colesevelam

Action and Spectrum

Actions and Spectrum: 

colesevelam is a medication primarily used to treat hyperlipidemia (high cholesterol) and type 2 diabetes. It relates to a category of medications called bile acid sequestrants. Here’s a breakdown of the action and spectrum of colesevelam: 

Action: 

• Bile Acid Sequestration: colesevelam is not absorbed systemically and remains in the gastrointestinal tract. It generally binds to bile acids in the intestine, forming a complex that is then excreted in the feces. This binding activity leads to an increased clearance of bile acids from the body. 
• Cholesterol Lowering: By sequestering bile acids, colesevelam interrupts the enterohepatic circulation of bile acids. This stimulates the liver to use more cholesterol to synthesize new bile acids, ultimately reducing low-density lipoprotein cholesterol (LDL-C) levels in the blood. 

The Spectrum of Use: 

• Hyperlipidemia: colesevelam is approved for treating primary hyperlipidemia (elevated cholesterol) and mixed dyslipidemia (high cholesterol and elevated triglycerides). It is typically used as an addition to diet and lifestyle modifications when insufficient statins or not tolerated alone. 
• Type 2 Diabetes: colesevelam can be used as an addition to diet and exercise in managing type 2 diabetes. It helps improve glycemic control by reducing postprandial blood glucose levels. It is often prescribed with other antidiabetic medications, such as metformin or sulfonylureas. 

Drug Interaction

Adverse Reaction

Frequency defined 

>10% 

Constipation (6.5-11%) 

1-10% 

Accidental injury (3.7%) 

Nasopharyngitis (5.4-6.2%) 

Hypertension (2.6%) 

Influenza (3.8%) 

Myalgia (2.1%) 

Vomiting (2.3%) 

Rhinitis (2.3%) 

Pharyngitis (3.2%) 

Hypoglycemia (3.4%) 

Creatine phosphokinase increase (2.3%) 

Nausea (2.6-3.8%) 

Headache (3.9-7.6%) 

Fatigue (3.9%) 

Upper respiratory tract infection (4.9%) 

Dyspepsia (2.8-8.3%) 

Asthenia (3.6%) 

Flu syndrome (3.2%) 

Nausea (4.2%) 

Back pain (2.3%) 

Black Box Warning

Black Box Warning: 

None 

Contraindication / Caution

Contraindication/Caution: 

Contraindication 

colesevelam has several contraindications, which are medical conditions or situations where medication use is not recommended due to potential risks or lack of effectiveness. Here are some contraindications for colesevelam: 

• Bowel Obstruction: colesevelam is contraindicated in patients with a history of bowel obstruction or those at risk of developing bowel obstruction. The medication can exacerbate the condition or impede bowel function. 
• Hypertriglyceridemia: colesevelam is not recommended to treat elevated triglyceride levels (hypertriglyceridemia). It primarily targets LDL cholesterol levels and may not effectively address elevated triglycerides. 
• Phenylketonuria (PKU): colesevelam contains phenylalanine, and individuals with PKU, a genetic disorder that affects the breakdown of phenylalanine, should avoid medications containing this ingredient. 
• Hypersensitivity: colesevelam is contraindicated in individuals with known hypersensitivity or allergy to colesevelam or its components. Allergic reactions can differ from mild-severe and may include symptoms like rash, itching, swelling, or difficulty breathing. 
• Complete Biliary Obstruction: If a patient has a complete biliary obstruction, which prevents bile flow from the liver to the intestines, colesevelam is contraindicated. This is because the medication works by generally binding bile acids in the intestines, and in the absence of bile flow, its action may be impaired. 
• Pre-existing Bowel Conditions: Individuals with certain bowel disorders, such as severe constipation, Crohn’s disease, or ulcerative colitis, may be at increased risk of complications when using colesevelam. The medication may exacerbate these conditions or interfere with normal bowel function. 

It’s important to note that this list may not be exhaustive, and other contraindications or precautions may exist. It is key to consult with a healthcare professional or refer to the prescribing information for colesevelam to obtain comprehensive and accurate information regarding its contraindications and precautions before initiating treatment. 

