Dosing & Uses
Dosage Forms & Strengths
injection, SC solution
- 189mg/mL (single-dose vial)
Acute Hepatic Porphyria
Indicated for acute hepatic porphyria (AHP)
2.5 mg/kg SC qMonth; dose based on actual body weight
Dosage Modifications
Transaminase elevations
- Interrupt or discontinue for severe or clinically significant transaminase elevations
- Severe or clinically significant transaminase elevations: Reduce dose to 1.25 mg/kg qMonth in patients who have dose interruption and subsequent transaminase improvement
- In patients who resume dosing at 1.25 mg/kg qMonth without recurrence of severe or clinically significant transaminase elevations, may increase dose to 2.5 mg/kg qMonth
Renal impairment
- Mild, moderate, or severe (eGFR 15 to <89 mL/min/1.73m2): No clinically meaningful differences in pharmacokinetics or pharmacodynamics
- End-stage renal disease: Unknown
Hepatic impairment
- Mild (bilirubin ≤1× ULN and AST >1 x ULN, or bilirubin >1-1.5 x ULN): No clinically meaningful differences in pharmacokinetics or pharmacodynamics
- Moderate-to-severe: Unknown
Dosing Considerations
Measure liver function tests before initiating treatment, repeat every month during the first 6 months of treatment, and as clinically indicated thereafter
Safety and efficacy not established
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Contraindicated (1)
- fezolinetant
givosiran will increase the level or effect of fezolinetant by affecting hepatic enzyme CYP1A2 metabolism. Contraindicated. Fezolinetant AUC and peak plasma concentration are increased if coadministered with drugs that are weak, moderate, or strong CYP1A2 inhibitors
Serious - Use Alternative (86)
- alosetron
givosiran will increase the level or effect of alosetron by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP1A2 substrates with givosiran. If unavoidable, decrease the CYP1A2 substrate dosage in accordance with approved product labeling.
- amitriptyline
givosiran will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP2D6 substrates with givosiran. If unavoidable, decrease the CYP2D6 substrate dosage in accordance with approved product labeling.
- amoxapine
givosiran will increase the level or effect of amoxapine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP2D6 substrates with givosiran. If unavoidable, decrease the CYP2D6 substrate dosage in accordance with approved product labeling.
- aripiprazole
givosiran will increase the level or effect of aripiprazole by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP2D6 substrates with givosiran. If unavoidable, decrease the CYP2D6 substrate dosage in accordance with approved product labeling.
- atomoxetine
givosiran will increase the level or effect of atomoxetine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP2D6 substrates with givosiran. If unavoidable, decrease the CYP2D6 substrate dosage in accordance with approved product labeling.
- bendamustine
givosiran will increase the level or effect of bendamustine by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP1A2 substrates with givosiran. If unavoidable, decrease the CYP1A2 substrate dosage in accordance with approved product labeling.
- brexpiprazole
givosiran will increase the level or effect of brexpiprazole by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP2D6 substrates with givosiran. If unavoidable, decrease the CYP2D6 substrate dosage in accordance with approved product labeling.
- caffeine
givosiran will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP1A2 substrates with givosiran. If unavoidable, decrease the CYP1A2 substrate dosage in accordance with approved product labeling.
- captopril
givosiran will increase the level or effect of captopril by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP2D6 substrates with givosiran. If unavoidable, decrease the CYP2D6 substrate dosage in accordance with approved product labeling.
- carvedilol
givosiran will increase the level or effect of carvedilol by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP2D6 substrates with givosiran. If unavoidable, decrease the CYP2D6 substrate dosage in accordance with approved product labeling.
- chloroquine
givosiran will increase the level or effect of chloroquine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP2D6 substrates with givosiran. If unavoidable, decrease the CYP2D6 substrate dosage in accordance with approved product labeling.
- chlorpromazine
givosiran will increase the level or effect of chlorpromazine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP2D6 substrates with givosiran. If unavoidable, decrease the CYP2D6 substrate dosage in accordance with approved product labeling.
- cinacalcet
givosiran will increase the level or effect of cinacalcet by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP2D6 substrates with givosiran. If unavoidable, decrease the CYP2D6 substrate dosage in accordance with approved product labeling.
- citalopram
givosiran will increase the level or effect of citalopram by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP2D6 substrates with givosiran. If unavoidable, decrease the CYP2D6 substrate dosage in accordance with approved product labeling.
