Tegsedi: Uses, Dosage & Side Effects
An antisense oligonucleotide for the treatment of hereditary transthyretin amyloidosis with stage 1 or stage 2 polyneuropathy in adults
Tegsedi (inotersen) is a prescription antisense oligonucleotide medication used to treat adults with hereditary transthyretin amyloidosis (hATTR) who have stage 1 or stage 2 polyneuropathy. It works by binding to transthyretin (TTR) messenger RNA in the liver and triggering its degradation, thereby reducing the production of both mutant and wild-type TTR protein. This mechanism slows or prevents the accumulation of amyloid fibrils in peripheral nerves and other organs. Tegsedi is administered as a 284 mg subcutaneous injection once weekly using a pre-filled syringe. Due to the risk of serious adverse effects including thrombocytopenia and glomerulonephritis, regular blood and urine monitoring is mandatory throughout treatment and for 8 weeks after discontinuation.
Quick Facts: Tegsedi
Key Takeaways
- Tegsedi (inotersen) is an antisense oligonucleotide that reduces transthyretin protein production in the liver, treating hereditary transthyretin amyloidosis (hATTR) with polyneuropathy in adults.
- Administered as a once-weekly subcutaneous injection of 284 mg using a pre-filled syringe, Tegsedi can be self-administered at home after proper training from a healthcare professional.
- The NEURO-TTR pivotal trial demonstrated that inotersen significantly slowed the progression of neuropathy and preserved quality of life compared with placebo over 15 months of treatment.
- Serious risks include thrombocytopenia (low platelet count), glomerulonephritis (kidney inflammation), liver damage, and vitamin A deficiency, requiring mandatory regular monitoring of blood counts, kidney function, liver function, and vitamin A levels.
- Tegsedi should be stored refrigerated (2–8 °C) but can be kept at room temperature (up to 30 °C) for a maximum of 6 weeks; it must not be frozen.
What Is Tegsedi and What Is It Used For?
Tegsedi contains the active substance inotersen, a 2’-O-methoxyethyl (2’-MOE) modified antisense oligonucleotide. Antisense oligonucleotides are a class of synthetic, short stretches of chemically modified nucleotides that are designed to bind to specific messenger RNA (mRNA) sequences in cells. In the case of inotersen, the target is the mRNA that encodes transthyretin (TTR), a protein primarily produced by the liver that normally transports thyroid hormone (thyroxine) and retinol-binding protein (the carrier of vitamin A) throughout the body.
Hereditary transthyretin amyloidosis (hATTR) is a rare, progressive, and ultimately fatal genetic disorder caused by mutations in the TTR gene. More than 130 different mutations have been identified worldwide, with the Val30Met (also known as V30M) mutation being the most common globally. These mutations cause the transthyretin protein to misfold and aggregate into insoluble amyloid fibrils. Over time, these fibrils deposit in various tissues and organs throughout the body, particularly affecting the peripheral nervous system, the heart, the kidneys, the eyes, and the gastrointestinal tract. The condition was historically known as familial amyloid polyneuropathy (FAP) or, in endemic regions such as northern Sweden, as Skelleftesjukan.
When amyloid fibrils accumulate in peripheral nerves, they cause a condition called polyneuropathy, which manifests as progressive sensory loss, pain, numbness, weakness, and autonomic dysfunction (such as orthostatic hypotension, gastrointestinal disturbances, and urinary problems). Without treatment, hATTR polyneuropathy typically progresses through three stages over a period of 5 to 15 years: stage 1 (ambulatory with preserved walking ability), stage 2 (requiring assistance with walking), and stage 3 (wheelchair-bound or bedridden). Tegsedi is indicated for the treatment of adults with hATTR who have stage 1 or stage 2 polyneuropathy.
The mechanism of action of inotersen involves binding to the TTR mRNA within hepatocytes (liver cells). Once bound, the inotersen-mRNA complex is recognized and cleaved by the enzyme RNase H1, a naturally occurring cellular enzyme that degrades RNA in RNA-DNA hybrid duplexes. This cleavage leads to the destruction of the TTR mRNA, preventing it from being translated into the transthyretin protein. As a result, the production of both mutant (misfolded) and wild-type (normal) transthyretin is substantially reduced. In clinical trials, inotersen treatment achieved a mean reduction of approximately 70% in serum TTR levels. By reducing the amount of transthyretin available to form amyloid fibrils, inotersen slows or prevents further amyloid deposition in tissues and organs, thereby stabilizing or improving neurological function.
