What are the indications for atorvastatin therapy. How does atorvastatin work to lower cholesterol levels. What are the potential side effects of atorvastatin. How is atorvastatin administered and what are its pharmacokinetic properties.

Understanding Atorvastatin: A Potent Statin Medication

Atorvastatin, a member of the statin family, is a widely prescribed medication used to manage cholesterol levels and reduce the risk of cardiovascular events. As a powerful HMG-CoA reductase inhibitor, atorvastatin plays a crucial role in both primary and secondary prevention of coronary heart disease. This comprehensive guide delves into the various aspects of atorvastatin, including its indications, mechanism of action, pharmacokinetics, and administration.

Indications for Atorvastatin Therapy: Primary and Secondary Prevention

Atorvastatin has received FDA approval for a range of indications, encompassing both primary and secondary prevention strategies. These indications highlight the versatility and effectiveness of atorvastatin in managing cardiovascular risk factors and lipid abnormalities.

Primary Prevention

• Reduction of cardiovascular event risk in patients with multiple cardiac risk factors
• Lowering the risk of myocardial infarction and stroke in patients with type 2 diabetes mellitus and multiple risk factors

Secondary Prevention

• Reducing the risk of nonfatal myocardial infarction, fatal and nonfatal stroke, revascularization procedures, hospitalizations for congestive heart failure, and angina in patients with established coronary heart disease

Treatment of Dyslipidemias

Atorvastatin is also indicated for the treatment of various dyslipidemias, including:

• Primary hyperlipidemia (heterozygous familial and nonfamilial) and mixed dyslipidemia in adults
• Hypertriglyceridemia
• Primary dysbetalipoproteinemia
• Homozygous familial hypercholesterolemia
• Heterozygous familial hypercholesterolemia in pediatric patients (after dietary modifications have failed)

It’s important to note that atorvastatin has not been studied in Fredrickson Type I and V dyslipidemias, and its use in these conditions is not recommended.

Mechanism of Action: How Atorvastatin Lowers Cholesterol

Atorvastatin’s effectiveness in managing cholesterol levels stems from its unique mechanism of action. Understanding how this medication works provides insight into its therapeutic benefits and potential side effects.

Competitive Inhibition of HMG-CoA Reductase

The primary mechanism of action for atorvastatin is the competitive inhibition of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase. This enzyme plays a crucial role in cholesterol synthesis within the liver. By inhibiting HMG-CoA reductase, atorvastatin prevents the conversion of HMG-CoA to mevalonate, effectively reducing cholesterol production.

Increased LDL Receptor Expression

In addition to inhibiting cholesterol synthesis, atorvastatin also increases the number of LDL receptors on the surface of hepatic cells. This dual action enhances the liver’s ability to remove LDL cholesterol from the bloodstream, further contributing to the medication’s lipid-lowering effects.

Impact on Lipid Profiles

Atorvastatin’s mechanism of action results in significant improvements in lipid profiles across various patient populations. Clinical studies have demonstrated that atorvastatin can:

• Reduce total cholesterol (TC)
• Lower low-density lipoprotein cholesterol (LDL-C)
• Decrease apolipoprotein B (apo B)
• Reduce very-low-density lipoprotein (VLDL-C)
• Lower triglycerides (TGs)
• Increase high-density lipoprotein cholesterol (HDL-C)

In patients with dysbetalipoproteinemia, atorvastatin has also been shown to decrease intermediate-density lipoprotein (IDL-C) levels.

Pharmacokinetics of Atorvastatin: Understanding its Journey Through the Body

The pharmacokinetic properties of atorvastatin play a crucial role in its effectiveness and dosing considerations. Let’s explore the key aspects of atorvastatin’s pharmacokinetics:

Absorption

Atorvastatin is rapidly absorbed following oral administration. The peak plasma concentration is typically reached within 1 to 2 hours after ingestion. However, due to extensive first-pass metabolism, the bioavailability of atorvastatin is relatively low at approximately 14%.

Distribution

Once absorbed, atorvastatin demonstrates high plasma protein binding, with over 98% of the drug bound to proteins in the bloodstream. The volume of distribution for atorvastatin is approximately 380 liters, indicating extensive tissue distribution.

Metabolism

Atorvastatin undergoes metabolism primarily through the cytochrome P450 3A4 (CYP3A4) enzyme system in the liver. This process results in the formation of active ortho- and para-hydroxylated metabolites, which contribute to the overall lipid-lowering effects of the medication.

