Aspirin with Cyclosporine Interaction Details

Brand Names Associated with Aspirin

Brand Names Associated with Cyclosporine

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

Interaction Effect

An increased risk of cycloSPORINE nephrotoxicity

Interaction Summary

Concomitant use of cycloSPORINE with an NSAID may potentiate renal dysfunction, especially in dehydrated patients. Pharmacodynamic interactions between cycloSPORINE and both naproxen and sulindac have been associated with worsening of renal function[1]. NSAIDs can affect renal prostaglandins, potentially increasing the risk of cycloSPORINE-related nephrotoxicity due to decreased synthesis of renal prostacyclin [2][3][4]. Additionally, the AUC of diclofenac was increased significantly when it was coadministered with cycloSPORINE in patients with rheumatoid arthritis. Reversible declines in renal function have occasionally been reported with concomitant use of cycloSPORINE and diclofenac [1]. Interactions leading to renal impairment have been reported with a number of NSAIDs, including diclofenac, mefenamic acid, sulindac, and naproxen. It should be assumed that such interactions may occur with any combination of NSAID and cycloSPORINE [5][6][7][8]. Use caution when coadministering an NSAID with cycloSPORINE and closely monitor renal function, including serum creatinine. In patients with rheumatoid arthritis, monitoring of serum creatinine and blood pressure is recommended after initiation of a new NSAID or an NSAID dose increase. Use lower doses of a NSAID, such as diclofenac, if concomitant administration with cycloSPORINE is necessary [1].

Severity

Major

Onset

Delayed

Evidence

Established

How To Manage Interaction

Concomitant use of cycloSPORINE with an NSAID may potentiate cycloSPORINE-related renal dysfunction, especially in dehydrated patients. Additionally, cycloSPORINE may decrease the clearance of the NSAID[1]. Use caution when coadministering an NSAID with cycloSPORINE, and closely monitor renal function [2][3][4], including serum creatinine. In patients with rheumatoid arthritis, monitoring of serum creatinine and blood pressure is recommended after initiation of a new NSAID or an NSAID dose increase. Use lower doses of a NSAID, such as diclofenac, if concomitant administration with cycloSPORINE is necessary [1].

Mechanism Of Interaction

Decreased synthesis of renal prostacyclin

Literature Reports

A) Intact renal prostacyclin synthesis is important in maintaining glomerular filtration rate and renal blood flow in patients treated with cycloSPORINE, and the use of cyclooxygenase inhibitors, such as NSAIDs, may enhance the toxic effects of cycloSPORINE [8]. Interactions leading to renal impairment have been reported with a number of NSAIDs, including diclofenac, mefenamic acid, sulindac, and naproxen. It should be assumed that such interactions may occur with any combination of NSAID and cycloSPORINE [5][6][7][8].

B) The effects of NSAIDs and cycloSPORINE administration on renal function were studied in 11 patients with rheumatoid arthritis [6]. The combination resulted in more pronounced reductions in glomerular filtration rate and effective renal plasma flow than either drug alone, but this did not reach statistical significance. Similarly, in a study involving patients with rheumatoid arthritis stabilized on cycloSPORINE therapy, the coadministration of ketoprofen, indomethacin, or sulindac did not cause a clinically significant difference in the calculated creatinine clearance [9].

C) Concomitant administration of sulindac and cycloSPORINE resulted in elevations in cycloSPORINE serum levels in a 47-year-old renal transplant recipient [10]. The trough cycloSPORINE serum levels increased from 525 nanograms/milliliter (ng/mL) to 1218 ng/mL following 3 days of oral sulindac 150 mg twice daily. The levels decreased following withdrawal of sulindac. Increased cycloSPORINE concentrations have also been reported following the use of mefenamic acid [7]. Studies with diclofenac have not demonstrated an increase in cycloSPORINE concentrations, although the bioavailability of diclofenac was approximately doubled [5].

D) Ten healthy male volunteers were included in a placebo-controlled, randomized crossover study to determine how an imbalance in intrarenal prostaglandins plays a part in cycloSPORINE-induced nephrotoxicity. CycloSPORINE (10 mg/kg twice daily) for 4 days had no effect on glomerular filtration rate (GFR) and effective renal plasma flow (ERPF). However, when the same dose of cycloSPORINE was combined with indomethacin (50 mg twice daily), the GFR was decreased by 37% and the ERPF fell by 32%. Therefore, it appears that cycloSPORINE-induced renal vasoconstriction is influenced by prostaglandins [11].

