Colesevelam interactions. Colesevelam: Mechanism, Indications, and Interactions – A Comprehensive Guide

21.08.202317.07.2023 by alexxlab

What are the main indications for colesevelam. How does colesevelam work to lower cholesterol and blood glucose. What are the potential side effects and drug interactions of colesevelam. How should colesevelam be administered for optimal efficacy.

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Understanding Colesevelam: A Novel Bile Acid Sequestrant

Colesevelam is an FDA-approved antihyperlipidemic medication that belongs to the class of drugs known as bile acid sequestrants. It has gained prominence in the treatment of hyperlipidemia and type 2 diabetes mellitus due to its unique mechanism of action and favorable side effect profile.

Key Features of Colesevelam

Approved for use in adults and adolescents (10-17 years) with hyperlipidemia
Can be used as monotherapy or in combination with other lipid-lowering agents
Effective in improving glycemic control in adults with type 2 diabetes
Available in multiple formulations: tablets, suspension, and chewable bars

Indications for Colesevelam: Beyond Cholesterol Management

Colesevelam’s versatility extends beyond its primary use in lipid management. Its approved indications encompass several clinical scenarios:

Primary Indications

Lowering elevated LDL cholesterol in patients with primary hyperlipidemia
Reducing LDL-C levels in adolescents (10-17 years) with heterozygous familial hypercholesterolemia
Improving glycemic control in adults with type 2 diabetes mellitus

Does colesevelam have any off-label uses. While not FDA-approved, studies have shown that colesevelam may improve stool consistency in patients with irritable bowel syndrome with diarrhea (IBS-D). This effect is attributed to its ability to sequester bile acids in the intestinal lumen, potentially offering relief to IBS-D patients.

Mechanism of Action: How Colesevelam Works Its Magic

Colesevelam’s efficacy in managing hyperlipidemia and improving glycemic control stems from its unique mechanism of action:

Lipid-Lowering Effects

Colesevelam forms non-absorbable complexes with bile acids in the gastrointestinal tract, preventing their reabsorption. This process triggers a cascade of events:

Reduction in total bile acid pool
Upregulation of 7-alpha-hydroxylase enzyme
Increased conversion of intracellular cholesterol to bile acids
Upregulation of hepatic LDL receptors
Decreased plasma LDL and total cholesterol levels

Glucose-Lowering Effects

The exact mechanism by which colesevelam reduces plasma glucose levels is not fully elucidated. However, animal studies suggest the following pathway:

Increased production of glucagon-like peptide-1 (GLP-1) and other incretins
Activation of TGR5 receptors in the intestine
Suppression of hepatic glycogenolysis
Reduction in serum glucose levels

How does colesevelam’s mechanism of action differ from other lipid-lowering agents. Unlike statins that inhibit cholesterol synthesis or fibrates that enhance lipid breakdown, colesevelam works by sequestering bile acids. This unique approach makes it a valuable option for patients who cannot tolerate or have contraindications to other lipid-lowering medications.

Administration and Dosage: Optimizing Colesevelam Therapy

Proper administration of colesevelam is crucial for achieving optimal therapeutic effects while minimizing potential side effects and drug interactions.

Available Formulations

Oral tablets
Prepared suspension
Chewable bars (recently approved)

Dosing Recommendations

Colesevelam is typically administered once or twice daily. The specific dosage depends on the indication and patient factors:

For hyperlipidemia: 3.75 g daily or 1.875 g twice daily
For type 2 diabetes: 3.75 g daily or 1.875 g twice daily

What precautions should be taken when administering colesevelam with other medications. To avoid potential interactions, it’s recommended to take fat-soluble vitamins, folic acid, and statins at least 4 hours after colesevelam administration. This timing ensures proper absorption of these essential nutrients and medications.

Adverse Effects: Understanding the Risks of Colesevelam

While colesevelam is generally well-tolerated, patients and healthcare providers should be aware of potential adverse effects:

Common Side Effects

Constipation
Dyspepsia
Nausea
Abdominal pain
Flatulence

Less Common but Serious Side Effects

Bowel obstruction (rare)
Hypertriglyceridemia (in patients with pre-existing hypertriglyceridemia)
Fat-soluble vitamin deficiencies (with long-term use)

How can the risk of adverse effects be minimized when using colesevelam. Proper patient education, gradual dose titration, and adequate fluid intake can help mitigate the risk of gastrointestinal side effects. Regular monitoring of lipid profiles and vitamin levels may be necessary for patients on long-term therapy.

