Atorvastatin with Cyclosporine Interaction Details

Brand Names Associated with Atorvastatin

Brand Names Associated with Cyclosporine

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Mar 04, 2024

Interaction Effect

Increased atorvastatin exposure and an increased risk of myopathy or rhabdomyolysis

Interaction Summary

The risk of myopathy/rhabdomyolysis is increased when cycloSPORINE is administered concurrently with atorvastatin. Atorvastatin is metabolized by the CYP3A4 isozyme. Also, atorvastatin and its metabolites are substrates of the OATP1B1 transporter. Coadministration with inhibitors of OATP1B1 and CYP3A4, such as cycloSPORINE, can cause an increase in atorvastatin bioavailability; when the 2 drugs were coadministered; an 8.7-fold increase in AUC and a 10.7-fold increase in Cmax has occurred[1][2]. Concomitant use of atorvastatin with cycloSPORINE should be avoided. Lower starting and maintenance doses of atorvastatin should be considered if taken concomitantly. Consider periodic assessment of creatine phosphokinase. However, monitoring may not prevent the occurrence of severe myopathy [2].

Severity

Major

Onset

Delayed

Evidence

Established

How To Manage Interaction

Coadministration of atorvastatin (a CYP3A4 and an OATP1B1 substrate) with cycloSPORINE (a CYP3A4 and an OATP1B1 inhibitor) significantly increased plasma levels of atorvastatin. Concomitant use of atorvastatin with cycloSPORINE should be avoided due to an increased risk of myopathy/rhabdomyolysis[1][2]. Lower starting and maintenance doses of atorvastatin should be considered if taken concomitantly. Consider periodic assessment of creatine phosphokinase. However, monitoring may not prevent the occurrence of severe myopathy [2].

Mechanism Of Interaction

Inhibition of CYP3A4-mediated metabolism of atorvastatin by cycloSPORINE; inhibition of OATP1B1-mediated efflux transport of atorvastatin by cycloSPORINE

Literature Reports

A) Coadministration of atorvastatin 10 mg once daily for 28 days and cycloSPORINE 5.2 mg/kg/day led to an 8.7-fold increase in atorvastatin AUC and a 10.7-fold increase in Cmax [3][1].

B) A 40-year-old Asian woman with a history of a cadaveric renal transplant and systemic lupus erythematosus (SLE) presented with increased levels of creatine kinase (1846 units/L), aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, and alkaline phosphatase. She also had bilateral lower extremity weakness, resulting in her inability to walk. Medications included a two-month history of concomitant therapy with atorvastatin 10 mg daily and cycloSPORINE 125 mg daily. Her cycloSPORINE level was measured at 124 nanogram/mL (103.1 nanomol/L). After discontinuation of atorvastatin, her creatine kinase concentrations dramatically declined and symptoms resolved. This suggests that atorvastatin, similar to other members of the HMG-CoA reductase class, may in fact interact with cycloSPORINE and potentially result in rhabdomyolysis [4].

C) A randomized, open-arm study was conducted involving 30 renal transplant patients under an immunosuppressive regimen with corticosteroids and cycloSPORINE [5]. The patients were randomly allocated into three groups. Patients in group A were administered 10 mg atorvastatin once daily in the evening for 3 months, group B 0.2 mg cerivastatin once daily in the evening for 3 months, group C was the control group with no drug treatment. Total serum cholesterol (-30%), LDL cholesterol (-42%) and triglycerides (-23%) were significantly lower after atorvastatin therapy (p less than or equal to 0.05). An increase in HDL cholesterol (+10%) was also observed. CycloSPORINE blood trough levels greater than or equal to 25% of baseline values occurred in four of ten patients, requiring a decrease in cycloSPORINE daily dose (from 211 +/- 40 mg before to 177 +/- 333 mg after atorvastatin therapy). CycloSPORINE dosage per kg body weight was lowered from 3.1 +/- 0.8 mg/kg before to 2.7 +/- 0.7 mg/kg after starting therapy. No relevant increase in cycloSPORINE blood trough levels were observed in the other six patients. No significant changes in liver enzymes, CPK, or serum creatinine levels occurred. Myalgia or myopathy was not observed. Renal transplant patients treated with cycloSPORINE have an increased risk of drug-interaction-induced variations in cycloSPORINE blood trough levels. Long-term effects of atorvastatin with cycloSPORINE should be investigated in a larger population of kidney transplant patients.

References

1 ) Product Information: ATORVALIQ(R) oral suspension, atorvastatin calcium oral suspension. CMP Pharma Inc (per FDA), Farmville, NC, 2023.

2 ) Product Information: LIPITOR(R) oral tablets, atorvastatin calcium oral tablets. Parke-Davis (per FDA), New York, NY, 2017.

3 ) Product Information: LIPITOR(R) oral tablets, atorvastatin calcium oral tablets. Pfizer (Per FDA), New York, NY, 2012.

4 ) Maltz HC, Balog DL, & Cheigh JS: Rhabdomyolysis associated with concomitant use of atorvastatin and cyclosporine. Ann Pharmacother 1999; 33:1176-1179.