Excretion

The elimination of atorvastatin and its metabolites occurs primarily through biliary excretion. Unlike some other medications, atorvastatin is not known to undergo enterohepatic recirculation. The half-life of atorvastatin is approximately 14 hours, while its active metabolites have a longer half-life of about 20 to 30 hours.

Administration and Dosing of Atorvastatin: Optimizing Therapeutic Outcomes

Proper administration of atorvastatin is essential for achieving optimal therapeutic outcomes and minimizing potential side effects. Here are the key considerations for atorvastatin administration:

Available Formulations

Atorvastatin is available as atorvastatin calcium tablets in the following strengths:

• 10 mg
• 20 mg
• 40 mg
• 80 mg

Dosing Flexibility

Atorvastatin offers flexible dosing options to accommodate various patient needs:

• Can be taken with or without food
• Should be administered at the same time each day for consistency
• Traditionally recommended for bedtime administration, but the longer half-life of atorvastatin allows for greater flexibility compared to shorter-acting statins

Timing Considerations

While it is generally recommended to administer statins at bedtime due to the cyclical nature of endogenous cholesterol synthesis, atorvastatin’s longer half-life provides more flexibility. This characteristic allows for administration at any time of day, as long as the dosing remains consistent.

Potential Side Effects and Monitoring: Ensuring Safe and Effective Atorvastatin Use

While atorvastatin is generally well-tolerated, it’s important to be aware of potential side effects and implement appropriate monitoring strategies. Common side effects and monitoring recommendations include:

Common Side Effects

• Muscle pain or weakness
• Headache
• Digestive issues (nausea, diarrhea, constipation)
• Mild elevation in liver enzymes

Monitoring Recommendations

1. Baseline liver function tests before initiating therapy
2. Regular lipid profile assessments to evaluate treatment efficacy
3. Periodic liver function tests during treatment
4. Monitoring for signs of muscle pain or weakness
5. Consideration of creatine kinase levels in patients with muscle symptoms

Patients should be educated about potential side effects and encouraged to report any concerning symptoms promptly.

Atorvastatin in Special Populations: Tailoring Treatment to Individual Needs

Atorvastatin use may require special considerations in certain patient populations. Understanding these factors is crucial for optimizing treatment outcomes and minimizing risks.

Pediatric Patients

Atorvastatin is approved for use in pediatric patients with heterozygous familial hypercholesterolemia. However, dosing and monitoring may differ from adult patients, and treatment should be initiated only after dietary modifications have proven insufficient.

Elderly Patients

Elderly patients may be more susceptible to certain side effects of atorvastatin. Careful dose titration and monitoring are recommended in this population.

Patients with Renal Impairment

While dose adjustments are not typically required in patients with renal impairment, caution should be exercised, and monitoring may need to be more frequent.

Patients with Hepatic Impairment

Atorvastatin is contraindicated in patients with active liver disease. In patients with a history of liver disease or elevated liver enzymes, close monitoring is essential.

Drug Interactions: Navigating Potential Complications with Atorvastatin

Atorvastatin can interact with various medications, potentially altering its effectiveness or increasing the risk of side effects. Key drug interactions to be aware of include:

CYP3A4 Inhibitors

Medications that inhibit CYP3A4, such as certain antifungals, antibiotics, and HIV protease inhibitors, can increase atorvastatin levels in the body. This may necessitate dose adjustments or alternative treatments.

Grapefruit Juice

Grapefruit juice can inhibit CYP3A4, potentially increasing atorvastatin levels. Patients should be advised to avoid consuming large quantities of grapefruit juice while taking atorvastatin.

Fibrates

Concomitant use of atorvastatin with fibrates may increase the risk of myopathy. If combination therapy is necessary, close monitoring is essential.

Cyclosporine

Cyclosporine can significantly increase atorvastatin levels. Dose reductions and careful monitoring are required when these medications are used together.

Healthcare providers should conduct thorough medication reviews and consider potential interactions when prescribing atorvastatin.

Atorvastatin – StatPearls – NCBI Bookshelf

Continuing Education Activity

HMG-CoA reductase inhibitors (statins) are lipid-lowering medications used in the primary and secondary prevention of coronary heart disease. Atorvastatin competitively inhibits 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase. By preventing the conversion of HMG-CoA to mevalonate, statin medications decrease cholesterol production in the liver. Atorvastatin also increases the number of LDL receptors on the surface of hepatic cells. This activity reviews the indications, contraindications, and mechanism of action of atorvastatin to manage coronary heart disease and familial dyslipidemias, covering the indications, contraindications, activity, adverse events, and other key elements of atorvastatin therapy.

