Meta Information
ID:ezetimibe
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:
/class/bile-acid-sequestrants
Target name:
Bile Acid Sequestrants
Severity:
major
Interaction type:
diminishing
Nature:
temporal
Temporal spacing:
Hours before target:
2
Hours after target:
4
Description:
Bile acid sequestrants (e.g., cholestyramine, colestipol) bind to ezetimibe in the intestine, preventing its absorption and significantly reducing its effectiveness.
Actionable advice:
Ezetimibe should be taken at least 2 hours before or 4 hours after a bile acid sequestrant.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
• Administer ezetimibe tablets at least 2 hours before or 4 hours after administration of a bile acid sequestrant [see Drug Interactions ( 7 )] .
Label source:
Action type:
separate
Target id:
/class/fibrates
Target name:
Fibrates
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Combining ezetimibe with fibrates (especially gemfibrozil) increases the concentration of cholesterol in the bile, significantly raising the risk of developing gallstones (cholelithiasis).
Actionable advice:
Co-administration with gemfibrozil should be avoided; use with fenofibrate requires caution and medical supervision.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Fibrates may increase cholesterol excretion into the bile, leading to cholelithiasis.
Label source:
Action type:
avoid
Target id:
/class/immunosuppressants
Target name:
Cyclosporine (Calcineurin Inhibitor)
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Cyclosporine significantly increases the concentration of ezetimibe in the blood, and ezetimibe can slightly increase cyclosporine levels, raising the risk of side effects for both drugs.
Actionable advice:
Co-administration should be avoided; if necessary, it requires close medical supervision and dose adjustments.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Cyclosporine concentrations should be monitored in patients taking ezetimibe concomitantly.
Label source:
Action type:
avoid
Target id:
/condition/hepatic-impairment
Target name:
Moderate to Severe Liver Disease
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
In people with moderate to severe liver disease, the body's ability to process ezetimibe is impaired, leading to significantly increased drug levels and unknown safety risks.
Actionable advice:
Ezetimibe should not be used by people with moderate to severe liver disease.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Statin contraindications apply when ezetimibe is used with a statin: Active liver disease, which may include unexplained persistent elevations in hepatic transaminase levels ( 4 , 5.2 ) Women who are pregnant or may become pregnant ( 4, 8.1 ) Nursing mothers ( 4, 8.3 ) Known hypersensitivity to product components ( 4, 6.2)
5 WARNINGS AND PRECAUTIONS Ezetimibe is not recommended in patients with moderate or severe hepatic impairment.
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:
The safety of ezetimibe during pregnancy has not been established, and it is generally not recommended due to potential risks to the fetus.
Actionable advice:
Ezetimibe should not be used during pregnancy or when planning to become pregnant.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Ezetimibe should be used during pregnancy only if the potential benefit justifies the risk to the fetus.
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 ezetimibe passes into breast milk; therefore, its use is generally not recommended while breastfeeding to avoid potential risk to the infant.
Actionable advice:
Ezetimibe should not be used while breastfeeding.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Because statins may pass into breast milk, and because statins have the potential to cause serious adverse reactions in nursing infants, women who require ezetimibe tablets treatment in combination with a statin should be advised not to nurse their infants [see Use in Specific Populations (8.3) ].
Label source:
Action type:
avoid
Target id:
/class/statins
Target name:
Statins (HMG-CoA Reductase Inhibitors) (Mechanism Synergy)
Severity:
major
Interaction type:
synergistic
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Ezetimibe inhibits cholesterol absorption from the gut while statins inhibit cholesterol production in the liver, providing a powerful dual mechanism for lowering LDL cholesterol.
Actionable advice:
It should be taken as prescribed with a statin for enhanced cholesterol-lowering effects.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Because statins decrease cholesterol synthesis and possibly the synthesis of other biologically active substances derived from cholesterol, ezetimibe tablets in combination with a statin may cause fetal harm when administered to pregnant women.