Drug Interactions: Navigating Colesevelam’s Impact on Other Medications

Colesevelam’s mechanism of action in the gastrointestinal tract can potentially affect the absorption of other medications. Healthcare providers should be aware of these interactions to ensure optimal therapeutic outcomes:

Medications Requiring Cautious Co-administration

Fat-soluble vitamins (A, D, E, K)
Folic acid
Oral contraceptives
Thyroid hormones
Warfarin
Statins
Cyclosporine

To mitigate potential interactions, these medications should be taken at least 4 hours before or after colesevelam administration.

Medications with Enhanced Effects

Interestingly, colesevelam may enhance the effects of certain medications:

Metformin: Colesevelam may increase metformin’s glucose-lowering effects
Sulfonylureas: Enhanced glycemic control when used in combination

What strategies can healthcare providers employ to manage potential drug interactions with colesevelam. Careful medication reconciliation, patient education on proper timing of drug administration, and regular monitoring of therapeutic effects and potential adverse reactions are crucial for managing drug interactions effectively.

Clinical Considerations: Maximizing the Benefits of Colesevelam Therapy

When prescribing colesevelam, healthcare providers should consider several factors to ensure optimal patient outcomes:

Patient Selection

Ideal candidates: Patients with primary hyperlipidemia or type 2 diabetes who have not achieved target lipid or glucose levels with lifestyle modifications or first-line therapies
Caution in patients with: Triglyceride levels >300 mg/dL, history of bowel obstruction, or gastroparesis

Monitoring and Follow-up

Baseline lipid profile and HbA1c (if used for diabetes management)
Follow-up lipid panel and HbA1c at 4-6 weeks after initiation or dose adjustment
Regular monitoring of fat-soluble vitamin levels in long-term use
Assessment of gastrointestinal symptoms and adherence at each visit

How frequently should patients on colesevelam be monitored for efficacy and safety. While initial follow-up is recommended at 4-6 weeks, subsequent monitoring intervals can be individualized based on patient response, comorbidities, and concomitant medications. Typically, every 3-6 months is appropriate for stable patients.

Future Perspectives: Expanding the Role of Colesevelam in Clinical Practice

As research on colesevelam continues, new potential applications and insights are emerging:

Emerging Areas of Interest

Role in non-alcoholic fatty liver disease (NAFLD) management
Potential use in pediatric populations with metabolic disorders
Combination therapy with novel antidiabetic agents
Development of extended-release formulations for improved tolerability

Ongoing Research

Current studies are exploring:

Long-term cardiovascular outcomes in patients using colesevelam
Impact on gut microbiome and its potential metabolic effects
Utility in managing bile acid malabsorption syndromes
Cost-effectiveness compared to newer lipid-lowering therapies

What potential new indications might emerge for colesevelam in the coming years. Given its unique mechanism of action and favorable safety profile, colesevelam may find applications in managing conditions related to bile acid dysregulation, such as primary biliary cholangitis or certain types of chronic diarrhea. However, further research is needed to establish its efficacy in these areas.

In conclusion, colesevelam represents a valuable addition to the therapeutic armamentarium for managing hyperlipidemia and type 2 diabetes. Its unique mechanism of action, coupled with a favorable side effect profile, makes it an attractive option for patients who cannot tolerate or have inadequate response to other lipid-lowering agents. As research continues to uncover new potential applications, colesevelam’s role in clinical practice may expand, offering hope for improved outcomes in metabolic and gastrointestinal disorders.

Colesevelam – StatPearls – NCBI Bookshelf

Parth H. Patel; Ahmet S. Can.

Author Information and Affiliations

Last Update: May 1, 2023.

