Givlaari

Therapy should be initiated under the supervision of a healthcare professional experienced in the management of porphyria. 5 mg/kg once monthly, administered via subcutaneous injection. Dosing is based on actual body weight. 5 mg/kg) = total amount (mg) of medicinal product to be administered.

Total amount (mg) divided by vial concentration (189 mg/mL) = total volume of medicinal product (mL) to be injected. Missed dose If a dose is missed, treatment should be administered as soon as possible. Dosing should be resumed at monthly intervals following administration of the missed dose.

8). 2). 5×ULN). 4). 73 m²). 4). 2). The safety and efficacy of Givlaari in children aged < 12 years of age has not been established. No data are available. Method of administration For subcutaneous use only. This medicinal product is provided as a ready-to-use solution in a single use vial.

• The required volume of Givlaari should be calculated based on the recommended weight-based dose. 5 mL. If the dose is more than 1 mL, more than one vial will be needed. 5 mL should be administered as multiple injections (the total monthly dose divided equally between syringes with each injection containing approximately the same volume) to minimise potential injection site discomfort due to injection volume.

• This medicinal product should be injected subcutaneously into the abdomen; alternative injection sites include the thigh or upper arm. • For subsequent injections or doses, rotating the injection site is recommended. • This medicinal product should not be administered into scar tissue or areas that are reddened, inflamed, or swollen.

For detailed instructions, please refer to the instructions for use intended for healthcare professionals only, provided with the package leaflet.

5%). 9%). Tabulated list of adverse reactions The adverse reactions are presented as MedDRA preferred terms under the MedDRA system organ class (SOC) by frequency. Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.

The frequency of the adverse reactions is expressed according to the following categories: • Very common (≥ 1/10) • Common (≥ 1/100 to < 1/10) • Uncommon (≥ 1/1 000 to < 1/100) 6 Table 1: Adverse reactions System organ class Adverse reaction Frequency Immune system disorders Hypersensitivity Common Anaphylactic reaction Uncommon Gastrointestinal disorders Nausea Very common Pancreatitis Common Hepatobiliary disorders Transaminase elevations Very common Skin and subcutaneous tissue disorders Rasha Very common Renal and urinary disorders Glomerular filtration rate (GFR) decreasedb Very common General disorders and administration site conditions Injection site reactions Very common Fatigue Very common Investigations Blood homocysteine increasedc Common a Includes pruritus, eczema, erythema, rash, rash pruritic, urticaria.

b Includes blood creatinine increased, GFR decreased, chronic kidney disease (estimated GFR (eGFR) decreased), renal impairment. c Includes blood homocysteine abnormal, hyperhomocysteinemia, blood homocysteine increased. 2%) patient treated with placebo had an increased alanine aminotransferase (ALT) more than 3 times the ULN.

5 mg/kg. 25 mg/kg. ALT elevations in both patients resolved. Injection site reactions In placebo-controlled and open-label clinical studies, injection site reactions have been reported in 36% of patients and generally have been mild or moderate in severity, mostly transient and resolved without treatment.

The most commonly reported symptoms included erythema, pain, and pruritus. 8% of injections and did not result in discontinuation of treatment. 7%) experienced single, transient, recall reactions of erythema at a prior injection site with a subsequent dose administration.

1). This should be taken into consideration when assessing the individual benefit-risk in these rare AHP subtypes. 8). Signs and symptoms of anaphylaxis should be monitored. If anaphylaxis occurs, administration of this medicinal product should be immediately discontinued, and appropriate medical treatment should be instituted.

Transaminase elevations Transaminase elevations have been observed in patients treated with givosiran. 8). Liver function tests should be performed prior to initiating treatment. These tests should be repeated monthly during the first 6 months of treatment, and as clinically indicated thereafter.

Interrupting or discontinuing treatment should be considered for clinically relevant transaminase elevations. 2). There are limited data on efficacy and safety of the lower dose, particularly in patients who previously experienced transaminase elevations.

8). Blood homocysteine increased Blood homocysteine levels may be increased in patients with AHP, vitamin deficiencies, or chronic kidney disease. 8). The clinical relevance of the elevations in blood homocysteine during treatment with givosiran is unknown.

However, homocysteine elevations have been previously associated with an increased risk of thromboembolic events. Measurement of blood homocysteine levels prior to initiating treatment and monitoring for changes during treatment with givosiran is recommended.

In patients with elevated homocysteine levels, homocysteine-lowering therapy can be considered. 8). 5 mg/kg givosiran. Progression of renal impairment has been observed in some patients with pre-existing renal disease. Careful monitoring of renal function during treatment is required in such cases.

Excipients This medicinal product contains less than 1 mmol sodium (23 mg) per mL, that is to say essentially ‘sodium-free’.

g. 1.