Objectives:

• Describe the indications for atorvastatin therapy.

• Identify potential adverse events when using therapy with atorvastatin.

• Outline the appropriate follow-up and monitoring of lipid-lowering therapy with atorvastatin.

• Review interprofessional team strategies for improving care coordination and communication to enhance patient adherence to atorvastatin in treating coronary artery disease and hyperlipidemia.

Access free multiple choice questions on this topic.

Indications

In combination with dietary modifications, atorvastatin is FDA approved to prevent cardiovascular events in patients with cardiac risk factors and also patients with abnormal lipid profiles.[1]

Primary Prevention

For patients without coronary heart disease but with multiple risk factors, the FDA has approved atorvastatin to reduce the risk of myocardial infarction, stroke, revascularization procedures, and angina.

For patients diagnosed with type 2 diabetes mellitus without coronary heart disease but with multiple risk factors, atorvastatin has FDA approval to reduce the risk of myocardial infarction and stroke.  

Secondary Prevention

For patients with coronary heart disease, atorvastatin has received approval as a therapy to reduce the risk of nonfatal myocardial infarction, fatal and nonfatal stroke, revascularization procedures, hospitalizations for congestive heart failure, and angina.  

Atorvastatin has FDA approval for the treatment of the following dyslipidemias: 

• Adults with primary hyperlipidemia (heterozygous familial and nonfamilial) and mixed dyslipidemia

• Hypertriglyceridemia

• Primary dysbetalipoproteinemia

• Homozygous familial hypercholesterolemia

• Pediatric patients with heterozygous familial hypercholesterolemia (after failing dietary modifications)

Atorvastatin has not been studied in Fredrickson Type I and V dyslipidemias.

Mechanism of Action

Atorvastatin competitively inhibits 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase.[2] By preventing the conversion of HMG-CoA to mevalonate, statin medications decrease cholesterol production in the liver. Atorvastatin also increases the number of LDL receptors on the surface of hepatic cells. 

In patients with homozygous or heterozygous familial hypercholesterolemia, mixed dyslipidemia, isolated hypertriglyceridemia, or nonfamilial hypercholesterolemia, atorvastatin has been shown to reduce total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (apo B), very-low-density lipoprotein (VLDL-C) and triglycerides (TGs) while increasing high-density lipoprotein cholesterol (HDL-C).  

In patients with dysbetalipoproteinemia, atorvastatin has been shown to decrease intermediate-density lipoprotein (IDL-C).   

Pharmacokinetics

Pharmacokinetic attributes of atorvastatin are covered below.[3] 

Absorption 

Atorvastatin is rapidly absorbed after oral administration with a peak plasma concentration at 1 to 2 hours. The bioavailability is low at 14% due to extensive first-pass metabolism.

Distribution

Atorvastatin is highly plasma protein bound (over 98%) and has a volume of distribution of about 380 liters. 

Metabolism

Atorvastatin is metabolized by cytochrome P450 3A4 (CYP3A4) to active ortho- and para-hydroxylated metabolites. 

Excretion

Atorvastatin and its metabolites get eliminated in bile. Atorvastatin is not known to go through enterohepatic recirculation. The half-life of atorvastatin is about 14 hours, while its active metabolites have a half-life of about 20 to 30 hours.  

Administration

Atorvastatin is available as atorvastatin calcium tablets in strengths of 10, 20, 40, and 80 mg.  

This medication can be administered with or without food and should be taken at the same time every day. It is generally recommended to administer statins at bedtime since endogenous cholesterol synthesis is cyclical, with the highest production levels during fasting as at night. However, the longer half-life of atorvastatin compared to other shorter half-life statins (e.g., lovastatin, fluvastatin, and simvastatin) offers greater flexibility regarding dosing times.

Adult Dosing 

The dosing of atorvastatin can have its basis in LDL-C lowering ability (intensity), or doses are titratable to specific lipid goals. 

