- Drugs List
- Therapeutic Indications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
Injections of givosiran.
Treatment of acute attacks of hepatic porphyria
Dosage should be based on actual body weight.
2.5mg/kg once a month subcutaneously.
Children aged 12 years and older
2.5mg/kg once a month subcutaneously.
Additional Dosage Information
Dose modification for adverse reactions
Dose should be interrupted in patients with clinically relevant transaminase elevations. Upon improvement, dose can be resumed at 1.25mg/kg once a month. There are no data on sequentially increasing the 1.25mg/kg dose to 2.5mg/kg after dose interruption for transaminase elevations.
Dosing should be resumed at monthly intervals following administration of the missed dose.
For subcutaneous use only.
Givosiran should be injected subcutaneously into the abdomen, alternative injection sites include the thigh or upper arm. Rotating the injection site is recommended.
The maximum volume of medicinal product per injection site is 1.5ml. If more than 1.5ml is required, the total volume should be split equally and should be administered at two different injection sites in order to minimise potential injection site discomfort due to injection volume.
Children under 12 years
Precautions and Warnings
End stage renal disease
Moderate hepatic impairment
Treatment to be initiated and supervised by a specialist
Avoid injection into scar tissue
Record name and batch number of administered product
Rotate the injection site
Monitor hepatic function before, monthly for 6 months & then as indicated
Monitor for signs and symptoms of allergic reaction
Monitor renal function in patients with renal impairment
Consider discontinuing treatment if serum transaminase levels rise
Discontinue if serious allergic or anaphylactic reaction occurs
The efficacy and safety data is limited in patients with acute hereditary porphyria (AHP) subtypes other than acute intermittent porphyria (AIP) such as hereditary coproporphyria (HCP), variegate porphyria (VP) and ALA dehydratase-deficient porphyria (ADP). This should be taken into consideration when assessing the individual benefit-risk in these rare AHP subtypes.
Abnormal liver function tests in some patients typically occur between 3 to 5 months after starting treatment with givosiran.
Increases in serum creatinine levels and decreases in eGFR have been reported during treatment with givosiran.
Pregnancy and Lactation
Use givosiran with caution during pregnancy.
The manufacturer advises that use of givosiran could be considered during pregnancy taking into account the expected health benefit to the women but the potential risks to the fetus. The careful assessment of the suitability of the treatment is required. If the woman is informed of the possible risks for severe adverse effects in the embryo and fetus and informed consent is obtained, then treatment with givosiran could be used. Animal studies have shown reproductive toxicity. At the time of writing there is no or limited human data available. Risks are unknown.
Givosiran is contraindicated during breastfeeding.
The manufacturer recommends that a decision should be made whether to discontinue breastfeeding or to discontinue/abstain from givosiran therapy taking into account the benefit of breastfeeding for the child and the benefit of therapy for the woman. Animal data reports that givosiran is excreted in milk, however, presence in human breast milk is unknown. A risk to the newborns/infants cannot be excluded.
Chronic kidney disease
Decrease in glomerular filtration rate
Increase of liver transaminases
Injection site reactions
Serum creatinine increased
It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.
The following number will direct the caller to the relevant local centre (0844) 892 0111
Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Last Full Review Date: May 2022
Summary of Product Characteristics: Givlaari 189 mg/ml solution for injection. Alnylam UK Ltd. Revised November 2021.
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