WARNINGS
No infromation provided.
PRECAUTIONS
Prior to initiating therapy with COLESTID Tablets, 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 - [(Triglycerides/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 COLESTID
Tablets may not be indicated.
Because it sequesters bile acids, colestipol hydrochloride
may interfere with normal fat absorption and thus, may
reduce absorption of folic acid and fat soluble vitamins
such as A, D and K.
Chronic use of colestipol hydrochloride may be associated
with an increased bleeding tendency due to hypoprothrombinemia
from vitamin K deficiency. This will usually respond promptly
to parenteral vitamin K, and recurrences can be prevented
by oral administration of vitamin K.
Serum cholesterol and triglyceride levels should be determined
periodically based on NCEP guidelines to confirm a favorable
initial and adequate long-term response.
COLESTID Tablets may produce or severely worsen pre-existing
constipation. The dosage should be increased gradually
in patients to minimize the risk of developing fecal impaction.
In patients with preexisting constipation, the starting
dose should be 2 grams once or twice a day. Increased
fluid 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 a further 2 to 4 grams/day
(at monthly intervals) with periodic monitoring of serum
lipoproteins. If constipation worsens or the desired therapeutic
response is not achieved at 2 to 16 grams/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 COLESTID Tablets may aggravate hemorrhoids.
While there have been no reports of hypothyroidism induced
in individuals with normal thyroid function, the theoretical
possibility exists, particularly in patients with limited
thyroid reserve.
Since colestipol hydrochloride is a chloride form of
an anion exchange resin, there is a possibility that prolonged
use may lead to the development of hyperchloremia acidosis.
Carcinogenesis, Mutagenesis and Impairment of
Fertility
In studies conducted in rats in which cholestyramine
resin (a bile acid sequestering agent similar to colestipol
hydrochloride) 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 with cholestyramine resin to the clinical use
of COLESTID Tablets 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.
Further follow-up of the LRC-CPPT participants by the
sponsors of that study is planned for cause-specific mortality
and cancer morbidity. When colestipol hydrochloride was
administered in the diet to rats for 18 months, there
was no evidence of any drug related intestinal tumor formation.
In the Ames assay, colestipol hydrochloride was not mutagenic.
Use in Pregnancy
Since colestipol hydrochloride is essentially not absorbed
systemically (less than 0.17% of the dose), it is not
expected to cause fetal harm when administered during
pregnancy in recommended dosages. There are no adequate
and well-controlled studies in pregnant women, and the
known interference with absorption of fat-soluble vitamins
may be detrimental even in the presence of supplementation.
Nursing Mothers
Caution should be exercised when COLESTID Tablets are
administered to a nursing mother. The possible lack of
proper vitamin absorption described in the "Pregnancy"
section may have an effect on nursing infants.
Pediatric Use: Safety and effectiveness in the pediatric
population have not been established.
Information for Patients
See PATIENT INFORMATION section |
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