COMPOSITION Each sachet of QUESTRAN LITE powder contains 4 g or 8 g of anhydrous cholestyramine, the active ingredient. Each 4 g sachet contains 16,8 mg phenylalanine and each 8 g sachet contains 33,6 mg phenylalanine, from aspartame, as sweetener.
PHARMACOLOGICAL ACTION QUESTRAN LITE is the chloride salt of a basic anion-exchange resin, cholestyramine. Cholestyramine is very hydrophilic, but it is not soluble in water, nor is it hydrolysed by digestive enzymes. Thus, QUESTRAN LITE is not absorbed from the intestinal tract.
Cholestyramine resin adsorbs and combines with the bile acids in the intestine to form an insoluble complex which is excreted in the faeces. The increased faecal loss of bile acids leads to an increased oxidation of cholesterol to bile acids and a decrease in serum cholesterol levels and low density lipoprotein cholesterol serum levels.
When administered properly, QUESTRAN LITE usually leads to a significant reduction (15% or more) in serum cholesterol levels.
In patients with pruritis associated with partial biliary obstruction the reduction of serum bile acid levels by QUESTRAN LITE is thought to reduce excess bile acids deposited in the dermal tissues and promote their excretion with the faeces. The relief from itching afforded to most of these patients by QUESTRAN LITE is attributed to this mobilisation. It is postulated that in "bile-salt" diarrhoea, QUESTRAN LITE binds conjugated dihydroxy bile salts which are known to have a cathartic effect.
INDICATIONS For reduction of serum cholesterol and low density cholesterol, lipoprotein levels in primary hypercholesterolaemia in conjunction with an appropriate diet. QUESTRAN LITE is indicated as adjunctive therapy to diet for the reduction of elevated serum cholesterol in patients with primary hypercholesterolaemia (elevated low density lipoproteins) who do not respond adequately to diet.
QUESTRAN LITE may be useful to lower elevated cholesterol that occurs in patients with combined hypercholesterolaemia and hypertriglyceridaemia, but it is not indicated where hypertriglyceridaemia is the abnormality of most concern.
For the reduction of pruritus associated with partial biliary obstruction eg as in cholestatic jaundice.
For the treatment of diarrhoea due to bile acid malabsorption. (see SPECIAL PRECAUTIONS: ORAL REHYDRATION THERAPY.)
CONTRA-INDICATION QUESTRAN LITE is contra-indicated in patients with complete biliary obstruction and in those individuals who have shown hypersensitivity to any of its components. The safety in pregnancy and lactation has not been established.
WARNINGS PHENYLKETONURICS: This formulation contains 3,36 mg phenylalanine per gram of QUESTRAN LITE powder.
QUESTRAN LITE should not be used in patients with exudative or bloody diarrhoea.
DOSAGE AND DIRECTIONS FOR USE:
QUESTRAN LITE should not be taken in its dry form. It should be mixed with water or other fluids before ingesting. Hypercholesterolaemia and hyperlipoproteinaemia may be manifestations of altered metabolism resulting from either dietary excesses or diseases such as hypothyroidism, diabetes, nephrosis, pancreatitis or biliary cirrhosis. The primary objective of therapy should be to control any underlying disease. Proper diet and weight control in these patients is also essential. Adults: To reduce cholesterol:
Begin with one 4 g sachet (see PREPARATION) once or twice daily. The dose can be increased to 8 g in the morning and in the evening. If necessary, medication may be increased to the maximum of 24 g of cholestyramine resin per day. It is recommended that increases in dose be gradual. If dose increases are necessary, they should be done gradually, and with periodic assessment of lipid/lipoprotein levels at intervals of not less than 4 weeks. The suggested time of administration is mealtime, but this may be modified to avoid interference with absorption of other medications. Although the recommended dosing schedule is twice daily, QUESTRAN LITE may be administered in 1-4 doses per day. No more than 24 g (6 small sachets or 3 large sachets) of the active ingredient a day should be administered as larger doses of QUESTRAN LITE may interfere with normal fat absorption.
To relieve pruritus due to partial biliary obstruction:
4 g (one small sachet) or 8 g (two small sachets or one large sachet) daily.
