COLESTID ORANGE 5G - summary of medicine characteristics

1 NAME OF THE MEDICINAL PRODUCT

Colestid Orange 5g

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Colestipol hydrochloride 5 g

Excipient with known effect

Colestid Orange 5g contains 32.5 mg aspartame per sachet.

For the full list of excipients, see section 6.1.

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 hypercholeste­rolemia 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 hypercholeste­rolemia, 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.

Posology

Adults:

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

For adults colestipol hydrochloride is recommended in doses of 5 g-30 g taken as one dose or two divided doses. Initiation of therapy is recommended at 5 g either once or twice daily with 5 g increments at one month intervals.

Appropriate use of lipid profiles including LDL-C 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 g-30 g per day with good compliance and acceptable side-effects, combined therapy or alternate treatment should be considered.

Patients should take other drugs at least 1 hour before or 4 hours after the administration of 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).

Method of administration 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 to 150 ml 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.

Paediatric population: Dosage in children has not been established.

4.3 Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

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 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.

Paediatric population:

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:

Effect on vitamin absorption

Because it sequesters bile acids, Colestid may interfere with normal fat absorption and may thus alter the absorption of fat soluble vitamins such as A, D, E and K. A study in humans found only one patient in whom a prolonged prothrombin 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.

Excipient information

Colestid Orange contains aspartame which is a source of phenylalanine (see section 2). Phenylalanine may be harmful to patients with phenylketonuri­a (PKU).

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, asparin, 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 betablockers have not been determined. Patients on propranolol should be observed when Colestid is either added or deleted from a therapeutic regimen.

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.

4.6 Fertility, pregnancy and lactation

Pregnancy

No clinical data are available on the use of colestipol hydrochloride in pregnant women. Though animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonic/foetal development, parturition or postnatal development (see section 5.3), caution should be exercised when prescribing to pregnant women.

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.

Breast-feeding

The safety of colestipol hydrochloride has not been established in breastfeeding women. Caution should be exercised when prescribing to breastfeeding wo­men.

Fertility

There are no data on the effect of colestipol hydrochloride on fertility in humans. A study conducted in rats did not result in any differences in reproductive parameters that might imply reproductive effects attributable to colestipol hydrochloride.

4.7 Effects on ability to drive and use machines

No adverse effect has been reported.

4.8. Undesirable effects

Adverse events are described by system organ class and frequency (very common >1/10; common >1/100 to < 1/10; uncommon >1/1,000 to < 1/100; rare >1/10,000 to < 1/1,000; very rare <1/10,000) in the table below:

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at:

www.mhra.gov.uk/y­ellowcard. By reporting side effects you can help provide more information on the safety of this medicine.

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

Pharmacotherapeutic group: bile acid sequestrants, ATC code: C10AC02

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 gastrointestinal 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.

Reproduction and teratologic studies in animals gave no evidence of drug toxicity in parents or offspring.

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Mannitol

Methylcellulose (15CPS)

Citric Acid

Orange Durarome Wonf

Aspartame Powder (E951)

Maltol

Ethyl Vanillin

Beta Carotene 1%

Glycerol

Purified Water

6.2 Incompatibilities

Not applicable.

6.3 Shelf life

2 years

6.4 Special precautions for storage

Do not store above 25°C.

6.5 Nature and contents of container

HDPE bottle with plastic caps or tinplate screwcaps containing 450 grams or foil sachets in packs of 8, 28, 30, 56, 60 and 250 sachets.

6.6 Special precautions for disposal

No special requirements for disposal.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

Pfizer Limited Ramsgate Road Sandwich

Kent CT13 9NJ United Kingdom

8 MARKETING AUTHORISATION NUMBER(S)

PL 00057/0951

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THEAUTHORISATION

Date of Grant: 25 February 1992

Date of Renewal: 30 Oct 2002