The American College of Cardiology/American Heart Association Guidelines recommends either moderate intensity (atorvastatin 10 to 20 mg) or high intensity (atorvastatin 40 to 80 mg) therapy depending on the statin benefit group to which a patient belongs. Moderate-intensity statins should lower LDL-C by about 30 to 50%, while high-intensity statins should lower LDL-C by over 50 %.[4]

Both the National Lipid Association and the American Association of Clinical Endocrinologists recommend utilizing statin therapy to reach specific lipid goals based on atherosclerotic cardiovascular disease risk.[5][6]

Pediatrics 

Doses above 20 mg do not have study data for pediatric patients with heterozygous familial hypercholesterolemia. Doses up to 80 mg have been used in a limited number of pediatric patients with familial hypercholesterolemia. Studies have not evaluated atorvastatin use in pre-pubescent patients or those under ten years old. 

Geriatrics

Patients over 65 years old may have higher plasma concentrations of atorvastatin than young adults. Older patients may be at increased risk of statin-induced myopathies. 

Renal Impairment 

Atorvastatin and its metabolites do not undergo renal elimination, so no dose adjustments are required with reduced renal function. Hemodialysis will not likely remove atorvastatin due to plasma protein binding. 

Hepatic Impairment

Increased plasma concentrations of atorvastatin have occurred in patients with chronic alcoholic liver disease. Drug exposure is four times higher in patients with Child-Pugh Class A and 11x higher in patients with Child-Pugh Class B. Atorvastatin is contraindicated in patients with active liver disease.[7]

Drug Interactions
[8]
 

Using atorvastatin with potent CYP3A4 inhibitors can lead to increased plasma concentrations, which may enhance adverse events, including myopathy. OATP1B1 inhibitors can increase the bioavailability of atorvastatin.[9]

CYP3A4 inducers may cause decreased plasma concentrations of atorvastatin. 

Patients taking digoxin should undergo monitoring when starting atorvastatin as plasma concentrations of digoxin may increase.

Atorvastatin may also increase drug concentrations of norethindrone and ethinyl estradiol.

Adverse Effects

Common adverse effects for patients taking atorvastatin include arthralgia, dyspepsia, diarrhea, nausea, nasopharyngitis, insomnia, urinary tract infection, and pain in the extremities.

Myopathies have occurred in patients taking atorvastatin, including muscle aches, muscle tenderness, or muscle weakness, with elevated creatine phosphokinase greater than ten times the upper limit of normal. Rhabdomyolysis has been reported in patients using atorvastatin.[10] Patients with impaired renal function may be at increased risk of developing rhabdomyolysis. Using atorvastatin in combination with other medications that increase atorvastatin plasma concentrations increases the risk for myopathies and rhabdomyolysis.[11] Management of statin-induced myopathies includes temporarily holding therapy, switching to an alternative statin, or reducing the dose. 

Some data suggest that statins may increase the risk of developing diabetes mellitus. In 2012, the FDA added safety label changes to statin safety labeling, indicating that they have been shown to increase glycosylated hemoglobin and fasting serum glucose. [12] The ACC/AHA guidelines group and other experts state that the risk-reducing benefits of statin therapy outweigh the generally mild rise in serum glucose levels or new-onset diabetes.[13] Clinicians are encouraged to use this opportunity to discuss healthy lifestyle measures with their patients, including weight loss, engaging in an exercise program, and consuming a healthy diet.

Atorvastatin can cause liver function test abnormalities.[7] If patients develop serum transaminases over three times the upper limit of normal, plasma concentrations require more frequent monitoring until normalized, or atorvastatin therapy should undergo dose reduction or be discontinued. 

Contraindications

Atorvastatin contraindications include patients with hypersensitivity to any of its components.

While atorvastatin contraindications also include patients with active liver disease, the benefits of lipid-lowering therapy in chronic liver diseases, such as non-alcoholic fatty liver disease and hepatitis, likely outweigh the possible risks. [14]

Atorvastatin is contraindicated during pregnancy or in female patients who may become pregnant. All female patients of childbearing age should receive counseling on the potential risks to a fetus should they become pregnant while on atorvastatin. This risk is most pronounced in the first trimester, so current guidelines recommend ceasing statin therapy for at least three months prior to becoming pregnant. The patient should discontinue this medication immediately if they become pregnant. However, a recent meta-analysis has called this restriction into question; more research will be necessary to accurately assess the risk-benefit ratio of using statins during pregnancy.[15]

Female patients should also avoid atorvastatin if they are nursing. If patients require atorvastatin therapy, they should receive direction to discontinue breastfeeding. 

