Tegsedi

Tegsedi is a prescription medication used to treat polyneuropathy (multiple types of nerve damage) caused by a rare genetic disease called hATTR amyloidosis. Nerve damage from hATTR amyloidosis results from amyloid buildup damaging organs and tissues. Amyloid is made up of clusters of the TTR protein.

This medication belongs to a group of drugs called antisense oligonucleotide (ASO) inhibitors of human transthyretin (TTR) protein synthesis. Tegsedi works by preventing the creation of TTR proteins, thereby reducing the amount of amyloid that builds up.

This medication comes in an injectable form to be injected subcutaneously (under the skin) once weekly.

Common side effects of Tegsedi include injection site reactions, nausea, and headache. Tegsedi can also cause extreme tiredness. Do not drive or operate heavy machinery until you know how Tegsedi affects you.

Tegsedi is a prescription medication used to treat the polyneuropathy of hereditary transthyretin-mediated (hATTR) amyloidosis in adults. It is not known if Tegsedi is safe and effective in children.

This medication may be prescribed for other uses. Ask your doctor or pharmacist for more information.

Serious side effects have been reported with Tegsedi. See the “Tegsedi Precautions” section.

Common side effects of Tegsedi include the following:

• Injection site reactions
• Nausea
• Headache
• Extreme tiredness (fatigue) 
• Low platelet count - increased bleeding risk
• Fever/Chills

This is not a complete list of Tegsedi side effects. Ask your doctor or pharmacist for more information. Tell your doctor if you have any side effects that bother you or that do not go away. Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Tell your doctor about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements. Especially tell your doctor if you take:

• Vitamin A or beta-carotene supplements. Your healthcare provider should tell you to take vitamin A, but only take the amount they tell you to take.

• Antiplatelet or anticoagulation (blood thinning) medications like aspirin, clopidogrel (Plavix), warfarin (Coumadin) , and others.

• Drugs that can decrease kidney function such as

  • NSAIDs such as aspirin, ibuprofen, and naproxen
  • Acyclovir
  • Aminoglycoside medications
  • Certain antibiotics
  • ACEIs such as lisinopril or quinapril
  • Statins such as rosuvastatin and simvastatin
  • Water pills (diuretic medications)

This is not a complete list of Tegsedi drug interactions. Ask your doctor or pharmacist for more information.

Serious side effects have been reported with Tegsedi including:

Low platelet counts (thrombocytopenia): Tegsedi may cause the number of platelets in your blood to be reduced. This is a common side effect of Tegsedi. When your platelet count is too low, your body cannot form clots. You could have serious bleeding that could lead to death. Call your healthcare provider immediately if you have:

• Unusual bruising or a rash of tiny reddish-purple spots, often on the lower legs
• Bleeding from skin cuts that does not stop or oozes
• Bleeding from your gums or nose 
• Blood in urine or stools
• Bleeding into the whites of your eyes
• Sudden severe headaches or neck stiffness
• Vomiting or coughing up blood
• Abnormal or heavy periods (menstrual bleeding)

Kidney inflammation (glomerulonephritis): Your kidneys may stop working properly. Glomerulonephritis can lead to severe kidney damage and kidney failure that need dialysis. Call your healthcare provider immediately if you have:

• Puffiness or swelling in your face, feet, or hands
• New onset or worsening shortness of breath and coughing
• Blood in your urine or brown urine
• Foamy urine (proteinuria)
• Passed less urine than usual

Because of the risk of serious bleeding caused by low platelet counts and because of the risk of kidney problems, Tegsedi is available only through a restricted program called the Tegsedi Risk Evaluation and Mitigation Strategy (REMS) Program. Talk to your healthcare provider about how to enroll in the Tegsedi REMS Program.

Do not use Tegsedi if you have:

• A platelet count that is low
• Had kidney inflammation (glomerulonephritis) caused by Tegsedi
• Had an allergic reaction to inotersen or any of the ingredients in Tegsedi. 

Before you start Tegsedi, tell your healthcare provider about all of your health issues, including if you:

• Have or had bleeding problems
• Have or had kidney problems
• Are pregnant or plan to become pregnant. It is not known if Tegsedi can harm your unborn baby
• Are breastfeeding or plan to breastfeed. It is not known if Tegsedi can pass into your breast milk or harm your baby. Talk with your healthcare provider about the best way to feed your baby while you are taking Tegsedi

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Especially tell your healthcare provider if you take vitamin A or beta-carotene supplements, blood thinners (anticoagulants), or drugs that affect blood clotting.

