Overdose
Overdosage of COLESTID Tablets has not been reported.
Should overdosage occur, however, the chief potential harm would be obstruction
of the gastrointestinal tract. The location of such potential obstruction, the
degree of obstruction and the presence or absence of normal gut motility would
determine treatment.
Contraindications
COLESTID Tablets are contraindicated in those individuals
who have shown hypersensitivity to any of their components.
Undesirable effects
Gastrointestinal
The most common adverse reactions are confined to the
gastrointestinal tract. To achieve minimal GI disturbance with an optimal LDL-C
lowering effect, a gradual increase of dosage starting with 2 grams, once or
twice daily is recommended. Constipation is the major single complaint and at
times is severe. Most instances of constipation are mild, transient, and
controlled with standard treatment. Increased fluid intake and inclusion of
additional dietary fiber should be the first step; a stool softener may be
added if needed. Some patients require decreased dosage or discontinuation of
therapy. Hemorrhoids may be aggravated.
Other, less frequent gastrointestinal complaints consist
of abdominal discomfort (abdominal pain and cramping), intestinal gas (bloating
and flatulence), indigestion and heartburn, diarrhea and loose stools, and
nausea and vomiting. Bleeding hemorrhoids and blood in the stool have been
infrequently reported. Peptic ulceration, cholecystitis, and cholelithiasis
have been rarely reported in patients receiving colestipol hydrochloride
granules, and are not necessarily drug related.
Difficulty swallowing and transient esophageal
obstruction have been rarely reported in patients taking COLESTID Tablets.
Transient and modest elevations of aspartate
aminotransferase (AST, SGOT), alanine aminotransferase (ALT, SGPT) and alkaline
phosphatase were observed on one or more occasions in various patients treated
with colestipol hydrochloride.
The following nongastrointestinal adverse reactions have
been reported with generally equal frequency in patients receiving COLESTID
Tablets, colestipol granules, or placebo in clinical studies:
Cardiovascular
Chest pain, angina, and tachycardia have been
infrequently reported.
Hypersensitivity
Rash has been infrequently reported. Urticaria and
dermatitis have been rarely noted in patients receiving colestipol
hydrochloride granules.
Musculoskeletal
Musculoskeletal pain, aches and pains in the extremities,
joint pain and arthritis, and backache have been reported.
Neurologic
Headache, migraine headache, and sinus headache have been
reported. Other infrequently reported complaints include dizziness,
light-headedness, and insomnia.
Miscellaneous
Anorexia, fatigue, weakness, shortness of breath, and
swelling of the hands or feet, have been infrequently reported.
Therapeutic indications
Since no drug is innocuous, strict attention should be
paid to the indications and contraindications, particularly when selecting
drugs for chronic long-term use.
COLESTID Tablets are indicated as adjunctive therapy to
diet for the reduction of elevated serum total and LDL-C in patients with
primary hypercholesterolemia (elevated LDL-C) who do not respond adequately to
diet. Generally, COLESTID Tablets have no clinically significant effect on
serum triglycerides, but with their use, triglyceride levels may be raised in some
patients.
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
(see NCEP guidelines). A minimum of six months of intensive dietary
therapy and counseling should be carried out prior to initiation of drug
therapy. Shorter periods may be considered in patients with severe elevations
of LDL-C or with definite CHD.
According to the NCEP guidelines, the goal of treatment
is to lower LDL-C, and LDL-C is to be used to initiate and assess treatment
response. Only if LDL-C levels are not available, should the Total-C be used to
monitor therapy. The NCEP treatment guidelines are shown below.
| Definite Atherosclerotic Disease* |
Two or More Other Risk Factors** |
Initiation Level |
Goal |
| No |
No |
≥ 190
( ≥ 4.9) |
< 160
( < 4.1) |
| No |
Yes |
≥ 160
( ≥ 4.1) |
< 130
( < 34) |
| Yes |
Yes or No |
≥ 130
( ≥ 3.4) |
≤ 100
( ≤ 26) |
* 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; female: ≥ 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). |
Qualitative and quantitative composition
COLESTID Tablets are yellow, elliptical, imprinted U, and
are supplied as follows:
Bottles of 120 NDC 0009-0450-03
Bottles of 500 NDC 0009-0450-04
Each tablet contains 1 gram of colestipol hydrochloride.
