Ciprofloxacin Ciclosporin

CICLOSPORIN CIPROFLOXACIN Ciprofloxacin may 1 immunosuppressive effect (pharmacodynamic interaction) Ciprofloxacin 1 inhibitory effect of ciclosporin on IL-2 production to 1 immunosuppressive effect Avoid co-administration... 

There is an increased risk of hyperkalaemia when ciclosporin is given with Coversyl, which contains perindopril, an angiotensin-converting enzyme inhibitor. Risk of nephrotoxicity associated with ciclosporin is increased with concomitant use with quinolones. Ciproxin contains ciprofloxacin, which is a quinolone. Tenormin contains atenolol, which is a beta-adrenoceptor blocker and there are no interactions between these agents and ciclosporin. 

Although ciprofloxacin was initially thought to increase ciclosporin blood concentrations and enhance ciclosporin nephrotoxicity, no definite evidence to support this interaction has been found (245). A norfloxacin-induced increase in ciclosporin blood concentrations has been... 

In 42 patients who had received a kidney transplant, cases were treated with ciprofloxacin in the first 1-6 months after transplantation, and matched controls (two per case) were not. The proportion of cases with at least one episode of biopsy-proven rejection 1-3 months after transplantation (45%) was significantly higher than in the controls (19%). The authors speculated that ciprofloxacin increases rejection rates in renal transplant recipients by antagonizing ciclosporin-dependent inhibition of interleukin-2 production (69). 

Four transplant patients who were taking eiclosporin developed seizures when they were given imipenem/cilastatin 1 g daily, and a fifth patient developed myoclonia. These patients all had chronic renal impairment. In contrast, imipenem/cilastatin 2 g daily for 4 weeks, given with ciprofloxacin, was effectively and successfully used in another patient taking ciclosporin after a heart transplant. This patient was switched to imipenem/cilastatin and ciprofloxacin after developing acute renal failure while receiving amikacin. Reduced serum ciclosporin levels following the use of imipenem/cilastatin have been seen in rats ... 

Ciclosporin serum levels are normally unchanged by the use of ciprofloxacin, but increased serum levels and nephrotoxicity may occur in a small number of patients. There is also some evidence that the immunosuppressant effects of ciclosporin are reduced by ciprofloxacin. One study, and two case reports describe rises in ciclosporin levels in patients given norfloxacin, but another study found no change. Similar results have been found with levo-floxacin. No significant interaction appears to occur between ciclosporin and enoxacin, ofloxacin, pefloxacin and trovafloxacin. 

The interaction between ciclosporin and norfloxacin probably occurs because norfloxacin inhibits the cytochrome P450 isoenzyme CYP3A4, resulting in a reduction in ciclosporin metabolism. The interaction between ciclosporin and ciprofloxacin may possibly be due to some antagonism by ciprofloxacin of the ciclosporin-dependent inhibition of inter-leukin-2, which thereby opposes its immunosuppressant action. " ... 

No pharmacokinetic interaction usually occurs between ciclosporin and ciprofloxacin but very occasionally and unpredictably an increase in serum ciclosporin levels and/or kidney toxicity occurs. There is also some evidence that the immunosuppressant effects of ciclosporin may be reduced. " Bear these interactions in mind if both drugs are given. 

Nasir M, Rotellar C, Hand M, Kulczycki L, Alijani MIR, Winchester JF. Interaction between ciclosporin and ciprofloxacin. Nephron (1991) 57, 245-6. 

On the basis of the study above and of some quite unexpected rises in drug levels and subsequent nephrotoxicity in a handful of patients taking the similarly metabolised immunosuppressant, ciclosporin, with a qui-nolone antibacterial (see Ciclosporin + Antibacterials Quinolones , p.1018), one review suggested that close monitoring would be appropriate if tacrolimus is given with any quinolone. However, in vitro studies have suggested that enoxacin does not affect the metabolism of tacrolimus, and ciprofloxacin does not affect the immunosuppressant activity of tacrolimus. Further study is needed. 

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