5 ) Renders L, Mayer-Kadner I, Koch C, et al: Efficacy and drug interactions of the new HMG-CoA reductase inhibitors cerivastatin and atorvastatin in CsA-treated renal transplant recipients. Nephrol Dial Transplant 2001; 16:141-146.

Atorvastatin Overview

• Atorvastatin is used together with diet, weight loss, and exercise to reduce the risk of heart attack and stroke and to decrease the chance that heart surgery will be needed in people who have heart disease or who are at risk of developing heart disease. Atorvastatin is also used to decrease the amount of fatty substances such as low-density lipoprotein (LDL) cholesterol ('bad cholesterol') and triglycerides in the blood and to increase the amount of high-density lipoprotein (HDL) cholesterol ('good cholesterol') in the blood. Atorvastatin may also be used to decrease the amount of cholesterol and other fatty substances in the blood in children and teenagers 10 to 17 years of age who have familial heterozygous hypercholesterolemia (an inherited condition in which cholesterol cannot be removed from the body normally). Atorvastatin is in a class of medications called HMG-CoA reductase inhibitors (statins). It works by slowing the production of cholesterol in the body to decrease the amount of cholesterol that may build up on the walls of the arteries and block blood flow to the heart, brain, and other parts of the body.

• Accumulation of cholesterol and fats along the walls of your arteries (a process known as atherosclerosis) decreases blood flow and, therefore, the oxygen supply to your heart, brain, and other parts of your body. Lowering your blood level of cholesterol and fats with atorvastatin has been shown to prevent heart disease, angina (chest pain), strokes, and heart attacks.

Cyclosporine Overview

• Cyclosporine and cyclosporine (modified) are used with other medications to prevent transplant rejection (attack of the transplanted organ by the immune system of the person who received the organ) in people who have received kidney, liver, and heart transplants. Cyclosporine (modified) is also used alone or with methotrexate (Rheumatrex) to treat the symptoms of rheumatoid arthritis (arthritis caused by swelling of the lining of the joints) in patients whose symptoms were not relieved by methotrexate alone. Cyclosporine (modified) is also used to treat psoriasis (a skin disease in which red, scaly patches form on some areas of the body) in certain patients who have not been helped by other treatments. Cyclosporine and cyclosporine (modified) are in a class of medications called immunosuppressants. They work by decreasing the activity of the immune system.

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Definitions

Severity Categories

Contraindicated

These drugs, generally, should not be used together simultaneously due to the high risk of severe adverse effects. Combining these medications can lead to dangerous health outcomes and should be strictly avoided unless otherwise instructed by your provider.

Major

This interaction could result in very serious and potentially life-threatening consequences. If you are taking this drug combination, it is very important to be under close medical supervision to minimize severe side effects and ensure your safety. It may be necessary to change a medication or dosage to prevent harm.

Moderate

This interaction has the potential to worsen your medical condition or alter the effectiveness of your treatment. It's important that you are monitored closely and you potentially may need to make adjustments in your treatment plan or drug dosage to maintain optimal health.

Minor

While this interaction is unlikely to cause significant problems, it could intensify side effects or reduce the effectiveness of one or both medications. Monitoring for changes in symptoms and your condition is recommended, and adjustments may be made if needed to manage any increased or more pronounced side effects.

Onset

Rapid: Onset of drug interaction typically occurs within 24 hours of co-administration.

Delayed: Onset of drug interaction typically occurs more than 24 hours after co-administration.

Evidence

Level of documentation of the interaction.

Established: The interaction is documented and substantiated in peer-reviewed medical literature.

Theoretical: This interaction is not fully supported by current medical evidence or well-documented sources, but it is based on known drug mechanisms, drug effects, and other relevant information.

How To Manage The Interaction

Provides a detailed discussion on how patients and clinicians can approach the identified drug interaction as well as offers guidance on what to expect and strategies to potentially mitigate the effects of the interaction. This may include recommendations on adjusting medication dosages, altering the timing of drug administration, or closely monitoring for specific symptoms.

It's important to note that all medical situations are unique, and management approaches should be tailored to individual circumstances. Patients should always consult their healthcare provider for personalized advice and guidance on managing drug interactions effectively.

Mechanism Of Interaction

The theorized or clinically determined reason (i.e., mechanism) why the drug-drug interaction occurs.

Disclaimer: The information provided on this page is for informational purposes only and should not be considered medical advice. Always consult with a qualified healthcare professional regarding your specific circumstances and medical conditions.

Where Does Our Information Come From?

Information for our drug interactions is compiled from several drug compendia, including:

• Gold Standard Drug Database
• Micromedex
• Lexicomp
• DrugBank

The prescribing information for each drug, as published on DailyMED, is also used. 

Individual drug-drug interaction detail pages contain references specific to that interaction. You can click on the reference number within brackets '[]' to see what reference was utilized.

The information posted is fact-checked by HelloPharmacist clinicians and reviewed quarterly.