Donidalorsen sodium: clinical use

Prescribing considerations

• Initiate under supervision of a clinician experienced in diagnosing and managing HAE.
• Ensure patients understand that treatment is preventive and retain access to an appropriate acute-attack plan.
• Data are limited in HAE with normal C1-inhibitor; genetically defined variants outside the kallikrein–kinin pathway are not expected to respond.
• Safety and efficacy have not been established below 12 years of age.
• Clinical data are lacking in moderate or severe hepatic or renal impairment and end-stage renal disease.

Contraindications and cautions

• Hypersensitivity to donidalorsen or any excipient.

Monitoring

• Assess HAE attack control and continued clinical response.
• Be alert to hypersensitivity following administration.
• Review liver tests where clinically appropriate because hepatic-enzyme increases are very common; the product information does not specify a routine testing schedule.
• Report suspected adverse reactions through the Yellow Card Scheme.

Clinical pharmacology

A GalNAc-conjugated, 2′-O-methoxyethyl-modified antisense oligonucleotide that selectively binds prekallikrein mRNA and causes RNase H1-mediated degradation. It is metabolised by nucleases rather than CYP enzymes.

Formulation and product differences

• Clear, colourless-to-yellow solution in a single-use pre-filled pen for subcutaneous injection.
• Keep refrigerated and protected from light. It may be kept at room temperature up to 30°C for one continuous period of up to six weeks, without exceeding the expiry date; record the discard date.

Injection

Route: Parenteral

Strengths: 80 mg