- clomipramine
givosiran will increase the level or effect of clomipramine by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP1A2 substrates with givosiran. If unavoidable, decrease the CYP1A2 substrate dosage in accordance with approved product labeling.
givosiran will increase the level or effect of clomipramine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP2D6 substrates with givosiran. If unavoidable, decrease the CYP2D6 substrate dosage in accordance with approved product labeling. - clozapine
givosiran will increase the level or effect of clozapine by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP1A2 substrates with givosiran. If unavoidable, decrease the CYP1A2 substrate dosage in accordance with approved product labeling.
- codeine
givosiran will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP2D6 substrates with givosiran. If unavoidable, decrease the CYP2D6 substrate dosage in accordance with approved product labeling.
- conjugated estrogens
givosiran will increase the level or effect of conjugated estrogens by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP1A2 substrates with givosiran. If unavoidable, decrease the CYP1A2 substrate dosage in accordance with approved product labeling.
- cyclobenzaprine
givosiran will increase the level or effect of cyclobenzaprine by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP1A2 substrates with givosiran. If unavoidable, decrease the CYP1A2 substrate dosage in accordance with approved product labeling.
- dacarbazine
givosiran will increase the level or effect of dacarbazine by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP1A2 substrates with givosiran. If unavoidable, decrease the CYP1A2 substrate dosage in accordance with approved product labeling.
- desipramine
givosiran will increase the level or effect of desipramine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP2D6 substrates with givosiran. If unavoidable, decrease the CYP2D6 substrate dosage in accordance with approved product labeling.
- deutetrabenazine
givosiran will increase the level or effect of deutetrabenazine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP2D6 substrates with givosiran. If unavoidable, decrease the CYP2D6 substrate dosage in accordance with approved product labeling.
- doxepin
givosiran will increase the level or effect of doxepin by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP2D6 substrates with givosiran. If unavoidable, decrease the CYP2D6 substrate dosage in accordance with approved product labeling.
- doxorubicin
givosiran will increase the level or effect of doxorubicin by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP2D6 substrates with givosiran. If unavoidable, decrease the CYP2D6 substrate dosage in accordance with approved product labeling.
- doxorubicin liposomal
givosiran will increase the level or effect of doxorubicin liposomal by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP2D6 substrates with givosiran. If unavoidable, decrease the CYP2D6 substrate dosage in accordance with approved product labeling.
- duloxetine
givosiran will increase the level or effect of duloxetine by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP1A2 substrates with givosiran. If unavoidable, decrease the CYP1A2 substrate dosage in accordance with approved product labeling.
givosiran will increase the level or effect of duloxetine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP2D6 substrates with givosiran. If unavoidable, decrease the CYP2D6 substrate dosage in accordance with approved product labeling. - eliglustat
givosiran will increase the level or effect of eliglustat by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP2D6 substrates with givosiran. If unavoidable, decrease the CYP2D6 substrate dosage in accordance with approved product labeling.
- estradiol
givosiran will increase the level or effect of estradiol by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP1A2 substrates with givosiran. If unavoidable, decrease the CYP1A2 substrate dosage in accordance with approved product labeling.
- estrogens esterified
givosiran will increase the level or effect of estrogens esterified by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP1A2 substrates with givosiran. If unavoidable, decrease the CYP1A2 substrate dosage in accordance with approved product labeling.
- estropipate
givosiran will increase the level or effect of estropipate by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP1A2 substrates with givosiran. If unavoidable, decrease the CYP1A2 substrate dosage in accordance with approved product labeling.
- fesoterodine
givosiran will increase the level or effect of fesoterodine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP2D6 substrates with givosiran. If unavoidable, decrease the CYP2D6 substrate dosage in accordance with approved product labeling.
- flecainide
givosiran will increase the level or effect of flecainide by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP2D6 substrates with givosiran. If unavoidable, decrease the CYP2D6 substrate dosage in accordance with approved product labeling.
- fluoxetine
givosiran will increase the level or effect of fluoxetine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP2D6 substrates with givosiran. If unavoidable, decrease the CYP2D6 substrate dosage in accordance with approved product labeling.
- fluphenazine
givosiran will increase the level or effect of fluphenazine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP2D6 substrates with givosiran. If unavoidable, decrease the CYP2D6 substrate dosage in accordance with approved product labeling.
