givosiran
General
Pronunciation:
giv-o-si-ran
Trade Name(s)
- Givlaari
Ther. Class.
none assigned
Pharm. Class.
temporary class
aminolevulinate synthase 1-directed small interfering ribonucleic acidsIndications
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.
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Anesthesia Central is an all-in-one web and mobile solution for treating patients before, during, and after surgery. This collection of drugs, procedures, and test information is derived from Davis’s Drug, MGH Clinical Anesthesia Procedures, Pocket Guide to Diagnostic Tests, and PRIME Journals. Complete Product Information.