Document
DailyMed Label: Cholestyramine
Title
DailyMed Label: Cholestyramine
Date
2010
Document type
DailyMed Prescription
Name
Cholestyramine
Generic name
cholestyramine
Manufacturer
Physicians Total Care, Inc.
Product information
NDC: 54868-4812
Product information
NDC: 54868-4812
Product information
NDC: 54868-5526
Product information
NDC: 54868-5526
Description
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 Cholestyramine is not absorbed from the
digestive tract. Four grams of anhydrous cholestyramine resin is contained in 9
grams of Cholestyramine for Oral Suspension USP. Four grams of anhydrous
cholestyramine resin is contained in 5 grams of Cholestyramine for Oral
Suspension USP, Light. It is represented by the following structural formula:
Cholestyramine for Oral Suspension USP 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. Cholestyramine for Oral Suspension USP, 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.
image of chemical structure
Indications
1) 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. Cholestyramine 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 Cholestyramine, 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
(less than 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 Cholestyramine 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 Cholestyramine
therapy. The therapy should be continued to sustain cholesterol reduction. If
adequate cholesterol reduction is not attained, increasing the dosage of
Cholestyramine or adding other lipid-lowering agents in combination with
Cholestyramine 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.
LDL-Cholesterol mg/dL (mmol/L)
Definite Atherosclerotic Disease*
Two or More Other Risk Factors**
Initiation Level
Goal
NO
NO
Greater Than or Equal to 190 (Greater Than or Equal To 4.9)
Less Than 160 (Less Than 4.1)
NO
YES
Greater Than or Equal To 160 (Greater Than or Equal To 4.1)
Less Than 130 (Less Than 3.4)
YES
YES or NO
Greater Than or Equal To 130 (Greater Than or Equal To 3.4)
Less Than or Equal To 100 (Less Than or Equal To 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 greater than or equal to 45 years;
females greater than or equal to 55 years or premature menopause without estrogen replacement therapy);
family history of premature CHD; current cigarette smoking; hypertension;
confirmed HDL-C less than 35 mg/dL (less than 0.91 mmol/L); and diabetes mellitus. Subtract
one risk factor if HDL-C is greater than or equal to 60 mg/dL (greater than or equal to 1.6 mmol/L).
Cholestyramine
monotherapy has been demonstrated to retard the rate of progression 2,3 and increase the rate of regression 3
of coronary atherosclerosis.
2) Cholestyramine for
oral suspension is indicated for the relief of pruritus associated with partial
biliary obstruction. Cholestyramine 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.
Dosage
The recommended starting
adult dose for all cholestyramine for oral suspension powdered products
(Cholestyramine for Oral Suspension USP and Cholestyramine for Oral Suspension
USP, Light) is one packet or one level scoopful once or twice a day. The
recommended maintenance dose for all cholestyramine for oral suspension 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 Cholestyramine as
follows:
Cholestyramine for Oral Suspension USP
9 grams
Cholestyramine for Oral Suspension USP, 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 cholestyramine for oral suspension (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,
cholestyramine for oral suspension may be administered in 1–6 doses per day.
Cholestyramine should not be taken in its dry form. Always mix
Cholestyramine with water or other fluids before ingesting. See Preparation
Instructions.
Concomitant Therapy
Preliminary evidence
suggests that the lipid-lowering effects of Cholestyramine 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/Cholestyramine
therapy. See the Drug Interactions subsection of the
PRECAUTIONS section for recommendations on administering
concomitant therapy.
PREPARATION
The color of
Cholestyramine may vary somewhat from batch to batch but this variation does not
affect the performance of the product. Place the contents of one single-dose
packet or one level scoopful of Cholestyramine in a glass or cup. Add an amount
of water or other noncarbonated beverage of your choice depending on the product
being used:
Product
Formula
Amount of Water or
other Non-Carbonated Liquid
Cholestyramine for Oral Suspension USP
2-6 ounces per dose
Cholestyramine for Oral Suspension USP, Light
2-6 ounces per dose
Stir to a uniform
consistency and drink.
Cholestyramine may also
be mixed with highly fluid soups or pulpy fruits with a high moisture content
such as applesauce or crushed pineapple.
