Ciclosporin Amphotericin

AMPHOTERICIN CICLOSPORIN t risk of nephrotoxicity Additive nephrotoxic effects Monitor renal function... 

Amphotericin colloidal dispersion has been compared with amphotericin deoxycholate in a prospective, randomized, double-blind study in the empirical treatment of fever and neutropenia in 213 patients (25). Patients were stratified by age and concomitant use of ciclosporin or tacrolimus and then randomized to receive ABCD (4 mg/kg/day) or amphotericin deoxycholate (0.8 mg/ kg/day) for 14 days. Renal dysfunction was less likely to develop and occurred later with ABCD than with amphotericin deoxycholate. Likewise, the absolute and percentage fall in the serum potassium concentration from baseline to the end of therapy was greater with amphotericin deoxycholate than ABCD. However, probable or possible infusion-related hypoxia and chills were more common with ABCD than amphotericin deoxycholate. There was a therapeutic response in 50% of the patients who received ABCD and 43% of those who received amphotericin deoxycholate. Thus, ABCD was of comparable efficacy and less nephrotoxic than amphotericin deoxycholate, but infusion-related events were more common with ABCD. 

Amphotericin-associated nephrotoxicity has been studied in a retrospective analysis of 69 recipients of blood stem-cell transplants with multiple myeloma who received at least two doses of amphotericin deoxycholate during 1992-95 (111). Nephrotoxicity occurred in 30 patients (43%) and developed rapidly. Patients who developed nephrotoxicity were similar to those who did not in many aspects associated with their treatment. However, baseline-estimated creatinine clearance, ciclosporin therapy, nephrotoxic drug therapy within 30 days of starting amphotericin, and the number of concomitant... 

In a retrospective study, renal function was investigated in patients receiving ciclosporin alone or in combination with amphotericin (24-hour infusion) after allogeneic stem-cell transplantation (112). Of 84 patients, 22 were treated with amphotericin. There was a statistically significant reduction in renal function compared with the 62 patients who received ciclosporin alone. However, renal insufficiency in all patients remained in a clinically acceptable range and was reversible in patients who survived to 1 year after transplantation. 

Continuous infusion of amphotericin has been assessed in an open study in six lung transplant recipients with invasive or semi-invasive bronchopulmonary azole-resistant candidal infections who were treated for 40 (17-73) days by 24-hour continuous infusions of amphotericin 1 mg/kg (113). They received at least 1000 ml/day of 0.9% saline intravenously. Apart from ciclosporin, five patients received aminoglycosides for at least 2 weeks, and four received ganciclovir. Calculated creatinine clearance fell from 57 (43-73) ml/minute to a nadir of 35 (28-39) and recovered to 52 (33-60) after the end of therapy. One patient needed temporary hemofiltration for 7 days. Besides three episodes of mild hypokalemia there were no adverse effects attributable to amphotericin. Asymptomatic colonization with Candida persisted for 10 months in one case, but the other five patients were cured. 

Because ciclosporin causes a reduction in renal function, there is increased nephrotoxicity if amphotericin is also given (112,147). 

Tacrolimus (FK 506), a macrolide immunosuppressant, has adverse effects similar to those of ciclosporin, including nephrotoxicity. Increased nephrotoxicity can be expected when it is given with amphotericin (156). 

ADEFOVIR DIPIVOXIL 1. ANTIBIOTICS-aminoglycosides, vancomycin 2. ANTICANCER AND IMMUNOMODULATING DRUGS-ciclosporin, tacrolimus 3. ANTIFUNGALS-amphotericin, 4. ANTIPROTOZOALS-pentamidine 5. ANTIVIRALS - cidofovir, foscarnet sodium, tenofovir Possible t efficacy and side-effects Competition for renal excretion Monitor renal function weekly... 

Ringden O, Andstrom E, RembergerM, SvahnB-M,ToUemar J. Safety of liposomal amphotericin B (AmBisome) in 187 transplant recipients treated with ciclosporin. Bone Marrow Transplant 99A) 14, (Suppl 5) S10-S14. 

Renal insufficiency, usually reversible, is common after the procedure and commonly related to the use of nephrotoxic drugs such as ciclosporin, tacrolimus, vancomycin or amphotericin B. In a minority of instances dialysis may be required. Microangiopathic hemolysis and thrombocytopenia secondary to ciclosporin or tacrolimus may further... 

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