Crizanlizumab

Crizanlizumab is a humanised monoclonal antibody against P-selectin, given by intravenous infusion to reduce vaso-occlusive crises in sickle cell disease. It is not available or licensed in all regions, and the European authorisation was withdrawn in 2023 after a larger follow-up study failed to confirm benefit; where it is still licensed its value is contested.

Classification. Monoclonal antibody; P-selectin inhibitor.

Mechanism. Blocks P-selectin on endothelium and platelets, preventing adhesion of sickle red cells, leukocytes and platelets to the vessel wall.

Pharmacokinetics. Terminal half-life is about 10 to 11 days. Clearance is by proteolysis, and no hepatic or renal dose adjustment is established.

Sickle cell disease, to reduce the frequency of vaso-occlusive crises (age 16 years and over).

• Dose: 5 mg/kg by intravenous infusion over 30 minutes on week 0 and week 2, then every 4 weeks.
• Maximum: 5 mg/kg for each dose. Loading dose: the week 0 and week 2 doses. Titration: none.
• A missed dose is given as soon as possible: within 2 weeks of the planned date, continue the original schedule; later, give it and restart the 2 week then 4 week interval.
• May be used with or without hydroxyurea.

Adjustments. Kidney and liver: no adjustment established. Weight: dosed on actual weight. Pregnancy and breastfeeding: avoid unless essential.

Contraindications. Hypersensitivity to crizanlizumab or its components.

Adverse effects. Common: nausea, arthralgia, back pain, pyrexia, headache, abdominal pain, diarrhoea, musculoskeletal pain. Infusion-related reactions (fever, chills, nausea, fatigue, back pain, vomiting, pain) occur mainly with the first infusions; anaphylaxis is rare.

Interactions. No important drug interactions. It interferes with automated platelet counts, causing platelet clumping and falsely low values.

Pregnancy and breastfeeding. Avoid unless clearly needed.

Regional points. Availability and cost make routine use in East Africa unlikely; hydroxyurea remains the practical disease-modifying therapy.

Common errors. Relying on automated platelet counts; giving as a rapid bolus; using without hydroxyurea optimisation.

Administration. Dilute in 0.9% sodium chloride or 5% glucose to a final volume of 100 to 250 mL; infuse over 30 minutes through a 0.2 micron in-line filter. Store vials at 2 to 8°C, protected from light; do not shake.

Baseline. Full blood count (collect platelet samples in a citrate tube, or use blood smear confirmation), crisis history, hydroxyurea status.

Monitoring. Observe for infusion reactions during and after the infusion. Review crisis frequency and admissions every 3 months; stop if there is no reduction after 6 to 12 months.

Referral and escalation. Stop for severe infusion reactions or anaphylaxis, give adrenaline 0.5 mg intramuscularly (adults), and refer.