- flutamide
givosiran will increase the level or effect of flutamide by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP1A2 substrates with givosiran. If unavoidable, decrease the CYP1A2 substrate dosage in accordance with approved product labeling.
- fluvoxamine
givosiran will increase the level or effect of fluvoxamine by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP1A2 substrates with givosiran. If unavoidable, decrease the CYP1A2 substrate dosage in accordance with approved product labeling.
givosiran will increase the level or effect of fluvoxamine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP2D6 substrates with givosiran. If unavoidable, decrease the CYP2D6 substrate dosage in accordance with approved product labeling. - guanabenz
givosiran will increase the level or effect of guanabenz by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP1A2 substrates with givosiran. If unavoidable, decrease the CYP1A2 substrate dosage in accordance with approved product labeling.
- haloperidol
givosiran will increase the level or effect of haloperidol by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP2D6 substrates with givosiran. If unavoidable, decrease the CYP2D6 substrate dosage in accordance with approved product labeling.
- iloperidone
givosiran will increase the level or effect of iloperidone by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP2D6 substrates with givosiran. If unavoidable, decrease the CYP2D6 substrate dosage in accordance with approved product labeling.
- imipramine
givosiran will increase the level or effect of imipramine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP2D6 substrates with givosiran. If unavoidable, decrease the CYP2D6 substrate dosage in accordance with approved product labeling.
- lidocaine
givosiran will increase the level or effect of lidocaine by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP1A2 substrates with givosiran. If unavoidable, decrease the CYP1A2 substrate dosage in accordance with approved product labeling.
- maprotiline
givosiran will increase the level or effect of maprotiline by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP2D6 substrates with givosiran. If unavoidable, decrease the CYP2D6 substrate dosage in accordance with approved product labeling.
- methamphetamine
givosiran will increase the level or effect of methamphetamine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP2D6 substrates with givosiran. If unavoidable, decrease the CYP2D6 substrate dosage in accordance with approved product labeling.
- metoprolol
givosiran will increase the level or effect of metoprolol by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP2D6 substrates with givosiran. If unavoidable, decrease the CYP2D6 substrate dosage in accordance with approved product labeling.
- mexiletine
givosiran will increase the level or effect of mexiletine by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP1A2 substrates with givosiran. If unavoidable, decrease the CYP1A2 substrate dosage in accordance with approved product labeling.
- mirtazapine
givosiran will increase the level or effect of mirtazapine by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP1A2 substrates with givosiran. If unavoidable, decrease the CYP1A2 substrate dosage in accordance with approved product labeling.
givosiran will increase the level or effect of mirtazapine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP2D6 substrates with givosiran. If unavoidable, decrease the CYP2D6 substrate dosage in accordance with approved product labeling. - nebivolol
givosiran will increase the level or effect of nebivolol by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP2D6 substrates with givosiran. If unavoidable, decrease the CYP2D6 substrate dosage in accordance with approved product labeling.
- nortriptyline
givosiran will increase the level or effect of nortriptyline by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP2D6 substrates with givosiran. If unavoidable, decrease the CYP2D6 substrate dosage in accordance with approved product labeling.
- olanzapine
givosiran will increase the level or effect of olanzapine by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP1A2 substrates with givosiran. If unavoidable, decrease the CYP1A2 substrate dosage in accordance with approved product labeling.
- paroxetine
givosiran will increase the level or effect of paroxetine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP2D6 substrates with givosiran. If unavoidable, decrease the CYP2D6 substrate dosage in accordance with approved product labeling.
- perphenazine
givosiran will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP2D6 substrates with givosiran. If unavoidable, decrease the CYP2D6 substrate dosage in accordance with approved product labeling.
- pimozide
givosiran will increase the level or effect of pimozide by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP1A2 substrates with givosiran. If unavoidable, decrease the CYP1A2 substrate dosage in accordance with approved product labeling.
givosiran will increase the level or effect of pimozide by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP2D6 substrates with givosiran. If unavoidable, decrease the CYP2D6 substrate dosage in accordance with approved product labeling. - pindolol
givosiran will increase the level or effect of pindolol by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP2D6 substrates with givosiran. If unavoidable, decrease the CYP2D6 substrate dosage in accordance with approved product labeling.
- pirfenidone
givosiran will increase the level or effect of pirfenidone by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP1A2 substrates with givosiran. If unavoidable, decrease the CYP1A2 substrate dosage in accordance with approved product labeling.
