Evolocumab

Evolocumab is a human monoclonal antibody against PCSK9 given by subcutaneous injection every 2 weeks or monthly. It lowers LDL cholesterol by about 60% on top of a statin and lowers heart attacks, strokes and coronary revascularisation in people with established cardiovascular disease. It is used in familial hypercholesterolaemia and in high risk patients who do not reach the LDL target on the maximum tolerated statin and ezetimibe. It is expensive and is rarely available in East Africa.

Classification. PCSK9 inhibitor; human monoclonal antibody (IgG2).

Mechanism. Binds circulating PCSK9, stopping it from destroying LDL receptors on liver cells; more LDL receptors remain and clear more LDL from the blood.

Pharmacodynamics. LDL cholesterol falls within 2 weeks, with the full effect at 4 to 8 weeks. LDL returns to baseline within weeks of stopping.

Pharmacokinetics. Subcutaneous bioavailability about 72%. Peak at 3 to 4 days. Half life 11 to 17 days. Cleared by target mediated binding and by proteolysis; no CYP metabolism. No kidney clearance.

Primary hypercholesterolaemia (including heterozygous familial) and established cardiovascular disease, adult. 140 mg SC every 2 weeks, or 420 mg SC once monthly (the two regimens are equal in effect). Give with the maximum tolerated statin and ezetimibe.

Homozygous familial hypercholesterolaemia, adult and children aged 10 years and over. 420 mg SC once monthly; if the response is not enough after 12 weeks, 420 mg every 2 weeks. Patients on apheresis: 420 mg every 2 weeks, given at the end of the apheresis session (specialist).

Heterozygous familial hypercholesterolaemia in children aged 10 years and over (specialist). 140 mg every 2 weeks or 420 mg once monthly.

Kidney impairment. No adjustment.

Liver impairment. Mild to moderate: no adjustment; severe: not studied.

Contraindications. Hypersensitivity to evolocumab or its ingredients.

Warnings. Hypersensitivity reactions including rash and urticaria; injection site reactions; neurocognitive events (not confirmed); low LDL levels are safe; antibody formation (rare); the prefilled pen needle cover contains dry natural rubber (latex) in some presentations.

Adverse effects. Nasopharyngitis, upper respiratory infection, back pain, influenza, injection site reactions, joint pain, nausea.

Interactions. No clinically important interactions. Statins: LDL lowering is additive.

Special groups.

• Pregnancy: avoid unless essential; IgG crosses the placenta, mainly in the third trimester.

• Breastfeeding: avoid unless essential; large proteins pass poorly into milk.

• Patients of African ancestry: no dose change; response is similar.

• Older adults: no adjustment.

• Kidney impairment: no adjustment.

• Liver impairment: mild to moderate: no adjustment.

Formulations. Prefilled pen 140 mg/mL; prefilled syringe 140 mg/mL; on-body infusor 420 mg/3.5 mL.

Administration. SC injection into the thigh, abdomen or upper arm, rotating sites. For the 420 mg monthly dose, give three 140 mg injections within 30 minutes, or use the infusor over 9 minutes. Store at 2 to 8 degrees C in the original carton; it can be kept at room temperature (below 25 degrees C) for up to 30 days in the dark, and must then be used or discarded. Let the pen reach room temperature for 30 minutes before use. Do not shake.

Baseline. Lipid profile, alanine aminotransferase, pregnancy status, a full list of other lipid lowering drugs.

Monitoring. Lipid profile 4 to 12 weeks after starting or changing the dose, then every 6 to 12 months. Injection sites and allergic symptoms.

Stopping. Stop for serious hypersensitivity. LDL returns to baseline within weeks of stopping.

Common prescribing errors. Giving it without a statin or ezetimibe when these could be used; storing outside the cold chain; giving one 140 mg injection when 420 mg is meant; shaking the pen; forgetting that the 420 mg monthly regimen needs three injections.