OLESTYR Oral suspension Ref.[49692] Active ingredients: Colestyramine

Please see 3 SERIOUS WARNINGS AND PRECAUTIONS BOX.

General

Before instituting therapy with OLESTYR, an attempt should be made to control serum cholesterol by appropriate dietary regimen, weight reduction, and the treatment of any underlying disorder such as hypothyroidism, diabetes mellitus, nephrotic syndrome, dysproteinemias and obstructive liver disease which might be the cause of hypercholesterolemia. In addition, the current medications of the patient should be reviewed for their potential to increase serum LDL-C or total cholesterol. A favorable trend in cholesterol reduction should occur during the first month of cholestyramine therapy. The therapy should be continued to sustain cholesterol reduction.

Carcinogenesis and Mutagenesis

Please see section 16 NON-CLINICAL TOXICOLOGY, Carcinogenicity / Genotoxicity.

Driving and Operating Machinery

OLESTYR has not been shown to impair the patient’s ability to drive or use machines.

Endocrine and Metabolism

There is a possibility that prolonged use of cholestyramine resin, since it is a chloride form of anion exchange resin, may produce hyperchloremic acidosis. This would especially be true in younger and smaller patients where the relative dosage may be higher.

Because cholestyramine binds bile acids, it may interfere with normal fat digestion and absorption and thus may prevent absorption of fat-soluble vitamins such as A, D and K. When OLESTYR is given for long periods of time, concomitant supplementation of water-miscible parenteral forms of vitamins A and D should be considered.

Chronic use of OLESTYR may be associated with increased bleeding tendency due to hypoprothrombinemia associated with vitamin K deficiency. This will usually respond promptly to parenteral vitamin K1 and recurrences can be prevented by oral administration of vitamin K1.

Reduction of serum or red cell folate has been reported over long-term administration of cholestyramine resin. Supplementation with folic acid should be considered in these cases.

Gastrointestinal

Cholestyramine resin may produce or worsen pre-existing constipation. Dosage should be reduced or discontinued in such cases. Fecal impaction and aggravation of hemorrhoids may occur. Every effort should be made to avert severe constipation and its inherent problems in those patients with clinically symptomatic coronary artery disease.

Cholestyramine potentially may cause steatorrhea or accentuate pre-existing steatorrhea, and this may require reduction and adjustment of dosage.

Hepatic / Biliary / Pancreatic

Occasional calcified material has been observed in the biliary tree, including calcification of the gallbladder, in patients to whom cholestyramine resin has been given. This may be a manifestation of the liver disease and not drug related.

Monitoring and 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.

Reproductive Health: Female and Male Potential

• Fertility: The effect of OLESTYR on human fertility is unknown (see 16 Reproductive and Developmental Toxicology).
• Teratogenic Risk: There is non-clinical evidence suggesting that cholestyramine is not embryotoxic or teratogenic (see 16 Reproductive and Developmental Toxicology). There are, however, no adequate and well controlled studies in pregnant women and fetal health (see 7.1.1 Pregnant Women).

7.1 Special Populations

7.1.1 Pregnant Women

Since cholestyramine is not absorbed systemically, it is not expected to cause fetal harm when administered during pregnancy in recommended dosages. There are, however, no adequate and well controlled studies in pregnant women. Use in pregnancy or lactation requires that the potential benefits of drug therapy be weighed against the possible hazards to the mother and child. The known interference with absorption of fat-soluble vitamins may be detrimental even in the presence of supplementation.

7.1.2 Breast-feeding

Caution should be exercised when OLESTYR is administered to a nursing mother. The possible lack of proper vitamin absorption (see 7 Endocrine and Metabolism) may have an effect on nursing infants. Use in pregnancy or lactation requires that the potential benefits of drug therapy be weighed against the possible hazards to the mother and child.

7.1.3 Pediatrics

Pediatrics (birth to 18 year of age): Based on the data submitted and reviewed by Health Canada, the safety and efficacy of OLESTYR in pediatric patients has not been established; therefore, Health Canada has not authorized an indication for pediatric use.