Monitoring

Patients starting atorvastatin should have liver function tests and a lipid panel performed at baseline, with a repeat lipid panel after six weeks of therapy. Liver function tests should be repeated as clinically indicated. Once the patient is stable, lipids can be checked every 6 to 12 months. It may also be prudent to periodically monitor serum blood glucose levels in patients with diabetes or at risk for diabetes.

Toxicity

There are no antidotes available for atorvastatin overdose. Patients should be monitored for adverse events and provided with supportive care. 

Enhancing Healthcare Team Outcomes

The success of statins in lowering lipids or preventing cardiovascular events depends on the patient’s medication adherence. Some barriers to successful statin therapy include experiencing adverse effects, lack of understanding of the importance of statin therapy, and cost; these factors may prevent patients from taking these medications as prescribed. It is also crucial for the interprofessional team to emphasize the importance of lifestyle modification in treating hyperlipidemia. This includes eating a proper, healthy diet, adding exercise or activity several times a week, and losing weight if necessary. A dietician or nutritionist may be a valuable addition to the healthcare team to help guide patients through the necessary dietary changes.

All interprofessional health care team members can help identify barriers to adherence. Additional education and counseling around patient concerns and medication benefits may help improve compliance.[16] [Level 3] Healthcare team members need to communicate across disciplinary lines to optimize therapy. Clinicians (MDs, DOs, NPs, PAs) will make the initial assessment and prescribe statin therapy. Nursing can counsel the patients on how to take their medication, check for adherence to treatment and adverse effects on subsequent visits, and report back to the prescriber. Pharmacists can counsel the patients on optimal dosing (e.g., take the drug at bedtime) and check for drug-drug interactions, reporting to the prescriber or nurse. Pharmacists can also inquire about the most common adverse effects since they often will see the patient more frequently and let nursing know so it can be relayed to the prescriber as well; open communication between all interprofessional team members combined with accurate record keeping is crucial to optimal care and improved patient outcomes. These are a few examples of how interprofessional team interaction can optimize atorvastatin therapy. [Level 5]

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• Access free multiple choice questions on this topic.

• Comment on this article.

References

1.

Raddino R, Della Pina P, Gorga E, Caretta G, Madureri A, Dei Cas L. [Indications for statin therapy in patients with acute coronary syndrome of ischemic origin]. G Ital Cardiol (Rome). 2010 Oct;11(10 Suppl 1):78S-83S. [PubMed: 21416832]

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Dagli-Hernandez C, Zhou Y, Lauschke VM, Genvigir FDV, Hirata TDC, Hirata MH, Hirata RDC. Pharmacogenomics of statins: lipid response and other outcomes in Brazilian cohorts. Pharmacol Rep. 2022 Feb;74(1):47-66. [PubMed: 34403130]

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Karvaly GB, Karádi I, Vincze I, Neely MN, Trojnár E, Prohászka Z, Imreh É, Vásárhelyi B, Zsáry A. A pharmacokinetics-based approach to the monitoring of patient adherence to atorvastatin therapy. Pharmacol Res Perspect. 2021 Oct;9(5):e00856. [PMC free article: PMC8415218] [PubMed: 34478238]

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Stone NJ, Robinson JG, Lichtenstein AH, Bairey Merz CN, Blum CB, Eckel RH, Goldberg AC, Gordon D, Levy D, Lloyd-Jones DM, McBride P, Schwartz JS, Shero ST, Smith SC, Watson K, Wilson PW, Eddleman KM, Jarrett NM, LaBresh K, Nevo L, Wnek J, Anderson JL, Halperin JL, Albert NM, Bozkurt B, Brindis RG, Curtis LH, DeMets D, Hochman JS, Kovacs RJ, Ohman EM, Pressler SJ, Sellke FW, Shen WK, Smith SC, Tomaselli GF., American College of Cardiology/American Heart Association Task Force on Practice Guidelines. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014 Jun 24;129(25 Suppl 2):S1-45. [PubMed: 24222016]

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Jacobson TA, Ito MK, Maki KC, Orringer CE, Bays HE, Jones PH, McKenney JM, Grundy SM, Gill EA, Wild RA, Wilson DP, Brown WV. National lipid association recommendations for patient-centered management of dyslipidemia: part 1–full report. J Clin Lipidol. 2015 Mar-Apr;9(2):129-69. [PubMed: 25911072]

