Interaction between cyclosporin and fluoxetineBMJ 1995; 311 doi: http://dx.doi.org/10.1136/bmj.311.7002.422 (Published 12 August 1995) Cite this as: BMJ 1995;311:422
- R C Horton,
- R S Bonser
Dr R C HORTON and Mr R S BONSER (Queen Elizabeth Hospital, Birmingham B15 2TH) write: We report an interaction between cyclosporin and fluoxetine causing a rise in cyclosporin concentrations.
A 59 year old man underwent cardiac transplantation for end stage heart failure. Cyclosporin was given as an immunosuppressant, and he was maintained on 225 mg twice daily with a stable trough whole blood concentration of 300 µg/l. Progress in hospital was satisfactory, but 17 days postoperatively he developed an acute depressive illness and was given fluoxetine 20 mg once daily. No other changes were made to his drug treatment (azathioprine, prednisolone, ranitidine, aspirin, amphotericin, and co-trimoxazole). After 10 days his cyclosporin concentration had risen to 588 µg/l. We reduced the dose of cyclosporin to 75 mg twice daily and his blood concentration then remained at 250 µg/l. The patient did not respond to fluoxetine, so the drug was stopped. After seven days his cyclosporin concentration had fallen to 95 µg/l, necessitating a dose increase to 200 mg twice daily. His blood cyclosporin concentration then remained at 300 µg/l. Hepatic and renal function were normal throughout.
Several drugs are known to interfere with the metabolism of cyclosporin. Those that induce hepatic cytochrome P-450 enzymes may reduce blood cyclosporin concentrations, while inhibitors of hepatic metabolism may increase concentrations.1 In our patient fluoxetine administration led to increased cyclosporin concentrations. This is probably a consequence of fluoxetine's potent inhibition of the cytochrome P-450 enzyme P450IID6.2 A less likely possibility is that fluoxetine increased the systemic availability of cyclosporin by changed absorption. Since a whole blood (lysed cells) radioimmunoassay was used, altered binding of cyclosporin to red cells cannot be implicated.
Cyclosporin concentrations should be carefully monitored in patients who have undergone transplantation and are given fluoxetine. Raised concentrations may lead to cyclosporin related nephrotoxicity,3 while reduced concentrations may lead to inadequate immunosuppression and graft loss.