Contraindications
Cholestyramine for oral suspension is contraindicated in patients with complete
biliary obstruction where bile is not secreted into the intestine and in those
individuals who have shown hypersensitivity to any of its components.
Precautions
General
Chronic use of
cholestyramine resin may be associated with increased bleeding tendency due to
hypoprothrombinemia associated with Vitamin K deficiency. This will usually
respond promptly to parenteral Vitamin K1 and recurrences can be prevented by
oral administration of Vitamin K1. Reduction of serum or red cell folate has
been reported over long term administration of cholestyramine resin.
Supplementation with folic acid should be considered in these cases.
There is a possibility
that prolonged use of cholestyramine resin, since it is a chloride form of anion
exchange resin, may produce hyperchloremic acidosis. This would especially be
true in younger and smaller patients where the relative dosage may be higher.
Caution should also be exercised in patients with renal insufficiency or volume
depletion, and in patients receiving concomitant spironolactone.
Cholestyramine resin may
produce or worsen pre-existing constipation. The dosage should be increased
gradually in patients to minimize the risk of developing fecal impaction. In
patients with pre-existing constipation, the starting dose should be 1 packet or
1 scoop once daily for 5–7 days, increasing to twice daily with monitoring of
constipation and of serum lipoproteins, at least twice, 4–6 weeks apart.
Increased fluid intake and fiber intake should be encouraged to alleviate
constipation and a stool softener may occasionally be indicated. If the initial
dose is well tolerated, the dose may be increased as needed by one dose/day (at
monthly intervals) with periodic monitoring of serum lipoproteins. If
constipation worsens or the desired therapeutic response is not achieved at one
to six doses/day, combination therapy or alternate therapy should be considered.
Particular effort should be made to avoid constipation in patients with
symptomatic coronary artery disease. Constipation associated with cholestyramine
resin may aggravate hemorrhoids.
Information for Patients
Inform your physician if
you are pregnant or plan to become pregnant or are breastfeeding. Drink plenty
of fluids and mix each 9 gram dose of Cholestyramine for Oral Suspension USP in
at least 2 to 6 ounces of fluid. Mix each 5 gram dose of Cholestyramine for Oral
Suspension USP, Light in at least 2 to 6 ounces of fluid before taking. Sipping
or holding the resin suspension in the mouth for prolonged periods may lead to
changes in the surface of the teeth resulting in discoloration, erosion of
enamel or decay; good oral hygiene should be maintained.
Laboratory Tests
Serum cholesterol levels
should be determined frequently during the first few months of therapy and
periodically thereafter. Serum triglyceride levels should be measured
periodically to detect whether significant changes have occurred.
The LRC-CPPT showed a
dose-related increase in serum triglycerides of 10.7%–17.1% in the
cholestyramine-treated group, compared with an increase of 7.9%–11.7% in the
placebo group. Based on the mean values and adjusting for the placebo group, the
cholestyramine-treated group showed an increase of 5% over pre-entry levels the
first year of the study and an increase of 4.3% the seventh year.
Drug Interactions
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. Cholestyramine may interfere with the
pharmacokinetics of drugs that undergo enterohepatic circulation. The
discontinuance of Cholestyramine 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 Cholestyramine.
Because cholestyramine
binds bile acids, Cholestyramine 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 Cholestyramine is given for long periods of time, concomitant
supplementation with water-miscible (or parenteral) forms of fat-soluble
vitamins should be considered.
SINCE CHOLESTYRAMINE 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 CHOLESTYRAMINE (OR AT AS GREAT AN INTERVAL AS
POSSIBLE) TO AVOID IMPEDING THEIR ABSORPTION.
Carcinogenesis and Mutagenesis and Impairment of
Fertility
In studies conducted in
rats in which cholestyramine resin was used as a tool to investigate the role of
various intestinal factors, such as fat, bile salts and microbial flora, in the
development of intestinal tumors induced by potent carcinogens, the incidence of
such tumors was observed to be greater in cholestyramine resin-treated rats than
in control rats.
The relevance of this
laboratory observation from studies in rats to the clinical use of
Cholestyramine is not known. In the LRC-CPPT study referred to above, the total
incidence of fatal and nonfatal neoplasms was similar in both treatment groups.
When the many different categories of tumors are examined, various alimentary
system cancers were somewhat more prevalent in the cholestyramine group. The
small numbers and the multiple categories prevent conclusions from being drawn.
