Fluconazole and Cyclosporine Ophthalmic: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Fluconazole
Cyclosporine Ophthalmic
How we grade severity & evidence
Severity levels
- Contraindicated: These should generally not be used together.
- Major: Potentially serious — often needs a change or close monitoring.
- Moderate: Can be significant — usually manageable with monitoring.
- Minor: Usually limited clinical impact.
Evidence grades
- Established: Well documented — supported by controlled studies or strong clinical data.
- Probable: Good supporting evidence, though not definitively proven.
- Suspected: Some evidence suggests this interaction, but it is not well established.
- Possible: Limited or conflicting evidence; the interaction may occur.
- Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.
Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.
What happens
Increased cycloSPORINE exposure and an increased risk of cycloSPORINE toxicity (renal dysfunction, cholestasis, paresthesias)
Interaction Deep Dive
Concomitant use of cycloSPORINE and fluconazole significantly increases cycloSPORINE exposure in renal transplant recipients with or without renal impairment. If concomitant use is required, dose reduction of cycloSPORINE and careful monitoring of cycloSPORINE concentrations and serum creatinine is recommended. Following the administration of fluconazole 200 mg orally once daily for 14 days in 8 transplant recipients receiving a stable regimen of cycloSPORINE, AUC values for cycloSPORINE increased by 92%, the Cmax increased by 60% and the Cmin increased by 157%. The apparent oral clearance decreased by 45%12. Dose reduction of cycloSPORINE by 50% was used in patients treated with fluconazole; however, a large interindividual variability in the degree of drug interaction exists 8.
Why it happens (mechanism)
Inhibition of CYP3A4-mediated metabolism of cycloSPORINE
Literature reports
6 reports — tap to read
a) Concomitant use of cycloSPORINE and fluconazole significantly increased cycloSPORINE exposure in renal transplant recipients with or without renal impairment. Following the administration of fluconazole 200 mg orally once daily for 14 days in 8 transplant recipients receiving a stable regimen of cycloSPORINE, AUC values for cycloSPORINE increased by 92% (+/- 43%; range, 18% to 147%), the Cmax increased by 60% (+/- 48%; range, -5% to 113%) and the Cmin increased by 157% (+/- 96%; range, 33% to 360%). The apparent oral clearance decreased 45% (+/- 15%; range, -15% to -60%) 12.
b) An increase in the trough cycloSPORINE concentration was reported with increase in serum creatine after addition of fluconazole in a 43-year-old female with double renal-pancreatic transplantation. She was on triple immunosuppressive regimen of azaTHIOprine 2.5 mg/kg daily, predniSONE 2 mg daily, and cycloSPORINE 10 mg/kg daily after transplantation. She became febrile and was initiated on fluconazole 100 mg daily with gentamicin and imipenem after obtaining culture. Positive culture for C. albicans persisted with treatment; thus, fluconazole was increased to 300 mg daily with discontinuation of gentamicin and imipenem. Three days after the increase in dose, the trough cycloSPORINE concentration increased dramatically and continued to increase; furthermore, the serum creatine also increased. Decreasing fluconazole to 100 mg daily caused a sharp decrease in the trough cycloSPORINE concentration to almost the pretreatment level 3. Another report found no significant interaction between the two drugs in bone marrow transplant recipients 4.
c) A 46-year-old female with diabetes was on immunosuppressive therapy of predniSONE, azaTHIOprine, and cycloSPORINE for the renal transplantation. However, after initiation of fluconazole 100 mg daily, with a loading dose of 200 mg, the cycloSPORINE concentration doubled after just six days of therapy 5.
d) Concurrent cycloSPORINE and fluconazole in a 54-year-old patient with diabetes (two years post-renal-transplantation) produced a precipitous rise in creatinine levels. After reducing the cycloSPORINE and halving the dose of fluconazole, levels slowly returned to normal and he was successfully treated. The authors stated that measurement of the patient's serum cycloSPORINE had not been clinically useful (many fluctuations were recorded) and they also noted other reports of neurotoxicity that had occurred despite normal blood levels of cycloSPORINE and fluconazole 6.
