Flumecinol for the treatment of pruritus associated with primary biliarg cirrhosis

Abstract

Objective : To determine whether flumecinol (3-trifluoromethyl-a-ethylbenzhydrol, Zixoryn) is effective in ameliorating pruritus of cholestasis, particularly in primary bilary cirrhosis. Methods and Results: 50 patients (46 with primary biliary cirrhosis, PBC) took oral flumecinol 600 mg or identical placebo once weekly for 3 weeks. Patients assessed pruritus by scoring a daily 100 mm visual analogue scale (VAS; 0 = no itch, 100 = severe, continuous, day and night intolerable itch). Quality of life was similarly measured. Patients scored the VAS daily for a 7-day baseline and for a further 21 days. Subjectively, pruritus improved in 13 of 24 on flumecinol and 10 of 26 on placebo (x' = 1.24, P = 0.2 7). Median difference in fall in VAS pruritus score between baseline week (mean score for each individual used) and the last week was 8.0 [95 % confidence interval (CI) -2.1 to 20.81 and for VAS quality of life was 5.0 (95% C1 0.4 to 13.0) both in favour of flumecinol over placebo. Later, 1 9 patients (all PBC) were randomised to flumecinol 300 mg or placebo daily for 3 weeks. Subjectively, pruritus improved in 7 of 10 on flumecinol and 1 of 9 on placebo (Fisher's exact test, P = 0.02). Median difference in fall in VAS pruritus score was 19.8 mm (95 % CI 3.3 to 40.7 mm) in favour of flumecinol over placebo and for quality of life was 3.5 mm (95 % C1 -5.9 to 24.9 mm). Flumecinol did not significantly affect liver function tests, antipyrine clearance or serum total bile acids, and was not associated with any significant side-effects. Conclusion: Flumecinol was safe at the above doses and short term treatment with 300 mg daily, significantly ameliorated pruritus in primary biliary cirrhosis.

Efficacy of Treatments for Cholestatic Pruritus: A Systemic Review and Meta-analysis

“…Flumecinol (1 study). Turner et al ( 105 ) conducted a randomized double-blind placebo-controlled parallel study evaluating 2 different doses of flumecinol (600 mg weekly and 300 mg a day). Initially, 50 patients who complained of itch related to cholestatic disorders were randomized to receive flumecinol 600 mg or placebo.…”

The pruritus of cholestasis

“…Other therapeutic modalities that have been used to treat the pruritus of cholestasis include flumecinol [122], antioxidants [123], and androgens [124]. In the context of steroid treatment, of prednisone has been used anecdotally to treat the pruritus of cholestasis by some clinicians (NVBergasa, personal conversations).…”

Drug Treatments for Pruritus in Adult Palliative Care

“…Flumecinol (3-trifluoromethyl-alpha-ethylbenzhydrol) was investigated in two studies at different dosages (600 mg/week and 300 mg/d) (28). The pruritus measurement in one of the studies (600 mg/week) resulted in a group difference relating to the median improvement of 8 mm on the VAS (0-100 mm; 95% CI: -2.1 mm to 20.8 mm; p=0.17) in favor of the intervention group.…”

“…For flumecinol, efficacy was seen only for a dosage of 300 mg twice daily, but not for 600 mg/week (28). Since no adverse effects or dropouts were reported, one may cautiously assume relative safety for flumecinol, in spite of the small case numbers.…”