Atorvastatin is a statin used to lower "bad" cholesterol (LDL) and reduce the risk of heart attack and stroke. It is generally well tolerated; the main effect to watch for is unexplained muscle pain.
Also known as: Lipitor
Risk of myopathy and rhabdomyolysis. Clarithromycin raises Atorvastatin levels.
Atorvastatin is metabolised by CYP3A4; clarithromycin, a potent inhibitor, can raise its concentrations several-fold, with risk of myopathy, rhabdomyolysis and renal failure. Hold atorvastatin during the clarithromycin course (and a few days after) or switch to a statin less dependent on CYP3A4 (e.g. pravastatin); monitor myalgia, weakness and CPK in patients who keep the combination.
Atorvastatin + clarithromycin: clarithromycin inhibits CYP3A4 and can markedly raise atorvastatin levels, with risk of myopathy/rhabdomyolysis. Hold the statin during the antibiotic.
Inhibition of CYP3A4, the main Atorvastatin metabolic pathway.
Muscle symptoms (pain, weakness, dark urine) during and after the antibiotic.
Severe muscle pain, proximal weakness, dark-coloured urine (possible rhabdomyolysis).
Hold the statin during a short course of Clarithromycin or prefer Azithromycin.
DailyMed/FDA (NIH/NLM) — approved Clarithromycin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d836ae7e-fdbf-4dcb-a90d-ede1dcbc3e67 ; approved Atorvastatin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=86841382-4229-4e03-958e-3ac22639efd4
Colchicine + statin: increased risk of myopathy/rhabdomyolysis.
Both colchicine and statins can cause myopathy, and the combination increases the risk of rhabdomyolysis, especially in patients with renal impairment, the elderly or with high colchicine doses (e.g., acute gout flare in a patient on a statin). Colchicine is also a CYP3A4/P-gp substrate, sharing pathways with atorvastatin. In practice, use the lowest effective colchicine dose for the shortest time, monitor muscle symptoms and CK, and consider temporarily stopping the statin during a colchicine course in at-risk patients.
Atorvastatin + colchicine: additive risk of myopathy/rhabdomyolysis. Use with caution, especially with renal impairment.
Additive effect on skeletal muscle, especially in patients with reduced renal function.
CPK and renal function in symptomatic patients.
Myalgia, muscle weakness, dark urine.
Watch for muscle symptoms; consider reducing colchicine or stopping the statin.
DailyMed (FDA) — approved Colchicine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5ae87893-a065-468e-b8da-f1db86afcaef ; approved Atorvastatin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=fbd1c5da-67fb-4412-acb5-4d4c74a43654 — additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
Rifampin greatly reduces Atorvastatin levels — loss of the lipid-lowering effect.
Rifampicin is a potent inducer of CYP3A4, the main pathway of atorvastatin metabolism; with chronic use it substantially reduces its concentrations and compromises lipid control. Monitor the lipid profile and increase the atorvastatin dose as needed, or prefer a statin less dependent on CYP3A4 (e.g. pravastatin, rosuvastatin) during rifampicin treatment.
Atorvastatin + rifampicin: rifampicin induces CYP3A4 and lowers atorvastatin levels, reducing the lipid-lowering effect. Monitor LDL and adjust the dose.
CYP3A4 induction, the main Atorvastatin metabolic pathway.
Lipid profile.
Rising LDL despite therapy.
Consider another statin or adjust the dose while monitoring lipids.
DailyMed/FDA (NIH/NLM) — approved Rifampin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b389b1a3-672f-47e3-916c-4a9c044b211b ; approved Atorvastatin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=86841382-4229-4e03-958e-3ac22639efd4
Rifabutin lowers Atorvastatin levels — reduced lipid-lowering effect.
Rifabutin, like rifampicin, is an enzyme inducer (CYP3A4 and transporters) that accelerates atorvastatin metabolism, potentially lowering its concentrations and compromising lipid control during antimycobacterial treatment (e.g., prophylaxis in HIV). The effect is less marked than with rifampicin, but monitoring the lipid profile is recommended and, if needed, adjusting the statin dose (or considering a statin less dependent on CYP3A4, such as pravastatin).
