Inotersen (Tegsedi) - Uses, Dose, Side effects, MOA, Brands

A 2′-O-methoxyethyl modified antisense oligonucleotide called inotersen (Tegsedi) lowers transthyretin synthesis.

In initial hereditary transthyretin amyloidosis polyneuropathy, it has recently been shown to lessen nerve degeneration and, as a result, enhance the quality of life.

Inotersen (Tegsedi) Uses:

  • Amyloidosis-mediated polyneuropathy caused by inherited transthyretin: 

    • Treatment of hereditary Amyloi's polyneuropathy caused by transthyretin

Inotersen (Tegsedi) Use in Adults:

Treatment of polyneuropathy caused by familial transthyretin-mediated amyloidosis with inotersen (Tegsedi) dosage

  • 284 mg once a week as a sub-Q
  • Missed doses:

    • If you forget to take your medicine, take it as soon as you remember.

    • If the next dose is less than two days away, just skip the missed dose and take the next one as scheduled.

Use in children:

Not recommended for children

Pregnancy Risk Category: N (Not assigned)

  • Some negative effects were noticed in animal reproduction studies.
  • To support the growth of embryos, there needs to be sufficient Vitamin A levels, but inotersen lowers the levels of Vitamin A in the blood.
  • It is important to suggest reliable birth control methods for women capable of becoming pregnant and for men with female partners. (Benson 2018, p. )

Use of Inotersen during breastfeeding

  • It's unclear whether inotersen is present in breast milk.

  • The company recommends weighing the benefits of the treatment for the mother against the potential risks of the drug exposure to the child.

Inotersen (Tegsedi) Dose in Kidney Disease:

  • Renal impairment prior to treatment initiation:

    • If the estimated glomerular filtration rate (eGFR) is 30 mL/min/1.73 m2, there is no need to adjust the dose.
    • There are no specified changes in dosage for eGFR less than 30 mL/minute/1.73 m2 as it hasn't been studied according to the manufacturer's labeling.
  • Renal toxicity during treatment:

    • If the estimated glomerular filtration rate (eGFR) is 45 mL/min/1.73 m2 or the urine protein to creatinine ratio (UPCR) is 1,000 mg/g, it's recommended to postpone starting the therapy until the cause is investigated.
    • Once the underlying cause is resolved or the eGFR reaches 45 mL/min/1.73 m2 and UPCR reaches 1,000 mg/g, the dosage of 284 mg once a week can be resumed.

Note: If acute glomerulonephritis and a UPCR of less than 2,000 mg/g are verified, therapy should be completely stopped.

Inotersen (Tegsedi) Dose in Liver disease:

  • Before treatment begins, hepatic impairment

    • Mild impairment
      • There is no need to change the dosage.
    • Moderate to severe impairment
      • The labeling provided by the manufacturer does not mention dose adjustments.
      • There has been no testing.
  • Treatment for Hepatotoxicity

    • If patients show signs or symptoms of liver problems, it's important to check their blood for markers like transaminases or total bilirubin.

    • If needed, the treatment should be either stopped or temporarily halted.

    • For patients who have undergone liver transplants and are facing rejection, immediate treatment is necessary.

Common Side Effects of Inotersen (Tegsedi):

  • Cardiovascular:

    • Peripheral Edema
    • Cardiac Arrhythmia
    • Presyncope
    • Syncope
  • Central Nervous System:

    • Headache
    • Fatigue
    • Chills
    • Paresthesia
  • Gastrointestinal:

    • Nausea
  • Hematologic & Oncologic:

    • Thrombocytopenia
    • Anemia
  • Immunologic:

    • Antibody Development
  • Local:

    • Injection Site Reaction
  • Neuromuscular & Skeletal:

    • Myalgia
    • Arthralgia
  • Renal:

    • Renal Insufficiency
  • Miscellaneous:

    • Fever

Less Common Side Effects of Inotersen (Tegsedi):

  • Cardiovascular:

    • Orthostatic hypotension
  • Gastrointestinal:

    • Decreased appetite
    • Xerostomia
  • Hematologic & oncologic:

    • Bruise
    • Eosinophilia
  • Hepatic:

    • Increased liver enzymes
  • Infection:

    • Increased serum alanine aminotransferase
    • Bacterial infection
  • Renal:

    • Glomerulonephritis
  • Respiratory:

    • Dyspnea
    • Flu-like symptoms

Frequency not defined:

  • Endocrine & metabolic:

    • Vitamin A deficiency

Contraindications to Inotersen (Tegsedi):

If there is intolerance to inotersen or any ingredient in its formulation, if the platelet count is less than 100,000/mm3, or if there is a history of inotersen-related acute glomerulonephritis, the use of inotersen is not recommended.

