Cholestagel

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ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 
 



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1. NAME OF THE MEDICINAL PRODUCT 
 
Cholestagel 625 mg film-coated tablets 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each tablet contains 625 mg colesevelam (as hydrochloride). 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Film-coated tablet (tablet). 
Off-white, capsule-shaped film-coated tablets imprinted with “C625” on one side. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
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). 
 
4.2 Posology and method of administration 
 
Posology 
Combination therapy 
The recommended dose of Cholestagel for combination with a statin with or without ezetimibe is 4 to 
6 tablets per day. The maximum recommended dose is 6 tablets per day taken as 3 tablets twice per 
day with meals or 6 tablets taken once per day with a meal. Clinical trials have shown that Cholestagel 
and statins can be co-administered or dosed apart, and that Cholestagel and ezetimibe can be co-
administered or dosed apart. 
 
Monotherapy 
The recommended starting dose of Cholestagel is 6 tablets per day taken as 3 tablets twice per day 
with meals or 6 tablets once per day with a meal. The maximum recommended dose is 7 tablets per 
day. 
 
During therapy, the cholesterol-lowering 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 for which minor 
variations in the therapeutic level would be clinically important, or where no clinical data are available 
on co-administration, Cholestagel should be administered at least four hours before or at least four 



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hours after the concomitant medication in order to minimize the risk of reduced absorption of the 
concomitant medication (see section 4.5).  
 
Elderly population 
There is no need for dose adjustment when Cholestagel is administered to elderly patients. 
 
Paediatric population 
The safety and efficacy of Cholestagel in children aged 0 to 17 years have not yet been established. 
Currently available data are described in section 5.1 but no recommendation on a posology can be 
made.  
 
Method of administration 
Cholestagel tablets should be taken orally with a meal and liquid.  
The tablets should be swallowed whole and not broken, crushed or chewed. 
 
4.3 Contraindications 
 
• Hypersensitivity to the active substance or to any of the excipients listed in section 6.1 
• Bowel or biliary obstruction 
 
4.4 Special warnings and special precautions for use 
 
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. 
 



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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 anticoagulant effect (see also section 4.5). 
 
Oral contraceptives 
Cholestagel can affect the bioavailability of the oral contraceptive pill when administered 
simultaneously. It is important to ensure that Cholestagel is administered at least 4 hours after the oral 
contraceptive pill to minimise the risk of any interaction (see also section 4.5). 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
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 Cholestagel was administered one hour after the oral 
contraceptive pill. However no interaction was observed when Cholestagel was administered four 
hours after the oral contraceptive pill. 
 
Ciclosporin 
In 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 



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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. 
 
Statins 
When Cholestagel was co-administered with statins in clinical studies, an expected add-on LDL-C 
lowering effect was observed, and no unexpected effects were observed. Cholestagel had no effect on 
the bioavailability of lovastatin in an interaction study. 
 
Antidiabetic agents 
Co-administration of colesevelam and metformin extended-release (ER) tablets increases the exposure 
of metformin. Patients receiving concomitant metformin ER and colesevelam should be monitored for 
clinical response as is usual for the use of anti-diabetes drugs.  
 
Colesevelam binds to glimepiride and reduces glimepiride absorption from the gastrointestinal tract. 
No interaction was observed when glimepiride was taken at least 4 hours before colesevelam. 
Therefore glimepiride should be administered at least 4 hours prior to colesevelam. 
 
Co-administration of colesevelam and glipizide decreases the exposure of glipizide. Glipizide should 
be administered at least 4 hours prior to colesevelam. 
 
Co-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 volunteers 
 
Ursodeoxycholic acid 
Cholestagel predominantly binds hydrophobic bile acids. In a clinical study Cholestagel did not affect 
the faecal excretion of endogenous (hydrophilic) ursodeoxycholic acid. However, formal interaction 
studies with ursodeoxycholic acid have not been performed. As noted in general, when a drug 
interaction cannot be excluded with a concomitant medicinal product, Cholestagel should be 
administered at least four hours before or at least four hours after the concomitant medication to 
minimise the risk of reduced absorption of the concomitant medication. Monitoring of the clinical 
effects of treatment with ursodeoxycholic acid should be considered. 
 
Other forms of interaction 
Cholestagel 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. 
 