To relieve diarrhoea induced by bile acid malabsorption:
The initial dosage of QUESTRAN LITE should be 4 g (one small sachet) three times a day, with subsequent adjustment as needed. NOTE: IN ALL PATIENTS PRESENTING WITH A DIARRHOEA INDUCED BY BILE ACID MALABSORPTION, A RESPONSE SHOULD BE SEEN WITHIN 3 DAYS. IF THIS IS NOT THE CASE, ALTERNATE THERAPY SHOULD BE INITIATED. To familiarize the patient with QUESTRAN LITE and to minimise gastrointestinal side-effects, it is desirable to begin all therapy with one dose of QUESTRAN LITE daily. The dosage is then increased within a day or two to the starting dose for effective control. NOTE:
QUESTRAN LITE SHOULD NOT BE TAKEN IN ITS DRY FORM. ALWAYS ADMIX QUESTRAN LITE WITH WATER OR OTHER FLUIDS BEFORE INGESTING. ALSO REFER TO SPECIAL PRECAUTIONS.
One 4 g sachet
4,68 g QUESTRAN LITE powder
4 g anhydrous cholestyramine
One 8 g sachet
9,4 g QUESTRAN LITE powder
8 g anhydrous cholestyramine
Children: The precise dosage for children has not yet been established.
PREPARATION Place the contents of a 4 g sachet QUESTRAN LITE on the surface of 115-170 mL of water or beverage, such as milk, fruit juice or broth. Use more water or beverage for the two sachets (200-300 mL). Stir to a uniform suspension. QUESTRAN LITE may also be used with pulpy fruits, such as apple sauce or crushed pineapple. NEVER INGEST QUESTRAN LITE IN ITS DRY FORM.
SIDE-EFFECTS AND SPECIAL PRECAUTIONS
Side-effects The most common adverse reaction is constipation. Predisposing factors for most of these complaints when QUESTRAN LITE is used as a cholesterol lowering agents are: high dose and increased age (more than 60 years old). Most instances of constipation are mild, transient and controlled with conventional therapy. Some patients require a temporary decrease in dosage or discontinuation of therapy. Less Frequent Adverse Events: Abdominal discomfort, flatulence, nausea, vomiting, diarrhoea, heartburn, anorexia, dyspepsia and steatorrhoea, bleeding tendencies due to hypoprothrombinemia (Vitamin K deficiency) as well as Vitamin A (night blindness has been reported and D deficiencies, hyperchloraemic acidosis in children, and osteoporosis. Rash and irritation of skin, tongue and perianal area. Reports of intestinal obstruction have been received postmarketing, including two deaths in paediatric patients. Calcified material has occasionally been observed in the biliary tree, including calcification of gall-bladder, in patients to whom cholestyramine resin has been given. However, this may be a manifestation of the liver disease and not drug related.
One patient experienced biliary colic on each of three occasions on which he took cholestyramine. One patients diagnosed as acute abdominal symptom complex was found to have a pasty massin the transverse colon on X-ray.
Other events (not necessarily drug related) reported in patients taking QUESTRAN LITE include: Gastrointestinal - GI-rectal bleeding, black stools, haemorrhoidal bleeding, bleeding from known duodenal ulcer, dysphagia, hiccups, ulcer attack, sour taste, pancreatitis, rectal pain, diverticulitis eructation Laboratory Test Changes - Liver function abnormalities Haematologic - Decreased or increased prothrombin time, ecchymoses, anaemia Hypersensitivity - Urticaria, asthma, wheezing, shortness of breath Musculoskeletal - Backache, muscle and joint pains, arthritis Neurologic - Headache, anxiety, vertigo, dizziness, fatigue, tinnitus, syncope, drowsiness, femoral nerve pain, paresthesia Eye - Uveitis Renal - Haematuria, dysuria, burnt odour to urine, diuresis Miscellaneous - Weight loss, weight gain, increased libido, swollen glands, oedema, dental bleeding, dental caries.
