givosiran
General
Pronunciation:
giv-o-si-ran
Trade Name(s)
- Givlaari
Ther. Class.
none assigned
Pharm. Class.
aminolevulinate synthase 1 directed small interfering ribonucleic acids
Indications
Acute hepatic porphyria.
Action
Causes degradation of aminolevulinate synthase 1 (ALAS1) 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 Effect(s):
Reduction of porphyria attacks associated with hospitalizations, urgent healthcare visits, or IV hemin administration at home.
Pharmacokinetics
Absorption: Unknown.
Distribution: Distributed primarily to liver.
Protein Binding: 90%.
Metabolism and 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 |
---|---|---|---|
Subcut | unknown | 3 hr (givosiran); 7 hr (active metabolite) | unknown |
Contraindication/Precautions
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.
Adverse Reactions/Side Effects
Derm: rash
GI: ↑ liver enzymes, nausea
GU: renal impairment
Local: injection site reactions
Misc: HYPERSENSITIVITY REACTIONS (including anaphylaxis), fatigue
* CAPITALS indicate life-threatening.
Underline indicate most frequent.
Interactions
Drug-Drug
- May ↑ levels and risk of toxicity of CYP1A2 substrates, including caffeine ; avoid concurrent use; if concurrent use unavoidable, ↓ dose of CYP1A2 substrate.
- May ↑ levels and risk of toxicity of CYP2D6 substrates, including dextromethorphan ; avoid concurrent use; if concurrent use unavoidable, ↓ dose of CYP2D6 substrate.
Route/Dosage
Subcut (Adults): 2.5 mg/kg (actual body weight) once monthly.
Availability
Solution for injection: 189 mg/mL
Assessment
Monitor for signs and symptoms of anaphylactic reactions (rash, hives, dyspnea, swelling of lips, face and throat) during therapy.
- Assess for signs and symptoms of injection site reactions (erythema, pain, pruritus, rash, discoloration, swelling around injection site) during therapy.
Lab Test Considerations:
Measure liver function tests before starting therapy, repeat monthly during first 6 mo, and as clinically indicated. If clinically significant transaminase elevations occur, hold or discontinue therapy.
- May cause ↑ serum creatinine and ↓ glomerular filtration rate. Monitor renal function periodically during therapy.
Potential Diagnoses
- Deficient knowledge, related to medication regimen (Patient/Family/Teaching)
Implementation
Administer by health care professional only. Have medical support available during injections to manage anaphylactic reactions.
- Subcut Solution is clear and colorless to yellow; do not inject solutions that are cloudy, discolored, or contain particulate matter. Withdraw dose required using a 21–gauge or larger needle. Divide doses >1.5 mL equally into multiple doses. Replace needle with 25–27 gauge needle with 1/2 or 5/8 inch needle length. Avoid having givosiran on needle tip until needle is in the subcutaneous space. Inject into abdomen, back or side of upper arm, or thigh; rotate injection sites. Avoid scar tissue or areas that are red, inflamed, or swollen; if more than 1 injection needed, keep at least 2 cm between sites. Discard unused solution. Administer missed doses as soon as remembered; resume dosing at monthly intervals after administration of missed dose.
Patient/Family Teaching
- Explain purpose of givosiran to patient.
Advise patient to notify health care professional immediately if signs and symptoms of anaphylaxis occur.
- Advise patient to notify health care professional if signs and symptoms of injection site reaction occur.
- Advise patient to notify health care professional if pregnancy is planned or suspected or if breastfeeding.
- Emphasize the importance if routine lab tests to monitor of side effects.
Evaluation/Desired Outcomes
Reduction of porphyria attacks associated with hospitalizations, urgent healthcare visits, or IV hemin administration at home.