Meta Information
ID:atorvastatin
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:
/dietary/grapefruit-pomelo
Target name:
Grapefruit or Grapefruit Juice
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Grapefruit is a strong inhibitor of the CYP3A4 enzyme in the gut, which is responsible for breaking down atorvastatin. This can lead to dangerously high levels of the drug in the blood, increasing the risk of muscle damage (myopathy) and rhabdomyolysis.
Actionable advice:
Grapefruit or grapefruit juice should not be consumed at all while taking atorvastatin.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Grapefruit juice consumption, especially excessive consumption, more than 1.2 Clinical Impact: liters/daily, can raise the plasma levels of atorvastatin and may increase the risk of myopathy and rhabdomyolysis.
Label source:
FDA label: Atorvastatin (Lipitor)
Action type:
avoid
Target id:
/class/cyp3a4-strong-inhibitors
Target name:
Strong CYP3A4 Inhibitors
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
These drugs potently block the CYP3A4 enzyme, the primary pathway for atorvastatin metabolism, leading to a significant increase in atorvastatin blood levels and a high risk of severe muscle toxicity.
Actionable advice:
Co-administration should be avoided; this combination is generally contraindicated.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Grapefruit juice consumption, especially excessive consumption, more than 1.2 Clinical Impact: liters/daily, can raise the plasma levels of atorvastatin and may increase the risk of myopathy and rhabdomyolysis.
Label source:
FDA label: Atorvastatin (Lipitor)
Action type:
avoid
Target id:
/class/immunosuppressants
Target name:
Cyclosporine
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Cyclosporine is a potent inhibitor of both CYP3A4 and the OATP1B1 transporter, leading to a very large increase in atorvastatin exposure and a high risk of myopathy.
Actionable advice:
This combination should be avoided; if necessary, the atorvastatin dose should not exceed 10 mg daily.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Table 2: Drug Interactions that may Increase the Risk of Myopathy and Rhabdomyolysis with LIPITOR Cyclosporine or Gemfibrozil Atorvastatin plasma levels were significantly increased with concomitant administration of LIPITOR and cyclosporine, an inhibitor of CYP3A4 and OATP1B1 Clinical Impact: [see Clinical Pharmacology (12.3)].
Label source:
FDA label: Atorvastatin (Lipitor)
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 inhibits atorvastatin's uptake into the liver (via OATP1B1) and its breakdown, drastically increasing drug levels and the risk of severe muscle damage (rhabdomyolysis).
Actionable advice:
This combination should be strictly avoided; it is contraindicated.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
The risk of myopathy and Clinical Impact: rhabdomyolysis is increased with concomitant use of fibrates with LIPITOR.
Label source:
FDA label: Atorvastatin (Lipitor)
Action type:
avoid
Target id:
/class/hiv-protease-inhibitors
Target name:
Certain Antiretrovirals (for HIV) (Hiv Protease Inhibitors)
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Many HIV protease inhibitors (e.g., ritonavir, tipranavir) are potent inhibitors of CYP3A4, which can dramatically increase atorvastatin levels and the risk of rhabdomyolysis.
Actionable advice:
Combination requires careful dose limitation of atorvastatin or use of an alternative statin.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Cases of myopathy and rhabdomyolysis have been reported with concomitant use of ledipasvir plus sofosbuvir with LIPITOR. • Concomitant use of tipranavir plus ritonavir or glecaprevir plus pibrentasvir with LIPITOR is not recommended. • In patients taking lopinavir plus ritonavir, or simeprevir, consider the risk/benefit of concomitant use with atorvastatin. • In patients taking saquinavir plus rit
Label source:
FDA label: Atorvastatin (Lipitor)
Action type:
informational_none
Target id:
/class/hcv-direct-acting-antivirals
Target name:
Certain Hepatitis C Antivirals (Hcv Direct Acting Antivirals)
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Certain direct-acting antivirals for Hepatitis C (e.g., elbasvir/grazoprevir, glecaprevir/pibrentasvir) can inhibit drug transporters (OATP1B1), increasing atorvastatin levels and the risk of myopathy.
