Colestipolum

Uses

Colestipolum is a bile acid sequestrant used as an adjunct to diet and exercise to reduce LDL-C cholesterol levels in patients with primary hypercholesterolemia.

Colestipolum is indicated as adjunctive therapy to diet for the reduction of elevated serum total and low-density lipoprotein cholesterol (LDL-C) in patients with primary hypercholesterolemia (a condition that features elevated LDL-C) who do not respond adequately to dietary changes .

Therapy with lipid-altering agents like colestipol 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 . In general, a minimum of six months of intensive dietary therapy and counseling should be carried out prior to initiation of drug therapy such as that with colestipol . Shorter periods may be considered in patients with severe elevations of LDL-C or with definite coronary heart disease .

Although colestipol is effective in all types of hypercholesterolemia, some regional prescribing information note in particular that it is medically most appropriate in patients with Fredrickson's type II hyperlipoproteinemia . Nevertheless, in patients with combined hypercholesterolemia and hypertriglyceridemia, although colestipol may be helpful in reducing elevated cholesterol, it is not formally indicated where hypertriglyceridemia is the abnormality of greatest concern .

Colestipolum is also used to associated treatment for these conditions: Primary Hypercholesterolemia

How Colestipolum works

Colestipolum is a lipid-lowering polymer that binds with bile acids in the intestine forming a complex that is excreted in the feces . This non-systemic action results in a continuous, partial removal of bile acids from the enterohepatic circulation preventing their reabsorption . This increased fecal loss of bile acids due to colestipol hydrochloride administration leads to increased oxidation of cholesterol to bile acids . This results in an increase in the number of hepatic low-density lipoprotein (LDL) receptors, and consequently an increased uptake of LDL and a decrease in serum/plasma beta lipoprotein or total and LDL cholesterol levels . Although hydrochloride produces an increase in the hepatic synthesis of cholesterol in man, serum cholesterol levels fall .

Toxicity

Overdosage with colestipol has not been reported . Regardless, in the case of overdosage, 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 .

No clinical data are available on the use of colestipol in pregnant women and during lactation . Colestipolum does not appear to be absorbed systematically . Due to its known interference with absorption of fat-soluble vitamins, the use of colestipol in pregnancy or lactation or by women of childbearing potential requires that the benefits of drug therapy be weighed against the possible hazards to the mother and the child .

There are no data on the effect of colestipol on fertility in humans .

The use of colestipol in children is limited . Clinical trials conducted in children with colestipol ranules have usually employed doses of 5 to 20 g/day . The National Cholesterol Education Program (NCEP) Expert Panel recommends drug therapy be considered in children 10 years or older, who have previously undergone an adequate trial of diet therapy but still have unacceptably high serum cholesterol levels . In certain situations where a young child has extremely high serum cholesterol levels, drug treatment may even be initiated before 10 years of age . If the child is started on drug therapy, a carefully assessed diet therapy should also be continued in order to obtain optimal results . However, the safety of using colestipol tablets in patients under the age of 18 years has not been established . Furthermore, because bile acid sequestrants like colestipol may interfere with the absorption of fat-soluble vitamins, appropriate monitoring of growth and development is essential if colestipol is used in children .

Appropriate studies on the relationship of age to the effects of colestipol have not been performed in the geriatric population . However, patients over 60 years of age may be more likely to experience gastrointestinal side effects, as well as adverse nutritional effects .

Additionally, it has been determined that the oral LD₅₀ in rats is > 1000 mg/kg .

Food Interaction

• Drink plenty of fluids. The tablet and granule formulations must be taken with plenty of water or other fluids.
• Take with food.

Colestipolum multivitamins interaction

[Moderate] ADJUST DOSING INTERVAL: Bile acid sequestrants and the phosphate binder, sevelamer, can decrease the absorption of fat-soluble vitamins A, D, E, and K.

In non-clinical safety studies, rats administered colesevelam at doses greater than 30-fold the projected human clinical dose developed hemorrhage in association with vitamin K deficiency.

In a crossover study involving healthy subjects, coadministration of sevelamer with calcitriol resulted in a significant reduction in bioavailability for calcitriol (calcitriol with sevelamer vs calcitriol alone: AUC 137 pg*h
Oral vitamin supplements should be administered at least 4 hours before colesevelam and either 1 hour before or 4 to 6 hours after other bile acid sequestrants and sevelamer.

Colestipolum Drug Interaction

Moderate: ergocalciferol, ergocalciferol, cholecalciferol, cholecalciferolUnknown: aspirin, aspirin, duloxetine, duloxetine, omega-3 polyunsaturated fatty acids, omega-3 polyunsaturated fatty acids, metoprolol, metoprolol, acetaminophen, acetaminophen, cyanocobalamin, cyanocobalamin, ascorbic acid, ascorbic acid, cetirizine, cetirizine

Colestipolum Disease Interaction

Major: biliary obstructionModerate: constipation, hyperchloremia, PKU, vitamin/folate deficiency

Volume of Distribution

Colestipolum is not absorbed into the systemic circulation .

Elimination Route

Colestipolum is hydrophilic, but it is virtually water-insoluble (99.75%) . This water insolubility, combined with the high molecular weight polymer in colestipol basically means the agent and the complexes it forms when it binds with bile acids are not absorbed . The action of colestipol is ultimately limited to the lumen of the gastrointestinal tract . It binds bile acids in the intestinal lumen and causes them to be excreted in the feces together with the polymer . When the enterohepatic circulation of bile acids is interrupted, cholesterol conversion to bile acids is enhanced and plasma cholesterol levels are thereby lowered .

Half Life

Colestipolum is not absorbed into the systemic circulation nor is it hydrolyzed by any digestive enzymes . Its action is ultimately limited to the lumen of the gastrointestinal tract, where it is eventually passed into the feces .

Clearance

Colestipolum is not absorbed into the systemic circulation .

Elimination Route

Colestipolum hydrochloride binds bile acids in the intestine forming a complex that is then ultimately excreted in the feces . In humans, less than 0.17% of a single 14C-labeled colestipol hydrochloride dose is excreted in the urine when given following 60 days of chronic dosing of 20 grams of colestipol hydrochloride per day . The increased fecal loss of bile acids due to colestipol hydrochloride administration leads to increased oxidation of cholesterol to bile acids .

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