1) A study in human volunteers (n=11) showed a reduction in serum amiodarone levels and elimination half-life after an oral 400 mg dose of amiodarone followed by cholestyramine 4 grams/hour for 4 hours (Nitsch & Luderitz, 1986). Another study recommended the use of cholestyramine (4 grams) immediately after gastric lavage, followed by further dosing for up to 12 hours, because of the potential for delayed absorption of amiodarone (Goddard & Whorwell, 1989).

1) ANIMAL STUDIES - Cholestyramine pretreatment prevented hepatic necrosis but not steatosis in rats injected intraperitoneally with carbon tetrachloride (Bioulac et al, 1981). The place of this agent in therapy of human poisonings is presently undefined.

1) Cholestyramine has been used to decrease serum digitoxin levels following an overdose (Hantson et al, 1991; Kuhlmann, 1984; Pieroni & Fisher, 1981; Cady et al, 1979; Gilfrich et al, 1978); however, the use of cholestyramine has not been shown to affect the outcome. Routine use is not recommended.

1) Cholestyramine has been recommended to chelate bile acids, which are necessary for absorption of iopanoic acid. It also has a high affinity for iopanoic acid, and interferes with its absorption (Nelson, 1974).

1) Cholestyramine (4 grams every eight hours) accelerated excretion of kepone and chlordane in excessively exposed workers, and probably would have a similar effect on other slowly excreted organochlorines which are trapped in the enterohepatic circulation (Garrettson et al, 1984-85; Cohn et al, 1978; Boylan et al, 1978).
2) In a randomized, placebo controlled clinical trial (n=22), 5 months of cholestyramine treatment in 12 patients increased the rate of clearance of chlordecone with an average of 50% decrease in the chlordecone half-life in the blood. A significant decrease in half-life was only observed in 1 of the 10 patients given placebo (Guzelian, 1982).
3) ANIMAL STUDIES - In animal studies of rats treated with radioactive chlordecone, cholestyramine increased fecal excretion and decreased total body concentrations of radioactive chlordecone compared to placebo-fed control animals (Guzelian, 1982).

1) Cholestyramine may also be an effective decontamination method following leflunomide overdose ingestions. Three healthy volunteers, given oral cholestyramine 8 grams three times daily for 24 hours, showed decreased plasma levels of M1 (the active metabolite of leflunomide) by approximately 40% in 24 hours and by 49% to 65% in 48 hours (Prod Info ARAVA(R) oral tablets, 2007).

1) ANIMAL STUDIES - The effects of cholestyramine and activated charcoal were compared in acutely poisoned mice, at doses of 2.25 g/kg each. It was found that cholestyramine was more effective than charcoal in preventing absorption of lindane. In addition, oral administration of cholestyramine reduced the incidence of seizures and death to a greater degree than activated charcoal in lindane-poisoned mice when used in equal doses. However, this dose of cholestyramine would not be feasible for humans (Kassner et al, 1993).

1) In one case report, oral cholestyramine (2 grams every 6 hours) and leucovorin effectively reduced serum methotrexate concentrations in a patient with methotrexate-induced nephrotoxicity (Shinozaki et al, 2000).
2) One study reported that oral cholestyramine may be of clinical value in patients receiving methotrexate who develop early renal function impairment by preventing reabsorption of methotrexate excreted via the bile, and improving the elimination of the drug in the feces (Merino-Sanjuan et al, 2004).

1) During clinical trials it was observed that the use of bile acid sequestrants, such as cholestyramine, increased the excretion of mycophenolic acid by interfering with enterohepatic circulation of the drug (Prod Info CellCept(R) capsules, tablets, oral suspension, injection, 2005). At the time of this review, it is not known to what extent this therapy may have utility or be effective following an acute exposure.

1) Cholestyramine 4 grams three times daily for 10 days, started 3.5 hours after a single oral dose of piroxicam 20 milligrams, decreased the elimination half-life of piroxicam (from 46.8 hours to 28.1 hours) and increased clearance by 60%. Similar effects were observed for intravenous tenoxicam 20 mg when cholestyramine was begun two hours before injection of tenoxicam. The elimination half-life was decreased from 67.4 hours to 31.9 hours (Guentert et al, 1988).
2) Cholestyramine 4 grams four times daily beginning 24 hours after a single 20 milligram dose of piroxicam resulted in a reduction of the mean piroxicam elimination half life from 53.1 hours to 29.6 hours in 8 subjects (Ferry et al, 1990).

1) Cholestyramine was effective in reducing the gastrointestinal absorption and increasing the elimination of phenprocoumon by interrupting its enterohepatic recycling. In one case report of a man who ingested 30 to 35 phenprocoumon tablets (90 to 105 mg), cholestyramine (4 grams three times daily for 10 days) decreased the phenprocoumon plasma concentration and decreased the elimination half-life from 6.8 days to 3.5 days (Meinertz et al, 1977).

1) In an uncontrolled case series, cholestyramine plus sorbitol appeared to have beneficial effects in patients exposed to Pfiesteria toxin. The proposed mechanism of action was binding of the toxin in the small intestine with subsequent excretion (Shoemaker, 1998). Further studies are necessary to determine the role of cholestyramine in treatment of Pfiesteria-related illness.

1) Thyroid hormone elimination appears to be enhanced by the serial administration of cholestyramine, 4 grams orally every 6 to 8 hours. In thyrotoxic states, the enterohepatic circulation of thyroid hormones is increased. In one case, the thyroid hormone level declined to normal values following 6 days of cholestyramine therapy (de Luis et al, 2002).

1) The administration of 8 grams twice a day to a man with acute vitamin D intoxication appeared to produce a more sustained decrease in serum calcium than high dose corticosteroids (Jibani & Hodges, 1985).
2) Cholestyramine 12 grams/day was given to a woman with acute vitamin D intoxication. Despite similar initial vitamin D serum levels to her husband, who was not treated with cholestyramine, there was a more rapid fall in vitamin D levels after 10 weeks of therapy (221 vs 412 nanomoles/liter) in the woman (Thomson & Johnson, 1986).
3) ANIMAL STUDIES - Oral cholestyramine was effective in the treatment of vitamin D toxicity in experimental animals (Queener & Bell, 1976).

1) The warfarin elimination half-life was decreased from 53 hours to 33 hours (38%) following administration of oral cholestyramine 4 grams four times a day, in a 25-year-old man who overdosed on warfarin (Renowden et al, 1985). In another study, a decrease in elimination half-life of around 30% has been demonstrated in volunteers given 4 grams three times a day following a single IV dose of warfarin (Jahnchen et al, 1978).

a) The most common adverse effect following therapeutic use is constipation. Age greater than 60 years and high-dose therapy are predisposing factors for the development of constipation, and the constipation is typically mild and transient (Prod Info QUESTRAN(R) oral suspension, 2006).

a) Two deaths involving intestinal obstruction have been reported in pediatric patients (Prod Info QUESTRAN(R) oral suspension, 2006; Merten & Grossman, 1980; Cohen et al, 1969)
b) Complete intestinal obstruction developed in a neonate being treated with cholestyramine resin for hyperbilirubinemia. Following birth, the infant experienced respiratory distress, recurrent abdominal distention and congestive heart failure. At one month of age, the patient also had hyperbilirubinemia which gradually increased to a total serum bilirubin of 22.8 g/dL at 53 days. The patient was at this time treated with oral cholestyramine powder mixed with dilute formula (0.5 g every 6 hours). Although bilirubin levels were decreasing, the infant had no stools for 9 days and developed sudden abdominal distention and emesis. At laparotomy, almost the entire small bowel and 2/3 of the large bowel were impacted. Cholestyramine therapy in combination with diminished bowel movement ability associated with prematurity and debilitation led to fecal impaction and ultimate obstruction (Merten & Grossman, 1980).

a) Abdominal pain has been reported following cholestyramine treatment (Prod Info QUESTRAN(R) oral suspension, 2006).

a) Flatulence has been reported following cholestyramine treatment (Prod Info QUESTRAN(R) oral suspension, 2006).

a) Nausea and vomiting have been reported following cholestyramine treatment (Prod Info QUESTRAN(R) oral suspension, 2006).

a) Diarrhea has been reported following cholestyramine treatment (Prod Info QUESTRAN(R) oral suspension, 2006).

a) Anorexia has been reported following cholestyramine treatment (Prod Info QUESTRAN(R) oral suspension, 2006).

a) Steatorrhea has been reported following cholestyramine treatment (Prod Info QUESTRAN(R) oral suspension, 2006).

a) Teeth discoloration, erosion of enamel or decay may result from sipping or holding the resin suspension in the mouth for prolonged periods (Prod Info QUESTRAN(R) oral suspension, 2006).
b) Loss of dental enamel occurred in a 7-year-old boy receiving cholestyramine 4 grams twice daily over a 2-year period. Change in tooth color was noted by the parents of the boy, and a subsequent dental examination revealed loss of enamel. Cholestyramine was mixed in Kool-Aid to improve taste, and this mixture was "swished" in the mouth for 10 to 15 minutes. Enamel loss was characteristic of a classic bulimic pattern where teeth are exposed to the low pH of gastric contents. Kool-Aid plus cholestyramine has a pH of 2.4 (Curtis et al, 1991).

a) Urinary tract calculi was associated with cholestyramine therapy in a 56-year-old man who experienced urethral calculi on 4 occasions corresponding to the initiation of cholestyramine therapy. With continued cholestyramine therapy, the calculi increased in size. Upon discontinuation of therapy, the passage of calculi ceased. The authors postulate that cholestyramine induced acidification of the urine causing precipitation of uric acid calculi (Courtney & Wightman, 1991).

a) Prolonged use of cholestyramine may result in hyperchloremic acidosis, especially in younger and smaller patients where the relative dosage may be higher. Patients with renal insufficiency or volume depletion have a greater risk of developing hyperchloremic acidosis (Prod Info QUESTRAN(R) oral suspension, 2006).
b) CASE REPORT/INFANT - An infant with an ileoresection, who received total parenteral nutrition, began oral feedings and developed severe diarrhea. The patient was then treated with oral cholestyramine 2.3 g/kg/day and in 5 days was noted to be pale, mottled, and lethargic. The infant's serum chloride level was found to be 125 mEq/liter with arterial pH of 7.15. Discontinuation of cholestyramine and institution of IV fluid therapy resulted in normalization of the patient's chloride and pH within 36 hours(Hartline, 1976).
c) CASE REPORT/CHILD - A 1-year-old child received oral cholestyramine therapy in a dose of 1.1 g/kg/day for 7 days for the treatment of severe diarrhea complicated by acute tubular necrosis. She developed hyperchloremia (serum level of 111.2 mEq/L) (Hartline, 1976)
d) CASE REPORT/CHILD - Hyperchloremic acidosis (pH = 7.18; CO2 = 9 mEq/L and Cl = 114 mEq/L) developed in a 9-year-old girl with decreased renal function, treated for 3 years with 4 to 8 grams/day of cholestyramine for elevated bile acids and hyperlipemia. The patient's hyperchloremic acidosis responded to therapy with sodium bicarbonate for 3 days (pH 7.40, CO2 = 22 mEq/L and Cl = 105 mEq/L). Rechallenge of the patient with cholestyramine resulted in a reduction of arterial pH to 7.29. Subsequently, the patient was discharged on combination therapy with sodium bicarbonate and 8 g/day of cholestyramine (Kleinman, 1974).
e) Concurrent use of cholestyramine with spironolactone can increase the risk of developing hyperchloremic acidosis (Prod Info QUESTRAN(R) oral suspension, 2006).
f) CASE REPORT/ADULT - Cholestyramine was associated with a hyperchloremic acidosis in a 70-year-old woman with hepatic encephalopathy. The patient had active cirrhosis secondary to hepatitis B and had been receiving spironolactone 100 mg/day for treatment of ascites and peripheral edema. This condition developed after administration of 3 'sachets' of cholestyramine daily for one month, increasing to 4 sachets daily one week prior to onset of the acidosis. The patient was given lactulose for the encephalopathy and cholestyramine was withdrawn. Hyperchloremic acidosis resolved spontaneously with normalization of plasma bicarbonate and plasma chloride within three days. It is suggested that concomitant therapy with spironolactone contributed to the acidosis (Clouston & Lloyd, 1985). Similar results were found in a 70-year-old female with a two-year history of primary biliary cirrhosis and cholestyramine-induced hyperchloremic metabolic acidosis (Eaves & Korman, 1984).
g) CASE REPORT/ADULT - A 45-year-old man with type 2 diabetes mellitus and nephropathy developed hyperchloremic metabolic acidosis (pH 7.12, HCO3 8 mmol/L, Cl 127 mmol/L, base excess -19 mmol/L) with a normal anion gap. His medication list at the time of admission included aspirin, felodipine, frusemide, isosorbide mononitrate, cholestyramine, and methyldopa. Discontinuation of cholestyramine therapy resulted in improvement in the patient's acidosis (Fan et al, 2008).

a) Bleeding tendencies due to hypoprothrombinemia have been reported with cholestyramine therapy (Prod Info QUESTRAN(R) oral suspension, 2006; Prod Info Questran Light(R), 97).
b) Supplementation of fat soluble vitamins may be necessary in some patients receiving long-term treatment with cholestyramine. A 57-year-old woman with chloretic enteropathy was treated with cholestyramine 12 g/day for 3 weeks. She was also receiving vitamin D and calcium. Three weeks after initiating therapy, the patient was noted to have gross hematuria, bloody colostomy discharge, and postural hypotension. The patient's hematocrit was 18.5% and prothrombin was greater than 100 seconds with a control of 12 seconds. The patient's partial thromboplastin time was 125 seconds with a control of 38 seconds. The platelet count was within normal limits. The patient was immediately treated with vitamin K 10 mg IM and after 4 hours the prothrombin time was 16 seconds and the following day was normal. The patient's bleeding ceased within 24 hours. Vitamin K was added to the patient's drug therapy regimen with maintenance of normal PT levels (Gross & Brotman, 1970a).

a) PLATELET GIGANTISM occurred in a 9-year-old boy undergoing treatment with cholestyramine to correct hypercholesterolemia (cholesterol level 446 mg/dL) and type IIa hyperlipoproteinemia associated with cutaneous xanthoma. Three months after initiation of cholestyramine, the boy was diagnosed with thrombocytopenia without any bleeding. Cholestyramine was stopped. Platelet count returned to reference range. Cholestyramine was re-instituted twice, with apparent thrombocytopenia recurring twice, but rapidly resolving after withdrawal of the drug. Platelet counts using 2 different automated analyzers showed values of 97 x 10(9)/liter during his cholestyramine therapy. A stained blood smear analysis was performed and revealed large and giant-size platelets. Other blood cells appeared normal; platelet aggregation was normal. According to contrast phase microscopy, platelet count after dilution was within the normal range (198 x 10(9)/liter). It was concluded that his previous platelet counts were spurious due to the presence of platelets of abnormally increased volume that were not properly counted by the automatic counters. His parents were found to have no blood cell abnormalities or deficiencies (Latger-Cannard et al, 2001).

a) Rash and irritation of skin, tongue, and perianal area have been reported following cholestyramine treatment (Prod Info QUESTRAN(R) oral suspension, 2006).

a) Osteoporosis has been reported following cholestyramine treatment (Prod Info QUESTRAN(R) oral suspension, 2006).

a) Cholestyramine may interfere with normal fat absorption and thus prevent absorption of fat soluble vitamins A, D, and K (Prod Info QUESTRAN(R) oral suspension, 2006).

a) Elevated thyrotropin levels with a corresponding reduction in serum free thyroxine values occurred in 7 hypothyroid patients who were receiving thyroid hormone and cholestyramine concurrently (Hamburger, 1990). It is unknown if the alterations in the thyroid function tests were due to a drug interaction or an alteration of thyroid function.