Summary of Product Characteristics (SmPC) - Questran Light 4 g/sachet powder for oral suspension
1 NAME OF THE MEDICINAL PRODUCT
Questran Light 4g/sachet Powder for Oral Suspension
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each sachet contains 4 g anhydrous colestyramine (a basic anion-exchange resin).
Excipients with known effect:
Each sachet contains 30 mg aspartame and 32.5 mg propylene glycol (as alginate).
For the full list of excipients, see section 6.1.
3 PHARMACEUTICAL FORM
Powder for Oral Suspension.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Questran Light is used for:
- 1. Primary prevention of coronary heart disease in men between 35 and 59 years of age and with primary hypercholesterolaemia who have not responded to diet and other appropriate measures.
- 2. Reduction of plasma cholesterol in hypercholesterolaemia, particularly in those patients who have been diagnosed as Fredrickson’s Type II (high plasma cholesterol with normal or slightly elevated triglycerides).
- 3. Relief of pruritus associated with partial biliary obstruction and primary biliary cirrhosis.
- 4. Relief of diarrhoea associated with ileal resection, Crohn’s disease, vagotomy and diabetic vagal neuropathy.
- 5. Management of radiation-induced diarrhoea.
4.2 Posology and method of administration
Posology
Adults:
- 1. Monotherapy: For primary prevention of coronary heart disease and to reduce cholesterol: After initial introduction over a three to four week period, 3 to 6 Questran Light sachets per day, administered either as a single daily dose or in divided doses up to four times daily, according to dosage requirements and patient acceptability. Dosage may be modified according to response and can be increased to 9 sachets per day if necessary.
Occasional slight gastrointestinal upsets, e.g. constipation, may occur when starting Questran Light. These usually pass with continued usage of Questran Light and are minimised by starting therapy gradually.
| Final dose required | Week 1 | Week 2 | Week 3 | Week 4 |
| Sachets per day | ||||
| 3 | 1 | 2 | 3 | 3 |
| 4 | 1 | 2 | 3 | 4 |
| 6 | 1 | 2 | 3 | 6 |
Combination therapy
The cholesterol-lowering effect of colestyramine on total and LDL-cholesterol is enhanced when it is combined with an HMG-CoA reductase inhibitor (e.g. pravastatin, simvastatin, lovastatin). Enhanced lowering of LDL-cholesterol is also seen with combined nicotinic acid/colestyramine therapy. There is also evidence to support the addition of colestyramine to gemfibrozil therapy in order to further lower LDL-cholesterol in patients with high LDL-cholesterol and triglycerides and low HDL-cholesterol.
- 2. To relieve pruritus: One or two sachets daily are usually sufficient.
- 3. To relieve diarrhoea: As for reduction of cholesterol but it may be possible to reduce this dosage. In all patients presenting with diarrhoea induced by bile acid malabsorption, if a response is not seen within 3 days, then alternative therapy should be initiated.
Doses of more than 24 g a day of colestyramine resin may interfere with normal fat absorption.
Paediatric
population
Children 6
12 years: The initial dose is determined by the following formula:
Child's Weight in Kg x Adult Dose
70
Subsequent dosage adjustment may be necessary where clinically indicated.
To minimise potential gastrointestinal side effects, it is desirable to begin all therapy in children with one dose of Questran Light daily. The dosage is then increased gradually, every five to seven days to the desired level for effective control.
Children under 6 years:
Questran Light should not be used in children under 6 years. There are no data to support its use.
Questran Light should not be used in patients with exudative or bloody diarrhoea.
Elderly
No dosage adjustment is
necessary. Method of
administration
As a precautionary measure, where concurrent drug therapy exists then such drugs should be administered at least one hour before or 4-6 hours after Questran Light.
Questran Light should not be taken in its dry form.
Questran Light should be administered mixed with water or a suitable liquid, such as fruit juice, and stirred to a uniform consistency.
Questran Light may also be mixed with skimmed milk, thin soups, pulpy fruits with high moisture content, e.g. apple sauce, etc.
The suggested time of administration is mealtime, but this may be modified to avoid interference with absorption of other medications.
