HMG-CoA reductase inhibitors (statins)
ATC code: C10AA05 (Atorvastatin)
Brand names
Lipitor, Atorvaliq
Reversible competitive inhibitor of HMG-CoA reductase, the rate-limiting enzyme of hepatic cholesterol synthesis. Depletes intracellular cholesterol, upregulates receptors on hepatocytes, and increases LDL clearance from plasma. Lowers LDL by 35–55 % depending on dose, triglycerides by 15–30 %, with a small rise in .
First line
In adults without established CVD, statin therapy is guided by risk stratification. 2022 recommends statins in adults 40–75 with at least one CV risk factor and a 10-year ASCVD risk of 10 % or more. 2019 uses and titrates aggressiveness by risk category.
First line
High-intensity statins (atorvastatin 40–80 mg daily) are the foundation of secondary prevention after ACS, MI, ischemic stroke, TIA, revascularization, or in established atherosclerotic vascular disease. Target per 2019 is a ≥ 50 % reduction from baseline and LDL below 1.4 mmol/L. Cholesterol Treatment Trialists meta-analyses show a 20 % reduction in major vascular events per 1 mmol/L LDL lowering.
First line
Heterozygous FH requires high-intensity statins started early (from age 8–10 per pediatric consensus). target is below 2.5 mmol/L in adults without additional risk factors and below 1.8 mmol/L with them. Ezetimibe and, if needed, PCSK9 inhibitors are added when targets are not met.
The drug is promoted for these uses outside international guidelines. Each entry below is analyzed against AEMPS, FDA, EMA, Cochrane and major RCTs.
Not recommended
— Vessel cleansing: 'Vessel cleansing' is not a concept used in international clinical guidelines. Statins are prescribed based on cardiovascular risk stratification, not for 'cleansing'. The idea of mechanically 'removing plaques' with a drug contradicts pharmacokinetics. The evidence-based benefit of statins is reduced cardiovascular mortality via plaque stabilization and reduction, not 'dissolution'.
32 pairs found. Sorted from critical to minor.
Mechanism
Clarithromycin is a strong CYP3A4 and P-glycoprotein inhibitor. Atorvastatin plasma concentration rises 4–5 fold, increasing risk of rhabdomyolysis with acute kidney injury. caps atorvastatin at 20 mg/day during co-administration; recommends temporary statin withdrawal.
Symptoms
Within 5–10 days: muscle pain, especially thighs and shoulder girdle, dark urine, creatine kinase above 10× ULN, rising creatinine.
Management
Hold or reduce atorvastatin to 10–20 mg/day for the duration of clarithromycin (typically 7–14 days). Alternative: switch clarithromycin to azithromycin, which lacks CYP3A4 inhibition.
Sources
Mechanism
Atorvastatin uses hepatic CYP3A4 for ~70% of its clearance. Ritonavir is the strongest available CYP3A4 inhibitor. Atorvastatin plasma levels rise 5- to 7-fold.
Symptoms
Pain and weakness in large muscle groups (thighs, shoulders, calves), dark urine, elevated creatine kinase. Severe cases progress to rhabdomyolysis with acute kidney injury. Symptoms appear within 1–2 weeks of co-prescription.
Management
Cap atorvastatin at 10 mg/day. Preferable strategy: switch to pravastatin or rosuvastatin (cap rosuvastatin at 10 mg/day on ritonavir). Check creatine kinase at 4–6 weeks and on muscle symptoms.
Mechanism
Amiodarone moderately blocks CYP3A4 – a partial atorvastatin metabolic route. Atorvastatin plasma levels rise 1.5- to 2-fold; myopathy risk grows at doses of 40 mg and above.
Symptoms
Pain and weakness in large muscle groups (thighs, shoulders, calves), dark urine, elevated creatine kinase. Severe cases progress to rhabdomyolysis with acute kidney injury. Symptoms appear within 1–4 weeks of co-administration.
Management
Cap atorvastatin at 20 mg/day when amiodarone is added. If targets are missed, switch to pravastatin or rosuvastatin (less CYP3A4-dependent). Check creatine kinase at 4–6 weeks and on muscle symptoms.
Mechanism
Carbamazepine induces CYP3A4 – the main atorvastatin metabolic route. Atorvastatin plasma levels fall by 30–60%; lipid-lowering effect drops proportionally.
Symptoms
The patient feels nothing. Laboratory: cholesterol and total cholesterol rise. In high cardiovascular risk patients, myocardial infarction and stroke risk increase.
Management
During carbamazepine therapy, increase atorvastatin 1.5- to 2-fold with lipid profile and creatine kinase monitoring, or switch to pravastatin (CYP3A4-independent). Alternative anticonvulsants without induction: levetiracetam, lamotrigine.
Mechanism
Cyclosporine blocks the OATP1B1 transporter and CYP3A4 – two atorvastatin clearance routes. Atorvastatin plasma levels rise 8- to 15-fold, with high myopathy and rhabdomyolysis risk, particularly in transplant patients.
Symptoms
Pain and weakness in large muscle groups (thighs, shoulders, calves), dark urine, elevated creatine kinase. Severe cases progress to rhabdomyolysis with acute kidney injury. Symptoms appear within 1–4 weeks of co-administration.
Management
For transplant patients needing a statin, use pravastatin up to 20 mg/day or fluvastatin (minimal cyclosporine interaction). Use atorvastatin only when no alternative exists, capped at 10 mg/day, with creatine kinase every 4 weeks.
Mechanism
Additive myopathy and rhabdomyolysis risk. Atorvastatin injures muscle fibre by suppressing ubiquinone synthesis; colchicine disrupts microtubule function in myocytes. Particularly dangerous in older patients and chronic kidney disease.
Symptoms
Pain and weakness in large muscle groups (thighs, shoulders, calves), dark urine, elevated creatine kinase. Severe cases progress to rhabdomyolysis with acute kidney injury. Symptoms appear within 1–4 weeks of co-administration.
Management
Avoid prolonged combination. For acute gout, a short colchicine course (3–5 days) at 0.3 mg every other day is acceptable with muscle symptom and creatine kinase monitoring. Alternative for gout: intra-articular or short systemic glucocorticoid.
Mechanism
Diltiazem moderately inhibits CYP3A4 – a partial atorvastatin metabolic route. Atorvastatin plasma levels rise 2- to 3-fold. The effect is smaller than with simvastatin (atorvastatin's CYP3A4 dependence is weaker).
Symptoms
Pain and weakness in large muscle groups (thighs, shoulders, calves), dark urine, elevated creatine kinase. Severe cases progress to rhabdomyolysis with acute kidney injury. Symptoms appear within 1–4 weeks of co-administration.
Management
Cap atorvastatin at 20 mg/day when combined. If targets are missed, switch to pravastatin or rosuvastatin. Alternative to diltiazem: amlodipine or a beta-blocker.
Mechanism
Fluconazole at 200 mg/day or above moderately inhibits CYP3A4; at 400 mg/day, strongly. Atorvastatin plasma levels rise 2- to 4-fold depending on fluconazole dose.
Symptoms
Pain and weakness in large muscle groups (thighs, shoulders, calves), dark urine, elevated creatine kinase. Severe cases progress to rhabdomyolysis with acute kidney injury. Symptoms appear within 1–4 weeks of co-administration.
Management
For short fluconazole courses (up to 7 days), halve atorvastatin or hold it. For prolonged systemic therapy, alternative antifungals: echinocandins (micafungin, caspofungin); or switch to pravastatin/rosuvastatin.
Sources
Mechanism
Itraconazole inhibits CYP3A4 and P-glycoprotein. Atorvastatin concentration rises 3–4 fold. does not contraindicate the combination outright but caps atorvastatin at 20 mg/day and requires CK monitoring.
Symptoms
Myalgia and weakness within 1–3 weeks; CK above 5× ULN.
Management
Cap atorvastatin at 20 mg/day. For short itraconazole courses (up to 14 days) the safer option is to hold atorvastatin altogether.
Mechanism
Ketoconazole strongly inhibits CYP3A4 – the main atorvastatin metabolic route. Atorvastatin plasma levels rise 3- to 4-fold. Lipitor 2017 advises avoiding concomitant use.
Symptoms
Pain and weakness in large muscle groups (thighs, shoulders, calves), dark urine, elevated creatine kinase. Severe cases progress to rhabdomyolysis with acute kidney injury. Symptoms appear within 1–4 weeks of co-administration.
Management
During ketoconazole therapy, hold atorvastatin or switch to pravastatin/rosuvastatin (no CYP3A4 dependence). Alternative antifungals: terbinafine for dermatophytosis or echinocandins for systemic mycoses.
Mechanism
Posaconazole inhibits CYP3A4. Atorvastatin rises 3–4 fold, myopathy risk.
Symptoms
Myalgia, CK rise within 2 weeks.
Management
Cap atorvastatin at 10 mg/day. For long courses, switch to pravastatin or rosuvastatin.
Mechanism
Rifampicin strongly induces CYP3A4 and the OATP1B1 transporter – two atorvastatin clearance routes. Atorvastatin plasma levels fall by 80%; lipid-lowering effect weakens.
Symptoms
The patient feels nothing. Laboratory: cholesterol and total cholesterol rise. In high cardiovascular risk patients, myocardial infarction and stroke risk increase.
Management
During anti-TB therapy, switch to pravastatin (less induction-sensitive metabolism) or temporarily stop the statin for a short course. Induction persists for 2 weeks after rifampicin stops.
Mechanism
Atorvastatin weakly inhibits CYP3A4 and CYP2C9 – the warfarin clearance route. Some patients show a 20–30% INR rise within 2–4 weeks; a small share experience clinically significant effects.
Symptoms
Gum bleeding, epistaxis, bruising without trauma, blood in urine or stool, menorrhagia. Severe cases include gastrointestinal or intracranial haemorrhage. Risk rises in patients over 65 and with prior peptic ulcer disease.
Management
The combination is acceptable. After starting atorvastatin, check INR at 2 and 4 weeks, then resume routine monitoring. If INR rises above target, reduce warfarin by 10–20%.
Sources
Mechanism
Amlodipine weakly inhibits CYP3A4 – a partial atorvastatin metabolic route. Atorvastatin plasma levels rise by about 18%. Clinically significant myopathy is rare.
Symptoms
Usually no additional symptoms. In patients with risk factors (older age, chronic kidney disease, hypothyroidism): muscle pain and weakness are possible.
Management
The combination is acceptable without dose change. Cap atorvastatin at 40 mg/day if needed. Check creatine kinase on muscle symptoms.
Sources
Mechanism
Ciprofloxacin is a weak CYP3A4 inhibitor. Atorvastatin plasma levels may rise slightly during short ciprofloxacin courses.
Symptoms
Usually no changes. In patients with myopathy risk factors: rare muscle pain.
Management
For short ciprofloxacin courses (5–7 days), no special adjustment. In patients with myopathy risk factors, check creatine kinase on muscle symptoms.
Mechanism
Dexamethasone induces CYP3A4. With prolonged therapy, atorvastatin plasma levels may fall modestly and lipid-lowering effect weakens.
Symptoms
The patient feels nothing. Laboratory: cholesterol and total cholesterol rise during prolonged systemic glucocorticoid therapy.
Management
For short dexamethasone courses, no adjustment. For prolonged systemic therapy, monitor lipid profile every 2–3 months; increase atorvastatin by 25–50% if needed.
Mechanism
Atorvastatin blocks intestinal P-glycoprotein (one of the digoxin clearance routes). Digoxin plasma levels rise by about 20%.
Symptoms
Nausea, anorexia, visual disturbances (yellow-green halos around lights), arrhythmias. Older patients: confusion.
Management
After starting atorvastatin, check digoxin level at 2–4 weeks. If it rises above target, reduce digoxin by 25%.
Mechanism
Dronedarone blocks CYP3A4 – a partial atorvastatin metabolic route. Atorvastatin plasma levels rise 2-fold, raising myalgia risk.
Symptoms
Pain and weakness in large muscle groups (thighs, shoulders, calves), dark urine, elevated creatine kinase. Symptoms usually appear 2–6 weeks after starting the combination.
Management
Cap atorvastatin at 20 mg/day when combined. If targets are missed, switch to pravastatin or rosuvastatin (no CYP3A4 dependence).
Mechanism
Esomeprazole weakly affects CYP3A4 (mainly via CYP2C19). Atorvastatin levels are essentially unchanged. DDInter notes rare myalgia.
Symptoms
Usually no changes. Rare muscle pain cases, especially in patients with myopathy risk factors.
Management
The combination is acceptable without dose change. In patients with myopathy risk factors (older age, chronic kidney disease, hypothyroidism), check creatine kinase on muscle symptoms.
Mechanism
Fluvoxamine blocks CYP3A4 – a partial atorvastatin metabolic route. Atorvastatin plasma levels may rise modestly, raising myalgia risk.
Symptoms
Pain and weakness in large muscle groups (thighs, shoulders, calves), dark urine, elevated creatine kinase. Symptoms usually appear 2–6 weeks after starting the combination.
Management
When combined, cap atorvastatin at 40 mg/day if needed. Check creatine kinase on muscle symptoms. Alternative antidepressants without CYP3A4 effect: sertraline or escitalopram.
Sources
Mechanism
Linezolid is associated with rhabdomyolysis in combination with statins (rare post-marketing cases; mechanism not fully established).
Symptoms
Pain and weakness in large muscle groups (thighs, shoulders, calves), dark urine, elevated creatine kinase. Symptoms usually appear 2–6 weeks after starting the combination.
Management
For short linezolid courses (10–14 days), no special adjustment. In patients with myopathy risk factors, check creatine kinase before start and on muscle symptoms. In severe gram-positive infections on statins: alternative antibiotics (daptomycin with its own myopathy risk, vancomycin, ceftaroline).
Mechanism
Atorvastatin blocks OATP1B1 – the hepatic methotrexate uptake route. Methotrexate plasma levels may rise. The effect is clinically significant at high oncologic methotrexate doses.
Symptoms
Stomatitis, diarrhoea, falling leukocyte and platelet counts. In patients with borderline renal function: severe toxicity risk.
Management
At low rheumatological methotrexate doses (5–25 mg/week), the combination is acceptable without adjustment. At high oncologic doses, temporarily withhold atorvastatin for 24–48 hours after methotrexate administration.
Mechanism
Metronidazole does not block CYP3A4 but increases myopathy risk with statins (mechanism not fully established; reported in post-marketing data). The effect is rare.
Symptoms
Pain and weakness in large muscle groups (thighs, shoulders, calves), dark urine, elevated creatine kinase. Symptoms usually appear 2–6 weeks after starting the combination.
Management
For short metronidazole courses (5–7 days), no special adjustment. In patients with myopathy risk factors, check creatine kinase on muscle symptoms. For prolonged metronidazole therapy, temporarily reduce atorvastatin.
Mechanism
Omeprazole weakly blocks CYP3A4 – atorvastatin exposure rises modestly (by 10–20%). Clinically significant myopathy beyond baseline is rare.
Symptoms
Usually no changes. In patients with risk factors (older age, chronic kidney disease, hypothyroidism): muscle pain and weakness possible.
Management
The combination is acceptable without dose change. In patients with myopathy risk factors, check creatine kinase on muscle symptoms. Alternative PPI without CYP3A4 effect: pantoprazole or rabeprazole.
Sources
Mechanism
Pantoprazole is the most CYP-neutral PPI. No clinically significant interaction with statins.
Symptoms
No changes.
Management
The combination is acceptable without dose change. Pantoprazole is the preferred PPI in patients on statins and other CYP3A4-dependent drugs.
Mechanism
Dual statin therapy – doubling the same pharmacological class with additive myopathy risk and no therapeutic benefit.
Symptoms
Pain and weakness in large muscle groups (thighs, shoulders, calves), dark urine, elevated creatine kinase. Symptoms usually appear 2–6 weeks after starting the combination.
Management
The combination is not prescribed. Use one statin titrated to target. If LDL is not at goal on the maximum statin dose, add ezetimibe or a PCSK9 inhibitor, not a second statin.
Mechanism
Dual statin therapy – additive myopathy and rhabdomyolysis risk. Simvastatin additionally depends on CYP3A4 (by 98%), amplifying risk.
Symptoms
Pain and weakness in large muscle groups (thighs, shoulders, calves), dark urine, elevated creatine kinase. Symptoms usually appear 2–6 weeks after starting the combination.
Management
The combination is not prescribed. Use one statin titrated to target. If insufficient, add ezetimibe.
Mechanism
Tacrolimus is a weak CYP3A4 inhibitor; atorvastatin is a substrate. Atorvastatin plasma levels rise by 30–50%, raising myalgia risk. Tacrolimus itself can cause myopathy.
Symptoms
Pain and weakness in large muscle groups (thighs, shoulders, calves), dark urine, elevated creatine kinase. Symptoms usually appear 2–6 weeks after starting the combination.
Management
For transplant patients needing a statin, use pravastatin up to 20 mg/day or fluvastatin (minimal tacrolimus interaction). Atorvastatin is acceptable when no alternative exists, capped at 10 mg/day with creatine kinase every 4 weeks.
Mechanism
Verapamil is a moderate CYP3A4 inhibitor. Atorvastatin plasma levels rise 2-fold, raising myalgia risk.
Symptoms
Pain and weakness in large muscle groups (thighs, shoulders, calves), dark urine, elevated creatine kinase. Symptoms usually appear 2–6 weeks after starting the combination.
Management
Cap atorvastatin at 20 mg/day when combined. If targets are missed, switch to pravastatin or rosuvastatin. Alternative to verapamil: amlodipine or a beta-blocker.
Mechanism
Azithromycin does not clinically significantly inhibit CYP3A4 (Indiana Flockhart Table). Atorvastatin AUC is unchanged.
Symptoms
The combination usually causes no specific symptoms. Each drug's individual side effects remain.
Management
No dose adjustment needed. When a macrolide is needed in a patient on atorvastatin, azithromycin remains the preferred choice (unlike clarithromycin and erythromycin — strong CYP3A4 inhibitors).
Mechanism
An early study (Lau et al., Circulation 2003) in 44 patients showed in vitro competition between atorvastatin and clopidogrel for CYP3A4. Subsequent large clinical trials (PROVE-IT, MIRACL, CHARISMA) did not confirm clinically significant attenuation of clopidogrel's antiplatelet activity.
Symptoms
The combination usually causes no specific symptoms. Each drug's individual side effects remain.
Management
Standard combination after acute coronary syndrome and in coronary artery disease. No dose adjustment needed. In patients at high risk of recurrent thrombosis with unclear antiplatelet activity, consider switching to ticagrelor or prasugrel (CYP3A4-independent).
Mechanism
Hypothyroidism itself raises . Restoring euthyroid status on levothyroxine reduces statin need. No direct pharmacokinetic interaction.
Symptoms
The combination usually causes no specific symptoms. Each drug's individual side effects remain.
Management
On starting levothyroxine in patients on stable atorvastatin, check lipids 6–8 weeks after TSH normalises. If drops below target, atorvastatin can be reduced. In newly diagnosed hypothyroidism with hypercholesterolaemia, delay statin start until euthyroid status is achieved.
Sources
Opens the checker prefilled with this drug. Pick the second one from your regimen.
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In July 2021 the FDA removed the automatic contraindication during pregnancy from labels of all statins (Drug Safety Communication, 2021-07-20). The FDA pregnancy categories (A/B/C/D/X) were retired in 2015 under the PLLR — historically atorvastatin was classified as X. The decision is now individualized: in patients without atherosclerotic CVD, statins are usually discontinued before conception and throughout pregnancy; in those with documented atherosclerosis and high event risk, continuation is possible after shared decision-making with a cardiologist. An unplanned pregnancy is a trigger for discussion, not for default discontinuation.
Systemic safety data during lactation are limited. The manufacturer and most international sources recommend avoidance. In patients with a statin indication, options include a temporary switch to formula feeding or deferring therapy until breastfeeding is complete.
Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.
Atorvastatin is evaluated for the following indications with varying evidence strength: Familial hypercholesterolemia (evidence tier A), Dyslipidemia, primary CV prevention (evidence tier A), Established ASCVD, secondary prevention (evidence tier A). See the full indication matrix with dosing and citations above on this page.
Common side effects of Atorvastatin (≥ 1 in 100): Myalgia without CK elevation, Headache, Dyspepsia, nausea, Arthralgia, Transient transaminase elevation (usually below 3× ULN). See the Safety section for uncommon and serious reactions.
FDA category X. In July 2021 the FDA removed the automatic contraindication during pregnancy from labels of all statins (Drug Safety Communication, 2021-07-20). The FDA pregnancy categories (A/B/C/D/X) were retired in 2015 under the PLLR — historically atorvastatin was classified as X. The decision is now individualized: in patients without atherosclerotic CVD, statins are usually discontinued before conception and throughout pregnancy; in those with documented atherosclerosis and high event risk, continuation is possible after shared decision-making with a cardiologist. An unplanned pregnancy is a trigger for discussion, not for default discontinuation.
Systemic safety data during lactation are limited. The manufacturer and most international sources recommend avoidance. In patients with a statin indication, options include a temporary switch to formula feeding or deferring therapy until breastfeeding is complete.
Atorvastatin is contraindicated in: Active liver disease or unexplained persistent transaminase elevation; Pregnancy and planned pregnancy; Breastfeeding; Hypersensitivity to any component. Full list in the Safety section.
clinically significant transaminase elevation occurs in less than 1 % of patients and is usually transient. Routine liver enzyme monitoring in asymptomatic patients is not required.
statins are long-term (usually lifelong) therapy. Discontinuation rapidly returns LDL to baseline and raises cardiovascular risk.
a small excess risk exists (roughly 1 case of T2D per 250 patients over 4 years), but the benefit from reduced cardiovascular events clearly outweighs it in patients with an indication.