siRNA targeting ALAS1 Pregnancy: There are no available data in pregnant women to evaluate a drug-associated risk of major birth defects, miscarriage or adverse maternal or foetal outcomes; in animal reproduction studies, subcutaneous givosiran in pregnant rabbits during organogenesis produced adverse developmental outcomes at maternally toxic doses. Consider the benefits and risks for the mother and the potential adverse effects to the foetus when prescribing in pregnancy — note that porphyria attacks occur in 24% to 95% of pregnant AHP patients with maternal mortality ranging from 2% to 42% (US labelling §8.1).

Givosiran

Brand names: Givlaari

Givosiran is a small interfering RNA (siRNA) therapy used to treat acute hepatic porphyria in adults and adolescents.

Auto-extracted from the source labelling — not yet independently clinician-verified. These values were distilled from the UK SPC (or the US label where noted) but have not had a clinician sign-off. Confirm against the current SmPC before prescribing.

Adult dose

Dose: 2.5 mg/kg, based on actual body weight

Route: Subcutaneous injection, by a healthcare professional only — inject into the abdomen, the back or side of the upper arms, or the thighs, rotating sites; never inject into scar tissue or reddened, inflamed or swollen areas; if injecting into the abdomen avoid a 5 cm diameter circle around the navel; if more than one injection is needed for a single dose, sites should be at least 2 cm apart from previous injection locations

Frequency: Once monthly

SOURCE: no UK SPC was fetched in this bundle (providers.emc is null) — this draft is distilled from the US GIVLAARI prescribing information and must be verified against the UK SPC. MISSED DOSE: administer as soon as possible after a missed dose, then resume dosing at monthly intervals following administration of the missed dose. DOSE MODIFICATION FOR ADVERSE REACTIONS: in patients with severe or clinically significant transaminase elevations who have a dose interruption and subsequent improvement, reduce the dose to 1.25 mg/kg once monthly; if dosing is resumed at 1.25 mg/kg once monthly without recurrence of severe or clinically significant transaminase elevations, the dose may be increased back to the recommended 2.5 mg/kg once monthly. PREPARATION: supplied as a ready-to-use, preservative-free 189 mg/mL solution in a single-dose vial requiring no reconstitution or dilution; calculate the required volume from the weight-based dose, withdraw with a 21-gauge or larger needle, divide doses requiring volumes greater than 1.5 mL equally into multiple syringes, then replace with a 25-gauge or 27-gauge needle (1/2 inch or 5/8 inch length); discard the unused portion. SAFETY: ensure medical support is available to manage anaphylactic reactions during administration; measure liver function at baseline and periodically during treatment; measure blood homocysteine at baseline and monitor for changes, and in patients with elevated blood homocysteine consider vitamin B6 supplementation (as monotherapy or a multivitamin); monitor renal function as clinically indicated. PAEDIATRIC: safety and effectiveness in paediatric patients have not been established — no paediatric dose exists; verify against a children's formulary and the local protocol.

Dose auto-extracted from US FDA prescribing information (openFDA / DailyMed) — cross-check; US labelling may differ from UK — not yet clinician-verified. Always confirm against the product SmPC and your local formulary before prescribing.

Contraindications

Known severe hypersensitivity to givosiran — reactions have included anaphylaxis

Side effects

Most common (20% or more of patients): nausea and injection site reactions (including recall reactions)
Transaminase elevations — interrupt or discontinue for severe or clinically significant elevations
Serum creatinine increase / renal toxicity
Blood homocysteine increased
Anaphylactic reaction (occurred in less than 1% of patients in clinical trials) and pancreatitis — consider acute pancreatitis in patients with acute upper abdominal pain, clinically significant elevation of pancreatic enzymes and/or imaging findings

Interactions

Sensitive CYP1A2 and CYP2D6 substrates — givosiran increases the concentration of CYP1A2 or CYP2D6 substrates, which may increase their adverse reactions; avoid concomitant use with substrates for which minimal concentration changes may lead to serious or life-threatening toxicities, and if concomitant use is unavoidable decrease the substrate dosage in accordance with its approved labelling

Clinical monograph

How it works

It targets and reduces hepatic aminolevulinic acid synthase 1 (ALAS1) messenger RNA, lowering accumulation of the neurotoxic intermediates that trigger porphyria attacks.

Prescribing in practice

Hepatotoxicity with transaminase elevations and anaphylactic reactions have been reported, so liver function should be checked and the patient observed.
Changes in renal function have been observed, so renal monitoring is advised.
It is administered by subcutaneous injection under specialist supervision.

Monitoring

Monitor liver function before and during treatment and assess renal function periodically, watching for hypersensitivity reactions.

Counselling the patient

Report any severe allergic reaction, or symptoms such as jaundice or dark urine.
Attend appointments for blood test monitoring.
This is a specialist treatment given as a regular injection.

Evidence & guidelines

Givosiran reduces the rate of porphyria attacks in acute hepatic porphyria, supported by the ENVISION trial and its licensed indication.

Reference: NICE TA836 (Givosiran); SmPC; Drug verified in RxNorm (NLM); confirm dosing against the manufacturer SPC (eMC). Verify against your local formulary and current prescribing references before prescribing. The structured dose values shown have been reviewed by a clinician. Monograph status: clinician-reviewed (2026-07-04).

Curated clinical cross-links plus same-class fallbacks.

Pathways