10% Off All Tests - Spring 2025

PGx Testing

Resources

Buy Now

Simvastatin

Taken at night; higher risk of muscle side effects.

Introduction to Simvastatin

Simvastatin, like all statins, continues to surprise scientists and doctors—sometimes in positive ways, and sometimes in negative ones. Its positive “extras” are known as pleiotropic effects—beneficial actions that go beyond simply lowering cholesterol, such as improving blood vessel function or reducing inflammation (7). However, like other statins, simvastatin can also cause side effects, particularly muscle-related symptoms, which are an important consideration for patients and clinicians alike.

In both individual and meta-analytic studies, simvastatin has been shown to reduce sympathetic nervous system activity—the system responsible for the body’s "fight or flight" response during stress or physical effort—resulting in lower blood pressure (16, 17). While researchers are still investigating how significant this effect is in daily clinical care, it adds to the growing recognition of statins as medications with multiple modes of action, not just cholesterol control.

Considerations for Patients Taking Simvastatin

When prescribing or taking simvastatin, it’s important to consider not only its cholesterol-lowering properties but also its broader impact on heart health—and the timing of when it’s taken. Like other statins, simvastatin has effects that extend well beyond lipid control, many of which contribute meaningfully to reducing the risk of heart attacks, strokes, and other cardiovascular events (2, 3, 4, 7).

Statins Do Much More Than Just Lower Cholesterol

An increasing body of evidence shows that statins reduce mortality across a wide range of cardiovascular conditions—including heart failure—and even lessen the extent of heart damage after a heart attack. Interestingly, many of these benefits occur independently of cholesterol levels, thanks to the pleiotropic actions of statins: additional effects such as anti-inflammatory activity and improved vascular function. These added benefits include (2, 3, 4, 7):

Stabilising cholesterol deposits (atherosclerotic plaques), making them less likely to rupture and trigger blood clots. This occurs through mechanisms linked to inflammation, oxidative stress (free radicals), and immune regulation.
Improving blood vessel function by enhancing their ability to dilate and reducing blood viscosity, leading to better circulation.
Enhanced anti-inflammatory action in lipophilic statins: Simvastatin, a lipophilic statin, tends to show stronger anti-inflammatory and lipid-lowering effects compared to hydrophilic statins such as rosuvastatin and pravastatin.

The Body Makes More Cholesterol at Night

Cholesterol production in the liver follows a natural circadian rhythm—peaking between 8 p.m. and midnight, with synthesis rates up to four times higher than in the morning (12). Because of this, taking statins at night—especially short-acting ones like simvastatin—can help maximise their cholesterol-lowering effects.

Explore PGX for Cardiovascular

Why Have I Been Prescribed Statins?

Statins like simvastatin may be prescribed for several reasons (5):

Elevated cholesterol levels that haven’t improved enough through lifestyle changes such as a healthy diet and regular physical activity.
Primary prevention of cardiovascular events in people at high risk of developing heart disease or having a stroke.
Secondary prevention of cardiovascular events—such as after a heart attack or stroke. While this is a common use, it may be considered off-label in some regions. However, it is strongly supported by clinical evidence.

Simvastatin Doses

How and when to take it:

Simvastatin is usually taken once daily at night, as this aligns with the body’s natural rhythm of cholesterol production. Dosage depends on the reason for prescribing and may be adjusted over time, typically at 4-week intervals, based on your cholesterol levels and overall risk profile (5). Common dosing scenarios:

Elevated cholesterol not responding to diet and exercise:
Start with 10–20 mg at night. The dose may be adjusted up to a maximum of 80 mg per day, with increases made at least every 4 weeks.
Familial hypercholesterolemia:
Start with 40 mg at night, with potential increases up to 80 mg, adjusted at 4-week intervals.
Prevention of cardiovascular events (e.g. heart attack or stroke):
Typical starting dose is 20–40 mg at night, with adjustments up to a maximum of 80 mg, reviewed every 4 weeks as needed.

Simvastatin Side Effects

Simvastatin is generally well tolerated and widely prescribed. However, like all medications, it can cause side effects in some individuals. Being aware of both common and less common side effects can help you monitor your health and know when to seek advice.

Muscle-Related Side Effects

Simvastatin is a lipophilic statin, meaning it easily enters body tissues such as muscles and the brain. This property helps it lower cholesterol and reduce inflammation—but it also increases the chance of certain side effects.