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Jellinger PS, Handelsman Y, Rosenblit PD, Bloomgarden ZT, Fonseca VA, Garber AJ, Grunberger G, Guerin CK, Bell DSH, Mechanick JI, Pessah-Pollack R, Wyne K, Smith D, Brinton EA, Fazio S, Davidson M. AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY GUIDELINES FOR MANAGEMENT OF DYSLIPIDEMIA AND PREVENTION OF CARDIOVASCULAR DISEASE. Endocr Pract. 2017 Apr;23(Suppl 2):1-87. [PubMed: 28437620]

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Filppula AM, Hirvensalo P, Parviainen H, Ivaska VE, Lönnberg KI, Deng F, Viinamäki J, Kurkela M, Neuvonen M, Niemi M. Comparative Hepatic and Intestinal Metabolism and Pharmacodynamics of Statins. Drug Metab Dispos. 2021 Aug;49(8):658-667. [PubMed: 34045219]

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Hirota T, Fujita Y, Ieiri I. An updated review of pharmacokinetic drug interactions and pharmacogenetics of statins. Expert Opin Drug Metab Toxicol. 2020 Sep;16(9):809-822. [PubMed: 32729746]

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Božina N, Ganoci L, Simičević L, Gvozdanović K, Domjanović IK, Fistrek Prlić M, Križ T, Borić Bilušić A, Laganović M, Božina T. Drug-drug-gene interactions as mediators of adverse drug reactions to diclofenac and statins: a case report and literature review. Arh Hig Rada Toksikol. 2021 Jun 28;72(3):114-128. [PMC free article: PMC8265195] [PubMed: 34187111]

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Nemati M, Srai M, Rudrangi R. Statin-Induced Autoimmune Myopathy. Cureus. 2021 Feb 26;13(2):e13576. [PMC free article: PMC8007198] [PubMed: 33815984]

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Jayatilaka S, Desai K, Rijal S, Zimmerman D. Statin-Induced Autoimmune Necrotizing Myopathy. J Prim Care Community Health. 2021 Jan-Dec;12:21501327211028714. [PMC free article: PMC8255573] [PubMed: 34219515]

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Chogtu B, Magazine R, Bairy KL. Statin use and risk of diabetes mellitus. World J Diabetes. 2015 Mar 15;6(2):352-7. [PMC free article: PMC4360430] [PubMed: 25789118]

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Keni R, Sekhar A, Gourishetti K, Nayak PG, Kinra M, Kumar N, Shenoy RR, Kishore A, Nandakumar K. Role of Statins in New-onset Diabetes Mellitus: The Underlying Cause, Mechanisms Involved, and Strategies to Combat. Curr Drug Targets. 2021;22(10):1121-1128. [PubMed: 33494673]

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Tandra S, Vuppalanchi R. Use of statins in patients with liver disease. Curr Treat Options Cardiovasc Med. 2009 Aug;11(4):272-8. [PubMed: 19627660]

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Zarek J, Koren G. The fetal safety of statins: a systematic review and meta-analysis. J Obstet Gynaecol Can. 2014 Jun;36(6):506-509. [PubMed: 24927189]

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Maningat P, Gordon BR, Breslow JL. How do we improve patient compliance and adherence to long-term statin therapy? Curr Atheroscler Rep. 2013 Jan;15(1):291. [PMC free article: PMC3534845] [PubMed: 23225173]

Disclosure: Lindsey McIver declares no relevant financial relationships with ineligible companies.

Disclosure: Momin Siddique declares no relevant financial relationships with ineligible companies.

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

Uses

Atorvastatin is used along with a proper diet to help lower “bad” cholesterol and fats (such as LDL, triglycerides) and raise “good” cholesterol (HDL) in the blood. It belongs to a group of drugs known as “statins.” It works by reducing the amount of cholesterol made by the liver. Lowering “bad” cholesterol and triglycerides and raising “good” cholesterol decreases the risk of heart disease and helps prevent strokes and heart attacks.In addition to eating a proper diet (such as a low-cholesterol/low-fat diet), other lifestyle changes that may help this medication work better include exercising, losing weight if overweight, and stopping smoking. Consult your doctor for more details.

How to use Atorvastatin 20 Mg/5 Ml (4 Mg/Ml) Oral Suspension

Read the Patient Information Leaflet if available from your pharmacist before you start taking atorvastatin and each time you get a refill. If you have any questions, ask your doctor or pharmacist.

Take this medication by mouth as directed by your doctor, usually once daily. It should be taken on an empty stomach, 1 hour before or 2 hours after a meal.