General Before instituting therapy with QUESTRAN LITE, diseases contributing to increased blood cholesterol such as hypothyroidism, diabetes mellitus, nephrotic syndrome, dysproteinemias and obstructive liver disease should be looked for and specifically treated. In addition, prior to instituting therapy with QUESTRAN LITE, an attempt should be made to control serum cholesterol by appropriate dietary regimen, weight reduction and the treatment of any underlying disorder which might be the cause of the hypercholsterolemia. Serum cholesterol levels should be determined frequently during the first few months of therapy and periodically thereafter. A favourable trend in cholesterol reduction should occur during the first month of QUESTRAN LITE therapy. The therapy should be continued to sustain cholesterol reduction. Serum triglyceride levels should be measured periodically to detect whether significant changes have occurred. IF ADEQUATE CHOLESTEROL REDUCTION IS NOT ATTAINED, THERAPY WITH QUESTRAN LITE SHOULD BE DISCONTINUED There is a possibility that prolonged use of QUESTRAN LITE in high doses may produce hyperchloraemic acidosis, since it is the chloride form of an anion exchange resin. This is especially true in younger and smaller patients where the relative dosage may be higher.
Cholestyramine resin may produce or aggravate pre-existing constipation or related conditions such as haemorrhoids. In patient with constipation, the dosage of cholestyramine resin should be decreased, since it may produce impaction. In patients presenting with clinically symptomatic coronary artery disease, where straining of the stool is to be avoided, the dosage of QUESTRAN LITE should be titrated to avert constipation.
Chronic use of cholestyramine resin may be associated with increased bleeding tendency due to hypoprothrombinemia associated with vitamin K deficiency. This will usually respond promptly to parenteral vitamin K administration; recurrences can be prevented by oral administration of vitamin K. Reduction of serum or red cell folate has been reported and treatment with folic acid should be considered in these cases
QUESTRAN LITE should be used with caution in patients with peptic ulcers or with a history of peptic ulcer disease as it might aggravate or activate this condition. Oral Rehydration Therapy In patients with diarrhoea, fluid and electrolyte depletion may occur. Administration of appropriate fluid and electrolyte replacement is the most important measure. Drug Interactions SINCE QUESTRAN LITE MAY BIND OTHER MEDICINES GIVEN CONCURRENTLY, PATIENTS SHOULD TAKE OTHER MEDICINE AT LEAST ONE HOUR BEFORE OR 4-6 HOURS AFTER QUESTRAN LITE TO AVOID IMPEDING THEIR ABSORPTION, OR AT AS GREAT AN INTERVAL AS POSSIBLE.
Since cholestyramine is an anion-exchange resin, QUESTRAN LITE has a strong affinity for acidic materials.
QUESTRAN LITE may delay or reduce the absorption of concomitant oral medication such as phenylbutazone, warfarin, chlorothiazide (acidic), or propranolol as well as tetracycline, penicillin G, phenobarbital, aspirin, thyroid and thyroxine preparations, and digitalis. The discontinuance of QUESTRAN LITE (cholestyramine) could pose a hazard to health if a potentially toxic medicine such as digitalis has been titrated to a maintenance level while the patient was taking QUESTRAN LITE. Also, QUESTRAN LITE may interfere with the pharmacokinetics of medicines (e.g., estrogens) that undergo enterohepatic recirculation. Absorption of fat-soluble vitamins: Because it sequesters bile acids, QUESTRAN LITE may interfere with normal fat absorption. QUESTRAN LITE may prevent absorption of fat-soluble vitamins, such as vitamins A, D and K. Therefore when QUESTRAN LITE is to be given for long periods, daily water miscible or parenteral supplements of vitamins A, D and K should be considered.
Laboratory Tests Serum cholesterol levels should be determined frequently during the first few months of therapy and periodically thereafter. Serum triglyceride levels should be measured periodically to detect whether significant changes have occurred.
KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT One case of overdosage with QUESTRAN LITE has been reported in a patient taking 150% of the maximum recommended daily dosage for several weeks. No ill effects were observed. Should overdosage occur, 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.
IDENTIFICATION Off-white fine powder with a faint orange odour.
PRESENTATION QUESTRAN LITE is available in 4 g or 8 g sachets, each sachet providing 4 g or 8 g of anhydrous cholestyramine. Sachets are in cartons of 50's.
STORAGE INSTRUCTIONS QUESTRAN LITE should be stored at room temperature not exceeding 25°C.
KEEP OUT OF REACH OF CHILDREN.
REGISTRATION NUMBER D/7.5/39
NAME AND BUSINESS ADDRESS OF APPLICANT Bristol-Myers Squibb (Pty) Ltd
47 Van Buuren Road
DATE OF PUBLICATION OF THIS PACKAGE INSERT: June 1999
Updated on this site: July 2005
Source: Pharmaceutical Industry