Clarithromycin with Cyclosporine Interaction Details

Brand Names Associated with Clarithromycin

Brand Names Associated with Cyclosporine

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Nov 08, 2023

Interaction Effect

An increased risk of cycloSPORINE toxicity (renal dysfunction, cholestasis, paresthesias)

Interaction Summary

Clarithromycin, when added to a stable cycloSPORINE regimen, has been reported to result in significantly increased cycloSPORINE trough concentrations. This has been proposed to be a result of inhibition of cytochrome P450-mediated metabolism of cycloSPORINE causing elevations in serum levels of cycloSPORINE . One report suggests that coadministration of cycloSPORINE and clarithromycin may be an effective means of lowering the cost and decreasing the side effects of cycloSPORINE treatment by decreasing the dose of cycloSPORINE .

Severity

Moderate

Onset

Delayed

Evidence

Probable

How To Manage Interaction

When clarithromycin is added to cycloSPORINE therapy, monitor cycloSPORINE levels and adjust cycloSPORINE dosage as early as the second day of the macrolide treatment if necessary. Also, monitor patients for increased cycloSPORINE toxicity (renal dysfunction, cholestasis, paresthesias).

Mechanism Of Interaction

Decreased cycloSPORINE metabolism due to cytochrome P450 3A4 enzyme inhibition

Literature Reports

A) A 23-year-old woman was prescribed cycloSPORINE 125 mg twice a day as part of an immunosuppression regimen after undergoing kidney transplant. CycloSPORINE levels remained fairly constant in the ten months following the transplant until the patient began taking clarithromycin 250 mg twice daily for pharyngitis. Three days after initiation of clarithromycin therapy, cycloSPORINE blood levels had increased from 135 ng/mL to 280 ng/mL. CycloSPORINE-induced nephrotoxicity was also noted, with serum creatinine increasing from 160 mmol/L to 217 mmol/L. After a reduction in cycloSPORINE dose, therapeutic plasma levels returned and symptoms of nephrotoxicity resolved .

B) A 43-year-old man was receiving cycloSPORINE 100 mg twice daily fifteen months after a renal transplant and developed left lower lobe pneumonia. He initially received intravenous erythromycin and ceftriaxone while in the hospital. The trough whole blood cycloSPORINE concentration increased from 203 ng/mL to 385 ng/mL, resulting in a decrease of the cycloSPORINE dosage to 75 mg twice daily. Upon discharge from the hospital on day 7, he was prescribed clarithromycin 500 mg twice daily for ten days and cefuroxime axetil. After eight days of outpatient clarithromycin therapy, the cycloSPORINE concentration was 554 ng/mL. Three weeks after the discontinuation of clarithromycin the dosage of cycloSPORINE was increased back to 200 mg per day. The proposed mechanism for the increase in cycloSPORINE levels is that clarithromycin increases cycloSPORINE bioavailability by inhibiting intestinal as well as hepatic cytochrome P450 metabolism .

C) Three kidney graft recipients stabilized on cycloSPORINE were seen to have a sharp increase in their cycloSPORINE trough levels during, or just after, clarithromycin treatment. In addition, serum creatinine levels were increased slightly during the increased cycloSPORINE concentrations. The inhibition of cycloSPORINE metabolism at the level of hepatic NADPH-dependent cytochrome P450III complex may have caused this interaction .

D) A 61-year-old male was stabilized on cycloSPORINE following a heart transplant. When clarithromycin 500 mg twice daily was added for a suspected sinus infection, his cycloSPORINE level more than doubled. After discontinuation of clarithromycin, the patient's cycloSPORINE level returned to baseline levels .

E) Six organ transplant recipients receiving cycloSPORINE, azathioprine, and corticosteroids were monitored during a course of clarithromycin. All patients experienced supratherapeutic cycloSPORINE concentrations, increasing from the second to the fourth day after clarithromycin was initiated. Dosage reductions of cycloSPORINE were necessary in all patients. Four to five days after the discontinuation of clarithromycin, all patients required an increase in their cycloSPORINE dose to maintain target trough blood concentrations .

F) Clarithromycin was added to the standard immunosuppressive regimen of nine patients following lung transplantation, resulting in a reduction of effective cycloSPORINE dose. All were maintained on cycloSPORINE, prednisone, and azithromycin, with a baseline mean cycloSPORINE dose of 9.9 +/-2.2 mg/kg/day. One month after initiating clarithromycin, the cycloSPORINE dose was decreased to 5.8 +/- 1.0 mg/kg/day and at one year to 4.1 +/- 0.8 mg/kg/day, while still maintaining adequate cycloSPORINE levels. There was not an increase in the incidence of graft rejection, infection, or emergence of resistant organisms, although this would require further validation .

Clarithromycin Overview

• Clarithromycin is used to treat certain bacterial infections, such as pneumonia (a lung infection), bronchitis (infection of the tubes leading to the lungs), and infections of the ears, sinuses, skin, and throat. It also is used to treat and prevent disseminated Mycobacterium avium complex (MAC) infection [a type of lung infection that often affects people with human immunodeficiency virus (HIV)]. It is used in combination with other medications to eliminate H. pylori, a bacterium that causes ulcers. Clarithromycin is in a class of medications called macrolide antibiotics. It works by stopping the growth of bacteria.

• Antibiotics such as clarithromycin will not work for colds, flu, or other viral infections. Taking antibiotics when they are not needed increases your risk of getting an infection later that resists antibiotic treatment.

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.