• Treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis.

Contraindicated in:

• Hypersensitivity
• Platelet count <100 × 10⁹/L
• History of acute glomerulonephritis due to inotersen
• Severe proteinuria (urine protein to creatinine ratio >1000 mg/g)
• Patients who are not candidates for immunosuppressive therapy
• Liver transplant recipients (↑ risk of rejection)
• Severe renal impairment or end-stage renal disease
• Moderate or severe hepatic impairment.

Use Cautiously in:

• OB: Safety not established in pregnancy
• Lactation: Use while breastfeeding only if potential maternal benefit justifies potential risk to infant
• Pedi: Safety and effectiveness not established in children
• Geri: Older adults may be at ↑ risk of adverse reactions.

CV: atrial fibrillation/flutter, bradycardia, peripheral edema, syncope, tachycardia.

GI: nausea, vomiting, ↑ liver enzymes, dry mouth.

GU: ↑ serum creatinine, proteinuria, glomerulonephritis, renal failure.

Hemat: anemia, bleeding, thrombocytopenia, eosinophilia.

Local: injection site reactions.

Metab: ↓ appetite.

MS: arthralgia, myalgia.

Neuro: carotid artery dissection, fatigue, headache, paresthesia, stroke.

Resp: dyspnea.

Misc: chills, fever, ↓ vitamin A concentrations, hypersensitivity reactions.

Drug-Drug:

• ↑ risk of bleeding with antiplatelet agents (including aspirin, clopidogrel, prasugrel, or ticagrelor), anticoagulants (including apixaban, dabigatran, edoxaban, heparin, rivaroxaban, or warfarin), and NSAIDs; consider discontinuing these medications if platelet count <50 × 10⁹/L.
• Concurrent use with nephrotoxic drugs may ↑ risk of nephrotoxicity.

• Solution for injection (prefilled syringes): 284 mg/1.5 mL;

• SC (Adults): 284 mg once weekly.

Tegsedi

• Acts as an antisense oligonucleotide that binds to and causes degradation of mutant and wild-type human transthyretin (TTR) mRNA , which subsequently results in a reduction of serum TTR protein and TTR protein deposits in tissues.

• Reduction in impairment from neuropathy and improved quality of life.

Therapeutic Classification: n/a

Pharmacologic Classification: antisense oligonucleotides

Absorption: Rapidly absorbed following SUBQ administration.

Distribution: Extensively distributed to tissues.

Protein Binding: >94%.

Metabolism/Excretion: Metabolized by nucleases to nucleotides of various lengths; primarily excreted in urine (<1% as unchanged drug).

Half-life: 32.3 days.

(plasma concentrations)

• REMS: Instruct patient on proper technique for administration including equipment , storage, discarding of syringes. Explain REMS program requirements to patient. Advise patient to read Medication Guide before starting therapy and with each Rx refill in case of changes.
• Advise patient to notify health care professional immediately if signs and symptoms of thrombocytopenia (unusual bruising or a rash of tiny reddish-purple spots, often on lower legs; bleeding from skin cuts that continue to ooze; bleeding from gums or nose; blood in urine or stools; bleeding into whites of eyes; sudden severe headache; neck stiffness; vomiting or coughing up blood; abnormal or heavy menstrual bleeding, kidney inflammation (puffiness or swelling in face, feet or hands; new onset or worsening shortness of breath; coughing; blood in urine or brown urine; foamy urine; passing less urine than usual), stroke (sudden numbness or weakness, especially on one side of body; severe headache or neck pain; confusion; problems with vision, speech, or balance; droopy eyelids), inflammatory and immune system problems (unexpected change in walking, weakness and spasms in legs; back pain; weight loss; headache; vomiting; problems with speech) liver injury (unexpected nausea and vomiting, stomach pain, being not hungry, yellowing of skin, having dark urine, or hypersensitivity reactions (joint pain, chills, redness on palms, muscle pain, chest pain, flushing, tremor, flu-like symptoms, high BP, difficulty swallowing) occur.
• Instruct patients to take recommended daily allowance of vitamin A. Advise patients to contact health care professional ocular symptoms (night blindness).
• Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care professional before taking other Rx, OTC, herbal products, especially Vitamin A or beta-carotene supplements or blood thinners.
• Rep: Advise patient to notify health care professional if pregnancy is planned or suspected or if breastfeeding. Inform patient of pregnancy exposure registry that monitors pregnancy outcomes in women exposed to inotersen during pregnancy. Register by calling: 1-877-465-7510, emailing: tegsedipregnancy@ubc.com, or visiting online at: .
• Emphasize importance of regular lab tests to monitor for side effects.

in-oh-TER-sen

NDC Code^*

• 72126- Akcea Therapeutics, Inc.
  • 72126-007- Tegsedi
    • 72126-007-01- 4 TRAY in 1 CARTON (72126-007-01) > 1 SYRINGE in 1 TRAY (72126-007-02) > 1.5 mL in 1 SYRINGE