cholestyramine

QUESTRAN®

(cholestyramine) for Oral Suspension USP


DRUG DESCRIPTION


QUESTRAN® (Cholestyramine for Oral Suspension USP), the chloride salt of a basic anion exchange resin,
a cholesterol lowering agent, is intended for oral administration.
Cholestyramine resin is quite hydrophilic, but insoluble in water. The
cholestyramine resin in QUESTRAN is not absorbed from the digestive
tract. Four grams of anhydrous cholestyra-mine resin is contained in 9
grams of QUESTRAN powder. Four grams of anhydrous cholestyramine resin
is contained in 5 grams of QUESTRAN LIGHT. It is represented by the
following structural formula:


QUESTRAN powder contains the following inactive ingredients:acacia,
citric acid, D&C Yellow No. 10, FD&C Yellow No.6, flavor
(natural and artificial Orange), polysorbate 80, propylene glycol
alginate and sucrose. QUESTRAN LIGHT contains the following inactive
ingredients: aspartame, citric acid, colloidal silicon dioxide, D&C
Yellow No. 10, FD&C Red No.40, flavor (natural and artificial
Orange), maltodextrin, propylene glycol alginate and xanthan gum

INDICATIONS
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 hypercholes-terolemia (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 hyper-triglyceridemia, 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 NCEP4 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.
LDL-Cholesterol mg/dL (mmol/L)

Definite Atherosclerotic Disease* Two or More Other Risk Factors** Initiation Level Goal
NO NO ≥ 190 < 160
( ≥ 4.9) ( < 4.1)
NO YES ≥ 160 < 130
( ≥ 4.1) ( < 3.4)
YES YES or NO ≥ 130 ≤ 100
( ≥ 3.4) ( ≤ 2.6)
*Coronary heart disease or peripheral vascular disease (including symptomatic carotid artery disease).
**Other risk factors for coronary heart disease (CHD) include:age
(males ≥ 45 years; females ≥ 55 years or premature menopause without
estrogen replacement therapy); family history of premature CHD; current
cigarette smoking; hypertension; confirmed HDL-C < 35 mg/dL ( <
0.91 mmol/L); and diabetes mellitus. Subtract one risk factor if HDL-C
is ≥ 60 mg/dL ( ≥ 1.6 mmol/L).

QUESTRAN monotherapy has been demonstrated to retard the rate of
progression2, 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 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.
DOSAGE AND ADMINISTRATION
The recommended starting adult dose for all QUESTRAN powdered products
(QUESTRAN Powder and QUESTRAN LIGHT) is one packet or one level
scoopful once or twice a day. The recommended maintenance dose for all
QUESTRAN powdered products is 2 to 4 packets or scoopfuls daily (8-16
grams anhydrous cholestyramine resin) divided into two doses. Four
grams of anhydrous cholestyramine resin is contained in each measured
dose of QUESTRAN as follows:

QUESTRAN Powder 9 grams
QUESTRAN LIGHT 5 grams

It is recommended that increases in dose be gradual with periodic
assessment of lipid/lipoprotein levels at intervals of not less than 4
weeks. The maximum recommended daily dose is six packets or scoopfuls
of QUESTRAN (24 grams of anhydrous cholestyramine resin). The suggested
time of administration is at mealtime but may be modified to avoid
interference with absorption of other medications. Although the
recommended dosing schedule is twice daily, QUESTRAN may be
administered in 1-6 doses per day.
QUESTRAN should not be taken in its dry form. Always mix QUESTRAN with
water or other fluids before ingesting. See Preparation Instructions.
Concomitant Therapy
Preliminary evidence suggests that the lipid-lowering effects of
QUESTRAN on total and LDL-cholesterol are enhanced when combined with a
HMG-CoA reductase inhibitor, e.g., pravastatin, lovastatin,
simvastatin, and fluvastatin. Additive effects on LDL-cholesterol are
also seen with combined nicotinic acid /QUESTRAN therapy. See the DRUG
INTERACTIONS subsection of the PRECAUTIONS section for recommendations
on administering concomitant therapy.
Preparation
The color of QUESTRAN may vary somewhat from batch to batch but this
variation does not affect the performance of the product. Place the
*******s of one single-dose packet or one level scoopful of QUESTRAN in
a glass or cup. Add an amount of water or other non-carbonated beverage
of your choice depending on the product being used:

Product Formula Amount of Water or other Non-Carbonated Liquid
QUESTRAN Powder 2-6 ounces per dose
QUESTRAN LIGHT 2-6 ounces per dose

Stir to a uniform consistency and drink.
QUESTRAN may also be mixed with highly fluid soups or pulpy fruits with
a high moisture ******* such as applesauce or crushed pineapple.
HOW SUPPLIED
QUESTRAN® Powder (Cholestyramine for Oral Suspension USP) is available
in cans containing 378 grams and in cartons of sixty 9 gram packets.
Four grams of anhydrous cholestyra-mine resin are contained in 9 grams
of QUESTRAN Powder. The 378 g can includes a 15 cc scoop. The scoop is
not interchangeable with scoops from other products.

NDC-49884-936-66 Can, 378 g
NDC-49884-936-65 Carton of 60, 9 g packets

QUESTRAN® LIGHT (Cholestyramine for Oral Suspension USP) is available
in cans containing 210 grams and in cartons of sixty 5 gram
packets.Four grams of anhydrous cholestyramine resin are contained in 5
grams of QUESTRAN LIGHT. The 210 g can includes a 9 cc scoop. The scoop
is not interchangeable with scoops from other products.

NDC-49884-937-67 Can, 210 g
NDC-49884-937-65 Carton of 60, 5 g packets

Storage
Store between 20°-25°C (68°-77°F).[See USP Controlled Room Temperature].Excursions permitted to 15°-30°C (59°-86°F).
REFERENCES
2. 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.
3. Watts, GF, Lewis B, Brunt JNH Lewis ES, et al.Effects on coronary
artery disease of lipid-lowering diet, or diet plus cholestyramine. In
the St. Thomas Atherosclerosis Regression Study (STARS). Lancet
1992;339:563-69.
4.National Cholesterol Education Program. Second Report of the Expert
Panel Detection. Evaluation, and Treatment of High Blood Cholesterol in
Adults (Adult Treatment Panel II). Circulation 1994 Mar; 89(3):1333-445.

SIDE EFFECTS
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 QUES-TRAN. 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.
DRUG INTERACTIONS
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