- pitolisant
givosiran will increase the level or effect of pitolisant by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP2D6 substrates with givosiran. If unavoidable, decrease the CYP2D6 substrate dosage in accordance with approved product labeling.
- pomalidomide
givosiran will increase the level or effect of pomalidomide by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP1A2 substrates with givosiran. If unavoidable, decrease the CYP1A2 substrate dosage in accordance with approved product labeling.
- procainamide
givosiran will increase the level or effect of procainamide by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP2D6 substrates with givosiran. If unavoidable, decrease the CYP2D6 substrate dosage in accordance with approved product labeling.
- promethazine
givosiran will increase the level or effect of promethazine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP2D6 substrates with givosiran. If unavoidable, decrease the CYP2D6 substrate dosage in accordance with approved product labeling.
- propafenone
givosiran will increase the level or effect of propafenone by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP2D6 substrates with givosiran. If unavoidable, decrease the CYP2D6 substrate dosage in accordance with approved product labeling.
- propranolol
givosiran will increase the level or effect of propranolol by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP1A2 substrates with givosiran. If unavoidable, decrease the CYP1A2 substrate dosage in accordance with approved product labeling.
givosiran will increase the level or effect of propranolol by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP2D6 substrates with givosiran. If unavoidable, decrease the CYP2D6 substrate dosage in accordance with approved product labeling. - protriptyline
givosiran will increase the level or effect of protriptyline by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP2D6 substrates with givosiran. If unavoidable, decrease the CYP2D6 substrate dosage in accordance with approved product labeling.
- ramelteon
givosiran will increase the level or effect of ramelteon by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP1A2 substrates with givosiran. If unavoidable, decrease the CYP1A2 substrate dosage in accordance with approved product labeling.
- rasagiline
givosiran will increase the level or effect of rasagiline by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP1A2 substrates with givosiran. If unavoidable, decrease the CYP1A2 substrate dosage in accordance with approved product labeling.
- riluzole
givosiran will increase the level or effect of riluzole by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP1A2 substrates with givosiran. If unavoidable, decrease the CYP1A2 substrate dosage in accordance with approved product labeling.
- risperidone
givosiran will increase the level or effect of risperidone by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP2D6 substrates with givosiran. If unavoidable, decrease the CYP2D6 substrate dosage in accordance with approved product labeling.
- ritonavir
givosiran will increase the level or effect of ritonavir by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP2D6 substrates with givosiran. If unavoidable, decrease the CYP2D6 substrate dosage in accordance with approved product labeling.
- ropinirole
givosiran will increase the level or effect of ropinirole by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP1A2 substrates with givosiran. If unavoidable, decrease the CYP1A2 substrate dosage in accordance with approved product labeling.
- ropivacaine
givosiran will increase the level or effect of ropivacaine by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP1A2 substrates with givosiran. If unavoidable, decrease the CYP1A2 substrate dosage in accordance with approved product labeling.
- sertraline
givosiran will increase the level or effect of sertraline by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP2D6 substrates with givosiran. If unavoidable, decrease the CYP2D6 substrate dosage in accordance with approved product labeling.
- stiripentol
givosiran will increase the level or effect of stiripentol by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP1A2 substrates with givosiran. If unavoidable, decrease the CYP1A2 substrate dosage in accordance with approved product labeling.
- tacrine
givosiran will increase the level or effect of tacrine by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP1A2 substrates with givosiran. If unavoidable, decrease the CYP1A2 substrate dosage in accordance with approved product labeling.
- tamsulosin
givosiran will increase the level or effect of tamsulosin by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP2D6 substrates with givosiran. If unavoidable, decrease the CYP2D6 substrate dosage in accordance with approved product labeling.
- tasimelteon
givosiran will increase the level or effect of tasimelteon by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP1A2 substrates with givosiran. If unavoidable, decrease the CYP1A2 substrate dosage in accordance with approved product labeling.
- theophylline
givosiran will increase the level or effect of theophylline by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP1A2 substrates with givosiran. If unavoidable, decrease the CYP1A2 substrate dosage in accordance with approved product labeling.
- thioridazine
givosiran will increase the level or effect of thioridazine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP2D6 substrates with givosiran. If unavoidable, decrease the CYP2D6 substrate dosage in accordance with approved product labeling.
