Products
Alirocumab was approved in the United States in 2015 as the first agent in the group of PCSK9 inhibitors in the form of a solution for injection (Praluent). Evolocumab (Repatha) followed as the second agent in the EU, also in 2015.
Structure and properties
PCSK9 inhibitors to date are monoclonal antibodies that must be injected. Small molecules, which can be taken in tablet form, are not yet available.
Effects
PCSK9 inhibitors (ATC C10AX) have lipid-lowering properties. They bind selectively to PCSK9 (proprotein convertase subtilisin kexin type 9). This serine protease binds to LDL-C receptors on the surface of liver cells and directs them to degradation in hepatocyte lysosomes. Inhibition of PCSK9 function increases the concentration of LDL receptors in the cell membrane, resulting in a reduction of LDL-C (low density lipoprotein cholesterol) in the blood as more LDL-C is taken up into liver cells. The effects of PCSK9 inhibitors are shown schematically in the following figure:
Agents
- Alirocumab (Praluent, Regeneron / Sanofi).
- Bococizumab (Pfizer)
- Evolocumab (Repatha, Amgen)
Indications
For the treatment of dyslipidemia (primary/familial hypercholesterolemia, mixed dyslipidemia) and clinically manifest heart disease due to atherosclerosis.
Dosage
According to the SmPC. Antibodies are injected subcutaneously by the patient using a prefilled syringe. The dosing interval depends on the drug and is two weeks for alirocumab, for example.
Contraindications
The drugs are contraindicated in the presence of hypersensitivity. For complete precautions, see the drug label.
Interactions
The potential for drug-drug interactions is considered low. PCSK9 inhibitors do not interact with CYP450 isozymes.
Adverse effects
The most common potential adverse effects include local injection site reactions.