4.6 Fertility, pregnancy and lactation 
 
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, 



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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. 
 
4.7 Effects on ability to drive and use machines 
 
Cholestagel has no or negligible influence on the ability to drive and use machines. 
 
4.8 Undesirable effects 
 
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. 
 



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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. 
 
4.9 Overdose 
 
Since Cholestagel is not absorbed, the risk of systemic toxicity is low. Gastrointestinal symptoms could 
occur. Doses in excess of the maximum recommended dose (4.5 g per day (7 tablets)) have not been 
tested. 
 
Should overdosage occur, however, 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. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: Lipid modifying agent, bile acid sequestrants, ATC code: C10A C 04 
 
Mechanism of action 
The mechanism of action for the activity of colesevelam, the active substance in Cholestagel, has been 
evaluated in several in vitro and in vivo studies. These studies have demonstrated that colesevelam 
binds bile acids, including glycocholic acid, the major bile acid in humans. Cholesterol is the sole 
precursor of bile acids. During normal digestion, bile acids are secreted into the intestine. A major 
portion of bile acids is then absorbed from the intestinal tract and returned to the liver via the 
enterohepatic circulation. 
 
Colesevelam is a non-absorbed, lipid-lowering polymer that binds bile acids in the intestine, impeding 
their reabsorption. The LDL-C lowering mechanism of bile acid sequestrants has been previously 
established as follows: As the bile acid pool becomes depleted, the hepatic enzyme, cholesterol 
7-α-hydroxylase, is upregulated, which increases the conversion of cholesterol to bile acids. This 
causes an increased demand for cholesterol in the liver cells, resulting in the dual effects of increasing 
transcription and activity of the cholesterol biosynthetic enzyme, hydroxymethyl-glutaryl-coenzyme A 
(HMG-CoA) reductase, and increasing the number of hepatic low-density lipoprotein receptors. A 
concomitant increase in very low density lipoprotein synthesis can occur. These compensatory effects 
result in increased clearance of LDL-C from the blood, resulting in decreased serum LDL-C levels. 
 
In a 6-month dose-response study in patients with primary hypercholesterolaemia receiving 3.8 or 
4.5 g Cholestagel daily, a 15 to 18% decrease in LDL-C levels was observed, which was evident 
within 2 weeks of administration. In addition, Total-C decreased 7 to 10%, HDL-C increased 3% and 
triglycerides increased 9 to 10%.  Apo B decreased by 12%. In comparison, in patients given placebo, 
LDL-C, Total-C, HDL-C and Apo-B were unchanged, while triglycerides increased 5%. Studies 
examining administration of Cholestagel as a single dose with breakfast, a single dose with dinner, or 
as divided doses with breakfast and dinner did not show significant differences in LDL-C reduction 
for different dosing schedules. However, in one study triglycerides tended to increase more when 
Cholestagel was given as a single dose with breakfast.  
 
In a 6 week study 129 patients with mixed hyperlipidaemia were randomised to fenofibrate 160 mg 
plus 3.8 g Cholestagel or fenofibrate alone. The fenofibrate plus Cholestagel group (64 patients) 
demonstrated a 10% reduction on LDL-C levels versus 2% increase for the fenofibrate group 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc
http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


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(65 patients). Reductions were also seen for non-HDL-C, Total-C and Apo B. A small 5%, 
non-significant increase in triglycerides was noted. The effects of combination of fenofibrate and 
Cholestagel on the risks of myopathy or hepatotoxicity are not known. 
 
Multi-centre, randomised, double-blind, placebo-controlled studies in 487 patients demonstrated an 
additive reduction of 8 to 16% in LDL-C when 2.3 to 3.8 g Cholestagel and a statin (atorvastatin, 
lovastatin or simvastatin) were administered at the same time. 
 
The effect of 3.8 g Cholestagel plus 10 mg ezetimibe versus 10 mg ezetimibe alone on LDL-C levels 
was assessed in a multicentre, randomised, double-blind, placebo-controlled, parallel-group study in 
86 patients with primary hypercholesterolaemia over a 6-week treatment period.  The combination of 
ezetimibe 10 mg and Cholestagel 3.8 g daily therapy in the absence of a statin resulted in a significant 
combined effect for LDL-C lowering by 32% demonstrating an additional effect of 11% LDL-C 
lowering with Cholestagel and ezetimibe compared to ezetimibe alone. 
 
