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Givosiran: Drug information

Givosiran: Drug information
(For additional information see "Givosiran: Patient drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
Brand Names: US
  • Givlaari
Brand Names: Canada
  • Givlaari
Pharmacologic Category
  • Aminolevulinate Synthase 1-Directed Small Interfering Ribonucleic Acid (siRNA)
Dosing: Adult
Acute hepatic porphyria

Acute hepatic porphyria: SUBQ: 2.5 mg/kg once monthly. Note: Dosing is based on actual body weight.

Missed dose: Administer as soon as possible; then resume dosing at monthly intervals.

Dosing: Kidney Impairment: Adult

eGFR ≥15 to <89 mL/minute/1.73 m2: There are no dosage adjustments provided in the manufacturer’s labeling; however, no clinically meaningful differences in givosiran pharmacokinetics were observed in patients with eGFR ≥15 to <89 mL/minute/1.73 m2.

eGFR <15 mL/minute/1.73 m2: There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).

Dosing: Hepatic Impairment: Adult

Preexisting hepatic impairment:

Mild impairment (bilirubin ≤ ULN and AST > ULN, or bilirubin >1 to 1.5 × ULN): There are no dosage adjustments provided in the manufacturer’s labeling; however, no clinically meaningful differences in givosiran pharmacokinetics were observed in patients with mild hepatic impairment.

Moderate or severe impairment: There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).

Hepatotoxicity during treatment: If severe or clinically significant transaminase elevations occur during therapy, discontinue givosiran. If transaminase levels improve after discontinuing givosiran, may restart at a reduced dose of 1.25 mg/kg once monthly and further increase dose to 2.5 mg/kg once monthly if no recurrence of elevated transaminases on the reduced dose.

Dosing: Older Adult

Refer to adult dosing.

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in adults.

>10%:

Dermatologic: Eczema (≤17%), erythema of skin (≤17%), pruritic rash (≤17%), pruritus (≤17%), skin rash (≤17%), urticaria (≤17%)

Endocrine & metabolic: Homocystinemia (16%)

Gastrointestinal: Nausea (27%)

Hepatic: Increased serum alanine aminotransferase (≥3 x ULN: 15%), increased serum transaminases (13%)

Local: Injection site reaction (25%; including transient recall erythema at prior injection site)

Renal: Chronic renal failure (≤15%), decreased estimated GFR (eGFR) (≤15%), increased serum creatinine (≤15%)

1% to 10%: Nervous system: Fatigue (10%)

<1%:

Hypersensitivity: Anaphylaxis, hypersensitivity reaction

Immunologic: Antibody development

Contraindications

Severe hypersensitivity (eg, anaphylaxis) to givosiran or any component of the formulation.

Warnings/Precautions

Concerns related to adverse effects:

• Anaphylaxis: Anaphylaxis has occurred; ensure the availability of proper medical support to appropriately manage anaphylactic reactions during administration. Discontinue and administer appropriate medical treatment if anaphylaxis occurs.

• Hepatic toxicity: Transaminase elevations (ALT) of ≥3 times the ULN have occurred, primarily between 3 to 5 months following initiation of therapy. Interrupt or discontinue use if severe or clinically significant transaminase elevations occur during therapy.

• Homocysteine: Increases in blood homocysteine levels have been reported; treat appropriately.

• Injection-site reactions: Injection-site reactions have been reported, including erythema, pain, pruritus, rash, discoloration, and swelling around the injection site; monitor and treat appropriately.

• Renal toxicity: Increases in serum creatinine and decreases in eGFR have been reported.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Subcutaneous, as sodium [preservative free]:

Givlaari: 189 mg/mL (1 mL)

Generic Equivalent Available: US

No

Pricing: US

Solution (Givlaari Subcutaneous)

189 mg/mL (per mL): $49,650.00

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Subcutaneous, as sodium:

Givlaari: 189 mg/mL (1 mL)

Administration: Adult

SubQ: For SubQ administration by a health care professional only. Ensure the availability of proper medical support to appropriately manage anaphylactic reactions during administration. Use a 25-gauge or 27-gauge needle with 1/2-inch or 5/8-inch needle length for administration; avoid givosiran solution on the needle tip until the needle is in the SubQ space. Administer into the abdomen (avoid the 5-cm diameter around the navel), thighs, or the back or side of upper arms. Rotate injection sites; do not inject into scar tissue or inflamed, reddened, or swollen areas. If more than one injection is needed for a single dose, space injection sites ≥2 cm apart. Discard unused portion.

