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.
PregnancyPregnancy 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.)