The dosage is based on your medical condition, response to treatment, age, and other medications you may be taking. Be sure to tell your doctor and pharmacist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products).

Shake the bottle well before each dose. Carefully measure the dose using a special measuring device/spoon. Do not use a household spoon because you may not get the correct dose.

Avoid eating grapefruit or drinking grapefruit juice while using this medication unless your doctor or pharmacist says you may do so safely. Grapefruit can increase the chance of side effects with this medicine. Ask your doctor or pharmacist for more details.

If you also take certain other drugs to lower your cholesterol (bile acid-binding resins such as cholestyramine or colestipol), take atorvastatin at least 1 hour before or at least 4 hours after taking these medications. These products can react with atorvastatin, preventing its full absorption.

Take this medication regularly in order to get the most benefit from it. Remember to take it at the same time each day. Keep taking this medication even if you feel well. Most people with high cholesterol or triglycerides do not feel sick.

It is very important to continue to follow your doctor’s advice about diet and exercise. It may take up to 4 weeks before you get the full benefit of this drug.

Side Effects

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.

A very small number of people taking atorvastatin may have mild memory problems or confusion. If these rare effects occur, talk to your doctor.

Rarely, statins may cause or worsen diabetes. Talk to your doctor about the benefits and risks.

This drug may rarely cause muscle problems (which can rarely lead to very serious conditions called rhabdomyolysis and autoimmune myopathy). Tell your doctor right away if you develop any of these symptoms during treatment and if these symptoms last after your doctor stops this drug: muscle pain/tenderness/weakness (especially with fever or unusual tiredness), signs of kidney problems (such as change in the amount of urine).

This medication may rarely cause liver problems. Tell your doctor right away if you develop symptoms of liver problems, including: nausea/vomiting that doesn’t stop, yellowing eyes/skin, dark urine, stomach/abdominal pain.

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 atorvastatin, 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: liver disease, kidney disease, alcohol use.

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

Limit alcoholic beverages. Daily use of alcohol may increase your risk for liver problems, especially when combined with atorvastatin. Ask your doctor or pharmacist for more information.

Older adults may be more sensitive to the side effects of this drug, especially muscle problems.

During pregnancy, this medication should be used only when clearly needed. It may harm an unborn baby. Discuss the risks and benefits with your doctor.

It is unknown if this medication passes into breast milk. Because of the possible risk to the infant, breast-feeding while using this drug is not recommended. Consult your doctor before breast-feeding.

Interactions

See also How to Use section.

Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor’s approval.

Some products that may interact with this drug include: daptomycin, gemfibrozil.

Other medications can affect the removal of atorvastatin from your body, which may affect how atorvastatin works. Examples include glecaprevir plus pibrentasvir, telithromycin, ritonavir, among others.

Do not take any red yeast rice products while you are taking atorvastatin because some red yeast rice products may also contain a statin called lovastatin. Taking atorvastatin and red yeast rice products together can increase your risk of serious muscle and liver problems.

Does Atorvastatin 20 Mg/5 Ml (4 Mg/Ml) Oral Suspension interact with other drugs you are taking?

Enter your medication into the WebMD interaction checker

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/triglyceride levels, liver function) should be done while you are taking this medication. Keep all medical and lab appointments. Consult your doctor for more details.

If you miss a dose, take it as soon as you remember unless it is more than 12 hours after the time you usually take the dose. In that case, 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. Store the suspension form in the original container. Discard the suspension form 60 days after opening the bottle, even if there is medication left. 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.

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Drug Survey

Are you currently using Atorvastatin 20 Mg/5 Ml (4 Mg/Ml) Oral Suspension?

This survey is being conducted by the WebMD marketing sciences department.

Selected from data included with permission and copyrighted by First Databank, Inc. This copyrighted material has been downloaded from a licensed data provider and is not for distribution, except as may be authorized by the applicable terms of use.

CONDITIONS OF USE: The information in this database is intended to supplement, not substitute for, the expertise and judgment of healthcare professionals. The information is not intended to cover all possible uses, directions, precautions, drug interactions or adverse effects, nor should it be construed to indicate that use of a particular drug is safe, appropriate or effective for you or anyone else. A healthcare professional should be consulted before taking any drug, changing any diet or commencing or discontinuing any course of treatment.

How does atorvastatin affect testosterone and other hormone levels in men and women?

