givosiran sodium: clinical use

Prescribing considerations

• Initiate under supervision of a healthcare professional experienced in porphyria management.
• Evidence is limited for hereditary coproporphyria, variegate porphyria and ALA dehydratase-deficient porphyria compared with acute intermittent porphyria.
• Moderate or severe hepatic impairment, end-stage renal disease and dialysis have not been adequately studied.
• Safety and efficacy are not established below 12 years.

Contraindications and cautions

• Severe hypersensitivity, including previous anaphylaxis, to givosiran or an excipient.

Monitoring

• Check liver function before treatment, monthly during the first six months and subsequently as clinically indicated.
• Monitor renal function, particularly in people with pre-existing renal disease.
• Measure homocysteine before and during treatment; consider vitamin B6 supplementation if elevated.
• Observe for anaphylaxis and discontinue administration immediately if it occurs.

Clinical pharmacology

Givosiran is a double-stranded, liver-targeted small interfering RNA that promotes degradation of ALAS1 messenger RNA. It is metabolised by nucleases rather than CYP450 enzymes, although its pharmacodynamic effect can indirectly reduce CYP1A2 and CYP2D6 activity.

Formulation and product differences

• The selected product is a ready-to-use, single-use subcutaneous injection solution.
• It is essentially sodium-free and must not be mixed with other medicines.