The efficacy of Tegsedi was established in the NEURO-TTR trial, a randomized, double-blind, placebo-controlled, phase III clinical trial that enrolled 172 adults with hATTR polyneuropathy at 24 centers across 10 countries. Patients received either inotersen 284 mg or placebo as a subcutaneous injection once weekly for 65 weeks (15 months). The two primary endpoints were the modified Neuropathy Impairment Score+7 (mNIS+7), a composite measure of peripheral nerve function, and the Norfolk Quality of Life–Diabetic Neuropathy (Norfolk QoL-DN) questionnaire, a patient-reported measure of quality of life.
Results of the NEURO-TTR trial demonstrated that patients treated with inotersen showed a statistically significant and clinically meaningful difference compared with placebo on both primary endpoints. The inotersen group showed a mean change from baseline in mNIS+7 of +5.8 points compared with +25.5 points in the placebo group (a difference of 19.7 points, p < 0.001), indicating that inotersen significantly slowed the progression of neurological impairment. Similarly, the inotersen group showed significantly better preservation of quality of life as measured by the Norfolk QoL-DN. These benefits were observed across different TTR mutation types, disease stages, and geographic regions, confirming the broad applicability of inotersen treatment.
Tegsedi was first approved by the European Medicines Agency (EMA) in July 2018 and subsequently by the U.S. Food and Drug Administration (FDA) in October 2018. It is marketed by Akcea Therapeutics, a subsidiary of Ionis Pharmaceuticals. Tegsedi represents an important treatment option for patients with hATTR polyneuropathy, particularly for those who are not eligible for or have not responded to liver transplantation, which was historically the only treatment option for this devastating condition.
Hereditary transthyretin amyloidosis is estimated to affect approximately 50,000 people worldwide, though many cases remain undiagnosed or misdiagnosed. The disease is autosomal dominant, meaning that a single copy of the mutated gene from one parent is sufficient to cause the disease. Endemic areas include northern Portugal, Sweden (particularly the Skellefteå region), Japan, and parts of Brazil. Early diagnosis is critical because treatment is most effective when started before irreversible nerve damage has occurred.
What Should You Know Before Taking Tegsedi?
Contraindications
Tegsedi must not be used in certain situations where the risks clearly outweigh the potential benefits. Understanding these contraindications is essential for safe prescribing and patient safety. Before initiating treatment, your healthcare provider will conduct a thorough assessment to ensure that Tegsedi is appropriate for you.
You must not use Tegsedi if you are allergic (hypersensitive) to inotersen or any of the other ingredients in this medicine (water for injections, sodium hydroxide, and hydrochloric acid). If tests show that you have a very low platelet count (thrombocytopenia), as this significantly increases the risk of life-threatening bleeding complications during treatment. Additionally, Tegsedi is contraindicated if tests of kidney function or urine protein levels show signs of severe kidney problems, as the medication may worsen renal function. Patients with severely impaired liver function must also not use Tegsedi, as the drug could further compromise hepatic function and its metabolism may be altered in the setting of severe liver disease.
Do not use Tegsedi if you have: (1) Very low platelet counts – risk of life-threatening bleeding, (2) Severe kidney impairment or significant proteinuria, (3) Severely impaired liver function, or (4) Known allergy to inotersen or any excipient. Your doctor must verify all of these before starting treatment.
Warnings and Precautions
Tegsedi carries several important warnings that require careful monitoring throughout treatment. Before you begin treatment, your doctor will check your blood cell counts, liver function, kidney function, vitamin A levels, and protein levels in your urine. You may also have a pregnancy test to ensure you are not pregnant. Treatment can only begin if all test results are at acceptable levels.
