Drug Class Description
Bile acid sequestrants
Generic Name
Colesevelam
Drug Description
Each tablet contains 625 mg colesevelam hydrochloride (hereafter referred to as colesevelam).Excipients:
Presentation
Film-coated tablet.Off-white, capsule-shaped film-coated tablets imprinted with “Cholestagel” on one side
Indications
Cholestagelco-administered with an HMG-CoA reductase inhibitor (statin) is indicated as adjunctive therapy to diet to provide an additive reduction in LDL-cholesterol (LDL-C) levels in patients with primary hypercholesterolaemia who are not adequately controlled with a statin alone. Cholestagel as monotherapy is indicated as adjunctive therapy to diet for reduction of elevated total and LDL-cholesterol in patients with isolated primary hypercholesterolaemia, in whom a statin is considered inappropriate or is not well tolerated. Cholestagel as monotherapy is indicated as adjunctive therapy to diet for reduction of elevated total and LDL-cholesterol in patients with isolated primary hypercholesterolaemia, in whom a statin is considered inappropriate or is not well tolerated.
Adult Dosage
Current European guidelines should be consulted to establish treatment approaches and goals for individual patients. Prior to initiating therapy with Cholestagel as combination therapy or monotherapy, patients should be placed on a cholesterol-lowering diet and a lipid profile performed to assess total-cholesterol (total-C), HDLcholesterol (HDL-C) and triglyceride levels.During therapy, this diet should be continued, and serum total-C, LDL-C and triglyceride levels should be determined periodically during treatment to confirm favourable initial and adequate long-term responses.When a drug interaction cannot be excluded with a concomitant medicinal product, Cholestagel should be administered at least four hours after the concomitant medication in order to minimize the risk of reduced absorption of the concomitant medication.Cholestagel tablets should be taken orally with a meal and liquid.AdultsCombination therapyTherapy with Cholestagel may be initiated when standard doses of the HMG-CoA reductase inhibitor are inadequate or not well tolerated; the SPC for that particular HMG-CoA reductase inhibitor should be consulted.The recommended dose of Cholestagel is 4 to 6 tablets per day. The maximum recommended dose is 3 tablets taken twice per day with meals or 6 tablets taken once per day with a meal. Co-administration with atorvastatin, lovastatin or simvastatin in clinical trials shows that Cholestagel can be dosed at the same time as one of these HMG-CoA reductase inhibitors or the two medicinal products can be dosed apart.MonotherapyThe recommended starting dose of Cholestagel is 3 tablets taken twice per day with meals or 6 tablets once per day with a meal. The maximum recommended dose is 7 tablets per day.
Child Dosage
The safety and efficacy of Cholestagel have not been established in children and adolescent patients; therefore, the use of Cholestagel in these patient populations is not recommended.
Elderly Dosage
There is no evidence for special considerations when Cholestagel is administered to elderly patients.
Contra Indications
Hypersensitivity to the active substance or to any of the excipients Bowel or biliary obstruction When Cholestagel is co-administered with a statin or any other medications, the SPC of the specific medicine should be consulted for contraindication information.
Special Precautions
Prior to initiating therapy with Cholestagel, secondary causes of hypercholesterolaemia (i.e., poorly controlled diabetes mellitus, hypothyroidism, nephrotic syndrome, dysproteinaemias, obstructive liver disease, other pharmacological therapy, alcoholism) should be excluded.When Cholestagel is co-administered with a statin or any other medications, the SPC of the specific medicine should be consulted for warnings and precautions for use.For patients on ciclosporin starting or stopping Cholestagel or patients on Cholestagel with a need to start ciclosporin: Cholestagel reduces the bioavailability of ciclosporin (see also section 4.5). Patients starting on ciclosporin already taking Cholestagel should have their ciclosporin blood concentrations monitored as normal and their dose adjusted as normal. Patients starting on Cholestagel already taking ciclosporin should have their blood concentrations monitored prior to combination therapy and frequently monitored immediately starting co-therapy with the ciclosporin dose adjusted accordingly. It should be noted that stopping Cholestagel therapy will result in increased ciclosporin blood concentrations. Therefore, patients taking both ciclosporin and Cholestagel should have their blood concentrations monitored prior to and frequently after when Cholestagel therapy is stopped with their ciclosporin dose adjusted accordingly.Caution should be exercised when treating patients with triglyceride levels greater than 3.4 mmol/L due to the triglyceride increasing effect with Cholestagel. Safety and efficacy are not established for patients with triglyceride levels greater than 3.4 mmol/L, since such patients were excluded from the clinical studies.The safety and efficacy of Cholestagel in patients with dysphagia, swallowing disorders, severe gastrointestinal motility disorders, inflammatory bowel disease, liver failure or major gastrointestinal tract surgery have not been established. Consequently, caution should be exercised when Cholestagel is used in patients with these disorders.Cholestagel can induce or worsen present constipation. The risk of constipation should especially be considered in patients with coronary heart disease and angina pectoris.Anticoagulant therapy should be monitored closely in patients receiving warfarin or similar agents, since bile acid sequestrants have been shown both to reduce absorption of vitamin K and to interfere with warfarin's anticoagulant effect.Cholestagel can affect the bioavailability of the combined oral contraceptive pill when administered simultaneously. It is important to ensure that Cholestagel is administered at least 4 hours after the combined oral contraceptive pill to minimise the risk of any interaction.
Interactions
In generalCholestagel may affect the bioavailability of other medicinal products. Therefore when a drug interaction cannot be excluded with a concomitant medicinal product, Cholestagel should be administered at least four hours after the concomitant medication to minimize the risk of reduced absorption of the concomitant medicationWhen administering medicinal products for which alterations in blood levels could have a clinically significant effect on safety or efficacy, physicians should consider monitoring serum levels or effects.Interaction studies have only been performed in adults.In interaction studies in healthy volunteers, Cholestagel had no effect on the bioavailability of digoxin, metoprolol, quinidine, valproic acid, and warfarin. Cholestagel decreased the Cmax and AUC of sustained-release verapamil by approximately 31% and 11%, respectively. Since there is a high degree of variability in the bioavailability of verapamil, the clinical significance of this finding is unclear.There have been very rare reports of reduced phenytoin levels in patients who have received Cholestagel administered with phenytoin.Anticoagulant therapyAnticoagulant therapy should be monitored closely in patients receiving warfarin or similar agents, since bile acid sequestrants have been shown both to reduce absorption of vitamin K and to interfere with warfarin's anticoagulant effect. Specific clinical interaction studies with colesevelam and vitamin K have not been performed.LevothyroxineIn an interaction study in healthy volunteers, Cholestagel reduced the AUC and Cmax of levothyroxine when administered either concomitantly or after 1 hour. No interaction was observed when Cholestagel was administered at least four hours after levothyroxine.Combined oral contraceptive pillIn an interaction study in healthy volunteers, Cholestagel reduced the Cmax of norethindrone as well as the AUC and Cmax of ethinylestradiol when administered simultaneously with the combined oral contraceptive pill. This interaction was also observed when Cholestagel was administered one hour after the combined oral contraceptive pill. However no interaction was observed when Cholestagel was administered four hours after the combined oral contraceptive pill.CiclosporinIn an interaction study in healthy volunteers, co-administration of Cholestagel and ciclosporin significantly reduced the AUC0-inf and Cmax of ciclosporin by 34% by 44%, respectively. Therefore advice is given to closely monitor ciclosporin blood concentrations (see also section 4.4). In addition, based on theoretical grounds Cholestagel should be administered at least 4 hours after ciclosporin in order to further minimise the risks related to the concomitant administration of ciclosporin and Cholestagel. Furthermore, Cholestagel should always be administered at the same times consistently since the timing of intake of Cholestagel and ciclosporin could theoretically influence the degree of reduced bioavailability of ciclosporin.StatinsWhen Cholestagel was co-administered with statins in clinical studies, an expected add-on LDL-cholesterol lowering effect was observed, and no unexpected effects were observed. Interaction studies with colesevelam in combination with pravastatin, rosuvastatin, or high dose HMG-CoA reductase inhibitors have not been performed.Antidiabetic agentsCo-administration of Cholestagel and glyburide (also known as glibenclamide) caused a decrease in the AUC0-inf and Cmax of glyburide by 32% and 47%, respectively. No interaction was observed when Cholestagel was administered four hours after glyburide.Co-administration of Cholestagel and repaglinide had no effect on the AUC and caused a 19% reduction in the Cmax of repaglinide, the clinical significance of which is unknown. No interaction was observed when Cholestagel was administered one hour after repaglinide.No interaction was observed when Cholestagel and pioglitazone were administered simultaneously in healthy volunteersOther forms of interactionCholestagel did not induce any clinically significant reduction in the absorption of vitamins A, D, E or K during clinical studies of up to one year. However, caution should be exercised when treating patients with a susceptibility to vitamin K or fat-soluble vitamin deficiencies, such as patients with malabsorption. In these patients, monitoring vitamin A, D and E levels and assessing vitamin K status through the measurement of coagulation parameters is recommended and the vitamins should be supplemented if necessary
Adverse Reactions
In controlled clinical studies involving approximately 1400 patients, the following adverse reactions were reported in 1% of patients given Cholestagel alone or placebo:PLACEBO (%)CHOLESTAGEL ONLY (%)Digestive SystemFlatulence1311Constipation610Dyspepsia26Diarrhoea53Nausea33Abnormal Stools11Vomiting11Body As A WholeAbdominal Pain44Headache02Constipation and dyspepsia were reported by a higher percentage in the Cholestagel treatment group. In addition to the above listed adverse reactions, 2% of Cholestagel only and no placebo patients experienced treatment emergent serum triglyceride levels of 6 mmol/L; 7% of Cholestagel and 5% of placebo patients experienced treatment emergent serum triglyceride levels 4 mmol/L. Isolated serum transaminase elevations 3 times normal were observed in 0.1% of Cholestagel only patients. Additionally, 0.4% of Cholestagel only and no placebo patients experienced myalgia as a treatment emergent adverse reaction.Adverse reactions were generally mild or moderate in intensity.Cholestagel in combination with statins did not result in any frequent unexpected adverse reactions compared with statins alone.
Manufacturer
Genzyme Therapeutics
Drug Availability
(POM)
Updated
12 August 2009