Atorvastatin + rifabutin: rifabutin induces enzymes and can lower statin levels, reducing the lipid-lowering effect. Monitor lipids.
CYP3A4 induction (weaker than rifampin, but significant).
Lipid profile.
High LDL.
Monitor lipids and adjust the dose.
DailyMed/FDA (NIH/NLM) — approved Rifabutin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c2026b67-4755-4236-96b6-a6b5e7399707 ; approved Atorvastatin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=86841382-4229-4e03-958e-3ac22639efd4
Ketoconazole (a potent CYP3A4 inhibitor) raises Atorvastatin levels, increasing the risk of myopathy and rhabdomyolysis.
Ketoconazole is a potent inhibitor of CYP3A4, the main enzyme that metabolises atorvastatin; co-administration markedly raises statin concentrations and the risk of myopathy, including rhabdomyolysis, especially at high doses or in patients with renal or hepatic dysfunction. The atorvastatin label recommends considering the risk/benefit of concomitant use with other azole antifungals (including ketoconazole) and monitoring all patients for signs of myopathy, particularly at initiation and during titration; no specific dose limit is given for ketoconazole (unlike itraconazole, 20 mg). Instruct the patient to stop the statin in the presence of muscle pain, weakness or dark urine.
Atorvastatin + ketoconazole: the azole inhibits CYP3A4 and can raise statin levels, with a risk of myopathy/rhabdomyolysis. Stop the statin or reduce the dose.
CYP3A4 inhibition by ketoconazole reduces first-pass metabolism of atorvastatin, increasing its systemic exposure.
Creatine kinase (CK), muscle symptoms (myalgia, weakness, dark urine).
Severe muscle pain, weakness, dark-coloured urine (sign of rhabdomyolysis).
Prefer a statin not metabolized by CYP3A4 (e.g., pravastatin, rosuvastatin) or discontinue ketoconazole during therapy. If unavoidable, use the lowest atorvastatin dose with monitoring.
DailyMed/FDA (NIH/NLM) — approved Ketoconazole label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f162e616-21b4-49b1-b437-15e21001a6f0 ; approved Atorvastatin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=86841382-4229-4e03-958e-3ac22639efd4 — with additional reference: Prontuário Terapêutico do INFARMED, INFARMED (11th ed., 2012)
Fluconazole raises Atorvastatin levels (CYP3A4 inhibition), with a risk of myopathy.
Fluconazole inhibits CYP3A4 (to a variable degree depending on dose) and can raise atorvastatin concentrations, increasing the risk of myopathy/rhabdomyolysis, especially with high fluconazole doses or prolonged courses. Monitor muscle symptoms and CK, use the lowest effective statin dose during antifungal treatment and instruct the patient to stop in the presence of muscle pain, weakness or dark urine. In patients with renal impairment, the risk is higher.
Atorvastatin + fluconazole: CYP3A4 inhibition raising statin levels. Monitor and consider dose reduction.
Moderate CYP3A4 inhibition by fluconazole reduces atorvastatin metabolism.
Creatine kinase (CK), myalgia, weakness.
Severe muscle pain, dark urine.
Watch for muscle symptoms and CK; consider an alternative statin or adjusted dose.
DailyMed/FDA (NIH/NLM) — approved Fluconazole label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7961c029-746c-48c3-888b-8f8344102873 ; approved Atorvastatin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=86841382-4229-4e03-958e-3ac22639efd4 — with additional reference: Prontuário Terapêutico do INFARMED, INFARMED (11th ed., 2012)
Voriconazole raises Atorvastatin levels, with a risk of myopathy and rhabdomyolysis.