Actionable advice:
Co-administration is contraindicated or requires significant atorvastatin dose reduction.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
• In patients taking saquinavir plus ritonavir, darunavir plus ritonavir, fosamprenavir, fosamprenavir plus ritonavir, elbasvir plus grazoprevir or letermovir, do not exceed LIPITOR 20 mg once daily. • In patients taking nelfinavir, do not exceed LIPITOR 40 mg once daily.
Label source:
FDA label: Atorvastatin (Lipitor)
Action type:
avoid
Target id:
/intervention/red-yeast-rice
Target name:
Red Yeast Rice
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Red yeast rice naturally contains monacolin K, a substance chemically identical to the statin drug lovastatin. Taking it with atorvastatin constitutes duplicative therapy and significantly increases the risk of statin-related side effects like muscle damage.
Actionable advice:
Red yeast rice supplements should not be taken while on atorvastatin therapy.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
INTRODUCTION: Food supplements containing red yeast rice (RYR) are proposed as an alternative in statin-intolerant patients, although they actually contain natural statin(s) and their safety in clinical practice is still incompletely characterized.
Label source:
PubMed: Adverse Events to Food Supplements Containing Red Yeast Rice: Comparative Analysis of FAERS and CAERS Reporting Systems. (PMID 29582393)
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:
Atorvastatin is contraindicated in pregnancy as it may cause fetal harm by interfering with cholesterol synthesis, which is essential for fetal development.
Actionable advice:
Atorvastatin should not be taken during pregnancy, when planning to become pregnant, or when pregnancy is possible.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
LIPITOR decreases synthesis of cholesterol and possibly other biologically active substances derived from cholesterol; therefore, LIPITOR may cause fetal harm when administered to pregnant patients based on the mechanism of action [see Clinical Pharmacology (12.1)].
Label source:
FDA label: Atorvastatin (Lipitor)
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 atorvastatin is excreted in human milk, but due to the potential for serious adverse reactions in a nursing infant, it is contraindicated.
Actionable advice:
Atorvastatin should not be taken 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 of the potential for serious adverse reactions in a breastfed infant, based on the mechanism of action, advise patients that breastfeeding is not recommended during treatment with LIPITOR [see Use in Specific Populations (8.1), Clinical Pharmacology (12.1)].
Label source:
FDA label: Atorvastatin (Lipitor)
Action type:
avoid
Target id:
/condition/hepatic-impairment
Target name:
Active Liver Disease
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Atorvastatin is metabolized by the liver, and its use in patients with active liver disease can lead to significantly increased drug levels and potential toxicity.
Actionable advice:
Atorvastatin is contraindicated in patients with active liver disease or unexplained high liver enzymes.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Patients who consume substantial quantities of alcohol and/or have a history of liver disease may be at increased risk for hepatic injury [see Use in Specific Populations (8.7)].
Label source:
FDA label: Atorvastatin (Lipitor)
Action type:
avoid
Target id:
/class/cyp3a4-moderate-inhibitors
Target name:
Moderate CYP3A4 Inhibitors
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
These drugs inhibit the CYP3A4 enzyme, increasing atorvastatin levels and the risk of muscle-related side effects, though to a lesser extent than strong inhibitors.
Actionable advice:
This is best used with caution and under medical supervision; a lower dose of atorvastatin 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:
Grapefruit juice consumption, especially excessive consumption, more than 1.2 Clinical Impact: liters/daily, can raise the plasma levels of atorvastatin and may increase the risk of myopathy and rhabdomyolysis.
Label source:
FDA label: Atorvastatin (Lipitor)
Action type:
informational_none
Target id:
/class/fibrates
Target name:
Fibrates (e.g., Fenofibrate)
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Combining fibrates with atorvastatin increases the risk of muscle-related side effects (myopathy), as both drug classes can independently cause muscle toxicity.
Actionable advice:
These are best used together only when benefits outweigh risks, with close monitoring for muscle pain or weakness.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
The risk of myopathy and Clinical Impact: rhabdomyolysis is increased with concomitant use of fibrates with LIPITOR.
Label source:
FDA label: Atorvastatin (Lipitor)
Action type:
monitor
Target id:
/intervention/niacin
Target name:
Niacin (≥1 g/day)
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
High doses of niacin (nicotinic acid) when combined with atorvastatin can increase the risk of developing muscle pain or severe muscle damage (myopathy).
