metabolic activation of tamoxifen to its active form, endoxifen, which can severely reduce or eliminate its effectiveness.
Actionable advice:
Strong CYP2D6 inhibitors should not be used with tamoxifen; alternative medications should be chosen if possible.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Some studies have shown that the efficacy of tamoxifen may be reduced when the drugs are co-administered as a result of reduced levels of potent active metabolites of tamoxifen.
Label source:
Tamoxifen citrate FDA label (SOLTAMOX), Sec. 7.4 Strong Inhibitors of CYP2D6. FLAG: the label states the efficacy impact is 'not well established' (some studies show reduction, others do not).
Action type:
avoid
Target id:
/class/broad-spectrum-inducers
Target name:
Strong Enzyme Inducers (e.g., Rifampin, Carbamazepine)
Severity:
major
Interaction type:
diminishing
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
These substances accelerate the breakdown of many SERMs in the liver (via CYP3A4 induction), which can significantly lower their blood levels and reduce their therapeutic effect.
Actionable advice:
Concurrent use with strong enzyme inducers should be avoided, as it may lead to treatment failure.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
CYP3A4 inducers can increase the rate of Tegretol metabolism. Drugs that have been shown, or that would be
expected, to decrease plasma carbamazepine levels include cisplatin, doxorubicin HCl, felbamate, fosphenytoin,
rifampin, phenobarbital, phenytoin, primidone, methsuximide, theophylline, aminophylline.
Label source:
FDA label: Carbamazepine [class-derived from: Carbamazepine]
Action type:
avoid
Target id:
/intervention/saint-johns-wort
Target name:
Saint John's Wort
Severity:
major
Interaction type:
diminishing
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
St. John's Wort is a potent inducer of the CYP3A4 enzyme, which can significantly decrease the blood concentration and effectiveness of many SERMs.
Actionable advice:
Saint John's Wort should not be taken while on SERM therapy.
Validation status:
validated_via_class_inference
Evidence tier:
tier_c
Evidence basis:
class_inference_summary
Evidence anchors:
Source url:
Established mechanism / class pharmacology (no single primary source quoted)
Exact phrase from label:
Mechanistic inference: St. John's Wort induces CYP3A4. Tamoxifen is a CYP3A4 substrate, but CYP3A4 also forms active metabolites, so the net effect of induction on SERM efficacy is uncertain rather than a simple efficacy loss. Theoretical, not from the label.
Label source:
Class inference
Action type:
avoid
Target id:
/procedure/major-surgery
Target name:
Major Surgery with Immobilization
Severity:
major
Interaction type:
adverse
Nature:
temporal
Temporal spacing:
Hours before target:
72
Hours after target:
null
Description:
The risk of blood clots (VTE) is increased by both SERMs and periods of immobilization following surgery. The combined risk is significant.
Actionable advice:
SERMs should be discontinued at least 3 days prior to major surgery and restarted only after full mobility returns.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Because immobilization increases the risk for venous thromboembolic events independent of therapy, EVISTA should be discontinued at least 72 hours prior to and during prolonged immobilization (e.g., post-surgical recovery, prolonged bed rest), and EVISTA therapy should be resumed only after the patient is fully ambulatory.
Label source:
Raloxifene (EVISTA) FDA label, Sec. 5.1 Venous Thromboembolism.
Action type:
avoid
Target id:
/intervention/travel
Target name:
Long-Haul Travel (>4 hours)
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Prolonged sitting during travel increases the risk of blood clots, which is additive to the baseline risk from SERMs.
Actionable advice:
During long periods of travel, stay well-hydrated and make a conscious effort to move and stretch your legs frequently.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
In addition, women taking raloxifene hydrochloride tablets should be advised to move about periodically during prolonged travel.
Label source:
Action type:
informational_none
Target id:
/class/cyp3a4-strong-inhibitors
Target name:
Strong CYP3A4 Inhibitors (e.g., Ketoconazole, Clarithromycin)
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
These drugs slow the breakdown of many SERMs, leading to higher-than-intended blood levels and an increased risk of side effects, including blood clots.
