Meta Information
ID:simvastatin
Name:
Schema Version:2.4_uniform_evidence_2026_06_18
Created
2026-05-25T18:50:05.062584+00:00
Model
claude-sonnet-4.6-wave15-stub-rebuild
Interactions
Target id:
/class/cyp3a4-inhibitors
Target name:
Strong CYP3A4 Inhibitors
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Strong CYP3A4 inhibitors (itraconazole, ketoconazole, posaconazole, HIV PIs, etc.) markedly increase simvastatin exposure; combination contraindicated.
Actionable advice:
This combination should be avoided; if unavoidable, it should be managed under specialist supervision with intensive monitoring.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
5.3 Nelfinavir † 1250 mg BID for 14 days 20 mg QD for 28 days simvastatin acid ‡ simvastatin 6 6.2 Itraconazole
Label source:
FDA label: Simvastatin (ZOCOR)
Action type:
avoid
Target id:
/intervention/cyclosporine
Target name:
Cyclosporine
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Cyclosporine contraindicated with simvastatin due to markedly increased myopathy risk.
Actionable advice:
This combination should be avoided; if unavoidable, it should be managed under specialist supervision with intensive monitoring.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
( 4 , 5.1 ) Concomitant administration of gemfibrozil, cyclosporine, or danazol.
Label source:
FDA label: Simvastatin (ZOCOR)
Action type:
avoid
Target id:
/intervention/gemfibrozil
Target name:
Gemfibrozil
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Gemfibrozil contraindicated with simvastatin due to significantly increased myopathy/rhabdomyolysis risk.
Actionable advice:
This combination should be avoided; if unavoidable, it should be managed under specialist supervision with intensive monitoring.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
( 4 , 5.1 ) Concomitant administration of gemfibrozil, cyclosporine, or danazol.
Label source:
FDA label: Simvastatin (ZOCOR)
Action type:
avoid
Target id:
/intervention/amiodarone
Target name:
Amiodarone/Amlodipine/Ranolazine
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Amiodarone, amlodipine, and ranolazine require simvastatin dose limits (e.g., 20 mg/day).
Actionable advice:
This is best used with caution, and it is a good idea to monitor for clinical effect; dose adjustment or monitoring may be required.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
lipid-lowering drugs (other fibrates, ≥1 g/day of niacin, or, for patients with HoFH, lomitapide), amiodarone
Label source:
FDA label: Simvastatin (ZOCOR)
Action type:
adjust_with_prescriber
Target id:
/dietary/grapefruit
Target name:
Grapefruit Juice
Severity:
moderate
Interaction type:
pharmacokinetic
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Large quantities of grapefruit juice (>1 quart daily) inhibit CYP3A4 and increase simvastatin exposure.
Actionable advice:
Grapefruit and grapefruit juice are best avoided while on this medication.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Table 4 displays the effect of coadministered drugs or grapefruit juice on simvastatin systemic exposure [see DRUG INTERACTIONS ( 7 )] .
Label source:
FDA label: Simvastatin (ZOCOR)
Action type:
avoid
Target id:
/intervention/niacin
Target name:
Niacin
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Lipid-modifying doses of niacin (≥1 g/day) may increase risk of myopathy.
Actionable advice:
This is best used with caution, and it is a good idea to monitor for clinical effect; dose adjustment or monitoring may be required.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
gainst the potential risks of combinations: other lipid-lowering drugs (other fibrates, ≥1 g/day of niacin
Label source:
FDA label: Simvastatin (ZOCOR)
Action type:
adjust_with_prescriber
Target id:
/intervention/colchicine
Target name:
Colchicine
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Combination with colchicine may increase myopathy/rhabdomyolysis risk.
Actionable advice:
This is best used with caution, and it is a good idea to monitor for clinical effect; dose adjustment or monitoring may be required.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
ases of myopathy, including rhabdomyolysis, have been reported with simvastatin coadministered with colchicine
Label source:
FDA label: Simvastatin (ZOCOR)
Action type:
adjust_with_prescriber
Target id:
/adverse/myopathy-rhabdomyolysis
Target name:
Myopathy / Rhabdomyolysis
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Simvastatin can cause myopathy and rhabdomyolysis; risk is dose-related and increased with interacting drugs.
Actionable advice:
Unexplained muscle pain, tenderness, weakness, or dark urine should be reported immediately; this may require CK measurement and drug discontinuation.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Rare cases of rhabdomyolysis with acute renal failure secondary to myoglobinuria have been reported.
Label source:
FDA label: Simvastatin (ZOCOR)
Action type:
monitor
Target id:
/adverse/hepatotoxicity
Target name:
Hepatic Effects
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Elevations in transaminases reported; monitor as clinically indicated.
Actionable advice:
Liver enzymes should be monitored per label, and it is worth reporting jaundice, dark urine, or persistent fatigue.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
( 5.1 ) Liver enzyme abnormalities: Persistent elevations in hepatic transaminases can occur.
Label source:
FDA label: Simvastatin (ZOCOR)
Action type:
monitor
Target id:
/condition/pregnancy
Target name:
Pregnancy
Severity:
major
Interaction type:
contraindication
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Discontinue simvastatin when pregnancy is recognized.
Actionable advice:
Use should be avoided during pregnancy unless the benefit clearly outweighs the risk, and it is worth discussing with a prescriber.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Women who are pregnant or may become pregnant.
Label source:
FDA label: Simvastatin (ZOCOR)
Action type:
avoid
Target id:
/condition/lactation
Target name:
Lactation
Severity:
major
Interaction type:
contraindication
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Use during breastfeeding is not recommended.
Actionable advice:
Not recommended while breastfeeding. If you are nursing, do not start simvastatin without your prescriber arranging an alternative or advising you to stop nursing.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Lactation Advise patients that breastfeeding is not recommended during treatment with simvastatin [see USE IN SPECIFIC POPULATIONS ( 8.2 )] .
Label source:
FDA label: Simvastatin (ZOCOR)
Action type:
avoid
Target id:
/class/cns-depressants
Target name:
CNS Depressants
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
null
Description:
General caution when combined with other active therapeutic agents.
Actionable advice:
It is important to talk to a physician before combining this with other medications.
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:
Generic placeholder row: the text is non-specific ('general caution') and there is no established CNS-depressant interaction for this agent. No validatable interaction claim - marked unvalidatable (candidate for removal).
Action type:
informational_none