Muscle-related symptoms are the most common side effects of statin therapy. Simvastatin, especially at higher doses, is associated with a greater risk of muscle side effects than some other statins (5, 6, 7).

Observe the Condition of Your Muscles

If you experience muscle pain, soreness, or tenderness that isn’t clearly linked to physical activity or a recent viral infection, speak with your pharmacist or GP. These could be early signs of statin-associated muscle symptoms (SAMS).

Muscle-related side effects occur in approximately 10–29% of patients (6) and are the leading reason people stop taking statins. The most commonly affected areas are the thighs, calves, and hip flexors, and symptoms are usually symmetrical (6).

Who Is at Greater Risk?

Certain factors increase the risk of developing muscle-related side effects from statins (11):

Age over 60
Diabetes
Hypothyroidism
Multisystem diseases
Vitamin D deficiency
Excessive or strenuous physical activity
Alcohol consumption
Major surgery
Higher statin doses — the strongest risk factor, increasing the likelihood sixfold compared to lower doses

Memory Issues

There are also increasing reports of memory issues in people taking statins—especially at higher doses. While the clinical evidence is mixed, if you notice memory lapses, poor focus, or low mood after starting or adjusting your dose, consult your pharmacist or GP (8, 9).

Myasthenia Gravis – A New Warning

If you have myasthenia gravis and notice a worsening of your symptoms while taking simvastatin, speak with your GP. Though rare, statins have been reported to aggravate this condition, and any changes should be reviewed promptly (5).

A Note on High-Dose Simvastatin (80 mg)

The 80 mg dose of simvastatin is significantly more likely to cause muscle-related side effects. This high dose is generally reserved for people with severe hypercholesterolemia who have not responded adequately to lower doses (5). It should only be used under close medical supervision.

Other Possible Side Effects

In addition to muscle-related symptoms, simvastatin may cause other side effects. These are generally less common but can still affect your daily life—especially if they persist (5):

Painful joints
General lack of energy or strength
Dizziness
Sleep disturbances
Liver disorders
Memory problems

Understanding your individual risk of side effects—especially from statins like simvastatin—can be challenging. A pharmacogenomics (PGx) test in the UK can help identify how your genes influence your response to medications like simvastatin, supporting safer, more personalised medicine through genetic testing for medication response.

Explore PGX for Cardiovascular

How Your Body and Genes Process Simvastatin

Simvastatin’s journey through the body—how it’s absorbed, distributed, metabolised, and eliminated—is shaped by both your biology and your genetics. These areas of research are known as pharmacokinetics and pharmacogenetics, and they help explain why people can respond so differently to the same medication (10).

Absorption

Simvastatin is primarily absorbed into liver cells via a protein called OATP1B1. Genetic differences in the SLCO1B1 gene (which encodes this transporter) can significantly affect how much of the drug reaches the liver, altering both its effectiveness and the risk of side effects.

Metabolism

Simvastatin is extensively metabolised in the liver and gut, with an absolute bioavailability of less than 5%. Most of this processing occurs via the enzymes CYP3A4 and CYP3A5, with smaller contributions from CYP2C8 and CYP2C9. Clinical studies also suggest that CYP2D6 polymorphisms may impact how well simvastatin works—and how well it’s tolerated.

Personalising Simvastatin with Pharmacogenetics

Genetic variation can influence both how effectively simvastatin works and how likely it is to cause side effects. One of the most important genes involved is SLCO1B1, which encodes the OATP1B1 transporter—a protein responsible for moving statins into liver cells, where they carry out their cholesterol-lowering effects (10, 11).

The Role of SLCO1B1 in Statin Response (10, 11):

SLCO1B1 is essential for liver uptake of statins.
Reduced function variants can lead to increased statin levels in the bloodstream, raising the risk of muscle-related side effects.
The c.521T>C variant (rs4149056) is strongly linked with statin-induced myopathy.
People with two copies of the C allele (C/C genotype) have a significantly higher risk of muscle damage from simvastatin and lovastatin, including rhabdomyolysis in rare cases.

Related Medications:

Pharmacogenetic considerations also apply to other statins, particularly:

Atorvastatin
Simvastatin
Rosuvastatin
Pravastatin

Explore PGX for Cardiovascular

References