Colesevelam

Anticoagulant therapy should be monitored closely in patients receiving warfarin or similar agents, since bile acid sequestrants, like colesevelam, 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.

In an interaction study in healthy volunteers, colesevelam reduced the C_max of norethindrone as well as the AUC and C_max of ethinylestradiol when administered simultaneously with the oral contraceptive pill. This interaction was also observed when colesevelam was administered one hour after the oral contraceptive pill. However no interaction was observed when colesevelam was administered four hours after the oral contraceptive pill.

In an interaction study in healthy volunteers, co-administration of colesevelam and ciclosporin significantly reduced the AUC_0-inf and C_max of ciclosporin by 34% by 44%, respectively. Therefore advice is given to closely monitor ciclosporin blood concentrations. In addition, based on theoretical grounds colesevelam should be administered at least 4 hours after ciclosporin in order to further minimise the risks related to the concomitant administration of ciclosporin and colesevelam. Furthermore, colesevelam should always be administered at the same times consistently since the timing of intake of colesevelam and ciclosporin could theoretically influence the degree of reduced bioavailability of ciclosporin.

Co-administration of colesevelam and glyburide (also known as glibenclamide) caused a decrease in the AUC_0-inf and C_max of glyburide by 32% and 47%, respectively. No interaction was observed when colesevelam was administered four hours after glyburide.

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.

In an interaction study in healthy volunteers, colesevelam reduced the AUC and C_max of levothyroxine when administered either concomitantly or after 1 hour. No interaction was observed when colesevelam was administered at least four hours after levothyroxine.

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.

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.

Co-administration of colesevelam and repaglinide had no effect on the AUC and caused a 19% reduction in the C_max of repaglinide, the clinical significance of which is unknown. No interaction was observed when colesevelam was administered one hour after repaglinide.

Colesevelam predominantly binds hydrophobic bile acids. In a clinical study colesevelam 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, colesevelam 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.

Colesevelam decreased the C_max 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.

Colesevelam can induce or worsen present constipation. The risk of constipation should especially be considered in patients with coronary heart disease and angina pectoris.

Caution should be exercised when treating patients with triglyceride levels greater than 3.4 mmol/L due to the triglyceride increasing effect with colesevelam. 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 colesevelam 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 colesevelam is used in patients with these disorders.

No clinical data are available on the use of colesevelam in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonic/foetal development, parturition or postnatal development. Caution should be exercised when prescribing to pregnant women.

The safety of colesevelam 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 colesevelam 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.

Colesevelam has no or negligible influence on the ability to drive and use machines.