Meta Information
ID:inclisiran
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/statins
Target name:
Statins (HMG-CoA Reductase Inhibitors)
Severity:
major
Interaction type:
synergistic
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Statins increase the number of LDL receptors on liver cells, while inclisiran prevents the breakdown of these receptors. This dual mechanism leads to a powerful, synergistic reduction in LDL cholesterol.
Actionable advice:
This is best used in combination with a statin, as prescribed, for maximal LDL-lowering benefit.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
did not have a clinically significant impact on atorvastatin or rosuvastatin concentrations
Label source:
FDA label: Inclisiran (Leqvio)
Action type:
informational_none
Target id:
/intervention/ezetimibe
Target name:
Ezetimibe
Severity:
moderate
Interaction type:
synergistic
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Ezetimibe reduces cholesterol absorption from the gut, which signals the liver to increase LDL receptors. Inclisiran enhances this effect by preventing receptor breakdown, providing an additional LDL-lowering effect.
Actionable advice:
Can be effectively combined with ezetimibe for further LDL cholesterol reduction.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Fifty-two percent (52%) of patients were treated with ezetimibe
Label source:
FDA label: Inclisiran (Leqvio)
Action type:
informational_none
Target id:
/intervention/bempedoic-acid
Target name:
Bempedoic Acid
Severity:
moderate
Interaction type:
synergistic
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Bempedoic acid inhibits cholesterol synthesis in the liver upstream of statins, leading to an increase in LDL receptors. This effect is complementary to inclisiran's mechanism, resulting in enhanced LDL lowering.
Actionable advice:
May be used in combination with bempedoic acid for an additive LDL-lowering effect, especially in statin-intolerant patients.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
LEQVIO® is indicated as an adjunct to diet and exercise to reduce low-density lipoprotein cholesterol (LDL-C)
Label source:
FDA label: Inclisiran (Leqvio)
Action type:
informational_none
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:
Cholesterol is essential for normal fetal development. All lipid-lowering therapies, including inclisiran, are generally contraindicated during pregnancy due to theoretical risks to the fetus.
Actionable advice:
This should be strictly avoided during pregnancy and discontinued before attempting to conceive.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Discontinue LEQVIO when pregnancy is recognized
Label source:
FDA label: Inclisiran (Leqvio)
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 unknown if inclisiran is present in human milk or what its effects might be on a nursing infant. Due to the potential for adverse effects, it is contraindicated during breastfeeding.
Actionable advice:
This 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:
8.2 Lactation
Label source:
FDA label: Inclisiran (Leqvio)
Action type:
avoid
Target id:
/condition/hepatic-impairment
Target name:
Severe Hepatic Impairment
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Inclisiran has not been studied in patients with severe liver disease (Child-Pugh class C). Its safety and efficacy in this population are unknown, and caution is advised as the liver is its site of action.
Actionable advice:
This is best used with caution and under specialist supervision in severe liver disease, where it may be contraindicated.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
LEQVIO has not been studied in patients with severe hepatic impairment
Label source:
FDA label: Inclisiran (Leqvio)
Action type:
avoid
Target id:
/intervention/mediterranean-diet
Target name:
Heart-Healthy Diet (e.g., Mediterranean, DASH)
Severity:
moderate
Interaction type:
synergistic
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
A diet low in saturated/trans fats and high in fiber supports the LDL-lowering goals of inclisiran therapy, leading to better overall cardiovascular outcomes.
Actionable advice:
Adopt a heart-healthy diet to complement the medication's effects and improve cardiovascular health.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
LEQVIO® is indicated as an adjunct to diet and exercise to reduce low-density lipoprotein cholesterol (LDL-C)
Label source:
FDA label: Inclisiran (Leqvio)
Action type:
informational_none
Target id:
/dietary/high-fat-meal
Target name:
Diet High in Saturated and Trans Fats
Severity:
moderate
Interaction type:
diminishing
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Consuming a diet high in saturated and trans fats actively raises LDL cholesterol, which directly counteracts the therapeutic effect and goal of inclisiran treatment.
Actionable advice:
Diets high in saturated and trans fats are best avoided, as they work against the medication's intended purpose.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
LEQVIO is not expected to cause drug-drug interactions or to be affected by inhibitors or inducers of cytochrome P450 enzymes
Label source:
FDA label: Inclisiran (Leqvio)
Action type:
avoid
Target id:
/biomarker/apolipoprotein-b
Target name:
Apolipoprotein B (ApoB) and LDL-C
Severity:
major
Interaction type:
synergistic
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Inclisiran is designed to potently lower levels of LDL cholesterol and its primary carrier protein, ApoB. Monitoring these biomarkers is essential to confirm the drug is working as intended.
Actionable advice:
Regularly monitor ApoB and LDL-C levels to confirm the therapeutic efficacy of the treatment.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
ApoB = apolipoprotein B
Label source:
FDA label: Inclisiran (Leqvio)
Action type:
monitor
Target id:
/biomarker/alanine-aminotransferase
Target name:
Liver Enzymes (ALT/AST)
Severity:
minor
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Inclisiran can cause mild, temporary increases in liver enzymes (transaminases) in a small percentage of patients, though this is rarely clinically significant.
Actionable advice:
It is a good idea to check liver function tests periodically as recommended by a physician.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
LEQVIO has not been studied in patients with severe hepatic impairment
Label source:
FDA label: Inclisiran (Leqvio)
Action type:
monitor
Target id:
/class/cyp3a4-substrates
Target name:
Drugs Metabolized by Cytochrome P450 Enzymes
Severity:
minor
Interaction type:
synergistic
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Inclisiran is an siRNA therapeutic not metabolized by the cytochrome P450 system, meaning it does not have clinically significant pharmacokinetic interactions with the vast majority of other drugs.
Actionable advice:
No dose adjustments are needed for other medications based on metabolic pathways, simplifying co-administration.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
LEQVIO is not expected to cause drug-drug interactions or to be affected by inhibitors or inducers of cytochrome P450
Label source:
FDA label: Inclisiran (Leqvio)
Action type:
adjust_with_prescriber