Ciprofloxacin with Cyclosporine Interaction Details

Brand Names Associated with Ciprofloxacin

Brand Names Associated with Cyclosporine

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Nov 19, 2023

Interaction Effect

Increased cycloSPORINE blood levels, loss of cycloSPORINE therapeutic effect or transient elevations in serum creatinine

Interaction Summary

Elevations in serum creatinine may occur with concomitant use of cycloSPORINE and ciprofloxacin. Case reports have shown increased serum creatinine (ie, from 143 to 200 mcmoL/L) when ciprofloxacin was added to therapy of patients receiving cycloSPORINE . However, several studies and case reports have not found a significant effect on cycloSPORINE pharmacokinetics caused by ciprofloxacin . A review of the literature, including controlled studies and case reports, concluded that ciprofloxacin may be safely coadministered with cycloSPORINE at recommended doses without increased monitoring of cycloSPORINE concentrations . In a case-control study, ciprofloxacin was found to antagonize the cycloSPORINE induced inhibition of interleukin-2 production .

Severity

Moderate

Onset

Delayed

Evidence

Established

How To Manage Interaction

When using ciprofloxacin in transplant patients receiving cycloSPORINE for immunosuppression, monitor cycloSPORINE blood levels and monitor for signs of organ rejection. Transient elevations in serum creatinine may occur.

Mechanism Of Interaction

Decreased cycloSPORINE metabolism; pharmacodynamic antagonism

Literature Reports

A) In a comprehensive review of the literature related to concurrent ciprofloxacin and cycloSPORINE, it was suggested that many of the adverse effects attributed to a drug-drug interaction could be explained by other factors (such as inadequate adjustment of doses in renal dysfunction) . High serum creatinine may be the result of competition between creatinine and ciprofloxacin for renal tubular secretion, an effect likely to have modest clinical impact. In contrast to suggestions of competitive inhibition due to metabolism of both drugs in the cytochrome P450 system, pharmacokinetic studies seem to indicate that the drugs are metabolized by two different cytochrome P450 isoenzymes. The weight of evidence indicates that ciprofloxacin and cycloSPORINE can be coadministered safely at recommended doses without increased monitoring.

B) Ciprofloxacin was found to significantly increase the risk of acute rejection in renal transplant patients receiving immunosuppression with cycloSPORINE in a case control study. Cases (42 patients) receiving ciprofloxacin had a 29% incidence of rejection temporally related to the use of ciprofloxacin, compared to a 2% incidence of rejection in controls not receiving ciprofloxacin. Ciprofloxacin may antagonize the inhibition of interleukin-2 production mediated by cycloSPORINE .

C) The administration of ciprofloxacin 750 mg twice daily to kidney transplant patients concurrently receiving cycloSPORINE does not appear to affect cycloSPORINE pharmacokinetics. Ten patients who underwent post-renal transplants were administered ciprofloxacin eight to 48 days after the kidney transplant was performed; cycloSPORINE was administered for 7 to 48 days after transplantation at a dosage of 2.4 mg/kg every 12 hours adjusted to achieve cycloSPORINE blood levels within the recommended range (100 to 200 nanograms/mL (80 to 170 nanomols/L)). Ciprofloxacin 750 mg was administered twice daily for 17 days (13 doses). No statistically significant difference was noted between the cycloSPORINE pharmacokinetic parameters before and during ciprofloxacin treatment. Serum creatinine levels were increased in 4 of 10 patients, however, the increase was not related to ciprofloxacin therapy. The author concludes that ciprofloxacin can be administered to renal transplant patients without altering the risk of developing cycloSPORINE-induced nephrotoxicity .

D) Renal failure resulted from concomitant use of ciprofloxacin and cycloSPORINE A in a 58-year-old male. The patient underwent bilateral hip arthroplasty 34 months following heterotopic cardiac transplantation. Seven days after surgery, wound cellulitis group C streptococcal bacteremia developed and the patient received a 17-day course of IV imipenem/cilastatin therapy. Oral ciprofloxacin therapy (750 mg every 8 hours) was initiated prior to hospital discharge. A four-fold rise in serum creatinine from previous baseline values occurred 4 days after ciprofloxacin had been initiated. The patient had been receiving cycloSPORINE over the preceding 12 months and he had stable renal function. CycloSPORINE concentrations ranged from 160 to 603 nanograms (ng)/mL (130 to 501.4 nanomols (nmol)/L), and the serum creatinine levels from 1.4 to 2.2 mg/dL (120 to 194 mcmol/L). The patient was readmitted and ciprofloxacin was discontinued. Serum creatinine level peaked at 14.1 mg/dL (1250 mcmol/L) 4 days after the admission but returned to baseline over the following 2 weeks. On the fourth day of ciprofloxacin therapy, the peak cycloSPORINE level was 754 ng/mL (627 nmol/L); a trough level the following day was 398 ng/mL (331 nmol/L). There is a strong temporal relationship between the initiation of ciprofloxacin and the onset of acute renal failure in this case. This suggests that ciprofloxacin and cycloSPORINE acted synergistically to produce nephrotoxicity. It could be postulated that ciprofloxacin produces nephrotoxicity by interfering with the metabolism of cycloSPORINE, since both are metabolized by the cytochrome P450 enzyme system .

Ciprofloxacin Overview

• Ciprofloxacin is used to treat or prevent certain infections caused by bacteria such as pneumonia; gonorrhea (a sexually transmitted disease); typhoid fever (a serious infection that is common in developing countries); infectious diarrhea (infections that cause severe diarrhea); and infections of the skin, bone, joint, abdomen (stomach area), and prostate (male reproductive gland), Ciprofloxacin is also used to treat or prevent plague (a serious infection that may be spread on purpose as part of a bioterror attack) and inhalation anthrax (a serious infection that may be spread by anthrax germs in the air on purpose as part of a bioterror attack). Ciprofloxacin may also be used to treat bronchitis, sinus infections, or urinary tract infections but should not be used for bronchitis and sinus infections, or certain types of urinary tract infections if there are other treatment options. Ciprofloxacin extended-release (long-acting) tablets are used to treat kidney and urinary tract infections; however, some types of urinary tract infections should only be treated with ciprofloxacin extended release tablets if no other treatment options are available. Ciprofloxacin is in a class of antibiotics called fluoroquinolones. It works by killing bacteria that cause infections.

• Antibiotics such as ciprofloxacin will not work for colds, flu, or other viral infections. Using 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.