The addition of Cholestagel 3.8 g daily to maximally-tolerated statin and ezetimibe therapy was 
assessed in a multi-centre, randomised, double-blind, placebo-controlled study in 86 patients with 
familial hypercholesterolaemia. A total of 85% of the patients were on either atorvastatin (50% of 
whom received 80 mg dose) or rosuvastatin (72% of whom received 40 mg dose). Cholestagel resulted 
in a statistically significant LDL-C reduction of 11% and 11% at 6 and 12 weeks vs an increase of 7% 
and 1% in the placebo group; mean baseline levels were 3.75 mmol/L and 3.86 mmol/L, respectively.  
Triglycerides in the Cholestagel group increased by 19% and 13% at 6 and 12 weeks vs an increase of 
6% and 13% in the placebo group, but the increases were not significantly different. HDL-C and 
hsCRP levels were also not significantly different compared to placebo at 12 weeks.  
 
Paediatric population 
In the paediatric population, the safety and efficacy of 1.9 or 3.8 g/day Cholestagel was assessed in an 
8 week multi-centre, randomised, double-blind, placebo-controlled study in 194 boys and 
postmenarchal girls, aged 10-17 years, with heterozygous FH on a stable dose of statins (47 patients, 
24%) or treatment-naïve to lipid-lowering therapy (147 patients, 76%).  For all patients, Cholestagel 
resulted in a statistically significant LDL-C reduction of 11% at 3.8 g/day and 4% at 1.9 g/day, versus 
a 3% increase in the placebo group.  For statin-naïve patients on monotherapy, Cholestagel resulted in 
a statistically significant LDL-C reduction of 12% at 3.8 g/day and 7% at 1.9 g/day, versus a 1% 
reduction in the placebo group (see section 4.2). There were no significant effects on growth, sexual 
maturation, fat-soluble vitamin levels or clotting factors, and the adverse reaction profile for 
Cholestagel was comparable to that seen with placebo. 
 
Cholestagel has not been compared directly to other bile acid sequestrants in clinical trials. 
 
So far, no studies have been conducted that directly demonstrate whether treatment with Cholestagel 
as monotherapy or combination therapy has any effect on cardiovascular morbidity or mortality. 
 
5.2 Pharmacokinetic properties 
 
Cholestagel is not absorbed from the gastrointestinal tract. 
 
5.3 Preclinical safety data 
 
Effects in non-clinical studies were observed only at exposures considered sufficiently in excess of the 
maximum human exposure indicating little relevance to clinical use. 
 
 



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6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Tablet core: 
Cellulose (E460), microcrystalline 
Silica, colloidal anhydrous 
Magnesium stearate 
Water, purified 
 
Film-coating: 
Hypromellose (E464) 
Diacetylated monoglycerides 
 
Printing ink: 
Iron oxide black (E172) 
Hypromellose (E464) 
Propylene glycol 
 
6.2 Incompatibilities 
 
Not applicable. 
 
6.3 Shelf life 
 
2 years. 
 
6.4 Special precautions for storage 
 
Keep the bottle tightly closed in order to protect from moisture. 
 
6.5 Nature and contents of container 
 
High density polyethylene bottles with a polypropylene cap. 
Package sizes are: 24 tablets (1 X 24) 
  100 tablets (2 X 50) 

 180 tablets (1 X 180) 
 
High density polyethylene bottles with a polypropylene cap without outer carton. 
Package sizes are: 180 tablets (1 X 180) 
 
Not all pack sizes may be marketed. 
 
6.6 Instructions precautions for disposal and other handling 
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Genzyme Europe B.V., Paasheuvelweg 25, 1105 BP Amsterdam, the Netherlands. 
 
