Ciprofloxacin nephrotoxicity

Anand A. Ciprofloxacin nephrotoxicity. Archives of internal medicine. 1993 Dec 13 153(23) 2705-6. 

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. 

Allergic reactions (e.g., rashes, urticaria, and eosino-philia) have been observed. These drugs have occasionally been associated with cholestatic jaundice, blood dyscrasias, hemolytic anemia, hypoglycemia, and nephrotoxicity. Recently the use of ciprofloxacin for prophylaxis protection against anthrax infection has been associated with damage to muscle ligaments. 

The severity of infection suggests that Gram-negative cover would also be prudent. Gentamicin is associated with increased nephrotoxicity in combination with vancomycin and ciprofloxacin offers an alternative option providing the patient is not at significant risk of seizures. 

Alternative or reserve drugs are used where there are problems of drug intolerance and bacterial resistance. They are in this class because of either greater toxicity or of lesser efficacy and include ethionamide (gastrointestinal irritation, allergic reactions), capreomycin (nephrotoxic), and cycloserine (effective but neurotoxic). Quinolone antibiotics such as ciprofloxacin and the more recently introduced macrolides such as clarithromycin and azithromycin also have useful activity against mycobacteria. 

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 a Medline search to investigate the incidence and features of fluoroquinolone nephrotoxicity only primarily case reports and temporally related events could be identified (50). Ciprofloxacin was associated with an increased... 

Patients who received bone marrow [267] and heart transplants [268] did not show any evidence of nephrotoxicity when receiving ciprofloxacin. Contrary to previous preliminary findings [253,269], more recent data suggest lack of relevant pharmacokinetic interaction of ciprofloxacin with cyclosporine[268]. Similar preliminary claims of norfloxacin [270], ofloxacin [271], and pefloxacin-cyclosporine [272] interactions have been made. 

It is reasonable to conclude that in general, quinolones are safe drugs from the renal point of view. It is often difficult, however, to ascertain the exact causative role of these agents in the appearance of nephrotoxicity. Judging by the recent accumulated experience with ciprofloxacin, physicians using quinolones should be alert for the development of acute interstitial nephritis leading to renal failure. This concern should be extended to the other newer fluoroquinolones despite the paucity of reports dealing with nephrotoxicity. 

Gerritsen WR, Peters A, Henny FC, Brouwers JR. Ciprofloxacin-induced nephrotoxicity. Nephrol Dial Transplant. 1987 2(5) 382-3. 

Avent CK, Krinsky D, Kirklin JK, Bourge RC, Figg WD. Synergistic nephrotoxicity due to ciprofloxacin and cyclosporine.The American journal of medicine. 1988 Sep 85(3) 452-3. 

The prevention of aminoglycoside-induced nephrotoxicity has received considerable attention in recent years. Alternative antibiotics should be used whenever possible and as soon as microbial sensitivities are known. Commonly used alternatives include fluoroquinolones (e.g., ciprofloxacin or levofloxacin) and third-generation cephalosporins (e.g., ceftazidime). When aminoglycosides are necessary, the specific drug used does not appear to significantly affect the risk of nephrotoxicity, and therapy should be selected to optimize antimicrobial efficacy. Furthermore, it is imperative to avoid volume depletion, limit the total aminoglycoside dose administered, and avoid concomitant therapy with other nephrotoxic drugs. 

La WK, Rolston KVI, Rubenstein EB, Bodey GP. Ciprofloxacin-induced nephrotoxicity in patients with cancer. Arch Intern Med... 

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. 

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. 

Some quinolones are only slightly soluble at neutral or alkaline conditions (e.g., norfloxacin and ciprofloxacine). They induce nephrotoxicity in laboratory animals due to crystallization of the drugs in renal tubules. 

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