Voriconazole inhibits CYP3A4 and can raise atorvastatin concentrations, increasing the risk of myopathy/rhabdomyolysis, especially in prolonged antifungal courses (e.g., invasive aspergillosis) or with renal impairment. The atorvastatin label recommends considering the risk/benefit of combination with other azole antifungals (including voriconazole), monitoring muscle symptoms and CK, and using the lowest effective statin dose. Instruct the patient to stop in the presence of muscle pain, weakness or dark urine. In patients on prolonged antifungal therapy, periodically reassess the need for and the dose of the statin.
Atorvastatin + voriconazole: the azole inhibits CYP3A4 and can raise statin levels. Monitor for myopathy and consider dose reduction.
CYP3A4 inhibition by voriconazole reduces atorvastatin metabolism.
Creatine kinase (CK), myalgia, weakness.
Severe muscle pain, dark urine.
Watch for muscle symptoms and CK; consider an alternative statin or reduced dose.
DailyMed/FDA (NIH/NLM) — approved Voriconazole label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f6a1a792-141b-42e8-8bd1-884e4408eb8a ; approved Atorvastatin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=86841382-4229-4e03-958e-3ac22639efd4 — with additional reference: Prontuário Terapêutico do INFARMED, INFARMED (11th ed., 2012)
Combining Daptomycin with Atorvastatin (statin) increases the risk of myopathy and rhabdomyolysis.
Daptomycin is associated with myopathy, with CK elevation, and the label recommends monitoring CK weekly (more frequently in patients on recent or concomitant statins) and considering the temporary suspension of agents associated with rhabdomyolysis, such as statins (HMG-CoA reductase), during daptomycin treatment. The risk is higher with high daptomycin doses, prolonged courses or renal impairment. In practice, consider interrupting atorvastatin (and other statins) during the antibiotic, monitor CK weekly and watch for muscle symptoms; the statin can be resumed after the end of treatment.
Atorvastatin + daptomycin: additive risk of myopathy/rhabdomyolysis. Stop the statin during daptomycin treatment.
Daptomycin and HMG-CoA reductase inhibitors (statins) can both cause myopathy; the additive effect potentiates muscle injury and the risk of rhabdomyolysis.
Monitor CPK, myopathy symptoms (muscle pain, weakness) and renal function.
Severe myalgia, weakness, dark urine or markedly elevated CPK require discontinuation and immediate evaluation.
Consider holding the statin during daptomycin therapy or choosing an alternative; watch for muscle symptoms.
DailyMed/FDA (NIH/NLM) — approved Daptomycin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f4ad8613-f25e-4b82-9621-cc5ff9525d3e ; approved Atorvastatin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=86841382-4229-4e03-958e-3ac22639efd4 — with additional reference: Prontuário Terapêutico do INFARMED, INFARMED (11th ed., 2012)
Combining Ritonavir with Atorvastatin increases Atorvastatin concentrations, with an increased risk of myopathy and rhabdomyolysis.
Ritonavir (a protease inhibitor, often used as a pharmacokinetic booster) is a potent CYP3A4 inhibitor, and co-administration with atorvastatin raises statin concentrations and the risk of myopathy/rhabdomyolysis. The atorvastatin label specifies: with saquinavir+ritonavir, darunavir+ritonavir or fosamprenavir(+ritonavir), do not exceed 20 mg of atorvastatin per day; with tipranavir+ritonavir the combination is not recommended; with lopinavir+ritonavir consider the risk/benefit. In practice (HIV on antiretroviral therapy), use the lowest appropriate dose and titrate slowly with monitoring of lipids, muscle symptoms and CK; alternatively, consider a statin less dependent on CYP3A4. Instruct the patient about myopathy signs.
Atorvastatin + ritonavir: ritonavir strongly inhibits CYP3A4 and raises statin levels. Do not exceed 20 mg/day with the ritonavir regimens indicated in the label.
By inhibiting CYP3A4, Ritonavir reduces the metabolism of Atorvastatin (a CYP3A4 substrate), raising its exposure and the risk of muscular toxicity.
