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Atorvastatin vs. Simvastatin – What’s the difference?

Drug vector

What are atorvastatin and simvastatin?

People inherently associate cholesterol with something “bad” that poses a health threat. That is not entirely accurate. Our bodies need cholesterol to build cells, but cholesterol can pose a problem when there is an excessive amount of it. Elevated cholesterol leads to an increased risk of cardiovascular diseases, such as heart disease and stroke [3].

Both atorvastatin and simvastatin belong to a drug class commonly referred to as the “statins.” Statins work by inhibiting 3-hydroxy-3-methyl-glutaryl-coenzyme A, also known as HMG-CoA reductase, the rate-limiting step in cholesterol synthesis [2]. As a result, cholesterol production in the liver reduces. By their mechanism of action, statins are classified as the HMG-CoA reductase inhibitors. These agents are the drug of choice for lipid-lowering therapy in patients at increased risks for cardiovascular diseases and stroke.

What are atorvastatin and simvastatin prescribed for?

Besides being the drug of choice for patients with high cardiovascular disease risks, statins are also prescribed for patients who already have existing cardiovascular disease; they have shown to reduce the risk for mortality, heart attack, and stroke among this patient population. Current guidelines also recommend statins as the lipid-lowering therapy in patients with diabetes to prevent coronary events with this patient population. Both atorvastatin and simvastatin are approved by the FDA as lipid-lowering therapy. However, there are some differences between the two agents that this article will be expounding on.

What are the main differences between atorvastatin and simvastatin?

The brand name of atorvastatin is Lipitor. Both atorvastatin and its brand name products are available in the tablet dosage form. Atorvastatin is available in 10 mg, 20 mg, 40 mg, and 80 mg. The common starting dose of atorvastatin is 10 to 20 mg once daily or 40 mg once daily for individuals with higher risks. Usual dosage ranges from 10 to 80 mg once daily based on lab results, patient’s tolerance, and prescribers’ clinical judgment [1]. Atorvastatin can be taken at any time during the day with or without food [2].

The brand name of simvastatin is Zocor. Simvastatin is available in 5mg, 10 mg, 20 mg, 40 mg, and 80 mg. The standard dose of simvastatin is 40 mg once daily every evening, with the range of 5 mg to 40 mg [1,4]. Simvastatin is recommended to be taken in the evening [2]. One unique fact about simvastatin is that it is available in both oral tablets and oral suspension of 40 m/ 5 mL for patients who have trouble swallowing [2].

Both atorvastatin and simvastatin are metabolized extensively in the liver by CYP3A4 [2]. In other words, CYP3A4’s job is to break down atorvastatin and simvastatin. CYP3A4 is also known as cytochrome P450 3A4, an abundant enzyme that resides in the liver and gastrointestinal tract; this enzyme is responsible for a large number of medications administered. If your medication regimen includes atorvastatin and simvastatin, it is crucial to inform your doctor about any new medicine you plan on taking, including over-the-counter and herbal products.

Can I have grapefruit when taking statins?

One common myth is that grapefruits and grapefruit juice must be avoided at all costs if your medication regimen includes a statin. This is only half true. As mentioned above, both simvastatin and atorvastatin are metabolized by CYP3A4. Grapefruit and grapefruit products reduce the activity of the enzyme CYP3A4. As a result, atorvastatin and simvastatin stay in the body longer, resulting in increased side effects and toxicity. So, should you avoid grapefruit if you take atorvastatin or simvastatin? The answer is yes. Should grapefruit products be avoided with all statins? No, there are other statins in the market whose efficacy and safety are not as gravely affected by grapefruit as atorvastatin and simvastatin due to their different mechanisms of action. However, if grapefruit is an essential part of your diet, it is acceptable to enjoy a small glass of grapefruit juice several hours after atorvastatin administration time [2]. It is advised to avoid grapefruit altogether with simvastatin [2]. It is important to know that eating a small portion of grapefruit is even less risky than drinking grapefruit juice since it takes several grapefruits to make one glass of juice [5]. Consult with your doctor or pharmacist if you have any questions about administration time and the appropriate portion of grapefruit and grapefruit juice. 

