Efficacy of Fenoverine and Trimebutine in the Management of Irritable Bowel Syndrome: Multicenter Randomized Double-blind Non-inferiority Clinical Study / 대한소화기학회지

BACKGROUND/AIMS: Antispasmodic agents have been used in the management of irritable bowel syndrome. However, systematic reviews have come to different conclusions about the efficacy in irritable bowel syndrome. Fenoverine acts as a synchronizer of smooth muscle in modulating the intracellular influx of calcium. We compared fenoverine with trimebutine for the treatment of patients with IBS. METHODS: A multicenter, randomized, double-blind, non-inferiority clinical study was conducted to compared fenoverine with trimebutine. Subjects were randomized to receive either fenoverine (100 mg three times a day) or trimebutine (150 mg three times a day) for 8 weeks. A total of 197 patients were analyzed by the intention-to-treat approach. The primary endpoint was the proportion of patients who had 30% reduction in abdominal pain or discomfort measured by bowel symptom scale (BSS) score at week 8 compared to the baseline. The secondary endpoints were changes of abdominal bloating, diarrhea, constipation, overall and total scores of BSS, and overall satisfaction. RESULTS: At week 8, fenoverine was shown to be non-inferior to trimebutine (treatment difference, 1.76%; 90% CI, -10.30-13.82; p=0.81); 69.23% (54 of 78 patients) of patients taking fenoverine and 67.47% (56 of 83 patients) of patients taking trimebutine showed 30% reduction in abdominal pain or discomfort compared to the baseline. There results of the secondary endpoints were also comparable between the fenoverine group and the trimebutine group. CONCLUSIONS: Fenoverine is non-inferior to trimebutine for treating IBS in terms of both efficacy and tolerability.

3 Cases of Fenoverine-Induced Rhabdomyolysis / 대한신장학회잡지

Fenoverine is a spasmolytic drug. It has been reported as a causative drug for rhabdomyolysis in France and also in Korea. Well known risk factors for fenoverine induced rhabdomyolysis are hepatic dysfunction, renal dysfunction, concomitant use of lipid lowering drug, mitochondrial myopathy, lipid storage myopathy or malignant hyperthermia. We describe the clinical findings of 3 cases of fenoverine-induced rhabdomyolysis. (Case 1) A 78 year-old male patient complained of generalized myalgia after 7 days medication of fenoverine 300 mg, daily. (Case 2) A 72 year-old female who had been on statin medication for 4 years, complained of generalized myalgia and weakness after 1 day medication of 300 mg of fenoverine. (Case 3) A 57 year-old female who was diagnosed with liver cirrhosis, complained of generalized myalgia, after 4 days medication of 300mg of fenoverine. Laboratory and Tc-99m MDP bone scan findings were compatible with rhabdomyolysis in all 3 patients: ARF was complicated in case 2 and 3. The renal function improved with supportive care. As far as our knowledge concerned, case 1 is the first report of fenoverine-induced rhabdomyolysis without previously known risk factors. So we suggest when physicians are prescribing fenoverine, careful monitoring of symptoms and signs of rhabdomyolysis should be taken to all patients.

A case of fenoverine-induced rhabdomyolysis in diabetic nephropathy / 대한내과학회지

Fenoverine is a non-atropine like spasmolytic drug that inhibits calcium channel currents in the smooth muscle. It has been occassionally reported that fenoverine can cause rhabdomyolysis under the certain conditions such as hepatic dysfunction, concomitant use of HMG-CoA reductase, mitochondrial myopathy, lipid storage myopathy or malignant hyperthermia. However, there is no report of fenoverine-induced rhabdomyolysis in type 2 diabetic nephropathy patient. So we describe here a case of fenoverine-induced rhabdomyolysis in type 2 diabetic patient. A 70-year-old man had both lower legs and shoulder pain for 5 days prior to hospital admission. He was a type 2 diabetic patient and had been managed for diabetic nephropathy. He had been consumed common doses of fenoverine for 20 days due to abdominal pain and diarrhea. Results of investigations showed evidence of rhabdomyolysis. Fenoverine therapy was stopped after admission and he was treated supportive care, his condition was recovered. In this case, renal function impairment may have been a predisposing factor for fenoverine-induced rhabdomyolysis. The incidence of muscular complications of fenoverine therapy could be reduced by avoidance of prescription of the drug in patients with diabetic nephropathy.

Fenoverine-induced Rhabdomyolysis in a Patient with Liver Cirrhosis / 대한신장학회잡지

Fenoverine is a drug with a phenothiazine structure which has a non-atropine-like spasmolytic action on the smooth muscle by inhibiting calcium channel currents. Recently, it has been occasionally reported that fenoverine can cause rhabdomyolysis under the certain conditions such as hepatic dysfunction, concomitant use of HMG-CoA reductase, mitochondrial myopathy, lipid storage myopathy or malingnat hyperthermia. We describe here a patient with fenoverine-induced rhabdomyolysis and ARF. An 38 year-old male liver cirrhosis patient, who had been received fenoverine 300mg daily for a month, admitted with generalache, weakness and oliguria. The patient showed typical laboratory findings of rhabdomyolysis and bone scan showed extensive uptake of Tc-99m MDP in muscle. No other traumatic, metabolic, toxic or enzymatic causes of the rhabdomyolysis were found in careful history. The patient recovered from rhabdomyolysis after drug discontinuation and dialysis treatment for ARF. Pre-existing hepatic dysfunction might had induced the accumulation of fenoverine and subsequent rhabdomyolysis in this patient. The incidence of muscular complications of fenoverine therapy could be reduced by avoidance of prescription of this drug in patients with hepatopathy or those being treated with cholesterol-lowing agents. Physicians shold be aware of life-threatening adverse effects of apparently innocuous drugs.

Fenoverine-induced Rhabdomyolysis in a Patient with Liver Cirrhosis / 대한신장학회잡지

Fenoverine is a drug with a phenothiazine structure which has a non-atropine-like spasmolytic action on the smooth muscle by inhibiting calcium channel currents. Recently, it has been occasionally reported that fenoverine can cause rhabdomyolysis under the certain conditions such as hepatic dysfunction, concomitant use of HMG-CoA reductase, mitochondrial myopathy, lipid storage myopathy or malingnat hyperthermia. We describe here a patient with fenoverine-induced rhabdomyolysis and ARF. An 38 year-old male liver cirrhosis patient, who had been received fenoverine 300mg daily for a month, admitted with generalache, weakness and oliguria. The patient showed typical laboratory findings of rhabdomyolysis and bone scan showed extensive uptake of Tc-99m MDP in muscle. No other traumatic, metabolic, toxic or enzymatic causes of the rhabdomyolysis were found in careful history. The patient recovered from rhabdomyolysis after drug discontinuation and dialysis treatment for ARF. Pre-existing hepatic dysfunction might had induced the accumulation of fenoverine and subsequent rhabdomyolysis in this patient. The incidence of muscular complications of fenoverine therapy could be reduced by avoidance of prescription of this drug in patients with hepatopathy or those being treated with cholesterol-lowing agents. Physicians shold be aware of life-threatening adverse effects of apparently innocuous drugs.