Labeling in Canada: more signs against (not in US labeling) Before therapy:

The creatinine to urine protein ratio is 113 mg/mol (1 g/mol), the estimated glomerular filtration rate (eGFR) is 45 mL/min/1.73m2, and there is evidence of serious liver damage.

Warnings and Precautions

  • Cerebrovascular:

    • Within two days of taking the first dose, there is a risk of potential side effects such as stroke and cervicocephalic arterial dissection.
    • Patients should be advised to promptly inform their doctor if they observe any symptoms that could suggest a stroke or arterial dissection.
  • Glomerulonephritis: [US Boxed Warning]:

    • If glomerulonephritis develops, it may require immunosuppressive treatment and could lead to renal failure, necessitating dialysis.

    • Patients with a urine protein to creatinine ratio (UPCR) of 1,000 mg/g or higher should not initiate the medication.

    • Before starting, assess serum creatinine, estimated glomerular filtration rate (eGFR), UPCR, and urinalysis results.

    • During treatment, monitor these levels every two weeks. Patients with a UPCR of 1,000 mg/g or more or an eGFR below 45 mL/minute/1.73 m2 should not continue the medication until the cause is investigated.

      If a dose is skipped, weekly dosing can resume if the underlying cause of the reduced kidney function is addressed, eGFR reaches 45 mL/minute/1.73 m2, and UPCR falls below 1,000 mg/g, or both.

    • One participant in a clinical trial with glomerulonephritis who did not receive immunosuppressive treatment continued to need dialysis.

    • For individuals with a UPCR of 2,000 mg/g or higher, evaluate further for acute glomerulonephritis as needed.

    • Immediately stop treatment if acute glomerulonephritis is identified.

    • Exercise caution in patients receiving nephrotoxic and other renal-harming medications concurrently.

    • Nephrotic syndrome, which may involve edema, increased blood clotting, and heightened infection susceptibility, was often seen with cases of glomerulonephritis.

    • Since immunosuppressive drugs are commonly used for glomerulonephritis, they should be avoided in patients for whom they are not recommended.

  • Hepatic effects:

    • Abnormal liver function tests (LFTs), such as an increase in ALT (alanine transaminase) to three times or more the upper limit of normal (ULN), have been observed.

    • These liver abnormalities may improve with ongoing use of the medication. There is also a risk of immune-mediated biliary disease.

      While undergoing treatment, it's important to monitor the levels of ALT, AST (aspartate transaminase), and total bilirubin.

    • Check these levels at the beginning of treatment and then every four months thereafter.

    • If patients show signs or symptoms of liver dysfunction, it is advisable to halt or discontinue the treatment.

    • Additionally, serum transaminases and total bilirubin levels should be assessed in such cases.

  • Hypersensitivity reactions:

    • Hypersensitivity reactions have been reported with this medication.

    • Symptoms typically occur within two hours of injection and may include flushing, chest discomfort, high blood pressure, chills, difficulty swallowing, increased eosinophils (a type of white blood cell), involuntary movements, headache, joint pain, muscle pain, redness of the palms, and flu-like symptoms.

    • In clinical studies, patients who had hypersensitivity reactions also developed antibodies against inotersen.

    • If a hypersensitivity reaction occurs, it is recommended to discontinue the use of the medication.

    • Patients who have previously experienced hypersensitivity reactions should not receive further treatment with this medication.

  • Inflammatory and immune effects:

    • Severe immunological and inflammatory side effects have been reported, such as immune thrombocytopenia, glomerulonephritis, and systemic vasculitis with positive antineutrophil cytoplasmic autoantibodies (ANCA).
    • Additionally, rare but severe neurological adverse reactions, including paraparesis (partial paralysis of the lower limbs) and impaired speech, have been documented.
  • Thrombocytopenia: [US Boxed Warning]:

    • This treatment can lead to a potentially life-threatening condition known as acute and unpredictable thrombocytopenia.

    • Unfortunately, one participant in a clinical study died due to a cerebral hemorrhage related to this condition. To manage this risk:

    • Platelet Count Check:

    • Before starting the treatment, it's crucial to check the platelet count. Patients with a platelet count below 100,000/mm3 should not use this medication.

    • Monitoring Platelet Counts:

    • If the platelet counts are 75,000/mm3 or higher, they should be checked weekly. If they fall below 75,000/mm3, more frequent monitoring is necessary.