Caution 

While colesevelam is generally considered safe and well-tolerated, there are some cautions and precautions to be aware of when using this medication. These include: 

• Gastrointestinal Disorders: colesevelam may worsen certain gastrointestinal disorders, such as severe constipation, bowel obstruction, or dysphagia (difficulty swallowing). Caution should be exercised in patients with these conditions, and the benefits and risks of treatment should be carefully evaluated. 
• Nutritional Deficiencies: Bile acid sequestrants like colesevelam may interfere with absorbing specific fat-soluble vitamins (vitamins A, D, E, and K) and folic acid. Regular monitoring of vitamin levels and appropriate supplementation may be necessary, especially in patients with pre-existing deficiencies or those on long-term treatment. 
• Medication Interactions: colesevelam can interact with other medications, reducing their absorption or effectiveness. Before starting colesevelam, you must inform your healthcare provider about all the medications, supplements, and over-the-counter drugs you are taking. It might be necessary to adjust the timing of administration or dosing of other medications to avoid potential interactions. 
• Pregnancy and Breastfeeding: The use of colesevelam during pregnancy or breastfeeding has not been extensively studied. Therefore, caution is advised, and the potential benefits should be generally weighed against the potential risks to the fetus or the infant. It is key to discuss the use of colesevelam with a healthcare professional if you are pregnant or breastfeeding. 
• Pediatric Use: The safety and efficacy of colesevelam in children have not been established. Its use in pediatric patients should be carefully evaluated, and the potential benefits and risks should be considered. 
• Renal Impairment: colesevelam is primarily eliminated through the gastrointestinal tract and does not undergo significant renal excretion. However, caution is still advised in patients with severe renal impairment or ESRD (end-stage renal disease). 

Pregnancy / Lactation

Pregnancy consideration:  

US FDA pregnancy category: Not assigned 

Lactation:   

Excreted into human milk is Not known.  

Pregnancy category: 

• Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester. 
• Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women. 
• Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.    
• Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.    
• Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.    
• Category N: There is no data available for the drug under this category 

Pharmacology

Pharmacology: 

colesevelam is a bile acid sequestrant that binds to bile acids in the intestines, preventing their reabsorption. Bile acids are generally synthesized in the liver and are necessary for digesting and absorbing dietary fats and fat-soluble vitamins. When colesevelam binds to bile acids, they are eliminated from the body through fecal excretion, decreasing the circulating bile acid pool. 

By reducing the number of bile acids available for reabsorption, colesevelam induces the liver to produce more bile acids from cholesterol, lowering the circulating levels of low-density lipoprotein cholesterol or else “bad” cholesterol. colesevelam has also been found to increase high-density lipoprotein cholesterol (HDL-C), or “good” cholesterol. 

In addition to its lipid-lowering effects, colesevelam has been found to have a modest impact on glycemic control in patients with DM type-2. colesevelam indirectly affects glucose metabolism and insulin sensitivity by binding bile acids in the intestines, although the exact mechanism is not fully understood. 

Pharmacodynamics: 

Mechanism of action: The action of colesevelam involves its interaction with bile acids in the gastrointestinal tract. Here’s a breakdown of its mechanism: 

• Bile Acid Sequestration: colesevelam is a bile acid sequestrant. It has a high affinity for bile acids, which are produced by the liver and released into the intestines to aid the digestion and absorption of dietary fats. colesevelam binds to bile acids in the small intestine, forming a non-absorbable complex. 
• Inhibition of Bile Acid Reabsorption: The bound bile acid-colesevelam complex prevents the reabsorption of bile acids in the intestines. Instead of being reabsorbed, the complex remains in the intestinal lumen. 
• Increased Bile Acid Synthesis: Due to the decreased reabsorption of bile acids, the body senses a loss of bile acids and compensates by increasing the synthesis of new bile acids in the liver. This process involves the utilization of cholesterol to produce more bile acids. 
• Reduction in Circulating Bile Acid Pool: The increased synthesis of bile acids and the reduced reabsorption lead to a reduction in the total pool of bile acids circulating in the body. This decrease in circulating bile acids triggers the upregulation of hepatic low-density lipoprotein receptors, which enhances the clearance of low-density lipoprotein cholesterol (LDL-C) from the bloodstream. 
• Decreased LDL-C Levels: As more LDL-C is cleared from the blood due to increased low-density lipoprotein receptor activity, the overall level of LDL-C in the bloodstream decreases. This is why colesevelam is primarily used as a lipid-lowering agent to lower LDL-C levels. 