 
8. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/03/268/001-004 



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9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 10 March 2004 
Date of latest renewal: 12 March 2009 
 
 
10. DATE OF REVISION OF THE TEXT 
 
 
Detailed information on this medicinal product is available on the website of the European 
Medicines Agency http://www.ema.europa.eu/. 

http://www.ema.europa.eu/
http://www.ema.europa.eu/


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ANNEX II 
 
Α MANUFACTURER RESPONSIBLE FOR BATCH RELEASE 
 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY 

AND USE 
 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE 

MARKETING AUTHORISATION 
 

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE 
SAFE AND EFFECTIVE USE OF THE MEDICINAL 
PRODUCT 

 



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A MANUFACTURER RESPONSIBLE FOR BATCH RELEASE 
 
Name and address of the manufacturer(s) responsible for batch release 
 
Genzyme Ireland Ltd., IDA Industrial Park, Old Kilmeaden Road, Waterford, Ireland 
 
 
B CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 
 
Medicinal product subject to medical prescription. 
 
 
C OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 
 
• Periodic Safety Update Reports 
The marketing authorisation holder shall submit periodic safety update reports for this product in 
accordance with the requirements set out in the list of Union reference dates (EURD list) provided for 
under Article 107c(7) of Directive 2001/83/EC and published on the European medicines web-portal. 
 
D CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 
 
• Risk Management Plan (RMP) 
The MAH shall perform the pharmacovigilance activities and interventions detailed in the agreed 
RMP presented in Module 1.8.2. of the Marketing Authorisation and any subsequent updates of the 
RMP. 
 
An updated RMP should be submitted: 
• At the request of the European Medicines Agency 
• Whenever the risk management system is modified, especially as the result of new information 

being received that may lead to a significant change to the benefit/risk profile or as the result of 
an important (pharmacovigilance or risk minimisation) milestone being reached.. 

 
If the dates for submission of a PSUR and the update of a RMP coincide, they can be submitted 
at the same time. 
 



13 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 
 



14 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 



15 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING AND THE IMMEDIATE 
PACKAGING 
 
OUTER CARTON AND BOTTLE LABEL (24, 100 AND 180  TABLETS) WITH CARTON 
BOTTLE LABEL (180 TABLETS) WITHOUT CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Cholestagel 625 mg film-coated tablets 
Colesevelam 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each tablet contains 625 mg of colesevelam (as hydrochloride). 
 
 
3. LIST OF EXCIPIENTS 
 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
24 film-coated tablets 
100 film-coated tablets 
180 film-coated tablets 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Oral use 
Tablets should be taken with liquid and with a meal. 
Read the package leaflet before use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Keep the bottle tightly closed in order to protect from moisture. 
 
 



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10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Genzyme Europe B.V. 
Paasheuvelweg 25,  
1105 BP Amsterdam 
The Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/03/268/001  24 tablets 
EU/1/03/268/002   100 tablets 
EU/1/03/268/003   180 tablets with carton 
EU/1/03/268/004   180 tablets without carton 
 
 
13. BATCH NUMBER 
 
Batch  
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Cholestagel 
625 mg 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
  
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC:  
SN:  
NN:  



17 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 



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Package leaflet: Information for the user 
 

Cholestagel 625 mg film-coated tablets 
Colesevelam 

 
Read all of this leaflet carefully before you start using this medicine because it contains 
important information for you. 
- Keep this leaflet. You may need to read it again. 
- If you have any further questions, ask your doctor or pharmacist. 
- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours. 
- If you get any side effects talk to your doctor or pharmacist.  This includes any possible side 

effects not listed in this leaflet. See section 4. 
 
 
What is in this leaflet:  
1. What Cholestagel is and what it is used for 
2. What you need to know before you take Cholestagel 
3. How to take Cholestagel 
4. Possible side effects 
5. How to store Cholestagel 
6. Contents of the pack and other information 
 
 
1. What Cholestagel is and what it is used for 
 
Cholestagel contains the active substance colesevelam (as hydrochloride). Taking Cholestagel helps to 
lower the level of cholesterol in your blood. Your doctor should only give you Cholestagel if a diet 
low in fat and cholesterol did not work well enough on its own. 
 
Cholestagel works in your intestinal system by binding bile acids produced by your liver and carrying 
the bile acids out of your body with your faeces. This prevents your body from recycling the bile acids 
from your intestines in the usual way. Without the recycling process, your liver has to make additional 
bile acids. Your liver uses cholesterol from your blood to do this, which lowers the level of cholesterol 
in your blood. 
 