Required monitoring

Your healthcare provider will test your blood and urine to check your platelet counts and kidney and liver function before you start Tegsedi. While you are receiving Tegsedi, you will be monitored closely for symptoms, which includes checking your platelet counts every week (or more frequently as needed), kidney function every 2 weeks, and liver function every 4 months. If your healthcare provider has you stop taking Tegsedi, you will need to continue to get your blood and urine tested for 8 more weeks after treatment.

Tegsedi may cause serious side effects, including:

Stroke. Tegsedi may cause a stroke. One person taking Tegsedi had a stroke, which occurred within 2 days after the first dose. Get emergency help immediately if you have symptoms of stroke, including sudden numbness or weakness, especially on one side of the body; severe headache or neck pain; confusion; problems with vision, speech, or balance; droopy eyelids.

Inflammatory and immune system problems. Some people taking Tegsedi had serious inflammatory and immune system problems. Symptoms of inflammatory and immune system problems included unexpected change in walking, weakness and spasms in legs, back pain, weight loss, headache, vomiting, and problems with speech.

Liver effects. Tegsedi may cause liver problems. Your healthcare provider should do laboratory tests to check your liver before you start Tegsedi and while you are using it. Tell your healthcare provider if you have symptoms that your liver may not be working right, which could include unexpected nausea and vomiting, stomach pain, being not hungry, yellowing of the skin, or having dark urine.

Allergic reactions. Tegsedi may cause serious allergic reactions. These allergic reactions often occur within 2 hours after injecting Tegsedi. Get emergency help immediately if you have any symptoms of a serious allergic reaction, including joint pain, chills, redness on palms of hands, muscle pain, chest pain, flushing, tremor or jerking movements, flu-like symptoms, high blood pressure, or difficulty swallowing.

Eye problems (low vitamin A levels). Treatment with Tegsedi will lower the vitamin A levels in your blood. Your healthcare provider will tell you how much supplemental vitamin A to take every day; only take the amount they tell you to take. Call your healthcare provider if you get eye problems, such as having difficulty seeing at night or in low-lit areas (night blindness).

The most common side effects of Tegsedi include injection site reactions (such as redness or pain at the injection site), nausea, headache, tiredness, low platelet counts (thrombocytopenia), and fever. These are not all of the possible side effects of Tegsedi. Talk to your healthcare provider about any side effects you may be experiencing.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088.

Medications can interact with certain foods. In some cases, this may be harmful and your doctor may advise you to avoid certain foods. In the case of Tegsedi, there are no specific foods that you must exclude from your diet when receiving this medication.

Before taking Tegsedi, tell your doctor about all of your medical conditions. Especially tell your doctor if you:

• are allergic to Tegsedi or to any of its ingredients

• have kidney problems

• have liver problems

• have heart problems or history of stroke

• are pregnant or plan to become pregnant

• are breastfeeding or plan to breastfeed

Tell your doctor about all the medicines you take including prescription and non-prescription medicines, vitamins, and herbal supplements.

Tell your doctor if you are pregnant or plan to become pregnant.

In animal studies, pregnant animals were given this medication and this resulted in premature delivery and reduced birth weights. No developmental adverse effects were seen. No well-controlled studies have been done in humans. Therefore, this medication may be used if the potential benefits to the mother outweigh the potential risks to the unborn child. Talk to your doctor about your risks with using Tegsedi.

Tell your doctor if you are breastfeeding or plan to breastfeed.

It is not known if Tegsedi crosses into human milk. Because many medications can cross into human milk and because of the possibility for serious adverse reactions in nursing infants with use of this medication, a choice should be made whether to stop nursing or stop the use of this medication. Your doctor and you will decide if the benefits outweigh the risk of using Tegsedi.

Take Tegsedi exactly as prescribed.