Use: Labeled Indications

Acute hepatic porphyria: Treatment of adults with acute hepatic porphyria.

Metabolism/Transport Effects

Inhibits CYP1A2 (moderate), CYP2C19 (weak), CYP2D6 (moderate), CYP3A4 (weak)

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

Agomelatine: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Agomelatine. Risk C: Monitor therapy

Ajmaline: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Ajmaline. Risk C: Monitor therapy

Alosetron: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Alosetron. Management: Avoid concomitant use of alosetron and moderate CYP1A2 inhibitors whenever possible. If combined use is necessary, monitor for increased alosetron effects/toxicities. Risk D: Consider therapy modification

ALPRAZolam: CYP3A4 Inhibitors (Weak) may increase the serum concentration of ALPRAZolam. Risk C: Monitor therapy

Amitriptyline: CYP2D6 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Amitriptyline. CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Amitriptyline. Risk C: Monitor therapy

Amoxapine: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Amoxapine. Risk C: Monitor therapy

Amphetamines: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Amphetamines. Management: Monitor for amphetamine toxicities (including serotonin syndrome) if used with a moderate CYP2D6 inhibitor. Initiate amphetamine therapy at lower doses, monitor frequently, and adjust doses as needed. Discontinue amphetamines if serotoinin syndrome occurs Risk C: Monitor therapy

Anagrelide: CYP1A2 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Anagrelide. CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Anagrelide. Risk C: Monitor therapy

ARIPiprazole: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of ARIPiprazole. Management: Monitor for increased aripiprazole pharmacologic effects. Aripiprazole dose adjustments may or may not be required based on concomitant therapy, indication, or dosage form. Consult full interaction monograph for specific recommendations. Risk C: Monitor therapy

ARIPiprazole Lauroxil: CYP2D6 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of ARIPiprazole Lauroxil. Risk C: Monitor therapy

Atomoxetine: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Atomoxetine. Risk C: Monitor therapy

Bendamustine: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Bendamustine. Management: Consider alternatives to moderate CYP1A2 inhibitors during therapy with bendamustine due to the potential for increased bendamustine plasma concentrations and increased bendamustine toxicity. Risk D: Consider therapy modification

Brexpiprazole: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Brexpiprazole. Management: If brexpiprazole is to be used together with both a moderate CYP2D6 inhibitor and a strong or moderate CYP3A4 inhibitor, the brexpiprazole dose should be reduced to 25% of the usual dose when treating indications other than major depressive disorder. Risk C: Monitor therapy

Bromazepam: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Bromazepam. Risk C: Monitor therapy

Caffeine and Caffeine Containing Products: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Caffeine and Caffeine Containing Products. Risk C: Monitor therapy

CarBAMazepine: CYP3A4 Inhibitors (Weak) may increase the serum concentration of CarBAMazepine. Risk C: Monitor therapy

Carvedilol: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Carvedilol. Risk C: Monitor therapy

CloBAZam: CYP2C19 Inhibitors (Weak) may increase serum concentrations of the active metabolite(s) of CloBAZam. CYP2C19 Inhibitors (Weak) may increase the serum concentration of CloBAZam. Risk C: Monitor therapy

ClomiPRAMINE: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of ClomiPRAMINE. Risk C: Monitor therapy

ClomiPRAMINE: CYP2D6 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of ClomiPRAMINE. CYP2D6 Inhibitors (Moderate) may increase the serum concentration of ClomiPRAMINE. Risk C: Monitor therapy

CloZAPine: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of CloZAPine. Risk C: Monitor therapy

CloZAPine: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of CloZAPine. Risk C: Monitor therapy

Codeine: CYP2D6 Inhibitors (Moderate) may diminish the therapeutic effect of Codeine. These CYP2D6 inhibitors may prevent the metabolic conversion of codeine to its active metabolite morphine. Risk C: Monitor therapy

