OPEN-LABEL TRIAL OF ORAL NALMEFENE THERAPY FOR THE PRURITUS OF CHOLESTASIS

The aims of this study were to determine whether long-term oral admini stration of the opiate antagonist nalmefene is associated with any ben eficial effects in patients with pruritus secondary to cholestatic liv er disease and to assess the safety of long-term administration of thi s drug to these patients. Fourteen patients with unrelieved chronic pr uritus of cholestasis were studied. Scratching activity, independent o f limb movements, was recorded continuously for 24-hour periods before and during treatment with an initial ameliorating dose of nalmefene. Simultaneously, during these periods, visual analogue scores (VASs) of pruritus were recorded every 4 hours while patients were awake. The d ose of nalmefene, which initially was 2 mg orally twice daily, was inc reased during the study, usually until a satisfactory clinical respons e was achieved. Five patients experienced a transient opioid withdrawa l-like reaction that did not preclude continuing with nalmefene therap y. Serum biochemical indices of cholestasis did not change appreciably during treatment. Thirteen patients reported amelioration of the perc eption of pruritus on nalmefene. In 5 patients, exacerbations of pruri tus occurred approximately 4 weeks after an initial ameliorating dose had been reached; these exacerbations were managed by increasing the d ose. Baseline mean values for VAS and scratching activity were higher than corresponding means during nalmefene therapy in 13 (P = .002) and 12 (P = .013) patients, respectively. Possible tolerance to nalmefene occurred in 3 patients. Three patients experienced marked exacerbatio n of pruritus after nalmefene therapy was suddenly discontinued, Blood levels of nalmefene were consistent with normal pharmacokinetics of t he drug. These results suggest that nalmefene may have a favorable ris k-to-benefit ratio when it is administered orally long-term to patient s with the pruritus of cholestasis.