Continuing Education Activity

Colesevelam is an FDA-approved antihyperlipidemic drug. When treating hyperlipidemia, colesevelam should be used in conjunction with restriction of cholesterol and fat intake and exercise and can be used as a monotherapy or combined with an HMG-CoA reductase inhibitor ezetimibe, or niacin. It is approved for the treatment of hyperlipidemia from heterozygous familial hypercholesterolemia in adults and as well as in adolescents (10 to 17 years of age) patients. Colesevelam is also indicated to improve glycemic control in adults with type 2 diabetes mellitus along with diet and exercise.

Objectives:

Identify the mechanism of action of colesevelam.
Describe the potential adverse effects of colesevelam.
Review the potential clinically significant drug-drug interactions of colesevelam.
Outline some interprofessional team strategies for improving care coordination and communication when using colesevelam and improve outcomes.

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Indications

Colesevelam is a bile acid sequestrant that is an FDA-approved drug to be used in adjunct with diet and exercise for a variety of indications. The main indication is to lower an elevated low-density lipoprotein cholesterol (LDL-C) in patients with primary hyperlipidemia and other diseases that cause hyperlipidemia. It can be used as a monotherapy or with an HMG-CoA reductase inhibitor (statin), ezetimibe, or niacin, or a three- or four-drug combination. Another approved use is to reduce LDL-C levels in boys and postmenarchal girls ages 10-17 who have heterozygous familial hypercholesterolemia. For this situation, colesevelam can be used as a monotherapy or with a statin only after a proper trial of diet and exercise has failed. Finally, the last FDA-approved indication is to improve glycemic control in type 2 diabetic adults.

While not an FDA-approved use, colesevelam has been shown to improve stool consistency in patients with irritable bowel syndrome with diarrhea, causing an overall improvement in bowel function.[1] Overall effects were consistent with increased hepatic bile synthesis and luminal bile acid sequestration by colesevelam.[1]

Mechanism of Action

Colesevelam is a novel drug created to help patients lower their LDL cholesterol levels. Its primary mechanism of action is to create nonabsorbable complexes when exposed to bile acids in the GI tract. It forms these complexes due to its numerous hydrophobic side chains, which enhance the binding of bile acids.[2] Once it forms the complexes, the bile acids are no longer able to be reabsorbed to participate in the enterohepatic bile acid recirculation system. This activity causes a reduction in the total amount of bile acids in the body, causing an upregulation of the 7-alpha-hydroxylase enzyme responsible for converting intracellular cholesterol into bile acids. With the need for bile acids increased, hepatic LDL receptors become upregulated to provide enough cholesterol for bile acid synthesis. As more and more cholesterol diverts into creating bile acids, there is an overall decrease in the plasma LDL cholesterol level, along with a decrease in total cholesterol levels.[3]

The main mechanism through which colesevelam reduces plasma glucose levels is not entirely understood. In animal studies, researchers have observed colesevelam increasing the hormone glucagon-like peptide-1, GLP-1, and other incretins. Mice models show that this occurs through the activation of TGR5 secondary to the binding of bile acids in the GI tract. Once GLP1 and other incretins are activated, overall hepatic glycogenolysis becomes suppressed. This suppression occurs because patients with type 2 diabetes have increased hepatic glucose production, contributing to elevated fasting serum glucose levels. By decreasing hepatic glycogenolysis, one can expect a reduction in serum glucose levels. [2][4]

Administration

Colesevelam comes in three major forms that are available to patients. Healthcare providers have the option of choosing an oral tablet formulation, a prepared suspension, as well as a recently approved chewable bar form. The recommendation is to take either once or twice daily to achieve therapeutic effects. Also, patients with susceptibility to fat-soluble vitamin and folic acid deficiencies should take the vitamins at least 4 hours after taking colesevelam to allow for proper absorption of the vitamins. This principle also applies to statins. Statins need to be taken at least 4 hours after taking colesevelam. Patients should be counseled on proper fluid intake once started on colesevelam.