Thrombocytopenia (low platelet count): Tegsedi can reduce the number of blood cells responsible for clotting (platelets), leading to a condition called thrombocytopenia. This can occur at any time during treatment and can be sudden and severe. If you do not have enough platelets, your blood may not clot fast enough to stop bleeding. This can lead to bruising as well as more serious problems such as extensive bleeding and internal hemorrhage. Your doctor will check your platelet count before treatment and regularly throughout the entire treatment period. It is essential that you have these regular blood tests for as long as you take Tegsedi due to the risk of serious bleeding caused by low platelet counts. If you stop taking Tegsedi, your blood levels must be monitored for 8 weeks after stopping treatment.
You should contact your doctor immediately if you experience unexplained bruising or a rash of small red spots on the skin (called petechiae), bleeding from skin cuts that does not stop or seeps, bleeding from the gums or nose, blood in urine or stool, or bleeding in the whites of the eyes. Seek emergency medical help if you have a stiff neck or unusual severe headache, as these symptoms could be caused by bleeding in the brain.
Glomerulonephritis and kidney problems: Glomerulonephritis is a condition of the kidneys that means they do not work properly due to inflammation and kidney damage. Some patients treated with inotersen have developed this condition. Symptoms of glomerulonephritis include foamy urine, pink or brown-colored urine, blood in the urine, and urinating less than usual. Additionally, some patients treated with inotersen have also developed a deterioration of kidney function without having had glomerulonephritis. Your doctor will check your kidney function before treatment and regularly during treatment with Tegsedi. If you stop taking Tegsedi, kidney function must be monitored for 8 weeks after stopping treatment. If you develop glomerulonephritis, you will receive treatment for it.
Vitamin A deficiency: Tegsedi can reduce your body’s levels of vitamin A (also called retinol), because transthyretin is the protein that normally carries retinol-binding protein in the blood. Your doctor will check these levels, and if they are already low, they should be corrected and any symptoms addressed before you start treatment with Tegsedi. Symptoms of vitamin A deficiency include dry eyes, reduced vision, impaired night vision, or blurred vision. If you experience visual problems or other eye issues while using Tegsedi, inform your doctor, who may refer you to an eye specialist for an assessment. Your doctor may ask you to take a vitamin A supplement daily during treatment.
Liver damage and monitoring: Tegsedi can cause serious liver problems. Before you start taking inotersen, you need to have a blood test to check that your liver is functioning properly. These blood tests must also be performed regularly for as long as you take this medicine. It is essential that you have these regular blood tests throughout your treatment with Tegsedi.
Liver transplant rejection: If you have had a liver transplant, talk to your doctor before using Tegsedi. Cases of liver transplant rejection have been reported in patients treated with Tegsedi. Your doctor will monitor you regularly for this during treatment.
Regular monitoring is not optional – it is a requirement for safe Tegsedi therapy. Your doctor must check: platelet counts (before each injection or at minimum every 2 weeks), kidney function (serum creatinine and urinalysis), liver function tests, and vitamin A levels. Monitoring must continue for at least 8 weeks after you stop treatment.
Pregnancy and Breastfeeding
If you are pregnant, breastfeeding, think you may be pregnant, or are planning to have a baby, consult your doctor before using this medicine. Tegsedi reduces vitamin A levels in the body, and vitamin A is essential for normal fetal development during pregnancy. It is not known whether vitamin A supplementation can compensate for the risk of vitamin A deficiency that could affect the unborn child.
Women of childbearing potential must use effective contraception, and any pregnancy must be ruled out before starting treatment with Tegsedi. If you are planning to become pregnant, you should stop taking inotersen including vitamin A supplements. Ensure that your vitamin A levels have returned to normal before attempting to become pregnant.
In the event of an unplanned pregnancy, you should stop taking inotersen. However, due to the long-acting activity of Tegsedi, your reduced vitamin A levels may persist. It is not known whether continued supplementation with 3,000 IU of vitamin A per day is harmful to the fetus during the first trimester of pregnancy, but this dose should not be exceeded. You should continue vitamin A supplementation during the second and third trimesters if your vitamin A levels have not yet returned to normal, as there is an increased risk of deficiency during the third trimester.
You should not use Tegsedi if you are pregnant unless your doctor has specifically advised you to do so. Inotersen may pass into breast milk, and a risk to the breastfed infant cannot be excluded. You should discuss with your doctor whether to stop breastfeeding or stop treatment with Tegsedi.
Children and Adolescents
Tegsedi should not be used in children or adolescents under 18 years of age. The safety and efficacy of inotersen have not been established in the pediatric population, and no clinical trial data are available for this age group.