Cholestagel is prescribed to treat a condition known as primary hypercholesterolaemia (when 
cholesterol in the blood is elevated) in adults. 
- Cholestagel may be prescribed on its own in addition to a diet low in fat and cholesterol when 

treatment with a statin (a class of cholesterol-lowering medicines that work in the liver) is 
inappropriate or not well tolerated.  

- Cholestagel may be used together with a statin and the diet low in fat and cholesterol when 
patients are not appropriately controlled by the statin on its own.  

- Cholestagel may also be used together with ezetimibe (a cholesterol-lowering medicine that works 
by reducing cholesterol absorption from the gut), with or without a statin. 

 
2. What you need to know before you take Cholestagel 
 
Do not take Cholestagel: 
- if you are allergic to colesevelam or to any of the other ingredients of this medicine (listed in 

section 6) 
- if you have a blockage in your intestines or bile ducts (tubes that carry bile) 
 
If you are prescribed Cholestagel and any other medicine together you must also read the patient 
information leaflet that comes with that particular medicine before you start to take your medicine.  
 



19 

Warnings and precautions 
Talk to your doctor or pharmacist before taking Cholestagel 
- if your triglyceride levels (a blood fat) are greater than 3.4 mmol/L 
- if you have difficulty in swallowing, or have a major stomach or intestinal disorder 
- if you suffer from constipation, as Cholestagel may induce or worsen this condition. This is 

especially important for patients with coronary heart disease and angina pectoris. 
 
If you think any of these apply to you, you should inform your doctor or pharmacist before taking 
Cholestagel. 
 
Before starting therapy with Cholestagel, your physician should make sure that certain conditions do 
not contribute to your elevated cholesterol levels. These could include poorly controlled diabetes, 
untreated hypothyroidism (low levels of thyroid hormone for which no treatment is being given 
currently), proteins in urine (nephrotic syndrome), altered protein levels in the blood 
(dysproteinaemias), and blockage of the bile transport to your gall bladder (obstructive liver disease). 
 
Children and adolescents 
The safety and efficacy in children (below the age of 18 years) has not been studied. Therefore, 
Cholestagel is not recommended for use in this population. 
 
Other medicines and Cholestagel 
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 
medicines. 
If your doctor suspects that Cholestagel may have an effect on the absorption of the other medication, 
you may be advised to take Cholestagel at least 4 hours before or at least 4 hours after taking the other 
medication. If you need to take other medicines more than once a day, remember that your Cholestagel 
tablets can be taken once a day. 
 
Cholestagel may affect the way in which the following medicines work: 

• Anticoagulant therapy (medicines, such as warfarin, used to thin blood).  If you are taking 
anticoagulant therapy you should consult with your physician to closely monitor 
anticoagulation levels, as Cholestagel may affect the absorption of vitamin K and therefore 
interfere with the activity of warfarin. 

• Thyroid replacement therapy (medicines, such as thyroxine or levothyroxine, used to treat low 
thyroid hormone levels) 

• Oral contraceptives (medicines to prevent pregnancy) 
It is important you take Cholestagel at least 4 hours after you take the oral contraceptive to 
ensure that the effectiveness of the contraceptive is not affected. 

• Verapamil or olmesartan (medicines used to treat high blood pressure). It is important that you 
take olmesartan at least 4 hours before you take Cholestagel. 

• Antidiabetic medications (medicines used to treat diabetes, such as metformin 
extended-release (ER) tablets, glimepiride, glipizide, pioglitazone, repaglinide or glyburide). 
If you are taking medicines for diabetes, you should consult with your physician so that you 
can be closely monitored. It is important that you take glimepiride and glipizide at least 4 
hours before you take Cholestagel. 

• Anti-epileptic medicines (medicines, such as phenytoin, used to treat epilepsy).  
• Ciclosporin (a medicine used to suppress the immune system).  
• Ursodeoxycholic acid (a medicine used to dissolve gallstones or treat specific chronic liver 

diseases). 

If you are going to take Cholestagel and one of these medicines, your doctor may want to do tests to 
make sure that Cholestagel does not interfere with these medicines.  
 
Additionally, if you have any condition that could cause you to have a deficiency of vitamins A, D, E 
or K, your doctor may want to check your vitamin levels periodically while you are taking 
Cholestagel. If necessary, your doctor may advise you to take vitamin supplements. 
 



20 

Pregnancy and breast-feeding 
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 
your doctor or pharmacist for advice before taking this medicine. 
 
