asfotase alfa: clinical use

Prescribing considerations

• Initiation and supervision should involve a physician experienced in metabolic or bone disorders.
• Confirm paediatric-onset hypophosphatasia and assess the bone manifestations being treated.
• Record the product name and batch number for biological traceability.
• Review injection technique, site rotation, local reactions and any reduced clinical response that could suggest immunogenicity.
• Evidence is limited in older people and in renal or hepatic impairment.
• After serious hypersensitivity, any supervised rechallenge requires an individual benefit–risk assessment.

Contraindications and cautions

• Severe or life-threatening hypersensitivity to asfotase alfa or an excipient when the hypersensitivity cannot be controlled.

Monitoring

• Clinical response, mobility, skeletal manifestations and growth where relevant
• Injection sites and injection technique
• Calcium and parathyroid hormone, particularly early in treatment
• Weight and nutritional status
• Baseline and periodic ophthalmology assessment and renal ultrasound
• In children below five years, head growth, fundoscopy and evidence of raised intracranial pressure
• Unexpected results from alkaline-phosphatase-dependent laboratory assays

Clinical pharmacology

Asfotase alfa is a recombinant fusion protein containing the catalytic domain of human tissue-nonspecific alkaline phosphatase, an IgG1 Fc region and a bone-targeting deca-aspartate sequence. It replaces deficient enzyme activity and promotes skeletal mineralisation. Its average elimination half-life after subcutaneous administration is approximately two days.

Formulation and product differences

• A clear to opalescent, colourless to slightly yellow solution in single-use vials.
• A few small translucent or white particles may be acceptable, but discolouration, lumps or large particles are not.
• The formulation is essentially sodium-free, must not be mixed with other medicinal products and requires refrigerated, light-protected storage.