CycloSPORINE (Systemic): CYP3A4 Inhibitors (Weak) may increase the serum concentration of CycloSPORINE (Systemic). Risk C: Monitor therapy

Desipramine: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Desipramine. Risk C: Monitor therapy

Deutetrabenazine: CYP2D6 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Deutetrabenazine. Risk C: Monitor therapy

Dextromethorphan: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Dextromethorphan. Risk C: Monitor therapy

Dofetilide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Dofetilide. Risk C: Monitor therapy

Doxepin (Systemic): CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Doxepin (Systemic). Risk C: Monitor therapy

Doxepin (Topical): CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Doxepin (Topical). Risk C: Monitor therapy

DOXOrubicin (Conventional): CYP2D6 Inhibitors (Moderate) may increase the serum concentration of DOXOrubicin (Conventional). Risk X: Avoid combination

DULoxetine: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of DULoxetine. Risk C: Monitor therapy

Eliglustat: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Eliglustat. Management: Eliglustat dose is 84 mg daily with CYP2D6 inhibitors. Use is contraindicated (COI) when also combined with strong CYP3A4 inhibitors. When also combined with a moderate CYP3A4 inhibitor, use is COI in CYP2D6 EMs or IMs and should be avoided in CYP2D6 PMs. Risk D: Consider therapy modification

Fezolinetant: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Fezolinetant. Risk X: Avoid combination

Finerenone: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Finerenone. Risk C: Monitor therapy

Flecainide: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Flecainide. Risk C: Monitor therapy

Flibanserin: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Flibanserin. Risk C: Monitor therapy

Fosphenytoin-Phenytoin: CYP2C19 Inhibitors (Weak) may increase the serum concentration of Fosphenytoin-Phenytoin. Risk C: Monitor therapy

Haloperidol: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Haloperidol. Risk C: Monitor therapy

Iboga: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Iboga. Risk C: Monitor therapy

Iloperidone: CYP2D6 Inhibitors (Moderate) may decrease serum concentrations of the active metabolite(s) of Iloperidone. Specifically, concentrations of the metabolite P95 may be decreased. CYP2D6 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Iloperidone. Specifically, concentrations of the metabolite P88 may be increased. CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Iloperidone. Risk C: Monitor therapy

Imipramine: CYP2D6 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Imipramine. Concentrations of desipramine may be increased. CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Imipramine. Risk C: Monitor therapy

Indoramin: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Indoramin. Risk C: Monitor therapy

Ixabepilone: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Ixabepilone. Risk C: Monitor therapy

Lemborexant: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Lemborexant. Management: The maximum recommended dosage of lemborexant is 5 mg, no more than once per night, when coadministered with weak CYP3A4 inhibitors. Risk D: Consider therapy modification

Lofepramine: CYP2D6 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Lofepramine. The active metabolite of lofepramine is desipramine. Risk C: Monitor therapy

Lomitapide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Lomitapide. Management: Patients on lomitapide 5 mg/day may continue that dose. Patients taking lomitapide 10 mg/day or more should decrease the lomitapide dose by half. The lomitapide dose may then be titrated up to a max adult dose of 30 mg/day. Risk D: Consider therapy modification

Lonafarnib: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Lonafarnib. Management: Avoid concurrent use of lonafarnib with weak CYP3A4 inhibitors. If concurrent use is unavoidable, reduce the lonafarnib dose to or continue at a dose of 115 mg/square meter. Monitor for evidence of arrhythmia, syncope, palpitations, or similar effects. Risk D: Consider therapy modification

Mavacamten: CYP2C19 Inhibitors (Weak) may increase the serum concentration of Mavacamten. Management: Start mavacamten at 5 mg/day if stable on a weak CYP2C19 inhibitor. For those stable on mavacamten who are initiating a weak CYP2C19 inhibitor, reduce mavacamten dose by one dose level. Risk D: Consider therapy modification

Melatonin: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Melatonin. Risk C: Monitor therapy

Mequitazine: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Mequitazine. Risk X: Avoid combination

Methadone: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Methadone. Risk C: Monitor therapy