Colesevelam comes in the following formulations:

Adverse Effects

Colesevelam is part of the drug class known as bile acid sequestrants. While overall, very effective and safe to use as a nonsystemic approach to lower cholesterol, tolerability and compliance issues are not uncommon. Colesevelam has the lowest rate of side effects associated with its use, but it still shares the same side effects as the rest of the drugs in its class. Due to the mechanism of action and causing increased bile acid in the gastrointestinal tract, the predominant side effects are gastrointestinal. Symptoms like constipation, diarrhea, gas, as well as nausea, abdominal pain, and weakness are common. Patients have also noted muscle pain to be a side effect of colesevelam.[5] Another notable side effect associated with the use of colesevelam is a significant increase in triglycerides.[6] Also, steatorrhea is a common side effect of these drugs as well. Due to this, patients should receive counsel that they should take this drug at least four hours before ingesting vitamin supplements and statins.[7]

Colesevelam may decrease the bioavailability of many drugs, including but not limited to: amiodarone, oral corticosteroids, cyclosporine (systemic), estrogen derivatives, progesterone, oral contraceptives, ezetimibe, glimepiride, glipizide, glyburide, leflunomide, lomitapide, loop diuretics like furosemide, thiazides, methotrexate, mycophenolate, nonsteroidal anti-inflammatory drugs, olmesartan, phenytoin, pravastatin, niacin, propranolol, raloxifene, tetracyclines, levothyroxine, ursodiol, oral vancomycin, warfarin and fat-soluble multivitamins A, E, D, K. If these drugs are on the treatment regimen of the patient, monitor therapy or consider therapy modification. These drugs require administration either one to two hours before or four hours after colesevelam administration (see product information of the medications mentioned above).

Contraindications

While a generally well-tolerated drug with relatively mild side effects, colesevelam still has a few side effects that healthcare providers should be aware of before prescribing a patient the medication. Clinicians should not give colesevelam to patients with a history of bowel obstruction. Additionally, patients with a history of serum triglyceride concentrations greater than 500mg/dL or a history of hypertriglyceridemia-induced pancreatitis should not be given this drug due to its ability to increase triglyceride levels.[5][8]

Monitoring

Colesevelam has relatively few monitoring needs. While the drug’s desired effect is easily attainable without monitoring, the real monitoring that is necessary is with concomitantly administered drugs. Colesevelam primarily has been shown to decrease levels of fat-soluble vitamins as the drug tends to cause steatorrhea and the malabsorption of these vitamins. Patients with known deficiencies of these vitamins should understand to take their supplements either an hour before or about four hours after the administration of colesevelam.[5]

In addition to fat-soluble vitamins, studies have shown that patients with hypothyroidism that get started on colesevelam show an increase in TSH levels. This increase indicates that colesevelam causes a decreased absorption of levothyroxine. To counter this, healthcare providers should monitor the patient’s TSH levels while on this drug and advise patients to take their levothyroxine four hours after taking colesevelam.[9] Lastly, patients with triglycerides above 300 mg/dL should be given this drug with caution. Due to colesevelam’s side effect of increasing triglyceride levels, patients with already elevated levels above 300 mg/dL are at risk for increased adverse events like triglyceride-induced pancreatitis and other adverse effects associated with high triglyceride levels. [10]

Toxicity

Overall, colesevelam is a very safe drug to use with a long history of clinical use and study. The medication does not cause toxicity outside of the adverse effects mentioned above. Healthcare providers should be on the lookout for adverse effects patients may experience and work with the clinical care team as well as the patient to see if the medication needs to be adjusted or changed to help alleviate the adverse effects. Healthcare providers should also consider using an alternative formulation of the drug if there are side effects, especially gastrointestinal side effects.

Enhancing Healthcare Team Outcomes

Colesevelam is a very safe drug in the class of bile acid sequestrants used for the treatment of various illnesses. While very safe to use, adverse events are possible. As such, all interprofessional healthcare team members should be on the lookout for the adverse effects. Also, the team members should be knowledgeable on the drug and its properties to help advise the patient on the proper information they should know when taking the medication. Clinicians can utilize pharmacist expertise if there is a question on whether the patient can take the drug safely or not and verify if any contraindications or drug-to-drug interactions might exist. Nursing can provide essential information to patients as well as education on common side effects. Also, nursing can monitor the common adverse effects and serious side effects that patients may experience and may require medical attention. Every member of the interprofessional healthcare team has a responsibility to provide the best care to their patients and should be aware of therapies they might be on to help achieve the best possible outcome for the patient. [Level 5]

