Colchicine Ciclosporin

CICLOSPORIN COLCHICINE t colchicine plasma concentrations and t toxic effects (hepatotoxicity, myopathy), t penetration of ciclosporin through blood-brain barrier and t risk of neurotoxicity Competitive inhibition of P-gp with t penetrations of ciclosporin to the tissues. Ciclosporin inhibits the transport of colchicine Avoid co-administration... 

Azathioprine (blood count and liver function) Colchicine (blood count, plasma creatinine) Ciclosporin (plasma creatinine)... 

Muscle disorders attributed to ciclosporin have been mostly described in anecdotal case reports (SED-14, 1291). In an analysis of pnblished or spontaneous case reports, the manufacturers found 29 cases of muscle disorders in patients taking ciclosporin the complications fell into two categories (162). Myopathic symptoms, that is myalgia and muscle weakness without rhabdomyolysis, were reported in 0.17% of patients and abated after dose reduction or treatment withdrawal. Rhabdomyolysis occurred in under 0.05% of patients and was mostly observed in patients taking other drugs, such as lovastatin or colchicine. 

This topic has been re-analysed in a systematic review of published papers, in which relevant information from a total of 34 patients was identified (163). AU but two patients were also taking concomitant drugs known to affect the muscles, among which glucocorticoids, simvastatin, lovastatin, colchicine, and pyrazinamide were the most frequently cited. Ciclosporin is therefore difficult to implicate in most patients, but at least one case with positive ciclosporin re-administration supported a causative role. The clinical picture was non-specific, with myalgia, cramps, and muscle weakness, sometimes associated with raised serum creatine kinase activity, and heterogeneous histopathology. FinaUy, skeletal muscle abnormalities have rarely been described in patients without muscle symptoms. 

The combination of colchicine with ciclosporin increased the risk of myopathy. In a retrospective study of 221 renal transplant patients, five of 10 patients who took both drugs developed acute or chronic proximal myopathy, whereas none of the 30 controls matched for age, sex, transplant duration, ciclosporin use, and cumulative dose of glucocorticoids had similar symptoms (238). 

Acute reversible ciclosporin toxicity occurred in a renal transplant patient a few days after colchicine was administered for an acute attack of gout (SEDA-16, 115). Other potential adverse effects of combining colchicine with ciclosporin include diarrhea, increases in serum liver enzymes, bilirubin, and creatinine, and less often severe myalgia (SEDA-19, 101). Acute myopathy, associated with neuropathy in one case, has been observed in two young renal transplant recipients (SEDA-22, 119). 

Sobh M, Sabry A,Moustafa F, Foda MA, Sally S,Ghoneim M. Effect of colchicine on chronic ciclosporin nephrotoxicity in Sprague-Dawley rats. Nephron 1998 79 452-457. 

Drug-drug iuteractions Colchicine is metabolized by CYP3A4 and transported by P glycoprotein. It can therefore accumulate and have toxic effects during concomitant therapy with inhibitors of CYP3A4 and P glycoprotein, such as clarithromycin, disulfiram, and ciclosporin. Three such cases have been described [93, 94, 95 ]. 

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See also in sourсe #XX -- [ ]

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