Label source:
Action type:
informational_none
Target id:
/biomarker/lipid-panel
Target name:
Lipid Panel (LDL-C, ApoB)
Severity:
major
Interaction type:
requirement
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Regular monitoring of your lipid panel is essential to assess the effectiveness of ezetimibe in lowering cholesterol levels.
Actionable advice:
The lipid panel should be checked 4-12 weeks after starting therapy and then periodically thereafter.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
12.2 Pharmacodynamics Ezetimibe Tablet reduces total cholesterol (total-C), LDL-C, apolipoprotein (Apo) B, and non-high-density lipoprotein cholesterol (non-HDL-C) in patients with hyperlipidemia.
Label source:
Action type:
monitor
Target id:
/class/anticoagulants-antiplatelets
Target name:
Warfarin and other Vitamin K Antagonists
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Ezetimibe may enhance the anticoagulant effect of warfarin, leading to an increased International Normalized Ratio (INR) and a higher risk of bleeding.
Actionable advice:
INR should be monitored closely when starting, stopping, or changing the dose of ezetimibe.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
7.5 Coumarin Anticoagulants If ezetimibe is added to warfarin, a coumarin anticoagulant, the International Normalized Ratio (INR) should be appropriately monitored.
Label source:
Action type:
monitor
Target id:
/biomarker/alanine-aminotransferase
Target name:
Liver Enzymes (ALT/AST)
Severity:
moderate
Interaction type:
requirement
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Ezetimibe, particularly when used with a statin, can rarely cause elevations in liver enzymes, indicating potential liver stress or injury.
Actionable advice:
Obtain baseline liver function tests before starting and monitor as recommended by your doctor.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
( 5.4 , 8.7 , 12.3 ) Liver enzyme abnormalities and monitoring: Persistent elevations in hepatic transaminase can occur when ezetimibe is added to a statin.
Label source:
Action type:
monitor
Target id:
/class/antacids
Target name:
Antacids (Aluminum/Magnesium)
Severity:
minor
Interaction type:
diminishing
Nature:
temporal
Temporal spacing:
Hours before target:
2
Hours after target:
2
Description:
Antacids containing aluminum and magnesium can slightly decrease the rate of ezetimibe absorption, though the overall amount absorbed is not significantly affected.
Actionable advice:
For maximum consistency, ezetimibe and antacids are best separated by at least 2 hours.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Exact phrase from label:
Antacids: In a study of twelve healthy adults, a single dose of antacid (SupraloxTM 20 mL)
Label source:
FDA label: Ezetimibe (Zetia) — Drug Interactions: Antacids
Action type:
separate
Target id:
/intervention/red-yeast-rice
Target name:
Red Yeast Rice
Severity:
minor
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Red yeast rice contains monacolin K, a naturally occurring statin, which when combined with ezetimibe may increase the risk of muscle-related side effects (myopathy).
Actionable advice:
Exercise caution and report any muscle pain if combining ezetimibe with red yeast rice.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Once asymptomatic and CK is reduced (if elevated previously), cholesterol goals can be approached by: 1) a different statin (e.g. fluvastatin or pravastatin), starting with a low dose and titrating up; 2) an alternate daily or weekly more potent statin (e.g. rosuvastatin or atorvastatin); or 3) the combination of the lowest tolerated statin with a cholesterol absorption inhibitor (ezetimibe) and/or bile acid sequestrant. Over-the-counter preparations, e.g. red yeast rice, containing natural statin-like agents, or plant sterols can also lower cholesterol.
Label source:
PubMed: Approach to the patient who is intolerant of statin therapy. (PMID 20444930)
Action type:
monitor
Target id:
/dietary/meal
Target name:
Any Caloric Meal
Severity:
minor
Interaction type:
informational
Nature:
temporal
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
The absorption of ezetimibe is not significantly affected by food, making it convenient to take at any time of day, with or without a meal.
Actionable advice:
Ezetimibe is generally best taken at a consistent time each day, either with or without food.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Effect of Food Concomitant food administration (high-fat or non-fat meals) had no effect on the extent of absorption of ezetimibe when administered as ezetimibe tablets 10-mg tablets.
Label source:
Action type:
informational_none