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References

1.: Camilleri M, Acosta A, Busciglio I, Boldingh A, Dyer RB, Zinsmeister AR, Lueke A, Gray A, Donato LJ. Effect of colesevelam on faecal bile acids and bowel functions in diarrhoea-predominant irritable bowel syndrome. Aliment Pharmacol Ther. 2015 Mar;41(5):438-48. [PMC free article: PMC4493894] [PubMed: 25594801]
2.: Nwose OM, Jones MR. Atypical mechanism of glucose modulation by colesevelam in patients with type 2 diabetes. Clin Med Insights Endocrinol Diabetes. 2013 Dec 08;6:75-9. [PMC free article: PMC3864737] [PubMed: 24348081]
3.: Sonnett T, Robinson J, Milani P, Campbell RK. Role of colesevelam in managing heterozygous familial hypercholesterolemia in adolescents and children. Adolesc Health Med Ther. 2010;1:53-60. [PMC free article: PMC3915789] [PubMed: 24600261]
4.: Brunetti L, DeSantis EH. Patient tolerance and acceptance of colesevelam hydrochloride: focus on type-2 diabetes mellitus. P T. 2015 Jan;40(1):62-7. [PMC free article: PMC4296594] [PubMed: 25628509]
5.: Zema MJ. Colesevelam hydrochloride: evidence for its use in the treatment of hypercholesterolemia and type 2 diabetes mellitus with insights into mechanism of action. Core Evid. 2012;7:61-75. [PMC free article: PMC3426253] [PubMed: 22936894]
6.: Aggarwal S, Loomba RS, Arora RR. Efficacy of colesevelam on lowering glycemia and lipids. J Cardiovasc Pharmacol. 2012 Feb;59(2):198-205. [PubMed: 21983746]
7.: Bays H, Jones PH. Colesevelam hydrochloride: reducing atherosclerotic coronary heart disease risk factors. Vasc Health Risk Manag. 2007;3(5):733-42. [PMC free article: PMC2291317] [PubMed: 18078024]
8.: Sekhri K, Saha L. Colesevelam hydrochloride: A novel agent in patients with type 2 diabetes. Int J Appl Basic Med Res. 2011 Jul;1(2):113-5. [PMC free article: PMC3657969] [PubMed: 23776789]
9.: Weitzman SP, Ginsburg KC, Carlson HE. Colesevelam hydrochloride and lanthanum carbonate interfere with the absorption of levothyroxine. Thyroid. 2009 Jan;19(1):77-9. [PMC free article: PMC2858370] [PubMed: 19119983]
10.: Kaufman MB. Drug-induced pancreatitis: A Potentially Serious and Underreported Problem. P T. 2013 Jun;38(6):349-51. [PMC free article: PMC3737994] [PubMed: 23946630]

: Disclosure: Parth Patel declares no relevant financial relationships with ineligible companies.
: Disclosure: Ahmet Can declares no relevant financial relationships with ineligible companies.

Colesevelam Oral: Uses, Side Effects, Interactions, Pictures, Warnings & Dosing

Uses

This medication is used along with a proper diet and exercise to lower cholesterol in people with high levels of cholesterol in the blood. Lowering cholesterol decreases the risk of heart disease and helps prevent strokes and heart attacks.Colesevelam is also used along with a proper diet and exercise to lower high blood sugar in people with type 2 diabetes. Controlling high blood sugar helps prevent kidney damage, blindness, nerve problems, loss of limbs, and sexual function problems. Proper control of diabetes may also lessen your risk of a heart attack or stroke. Colesevelam belongs to a class of drugs called bile acid-binding resins. Bile acid is a natural substance the liver makes by using cholesterol. This medication works by removing bile acid from the body. This causes the liver to make more bile acid by using cholesterol, which reduces cholesterol levels in the blood. It is not known how colesevelam works in lowering blood sugar.

How to use Colesevelam HCL

Take this medication by mouth with a meal as directed by your doctor, usually 1 to 2 times daily. Take the tablet form with a liquid (such as water, milk). If you have trouble swallowing the tablet, talk to your doctor about switching to the powder form of this medication.

If you are using the powder form of this medication, pour the contents of one packet into a glass. Add one cup (8 ounces/240 milliliters) of water, fruit juice, or diet soda. Stir the mixture well and drink all of it. Do not take the powder without mixing it in liquid.