- thiothixene
givosiran will increase the level or effect of thiothixene by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP1A2 substrates with givosiran. If unavoidable, decrease the CYP1A2 substrate dosage in accordance with approved product labeling.
- timolol
givosiran will increase the level or effect of timolol by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP2D6 substrates with givosiran. If unavoidable, decrease the CYP2D6 substrate dosage in accordance with approved product labeling.
- tizanidine
givosiran will increase the level or effect of tizanidine by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP1A2 substrates with givosiran. If unavoidable, decrease the CYP1A2 substrate dosage in accordance with approved product labeling.
- tolterodine
givosiran will increase the level or effect of tolterodine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP2D6 substrates with givosiran. If unavoidable, decrease the CYP2D6 substrate dosage in accordance with approved product labeling.
- tramadol
givosiran will increase the level or effect of tramadol by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP2D6 substrates with givosiran. If unavoidable, decrease the CYP2D6 substrate dosage in accordance with approved product labeling.
- trifluoperazine
givosiran will increase the level or effect of trifluoperazine by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP1A2 substrates with givosiran. If unavoidable, decrease the CYP1A2 substrate dosage in accordance with approved product labeling.
- trimipramine
givosiran will increase the level or effect of trimipramine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP2D6 substrates with givosiran. If unavoidable, decrease the CYP2D6 substrate dosage in accordance with approved product labeling.
- valbenazine
givosiran will increase the level or effect of valbenazine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP2D6 substrates with givosiran. If unavoidable, decrease the CYP2D6 substrate dosage in accordance with approved product labeling.
- venlafaxine
givosiran will increase the level or effect of venlafaxine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP2D6 substrates with givosiran. If unavoidable, decrease the CYP2D6 substrate dosage in accordance with approved product labeling.
- vortioxetine
givosiran will decrease the level or effect of vortioxetine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP2D6 substrates with givosiran. If unavoidable, decrease the CYP2D6 substrate dosage in accordance with approved product labeling.
- voxilaprevir
givosiran will increase the level or effect of voxilaprevir by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP1A2 substrates with givosiran. If unavoidable, decrease the CYP1A2 substrate dosage in accordance with approved product labeling.
Monitor Closely (3)
- melatonin
givosiran will increase the level or effect of melatonin by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor. Monitor melatonin effects if coadministered with moderate CYP1A2 inhibitors
- oliceridine
givosiran will increase the level or effect of oliceridine by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. If concomitant use is necessary, may require less frequent oliceridine dosing. Closely monitor for respiratory depression and sedation and titrate subsequent doses accordingly. If inhibitor is discontinued, consider increase oliceridine dosage until stable drug effects are achieved. Monitor for signs of opioid withdrawal.
- warfarin
givosiran will increase the level or effect of warfarin by Other (see comment). Use Caution/Monitor. Warfarin's less potent R-enantiomer is metabolized in part by CYP3A4 (and also CYP1A2 and CYP2C19). Monitor INR more frequently if coadministered with inhibitors of these isoenzymes and adjust warfarin dose if needed.
Minor (0)
Adverse Effects
>10%
Nausea (27%)
Injection-site reactions (25%)
Rash (17%)
Increased serum creatinine (15%)
Elevated transaminases (13%)
1-10%
Fatigue (10%)
<1%
Anaphylaxis
Postmarketing Reports
Blood homocysteine increased
Warnings
Contraindications
Severe hypersensitivity, including anaphylaxis
Cautions
Anaphylaxis observed; ensure medical support is available to appropriately manage anaphylactic reactions when administering; monitor for signs and symptoms of anaphylaxis
Transaminase elevations (ALT) of ≥3x ULN observed in the placebo-controlled trial; primarily occurred 3-5 months after initiating treatment; monitor
Increased serum creatinine levels and decreased eGFR reported; monitor renal function as clinically indicated
Injection-site reactions reported; symptoms included erythema, pain, pruritus, rash, discoloration, or swelling
Blood homocysteine
- Increases in blood homocysteine levels reported in patients receiving therapy; clinical relevance of elevations in blood homocysteine during therapy unknown