    • Symptoms of Thrombocytopenia:

    • If a patient shows signs or symptoms of thrombocytopenia, a platelet count should be obtained promptly.

    • Treatment should not continue until the platelet count is satisfactory based on a reliable blood sample.

    • Post-Treatment Monitoring:

    • After the therapy concludes, it's important to monitor the platelet count for about 8 weeks to ensure it remains above 75,000/mm3.

    • Caution with Antiplatelet or Anticoagulation Therapy:

    • Use this medication cautiously in patients receiving antiplatelet or anticoagulation therapy.

    • If the platelet count falls below 50,000/mm3, consider discontinuing antiplatelet or anticoagulation therapy.

    • Avoid in Certain Patients:

    • Inotersen therapy should be avoided in patients for whom corticosteroid medication is not recommended.

    • Corticosteroid therapy is advised for patients with a platelet count of 50,000/mm3 and for those with probable immune-mediated thrombocytopenia.

    • Patient Awareness:

    • Patients should be informed to contact their doctor if symptoms of thrombocytopenia manifest.

  • Vitamin A levels:

    This medication can lead to a decrease in the level of serum vitamin A. To address this:
    • Vitamin A Supplements:

    • During the treatment, it is recommended to take vitamin A supplements at the recommended dietary amount (RDA).

    • Caution with Vitamin A Dosage:

    • Since serum vitamin A levels may not accurately reflect the total vitamin A in the body, it's important not to exceed the recommended dietary amount (RDA) when administering vitamin A supplements.

    • Ocular Symptoms:

    • If there are ocular symptoms such as night blindness, it is advised to consult with an ophthalmologist.

Inotersen: Drug Interaction

Risk Factor C (Monitor therapy)

Agents with Antiplatelet Properties (e.g., P2Y12 inhibitors, NSAIDs, SSRIs, etc.)

Inotersen may enhance the antiplatelet effect of Agents with Antiplatelet Properties.


Inotersen may enhance the anticoagulant effect of Anticoagulants.


Monitoring parameters:

  • Here's a summary of the monitoring recommendations:

    Platelet Count:

  • Monitor at baseline.
  • Continue monitoring for eight weeks after treatment ends.
  • Extend monitoring for more than eight weeks if platelet count remains below 100,000/mm3.
  • Urinalysis:

  • After treatment cessation, monitor every two weeks at baseline and for an additional eight weeks.
  • AST, ALT, Total Bilirubin:

  • Observe every four months at baseline.
  • Continue observation for eight weeks following treatment cessation.
  • Liver Transplant Patients:

  • For liver transplant patients, monitor at baseline every four months during treatment and for eight weeks after discontinuation.

How to administer Inotersen (Tegsedi)?

Here are the instructions for administering the medication:


  • Administer the medication subcutaneously (SubQ).
  • Give the injection every week on the same day.

Prefilled Syringes:

  • Allow prefilled syringes to reach room temperature for about 30 minutes before administration.

Injection Sites:

  • You can self-inject in your upper thigh or abdomen.
  • Only a caregiver should administer treatment to the upper arm.
  • Avoid treating areas around the waistline or other regions with clothing pressure or friction.

Site Rotation:

  • Switch up injection sites after each administration to prevent discomfort or irritation.

Skin Care:

  • Do not apply anything to the skin that may cause infection or disease.

The way that Inotersen (Tegsedi) works is as follows:

Mechanism of Action:

Inotersen, classified as an antisense oligonucleotide, works by binding to TTR mRNA (messenger RNA) and breaking down both the normal (wild-type) and mutated TTR DNA messages.

This process leads to the formation of protein deposits in tissues and a reduction in serum TTR protein levels.


The absorption of inotersen is rapid, meaning it enters the bloodstream quickly after administration.

Protein Binding:

In the bloodstream, more than 94% of inotersen molecules are bound to proteins.


Inotersen undergoes metabolism by nucleases, resulting in the breakdown of the drug into nucleotides of various lengths.

Elimination Half-life:

The elimination half-life of inotersen is approximately 32.3 days, with a range of 29.4 to 35.5 days.

This indicates the time it takes for half of the administered dose to be cleared from the body.

Time to Peak:

Inotersen reaches its peak concentration in the bloodstream within 2 to 4 hours, with the median time falling within this range.


A minimal amount of inotersen (less than 1%) is excreted unchanged in the urine.

These pharmacokinetic details provide insights into how the drug is absorbed, distributed, metabolized, and eliminated in the body.

International Brands of Inotersen:

  • Tegsedi

Inotersen Brand Names in Pakistan:

No Brands Available in Pakistan.