• Acute hepatic porphyria.

Contraindicated in:

• Severe hypersensitivity.

Use Cautiously in:

• OB: Use during pregnancy only if potential maternal benefit justifies potential fetal risk
• Lactation: Use while breastfeeding only if potential maternal benefit justifies potential risk to infant
• Pedi: Safety and effectiveness not established in children.

Derm: rash.

GI: ↑liver enzymes, nausea, PANCREATITIS.

GU: renal impairment.

Hemat: ↑homocysteine levels.

Local: injection site reactions.
Misc: fatigue, (INCLUDING ANAPHYLAXIS)HYPERSENSITIVITY REACTIONS .

Drug-Drug:

• May ↑ levels and risk of toxicity of CYP1A2 substrates, including caffeine; avoid concurrent use; if concurrent use necessary, ↓ dose of CYP1A2 substrate.
• May ↑ levels and risk of toxicity of CYP2D6 substrates, including dextromethorphan; avoid concurrent use; if concurrent use necessary, ↓ dose of CYP2D6 substrate.

• Solution for injection: 189 mg/mL;

• SC (Adults): 2.5 mg/kg (actual body weight) once monthly.

Givlaari

• Causes degradation of aminolevulinate synthase 1 mRNA in hepatocytes through RNA interference, which subsequently reduces circulating levels of aminolevulinic acid and porphobilinogen, both of which accumulate in acute hepatic porphyria.

• Reduction of porphyria attacks associated with hospitalizations, urgent health care visits, or IV hemin administration at home.

Therapeutic Classification: n/a

Pharmacologic Classification:

Absorption: Unknown.

Distribution: Distributed primarily to liver.

Protein Binding: 90%.

Metabolism/Excretion: Metabolized by nucleases to oligonucleotides of shorter lengths, including an active metabolite. Primarily excreted in urine (5–14% as unchanged drug; 4–13% as active metabolite).

Half-life: Givosiran: 6 hr. Active metabolite: 6 hr.

(plasma concentrations)

• Explain purpose of givosiran to patient.
• Advise patient to notify health care professional immediately if signs and symptoms of anaphylaxis or acute upper abdominal pain occur.
• Advise patient to notify health care professional if signs and symptoms of injection site reaction occur.
• Emphasize the importance of routine lab tests to monitor of side effects.
• Advise patient to notify health care professional if pregnancy is planned or suspected or if breastfeeding.

GIV-o-si-ran