Compare and contrast Atorvastatin and Simvastatin

 

Atorvastatin

Simvastatin
Brand nameLipitorZocor
Generic available?Yes - atorvastatinYes - simvastatin
Drug classificationHMG-CoA reductase inhibitorsHMG-CoA reductase inhibitors
Starting dose

10 to 20 mg once daily; 

40 mg once daily for higher risks individuals

40 mg once daily
Dosage range10 to 80 mg once daily5 to 40 mg once daily
Renal dosing?YesYes
Dosage formsOral tabletOral tablet and oral suspension
Drug interactionMajor interaction with CYP3A4Major interaction with CYP3A4
AdministrationAny time during the day with or without foodIn the evening; For oral suspension, administer on an empty stomach
Interaction with grapefruit products?YesYes

Is one agent more effective than the other?

There is no substantial evidence that indicates that one agent is more efficacious than the other.

Both atorvastatin and simvastatin are approved by the FDA for the treatment of hypercholesterolemia and hyperglyceridemia.2 Though, only the oral suspension dosage form of simvastatin is approved by the FDA for the treatment of hyperglyceridemia. Regarding their role in reducing the risk of coronary events such as heart disease and heart attack, atorvastatin and simvastatin oral tablets are approved by the FDA. When it comes to stroke prevention, the FDA approves atorvastatin oral tablets and simvastatin oral suspension for this indication.

Statin dosing is classified into low-intensity, moderate-intensity, and high intensity. Low-intensity statins’ LDL (low-density lipoprotein) lowering is less than 30%, moderate-intensity statins’ LDL lowering is between 30-50%, while high-intensity statins are expected to reduce LDL at 50% or higher [4]. LDL is the “bad” cholesterol that we want to reduce.

 Low-intensityModerate-intensityHigh-intensity
Atorvastatin (Lipitor)None10 to 20 mg40 to 80 mg
Simvastatin (Zocor)10 mg20 to 40 mgNone

Common side effects

Atorvastatin’s common side effects include diarrhea, musculoskeletal or muscle pain, in addition to increased risk of upper respiratory tract infection and urinary tract infection. Simvastatin’s side effect profile includes abdominal pain, constipation, nausea, headache, and upper respiratory tract infection [2].

For any statin in general, muscle pain and gastrointestinal irritation are the most common side effects that often lead to therapy discontinuation by patients. Please discuss any side effects with your doctor so that dosing can be individualized optimally based on your indication and tolerance.

Warnings

Atorvastatin should be used cautiously in patients with a history of renal impairments. For patients with impaired renal functions, atorvastatin’s maximum recommended dose is 10 mg and should be used with caution. For simvastatin, 5 mg is the maximum recommended dose for this patient population.

Use in pregnancy, lactation, and pediatric populations

Atorvastatin and simvastatin are contraindicated during pregnancy and lactation. Both medications have shown fetal and infant risks. Current guidelines recommend working with your doctor about the discontinuation of statin medication for at least three months before becoming pregnant, then staying off statins for the duration of pregnancy (usually 40 weeks) [1].

Both atorvastatin and simvastatin are not approved by the FDA to be used in the pediatric population for any indications [2].

Summary

  • Atorvastatin and simvastatin are similar in efficacy and indications
  • Both medications are not indicated by the FDA to be used in the pediatric population
  • Both medications are contraindicated during pregnancy and lactation. If you are taking atorvastatin or simvastatin and plan to be pregnant in the near future, please discuss with your doctor for discontinuation and tips on non-pharmacological alternatives such as physical activities and dietary changes.
  • Both medications must be used with caution for renally impaired patients.
  • Minimize the number of grapefruit products with atorvastatin and try to avoid it altogether if you take simvastatin
  • Please report any signs or symptoms of muscle pain or aches, especially when accompanied by fever or malaise
  • Be familiar and be able to recognize the signs and symptoms of liver injury including jaundice (yellow of the skin and the white of the eyes), nausea, vomiting, disorientation, confusion, and ascites (swelling of the abdomen).

References:

1. American College of Cardiology/American Heart Association (ACC/AHA) grading system for recommendations

2. DynaMed [Internet]. Ipswich (MA): EBSCO Information Services. 1995 - . Record No. T116844, Statins; [updated 2018 Nov 30, cited 2021 Apr 13]. Available from https://www-dynamed-com.gcsom.idm.oclc.org/topics/dmp~AN~T116844

3. https://www.heart.org/en/health-topics/cholesterol/about-cholesterol

4. https://pharmacist.therapeuticresearch.com/Content/Segments/PRL/2016/Jul/Statin-Dose-Comparison-9914

5. https://www.health.harvard.edu/heart-health/grapefruit-juice-and-statins