Tegsedi

Tegsedi Uses, Dosage, Side Effects, Food Interaction and all others data.

Tegsedi is a transthyretin-directed antisense oligonucleotide for the treatment of the polyneuropathy caused by hereditary transthyretin-mediated amyloidosis in adults. It was FDA approved in October 2018. Tegsedi has been shown to improve the course of neurologic disease and quality of life in patients with hereditary transthyretin amyloidosis .

Hereditary transthyretin amyloidosis is caused by single-nucleotide variants in the gene encoding transthyretin (TTR), which lead to transthyretin misfolding and the deposition of amyloid substance systemically. Progressive amyloid accumulation may lead to multiorgan dysfunction and death .

The pharmacodynamic effects of inotersen were studied in hereditary transthyretin-mediated amyloidosis (hATTR) amyloidosis patients treated with 284 mg of inotersen via subcutaneous injection once weekly. With repeated dosing, the mean percentage decreases from baseline in serum TTR (transthyretin) from week 13 to Week 65 of treatment were measured from 68%-74% (median range: 75% to 79%). Similar TTR reductions were seen regardless of TTR mutation, sex, age, or race.

Tegsedi
Uses
Dosage
Side Effect
Precautions
Interactions
Uses during Pregnancy
Uses during Breastfeeding
Accute Overdose
Food Interaction
Half Life
Volume of Distribution
Clearance
Interaction With other Medicine
Contradiction
Storage

Trade Name	Tegsedi
Availability	Prescription only
Generic	Inotersen
Inotersen Other Names	Inotersen
Related Drugs	tafamidis, Vyndamax, Onpattro, Vyndaqel, Amvuttra
Weight	284mg/1.5ml,
Type	Injection, Subcutaneous Solution
Protein binding	Inotersen is highly bound to human plasma proteins (>94%) and the fraction bound is independent of drug concentration.
Groups	Approved, Investigational
Therapeutic Class
Manufacturer	Akcea Therapeutics UK Ltd
Available Country	United Kingdom, United States,
Last Updated:	September 19, 2023 at 7:00 am

Uses

Tegsedi is an antisense oligonucleotide used to treat polyneuropathy of hereditary transthyretin-mediated amyloidosis.

Tegsedi is a transthyretin-directed antisense oligonucleotide indicated for treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis in adults.

Tegsedi is also used to associated treatment for these conditions: Hereditary Transthyretin Amyloidosis, Polyneuropathies caused by Hereditary transthyretin-mediated amyloidosis

How Tegsedi works

Tegsedi is an antisense oligonucleotide that causes degradation of mutant and wild-type TTR mRNA through binding to the TTR mRNA, which results in a reduction of serum TTR protein and TTR protein deposits in tissues.

Toxicity

Thrombocytopenia

Tegsedi causes reductions in platelet count that can result in sudden and unpredictable thrombocytopenia that can be life-threatening. Monitor CBC at regular intervals and adjust/pause treatment as necessary. Do not initiate treatment with this drug in patients with a platelet count below 100 x 10^9/L.

Glomerulonephritis and Renal Toxicity

Tegsedi can cause glomerulonephritis that may result in dialysis-dependent renal failure. It may also exacerbate pre-existing renal dysfunction. Monitor kidney function before and during treatment.

Stroke and Cervicocephalic Arterial Dissection

Tegsedi may cause stroke and cervicocephalic arterial dissection.

Inflammatory and Immune Effects

Inflammatory and immune changes are an expected side effect of some antisense oligonucleotide drugs, including inotersen. In clinical studies, serious inflammatory and immune adverse reactions occurred in Tegsedi-treated patients, including immune thrombocytopenia and glomerulonephritis, as well as one case of antineutrophil cytoplasmic autoantibody (ANCA)- positive systemic vasculitis.

Liver Effects

The liver is a possible site of accumulation of antisense oligonucleotides. In clinical studies, 8% of inotersen-treated patients had an increased alanine aminotransferase (ALT) at least 3 times the upper limit of normal (ULN), compared to 3% of patients on placebo; 3% of inotersen-treated patients had an ALT at least 8 times the upper limit of normal, compared to no patient on placebo. Monitor liver function tests as indicated on the FDA label.

Hypersensitivity Reactions/Antibody Formation

Most of these reactions occur within 2 hours of administration of inotersen and included headache, chest pain, hypertension, chills, flushing, dysphagia, palmar erythema, eosinophilia, involuntary choreaform movements, arthralgia, myalgia, and flu-like symptoms.

Reduced Serum Vitamin A Levels

Tegsedi treatment leads to a decrease in serum vitamin A levels. Supplementation at the recommended daily allowance of vitamin A is advised for patients taking this drug .

Cardiac QT prolongation

Formal QTc studies have not been conducted with this drug. The risk of QTc prolongation with inotersen was evaluated in a randomized, placebo-controlled trial in healthy volunteers. No major changes in the mean QTc interval (>20 ms) were detected in the trial. In the 66-week controlled efficacy trial, 5.4% of the treated patients showed evidence of QRS prolongation on their electrocardiograms (ECGs) to greater than 160 msec and greater than 25% above baseline, compared to and in 1.7% of patients on placebo.

Effects on pregnancy

There are no or limited amount of data from the use of inotersen in pregnant women. Animal studies are insufficient with respect to reproductive toxicity. There are no or limited amount of data from the ingestion of inotersen in pregnant women. Animal studies are not sufficient with respect to reproductive toxicity.

Food Interaction

No interactions found.

Tegsedi Disease Interaction

Major: renal toxicity, thrombocytopeniaModerate: hepatic impairment, renal impairment, vitamin A deficiency

Volume of Distribution

Rapidly distributes broadly to tissues, with the highest concentrations observed in the kidney and liver. This drug does not cross the blood-brain barrier.

Elimination Route

Following subcutaneous administration, inotersen is absorbed rapidly into systemic circulation in a dose-dependent fashion, with the median time to maximum plasma concentrations (Cmax) of 2 to 4 hours.