If you are prescribed Cholestagel and a statin together it is important that you tell your doctor if you 
are pregnant or if you are planning to become pregnant because statins must not be used during 
pregnancy; the patient information leaflet that comes with that particular statin should be consulted. 
Tell your doctor if you are breast-feeding. Your doctor may stop your medicine. 
 
Driving and using machines 
Your ability to drive or operate machines is not affected by taking Cholestagel tablets. 
 
 
3. How to take Cholestagel 
 
Before starting therapy with Cholestagel, you should be advised to follow a cholesterol-lowering diet 
and you should continue this diet during treatment. 
 
Always take Cholestagel exactly as your doctor or pharmacist has told you. Check with your doctor or 
pharmacist if you are unsure. As described in Section 2, if you will be taking Cholestagel along with 
another medicine it is possible that your doctor will advise you to take Cholestagel at least 4 hours 
before or at least 4 hours after taking the other medicine. 
If you take a medicine called either Neoral® or ciclosporin, please ensure to take it with Cholestagel in 
a consistent pattern over the day; either always together or always separate for a set number of hours. 
 
You should take your Cholestagel tablets with food and liquid. The tablets should be swallowed 
whole. Do not break, crush or chew the tablets. 
 
Combination therapy: 
The recommended dose for Cholestagel, when used with a statin or ezetimibe or both together, is 4 to 
6 tablets a day by mouth. Your doctor may tell you to take the Cholestagel dose either once a day or 
twice a day; in either case Cholestagel should be taken with a meal. The dosing of the statin and the 
ezetimibe should follow the instructions for that particular medicine. The medicines may be taken at 
the same time or at separate times according to what your doctor has prescribed. 
 
Monotherapy: 
The recommended dose for Cholestagel is 3 tablets taken twice a day with meals or 6 tablets a day 
with a meal. Your doctor may increase your dose to 7 tablets per day. 
 
If you take more Cholestagel than you should 
Please contact your doctor. Constipation or bloating could occur. 
 
If you forget to take Cholestagel 
You may take your dose with a later meal, but never take in one day more than the total number of 
tablets that your doctor has prescribed to you in a single day. 
 
If you stop taking Cholestagel 
Your cholesterol may increase to the level it was before treatment was started. 
 
If you have any further questions on the use of this medicine, ask your doctor or pharmacist. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
The following side effects have been reported in patients taking Cholestagel:  



21 

Very common (may affect more than 1 in 10 people): flatulence (wind), constipation. 
Common (may affect up to 1 in 10 people): vomiting, diarrhoea, indigestion, abdominal pain, 
abnormal stools, feeling sick, bloating, headache, raised levels of triglycerides (fats) in your blood. 
Uncommon (may affect up to 1 in 100 people): muscle pain, raised levels of liver enzymes in your 
blood, difficulty in swallowing. 
Very rare (may affect up to 1 in 10,000 people): inflammation of the pancreas. 
Not known (frequency cannot be estimated from the available data): blockage of the intestines (which 
can increase among patients with a history of blockage of the intestines or intestinal removal). 
 
Reporting of side effects  
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects 
not listed in this leaflet. You can also report side effects directly via the national reporting system 
listed in Appendix V. By reporting side effects you can help provide more information on the safety of 
this medicine. 
 
 
5. How to store Cholestagel 
 
Keep this medicine out of the sight and reach of children. 
 
Do not use this medicine after the expiry date which is stated on the carton and bottle label after 
“EXP’’ 
 
Keep the bottle tightly closed in order to protect from moisture. 
 
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help to protect the environment. 
 
 
6. Contents of the pack and other information 
 
What Cholestagel contains 
 
- The active substance is colesevelam (as hydrochloride). Each tablet contains 625 mg 

colesevelam. 
 
- The other ingredients (excipients) are: 
Tablet core: 
Microcrystalline cellulose (E460) 
Silica colloidal anhydrous 
Magnesium stearate 
Purified water 
 
Film-coating: 
Hypromellose (E464) 
Diacetylated monoglycerides 
 
Printing ink: 
Iron oxide black (E172) 
Hypromellose (E464) 
Propylene glycol 
 



22 

What Cholestagel looks like and contents of the pack 
 
Cholestagel tablets are off-white, capsule-shaped film-coated tablets and imprinted with ‘C625’ on one 
side. The tablets are packed in plastic bottles with child resistant closures. Pack sizes are 24 (1 x 24), 
100 (2 x 50) and 180 (1 x 180) tablets. Not all pack sizes may be marketed. 
 
