Cholestagel · 4.5 Interaction with other medicinal products and other forms of interaction · 1

HOS-093666 · has-adverse-reaction-information · PDF-Seite 6

Summary of the safety profile The most frequently occurring adverse reactions are flatulence and constipation, found within the gastrointestinal disorders system organ class. Tabulated list of adverse reactions In controlled clinical studies involving approximately 1400 patients and during post-approval use, the following adverse reactions were reported in patients given Cholestagel. The reporting rate is classified as 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) and not known (cannot be estimated from the available data). Nervous system disorders Common: Headache Gastrointestinal disorders Very common: Flatulence*, constipation* Common: Vomiting, diarrhoea*, dyspepsia*, abdominal pain, abnormal stools, nausea, abdominal distension Uncommon: Dysphagia Very rare: Pancreatitis Not known: Intestinal obstruction*,** Musculoskeletal and connective tissue disorders Uncommon: Myalgia Investigations Common: Serum triglycerides increased Uncommon :Serum transaminases increased * see section below for further information ** adverse reactions from post-marketing experience Description of selected adverse events The background incidence of flatulence and diarrhoea were higher in patients receiving placebo in the same controlled clinical studies. Only constipation and dyspepsia were reported by a higher percentage among those receiving Cholestagel, compared with placebo. The incidence of intestinal obstruction is likely to be increased among patients with a history of bowel obstruction or removal. 6 Cholestagel in combination with statins and in combination with ezetimibe was well tolerated and the adverse reactions observed were consistent with the known safety profile of statins or ezetimibe alone. 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 national reporting system listed in Appendix V.

HOS-093662 · has-contraindication-information · PDF-Seite 3

• Hypersensitivity to the active substance or to any of the excipients listed in section 6.1 • Bowel or biliary obstruction

HOS-093661 · has-indication-information · PDF-Seite 2

Cholestagel co-administered with a 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase inhibitor (statin) is indicated as adjunctive therapy to diet to provide an additive reduction in low-density lipoprotein cholesterol (LDL-C) levels in adult 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-cholesterol and LDL-C in adult patients with primary hypercholesterolaemia, in whom a statin is considered inappropriate or is not well-tolerated. Cholestagel can also be used in combination with ezetimibe, with or without a statin, in adult patients with primary hypercholesterolaemia, including patients with familial hypercholesterolaemia (see section 5.1).

HOS-093664 · has-interaction-information · PDF-Seite 4

In general Cholestagel may affect the bioavailability of other medicinal products. Therefore when a drug interaction cannot be excluded with a concomitant medicinal product for which minor variations in the therapeutic level would be clinically important, Cholestagel should be administered at least four hours before or at least four hours after the concomitant medication to minimize the risk of reduced absorption of the concomitant medication. For concomitant medications which require administration via divided doses, it should be noted that the required dose of Cholestagel can be taken once a day. When 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. Co-administration of colesevelam and olmesartan decreases the exposure of olmesartan. Olmesartan should be administered at least 4 hours prior to colesevelam. There have been very rare reports of reduced phenytoin levels in patients who have received Cholestagel administered with phenytoin. Anticoagulant therapy Anticoagulant therapy should be monitored closely in patients receiving warfarin or similar agents, since bile acid sequestrants, like Cholestagel, have been shown to reduce absorption of vitamin K and therefore interfere with warfarin's anticoagulant effect. Specific clinical interaction studies with colesevelam and vitamin K have not been performed. Levothyroxine In 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. Oral contraceptive pill In 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 oral contraceptive pill. This interaction was also observed when Cho

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HOS-093665 · has-pregnancy-information · PDF-Seite 5

Pregnancy No clinical data are available on the use of Cholestagel in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonic/foetal development, 5 parturition or postnatal development (see section 5.3). Caution should be exercised when prescribing to pregnant women. Breast-feeding The safety of Cholestagel has not been established in breast-feeding women. Caution should be exercised when prescribing to breast-feeding women. Fertility There are no data on the effect of Cholestagel on fertility in humans. A study conducted in rats did not result in any differences in reproductive parameters between the groups that might imply reproductive effects attributable to colesevelam.

HOS-093663 · has-warning-information · PDF-Seite 3

Secondary causes of hypercholesterolaemia Prior to initiating therapy with Cholestagel, if secondary causes of hypercholesterolaemia (i.e., poorly controlled diabetes mellitus, hypothyroidism, nephrotic syndrome, dysproteinaemias, obstructive liver disease) are considered, these should be diagnosed and properly treated. Interaction with ciclosporin 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. Effects on triglyceride levels 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. Constipation Cholestagel can induce or worsen present constipation. The risk of constipation should especially be considered in patients with coronary heart disease and angina pectoris. 3 Anticoagulants Anticoagulant therapy should be monitored closely in patients receiving warfarin or similar agents, since bile acid sequestrants, like Cholestagel, have been shown to reduce absorption of vitamin K and therefore interfere with warfarin’s an

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