Take this medication regularly to get the most benefit from it. To help you remember, take it at the same time(s) each day.

It may take several weeks before you get the full benefit of this drug.

Colesevelam may decrease the absorption of other products you may be taking. Some examples include cyclosporine, glipizide, glimepiride, glyburide, levothyroxine, and phenytoin, as well as birth control pills that contain ethinyl estradiol and norethindrone. Take other medications as directed by your doctor, usually at least 4 hours before taking your colesevelam dose. Ask your pharmacist if you are not sure when to take your medications.

Side Effects

Constipation and upset stomach may occur. If any of these effects last or get worse, tell your doctor or pharmacist promptly.

To prevent constipation, eat dietary fiber, drink enough water, and exercise. You may also need to take a laxative. Ask your pharmacist which type of laxative is right for you.

Remember that this medication has been prescribed because your doctor has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor right away if you have any serious side effects, including: nausea/vomiting, stomach/abdominal pain, trouble swallowing, unusual bleeding/bruising.

This medication does not usually cause low blood sugar (hypoglycemia). Low blood sugar may occur if this drug is prescribed with other diabetes medications, or if you do not consume enough calories from food, or if you do unusually heavy exercise.

Symptoms of low blood sugar include sudden sweating, shaking, fast heartbeat, hunger, blurred vision, dizziness, or tingling hands/feet. It is a good habit to carry glucose tablets or gel to treat low blood sugar. If you don’t have these reliable forms of glucose, rapidly raise your blood sugar by eating a quick source of sugar such as table sugar, honey, or candy, or drink fruit juice or non-diet soda. Tell your doctor right away about the reaction and the use of this product. To help prevent low blood sugar, eat meals on a regular schedule, and do not skip meals. Check with your doctor or pharmacist to find out what you should do if you miss a meal.

Symptoms of high blood sugar (hyperglycemia) include thirst, increased urination, confusion, drowsiness, flushing, rapid breathing, and fruity breath odor. If these symptoms occur, tell your doctor right away. Your dosage may need to be increased.

A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

In the US – Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch.

In Canada – Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

Precautions

Before taking colesevelam, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: pancreatitis (caused by high triglyceride levels), high triglyceride levels, trouble swallowing, stomach/intestinal disorders (such as constipation, blockage, gastroparesis), recent major intestinal surgery, hemorrhoids.

Because this drug can interfere with the absorption of certain vitamins (such as vitamins A, D, E, K) when used for a long period of time, your doctor may direct you to take a multivitamin supplement. Take the multivitamin at least 4 hours before taking your colesevelam dose.

The powder form of this medication may contain aspartame. If you have phenylketonuria (PKU) or any other condition that requires you to restrict your intake of aspartame (or phenylalanine), consult your doctor or pharmacist about using this medication safely.

Before having surgery, tell your doctor or dentist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products).

Tell your doctor if you are pregnant before using this medication.

This medication is unlikely to pass into breast milk or harm a nursing infant. Consult your doctor before breast-feeding.

Interactions

Overdose

If someone has overdosed and has serious symptoms such as passing out or trouble breathing, call 911. Otherwise, call a poison control center right away. US residents can call their local poison control center at 1-800-222-1222. Canada residents can call a provincial poison control center.

Do not share this medication with others.

Lab and/or medical tests (such as blood cholesterol levels, blood sugar) should be done while you are taking this medication. Keep all medical and lab appointments. Consult your doctor for more details.

Lifestyle changes that may help this medication work better include exercising, stopping smoking, and eating a low-cholesterol/low-fat diet. Consult your doctor for more details.

Attend a diabetes education program to learn more about how to manage your diabetes with medications, diet, exercise, and regular medical exams.

Learn the symptoms of high and low blood sugar and how to treat low blood sugar. Check your blood sugar regularly as directed and share the results with your doctor.

If you miss a dose, take it as soon as you remember with a meal. If it is near the time of the next dose, skip the missed dose. Take your next dose at the regular time. Do not double the dose to catch up.

Store at room temperature away from light and moisture. Do not store in the bathroom. Keep all medications away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company.