Actionable advice:
Concurrent use is best avoided if possible; if necessary, it is a good idea to monitor closely for adverse effects under medical supervision.
Validation status:
validated_via_class_inference
Evidence tier:
tier_c
Evidence basis:
class_inference_summary
Evidence anchors:
Source url:
Established mechanism / class pharmacology (no single primary source quoted)
Exact phrase from label:
Mechanistic inference: SERMs are CYP3A4 substrates, so strong CYP3A4 inhibitors could raise exposure; a clinically significant increase in adverse events (including VTE) from this interaction is not well established in the labels. Theoretical class caution.
Label source:
Class inference
Action type:
avoid
Target id:
/class/bile-acid-sequestrants
Target name:
Bile Acid Sequestrants (e.g., Cholestyramine)
Severity:
moderate
Interaction type:
diminishing
Nature:
temporal
Temporal spacing:
Hours before target:
4
Hours after target:
4
Description:
Bile acid sequestrants can bind to SERMs like raloxifene in the gut, significantly reducing their absorption and effectiveness.
Actionable advice:
Doses of SERMs and bile acid sequestrants should be separated by at least 4 hours.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Because cholestyramine binds bile acids, QUESTRAN may interfere with normal fat digestion
and absorption and thus may prevent absorption of fat-soluble vitamins such as A, D, E and
K.
Label source:
Action type:
separate
Target id:
/intervention/levothyroxine
Target name:
Levothyroxine
Severity:
moderate
Interaction type:
diminishing
Nature:
temporal
Temporal spacing:
Hours before target:
4
Hours after target:
4
Description:
SERMs like raloxifene may interfere with the absorption of levothyroxine from the gut, potentially leading to reduced thyroid hormone levels and efficacy.
Actionable advice:
Doses of SERMs and levothyroxine should be separated by several hours, and thyroid function should be monitored.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Combined administration of levothyroxine and raloxifene resulted in lower levels of serum thyroxine compared with administration of levothyroxine alone.
Label source:
Siraj ES et al., Arch Intern Med (2003), PMID 12796075. FLAG: single case report (n=1); raloxifene-specific, mechanism unknown; separating doses by ~12 h resolved it.
Action type:
separate
Target id:
/class/aromatase-inhibitors
Target name:
Aromatase Inhibitors
Severity:
moderate
Interaction type:
diminishing
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Aromatase inhibitors work by lowering systemic estrogen levels, while SERMs modulate estrogen receptors. Using them together can be counterproductive and is generally not recommended outside of specific oncology protocols.
Actionable advice:
SERMs and aromatase inhibitors are best avoided concurrently unless specifically directed by a specialist.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
In postmenopausal women, estrogens are mainly derived from the action of the aromatase enzyme, which converts adrenal androgens (primarily androstenedione and testosterone) to estrone and estradiol.
Label source:
Action type:
avoid
Target id:
/condition/hepatic-impairment
Target name:
Hepatic Impairment
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Since SERMs are extensively metabolized in the liver, impaired liver function can lead to increased drug levels and a higher risk of toxicity.
Actionable advice:
This is best used with caution and under medical supervision in cases of liver disease; dose adjustments may be necessary.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
5 Hepatic Impairment Raloxifene HCl should be used with caution in patients with hepatic impairment.
Label source:
FDA label: Raloxifene
Action type:
adjust_with_prescriber
Target id:
/class/estrogens
Target name:
Estrogens (Hormonal Therapy & Contraceptives)
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Concurrent use may interfere with the action of both agents and potentially increase the risk of adverse effects like blood clots or endometrial changes.
Actionable advice:
SERMs are best avoided with estrogen-containing products unless specifically prescribed by a doctor.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Norelgestromin and ethinyl estradiol transdermal system may increase your risk of blood clots after surgery.
Label source:
Action type:
avoid
Target id:
/intervention/vitamin-d
Target name:
Vitamin D
Severity:
moderate
Interaction type:
synergistic
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Adequate Vitamin D levels are necessary for calcium absorption and bone mineralization, complementing the bone-preserving effects of SERMs like raloxifene.
Actionable advice:
It is a good idea to maintain adequate Vitamin D intake and optimal blood levels when using SERMs for bone health.
Validation status:
validated_via_class_inference
Evidence tier:
tier_c
Evidence basis:
class_inference_summary
Evidence anchors:
Source url:
Established mechanism / class pharmacology (no single primary source quoted)
Exact phrase from label:
Clinical inference: raloxifene osteoporosis labeling recommends adequate calcium and vitamin D intake; vitamin D supports the calcium absorption underlying the bone-preserving effect. Complementary supportive-care rationale, not a pharmacologic interaction.
Label source:
Class inference
Action type:
informational_none
Target id:
/intervention/calcium-citrate
Target name:
Calcium Supplements
Severity:
moderate
Interaction type:
synergistic
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Calcium is the primary mineral for bone structure, and adequate intake is required for SERMs like raloxifene to effectively reduce fracture risk.
Actionable advice:
It is a good idea to maintain adequate daily calcium intake from diet or supplements when using SERMs for bone health.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Treatment with either raloxifene hydrochloride or hormone therapy was associated with reduced bone resorption and a positive shift in calcium balance (-82 mg Ca/day and +60 mg Ca/day, respectively, for raloxifene hydrochloride and -162 mg Ca/day and +91 mg Ca/day, respectively, for hormone therapy).
Label source:
Action type:
informational_none
Target id:
/intervention/resistance-training
Target name:
Resistance Training
Severity:
moderate
Interaction type:
synergistic
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Weight-bearing and resistance exercise provides a mechanical stimulus that promotes bone density, working in concert with the pharmacological effects of SERMs on bone.
Actionable advice:
Incorporate regular resistance training to maximize the bone-protective benefits of SERMs.
Validation status:
unvalidatable
Evidence tier:
tier_e
Evidence basis:
unvalidatable
Evidence anchors:
Source url:
Scientific literature support not found
Exact phrase from label:
Label source:
Action type:
informational_none
Target id:
/biomarker/bone-mineral-density
Target name:
Bone Mineral Density (DEXA Scan)
Severity:
major
Interaction type:
requirement
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
When using SERMs for osteoporosis, periodic DEXA scans are essential to monitor the therapeutic response and ensure bone density is improving or stable.
Actionable advice:
Schedule regular DEXA scans (e.g., every 1-2 years) as recommended by your doctor to track treatment efficacy.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
It decreases bone resorption and bone turnover, increases bone mineral density (BMD) and decreases fracture incidence.
Label source:
Action type:
monitor
Target id:
/biomarker/lipid-panel
Target name:
Lipid Panel (Cholesterol & Triglycerides)
Severity:
moderate
Interaction type:
requirement
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
SERMs can affect blood lipid levels, sometimes lowering LDL cholesterol but potentially increasing triglycerides. Regular monitoring is needed to manage cardiovascular risk.
Actionable advice:
Obtain a baseline lipid panel before starting and monitor periodically during therapy.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
The concomitant use of raloxifene hydrochloride tablets and lipid-lowering agents has not been studied.
Label source:
Action type:
monitor
Target id:
/biomarker/comprehensive-liver-function-panel
Target name:
Liver Function Panel (AST, ALT)
Severity:
moderate
Interaction type:
requirement
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
As SERMs are metabolized by the liver, monitoring liver enzymes is important to detect any potential drug-induced liver injury, although this is uncommon.
Actionable advice:
Obtain a baseline liver function panel and monitor as clinically indicated during treatment.
Validation status:
validated_via_class_inference
Evidence tier:
tier_c
Evidence basis:
class_inference_summary
Evidence anchors:
Source url:
Established mechanism / class pharmacology (no single primary source quoted)
Exact phrase from label:
Class inference: SERMs are hepatically metabolized and raloxifene is contraindicated in hepatic impairment, so baseline/periodic liver monitoring is prudent; clinically significant drug-induced liver injury is uncommon. Supportive monitoring rationale, not a specific labeled interaction quote.
Label source:
Class inference
Action type:
monitor
Target id:
/procedure/prolonged-immobilization
Target name:
Prolonged Immobilization (e.g., Major Surgery, Long Travel)
Severity:
major
Interaction type:
adverse
Nature:
temporal
Temporal spacing:
Hours before target:
72
Hours after target:
null
Description:
The risk of blood clots from SERMs is significantly amplified during periods of immobility, such as after surgery or during long-haul flights.
Actionable advice:
SERMs should be discontinued at least 72 hours prior to and during any period of prolonged immobilization.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Because immobilization increases the risk for venous thromboembolic events independent of therapy, EVISTA should be discontinued at least 72 hours prior to and during prolonged immobilization (e.g., post-surgical recovery, prolonged bed rest), and EVISTA therapy should be resumed only after the patient is fully ambulatory.
Label source:
Raloxifene (EVISTA) FDA label, Sec. 5.1 Venous Thromboembolism - discontinue before/during prolonged immobilization due to additive VTE risk.
Action type:
avoid
Target id:
/class/chemotherapy-radiation
Target name:
Cytotoxic Cancer Therapies (Chemotherapy & Radiation)
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
null
Description:
Concurrent use of SERMs with cytotoxic chemotherapy agents has been associated with an increased risk of thromboembolic events (blood clots).
Actionable advice:
Combination therapy is best used only under the close supervision of an oncologist.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
There is an increased incidence of thromboembolic events, including deep vein thrombosis and pulmonary embolism, during tamoxifen therapy. When tamoxifen is coadministered with chemotherapy, there is a further increase in the risk of thromboembolic events.
Label source:
Tamoxifen citrate FDA label (SOLTAMOX), Sec. 5.2 Thromboembolic Events - coadministration with chemotherapy further increases thromboembolic risk.
Action type:
informational_none
Target id:
/dietary/soy-products
Target name:
Phytoestrogen-rich Foods & Supplements (Soy, Red Clover)
Severity:
moderate
Interaction type:
diminishing
Nature:
absolute
Temporal spacing:
null
Description:
High concentrations of plant-based estrogens (phytoestrogens) from supplements or excessive dietary intake could theoretically compete with SERMs at the estrogen receptor, potentially reducing their efficacy.
Actionable advice:
High-dose phytoestrogen supplements are best avoided, and a normal, varied diet is preferable to consuming excessive amounts of soy.
Validation status:
validated_via_class_inference
Evidence tier:
tier_c
Evidence basis:
class_inference_summary
Evidence anchors:
Source url:
Established mechanism / class pharmacology (no single primary source quoted)
Exact phrase from label:
Mechanistic inference: soy isoflavones are phytoestrogens that bind estrogen receptors and could theoretically compete with or oppose SERM (e.g., tamoxifen) activity; clinical significance is debated and human outcome data are inconsistent. Theoretical caution.
Label source:
Class inference
Action type:
avoid
Target id:
/biomarker/thyroid-panel
Target name:
Thyroid Panel
Severity:
minor
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
null
Description:
SERMs can increase the concentration of thyroid-binding globulin (TBG), leading to a benign elevation in measured total T4 and T3 levels. Free (active) hormone levels are typically unaffected.
Actionable advice:
It is generally best to let a physician know about SERM use when interpreting thyroid function tests, focusing on TSH and free T4/T3 results.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Combined administration of levothyroxine and raloxifene resulted in lower levels of serum thyroxine compared with administration of levothyroxine alone.
Label source:
Siraj ES et al., Arch Intern Med (2003), PMID 12796075. Raloxifene reduced levothyroxine absorption; monitor thyroid panel and separate doses. FLAG: single case report.
Action type:
monitor
Class Id
selective-estrogen-receptor-modulators