E) The combination of cycloSPORINE and an NSAID resulted in colitis in an 8-year-old female with rheumatoid arthritis. During the third month of treatment with cycloSPORINE 7 mg/kg, prednisolone 15 mg daily, and indomethacin 75 mg daily, she experienced the onset of abdominal pain and 10 to 14 bloody stools per day. Discontinuing the cycloSPORINE resolved her symptoms within 5 days. She was rechallenged approximately 3 weeks later, and her symptoms again appeared within 4 days. Her cycloSPORINE blood level at this time was 100 nanograms/milliliter (ng/mL). Colonoscopy revealed a nonspecific colitis, and indomethacin was stopped, with a resolution of symptoms within a week. However, because of exacerbation of rheumatoid arthritis, diclofenac was substituted for indomethacin. Over the next week, she again developed bloody stools, and her cycloSPORINE level was 120 ng/mL. Her disease was finally controlled with cycloSPORINE, methotrexate, and prednisolone without the recurrence of colitis [12].

References

1 ) Product Information: Sandimmune(R) oral capsules, oral solution, intravenous injection, cyclosporine oral capsules, oral solution, intravenous injection. Novartis Pharmaceuticals Corporation (per FDA), East Hanover, NJ, 2012.

2 ) Product Information: Mobic(R) oral tablets, oral suspension, meloxicam oral tablets, oral suspension. Boehringer Ingelheim Pharmaceuticals, Inc. (per FDA), Ridgefield, CT, 2012.

3 ) Product Information: Voltaren(R)-XR oral extended-release tablets, diclofenac sodium oral extended-release tablets. Novartis Pharmaceuticals Corporation, East Hanover, NJ, 2011.

4 ) Product Information: CLINORIL(R) oral tablets, sulindac oral tablets. Merck & CO., Inc., Whitehouse Station, NJ, 2010.

5 ) Kovarik JM, Kurki P, Mueller E, et al: Diclofenac combined with cyclosporine in treatment refractory rheumatoid arthritis: longitudinal safety assessment and evidence of a pharmacokinetic/dynamic interaction. J Rheumatol 1996; 23:2033-2038.

6 ) Altman RD, Perez GO, & Sfakianakis GN: Interaction of cyclosporine A and nonsteroidal anti-inflammatory drugs on renal function in patients with rheumatoid arthritis. Am J Med 1992; 93:396-402.

7 ) Agar JW: Cyclosporine A and mefenamic acid in a renal transplant patient. Aust N Z J Med 1991; 21:784-785.

8 ) Harris KP, Jenkins D, & Walls J: Nonsteroidal antiinflammatory drugs and cyclosporine: a potentially serious adverse interaction. Transplantation 1988; 46:598-599.

9 ) Tugwell P, Ludwin D, Gent M, et al: Interaction between cyclosporin A and nonsteroidal antiinflammatory drugs. J Rheumatol 1997; 24:1122-1125.

10 ) Sesin GP, O'Keefe E, & Roberto P: Sulindac-induced elevation of serum cyclosporine concentration. Clin Pharm 1989; 8(6):445-446.

11 ) Sturrock NDC, Lang CC, & Struthers AD: Indomethacin and cyclosporin together produce marked renal vasoconstriction in humans. J Hypertens 1994; 12:919-924.

12 ) Constantopoulos A: Colitis induced by interaction of cyclosporine A and non-steroidal anti-inflammatory drugs. Pediatr Intl 1999; 41:184-186.

Aspirin Overview

• Prescription aspirin is used to relieve the symptoms of rheumatoid arthritis (arthritis caused by swelling of the lining of the joints), osteoarthritis (arthritis caused by breakdown of the lining of the joints), systemic lupus erythematosus (condition in which the immune system attacks the joints and organs and causes pain and swelling) and certain other rheumatologic conditions (conditions in which the immune system attacks parts of the body). Nonprescription aspirin is used to reduce fever and to relieve mild to moderate pain from headaches, menstrual periods, arthritis, toothaches, and muscle aches. Nonprescription aspirin is also used to prevent heart attacks in people who have had a heart attack in the past or who have angina (chest pain that occurs when the heart does not get enough oxygen). Nonprescription aspirin is also used to reduce the risk of death in people who are experiencing or who have recently experienced a heart attack. Nonprescription aspirin is also used to prevent ischemic strokes (strokes that occur when a blood clot blocks the flow of blood to the brain) or mini-strokes (strokes that occur when the flow of blood to the brain is blocked for a short time) in people who have had this type of stroke or mini-stroke in the past. Aspirin will not prevent hemorrhagic strokes (strokes caused by bleeding in the brain). Aspirin is in a group of medications called salicylates. It works by stopping the production of certain natural substances that cause fever, pain, swelling, and blood clots.

• Aspirin is also available in combination with other medications such as antacids, pain relievers, and cough and cold medications. This monograph only includes information about the use of aspirin alone. If you are taking a combination product, read the information on the package or prescription label or ask your doctor or pharmacist for more information.

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.