Pharmacokinetics: 

Absorption 

colesevelam is not significantly absorbed into the bloodstream after oral administration. Instead, it remains within the gastrointestinal tract, exerting its therapeutic effects. 

Distribution 

As colesevelam is not absorbed systemically, it does not undergo distribution to tissues or organs beyond the gastrointestinal tract. 

Metabolism 

colesevelam is not metabolized in the body. It remains intact and unchanged throughout its journey in the gastrointestinal tract. 

Elimination and Excretion 

colesevelam is primarily excreted in feces. After binding to bile acids in the intestines, it forms a complex that is too large to be absorbed. This complex and any unbound colesevelam are eliminated in the feces. Only a minimal amount of colesevelam is excreted in the urine. 

Adminstartion

Administration: 

Oral administration 

colesevelam is typically taken orally in tablet form. Here are some general guidelines for the administration of colesevelam: 

• Dosage: The recommended dosage of colesevelam can vary depending on the condition being treated. It is key to follow the instructions provided by your healthcare provider and the specific dosage information on the medication label. Stay within the prescribed dose unless instructed by your healthcare provider. 
• Timing: colesevelam is usually taken with meals. This is due to its binding to bile acids in the intestines, which are released during digestion. Taking colesevelam with meals helps maximize its effectiveness and minimize the potential for gastrointestinal side effects. 
• Swallowing: Swallow the colesevelam tablet whole with sufficient water. It should not crush, break, or chew the tablet unless specifically instructed by your healthcare provider. 
• Other Medications: colesevelam may interact with other medications. Taking colesevelam at least four hours before or 4 hours after taking other medications is recommended to minimize potential interactions. Consult with your healthcare provider or pharmacist for appropriate medication timing. 
• Fluid Intake: Drinking adequate fluids when taking colesevelam is essential to prevent constipation. Ensuring an ample intake of water throughout the day can help prevent or alleviate any potential gastrointestinal discomfort associated with the medication. 
• Adherence: Take colesevelam as prescribed by your healthcare provider. If a dose is missed, taking it as soon as possible is generally recommended. However, if the next scheduled dose is missed, it should be skipped and the following dose should be taken at the appropriate time. It is important to avoid taking a double dose of the medication to compensate for the missed dose. 

It is key to follow your healthcare provider’s instructions and read the medication label for additional guidance.

Patient Information Leaflet

Patient information leaflet 

Generic Name: colesevelam 

Pronounced: [ KOE-le-SEV-e-lam ] 

Why do we use colesevelam? 

colesevelam is primarily used for the following purposes: 

• Management of Hypercholesterolemia: colesevelam is approved for treating high cholesterol levels in the blood. It can be generally used as an adjunct to diet and exercise to help lower low-density lipoprotein cholesterol, also known as “bad” cholesterol. By reducing LDL-C levels, colesevelam helps to decrease the risk of cardiovascular events, like the heart attacks and strokes. 
• Type 2 Diabetes Mellitus: In additive to its lipid-lowering effects, colesevelam has been found to have a modest impact on glycemic control in patients with type 2 diabetes mellitus. It can be generally used as an adjunct to diet and exercise to help improve blood glucose control. colesevelam indirectly affects glucose metabolism and insulin sensitivity by binding bile acids in the intestines. 

It’s important to note that colesevelam is not indicated for treating type 1 diabetes, diabetic ketoacidosis, or hypertriglyceridemia (elevated triglyceride levels). 

As with any medication, a healthcare professional should determine the use of colesevelam based on individual patient factors, like the severity of the condition, overall health, and response to other treatments.