Side Effects of Questran (cholestyramine)

Questran (cholestyramine) is a cholesterol-lowering agent used to reduce cholesterol levels in the blood, to relieve the itching of liver and biliary disease, and to treat overdoses of digoxin, or thyroid hormone. Questran also is recommended for the rapid elimination of leflunomide.

Cholesterol that is ingested or manufactured in the body is eliminated primarily by conversion to bile acids in the liver and excretion into the intestine with bile. The bile enters the intestine, and most of the bile acids are reabsorbed from the intestine. These reabsorbed bile acids are removed from the blood by the liver and excreted again into bile. Thus, bile acids re-circulate in the body. 

Questran binds to bile acids in the intestine. This prevents their absorption, and the cholestyramine/bile acid complexes are eliminated in the stool. As a result, the body loses bile acids. To compensate for this loss, the liver increases the conversion of cholesterol to bile acids. 

The conversion of cholesterol to bile acids reduces the cholesterol in the body, and the levels of cholesterol drop in the blood. One of the most troubling symptoms in patients with liver and biliary disease is itching. The itching is believed in some cases to be the result of accumulation of bile acids in the skin due to the inability of the liver or bile ducts to eliminate bile acids normally. 

By binding bile acids in the intestines and preventing their absorption, Questran hastens the elimination of bile acids from the body and skin, and the itching improves. Questran also binds some drugs in the intestine, preventing their absorption and hastening their elimination. Therefore, Questran is useful in some situations in which there has been an overdose of drugs.

Common side effects of Questran include

• constipation,
• abdominal pain,
• bloating,
• vomiting,
• diarrhea,
• belching,
• gallstones,
• weight loss,
• excessive gas (flatulence), and
• discolored teeth.

Serious side effects of Questran include

• gastric ulcer,
• gastrointestinal bleeding and
• deficiency of vitamins A, D, E, and K with long-term use.

Drug interactions of Questran include warfarin, thyroid hormones, digoxin, and thiazide diuretics, because Questran decreases their absorption. Therefore, these drugs should be administered 1 hour before or 4-6 hours after the administration of Questran. Questran decreases the conversion of leflunomide to its active form and reduces the absorption of vitamin A, D, E and K. 

Use of Questran in pregnant women has not been adequately evaluated. Since Questran is not absorbed into the bloodstream, the risk of adverse effects on the fetus probably is low.

Questran decreases the intestinal absorption of vitamins A, D, E and K by the mother. This could lead to a decrease in the concentration of these vitamins in the mother's milk and potentially cause vitamin deficiency in the infant. Consult your doctor before breastfeeding.

The most common side effects of cholestyramine are:

• constipation,
• abdominal pain,
• bloating,
• vomiting,
• diarrhea,
• belching,
• gallstones,
• weight loss, and
• excessive passage of gas (flatulence).

Other side effects include:

• discolored tooth,
• gastric ulcer, and
• gastrointestinal bleeding.

Long-term use of cholestyramine may cause a deficiency of vitamin A, D, E, and K. Constipation can be an important side effect of cholestyramine, perhaps because the presence of free bile acids in the intestine helps determine the amount of water in stool, and cholestyramine binds the free bile acids.

It is recommended that additional fluids be drunk when taking cholestyramine; however, it is not known for certain if this prevents constipation, and more aggressive treatment with fiber, stool softeners or even laxatives such as milk of magnesia may be necessary.

The most common adverse reaction is constipation. When used as a cholesterol-lowering agent predisposing factors for most complaints of constipation are high dose and increased age (more than 60 years old). Most instances of constipation are mild, transient, and controlled with conventional therapy. Some patients require a temporary decrease in dosage or discontinuation of therapy.

Less Frequent Adverse Reactions: Abdominal discomfort and/or pain, flatulence, nausea, vomiting, diarrhea, eructation, anorexia, and steatorrhea, bleeding tendencies due to hypoprothrombinemia (Vitamin K deficiency) as well as Vitamin A (one case of night blindness reported) and D deficiencies, hyperchloremic acidosis in children, osteoporosis, rash and irritation of the skin, tongue and perianal area. Rare reports of intestinal obstruction, including two deaths, have been reported in pediatric patients.

Occasional calcified material has been observed in the biliary tree, including calcification of the gallbladder, in patients to whom Questran has been given. However, this may be a manifestation of the liver disease and not drug related.

One patient experienced biliary colic on each of three occasions on which he took Questran. One patient diagnosed as acute abdominal symptom complex was found to have a “pasty mass” in the transverse colon on x-ray.

Other events (not necessarily drug related) reported in patients taking Questran include:

• Gastrointestinal: GI-rectal bleeding, black stools, hemorrhoidal bleeding, bleeding from known duodenal ulcer, dysphagia, hiccups, ulcer attack, sour taste, pancreatitis, rectal pain, diverticulitis.
• Laboratory test changes: Liver function abnormalities.
• Hematologic: Prolonged prothrombin time, ecchymosis, anemia
• Hypersensitivity: Urticaria, asthma, wheezing, shortness of breath.
• Musculoskeletal: Backache, muscle and joint pains, arthritis.
• Neurologic: Headache, anxiety, vertigo, dizziness, fatigue, tinnitus, syncope, drowsiness, femoral nerve pain, paresthesia.
• Eye: Uveitis.
• Renal: Hematuria, dysuria, burnt odor to urine, diuresis.
• Miscellaneous: Weight loss, weight gain, increased libido, swollen glands, edema, dental bleeding, dental caries, erosion of tooth enamel, tooth discoloration.

• Questran (Cholestyramine for Oral Suspension USP) may delay or reduce the absorption of concomitant oral medication such as phenylbutazone, warfarin, thiazide diuretics (acidic), or propranolol (basic), as well as tetracycline, penicillin G, phenobarbital, thyroid and thyroxine preparations, estrogens and progestins, and digitalis.
• Interference with the absorption of oral phosphate supplements has been observed with another positively-charged bile acid sequestrant. Questran may interfere with the pharmacokinetics of drugs that undergo enterohepatic circulation.
• The discontinuance of Questran could pose a hazard to health if a potentially toxic drug such as digitalis has been titrated to a maintenance level while the patient was taking Questran.
• Because cholestyramine binds bile acids, Questran may interfere with normal fat digestion and absorption and thus may prevent absorption of fat-soluble vitamins such as A, D, E and K.
• When Questran is given for long periods of time, concomitant supplementation with water-miscible (or parenteral) forms of fat-soluble vitamins should be considered.

SINCE Questran MAY BIND OTHER DRUGS GIVEN CONCURRENTLY, IT IS RECOMMENDED THAT PATIENTS TAKE OTHER DRUGS AT LEAST ONE HOUR BEFORE OR 4 TO 6 HOURS AFTER Questran (OR AT AS GREAT AN INTERVAL AS POSSIBLE) TO AVOID IMPEDING THEIR ABSORPTION.