Store at controlled room temperature 20° to 25°C (68° to
77°F).
Distributed by: Pharmacia & Upjohn Company, Division
of Pfizer Inc., NY, NY 10017. Revised 2013
Special warnings and precautions for use
WARNINGS
No information 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 K1 and
recurrences can be prevented by oral administration of vitamin K1.
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
pre-existing 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. The use of COLESTID tablets in
pregnancy or by women of childbearing potential requires that the potential
benefits of drug therapy be weighed against possible hazards to the mother or
child.
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.
Dosage (Posology) and method of administration
For adults, COLESTID Tablets are recommended in doses of
2 to 16 grams/day given once or in divided doses. The starting dose should be 2
grams once or twice daily. Dosage increases of 2 grams, once or twice daily
should occur at 1-or 2-month intervals. Appropriate use of lipid profiles as
per NCEP guidelines including LDL-C and triglycerides, is advised so that
optimal but not excessive doses are used to obtain the desired therapeutic
effect on LDL-C level. If the desired therapeutic effect is not obtained at a
dose of 2 to 16 grams/day with good compliance and acceptable side effects,
combined therapy or alternate treatment should be considered.
COLESTID Tablets must be taken one at a time and be
promptly swallowed whole, using plenty of water or other appropriate liquid. Do
not cut, crush, or chew the tablets. Patients should take other drugs at least
one hour before or four hours after COLESTID Tablets to minimize possible
interference with their absorption. (See DRUG INTERACTIONS.)
Before Administration of COLESTID Tablets
- Define the type of hyperlipoproteinemia, as described in
NCEP guidelines.
- Institute a trial of diet and weight reduction.
- Establish baseline serum total and LDL-C and triglyceride
levels.
During Administration of COLESTID Tablets
- The patient should be carefully monitored clinically,
including serum cholesterol and triglyceride levels. Periodic determinations of
serum cholesterol levels as outlined in the NCEP guidelines should be done to
confirm a favorable initial and long-term response.
- Failure of total or LDL-C to fall within the desired
range should lead one to first examine dietary and drug compliance. If these
are deemed acceptable, combined therapy or alternate treatment should be
considered.
- Significant rise in triglyceride level should be
considered as indication for dose reduction, drug discontinuation, or combined
or alternate therapy.
Interaction with other medicinal products and other forms of interaction
.)
Before Administration of COLESTID Tablets
- Define the type of hyperlipoproteinemia, as described in
NCEP guidelines.
- Institute a trial of diet and weight reduction.
- Establish baseline serum total and LDL-C and triglyceride
levels.
During Administration of COLESTID Tablets
- The patient should be carefully monitored clinically,
including serum cholesterol and triglyceride levels. Periodic determinations of
serum cholesterol levels as outlined in the NCEP guidelines should be done to
confirm a favorable initial and long-term response.
- Failure of total or LDL-C to fall within the desired
range should lead one to first examine dietary and drug compliance. If these
are deemed acceptable, combined therapy or alternate treatment should be
considered.
- Significant rise in triglyceride level should be
considered as indication for dose reduction, drug discontinuation, or combined
or alternate therapy.
HOW SUPPLIED
COLESTID Tablets are yellow, elliptical, imprinted U, and
are supplied as follows:
Bottles of 120 NDC 0009-0450-03
Bottles of 500 NDC 0009-0450-04
Each tablet contains 1 gram of colestipol hydrochloride.
Store at controlled room temperature 20° to 25°C (68° to
77°F).
Distributed by: Pharmacia & Upjohn Company, Division
of Pfizer Inc., NY, NY 10017. Revised 2013
Side Effects & Drug Interactions
SIDE EFFECTS
Gastrointestinal
The most common adverse reactions are confined to the
gastrointestinal tract. To achieve minimal GI disturbance with an optimal LDL-C
lowering effect, a gradual increase of dosage starting with 2 grams, once or
twice daily is recommended. Constipation is the major single complaint and at
times is severe. Most instances of constipation are mild, transient, and
controlled with standard treatment. Increased fluid intake and inclusion of
additional dietary fiber should be the first step; a stool softener may be
added if needed. Some patients require decreased dosage or discontinuation of
therapy. Hemorrhoids may be aggravated.