How Does Tegsedi Interact with Other Drugs?
Although inotersen is not metabolized by cytochrome P450 enzymes and is therefore not expected to have traditional pharmacokinetic drug interactions, several clinically important pharmacodynamic interactions exist. These interactions are primarily related to the additive risk of bleeding (due to the thrombocytopenic effect of inotersen) and the potential for additive nephrotoxicity (kidney damage).
It is essential to inform your doctor about all medications you are currently taking, have recently taken, or might take. The following drug classes warrant particular attention when prescribing Tegsedi:
Major Interactions
The most clinically significant interactions involve medications that affect blood clotting or platelet function. Since Tegsedi can cause thrombocytopenia (low platelet count), the concurrent use of anticoagulants or antiplatelet agents increases the risk of severe or life-threatening bleeding events. These include:
| Drug | Class | Interaction Risk | Clinical Advice |
|---|---|---|---|
| Warfarin | Vitamin K antagonist | Increased bleeding risk | Close INR monitoring; dose adjustment may be needed |
| Heparin | Anticoagulant | Increased bleeding risk | Monitor aPTT and platelet count closely |
| Rivaroxaban | Direct oral anticoagulant (DOAC) | Increased bleeding risk | Assess benefit-risk; increased platelet monitoring |
| Dabigatran | Direct thrombin inhibitor | Increased bleeding risk | Assess benefit-risk; increased platelet monitoring |
| Aspirin (acetylsalicylic acid) | Antiplatelet agent / NSAID | Increased bleeding risk | Consider alternatives; monitor for bleeding signs |
| Clopidogrel | Antiplatelet agent | Increased bleeding risk | Assess necessity; monitor platelets and bleeding |
Minor Interactions
In addition to blood-thinning medications, drugs that may affect kidney function or cause kidney damage deserve special consideration during Tegsedi treatment. Because inotersen itself carries a risk of glomerulonephritis and kidney impairment, the concurrent use of nephrotoxic agents may increase the risk of renal complications. These include:
| Drug / Class | Indication | Interaction Concern | Clinical Advice |
|---|---|---|---|
| Sulfonamides | Antibacterial agents | Additive nephrotoxicity | Use with caution; monitor kidney function |
| NSAIDs (ibuprofen, naproxen) | Pain, fever, inflammation | Nephrotoxicity + bleeding risk | Avoid if possible; monitor renal and platelet values |
| Aldosterone antagonists (spironolactone) | Diuretic | May alter kidney function | Monitor renal function and electrolytes |
| Opioid analgesics | Pain management | May affect kidney function | Use with standard renal monitoring |
Unlike many conventional small-molecule drugs, inotersen is a large, chemically modified nucleotide that is not a substrate for cytochrome P450 (CYP) enzymes. Therefore, it is not expected to affect the metabolism of other drugs through CYP-mediated pathways. However, the pharmacodynamic interactions described above (additive bleeding risk and nephrotoxicity) are clinically important and should be carefully considered when prescribing Tegsedi alongside other medications. Always ensure your healthcare provider has a complete list of all prescription and non-prescription medicines you are taking.
What Is the Correct Dosage of Tegsedi?
Always use this medicine exactly as your doctor has told you. Check with your doctor, pharmacist, or nurse if you are not sure. The dosing regimen for Tegsedi is straightforward compared with many other medications: a single, fixed dose is administered once weekly by subcutaneous injection.
Adults
Standard Adult Dosage
Dose: 284 mg inotersen (as inotersen sodium)
Route: Subcutaneous injection (under the skin)
Frequency: Once weekly, on the same day each week
Duration: Continuous treatment as directed by physician
Pre-filled syringe: Each syringe contains 284 mg in 1.5 mL solution
Before using the pre-filled syringe for the first time, your doctor or nurse will show you or your caregiver how to use it correctly. Injection sites include the abdomen (at least 5 cm from the navel), the front of the thigh, or the outer area of the upper arm. Sites should be rotated with each injection to minimize injection site reactions. Do not inject into areas where the skin is tender, bruised, red, or hard, and avoid areas with tattoos or scars.