Marketing Authorisation Holder and Manufacturer 
 
Marketing authorisation holder 
Genzyme Europe B.V., Paasheuvelweg 25, 1105 BP Amsterdam, the Netherlands 
 
Manufacturer 
Genzyme Ireland Ltd., IDA Industrial Park, Old Kilmeaden Road, Waterford, Ireland 
 
For any information about this medicinal product, please contact the local representative of the 
Marketing Authorisation Holder. 
 
België/Belgique/Belgien/ 
Luxembourg/Luxemburg 
Sanofi Belgium 
Tél/Tel: + 32 (0)2 710 54 00 
 

Lietuva 
UAB „SANOFI-AVENTIS LIETUVA“ 
Tel. +370 5 2755224 
 

България 
SANOFI BULGARIA EOOD 
Tел: +359 (0)2 970 53 00 
 

Magyarország 
SANOFI-AVENTIS Zrt. 
Tel.: +36 1 505 0050 

Česká republika 
sanofi-aventis, s.r.o. 
Tel: +420 233 086 111 
 

Malta 
Sanofi S.p.A. 
Tel: +39 02 39394275 

Danmark 
Sanofi A/S    
Tlf: +45 45 16 70 00 
 

Nederland 
Genzyme Europe B.V. 
Tel: +31 20 245 4000 
 

Deutschland 
Sanofi-Aventis Deutschland GmbH 
Tel.: 0800 52 52 010 
Tel. aus dem Ausland: +49 69 305 21 131 
 

Norge 
sanofi-aventis Norge AS 
Tlf: + 47 67 10 71 00 
 

Eesti 
sanofi-aventis Estonia OÜ 
Tel. +372 627 34 88 
 

Österreich 
sanofi-aventis GmbH 
Tel: + 43 1 80 185 - 0 

Ελλάδα 
sanofi-aventis AEBE 
Τηλ: +30 210 900 16 00 

Polska 
sanofi-aventis Sp. z o.o. 
Tel.: +48 22 280 00 00 
 

España 
sanofi-aventis, S.A. 
Tel: +34 93 485 94 00 
  

Portugal 
Sanofi – Produtos Farmacêuticos, Lda. 
Tel: +351 21 35 89 400  
 

 



23 

France 
sanofi-aventis France 
Tél: 0 800 222 555 
Appel depuis l’étranger: +33 1 57 63 23 23 
 

România 
Sanofi Romania SRL 
Tel: +40 (0) 21 317 31 36  

Hrvatska 
sanofi-aventis Croatia d.o.o. 
Tel: +385 1 600 34 00 
 

Slovenija 
sanofi-aventis d.o.o. 
Tel: +386 1 560 4800 
 

Ireland 
sanofi-aventis Ireland Ltd. T/A SANOFI 
Tel:  +353 (0) 1 403 56 00  
 

Slovenská republika 
sanofi-aventis Pharma Slovakia s.r.o. 
Tel.:  +421 2 33 100 100 

Ísland 
Vistor hf. 
Sími: +354 535 7000 
 

Suomi/Finland 
Sanofi Oy 
Puh/Tel: + 358 (0) 201 200 300 
 

Italia 
Sanofi S.p.A. 
Tel: 800.536 389 
 

Sverige 
Sanofi AB 
Tel: +46 (0)8 634 50 00 
 

Κύπρος 
sanofi-aventis Cyprus Ltd. 
Τηλ: +357 22 871600 

United Kingdom 
Sanofi 
Tel: +44 (0) 845 372 7101 
 

Latvija 
sanofi-aventis Latvia SIA 
Tel: +371 67 33 24 51 
 

 

 
This leaflet was last revised in 
 
Other sources of information 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu/ 
 
 

http://www.ema.europa.eu/
http://www.ema.europa.eu/

	SUMMARY OF PRODUCT CHARACTERISTICS
	A MANUFACTURER RESPONSIBLE FOR BATCH RELEASE
	B CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION
	D CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET