Usage
- Medical Conditions: Colesevelam is prescribed as an adjunct to diet and exercise to lower low-density lipoprotein cholesterol (LDL-C) in adults with primary hyperlipidemia (including heterozygous familial hypercholesterolemia). It is also used to improve glycemic control in adults with type 2 diabetes mellitus. In boys and postmenarchal girls (10-17 years old), it is used to lower LDL-C levels with HeFH when target LDL-C levels cannot be met with diet and lifestyle changes alone.
- Pharmacological Classification: Bile acid sequestrant.
- Mechanism of Action: Colesevelam binds to bile acids in the intestine, preventing their reabsorption. This leads to increased conversion of cholesterol to bile acids in the liver, reducing LDL-C levels.
Alternate Names
- International/Regional Variations: None specifically listed.
- Brand Names: Welchol®, Cholestagel®
How It Works
- Pharmacodynamics: Colesevelam lowers LDL-C by binding bile acids in the intestine, thereby interrupting their enterohepatic circulation. This promotes increased hepatic conversion of cholesterol to bile acids, resulting in lower serum LDL-C levels. It may also modestly increase high-density lipoprotein cholesterol (HDL-C) and lower triglycerides. For individuals with Type 2 Diabetes, it improves glycemic control, possibly by delaying glucose absorption.
- Pharmacokinetics: Colesevelam is not absorbed systemically, it remains within the gastrointestinal tract and is eliminated in the feces. It does not undergo metabolism by CYP enzymes.
- Mode of Action: Colesevelam is a non-absorbed polymer that binds bile acids in the intestine, forming a non-absorbable complex. The complex is then excreted in the feces.
- Receptor Binding/Enzyme Inhibition: Binds bile acids. No significant interaction with CYP450 enzymes.
- Elimination Pathways: Primarily eliminated in feces as a bile acid complex.
Dosage
Standard Dosage
Adults (Primary Hyperlipidemia and Type 2 Diabetes):
- Tablets: 3.75 g daily (six 625 mg tablets) administered as a single dose or in two divided doses of 3 tablets each, taken with meals and liquid.
- Oral Suspension: 3.75 g (one packet) daily, taken with meals and liquid. Mix with water, juice, or diet soda.
Children (HeFH, 10-17 years old):
- Tablets: 3.75 g daily (six 625 mg tablets) administered as a single dose or in two divided doses of 3 tablets each, taken with meals and liquid.
- Oral Suspension: 3.75 g (one packet) daily, taken with meals and liquid. Due to tablet size, the oral suspension is generally recommended for children. Mix with water, juice or diet soda.
Special Cases:
- Elderly Patients: No dosage adjustment is necessary.
- Patients with Renal Impairment: No dosage adjustment is necessary.
- Patients with Hepatic Dysfunction: No dosage adjustment is necessary.
- Patients with Comorbid Conditions: Monitor triglyceride levels, especially in patients with levels ≥ 300 mg/dL or a history of hypertriglyceridemia-induced pancreatitis. Exercise caution in patients with bowel obstruction or gastrointestinal disorders. If vitamin K or fat-soluble vitamin deficiency is suspected, monitor vitamin levels.
Clinical Use Cases
Colesevelam does not have any applications in the clinical scenarios listed below. It is indicated for chronic conditions: hyperlipidemia and type 2 diabetes mellitus as an adjunct to diet and lifestyle modification. It is not used in acute clinical situations:
- Intubation
- Surgical Procedures
- Mechanical Ventilation
- Intensive Care Unit (ICU) Use
- Emergency Situations
Dosage Adjustments
Generally, no dosage adjustments are needed for age, renal function, or hepatic function. However, individual patient response may necessitate adjustments.
Side Effects
Common Side Effects:
- Constipation
- Flatulence
- Upset stomach
- Nausea
- Vomiting
- Indigestion
- Headache
- Muscle pain
Rare but Serious Side Effects:
- Bowel obstruction (symptoms include severe abdominal pain and severe constipation)
- Pancreatitis (symptoms include severe pain in the upper abdomen radiating to the back, nausea, and vomiting)
- High triglyceride levels
- Allergic reactions
Long-Term Effects:
- Potential for malabsorption of fat-soluble vitamins (A, D, E, and K) with long-term use. Monitor and supplement as necessary.
Adverse Drug Reactions (ADR):
- As above in Rare but Serious Side Effects.
Contraindications
- Bowel obstruction
- Triglyceride levels > 500 mg/dL
- History of hypertriglyceridemia-induced pancreatitis
- Hypersensitivity to colesevelam
Drug Interactions
Colesevelam can reduce the absorption of various medications, including:
- Cyclosporine
- Glimepiride
- Glipizide
- Glyburide
- Levothyroxine
- Olmesartan
- Phenytoin
- Warfarin
- Oral contraceptives containing ethinyl estradiol and norethindrone
- Vitamins (A, D, E, and K)
To minimize interactions, administer other medications at least 4 hours before or after colesevelam. It can also bind to bile acids and reduce the absorption of fat-soluble vitamins. Monitor patients for these potential interactions and adjust dosages as needed.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: B. Limited human data are available on the use of colesevelam during pregnancy. It is not expected to harm a fetus due to its non-systemic absorption. Consult with a physician if considering use during pregnancy.
- Breastfeeding: Colesevelam is not absorbed systematically and is not expected to be present in breast milk, posing minimal risk to a nursing infant. Consult with a physician before using while breastfeeding.
Drug Profile Summary
- Mechanism of Action: Bile acid sequestrant; binds bile acids in the intestine.
- Side Effects: Constipation, flatulence, upset stomach, nausea, bowel obstruction, pancreatitis, increased triglycerides, allergic reactions.
- Contraindications: Bowel obstruction, high triglycerides (>500 mg/dL), history of hypertriglyceridemia-induced pancreatitis.
- Drug Interactions: Numerous, often requiring separated dosing by 4 hours; decreases absorption of several medications and potentially fat-soluble vitamins.
- Pregnancy & Breastfeeding: Category B; caution advised; generally considered low risk due to limited systemic absorption.
- Dosage: 3.75 g daily in adults and children 10-17 years old with primary hyperlipidemia or type 2 diabetes.
- Monitoring Parameters: LDL-C, HDL-C, triglycerides, liver function tests, and coagulation parameters (if indicated) before and during treatment.
Popular Combinations
Colesevelam is often used in combination with statins, ezetimibe or other lipid-lowering drugs to achieve greater reductions in LDL-C levels.
Precautions
- General Precautions: Monitor for gastrointestinal issues, high triglyceride levels and malabsorption of vitamins. Assess patient history for bowel obstructions.
- Specific Populations: Monitor pregnant women and breastfeeding mothers, although the drug is generally considered safe.
- Lifestyle Considerations: Diet and exercise are essential components of therapy.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Colesevelam?
A: 3.75 g daily for adults and children 10-17 years old, either as a single dose or in two divided doses. Children under 10 – Safety and efficacy not established.
Q2: How should Colesevelam be administered?
A: Orally with a meal and liquid. Tablets should be swallowed whole, not crushed or chewed. Oral suspension should be mixed with water, juice or a diet soft drink.
Q3: What are the most common side effects of Colesevelam?
A: Constipation, flatulence, nausea, and dyspepsia.
Q4: What are the serious side effects of Colesevelam?
A: Bowel obstruction, pancreatitis, increased triglycerides, and rare allergic reactions.
Q5: Can Colesevelam be used during pregnancy?
A: Limited human data available, pregnancy category B. Caution advised; consult with a physician.
Q6: Can Colesevelam be used while breastfeeding?
A: Minimal risk expected due to low systemic absorption; consult with a physician.
Q7: How does Colesevelam interact with other medications?
A: It can decrease the absorption of numerous medications. Administer other medications 4 hours before or after Colesevelam.
Q8: What are the contraindications for Colesevelam?
A: Bowel obstruction, high triglycerides (>500 mg/dL), and history of hypertriglyceridemia-induced pancreatitis.
Q9: How does Colesevelam affect vitamin levels?
A: It can reduce the absorption of fat-soluble vitamins (A, D, E, and K). Monitor vitamin levels and provide supplements if necessary.
Q10: What should I monitor in patients taking Colesevelam?
A: LDL-C, HDL-C, Triglycerides, liver function tests, and coagulation parameters (if required) before and during treatment.
