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Raloxifene (SERMs)

Evista

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Meta Information

ID:raloxifene
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/history-of-vte
Target name:
History of Venous Thromboembolism (VTE)
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Raloxifene significantly increases the risk of blood clots, including deep vein thrombosis (DVT) and pulmonary embolism (PE).
Actionable advice:
This should be strictly avoided with a personal history of blood clots.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Exact phrase from label:
(4.2, 8.1, 8.3) 4.1 Venous Thromboembolism Raloxifene HCl, USP is contraindicated in women with active or past history of venous thromboembolism (VTE), including deep vein thrombosis, pulmonary embolism and retinal vein thrombosis [see Warnings and Precautions (5.1) ] .
Label source:
Action type:
avoid
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:
Raloxifene can cause fetal harm and is classified as Pregnancy Category X.
Actionable advice:
This should be strictly avoided during pregnancy.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Exact phrase from label:
4.2 Pregnancy Raloxifene hydrochloride is contraindicated for use in pregnancy, as it may cause fetal harm [see Use in Specific Populations (8.1)].
Label source:
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 raloxifene is excreted in human milk, but it could potentially harm the nursing infant.
Actionable advice:
It should be avoided completely while breastfeeding.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Exact phrase from label:
Because many drugs are excreted in human milk, caution should be exercised when raloxifene is administered to a nursing woman.
Label source:
Action type:
avoid
Target id:
/condition/history-of-stroke
Target name:
History of Stroke
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
In women with coronary heart disease or at high risk for it, raloxifene was associated with an increased risk of death due to stroke.
Actionable advice:
This should be strictly avoided with a history of stroke or transient ischemic attack (TIA).
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Exact phrase from label:
5.2 Death Due to Stroke In a clinical trial of postmenopausal women with documented coronary heart disease or at increased risk for coronary events, an increased risk of death due to stroke was observed after treatment with raloxifene hydrochloride tablets.
Label source:
Action type:
avoid
Target id:
/procedure/prolonged-immobilization
Target name:
Prolonged Immobilization (e.g., Major Surgery, Bed Rest)
Severity:
major
Interaction type:
adverse
Nature:
temporal
Temporal spacing:
Hours before target:
72
Hours after target:
null
Description:
Periods of prolonged immobilization significantly increase the risk of blood clots, which is compounded by raloxifene.
Actionable advice:
This 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:
Exact phrase from label:
Because immobilization increases the risk for venous thromboembolic events independent of therapy, raloxifene HCl should be discontinued at least 72 hours prior to and during prolonged immobilization (e.g., post-surgical recovery, prolonged bed rest) and raloxifene HCl therapy should be resumed only after the patient is fully ambulatory.
Label source:
Action type:
avoid
Target id:
/intervention/travel
Target name:
Long-Haul Travel
Severity:
major
Interaction type:
adverse
Nature:
temporal
Temporal spacing:
Hours before target:
72
Hours after target:
null
Description:
Long periods of sitting during travel increase the risk of blood clots, a risk that is amplified by raloxifene.
Actionable advice:
Raloxifene raises clot risk during immobility. For long-haul travel, discuss pausing it ~72 hours beforehand with your prescriber, and stay mobile and hydrated during the trip.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Exact phrase from label:
In addition, women taking raloxifene HCl should be advised to move about periodically during prolonged travel.
Label source:
Action type:
separate
Target id:
/class/bile-acid-sequestrants
Target name:
Bile Acid Sequestrants (e.g., Cholestyramine)
Severity:
major
Interaction type:
diminishing
Nature:
temporal
Temporal spacing:
Hours before target:
4
Hours after target:
4
Description:
Bile acid sequestrants can bind to raloxifene in the gut, significantly reducing its absorption and effectiveness.
Actionable advice:
Administration of raloxifene 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:
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:
/class/estrogens
Target name:
Systemic Estrogens (Hormone Replacement Therapy)
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Concurrent use is not recommended as it may increase the risk of adverse effects like blood clots and endometrial changes, without established benefits.
Actionable advice:
Raloxifene should not be taken concurrently with systemic estrogen-containing medications.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
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:
/condition/hepatic-impairment
Target name:
Severe Liver Disease
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Raloxifene is metabolized by the liver; severe impairment can lead to significantly increased drug levels and risk of side effects.
Actionable advice:
Use should be avoided in cases of severe hepatic impairment or cholestasis.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Exact phrase from label:
The pharmacokinetics of raloxifene has not been studied in patients with moderate or severe hepatic impairment.
Label source:
Action type:
avoid
Target id:
/intervention/levothyroxine
Target name:
Levothyroxine
Severity:
moderate
Interaction type:
diminishing
Nature:
temporal
Temporal spacing:
Hours before target:
2
Hours after target:
2
Description:
Raloxifene may reduce the absorption of levothyroxine from the gut, potentially leading to undertreatment of thyroid conditions.
Actionable advice:
Administration of raloxifene and levothyroxine should be separated by at least 2 hours.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
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 et al., Arch Intern Med (2003), PMID 12796075. Raloxifene caused malabsorption of levothyroxine; monitor and separate doses. FLAG: single case report.
Action type:
separate
Target id:
/intervention/warfarin
Target name:
Warfarin
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Raloxifene can cause a small decrease in prothrombin time (PT), which may alter the anticoagulant effect of warfarin.
Actionable advice:
PT/INR is best monitored closely if these medications must be taken together.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Exact phrase from label:
(7.1, 12.3) Warfarin: Monitor prothrombin time when starting or stopping raloxifene HCl.
Label source:
Action type:
monitor
Target id:
/condition/renal-impairment
Target name:
Severe Kidney Disease
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
In severe renal impairment (CrCl <30 mL/min), raloxifene concentrations may increase, warranting caution.
Actionable advice:
This is best used with caution and under medical supervision in severe renal impairment.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Exact phrase from label:
When a single dose of 120 mg raloxifene HCl was administered to 10 renally impaired males [7 moderate impairment (CrCl = 31 to 50 mL/min); 3 severe impairment (CrCl ≤30 mL/min)] and to 10 healthy males (CrCl >80 mL/min), plasma raloxifene concentrations were 122% (AUC 0-∞ ) higher in renally impaired patients than those of healthy volunteers.
Label source:
Action type:
informational_none
Target id:
/intervention/vitamin-d
Target name:
Vitamin D
Severity:
moderate
Interaction type:
requirement
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
The bone-strengthening effects of raloxifene depend on having sufficient levels of vitamin D for calcium absorption and bone metabolism.
Actionable advice:
It is a good idea to maintain adequate daily intake of Vitamin D, as recommended by a physician.
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:
Supportive-care inference: raloxifene's bone benefit depends on adequate calcium/vitamin D status for mineralization; the Evista label recommends adequate calcium and vitamin D intake. Complementary supportive care, 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:
requirement
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Raloxifene helps direct calcium to the bones, but it cannot work effectively without an adequate supply of calcium.
Actionable advice:
It is a good idea to maintain adequate daily intake of calcium from diet or supplements.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
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:
/dietary/meal
Target name:
Any Caloric Meal
Severity:
minor
Interaction type:
informational
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Raloxifene's absorption is only minorly increased by food (~16%), thus offering flexibility in administration with or without a meal.
Actionable advice:
You can take raloxifene at any time of day, with or without food.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Exact phrase from label:
Administration of raloxifene HCl with a standardized, high-fat meal increases the absorption of raloxifene (C max 28% and AUC 16%), but does not lead to clinically meaningful changes in systemic exposure.
Label source:
Action type:
informational_none
Target id:
/biomarker/lipid-panel
Target name:
Lipid Panel
Severity:
minor
Interaction type:
assay_interference
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Raloxifene can beneficially decrease total and LDL cholesterol while slightly increasing HDL cholesterol, which affects the interpretation of lipid panel results.
Actionable advice:
It is generally best to let the interpreting physician know about raloxifene use when reviewing lipid results.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Exact phrase from label:
Women with this medical history should have serum triglycerides monitored when taking raloxifene HCl.
Label source:
Action type:
monitor
Target id:
/biomarker/thyroid-panel
Target name:
Thyroid Panel
Severity:
minor
Interaction type:
assay_interference
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Raloxifene can increase the concentration of thyroxine-binding globulin (TBG), leading to higher measured total T3 and T4 levels, though free hormone levels are typically unaffected.
Actionable advice:
Focus on TSH and free T4/T3 levels for accurate thyroid assessment.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
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 caused malabsorption of levothyroxine; monitor thyroid panel and separate doses. FLAG: single case report.
Action type:
monitor
Target id:
/biomarker/comprehensive-sex-hormone-panel
Target name:
Comprehensive Sex Hormone Panel
Severity:
minor
Interaction type:
assay_interference
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Raloxifene increases Sex Hormone-Binding Globulin (SHBG) levels, which can alter the total concentrations of sex hormones like testosterone and estradiol.
Actionable advice:
Consider measuring free or bioavailable hormone levels for a more accurate assessment.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Exact phrase from label:
These results are consistent with findings in clinical trials, which suggest that raloxifene HCl lacks estrogen-like effects on the uterus and breast tissue.
Label source:
Action type:
monitor
Target id:
/class/highly-protein-bound-drugs
Target name:
Other Highly Protein-Bound Drugs (e.g., Diazepam, Lidocaine)
Severity:
minor
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
There is a theoretical risk that raloxifene, which is highly protein-bound, could displace other protein-bound drugs, increasing their free concentration.
Actionable advice:
This theoretical interaction is worth keeping in mind, though it is not considered clinically significant for most drugs.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Exact phrase from label:
Other Highly Protein-Bound Drugs - In the osteoporosis treatment trial, there were no clinically relevant effects of co-administration of other highly protein-bound drugs (e.g., gemfibrozil) on plasma concentrations of raloxifene.
Label source:
Action type:
informational_none