Alirocumab

Alirocumab is a human monoclonal antibody against PCSK9 given by subcutaneous injection every 2 or 4 weeks. It lowers LDL cholesterol by 50% to 60% on top of a statin and lowers heart attacks and strokes in people with recent acute coronary syndrome. 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 (IgG1).

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 stays low while injections continue and returns to baseline within weeks of stopping.

Pharmacokinetics. Subcutaneous bioavailability about 85%. Peak at 3 to 7 days. Half life about 17 to 20 days at steady state. Cleared by target mediated binding and by proteolysis; no CYP metabolism. No kidney clearance.

Primary hypercholesterolaemia (including heterozygous familial) and established cardiovascular disease, adult.

• 75 mg SC every 2 weeks; increase to 150 mg every 2 weeks if the LDL response is inadequate after 4 to 8 weeks.

• Or 300 mg SC every 4 weeks (monthly) as an alternative to 150 mg every 2 weeks.

• Give with the maximum tolerated statin and ezetimibe.

Homozygous familial hypercholesterolaemia, adult. 150 mg every 2 weeks (specialist).

Heterozygous familial hypercholesterolaemia in children aged 8 years and over (specialist). Under 50 kg: 40 mg every 2 weeks or 80 mg every 4 weeks; 50 kg or more: 75 mg every 2 weeks or 150 mg every 4 weeks.

Kidney impairment. No adjustment.

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

Contraindications. Hypersensitivity to alirocumab or its ingredients.

Warnings. Hypersensitivity reactions including vasculitis and nummular eczema; injection site reactions; neurocognitive events (not confirmed); low LDL levels (below 0.65 mmol/L) are safe but should be checked; antibody formation (rare, 1% to 5%); needle cap contains latex in some presentations.

Adverse effects. Injection site reactions (redness, itching, swelling), nasopharyngitis, influenza like illness, urinary tract infection, diarrhoea, itching.

Interactions. No clinically important interactions. Statins: LDL lowering is additive (alirocumab slightly raises statin clearance).

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 or syringe 75 mg/mL, 150 mg/mL and 300 mg/2 mL.

Administration. SC injection into the thigh, abdomen or upper arm, rotating sites. Store at 2 to 8 degrees C in the original carton; if needed, it can be kept at room temperature up to 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 to 40 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 8 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; changing the dose before 4 to 8 weeks; giving 300 mg monthly then 75 mg twice monthly by mistake; shaking the pen.