• The effects of long-term drug administration, as well as its effect in maintaining lowered cholesterol levels in pediatric patients, are unknown. A pediatric dosage schedule has not been established.

7.1.4 Geriatrics

• Appropriate studies on the relationship of age to the effects of cholestyramine have not been performed in the geriatric population. However, patients over 60 years of age may be more likely to experience gastrointestinal side effects.(See 1.2 Geriatrics; 8.1 Adverse Reaction Overview).

8.1 Adverse Reaction Overview

The most frequent adverse effect of cholestyramine resin is constipation (see 8.5 Post-Market Adverse Reactions). When used as a cholesterol lowering agent, predisposing factors for most complaints of constipation [*] 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.

[*] The percentage of complaints that are associated with these predisposing factors is unknown.

8.2 Clinical Trial Adverse Reactions

The clinical trial data on which the original indication was authorized is not available.

8.5 Post-Market Adverse Reactions

The following table presents a listing of post-market adverse reactions with their frequency of occurrence in patients treated with cholestyramine.

The frequency of the following post-market adverse reactionsis unknown.

• Gastrointestinal: gastrointestinal-rectal bleeding, black stools, hemorrhoidal bleeding, bleeding from known duodenal ulcer, dysphagia, hiccups, ulcer attack, sour taste, pancreatitis, rectal pain, diverticulitis, eructation
• Hematologic: decreased or increased prothrombin time, ecchymosis, anemia, dental bleeding
• Hypersensitivity: asthma, wheezing, shortness of breath
• Monitoring and Laboratory Tests: liver function abnormalities
• Musculoskeletal: backache, muscle and joint pain, arthritis
• Neurologic: headache, anxiety, vertigo, dizziness, fatigue, tinnitus, syncope, drowsiness, femoral nerve pain, paresthesia
• Ophthalmologic: uveitis
• Renal: hematuria, dysuria, burnt odour of urine, diuresis
• Other: weight loss, weight gain, increased libido, swollen glands, edema, dental caries.

9.2 Drug Interactions Overview

Since cholestyramine resin is an anion-exchange resin, it may have strong affinity for anions other than the bile acids. Drug that are affected by co-administration of bile acid sequestrants vary widely in pharmacologic effect and mechanisms, magnitude of doses, and chemical characteristics. Therefore, it is not possible to predict a priori whether co-administration with cholestyramine will interfere with absorption. It should be assumed that concomitantly administered drugs have the potential interacting with cholestyramine unless clinical studies have shown otherwise.

Drug Interaction studies have been conducted with cholestyramine and various HMG-CoA reductase inhibitors. Although cholestyramine has been shown to reduce the bioavailability of HMG-CoA reductase inhibitors, the clinical cholesterol-lowering effects of an HMG-CoA reductase inhibitor and cholestyramine have been shown to be additive.

9.3 Drug-Behavioural Interactions

The effect of lifestyle choices (e.g., alcohol consumption, sexual activity, smoking) on the use of OLESTYR has not been established.

9.4 Drug-Drug Interactions

• Cholestyramine resin may delay or reduce the absorption of concomitant oral medication such as:
  • thyroid and thyroxine preparations
  • warfarin
  • chlorothiazide (acidic)
  • phenylbutazone
  • phenobarbital
  • tetracycline
  • penicillin G
  • digitalis
• The discontinuance of cholestyramine could pose a hazard to health if a potentially toxic drug such as digitalis has been titrated to maintenance level while the patient was taking cholestyramine. The concomitant drug should be re-titrated to avoid over-dosage when cholestyramine is discontinued.
• Cholestyramine may interfere with the pharmacokinetics of drugs (e.g., estrogens) that undergo enterohepatic recirculation.

9.5 Drug-Food Interactions

Interactions with food have not been established.

9.6 Drug-Herb Interactions

Interactions with herbal products have not been established.

9.7 Drug-Laboratory Test Interactions

Interactions with laboratory tests have not been established.