Metoclopramide: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Metoclopramide. Risk C: Monitor therapy

Metoprolol: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Metoprolol. Risk C: Monitor therapy

Midazolam: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Midazolam. Risk C: Monitor therapy

Nebivolol: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Nebivolol. Risk C: Monitor therapy

NiMODipine: CYP3A4 Inhibitors (Weak) may increase the serum concentration of NiMODipine. Risk C: Monitor therapy

Nortriptyline: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Nortriptyline. Risk C: Monitor therapy

OLANZapine: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of OLANZapine. Risk C: Monitor therapy

Oliceridine: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Oliceridine. Risk C: Monitor therapy

Olmutinib: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Olmutinib. Risk C: Monitor therapy

PARoxetine: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of PARoxetine. Risk C: Monitor therapy

Pentoxifylline: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Pentoxifylline. Risk C: Monitor therapy

Perhexiline: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Perhexiline. Risk C: Monitor therapy

Perphenazine: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Perphenazine. Risk C: Monitor therapy

Pimozide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Pimozide. Risk X: Avoid combination

Pirfenidone: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Pirfenidone. Management: Avoid concomitant use of pirfenidone and moderate CYP1A2 inhibitors whenever possible. If combined, decrease the pirfenidone dose to 1,602 mg per day (534 mg three times daily) and monitor for increased pirfenidone toxicities. Risk D: Consider therapy modification

Pitolisant: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Pitolisant. Risk C: Monitor therapy

Pomalidomide: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Pomalidomide. Risk C: Monitor therapy

Propafenone: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Propafenone. Risk C: Monitor therapy

Propranolol: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Propranolol. Risk C: Monitor therapy

Protriptyline: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Protriptyline. Risk C: Monitor therapy

Ramelteon: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Ramelteon. Risk C: Monitor therapy

Ramosetron: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Ramosetron. Risk C: Monitor therapy

Rasagiline: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Rasagiline. Management: Limit rasagiline dose to 0.5 mg once daily in patients taking moderate CYP1A2 inhibitors. Risk D: Consider therapy modification

RisperiDONE: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of RisperiDONE. Risk C: Monitor therapy

ROPINIRole: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of ROPINIRole. Risk C: Monitor therapy

ROPivacaine: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of ROPivacaine. Risk C: Monitor therapy

Sertindole: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Sertindole. Risk C: Monitor therapy

Simvastatin: CYP3A4 Inhibitors (Weak) may increase serum concentrations of the active metabolite(s) of Simvastatin. CYP3A4 Inhibitors (Weak) may increase the serum concentration of Simvastatin. Risk C: Monitor therapy

Sirolimus (Conventional): CYP3A4 Inhibitors (Weak) may increase the serum concentration of Sirolimus (Conventional). Risk C: Monitor therapy

Sirolimus (Protein Bound): CYP3A4 Inhibitors (Weak) may increase the serum concentration of Sirolimus (Protein Bound). Management: Reduce the dose of protein bound sirolimus to 56 mg/m2 when used concomitantly with a weak CYP3A4 inhibitor. Risk D: Consider therapy modification

Tacrolimus (Systemic): CYP3A4 Inhibitors (Weak) may increase the serum concentration of Tacrolimus (Systemic). Risk C: Monitor therapy

Tamoxifen: CYP2D6 Inhibitors (Moderate) may decrease serum concentrations of the active metabolite(s) of Tamoxifen. Specifically, CYP2D6 inhibitors may decrease the metabolic formation of highly potent active metabolites. Management: Consider alternatives to the use of moderate CYP2D6 inhibitors with tamoxifen when possible, as the combination may be associated with reduced clinical effectiveness of tamoxifen. Risk D: Consider therapy modification

Tamsulosin: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Tamsulosin. Risk C: Monitor therapy

Tasimelteon: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Tasimelteon. Risk C: Monitor therapy

Tetrabenazine: CYP2D6 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Tetrabenazine. Specifically, concentrations of the active alpha- and beta-dihydrotetrabenazine metabolites may be increased. Risk C: Monitor therapy