Watch for muscle symptoms (myalgia, weakness, dark urine) and, if symptomatic, check creatine kinase.
Severe myalgia, proximal weakness or brown urine require stopping the statin and medical evaluation.
Limit Atorvastatin to 20 mg/day during Ritonavir use, or choose a statin less dependent on CYP3A4 (e.g. pravastatin).
DailyMed/FDA (NIH/NLM) — approved Ritonavir label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=2849298e-de6e-47bb-8194-56e075b33fc3 ; approved Atorvastatin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=86841382-4229-4e03-958e-3ac22639efd4 — with additional reference: Prontuário Terapêutico do INFARMED, INFARMED (11th ed., 2012)
Erythromycin inhibits the CYP3A4 that metabolizes Atorvastatin, raising atorvastatin levels and the risk of myopathy and rhabdomyolysis.
Erythromycin is an inhibitor of CYP3A4, the enzyme that metabolises atorvastatin, and can raise statin concentrations and the risk of myopathy/rhabdomyolysis, especially in prolonged courses, high doses or with renal impairment. The atorvastatin label lists erythromycin among the CYP3A4 inhibitors whose combination requires a risk/benefit consideration (the 20 mg limit is explicit only for clarithromycin and itraconazole). During an erythromycin course, consider the lowest statin dose or temporary suspension, monitor muscle symptoms and CK, and inform the patient.
Atorvastatin + erythromycin: the macrolide inhibits CYP3A4 and can raise statin levels, with a risk of myopathy. Monitor and consider stopping.
Erythromycin is a CYP3A4 inhibitor; Atorvastatin is a substrate of this CYP. Enzymatic inhibition raises statin levels and the risk of muscle toxicity, especially at higher doses.
Watch for muscle symptoms (pain, weakness, cramps), CPK and dark urine during and after the combination.
Severe myalgia, muscle weakness, dark urine or markedly elevated CPK require immediate statin discontinuation.
Avoid the combination; if needed, choose a macrolide that does not inhibit CYP3A4 (e.g. azithromycin, when appropriate) or temporarily hold the statin.
DailyMed/FDA (NIH/NLM) — approved Erythromycin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=49b3ca93-43cc-439c-8f5d-e3ea2e87ad2f ; approved Atorvastatin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=86841382-4229-4e03-958e-3ac22639efd4 — with additional reference: Prontuário Terapêutico do INFARMED, INFARMED (11th ed., 2012)
Itraconazole (a potent CYP3A4 inhibitor) raises Atorvastatin levels, increasing the risk of myopathy and rhabdomyolysis.
Itraconazole is a potent CYP3A4 inhibitor and can markedly raise atorvastatin concentrations (and the risk of myopathy/rhabdomyolysis), especially in prolonged antifungal courses or with renal impairment. The atorvastatin label recommends not exceeding 20 mg of atorvastatin per day during itraconazole treatment (an explicit limit in the label), with monitoring of muscle symptoms and CK. Instruct the patient to stop the statin in the presence of muscle pain, weakness or dark urine.
Atorvastatin + itraconazole: the azole inhibits CYP3A4 and can markedly raise statin levels. Stop the statin or reduce the dose.
CYP3A4 inhibition by itraconazole reduces first-pass atorvastatin metabolism, increasing its exposure.
Creatine kinase (CK), muscle symptoms (myalgia, weakness, dark urine).
Severe muscle pain, weakness, dark-coloured urine (rhabdomyolysis).
Prefer a non-CYP3A4 statin (pravastatin, rosuvastatin) or stop itraconazole; otherwise use the lowest atorvastatin dose with monitoring.
DailyMed/FDA (NIH/NLM) — approved Itraconazole label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a4d555fa-787c-40fb-bb7d-b0d4f7318fd0 ; approved Atorvastatin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=86841382-4229-4e03-958e-3ac22639efd4 — with additional reference: Prontuário Terapêutico do INFARMED, INFARMED (11th ed., 2012)
Atorvastatin is metabolised by CYP3A4; grapefruit juice inhibits this enzyme and increases drug exposure (large amounts may raise AUC by up to around 2.5-fold).