Other, less frequent gastrointestinal complaints consist
of abdominal discomfort (abdominal pain and cramping), intestinal gas (bloating
and flatulence), indigestion and heartburn, diarrhea and loose stools, and
nausea and vomiting. Bleeding hemorrhoids and blood in the stool have been
infrequently reported. Peptic ulceration, cholecystitis, and cholelithiasis
have been rarely reported in patients receiving colestipol hydrochloride
granules, and are not necessarily drug related.
Difficulty swallowing and transient esophageal
obstruction have been rarely reported in patients taking COLESTID Tablets.
Transient and modest elevations of aspartate
aminotransferase (AST, SGOT), alanine aminotransferase (ALT, SGPT) and alkaline
phosphatase were observed on one or more occasions in various patients treated
with colestipol hydrochloride.
The following nongastrointestinal adverse reactions have
been reported with generally equal frequency in patients receiving COLESTID
Tablets, colestipol granules, or placebo in clinical studies:
Cardiovascular
Chest pain, angina, and tachycardia have been
infrequently reported.
Hypersensitivity
Rash has been infrequently reported. Urticaria and
dermatitis have been rarely noted in patients receiving colestipol
hydrochloride granules.
Musculoskeletal
Musculoskeletal pain, aches and pains in the extremities,
joint pain and arthritis, and backache have been reported.
Neurologic
Headache, migraine headache, and sinus headache have been
reported. Other infrequently reported complaints include dizziness,
light-headedness, and insomnia.
Miscellaneous
Anorexia, fatigue, weakness, shortness of breath, and
swelling of the hands or feet, have been infrequently reported.
DRUG INTERACTIONS
Since colestipol hydrochloride is an anion exchange
resin, it may have a strong affinity for anions other than the bile acids. In
vitro studies have indicated that colestipol hydrochloride binds a number of
drugs. Therefore, COLESTID Tablets may delay or reduce the absorption of
concomitant oral medication. The interval between the administration of
COLESTID Tablets and any other medication should be as long as possible.
Patients should take other drugs at least one hour before or four hours after
COLESTID Tablets to avoid impeding their absorption.
Repeated doses of colestipol hydrochloride given prior to
a single dose of propranolol in human trials have been reported to decrease
propranolol absorption. However, in a follow-up study in normal subjects,
single-dose administration of colestipol hydrochloride and propranolol and
twice-a-day administration for 5 days of both agents did not affect the extent
of propranolol absorption, but had a small yet statistically significant effect
on its rate of absorption; the time to reach maximum concentration was delayed
approximately 30 minutes. Effects on the absorption of other beta-blockers have
not been determined. Therefore, patients on propranolol should be observed when
COLESTID Tablets are either added or deleted from a therapeutic regimen.
Studies in humans show that the absorption of
chlorothiazide as reflected in urinary excretion is markedly decreased even
when administered one hour before colestipol hydrochloride. The absorption of
tetracycline, furosemide, penicillin G, hydrochlorothiazide, and gemfibrozil
was significantly decreased when given simultaneously with colestipol
hydrochloride; these drugs were not tested to determine the effect of
administration one hour before colestipol hydrochloride.
No depressant effect on blood levels in humans was noted
when colestipol hydrochloride was administered with any of the following drugs:
aspirin, clindamycin, clofibrate, methyldopa, nicotinic acid (niacin),
tolbutamide, phenytoin or warfarin. Particular caution should be observed with
digitalis preparations since there are conflicting results for the effect of
colestipol hydrochloride on the availability of digoxin and digitoxin. The
potential for binding of these drugs if given concomitantly is present.
Discontinuing colestipol hydrochloride could pose a hazard to health if a
potentially toxic drug that is significantly bound to the resin has been
titrated to a maintenance level while the patient was taking colestipol hydrochloride.
Bile acid binding resins may also interfere with the
absorption of oral phosphate supplements and hydrocortisone.
A study has shown that cholestyramine binds bile acids
and reduces mycophenolic acid exposure. As colestipol also binds bile acids,
colestipol may reduce mycophenolic acid exposure and potentially reduce
efficacy of mycophenolate mofetil.