Theophylline Derivatives: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Theophylline Derivatives. Management: Consider avoidance of this combination. If coadministration is necessary, monitor for increased theophylline serum concentrations and toxicities when combined. Theophylline dose reductions will likely be required. Risk D: Consider therapy modification

Thioridazine: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Thioridazine. Risk X: Avoid combination

Timolol (Systemic): CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Timolol (Systemic). Risk C: Monitor therapy

TiZANidine: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of TiZANidine. Management: If combined use cannot be avoided, initiate tizanidine in adults at 2 mg and increase in 2 to 4 mg increments based on patient response. Monitor for increased effects of tizanidine, including adverse reactions. Risk D: Consider therapy modification

TraMADol: CYP2D6 Inhibitors (Moderate) may decrease serum concentrations of the active metabolite(s) of TraMADol. CYP2D6 Inhibitors (Moderate) may increase the serum concentration of TraMADol. Risk C: Monitor therapy

Triazolam: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Triazolam. Risk C: Monitor therapy

Trimipramine: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Trimipramine. Risk C: Monitor therapy

Ubrogepant: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Ubrogepant. Management: In patients taking weak CYP3A4 inhibitors, the initial and second dose (given at least 2 hours later if needed) of ubrogepant should be limited to 50 mg. Risk D: Consider therapy modification

Valbenazine: CYP2D6 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Valbenazine. Risk C: Monitor therapy

Vortioxetine: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Vortioxetine. Risk C: Monitor therapy

Zuclopenthixol: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Zuclopenthixol. Risk C: Monitor therapy

Pregnancy Considerations

Adverse events were observed in animal reproduction studies.

Outcome information following exposure to givosiran in pregnancy is limited (Sardh 2019).

Breastfeeding Considerations

It is not known if givosiran is present in breast milk.

According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother.

Monitoring Parameters

Signs and symptoms of anaphylaxis; liver function at baseline, every month during the first 6 months of therapy, and as clinically indicated; renal function during therapy and as clinically indicated; homocysteine at baseline and during therapy; folate, vitamins B12 and B6 in patients with elevated homocysteine.

Mechanism of Action

Givosiran causes degradation of aminolevulinate synthase 1 (ALAS1) messenger RNA (mRNA) in hepatocytes through RNA interference, reducing the elevated levels of liver ALAS1 mRNA. This leads to reduced circulating levels of neurotoxic intermediates aminolevulinic acid and porphobilinogen, factors associated with attacks and other disease manifestations of acute hepatic porphyria.

Pharmacokinetics (Adult Data Unless Noted)

Distribution: Vd: 10.4 L.

Protein binding: 90% (concentration dependent; decreases with increasing concentrations).

Metabolism: Metabolized by nucleases to oligonucleotides of shorter lengths; AS(N-1)3’ is the active metabolite and is equipotent to givosiran.

Half-life elimination: 6 hours.

Time to peak: Givosiran: 3 hours (range: 0.5 to 8 hours); AS(N-1)3’ givosiran: 7 hours (range: 1.5 to 12 hours).

Excretion: Urine (5% to 14% as unchanged drug; 4% to 13% as AS[N-1]3’givosiran).

Brand Names: International
International Brand Names by Country
For country code abbreviations (show table)

  • (AT) Austria: Givlaari;
  • (BE) Belgium: Givlaari;
  • (BG) Bulgaria: Givlaari;
  • (BR) Brazil: Givlaari;
  • (ES) Spain: Givlaari;
  • (FR) France: Givlaari;
  • (GB) United Kingdom: Givlaari;
  • (IT) Italy: Givlaari;
  • (NL) Netherlands: Givlaari;
  • (PR) Puerto Rico: Givlaari;
  • (RO) Romania: Givlaari;
  • (SA) Saudi Arabia: Givlaari;
  • (SE) Sweden: Givlaari
  1. Givlaari (givosiran) [prescribing information]. San Diego, CA: Ajinomoto Althea Inc; February 2023.
  2. Sardh E, Harper P, Balwani M, et al. Phase 1 trial of an RNA interference therapy for acute intermittent porphyria. N Engl J Med. 2019;380(6):549-558. doi: 10.1056/NEJMoa1807838. [PubMed 30726693]
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