uired a permanent reduction in dose. Anti-diarrhea agents have proven useful in some patients.
Discontinuation of chenodiol because of failure to control diarrhea is to be expected in approximately 3% of patients treated. Steady epigastric pain with nausea typical of lithiasis (biliary colic) usually is easily distinguishable from the crampy abdominal pain of drug-induced diarrhea.
Other less frequent, gastrointestinal side effects reported include urgency, cramps, heartburn, constipation, nausea, and vomiting, anorexic, epigastric distress, dyspepsis, flatulence and nonspecific abdominal pain.
Serum Lipids: Serum total cholesterol and low-density lipoprotein (LDL) cholesterol may rise 10% or more during administration of chenodiol: no change has been seen in the high-density lipoprotein (HDL) fraction; small decreases in serum triglyceride levels for females have been reported.
Hematologic: Decreases in white cell count, never below 3000, have been noted in a few patients treated with chenodiol; the drug was continued in all patients without incident.
DRUG ABUSE AND DEPENDENCE
Overdosage
Accidental or intentional overdoses of chenodiol have not been reported. One patient tolerated 4 gm/day (58 mg/kg/day) for six months without incident.
DOSAGE AND ADMINISTRATION
The recommended dose range for Chenodiol is 13 to 16 mg/kg/day in two divided doses, morning and night, starting with 250 mg b.i.d. the first two weeks and increasing by 250 mg/day each week thereafter until the recommended or maximum tolerated dose is reached. If diarrhea occurs during dosage buildup or later in treatment, it usually can be controlled by temporary dosage adjustment until symptoms abate, after which the previous dosage usually is tolerated. Dosage less than 10 mg/kg usually is ineffective and may be associated with increased risk of cholecystectomy, so is not recommended.
Body Weight Recommended Tablets/Day Dose Range
mg/kg
lb kg
100-130 45-58 3 17-13
131-185 59-75 4 17-13
186-200 76-90 5 18-14
201-235 91-107 6 18-14
236-275 108-125 7 18-14
The optimal frequency of monitoring liver function tests is not known. It is suggested that serum aminotransferase levels should be monitored monthly for the first three months and every three months thereafter during Chenodiol administration. Under NCGS guidelines, if a minor, usually transient elevations (1 ½ to3 three times the upper limit of normal) persisted longer than three to six months. Chenodiol was discontinued and resumed only after the aminotransferase level returned to normal; however, allowing the elevations to persist over such an interval is not know to be safe. Elevations over three times the upper limit of normal require immediate discontinuation of Chenodiol and usually reoccur on challenge.
Serum cholesterol should be monitored at six months intervals. It may be advisable to discontinue Chenodiol if cholesterol rises above the acceptable age-adjusted limit for given patient.
Oral cholecystograms or ultrasonograms are recommend at six to nine month intervals to monitor response. Complete dissolutions should be confirmed by a repeat test after one to three months continued Chenodiol administration. Most patients who eventually achieve complete dissolution will show partial (or complete) dissolution at the first on-treatment test. |
