GIVLAARI Solution for injection Ref.[9926] Active ingredients: Givosiran

Therapy should be initiated under the supervision of a healthcare professional experienced in the management of porphyria.

Posology

The recommended dose of Givlaari is 2.5 mg/kg once monthly, administered via subcutaneous injection. Dosing is based on actual body weight.

The patient dose (in mg) and volume (in mL) should be calculated as follows:

Patient body weight (kg) × dose (2.5 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.

Dose modification for adverse reactions

In patients with clinically relevant transaminase elevations, who have dose interruption and subsequent improvement in transaminase levels, a dose resumption at 1.25 mg/kg once monthly could be considered (see sections 4.4 and 4.8).

Special populations

Elderly

No dose adjustment is required in patients aged > 65 years of age (see section 5.2).

Hepatic impairment

No dose adjustment is necessary in patients with mild hepatic impairment (bilirubin ≤ 1× the upper limit of normal (ULN) and aspartate aminotransferase (AST) > 1×ULN, or bilirubin > 1×ULN to 1.5×ULN). Givlaari has not been studied in patients with moderate or severe hepatic impairment (see section 4.4).

Renal impairment

No dose adjustment is necessary in patients with mild, moderate or severe renal impairment (estimated glomerular filtration rate [eGFR] ≥15 to < 90 mL/min/1.73 m²). Givlaari has not been studied in patients with end-stage renal disease or patients on dialysis (see section 4.4).

Paediatric population

No dose adjustment is required for patients aged ≥12 to <18 years of age (see section 5.2). 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.
• The maximum acceptable single injection volume is 1.5 mL. If the dose is more than 1 mL, more than one vial will be needed.
• Doses requiring more than 1.5 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.

No case of overdose has been reported. In case of overdose, it is recommended that the patient be monitored for any signs or symptoms of adverse reactions and appropriate symptomatic treatment be instituted.

3 years.

Once the vial is opened, the medicinal product should be used immediately.

Do not store above 25 °C.

Keep vial in the outer carton to protect from light.

Glass vial with a PTFE-coated chlorobutyl rubber stopper and a flip-off aluminium seal. Each vial contains 1 mL solution for injection.

Pack size of one vial.

This medicinal product is for single use only.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.