4.3 Contraindications
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
In patients with complete biliary obstruction, since Questran Light cannot be effective where bile is not secreted into the intestine.
4.4 Special warnings and precautions for use
Before instituting therapy with Questran Light, diseases contributing to increased blood cholesterol such as hypothyroidism, diabetes mellitus, nephrotic syndrome, dysproteinaemias and obstructive liver disease should be investigated and specifically treated. In addition, prior to instituting therapy with Questran Light, 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 hypercholesterolaemia. 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 Light therapy. The therapy should be continued to sustain cholesterol reduction. Serum triglyceride levels should be measured periodically to detect whether significant changes have occurred.
Reduction of serum folate concentrations has been reported in children with familial hypercholesterolaemia. Supplementation with folic acid should be considered in these cases.
Since Questran Light may interfere with the absorption of fat-soluble vitamins, the diet may require supplementation with Vitamins A, D and K during prolonged high dose administration.
Chronic use of Questran Light may be associated with increased bleeding tendency due to hypoprothrombinaemia 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.
Since colestyramine may bind other drugs given concurrently, the interval between the administration of colestyramine and other medication should be as great as is feasible.
Patients should take other drugs at least one hour before or four to six hours after colestyramine to avoid impeding their absorption.
There is a possibility that prolonged use of colestyramine resin in high doses may produce hyperchloremic 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 as well as in patients with renal impairment.
Colestyramine may produce or aggravate pre-existing constipation or related conditions, such as haemorrhoids. In patients with constipation, the dosage of colestyramine 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 Light should be titrated to avert constipation.
Questran Light contains 30 mg aspartame in each sachet. Aspartame is a source of phenylalanine. It may be harmful for patients who have phenylketonuria (PKU).
Neither non-clinical nor clinical data are available to assess aspartame use in infants below 12 weeks of age.
Questran Light contains 32.5 mg propylene glycol (as alginate) in each sachet. If the patient is less than 5 years old, co-administration with any substrate for alcohol dehydrogenase such as ethanol may induce adverse effects. For propylene glycol doses exceeding 50 mg/kg/day, medical monitoring is required in patients with impaired renal or hepatic function.
4.5 Interaction with other medicinal products and other forms of interaction
Questran Light may delay or reduce the absorption of certain drugs (such as digitalis, tetracycline, chlorothiazide, warfarin and thyroxine). The discontinuation of Questran Light could pose a hazard to health if a potentially toxic drug such as digitalis has been titrated to a maintenance level while the patient was taking Questran light. The response to concomitant medication should be closely monitored and appropriate adjustments made if necessary.
Questran Light may interfere with the pharmacokinetics of drugs that undergo enterohepatic recirculation.
Questran Light in combination with spironolactone may increase the potential for the development of hyperchloraemic acidosis.
Patients should take other drugs at least one hour before or 4-6 hours after Questran Light to minimise possible interference with their absorption.
Tabulated list of Colestyramine drug-drug interactions:
| Drug Class | Drug(s) |
| Anti-arrhythmics | Amiodarone |
| Anti-convulsants | Valproate |
| Anti-infectives | Vancomycin, tetracycline |
| Antimetabolites | Methotrexate |
| Bile acids | Ursodeoxycholic acid |
| Cholesterol lowering drugs | Ezetimibe |
| Combined hormonal contraceptive | Ethinylestradiol |
| Coumarins | Phenprocoumon, warfarin |
| Digitalis glycosides | Digitoxin, digoxin |
| Disease-modifying antirheumatics | Leflunomide |
| Immunosuppressants | Mycophenolate |
| Loop Diuretics | Furosemide |
| Nonsteroidal anti-inflammatory drugs | Diclofenac, meloxicam, piroxicam, sulindac, tenoxicam |
| Potassium sparing diuretics | Spironolactone |
| Thiazide diuretics | Chlorothiazide, hydrochlorothiazide |
| Thyroid hormones | Levothyroxine, liothyronine, thyroid extract |
4.6 Fertility, pregnancy and lactation
The safety of colestyramine in pregnancy and lactation has not been established and the possibility of interference with absorption of fat-soluble vitamins should be considered.