Remove the pre-filled syringe from the refrigerator approximately 30 minutes before injection to allow it to reach room temperature. Do not warm it in any other way. Inspect the solution visually before use – the solution should be clear and colorless to pale yellow. Do not use it if the solution is cloudy or contains particles.
Children
Pediatric Dosage
Tegsedi is not recommended for use in children and adolescents under 18 years of age. Safety and efficacy have not been established in pediatric patients. No clinical trial data are available for this age group.
Elderly
Elderly Patients
No dose adjustment is required in elderly patients. However, given the increased likelihood of comorbidities and concomitant medications in older adults, particularly close monitoring of platelet counts, kidney function, and liver function is recommended. Elderly patients may have reduced physiological reserves and may be more susceptible to the adverse effects of inotersen.
Missed Dose
If you miss a dose of Tegsedi, take the next dose as soon as possible, unless the next scheduled dose is within two days. If the next scheduled dose is within two days, skip the missed dose and take the next dose as planned. Do not take a double dose to make up for a missed dose. It is important to maintain the weekly dosing schedule as closely as possible for optimal efficacy.
Overdose
If you accidentally use more Tegsedi than prescribed, contact your doctor, pharmacist, or go to the nearest emergency department immediately, even if you do not have any symptoms. There is limited clinical experience with overdose of inotersen. In the event of an overdose, supportive care should be provided, with particular attention to monitoring platelet counts, kidney function, and liver function. There is no specific antidote for inotersen.
Do not stop using Tegsedi unless your doctor tells you to do so. Stopping treatment without medical supervision may lead to a rebound in transthyretin production and potential worsening of amyloid deposition and disease symptoms.
What Are the Side Effects of Tegsedi?
Like all medicines, Tegsedi can cause side effects, although not everybody gets them. Some side effects can be serious and require immediate medical attention. Understanding the different categories of side effects and their relative frequency is important for informed decision-making and for knowing when to seek medical help.
Stop using Tegsedi and contact your doctor immediately if you experience: symptoms of glomerulonephritis (foamy, pink, or brown urine; blood in urine; urinating less than usual), signs of severe thrombocytopenia (unexplained bruising, petechiae, bleeding that won’t stop, blood in urine or stool), or signs of liver damage (yellowing of skin/eyes, dark urine, upper right abdominal pain). Seek emergency help for stiff neck or severe headache, which could indicate bleeding in the brain.
Very Common
May affect more than 1 in 10 people
- Decreased red blood cell count (anemia) – may cause pale skin, weakness, or shortness of breath
- Decreased platelet count (thrombocytopenia) – may cause bruising and bleeding
- Headache
- Nausea or vomiting
- Increased body temperature (fever)
- Feeling cold or chills (rigors)
- Injection site reactions – pain, redness, itching, or bruising at the injection site
- Swelling of ankles, feet, or fingers (peripheral edema)
Common
May affect up to 1 in 10 people
- Increased number of white blood cells called eosinophils (eosinophilia)
- Decreased appetite
- Feeling faint or dizzy, especially when standing up (low blood pressure, hypotension)
- Bruising easily
- Blood collecting in tissues resembling severe bruising (hematoma)
- Itching (pruritus)
- Rash
- Glomerulonephritis – kidney inflammation leading to poor kidney function or kidney failure
- Kidney damage leading to poor kidney function or kidney failure
- Changes in blood and urine test results (which may indicate liver or kidney damage)
- Flu-like symptoms – high fever, body aches, and chills
- Swelling or skin discoloration at the injection site
Uncommon
May affect up to 1 in 100 people
- Allergic (hypersensitivity) reaction
The injection site reactions associated with Tegsedi are generally mild to moderate in severity and tend to become less frequent over time as treatment continues. Rotating injection sites with each weekly dose can help minimize these local reactions. If you notice any injection site reactions that are persistent, worsening, or accompanied by signs of infection (such as increasing warmth, swelling, or pus), contact your healthcare provider.
Thrombocytopenia is one of the most clinically significant adverse effects of Tegsedi. In the NEURO-TTR trial, platelet counts decreased below 100,000/µL in approximately 54% of inotersen-treated patients and below 25,000/µL in approximately 3% of patients. In rare cases, thrombocytopenia can be sudden and severe, potentially leading to life-threatening hemorrhagic events. This is why the mandatory monitoring program – with regular platelet count checks – is a non-negotiable component of Tegsedi therapy. If your platelet count drops below a critical threshold, your doctor may temporarily or permanently discontinue treatment.
