Olezarsen Sodium (Monograph)

Brand name: Tryngolza
Drug class: Antilipemic Agents, Miscellaneous

Introduction

Olezarsen sodium is an antisense oligonucleotide (ASO) directed against apolipoprotein C-III (apoC-III) mRNA and conjugated with N-acetyl galactosamine (GalNAc).

Uses for Olezarsen Sodium

Olezarsen has the following uses:

Olezarsen is indicated as an adjunct to diet to reduce triglycerides in adults with familial chylomicronemia syndrome (FCS).

Olezarsen Sodium Dosage and Administration

General

Olezarsen sodium is available in the following dosage form(s) and strength(s):

Injection: 80 mg/0.8 mL of olezarsen in a single-dose autoinjector.

Dosage

It is essential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:

Adults

Dosage and Administration

The recommended dosage of olezarsen is 80 mg administered subcutaneously once monthly.
Administer olezarsen into the abdomen or front of the thigh. The back of the upper arm can also be used as an injection site if a healthcare provider or caregiver administers the injection.
Maintain a low-fat diet (20 g fat per day) in conjunction with the use of olezarsen.

Cautions for Olezarsen Sodium

Contraindications

History of serious hypersensitivity reactions to olezarsen or any of the excipients in the formulation.

Warnings/Precautions

Hypersensitivity Reactions

Hypersensitivity reactions (including symptoms of bronchospasm, diffuse erythema, facial swelling, urticaria, chills, and myalgias) have been reported in patients treated with olezarsen. Advise patients on the signs and symptoms of hypersensitivity reactions and instruct patients to promptly seek medical attention and discontinue use of olezarsen if hypersensitivity reactions occur.

Specific Populations

Pregnancy

There are no available data on olezarsen use in pregnant women to inform drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Patients with familial chylomicronemia syndrome are at risk for pancreatitis during pregnancy because of defects in lipid metabolism and increased triglyceride levels.

In animal reproduction studies conducted with the unconjugated antisense oligonucleotide (lacking GalNAc) in rabbits and mice, no adverse effects on development or pregnancy were observed at doses 21 times or 20 times, respectively, the maximum recommended clinical dose.

The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20% respectively.

During pregnancy, triglyceride levels increase during the third trimester of pregnancy. In patients with underlying defects in lipid metabolism, such as familial chylomicronemia syndrome, severe gestational hypertriglyceridemia may occur, increasing the risk of acute pancreatitis during pregnancy.

Lactation

There are no data on the presence of olezarsen in either human or animal milk, the effects on the breastfed infant, or the effects on milk production. However, the unconjugated antisense oligonucleotide, which shares the same nucleotide sequence but lacks GalNAc, was present in the milk of lactating mice at low levels. When a drug is present in animal milk, it is likely that the drug will be present in human milk. Oligonucleotide-based products typically have poor oral bioavailability; therefore, it is considered unlikely that low levels present in milk will lead to clinically relevant levels in breastfed infants. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for olezarsen and any potential adverse effects on the breast-fed infant from olezarsen or from the underlying maternal condition.

Pediatric Use

Safety and effectiveness of olezarsen in pediatric patients have not been established.

Geriatric Use

No dose adjustment is recommended in patients 65 years of age and older. In clinical studies, 111 (38%) patients treated with olezarsen were ≥65 years of age. No overall differences in safety or effectiveness of olezarsen have been observed between patients 65 years of age and older and younger adult patients.

Renal Impairment

No dose adjustment is necessary in patients with mild to moderate renal impairment (estimated glomerular filtration rate [eGFR] ≥30 to <90 mL/minute). Olezarsen has not been studied in patients with severe renal impairment or end-stage renal disease.

Hepatic Impairment

No dose adjustment is recommended in patients with mild hepatic impairment. Olezarsen has not been studied in patients with moderate or severe hepatic impairment.

Common Adverse Effects

Most common adverse reactions (incidence >5% of olezarsen-treated patients and >3% higher frequency than placebo) were injection site reactions, decreased platelet count, and arthralgia.

Drug Interactions

Specific Drugs

It is essential that the manufacturer's labeling be consulted for more detailed information on interactions with this drug, including possible dosage adjustments. Interaction highlights:

Please see product labeling for drug interaction information.

Actions

Mechanism of Action

Olezarsen is an antisense oligonucleotide-GalNAc₃ conjugate that binds to apoC-III mRNA leading to mRNA degradation and resulting in a reduction of serum apoC-III protein. Reduction of apoC-III protein leads to increased clearance of plasma triglycerides (TG) and very low density lipoprotein (VLDL).

Advice to Patients

Advise the patient to read the FDA-approved patient labeling (Patient Information and Instructions for Use).
Inform patients that serious hypersensitivity reactions, including bronchospasm, diffuse erythema, facial swelling, urticaria, chills, and myalgia, have been reported in patients treated with olezarsen. Advise patients on the signs and symptoms of hypersensitivity reactions and instruct them to stop taking olezarsen and seek medical advice promptly if such symptoms occur.
Advise patients with familial chylomicronemia syndrome that use of lipid-regulating agents does not reduce the importance of adhering to a low-fat diet.
Instruct patients to take olezarsen as prescribed. If a dose is missed, instruct patients to take it as soon as they remember. Resume dosing at monthly intervals from the date of the most recently administered dose.

Additional Information

AHFSfirstRelease^™. For additional information until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual uses, dosage and administration, cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.