Actionable advice:
This combination is best used with caution, and it is worth monitoring for any signs of muscle toxicity.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Cases of myopathy/rhabdomyolysis have been reported with atorvastatin co-administered with lipid modifying doses (>1 gram/day) of niacin, fibrates, colchicine, and ledipasvir plus sofosbuvir [see Adverse Reactions (6.1)].
Label source:
FDA label: Atorvastatin (Lipitor)
Action type:
monitor
Target id:
/intervention/low-dose-colchicine
Target name:
Colchicine
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Concurrent use of colchicine and atorvastatin has been associated with an increased risk of myopathy and rhabdomyolysis, particularly in elderly patients or those with kidney problems.
Actionable advice:
Exercise caution and monitor for muscle pain or weakness when taking these drugs together.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Cases of myopathy/rhabdomyolysis have been reported with atorvastatin co-administered with lipid modifying doses (>1 gram/day) of niacin, fibrates, colchicine, and ledipasvir plus sofosbuvir [see Adverse Reactions (6.1)].
Label source:
FDA label: Atorvastatin (Lipitor)
Action type:
monitor
Target id:
/class/broad-spectrum-inducers
Target name:
Strong CYP3A4 Inducers (e.g., Rifampin, St. John's Wort)
Severity:
moderate
Interaction type:
diminishing
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
These agents speed up the metabolism of atorvastatin via the CYP3A4 enzyme, which can significantly lower its blood levels and reduce its cholesterol-lowering effectiveness.
Actionable advice:
This combination is best avoided, or cholesterol levels monitored closely to ensure atorvastatin remains effective.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Because phenytoin is hydroxylated in the liver by an enzyme system which is saturable at high serum levels, small incremental doses may increase the half-life and produce very substantial increases in serum levels, when these are in the upper range.
Label source:
FDA label: Phenytoin (target-side evidence)
Action type:
avoid
Target id:
/class/bile-acid-sequestrants
Target name:
Bile Acid Sequestrants
Severity:
moderate
Interaction type:
diminishing
Nature:
temporal
Temporal spacing:
Hours before target:
4
Hours after target:
1
Description:
Bile acid sequestrants can bind to atorvastatin in the intestine, preventing its absorption and reducing its effectiveness.
Actionable advice:
Atorvastatin is best taken at least 1 hour 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:
t least 4 hours prior to colesevelam hydrochoride ( 5.4 , 7 , 12.3 ). 5.1 Hypertriglyceridemia and Pancreatitis Colesevelam hydrochloride, like other bile acid sequestrants, can increase serum TG concentrations.
Label source:
FDA label: Colesevelam (target-side evidence)
Action type:
separate
Target id:
/class/hepatotoxic-agents
Target name:
Other Potentially Liver-Toxic Agents
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Atorvastatin can cause liver enzyme elevations. Combining it with other substances known to be hard on the liver (e.g., excessive alcohol, certain medications) can increase the risk of liver injury.
Actionable advice:
Alcohol consumption is best limited, and it is a good idea to let a doctor know about all other medications and supplements taken.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Patients who consume substantial quantities of alcohol and/or have a history of liver disease may be at increased risk for hepatic injury [see Use in Specific Populations (8.7)].
Label source:
FDA label: Atorvastatin (Lipitor)
Action type:
informational_none
Target id:
/intervention/daptomycin
Target name:
Daptomycin
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Both daptomycin and atorvastatin can cause muscle toxicity. Using them together increases the risk of myopathy and rhabdomyolysis.
Actionable advice:
Consider temporarily discontinuing atorvastatin during a course of daptomycin therapy.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Table 6: Adjudication Committee Clinical Success Rates at Test of Cure by Baseline Creatinine Clearance and Treatment Subgroup in the S. aureus Bacteremia/Endocarditis Trial in Adult Patients (Population: ITT) Success Rate n/N (%) CUBICIN Comparator Baseline CLCR 6 mg/kg every 24h Right-Sided Right-Sided Bacteremia Infective Bacteremia Infective Endocarditis Endocarditis >80 mL/min 30/50 (60%) 7/1
Label source:
FDA label: Daptomycin (target-side evidence)
Action type:
informational_none
Target id:
/circadian/sleep
Target name:
Bedtime / Evening
Severity:
minor
Interaction type:
synergistic
Nature:
temporal
Temporal spacing:
Hours before target:
1
Hours after target:
0
Description:
The body's cholesterol synthesis is highest during the night. Taking atorvastatin in the evening aligns its peak effect with this period, potentially enhancing its cholesterol-lowering efficacy.
