Givlaari (givosiran)

Advise patients of the potential risks of Givlaari treatment:

Anaphylactic Reaction

• Inform patients about the risk and possible symptoms of severe hypersensitivity reactions that could occur.

Hepatic Toxicity

• Inform patients that transaminase elevations may occur, and that laboratory testing will be conducted in the first 6 months of treatment and as clinically indicated thereafter.

Renal Toxicity

• Inform patients that increases in serum creatinine and decreases in eGFR have been reported and that laboratory testing will be conducted as clinically indicated.

Injection Site Reactions

• Inform patients of the signs and symptoms of injection site reactions (examples include redness, pain, itching, rash, discoloration, or localized swelling).

Common side effects of Givlaari include:

• nausea,
• injection site reactions (redness, pain, itching, rash, discoloration, or swelling), and
• fatigue

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

Missed Dose

• Administer Givlaari as soon as possible after a missed dose. 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 dose interruption and subsequent improvement, reduce the dose to 1.25 mg/kg once monthly.
• In patients who resume dosing at 1.25 mg/kg once monthly without recurrence of severe or clinically significant transaminase elevations, the dose may be increased to the recommended dose of 2.5 mg/kg once monthly.

Sensitive CYP1A2 And CYP2D6 Substrates

• Concomitant use of Givlaari increases the concentration of CYP1A2 or CYP2D6 substrates, which may increase adverse reactions of these substrates.
• Avoid concomitant use of Givlaari with CYP1A2 or CYP2D6 substrates, for which minimal concentration changes may lead to serious or life-threatening toxicities.
• If concomitant use is unavoidable, decrease the CYP1A2 or CYP2D6 substrate dosage in accordance with approved product labeling.

• There are no available data with Givlaari use in pregnant women to evaluate a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes.
• Consider the benefits and risks of Givlaari for the mother and potential adverse effects to the fetus when prescribing Givlaari to a pregnant woman.
• There are no data on the presence of Givlaari in human milk, the effects on the breastfed child, or the effects on milk production.
• The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for Givlaari and any potential adverse effects on the breastfed child from Givlaari or from the underlying maternal condition.