COLESTID Orange

1. Name Of The Medicinal Product

Colestid Orange

2. Qualitative And Quantitative Composition

Colestipol Hydrochloride USP 5.0 gram

3. Pharmaceutical Form

Granules for oral administration.

4. Clinical Particulars

4.1 Therapeutic Indications

Colestid is indicated as adjunctive therapy to diet in the management of patients with elevated cholesterol levels who have not responded adequately to diet. It may be used alone or in combination with additional lipid lowering agents.

Dietary therapy specific for the type of hypercholesterolaemia should be the initial treatment of choice. Excess body weight may be an important factor and weight reduction should be attempted prior to drug therapy in the overweight. The use of drugs should be considered only when reasonable attempts have been made to obtain satisfactory results with non-drug methods. When drug therapy is begun, the patient should be instructed of the importance of adhering to the correct diet.

Although Colestid is effective in all types of hypercholesterolaemia, it is medically most appropriate in patients with Fredrickson's type II hyperlipoproteinaemia.

4.2 Posology And Method Of Administration

Route of administration: Oral, mixed with water or other fluids.

Adults:

The recommended initial daily adult dosage of colestipol hydrochloride is 5 grams either once or twice daily.

For adults colestipol hydrochloride is recommended in doses of 5-30 grams taken as one dose or two divided doses. Initiation of therapy is recommended at 5 grams either once or twice daily with 5 gram increments at one month intervals. Appropriate use of lipid profiles including LDL-cholesterol and triglycerides is advised so that optimal, but not excessive doses are used to obtain the desired therapeutic effect on LDL-cholesterol level. If the desired therapeutic effect is not obtained at a dose of 5-30 grams/day with good compliance and acceptable side-effects, combined therapy or alternate treatment should be considered.

Patients should take other drugs at least one hour before or four hours after Colestid to minimise possible interference with their absorption. However, Colestid and gemfibrozil may be used in the same patient when administered 2 hours apart. (See interactions).

Preparation:

Colestid should always be taken mixed in a liquid such as orange or tomato juice, water, skimmed milk or non-carbonated beverage. The contents of the sachet or level scoopful should be added to 100 ml or more of the preferred aqueous vehicle and mixed thoroughly until dispersed. Colestid may also be taken in soups or with cereals, pulpy fruits with a high water content or yoghurt.

Elderly patients:

At present there are no extensive clinical studies with colestipol in patients over the age of 65. Review of available data does not suggest that the elderly are more predisposed to side-effects attributable to colestipol than the general population; however, therapy should be individualised and based on each patient's clinical characteristics and tolerance to the medication.

Children:

Dosage in children has not been established.

4.3 Contraindications

Colestipol is contra-indicated in individuals who have previously demonstrated hypersensitivity to its use.

4.4 Special Warnings And Precautions For Use

Warnings:

Before instituting therapy with Colestid, diseases contributing to increased blood cholesterol such as hypothyroidism, diabetes mellitus, nephrotic syndrome, dysproteinaemias and obstructive liver diseases should be looked for and specifically treated.

To avoid accidental inhalation or oesophageal distress, Colestid should not be taken in its dry form.

Colestid Orange contains 0.0325 g aspartame per sachet or level scoopful. This should be taken into consideration in patients suffering from phenylketonuria since excessive amounts of aspartame may interfere with the control of this condition.

Colestid may elevate serum triglyceride levels when used as sole therapy. This elevation is generally transient but may persist in some individuals. A significant rise in triglyceride level should be considered as an indication for dose reduction, drug discontinuation, or combined or alternate therapy.

The use of Colestid in children has been limited; however, it does appear to be effective in lowering serum cholesterol in older children and young adults. Because bile acid sequestrants may interfere with the absorption of fat-soluble vitamins, appropriate monitoring of growth and development is essential. Dosage and long term safety in children have not been established.