Glomerulonephritis occurred in approximately 3% of patients in the NEURO-TTR trial. This immune-mediated kidney inflammation can manifest as proteinuria (protein in the urine), hematuria (blood in the urine), decreased urine output, and edema. Early detection through regular urinalysis and serum creatinine monitoring is critical, as prompt treatment with immunosuppressive therapy can often reverse the kidney damage.
If you experience any side effects, even those not listed here, or if existing side effects worsen, talk to your doctor, pharmacist, or nurse. Reporting suspected adverse reactions after the medicine has been authorized is important. It allows continued monitoring of the benefit-risk balance of the medicine.
How Should You Store Tegsedi?
Keep this medicine out of the sight and reach of children. Do not use this medicine after the expiry date which is stated on the carton, tray, and pre-filled syringe after “EXP”. The expiry date refers to the last day of that month.
Tegsedi should be stored in a refrigerator at a temperature between 2 °C and 8 °C. The pre-filled syringes must not be frozen at any time. If a syringe has been accidentally frozen, it must be discarded and not used. Keep the medicine in its original packaging to protect it from light, as the solution is light-sensitive.
For convenience when traveling or in situations where refrigeration is not immediately available, Tegsedi can be stored outside the refrigerator for up to 6 weeks at a temperature not exceeding 30 °C. If stored outside the refrigerator and not used within 6 weeks, the medicine must be discarded. It should not be returned to the refrigerator after being stored at room temperature.
Before each injection, visually inspect the solution. The solution should appear clear and colorless to pale yellow. Do not use the medicine if you notice that the contents are cloudy or contain particles. Used syringes should be placed in an appropriate sharps disposal container. Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures help to protect the environment.
What Does Tegsedi Contain?
The active substance is inotersen. Each mL contains 189 mg of inotersen (as inotersen sodium). Each pre-filled syringe contains 284 mg of inotersen (as inotersen sodium) in 1.5 mL of solution. Inotersen sodium is a synthetic, 20-nucleotide antisense oligonucleotide that has been chemically modified with 2’-O-methoxyethyl (2’-MOE) groups and phosphorothioate linkages to enhance its stability, resistance to nuclease degradation, and binding affinity for the target TTR mRNA.
The other ingredients (excipients) are: water for injections, sodium hydroxide (for pH adjustment), and hydrochloric acid (for pH adjustment). This medicine contains less than 1 mmol (23 mg) of sodium per 1.5 mL, meaning it is essentially sodium-free. This is relevant for patients on a controlled sodium diet.
Tegsedi is supplied as a clear, colorless to pale yellow solution for injection in a pre-filled syringe. It is available in pack sizes of either 1 or 4 pre-filled syringes. Not all pack sizes may be marketed in all countries. The pre-filled syringe is equipped with a safety mechanism to help prevent accidental needle-stick injuries after use.
The marketing authorization holder is Akcea Therapeutics Ireland Ltd, St. James House, 72 Adelaide Road, Dublin 2, D02 Y017, Ireland. The manufacturer is ABF Pharmaceutical Services GmbH, Brunnerstraße 63/18-19, 1230 Vienna, Austria.
Frequently Asked Questions About Tegsedi
Hereditary transthyretin amyloidosis (hATTR) is a rare, progressive, life-threatening genetic disorder caused by mutations in the TTR gene. The mutated transthyretin protein misfolds and aggregates into amyloid fibrils that deposit in tissues and organs, particularly peripheral nerves, the heart, kidneys, and gastrointestinal tract. This leads to progressive polyneuropathy (nerve damage causing numbness, pain, weakness, and autonomic dysfunction), cardiomyopathy (heart muscle disease), and organ failure. The disease affects an estimated 50,000 people worldwide and is inherited in an autosomal dominant pattern, meaning you only need one copy of the mutated gene to develop the disease.
Tegsedi works through a unique mechanism called antisense technology. It is a synthetic oligonucleotide that binds directly to the TTR messenger RNA (mRNA) in liver cells, triggering its degradation by the enzyme RNase H1. This prevents the TTR mRNA from being translated into the transthyretin protein, reducing production of both mutant and wild-type TTR by approximately 70%. This differs from TTR stabilizers (like tafamidis) that prevent the already-formed TTR protein from misfolding, and from liver transplantation, which replaces the source of mutant TTR. Tegsedi targets the problem at the genetic level, before the protein is even made.
Transthyretin serves as a carrier protein in the blood – one of its normal functions is to transport retinol-binding protein (RBP), which in turn carries vitamin A (retinol). When Tegsedi reduces the production of transthyretin, there is less carrier protein available to transport vitamin A in the bloodstream. This leads to reduced circulating levels of vitamin A, even if dietary intake is adequate. Your doctor will typically prescribe daily vitamin A supplementation (usually around 3,000 IU per day) throughout your treatment with Tegsedi. However, it is important not to exceed this dose, especially during pregnancy, as both deficiency and excess of vitamin A can be harmful.
Yes, after receiving proper training from your healthcare professional, you or your caregiver can administer Tegsedi at home using the pre-filled syringe. Your doctor or nurse will demonstrate the correct injection technique during your initial visits. Injection sites include the abdomen (avoiding the area around the navel), the front of the thigh, or the outer upper arm. It is important to rotate injection sites each week to minimize local reactions. Always read the instructions for use provided with each prescription, inspect the solution before injection (it should be clear and colorless to pale yellow), and allow the syringe to reach room temperature for about 30 minutes before injecting.
Tegsedi begins reducing serum transthyretin levels within the first few weeks of treatment, with maximum suppression typically achieved by approximately week 13. However, the clinical benefits in terms of slowing neurological progression and preserving quality of life develop more gradually. In the NEURO-TTR trial, significant differences between inotersen and placebo were observed at the 15-month (65-week) assessment. Patients should understand that Tegsedi primarily slows disease progression rather than reversing existing damage, though some patients have reported stabilization or modest improvements in nerve function. Your doctor will typically evaluate the effectiveness of treatment at regular intervals.
If you need to stop Tegsedi for any reason, it is important to do so under medical supervision. After discontinuation, monitoring of platelet counts, kidney function, and liver function must continue for at least 8 weeks, as the effects of inotersen persist for some time after the last dose due to its long half-life (approximately 32 days). TTR levels will gradually return to baseline over several weeks after stopping treatment. Your doctor will discuss alternative treatment options and ensure a safe transition if Tegsedi needs to be discontinued.
References
- European Medicines Agency (EMA). Tegsedi (inotersen) – Summary of Product Characteristics. Last updated 2023. Available at: www.ema.europa.eu/en/medicines/human/EPAR/tegsedi
- U.S. Food and Drug Administration (FDA). Tegsedi (inotersen) Prescribing Information. Akcea Therapeutics, Inc. Revised 2023.
- Benson MD, Waddington-Cruz M, Berk JL, et al. Inotersen Treatment for Patients with Hereditary Transthyretin Amyloidosis. N Engl J Med. 2018;379(1):22-31. doi:10.1056/NEJMoa1716793
- Adams D, Ando Y, Beiroão JM, et al. Expert consensus recommendations to improve diagnosis of ATTR amyloidosis with polyneuropathy. J Neurol. 2021;268(6):2109-2122. doi:10.1007/s00415-019-09688-0
- Kerschen P, Planté-Bordeneuve V. Current and Future Treatment Approaches in Transthyretin Familial Amyloid Polyneuropathy. Curr Treat Options Neurol. 2019;21(12):54. doi:10.1007/s11940-019-0596-2
- World Health Organization (WHO). WHO Model List of Essential Medicines. 23rd List, 2023.
- Gertz MA, Benson MD, Dyck PJ, et al. Diagnosis, Prognosis, and Therapy of Transthyretin Amyloidosis. J Am Coll Cardiol. 2015;66(21):2451-2466. doi:10.1016/j.jacc.2015.09.075
- Sekijima Y, Ueda M, Koike H, Misawa S, Ishii T, Ando Y. Diagnosis and management of transthyretin familial amyloid polyneuropathy in Japan: red-flag symptom clusters and treatment algorithm. Orphanet J Rare Dis. 2018;13(1):6. doi:10.1186/s13023-017-0726-x
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