REPATHA

Indications

• Primary hypercholesterolemia
• Mixed dyslipidemia
• Homozygous familial hypercholesterolemia (in combination with other lipid-lowering therapies)
• Established atherosclerotic cardiovascular disease (as an adjunct to diet and maximally tolerated statin therapy)

Dosage

Children: For children aged 12 to 17 years, the initial dose is 420 mg subcutaneously every month. If necessary, the dose can be increased to

Adults: The usual adult dose is 140 mg subcutaneously every two weeks or 420 mg once a month. The exact dosing regimen may vary based on individual patient response and treatment goals.

Mechanism of action

Evolocumab binds to PCSK9, preventing it from interacting with LDL receptors on liver cells. This inhibition leads to increased LDL receptor availability on the hepatocyte surface, enhancing the clearance of LDL cholesterol from the plasma.

Pharmacodynamics

The pharmacodynamic effects of evolocumab are primarily demonstrated through its ability to lower LDL cholesterol levels. Clinical trials have shown that evolocumab can reduce LDL cholesterol by approximately 50% to 60% when administered in conjunction with statin therapy. Its effects on lipid profiles are dose-dependent and can improve cardiovascular outcomes in high-risk populations.

Pharmacokinetics

Evolocumab is administered via subcutaneous injection, with a bioavailability of approximately 73%. It has a half-life of about 17 to 20 days, allowing for infrequent dosing schedules. The drug is primarily metabolized through proteolytic pathways, similar to endogenous immunoglobulins, and it is not significantly excreted in the urine. Peak plasma concentrations are reached within 3 to 5 days after administration.

Contra-indications

• Aortic stenosis
• Cardiac tamponade
• Severe hypersensitivity to evolocumab or any of its excipients
• Active liver disease or unexplained persistent elevations of liver enzymes
• Pregnancy

Adverse effects

• Injection site reactions
• Nasopharyngitis
• Myalgia
• Back pain
• Fatigue
• Dizziness
• Elevated liver enzymes
• Allergic reactions

Interactions

• No significant drug interactions have been identified
• Monitor for potential interactions with other lipid-lowering therapies

Precautions

• Caution in patients with a history of hypersensitivity reactions
• Monitor liver function tests before starting and periodically during treatment
• Discontinue if persistent elevation of liver enzymes occurs
• Consider risk of muscle-related adverse effects in patients with a history of myopathy

Pregnancy

Evolocumab is not recommended during pregnancy due to a lack of safety data.

Breast-feeding

It is not known if evolocumab is excreted in human milk. Caution should be exercised when administering to a breastfeeding woman.

Storage

Store in a refrigerator (2°C to 8°C). Do not freeze. If necessary, the pre-filled pen may be stored at room temperature (up to 25°C) for up to 30 days. Protect from light.

Formulations

• Evolocumab 140 mg/mL solution for injection in a pre-filled pen
• Evolocumab 420 mg/3.5 mL solution for injection in a pre-filled pen