e) A randomized, double-blind, placebo-controlled study of 16 renal transplant patients was done in which comparisons were made of cycloSPORINE levels in those receiving concurrent fluconazole versus those receiving placebo with cycloSPORINE. The patients coadministered cycloSPORINE and fluconazole had significant increases in cycloSPORINE area under the concentration-time curve (AUC) and significant decreases in cycloSPORINE clearance. Neither group experienced increases in serum creatinine 7.
f) Six renal transplant recipients receiving immunosuppressive therapy with cycloSPORINE participated in a prospective, unblinded, crossover trial to determine the effects of fluconazole coadministration. All patients had evidence of systemic candidiasis and were receiving the microemulsion preparation of cycloSPORINE. Following a week of monitoring the cycloSPORINE area under the concentration-time curve (AUC), maximum concentration (Cmax), minimum concentration (Cmin), time to Cmax (Tmax), clearance, and serum creatinine, fluconazole 200 mg daily was added to therapy for seven days. Patients were instructed to decrease their dose of cycloSPORINE by 50% when fluconazole was initiated. Baseline values included AUC 2887.8 nanogram x hr/mL, Cmax 701.8 ng/mL, and serum creatinine 139.0 mcgmol/L. Both the AUC and Cmax of cycloSPORINE peaked at day 4 of the study (4750.5 nanogram x hr/mL and 941.5 nanogram x hr /mL, respectively) and had decreased by day 7 (4052.0 nanogram x hr/mL and 768.0 nanogram x hr/mL, respectively), raising the possibility of cytochrome P450 system autoinduction. All cycloSPORINE pharmacokinetic parameters were again evaluated at day 14. With the reduction of the cycloSPORINE dose by 50% at day 7, the AUC and Cmax decreased to 2230.8 nanogram x hr/mL and 498.0 nanogram x hr/mL, respectively, by day 14, and the serum creatinine was 147.8 mcgmol/L. However, because of large interindividual variability in the sensitivity of cycloSPORINE metabolism to inhibition by fluconazole, firm recommendations on empirical cycloSPORINE dose reductions can not be made 8.
Common questions
Can I take Fluconazole and Cyclosporine Ophthalmic together?
Increased cycloSPORINE exposure and an increased risk of cycloSPORINE toxicity (renal dysfunction, cholestasis, paresthesias) Always confirm with your pharmacist or prescriber before making any change.
How serious is the Fluconazole and Cyclosporine Ophthalmic interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
How quickly could this interaction happen?
The documented onset is "delayed". Effects tend to build up gradually over days to weeks.
How strong is the evidence for this interaction?
The evidence is graded "established". Well documented — supported by controlled studies or strong clinical data.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Fluconazole or Cyclosporine Ophthalmic need adjusting while I take them together?
- What symptoms should prompt me to call you or my prescriber right away?
- Does the timing of my doses matter for this combination?
- Is there a safer alternative to one of these medications for me?
References (8)
- Product Information: DIFLUCAN(R) oral tablets, suspension, fluconazole oral tablets, suspension. Roerig (per FDA), New York, NY, 2024. DailyMed
- Product Information: DIFLUCAN(R) intravenous injection, fluconazole intravenous injection. Roerig (per FDA), New York, NY, 2024. DailyMed
- Lopez-Gil JA: Fluconazole-cyclosporine interaction: a dose-dependent effect?. Ann Pharmacother 1993; 27:427-430. PubMed
- Kruger HU, Schuler U, Zimmermann R, et al: Absence of significant interaction of fluconazole with cyclosporin. J Antimicrob Chemother 1989; 24:781-786. DOI
- Sugar AM, Saunders C, Idelson BA, et al: Interaction of fluconazole and cyclosporine. Ann Intern Med 1989; 110:844. PubMed
- Collignon P, Hurley B, & Mitchell D: Interaction of fluconazole with cyclosporin. Lancet 1989; 1:1262. PubMed
- Canafax DM, Graves NM, Hilligoss DM, et al: Increased cyclosporine levels as a result of simultaneous fluconazole and cyclosporine therapy in renal transplant recipients: a double-blind, randomized pharmacokinetic and safety study. Transplant Proc 1991; 23:1041-1042.
- Sud K, Singh B, Krishna VS, et al: Unpredictable cyclosporin-fluconazole interaction in renal transplant recipients. Nephrol Dial Transplant 1999; 14:1698-1703. DOI
Keep reading about Fluconazole
Keep reading about Cyclosporine Ophthalmic
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