Precautions:

Because it sequesters bile acids, Colestid may interfere with normal fat absorption and thus may alter absorption of fat soluble vitamins such as A, D, E and K. A study in humans found only one patient in whom a prolonged prothombin time was noted. Most studies did not show a decrease in vitamin A, D or E levels during the administration of Colestid; however, if Colestid is to be given for a long period these vitamin levels should be monitored and supplements given if necessary.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

In man, Colestid may delay or reduce the absorption of certain concomitant oral drugs (digitalis and its glycosides, propranolol, chlorothiazide and hydrochlorothiazide, tetracycline hydrochloride, penicillin G, gemfibrozil and furosemide). Particular caution should be taken with digitalis preparations since conflicting results have been obtained for the effect of Colestid on the availability of digoxin and digitoxin. Colestid has been shown not to interfere with the absorption of clindamycin, clofibrate, aspirin, tolbutamide, warfarin, methyldopa and phenytoin. The clinical response to concomitant medication should be closely monitored and appropriate adjustments made.

Repeated doses of Colestid 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 Colestid and propranolol or multiple dose administration of both agents did not affect the extent of propranolol absorption. Effects on the absorption of other beta-blockers have not been determined. Patients on propranolol should be observed when Colestid is either added or deleted from a therapeutic regimen.

4.6 Pregnancy And Lactation

Safety for use in pregnant women has not been established. The use of Colestid in pregnancy or lactation or by women of childbearing age requires that the potential benefits of treatment be weighed against the possible hazards to the mother and child.

4.7 Effects On Ability To Drive And Use Machines

No adverse effect has been reported.

4.8 Undesirable Effects

Side-effects:

The most common adverse reactions reported with Colestid have been of a functional gastro-intestinal nature. The most frequent is constipation which is usually mild, transient and responsive to the usual adjunctive measures. At times, constipation can be severe and may be accompanied by impaction. As such, haemorrhoids can be aggravated, and infrequent blood in the stools has been reported. Less frequent gastro-intestinal complaints are abdominal discomfort, belching, flatulence, indigestion, nausea, vomiting and diarrhoea. Rarely, peptic ulceration and bleeding, cholelithiasis and cholecystitis have been reported, although these are not necessarily drug related.

Transient and modest elevation of SGOT and alkaline phosphatase have been observed. No medical significance is attached to these observed changes.

Although not necessarily drug-related, the following non-gastro-intestinal medical events have been reported during clinical trials at a similar incidence to placebo.

Cardiovascular: Chest pain, angina, and tachycardia have been infrequently reported.

Hypersensitivity: Rash has been infrequently reported. Urticaria and dermatitis have been rarely noted.

Musculoskeletal: Musculoskeletal pain, aches and pains in the extremities, joint pain and arthritis, and backache have been reported.

Neurological: 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.

4.9 Overdose

No toxic effects due to overdosage have been reported. Should overdosage occur, obstruction of the gastro-intestinal tract would be expected to occur. Treatment should be determined by the location and degree of obstruction.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Ion exchange resin which lowers plasma cholesterol through binding with bile acids in the intestinal lumen.

5.2 Pharmacokinetic Properties

Colestid is not absorbed; its action is limited to the lumen of the gastro-intestinal tract, and it is passed in the faeces. It binds bile acids in the intestinal lumen and causes them to be excreted in the faeces 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.

5.3 Preclinical Safety Data

Both clinical usage and animal studies with Colestid have provided no evidence of drug related intestinal neoplasms. Colestid is not mutagenic in the ames test.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Mannitol Ph. Eur.

Methylcellulose (15CPS) Ph. Eur.

Citric Acid Ph. Eur.

Orange Durarome Wonf HSE

Aspartame Powder NF

Maltol HSE

Ethyl Vanillin NF

Beta Carotene 1% HSE

Glycerol Ph. Eur.

Purified Water Ph. Eur.

6.2 Incompatibilities

None.

6.3 Shelf Life

24 months.

6.4 Special Precautions For Storage

Store at controlled room temperature (15-30°C).

6.5 Nature And Contents Of Container

Foil sachets in packs 30 sachets.

6.6 Special Precautions For Disposal And Other Handling

None.

7. Marketing Authorisation Holder

Pharmacia Limited

Ramsgate Road

Sandwich

Kent CT13 9NJ

United Kingdom

8. Marketing Authorisation Number(S)

PL 0032/0172

9. Date Of First Authorisation/Renewal Of The Authorisation

Date of Grant: 25 February 1992

Date of Renewal: 30 Oct 2002

10. Date Of Revision Of The Text

22 June 2007

Legal Category POM

Company Reference: CL3_0