danaparoid sodium: clinical use

Prescribing considerations

• Confirm the indication and assess bleeding risk, renal and hepatic function, platelet history, recent heparin exposure and planned invasive or neuraxial procedures.
• Danaparoid anti-Xa units are not interchangeable with those of heparin or low-molecular-weight heparins.
• Renal elimination may cause accumulation in renal impairment.
• There is no established reliable reversal agent; protamine only partially neutralises anticoagulant activity.
• Experience in children is limited, and interaction studies were conducted only in adults.

Contraindications and cautions

• Hypersensitivity to danaparoid, an excipient or sulphite.
• Uncontrollable active bleeding, severe uncontrolled hypertension or recent haemorrhagic stroke.
• Active gastroduodenal ulcer, diabetic retinopathy or acute bacterial endocarditis.
• Severe haemorrhagic diathesis or severe renal or hepatic insufficiency, subject to the SmPC's exception where heparin-induced thrombocytopenia is present and no alternative is available.
• Spinal, epidural or locoregional anaesthesia in the product-specific treatment setting described by the SmPC.

Monitoring

• Monitor clinically for bleeding, thrombosis and hypersensitivity.
• Check platelet counts serially because antibody-mediated thrombocytopenia and clinical cross-reactivity can occur.
• Routine anti-Xa monitoring is generally unnecessary, but may be appropriate with renal impairment, high body weight or concern about accumulation or inadequate effect.
• If anti-Xa activity is measured, use a suitable chromogenic assay calibrated with danaparoid; routine clotting assays are relatively insensitive.

Clinical pharmacology

Danaparoid is a non-heparin mixture of heparan, dermatan and chondroitin sulphates. Its antithrombotic action is predominantly antithrombin-mediated factor Xa inhibition, with comparatively little direct antithrombin activity. Subcutaneous bioavailability is high, the anti-Xa effect is prolonged, and elimination is mainly renal.

Formulation and product differences

• The selected UK product is a clear, colourless to pale-yellow solution in glass ampoules for subcutaneous injection or intravenous infusion.
• It contains sodium sulphite, which can cause bronchospasm or anaphylaxis in sulphite-sensitive people, particularly those with asthma.
• It may be added only to compatible infusion fluids specified in the SmPC and must not be administered intramuscularly.
• The active material is derived from porcine intestinal mucosa.