4.7 Effects on ability to drive and use machines
Questran Light has no or negligible influence on the ability to drive and use machines
4.8 Undesirable effects
Frequency categories are defined according to the following convention: 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), not known (cannot be estimated from the available data).
The most common adverse reaction is constipation. Predisposing factors for most of these complaints when Questran Light is used as a cholesterol lowering agent 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.
Tabulated list of adverse reactions:
| System Organ Class | Frequency | Adverse Reaction(s) |
| Blood and lymphatic system disorders | Uncommon | Bleeding tendencies due to hypoprothrombinaemia (Vitamin K deficiency) as well as Vitamin A (night blindness has been reported rarely) and D deficiencies |
| Not known | Anaemia | |
| Metabolism and nutrition disorders | Uncommon | Anorexia, hyperchloremic acidosis in children and patients with renal impairment |
| Not known | Oedema | |
| Gastrointestinal disorders | Very common | Constipation |
| Uncommon | Abdominal discomfort, flatulence, nausea, vomiting, diarrhoea, heartburn, dyspepsia and steatorrhea | |
| Rare | Reports of intestinal obstruction have been received post marketing, including deaths in paediatric patients | |
| Not known | Acute abdominal symptom complex ("pasty mass" in the transverse colon on X-ray), eructation | |
| Skin and subcutaneous tissue disorders | Uncommon | Rash and irritation of skin, tongue and perianal area |
| Musculoskeletal and connective tissue disorders | Uncommon | Osteoporosis |
| Not known | Arthritis, backache | |
| Renal and urinary disorders | Not known | Calcified material has occasionally been observed in the biliary tree (including calcification of the gall bladder), burnt odour to urine |
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 or search for MHRA Yellow Card in the Google Play or Apple App Store.
4.9 Overdose
One case of medication error experienced heartburn and nausea after taking colestyramine 27 g three times a day for a week. The potential problem in overdosage 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.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Bile acid sequestrants, ATC code: C10AC01.
Colestyramine resin absorbs and combines with the bile acids in the intestine to form an insoluble complex which is excreted in the faeces. This results in a continuous, though partial, removal of bile acids from the enterohepatic circulation by preventing their reabsorption. 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 serum levels. Colestyramine is hydrophilic but it is not soluble in water, nor is it hydrolysed by digestive enzymes.
In addition to the bile acids, cholestyramine can also bind other substances (e.g. certain drugs, fat-soluble vitamins) and interfere with their absorption and/or enterohepatic circulation.
In patients with partial biliary obstruction, the reduction of serum bile acid levels reduces excess bile acids deposited in the dermal tissue with resultant decrease in pruritus.
5.2 Pharmacokinetic properties
The colestyramine resin in Questran Light is not absorbed from the digestive tract.
5.3 Preclinical safety data
In studies conducted in rats in which colestyramine 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 tumours induced by potent carcinogens, the incidence of such tumours was observed to be greater in colestyramine-treated rats than in control rats. The relevance of laboratory observation from studies in rats to the clinical use of Questran Light is not known. A long-term study in humans does not reveal any significant difference between patients treated with cholestyramine and those treated with placebo with respect to the incidence of cancer.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Aspartame (E951)
Citric acid anhydrous
Colloidal anhydrous silica
Orange juice flavour
Propylene glycol alginate
Xanthan gum
6.2 Incompatibilities
Not applicable.
6.3 Shelf life
3 years.
6.4 Special precautions for storage
Do not store above 30°C.
6.5 Nature and contents of container
Original packs containing 50 or 60 laminate sachets composed of paper, polyethylene and aluminium. Not all pack sizes may be marketed.
6.6 Special precautions for disposal
No special instructions.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
7 MARKETING AUTHORISATION HOLDER
Neon Healthcare Limited
8 The Chase, John Tate Road,
Hertford, SG13 7NN,
United Kingdom
8 MARKETING AUTHORISATION NUMBER(S)
PL 45043/0046
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
25th July1988 / 26th November 1998
10 DATE OF REVISION OF THE TEXT
26/03/2024