Relevance

Statins are one of the most commonly prescribed drug classes, and atorvastatin is the most commonly used drug in this class. People take statins to lower their blood cholesterol and reduce their risk of heart disease. However, statins can also lower testosterone and other androgens (male sex hormones). These hormones play an important role in male and female health and development.

What have we done?

We wanted to evaluate the effect of atorvastatin on testosterone and other androgens. We searched the medical literature for all studies that compared the effects of atorvastatin at different doses with placebo or no treatment in men and women, and reported on their testosterone and other androgen levels. We looked for studies in which treatment decisions were randomized. This type of study usually provides the most reliable evidence about the effects of treatment. People of any age could take part in the studies.

After identifying these studies, we compared the results and summarized the evidence from all studies. We then assessed our confidence in this evidence (“certainty of evidence”) based on factors such as study methods and size, and the consistency of results across studies.

What did we find?

We found six studies with 265 participants. The studies were carried out in China, Finland, Iran, Turkey, Great Britain and the USA.

Evidence from four studies suggests that atorvastatin may have a potential beneficial effect in women with polycystic ovary syndrome (PCOS), a group of symptoms that may develop in women with higher than normal androgen levels. In women with PCOS, atorvastatin reduced total testosterone and other androgens.

We found two studies in men in which atorvastatin had no significant effect on total testosterone levels.

What does this mean?

The certainty of evidence for all outcomes ranged from low to very low. Our statistical estimates of the effect of atorvastatin on testosterone and other androgens in men and women may differ greatly from the true effects. More research is needed to answer this important question.

How relevant is this evidence?

The evidence from this review is current to November 2020.

If you found this evidence helpful, please consider donating to Cochrane. We are a charity that produces accessible evidence to help people make health and care decisions.

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Translation notes:

Translation: Kovalenko Alena Sergeevna. Editing: Yudina Ekaterina Viktorovna. Russian translation project coordination: Cochrane Russia – Cochrane Russia, Cochrane Geographic Associated to Cochrane Nordic. For questions related to this translation, please contact us at: cochranerussia@gmail. com.

Statins and why you shouldn’t be afraid of them,

March 29, 2017

Why should you take statins and why shouldn’t you be afraid of them?

Statins are the main class of drugs used to treat patients with hyperlipidemia and atherosclerosis.

Over the past 15 years, dozens of randomized clinical trials have been conducted with statins. According to their results, a significant reduction in cardiovascular and overall mortality was shown, regardless of gender, age, and baseline cholesterol levels.

Currently, 6 drugs of this class are registered in the Russian Federation: atorvastatin, lovastatin, simvastatin, pravastatin, rosuvastatin and fluvastatin.

Mechanism of action and pharmacological effects.

Statins have both lipid and non-lipid (pleiotropic) effects, which include anti-inflammatory, anti-proliferative and antioxidant effects. The reduction in LDL-C levels is dose-dependent with the statin. Each doubling of the dose results in an additional 6% reduction in LDL-C (rule of six). The effectiveness of different statins in lowering LDL-C levels is not the same. Each patient’s response to statin therapy may be different.

The effect of statins on levels of TG and High Density CS-L depends on their baseline values. This is due to the fact that along with a decrease in the level of LDL-C, statins intensify the process of catabolism of VLDL and LPP, which contain TG. Statins reduce TG levels by an average of 15-20%.

Pharmacokinetics of statins.

The main site of pharmacological action of all statins – is the liver. Minimal excretion of statins by the kidneys is observed in atorvastatin and fluvastatin. This circumstance must be taken into account when prescribing statins to patients with chronic kidney disease. The maximum plasma half-life of rosuvastatin (19hours) and atorvastatin (14 hours), which explains their more pronounced lipid-lowering effect compared to other statins.

Impact of statin therapy on cardiovascular morbidity and mortality.

Results from randomized clinical trials with statins demonstrated a significant reduction in cardiovascular mortality in both primary and secondary prevention trials. These studies, which lasted at least 5 years, involved over 100,000 patients. The decrease in the level of LDL-C on statin monotherapy was accompanied by a significant decrease in the incidence of complications of atherosclerosis, including cardiovascular death, non-fatal and fatal Myocardial infarction, MI, and peripheral atherosclerosis.

Statins and the liver.

Patients with chronic liver disease, nonalcoholic steatohepatitis, or fatty liver disease with normal liver enzymes should not be treated with statins.

Dietary recommendations for lowering total cholesterol and LDL cholesterol