====== Simvastatin (Zocor®) ======

<WRAP right 300px>
<WRAP infobox>
^ Drug Overview | {{ :cardio:lipids:simvastatin.svg |}}|
| Drug Class | [[cardio:lipids:start|Statins]] |
| Mechanism | HMG-CoA Reductase Inhibitor |
| Primary Uses | [[cardio:lipids:hyperlipidemia|Hyperlipidemia]]; [[cardio:lipids:ascvd|ASCVD Prevention]] |
| Route | Oral |
| Dose Range | 10–40 mg daily |
| Intensity | Low–Moderate |
| LDL Reduction | 25–45% |
| Metabolism | CYP3A4 |
| Half-life | ~2–3 hours (active metabolites longer) |
| Elimination | Hepatic |
| Renal Adjustment | No (caution in severe CKD) |
| Black Box Warning | No |
| FDA Approval | 1991 |
</WRAP>
</WRAP>

===== Overview =====

Simvastatin is a first-generation [[cardio:lipids:start|statin]] used for LDL reduction and ASCVD prevention.

It is less potent than [[cardio:lipids:atorvastatin|Atorvastatin]] and [[cardio:lipids:rosuvastatin|Rosuvastatin]], and carries a higher drug–drug interaction risk due to CYP3A4 metabolism.

The 80 mg dose is no longer recommended due to increased myopathy risk.

<WRAP clear></WRAP>

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===== Mechanism of Action =====

Primary Target:
  * HMG-CoA reductase (rate-limiting step in hepatic cholesterol synthesis)

Physiologic Effects:
  * ↓ Hepatic cholesterol production
  * ↑ LDL receptor expression
  * ↑ Circulating LDL clearance

Net Effect:
  * Moderate LDL reduction
  * Reduced cardiovascular events

LDL lowering is dose-dependent.

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===== Indications =====

  * [[cardio:lipids:hyperlipidemia|Hyperlipidemia]]
  * [[cardio:lipids:ascvd|ASCVD prevention]]
  * Secondary prevention after:
      * [[cardio:ischemia:mi|Myocardial Infarction]]
      * [[cardio:ischemia:stroke|Ischemic Stroke]]

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===== Dosing =====

Low-Intensity:
  * 10 mg daily

Moderate-Intensity:
  * 20–40 mg daily

Important:
  * 80 mg dose should NOT be initiated
  * Use 80 mg only if patient has tolerated long-term without adverse effects

Dose selection is based on ASCVD risk category.

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===== Pharmacokinetic Highlights =====

  * Lipophilic statin
  * Extensively metabolized by CYP3A4
  * Higher drug–drug interaction burden
  * Shorter half-life compared to [[cardio:lipids:atorvastatin|Atorvastatin]] and [[cardio:lipids:rosuvastatin|Rosuvastatin]]

Due to lipophilicity, may have greater muscle penetration.

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===== Adverse Effects =====

Muscle:
  * Myalgias
  * Myositis
  * Increased risk of rhabdomyolysis (dose-dependent)

Hepatic:
  * Mild ALT elevation

Metabolic:
  * Slight increase in diabetes risk

Myopathy risk increases with:
  * High dose (especially 80 mg)
  * CYP3A4 inhibitors
  * Combination with [[cardio:lipids:fibrates:start|Fibrates]] (especially [[cardio:lipids:gemfibrozil|Gemfibrozil]])

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===== Drug Interactions =====

High interaction risk due to CYP3A4 metabolism.

Avoid or use caution with:
  * Macrolide antibiotics
  * Azole antifungals
  * Protease inhibitors
  * Grapefruit juice

Higher myopathy risk when combined with:
  * [[cardio:lipids:fibrates:start|Fibrates]]
  * [[cardio:lipids:niacin|Niacin]]
  * [[cardio:lipids:atorvastatin|Other CYP3A4-metabolized statins]]

Compared to:
  * [[cardio:lipids:rosuvastatin|Rosuvastatin]] — higher interaction burden
  * [[cardio:lipids:pravastatin|Pravastatin]] — significantly higher interaction burden

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===== Monitoring =====

  * Lipid panel (4–12 weeks after initiation)
  * Baseline liver enzymes
  * Monitor for muscle symptoms

CK only if symptomatic.

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===== Comparison Within Class =====

Compared to [[cardio:lipids:atorvastatin|Atorvastatin]]:

  * Less potent
  * Higher CYP interaction risk
  * Lower LDL reduction at maximal dose

Compared to [[cardio:lipids:rosuvastatin|Rosuvastatin]]:

  * Significantly less potent
  * More drug interactions
  * Shorter half-life

Clinical Role:
  * Appropriate moderate-intensity option
  * Less favored when high-intensity therapy is indicated

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===== High-Yield Pearls =====

  * Avoid initiating 80 mg dose
  * CYP3A4 interactions are clinically significant
  * Lipophilic statin with moderate potency
  * Consider alternative statins in polypharmacy patients
  * Still effective for moderate-risk ASCVD prevention

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===== Related =====

  * [[cardio:lipids:start|Statins]]
  * [[cardio:lipids:atorvastatin|Atorvastatin]]
  * [[cardio:lipids:rosuvastatin|Rosuvastatin]]
  * [[cardio:lipids:pravastatin|Pravastatin]]
  * [[cardio:intro:start|Cardiovascular Pharmacology]]