====== Alirocumab (Praluent®) ======

<WRAP right 300px>
<WRAP infobox>
^ Drug Overview | {{:cardio:lipids:screenshot_2026-02-13_at_12.58.06 pm.png?400 |}}|
| Drug Class | [[cardio:lipids:pcsk9:start|PCSK9 Inhibitors]] |
| Mechanism | PCSK9 Monoclonal Antibody |
| Primary Uses | [[cardio:lipids:ascvd|ASCVD]]; [[cardio:lipids:familial_hypercholesterolemia|Familial Hypercholesterolemia]] |
| Route | Subcutaneous Injection |
| Dosing Interval | Every 2–4 weeks |
| LDL Reduction | ~50–60% |
| Metabolism | Reticuloendothelial degradation |
| Elimination | Proteolytic catabolism |
| Renal Adjustment | No |
| Hepatic Adjustment | No |
| Black Box Warning | No |
| FDA Approval | 2015 |
</WRAP>
</WRAP>

===== Overview =====

Alirocumab is a fully human monoclonal antibody that inhibits circulating PCSK9.

It is used in high-risk patients who require additional LDL reduction beyond maximally tolerated [[cardio:lipids:start|statins]] and [[cardio:lipids:ezetimibe|ezetimibe]].

It significantly reduces LDL cholesterol and improves cardiovascular outcomes.

<WRAP clear></WRAP>

--------------------------------------------------------------------

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

Normal Physiology:
  * PCSK9 binds LDL receptors
  * Promotes receptor degradation
  * ↓ LDL receptor recycling
  * ↑ Circulating LDL

Alirocumab Effect:
  * Binds circulating PCSK9
  * Prevents LDL receptor degradation
  * ↑ LDL receptor recycling
  * ↑ LDL clearance

Net Result:
  * 50–60% additional LDL reduction
  * Reduced ASCVD events

See:
  * [[cardio:lipids:pcsk9:start|PCSK9 Inhibitors]]
  * [[cardio:lipids:start|Statins]]

--------------------------------------------------------------------

===== Indications =====

  * Clinical [[cardio:lipids:ascvd|ASCVD]] requiring further LDL reduction
  * [[cardio:lipids:familial_hypercholesterolemia|Heterozygous Familial Hypercholesterolemia]]
  * LDL not at goal despite:
      * Maximally tolerated [[cardio:lipids:start|statin]]
      * ± [[cardio:lipids:ezetimibe|ezetimibe]]

Used primarily in secondary prevention.

--------------------------------------------------------------------

===== Dosing =====

Typical Dosing:

  * 75 mg subcutaneously every 2 weeks
  * May increase to 150 mg every 2 weeks if needed

Alternative:
  * 300 mg every 4 weeks (selected patients)

No renal or hepatic adjustment required.

--------------------------------------------------------------------

===== Clinical Outcomes =====

Demonstrated:

  * Significant LDL reduction (~50–60%)
  * Reduced major adverse cardiovascular events (MACE)

Typically lowers LDL to <55 mg/dL in very high-risk patients.

--------------------------------------------------------------------

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

Common:

  * Injection site reactions
  * Mild upper respiratory symptoms

Rare:

  * Hypersensitivity reactions

No significant myopathy signal.

No clinically significant hepatic toxicity.

--------------------------------------------------------------------

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

No CYP-mediated interactions.

Safe to combine with:

  * [[cardio:lipids:start|Statins]]
  * [[cardio:lipids:ezetimibe|Ezetimibe]]

Minimal pharmacokinetic interaction risk.

--------------------------------------------------------------------

===== Monitoring =====

  * Lipid panel 4–12 weeks after initiation
  * Assess LDL response
  * Monitor for injection site reactions

--------------------------------------------------------------------

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

Compared to [[cardio:lipids:evolocumab|Evolocumab]]:

  * Similar LDL reduction
  * Similar outcome data
  * Similar dosing frequency

Compared to [[cardio:lipids:inclisiran|Inclisiran]]:

  * More frequent dosing (every 2–4 weeks)
  * Monoclonal antibody vs siRNA mechanism
  * Faster onset

Clinical Role:
  * Add-on therapy after statin ± ezetimibe
  * Very high-risk ASCVD patients

--------------------------------------------------------------------

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

  * ~50–60% LDL reduction
  * Injectable therapy
  * Minimal drug interactions
  * Additive to statin therapy
  * Insurance authorization often required

--------------------------------------------------------------------

===== Related =====

  * [[cardio:lipids:pcsk9:start|PCSK9 Inhibitors]]
  * [[cardio:lipids:evolocumab|Evolocumab]]
  * [[cardio:lipids:inclisiran|Inclisiran]]
  * [[cardio:lipids:ezetimibe|Ezetimibe]]
  * [[cardio:lipids:start|Statins]]
  * [[cardio:intro:start|Cardiovascular Pharmacology]]