Questran

Common Side Effects of Cholestyramine

Tell your doctor if any of the following side effects are severe or don't go away:

• Constipation
• Gas or bloating
• Stomach pain
• Upset stomach
• Dizziness
• Vomiting or diarrhea
• Loss of appetite
• Heartburn or indigestion

Serious Side Effects of Cholestyramine

Call your doctor immediately if you experience any of the following serious side effects:

• Unusual bleeding (including gum bleeding or bleeding from the rectum)
• Signs of an allergic reaction, which may include rash; hives; difficulty breathing; chest tightness; or swelling of the mouth, face, lips, or tongue
• Black or bloody stools
• Severe nausea
• Shortness of breath
• Unusual bruising

Cholesterol is probably the sole precursor of bile acids. During normal digestion, bile acids are secreted into the intestines. A major portion of the bile acids is absorbed from the intestinal tract and returned to the liver via the enterohepatic circulation. Only very small amounts of bile acids are found in normal serum.

Cholestyramine resin adsorbs and combines with the bile acids in the intestine to form an insoluble Cholestyramine resin adsorbs and combines with the bile acids in the intestine to form an insoluble complex which is excreted in the feces. This results in a partial removal of bile acids from the enterohepatic circulation by preventing their absorption.

The increased fecal loss of bile acids due to Cholestyramine administration leads to an increased oxidation of cholesterol to bile acids, a decrease in beta lipoprotein or low density lipoprotein plasma levels and a decrease in serum cholesterol levels. Although in man, Cholestyramine produces an increase in hepatic synthesis of cholesterol, plasma cholesterol levels fall.

In patients with partial biliary obstruction, the reduction of serum bile acid levels by Cholestyramine reduces excess bile acids deposited in the dermal tissue with resultant decrease in pruritus.

Clinical Studies

In a large, placebo-controlled, multi-clinic study, LRC-CPPT 1, hypercholesterolemic subjects treated with QUESTRAN had mean reductions in total and low-density lipoprotein cholesterol (LDL-C) which exceeded those for diet and placebo treatment by 7.2% and 10.4%, respectively. Over the seven-year study period the QUESTRAN group experienced a 19% reduction (relative to the incidence in the placebo group) in the combined rate of coronary heart disease death plus non-fatal myocardial infarction (cumulative incidences of 7% QUESTRAN and 8.6% placebo). The subjects included in the study were men aged 35 - 59 with serum cholesterol levels above 265 mg/dL and no previous history of heart disease. It is not clear to what extent these findings can be extrapolated to females and other segments of the hypercholesterolemic population. (See also PRECAUTIONS: Carcinogenesis, Mutagenesis, Impairment Of Fertility.)

Two controlled clinical trials have examined the effects of QUESTRAN monotherapy upon coronary atherosclerotic lesions using coronary arteriography. In the NHLBI Type II Coronary Intervention Trial 2, 116 patients (80% male) with coronary artery disease (CAD) documented by arteriography were randomized to QUESTRAN or placebo for five years of treatment. Final study arteriography revealed progression of coronary artery disease in 49% of placebo patients compared to 32% of the QUESTRAN group (p<0.05).

In the St. Thomas Atherosclerosis Regression Study (STARS) 3, 90 hypercholesterolemic men with CAD were randomized to three blinded treatments: usual care, lipid-lowering diet, and lipid-lowering diet plus QUESTRAN. After 36 months, follow-up coronary arteriography revealed progression of disease in 46% of usual care patients, 15% of patients on lipid-lowering diet and 12% of those receiving diet plus QUESTRAN (p<0.02). The mean absolute width of coronary segments decreased in the usual care group, increased slightly (0.003mm) in the diet group and increased by 0.103mm in the diet plus QUESTRAN group (p<0.05). Thus in these randomized controlled clinical trials using coronary arteriography, QUESTRAN monotherapy has been demonstrated to slow progression 2,3 and promote regression3 of atherosclerotic lesions in the coronary arteries of patients with coronary artery disease.

The effect of intensive lipid-lowering therapy on coronary atherosclerosis has been assessed by arteriography in hyperlipidemic patients. In these randomized, controlled clinical trials, patients were treated for two to four years by either conventional measures (diet, placebo, or in some cases low dose resin), or intensive combination therapy using diet plus colestipol (an anion exchange resin with a mechanism of action and an effect on serum lipids similar to that of QUESTRAN and QUESTRAN LIGHT) plus either nicotinic acid or lovastatin. When compared to conventional measures, intensive lipid-lowering combination therapy significantly reduced the frequency of progression and increased the frequency of regression of coronary atherosclerotic lesions in patients with or at risk for coronary artery disease.

REFERENCES

The Lipid Research Clinics Coronary Primary Prevention Trial Results: (I) Reduction in Incidence of Coronary Heart Disease; (II) The Relationship of Reduction in Incidence of Coronary Heart Disease to Cholesterol Lowering. JAMA 1984; 251:351-374.

Brensike JF, Levy RI, Kelsey SF, et al. Effects of therapy with cholestyramine on progression of coronary arteriosclerosis: results of the NHLBI type II coronary intervention study. Circulation 1984;69:313-24.

Watts, GF, Lewis B, Brunt JNH, Lewis ES, et al. Effects on coronary artery disease of lipidlowering diet, or diet plus cholestyramine, in the St Thomas Atherosclerosis Regression Study (STARS). Lancet 1992;339:563-69.

Questran is part of the drug class:

• Bile acid sequestrants

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Overdose symptoms may include severe stomach pain or constipation.