- Measure blood homocysteine levels prior to initiating treatment and monitor for changes during treatment
- In patients with elevated blood homocysteine levels, assess folate, vitamins B12 and B6; consider treatment with a supplement containing vitamin B6 (as monotherapy or a multivitamin preparation)
Drug interaction overview
- In vitro studies indicate that givosiran does not directly inhibit or induce CYP enzymes; however, because of its pharmacological effects on the hepatic heme biosynthesis pathway, givosiran has the potential to reduce the activity of CYP enzymes in the liver
-
Sensitive CYP1A2 or CYP2D6 substrates
- Sensitive CYP1A2 substrates: Coadministration increased caffeine (sensitive CYP1A2 substrate) AUC by 3.1-fold and Cmax by 1.3-fold
- Sensitive CYP2D6 substrates: Coadministration increased dextromethorphan (sensitive CYP2D6 substrate) AUC by 2.4-fold and Cmax by 2-fold
- Avoid use with CYP1A2 or CYP2D6 substrates, for which minimal concentration changes may lead to serious or life-threatening toxicities
- If concomitant use is unavoidable, decrease CYP1A2 or CYP2D6 substrate dosage in accordance with its prescribing information
Pregnancy & Lactation
Pregnancy
Data are not available regarding use in pregnant women to evaluate a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes
Animal studies
- Administration to pregnant rabbits during organogenesis resulted in adverse developmental outcomes at doses that produced maternal toxicity
Clinical considerations
- Porphyria attacks during pregnancy, often triggered by hormonal changes, occur in 24-95% of patients with AHP, with maternal mortality ranging from 2-42%
- Pregnancy in patients with AHP is associated with higher rates of spontaneous abortion, hypertension, and low-birth-weight infants
Lactation
Data are not available regarding use in breastfeeding women
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
Double-stranded small-interfering RNA that causes degradation of aminolevulinate synthase 1 (ALAS1) 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 (ALA) and porphobilinogen (PBG), factors associated with attacks and other disease manifestations of AHP
Absorption
Peak plasma time: 3 hr (parent drug); 7 hr (metabolite)
Peak plasma concentration: 321 ng/mL (parent drug); 123 ng/mL (metabolite)
AUC: 4130 ng⋅hr/mL (parent drug); 1930 ng⋅hr/mL (metabolite)
Distribution
Vd: 10.4 L
Protein bound: 90% (parent drug)
Organ distribution: Parent drug and metabolite primarily distributed to liver
Metabolism
Metabolized by nucleases to oligonucleotides of shorter lengths
Not a substrate of CYP enzymes
Active metabolite: AS(N-1)3' givosiran is equipotent to givosiran in plasma; AUC0-24 represents 45% of givosiran AUC at the recommended dosage
Elimination
Half-life: 6 hr (parent drug or metabolite)
Clearance: 35.1 L/hr (18%; parent drug); 64.7 L/hr (33%; metabolite)
Excretion: Urine 5-14% (parent drug); 4-13% (metabolite)
Administration
SC Preparation
Ensure that medical support is available to appropriately manage anaphylactic reactions when administering
Inspect visually for particulate matter and discoloration before administration
Givosiran is a sterile, preservative-free, clear, colorless-to-yellow ready-to-use solution
Does not require additional reconstitution or dilution prior to administration
SC Administration
Intended for SC administration by a healthcare professional only
Calculate weight-based dose
Withdraw volume of solution from vial using ≥21-gauge needle
Divide doses requiring volumes >1.5 mL equally into multiple syringes
After withdrawing solution, replace the ≥21-gauge or larger needle with either a 25- or 27-gauge needle with 1/2” or 5/8” needle length
Avoid having solution on the needle tip until the needle is in the SC space
Administer SC into abdomen, back or side of upper arms, or thighs; rotate injection sites
Do not inject into scar tissue or areas that are reddened, inflamed, or swollen
If injecting into abdomen, avoid 5-cm diameter circle around the navel
If >1 injection needed for a single dose, the injection sites should be at least 2 cm apart from previous injection locations
Discard unused portion of the drug
Missed dose
- Administer as soon as possible after a missed dose
- Resume dosing at monthly intervals following administration of the missed dose
Storage
Store refrigerated or at controlled room temperature of 2-25°C (36-77°F)
Store in original container until ready for use
Images
Formulary
Adding plans allows you to compare formulary status to other drugs in the same class.
To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.
Adding plans allows you to:
- View the formulary and any restrictions for each plan.
- Manage and view all your plans together – even plans in different states.
- Compare formulary status to other drugs in the same class.
- Access your plan list on any device – mobile or desktop.