However, in view of the fact that cholestyramine resin is confined to the GI
tract and not absorbed, and in light of the animal experiments referred to
above, a six-year post-trial follow-up of the LRC-CPPT 5
patient population has been completed (a total of 13.4 years of in-trial plus
post-trial follow-up) and revealed no significant difference in the incidence of
cause-specific mortality or cancer morbidity between cholestyramine and placebo
treated patients.
Pregnancy
Pregnancy Category C
There are no adequate
and well controlled studies in pregnant women. The use of Cholestyramine in
pregnancy or lactation or by women of childbearing age requires that the
potential benefits of drug therapy be weighed against the possible hazards to
the mother and child. Cholestyramine is not absorbed systemically, however, it
is known to interfere with absorption of fat-soluble vitamins; accordingly,
regular prenatal supplementation may not be adequate (see PRECAUTIONS: Drug Interactions ).
Nursing Mothers
Caution should be
exercised when Cholestyramine is administered to a nursing mother. The possible
lack of proper vitamin absorption described in the “Pregnancy”
section
Pediatric Use
Although an optimal
dosage schedule has not been established, standard texts (6,7) list a usual pediatric dose of 240 mg/kg/day of anhydrous
cholestyramine resin in two to three divided doses, normally not to exceed 8
gm/day with dose titration based on response and tolerance.
In calculating pediatric
dosages, 44.4 mg of anhydrous cholestyramine resin are contained in 100 mg of
Cholestyramine for Oral Suspension USP and 80 mg of anhydrous cholestyramine
resin are contained in 100 mg of Cholestyramine for Oral Suspension USP,
Light.
The effects of long-term
administration, as well as its effect in maintaining lowered cholesterol levels
in pediatric patients, are unknown. (Also see ADVERSE
REACTIONS .)
Adverse reactions
How supplied
Cholestyramine for Oral
Suspension USP is available in cans containing 378 grams and in cartons of sixty
9 gram packets. Four grams of anhydrous cholestyramine resin are contained in 9
grams of Cholestyramine for Oral Suspension USP. The 378 g can includes a 15 cc
scoop. The scoop is not interchangeable with scoops from other products.
NDC 54868-4812-0
Can, 378 g
NDC 54868-4812-1
Carton of 60, 9 g packets
Cholestyramine for Oral
Suspension USP, Light 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 Cholestyramine for Oral Suspension USP, Light. The 210 g
can includes a 9 cc scoop. The scoop is not interchangeable with scoops from
other products.
NDC 54868-5526-0
Carton of 60, 5 g packets
Storage
Store between 20º-25ºC
(68º-77ºF). [See USP Controlled Room Temperature]. Excursions permitted to
15º-30ºC (59º-86ºF).
Clinical pharmacology
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
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 Cholestyramine 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 Cholestyramine 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%
Cholestyramine 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 Cholestyramine 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 Cholestyramine 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 Cholestyramine group (p less than 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 Cholestyramine.
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 Cholestyramine (p less than 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
Cholestyramine group (p less than 0.05). Thus in these randomized controlled clinical
trials using coronary arteriography, Cholestyramine monotherapy has been
demonstrated to slow progression 2,3 and promote
regression 3 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 Cholestyramine for Oral Suspension USP and Cholestyramine for Oral Suspension
USP, 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.
Package label
PRINCIPAL DISPLAY PANEL CARTON, 60 PACKETS PER CARTON
PRINCIPAL DISPLAY PANEL CARTON, 60 PACKETS PER CARTON
image of package label 01
image of package label 02
13 organizations
2 products
Organization
TAGI Pharma, Inc.Product
CholestyramineOrganization
A-S Medication SolutionsOrganization
Eon Labs, Inc.Organization
Zydus Lifesciences LimitedOrganization
PuraCap Laboratories LLC dba Blu PharmaceuticalsOrganization
Ajanta Pharma USA Inc.Organization
Epic Pharma, LLCOrganization
Precision Dose, Inc.Organization
Par Pharmaceutical, Inc.Organization
Zydus Pharmaceuticals (USA) Inc. Organization
Upsher-Smith Laboratories,LLCOrganization
bryant ranch prepackOrganization
Physicians Total Care, Inc.