givosiran

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.

Adv. Reactions/Side Effects ⬆ ⬇

Derm: rash

GI: ↑liver enzymes, nausea, PANCREATITIS

GU: renal impairment

Hemat: ↑homocysteine levels

Local: injection site reactions

Misc: fatigue, HYPERSENSITIVITY REACTIONS (INCLUDING ANAPHYLAXIS)

Interactions ⬆ ⬇

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.

Availability ⬆ ⬇

Solution for injection: 189 mg/mL

Route/Dosage ⬆ ⬇

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

US Brand Names ⬆ ⬇

Action ⬆ ⬇

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.

Therapeutic effects:

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

Classifications ⬆ ⬇

Therapeutic Classification: none assigned

Pharmacologic Classification: aminolevulinate synthase 1 directed small interfering ribonucleic acids

Pharmacokinetics ⬆ ⬇

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.

Time/Action Profile ⬆ ⬇

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
SUBQ	unknown	3 hr (givosiran); 7 hr (active metabolite)	unknown

Patient/Family Teaching ⬆ ⬇

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.
Rep: Advise patient to notify health care professional if pregnancy is planned or suspected or if breastfeeding.

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Indications ⬇

Contraind./Precautions ⬆ ⬇