• Read the detailed Instructions for Use that come with your Tegsedi.
• Your healthcare provider will show you or your caregiver how to inject Tegsedi the first time.
• If you or your caregiver have any questions, ask your healthcare provider.
• Tegsedi is injected under your skin (subcutaneously) in your stomach area (abdomen), or the front of your upper legs (thighs) by you or a caregiver. A caregiver may also give you an injection of Tegsedi in the outer area of your upper arm.
• Do not inject into the same site each time.
• Do not inject into the 2-inch area around the belly-button (naval).
• Do not inject where the skin is bruised, tender, red, or hard.
• Do not inject into areas with scars or tattoos.
• Do not inject through clothing.
• Follow your healthcare provider’s instructions on when to inject Tegsedi.
• Tegsedi should be injected 1 time each week on the same day.
• If you miss a dose, take the missed dose as soon as possible, unless your next scheduled dose is within 2 days. If your next scheduled dose is within 2 days, skip the missed dose and take your next scheduled dose on the scheduled day.

Take this medication exactly as prescribed by your doctor. Follow the directions on your prescription label carefully.

The dose your doctor recommends may be based on the following:

• the condition being treated
• other medical conditions you have
• other medications you are taking
• how you respond to this medication

The recommended dose/dose range of Tegsedi is 284 mg subcutaneously once weekly.

If you take too much Tegsedi, call your healthcare provider or local Poison Control Center, or seek emergency medical attention right away.

• Store Tegsedi in the refrigerator between 36°F to 46°F (2°C to 8°C) in the original container.
• Do not freeze.
• Tegsedi prefilled syringes can also be kept at room temperature that is no higher than 86°F (30°C) in the original container for up to 6 weeks.
• Do not let Tegsedi reach temperatures above 86°F (30°C).
• If you do not use Tegsedi kept at room temperature within 6 weeks, throw it away.
• Protect from light.
• Keep Tegsedi and all medicines out of the reach of children.

WARNING: THROMBOCYTOPENIA AND GLOMERULONEPHRITIS

Thrombocytopenia

Tegsedi causes reductions in platelet count that may result in sudden and unpredictable thrombocytopenia, which can be life-threatening. One clinical trial patient died from intracranial hemorrhage.

Tegsedi is contraindicated in patients with a platelet count below 100 x 109/L

Prior to starting Tegsedi, obtain a platelet count. During treatment, monitor platelet counts weekly if values are 75 x 109/L or greater, and more frequently if values are less than 75 x 109/L

If a patient develops signs or symptoms of thrombocytopenia, obtain a platelet count as soon as possible. The patient should not receive additional Tegsedi unless a platelet count is determined to be interpretable and acceptable by a medical professional.

Following discontinuation of treatment for any reason, continue to monitor platelet count for 8 weeks, or longer if platelet counts are less than 100 x 109/L, to verify that platelet counts remain above 75 x 109/L.

Glomerulonephritis

Tegsedi can cause glomerulonephritis that may require immunosuppressive treatment and may result in dialysis-dependent renal failure. One clinical trial patient who developed glomerulonephritis and did not receive immunosuppressive treatment remained dialysis-dependent. In clinical trials, cases of glomerulonephritis were accompanied by nephrotic syndrome, which can have manifestations of edema, hypercoagulability with venous or arterial thrombosis, and increased susceptibility to infection.

Tegsedi should generally not be initiated in patients with urinary protein to creatinine ratio (UPCR) of 1000 mg/g or higher.

Prior to starting Tegsedi, measure the serum creatinine, estimated glomerular filtration rate (eGFR), urine protein to creatinine ratio (UPCR), and perform a urinalysis. During treatment, monitor serum creatinine, eGFR urinalysis, and UPCR every every two weeks. Tegsedi should not be given to patients who develop a UPCR of 1000 mg/g or higher, or eGFR below 45 mL/minute/1.73 m2, pending further evaluation of the cause.

If a dose is held, once eGFR increases to ≥45 mL/minute/1.73 m2, UPCR decreases to below 1000 mg/g, or the underlying cause of the decline in renal function is corrected, weekly dosing may be re-initiated. In patients with UPCR of 2000 mg/g or higher, perform further evaluation for acute glomerulonephritis, as clinically indicated. If acute glomerulonephritis is confirmed, Tegsedi should be permanently discontinued.

Tegsedi REMS Program

Because of the risks of serious bleeding caused by severe thrombocytopenia and because of glomerulonephritis, both of which require frequent monitoring, Tegsedi is available only through a restricted distribution program under a Risk Evaluation and Mitigation Strategy (REMS) called the Tegsedi REMS Program.