Avoid large amounts of grapefruit juice during treatment; occasional small amounts have a limited effect.
EMC-UK (MHRA) — approved Atorvastatin SmPC: https://www.medicines.org.uk/emc/product/13672/smpc
Substantial alcohol intake, especially with pre-existing liver disease, increases the risk of transaminase elevation and is a predisposing factor for rhabdomyolysis.
Use with caution in patients with substantial alcohol intake; check liver enzymes and CK before initiation and periodically.
EMC-UK (MHRA) — approved Atorvastatin SmPC: https://www.medicines.org.uk/emc/product/13672/smpc
Atorvastatin is contraindicated in active liver disease or persistent transaminase elevations above 3 times the upper limit of normal.
Do not start the drug in these cases; if elevation persists during therapy, reduce the dose or discontinue.
EMC-UK (MHRA) — approved Atorvastatin SmPC: https://www.medicines.org.uk/emc/product/13672/smpc
A history of liver disease and substantial alcohol intake increase the risk of liver enzyme elevation and rhabdomyolysis.
Monitor liver function before and during treatment and measure CK before starting.
EMC-UK (MHRA) — approved Atorvastatin SmPC: https://www.medicines.org.uk/emc/product/13672/smpc
In the SPARCL trial, atorvastatin 80 mg was associated with a higher incidence of haemorrhagic stroke, particularly in patients with prior haemorrhagic stroke or lacunar infarct.
Carefully weigh risk-benefit before starting atorvastatin 80 mg in these patients.
EMC-UK (MHRA) — approved Atorvastatin SmPC: https://www.medicines.org.uk/emc/product/13672/smpc
Renal impairment, hypothyroidism, hereditary muscle disorders, age over 70 and prior statin muscle toxicity predispose to rhabdomyolysis.
Measure CK before starting; instruct the patient to report muscle pain, cramps or weakness and stop the drug if a clinically significant elevation occurs.
EMC-UK (MHRA) — approved Atorvastatin SmPC: https://www.medicines.org.uk/emc/product/13672/smpc
Contraindicated in pregnancy: safety is not established and congenital anomalies have been reported after intrauterine statin exposure.
Discontinue treatment during pregnancy or until it is confirmed that the woman is not pregnant.
Contraindicated during breastfeeding due to the potential for serious adverse reactions in the infant.
Women of child-bearing potential must use appropriate contraceptive measures during treatment; without effective contraception, the drug is contraindicated.
EMC-UK (MHRA) — approved Atorvastatin SmPC: https://www.medicines.org.uk/emc/product/13672/smpc
Clinical and educational support tool. The information does not replace a medical prescription or the opinion of a qualified healthcare professional.
Statins: LDL cholesterol and triglyceride reductions are dose-dependent and the maximum effect on LDL appears about 4 weeks after starting or adjusting the dose (with reduction already at 2 weeks). It also increases apoA-1 and HDL.
Selective, competitive inhibitor of HMG-CoA reductase, the rate-limiting enzyme in hepatic cholesterol synthesis. The reduction in hepatic intracellular cholesterol increases LDL receptor expression, enhancing the uptake and catabolism of plasma LDL.
Rapidly absorbed after oral administration, with peak plasma concentrations in 1 to 2 hours. Absolute bioavailability is about 14% (high first-pass effect). Food reduces the rate but not the extent of absorption (Cmax about 25% lower, LDL effect unchanged). It is more than 98% bound to plasma proteins.
Extensively metabolised in the liver, mainly by CYP3A4, with formation of active metabolites (ortho- and para-hydroxy-atorvastatin, responsible for about 70% of the HMG-CoA reductase inhibitory activity). Elimination is mainly biliary.
The plasma half-life is about 14 hours and that of the active metabolites 20 to 30 hours.