Tell your doctor about all your current medicines and any you start or stop using, especially:

• birth control pills or hormone replacement therapy;

• digoxin (digitalis);

• a diuretic or "water pill";

• penicillin G;

• phenobarbital;

• phenylbutazone;

• propranolol;

• spironolactone;

• tetracycline;

• thyroid medication such as levothyroxine (Synthroid and others); or

• warfarin (Coumadin, Jantoven).

This list is not complete. Other drugs may interact with cholestyramine, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed in this medication guide.

This section provides information on the proper use of a number of products that contain cholestyramine. It may not be specific to Questran. Please read with care.

Take this medicine exactly as directed by your doctor. Try not to miss any doses and do not take more medicine than your doctor ordered.

This medicine should never be taken in its dry form, since it could cause you to choke. Instead, always mix as follows:

• Place the medicine in 2 ounces of any beverage and mix thoroughly. Then add an additional 2 to 4 ounces of beverage and again mix thoroughly (it will not dissolve) before drinking. After drinking all the liquid containing the medicine, rinse the glass with a little more liquid and drink that also, to make sure you get all the medicine.
• You may also mix this medicine with milk in hot or regular breakfast cereals, or in thin soups such as tomato or chicken noodle soup. Or you may add it to some pulpy fruits such as crushed pineapple, pears, peaches, or fruit cocktail.

For patients taking this medicine for high cholesterol :

• Importance of diet—Before prescribing medicine for your condition, your doctor will probably try to control your condition by prescribing a personal diet for you. Such a diet may be low in fats, sugars, and/or cholesterol. Many people are able to control their condition by carefully following their doctor's orders for proper diet and exercise. Medicine is prescribed only when additional help is needed. Follow carefully the special diet your doctor gave you, since the medicine is effective only when a schedule of diet and exercise is properly followed.
• Also, this medicine is less effective if you are greatly overweight. It may be very important for you to go on a reducing diet. However, check with your doctor before going on any diet.
• Remember that this medicine will not cure your cholesterol problem but it will help control it. Therefore, you must continue to take it as directed if you expect to lower your cholesterol level.

Dosing

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For oral dosage form (powder for oral suspension):
  • For high cholesterol or pruritus (itching) related to biliary obstruction:
    • Adults—At first, 4 grams one or two times a day before meals. Then, your doctor may increase your dose to 8 to 24 grams a day. This is divided into two to six doses.
    • Children—At first, 4 grams a day. This is divided into two doses and taken before meals. Then, your doctor may increase your dose to 8 to 24 grams a day. This is divided into two or more doses.

Missed Dose

If you miss a dose of this medicine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

It is very important that your doctor check your progress at regular visits. This will allow your doctor to see if the medicine is working properly and to decide if you should continue to take it.

Do not take any other medicine unless prescribed by your doctor since cholestyramine may change the effect of other medicines.

Do not stop taking this medicine without first checking with your doctor. When you stop taking this medicine, your blood cholesterol levels may increase again. Your doctor may want you to follow a special diet to help prevent this from happening.

1) Questran (Cholestyramine for Oral Suspension USP), is indicated as adjunctive therapy to diet for the reduction of elevated serum cholesterol in patients with primary hypercholesterolemia (elevated low density lipoprotein [LDL] cholesterol) who do not respond adequately to diet. Questran may be useful to lower LDL cholesterol in patients who also have hypertriglyceridemia, but it is not indicated where hypertriglyceridemia is the abnormality of most concern.

Therapy with lipid-altering agents should be a component of multiple risk factor intervention in those individuals at significantly increased risk for atherosclerotic vascular disease due to hypercholesterolemia. Treatment should begin and continue with dietary therapy specific for the type of hyperlipoproteinemia determined prior to initiation of drug therapy. Excess body weight may be an important factor and caloric restriction for weight normalization should be addressed prior to drug therapy in the overweight.

Prior to initiating therapy with Questran, secondary causes of hypercholesterolemia (e.g., poorly controlled diabetes mellitus, hypothyroidism, nephrotic syndrome, dysproteinemias, obstructive liver disease, other drug therapy, alcoholism), should be excluded, and a lipid profile performed to assess Total cholesterol, HDL-C, and triglycerides (TG). For individuals with TG less than 400 mg/dL (<4.5 mmol/L), LDL-C can be estimated using the following equation:

LDL-C = Total cholesterol – [(TG/5) + HDL-C]

For TG levels >400 mg/dL, this equation is less accurate and LDL-C concentrations should be determined by ultracentrifugation. In hypertriglyceridemic patients, LDL-C may be low or normal despite elevated Total-C. In such cases Questran may not be indicated.

Serum cholesterol and triglyceride levels should be determined periodically based on NCEP guidelines to confirm initial and adequate long-term response. A favorable trend in cholesterol reduction should occur during the first month of Questran therapy. The therapy should be continued to sustain cholesterol reduction. If adequate cholesterol reduction is not attained, increasing the dosage of Questran or adding other lipid-lowering agents in combination with Questran should be considered.

Since the goal of treatment is to lower LDL-C, the NCEP 4 recommends that LDL-C levels be used to initiate and assess treatment response. If LDL-C levels are not available then Total-C alone may be used to monitor long-term therapy. A lipoprotein analysis (including LDL-C determination) should be carried out once a year. The NCEP treatment guidelines are summarized below.

1) Questran monotherapy has been demonstrated to retard the rate of progression 2,3 and increase the rate of regression3 of coronary atherosclerosis.

2) Questran is indicated for the relief of pruritus associated with partial biliary obstruction. Questran for oral suspension has been shown to have a variable effect on serum cholesterol in these patients. Patients with primary biliary cirrhosis may exhibit an elevated cholesterol as part of their disease.

PHENYLKETONURICS: CHOLESTYRAMINE for ORAL SUSPENSION USP, LIGHT CONTAINS 14.0 mg PHENYLALANINE PER 5 GRAM DOSE.