Actionable advice:
A daily dose is generally best taken in the evening or at bedtime for potentially optimal results.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Plasma LIPITOR concentrations are lower (approximately 30% for Cmax and AUC) following evening drug administration compared with morning.
Label source:
FDA label: Atorvastatin (Lipitor)
Action type:
informational_none
Target id:
/intervention/coenzyme-q10
Target name:
Coenzyme Q10 (CoQ10)
Severity:
minor
Interaction type:
synergistic
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Statins inhibit HMG-CoA reductase, an enzyme also involved in the synthesis of CoQ10, potentially leading to lower levels. Supplementation may help mitigate some statin side effects like muscle pain, although evidence is mixed.
Actionable advice:
Consider supplementing with CoQ10 to potentially offset statin-induced depletion.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Supplementation of CoQ10 can reduce muscle pain in patients with SAMS, which is relevant for their well-being and treatment continuation.
Label source:
PubMed: Effects of coenzyme Q10 supplementation on myopathy in statin-treated patients: a systematic review and meta-analysis. (PMID 41158831)
Action type:
informational_none
Target id:
/intervention/ezetimibe
Target name:
Ezetimibe (Myopathy Risk)
Severity:
minor
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
While generally safe, combining ezetimibe with atorvastatin may slightly increase the risk of muscle-related side effects or liver enzyme elevations compared to atorvastatin alone.
Actionable advice:
It is worth watching out for muscle symptoms, and having liver function checked as recommended by a doctor is advisable.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
CONTRAINDICATIONS Ezetimibe tablets are contraindicated in the following conditions: The combination of ezetimibe tablets with a statin is contraindicated in patients with active liver disease or unexplained persistent elevations in hepatic transaminase levels.
Label source:
FDA label: Ezetimibe (target-side evidence)
Action type:
monitor
Target id:
/intervention/digoxin
Target name:
Digoxin
Severity:
minor
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Atorvastatin can slightly increase the concentration of digoxin in the blood, potentially increasing the risk of digoxin toxicity.
Actionable advice:
It is a good idea to check digoxin levels when starting or adjusting atorvastatin therapy.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Symptoms such as weight loss, failure to thrive in infants, abdominal pain, and behavioral disturbances may be indications of digoxin toxicity. Suggest to the patient to monitor and record their heart rate and blood pressure daily. Instruct patients to use the calibrated dropper to measure their digoxin dose and to avoid less precise measuring tools, such as teaspoons.
Label source:
FDA label: Digoxin (target-side evidence)
Action type:
monitor
Target id:
/class/estrogens
Target name:
Oral Contraceptives
Severity:
minor
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Atorvastatin can cause a small increase in the levels of hormones (norethindrone and ethinyl estradiol) from oral contraceptives, though the clinical significance is generally low.
Actionable advice:
No specific action is usually required, but be aware of this potential interaction.
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: LIPITOR Effects on Other Drugs Oral Contraceptives Co-administration of LIPITOR and an oral contraceptive increased plasma Clinical Impact: concentrations of norethindrone and ethinyl estradiol [see Clinical Pharmacology (12.3)].
Label source:
FDA label: Atorvastatin (Lipitor)
Action type:
informational_none
Target id:
/class/antiretrovirals
Target name:
Certain Hepatitis C Antivirals
Severity:
major
Interaction type:
adverse
Nature:
absolute
Description:
Certain direct-acting antivirals for Hepatitis C (e.g., elbasvir/grazoprevir, glecaprevir/pibrentasvir) can inhibit drug transporters (OATP1B1), increasing atorvastatin levels and the risk of myopathy.
Actionable advice:
Co-administration is contraindicated or requires significant atorvastatin dose reduction.
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:
Established PK interaction: some hepatitis-C direct-acting antivirals (e.g., elbasvir/grazoprevir, glecaprevir/pibrentasvir) inhibit OATP1B1, raising atorvastatin exposure and myopathy risk; statin dose limits apply. Labeled interaction.
Label source:
Class inference
Action type:
avoid
Temporal spacing:
Hours before target:
0
Hours after target:
0