Pronunciation:

in-oh-TER-sen

Brand Names:

• Tegsedi

Dosage Forms:

• Solution

Warnings:

ThrombocytopeniaInotersen causes reductions in platelet count that may result in sudden and unpredictable thrombocytopenia, which can be life-threatening.Testing prior to treatment and monitoring during treatment is required.GlomerulonephritisInotersen can cause glomerulonephritis that may require immunosuppressive treatment and may result in dialysis-dependent renal failure.Testing Prior to treatment and monitoring during treatment is required.TEGSEDI is only available through a restricted distribution program call the TEGSEDI REMS Program .

Classifications:

Therapeutic—

Endocrine-Metabolic Agent

Pharmacologic—

Antisense Oligonucleotide

Uses of This Medicine:

Inotersen injection is used to treat polyneuropathy (nerve disease) of hereditary transthyretin-mediated amyloidosis.

This medicine is available only under a restricted distribution program called Tegsedi® REMS (Risk Evaluation and Mitigation Strategy) Program.

Before Using This Medicine:

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies—

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Children—

Appropriate studies have not been performed on the relationship of age to the effects of inotersen injection in the pediatric population. Safety and efficacy have not been established.

Older adults—

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of inotersen injection in the elderly. However, elderly patients are more likely to have serious unwanted effects (eg, heart failure, chills, myalgia, arm or leg pain), which may require caution in patients receiving this medicine.

Breast-feeding—

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Other medicines—

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Abciximab
• Aceclofenac
• Acemetacin
• Acenocoumarol
• Adenosine
• Amtolmetin Guacil
• Anagrelide
• Apixaban
• Ardeparin
• Argatroban
• Aspirin
• Bemiparin
• Betrixaban
• Bivalirudin
• Bromfenac
• Bufexamac
• Celecoxib
• Certoparin
• Choline Salicylate
• Cilostazol
• Clonixin
• Clopidogrel
• Dabigatran Etexilate
• Dalteparin
• Danaparoid
• Desirudin
• Dexibuprofen
• Dexketoprofen
• Diclofenac
• Diflunisal
• Dipyridamole
• Dipyrone
• Drotrecogin Alfa
• Droxicam
• Edoxaban
• Enoxaparin
• Eptifibatide
• Etodolac
• Etofenamate
• Etoricoxib
• Felbinac
• Fenoprofen
• Fepradinol
• Feprazone
• Floctafenine
• Flufenamic Acid
• Flurbiprofen
• Fondaparinux
• Heparin
• Ibuprofen
• Indomethacin
• Ketoprofen
• Ketorolac
• Lepirudin
• Lornoxicam
• Loxoprofen
• Lumiracoxib
• Meclofenamate
• Mefenamic Acid
• Meloxicam
• Morniflumate
• Nabumetone
• Nadroparin
• Naproxen
• Nepafenac
• Niflumic Acid
• Nimesulide
• Nimesulide Beta Cyclodextrin
• Oxaprozin
• Oxyphenbutazone
• Parecoxib
• Parnaparin
• Phenprocoumon
• Phenylbutazone
• Piketoprofen
• Piroxicam
• Pranoprofen
• Prasugrel
• Proglumetacin
• Propyphenazone
• Proquazone
• Protein C
• Reviparin
• Rivaroxaban
• Rofecoxib
• Salicylic Acid
• Salsalate
• Sodium Salicylate
• Sulfinpyrazone
• Sulindac
• Tenecteplase
• Tenoxicam
• Tiaprofenic Acid
• Ticagrelor
• Ticlopidine
• Tinzaparin
• Tirofiban
• Tolfenamic Acid
• Tolmetin
• Treprostinil
• Valdecoxib
• Vorapaxar
• Warfarin

Other interactions—

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other medical problems—

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

• Bleeding problems or
• Kidney disease or
• Liver disease or
• Stroke, history of or
• Vitamin A deficiency—Use with caution. May make these conditions worse.

• Glomerulonephritis (swelling of the kidneys), history of or
• Thrombocytopenia (low platelet count)—Should not be used in patients with these conditions.

Proper Use of This Medicine:

A nurse or other trained health professional will give you this medicine. It is given as a shot under your skin, usually in the stomach, thighs, or upper arms. You or your caregiver may be trained to prepare and inject the medicine at home. Be sure that you understand how to use the medicine.

If you use this medicine at home, you will be shown the body areas where this shot can be given. Use a different body area each time you give yourself a shot. Keep track of where you give each shot to make sure you rotate body areas. This will help prevent skin problems from the injections. Do not inject into skin areas that are tender, red, bruised, or hard, or areas with scars or tattoos.

It is very important that you understand the requirements of the Tegsedi® REMS program, and become familiar with the Tegsedi® Medication Guide and patient instructions. Read and follow these instructions carefully. Ask your doctor if you have any questions. Ask your pharmacist for the medication guide if you do not have one.

Allow the medicine to warm to room temperature for 30 minutes before you use it. Do not warm it in any other way.

Check the liquid in the prefilled syringe. It should be colorless or pale yellow. Do not use the medicine if the liquid is cloudy, discolored, or has particles in it. Do not shake.

Do not remove the needle cap from the prefilled syringe until you are ready to use it.

You might not use all of the medicine in each prefilled syringe. Use each prefilled syringe only one time. Do not save an open syringe.

Your healthcare provider may recommend vitamin A supplements while using this medicine. Do not take more vitamin A than your doctor has recommended.

Dosing—

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For injection dosage form (solution):
  • For polyneuropathy of hereditary transthyretin-mediated amyloidosis:
    • Adults—284 milligrams (mg) injected under the skin once a week.
    • Children—Use and dose must be determined by your doctor.

Missed dose—

If you miss a dose of this medicine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

If you miss a dose, inject it as soon as possible. If your next dose is within 2 days, skip the missed dose and go back to your regular dosing schedule.

Storage—

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

Store in the refrigerator. Do not freeze.

You may store this medicine at room temperature for up to 6 weeks. Throw any unused medicine after 6 weeks.

Throw away used syringes in a hard, closed container that the needles cannot poke through. Keep this container away from children and pets.

Precautions While Using This Medicine:

It is very important that your doctor check your progress at regular visits to make sure this medicine is working properly. Blood and urine tests may be needed to check for unwanted effects.

Inotersen injection will lower the number of some types of blood cells in your body. Because of this, you may bleed or get infections more easily. To help with these problems, avoid being near people who are sick or have infections. Wash your hands often. Stay away from rough sports or other situations where you could be bruised, cut, or injured. Brush and floss your teeth gently. Be careful when using sharp objects, including razors and fingernail clippers.

Check with your doctor right away if you have bloody urine, a decrease in frequency or amount of urine, an increase in blood pressure, increased thirst, loss of appetite, lower back or side pain, nausea, swelling of the face, fingers, or lower legs, troubled breathing, unusual tiredness or weakness, vomiting, or weight gain. These could be symptoms of a serious kidney problem.

This medicine may increase your risk for inflammatory or immune system problems, stroke, or arterial dissection (tear in the lining of a brain artery). Check with your doctor if you have confusion, difficulty in speaking, slow speech, inability to speak, inability to move the arms, legs, or facial muscles, double vision, headache, spasms in the legs, back pain, or weight loss.

Check with your doctor right away if you have pain or tenderness in the upper stomach, pale stools, dark urine, loss of appetite, nausea, vomiting, or yellow eyes or skin. These could be symptoms of a serious liver problem.

This medicine may cause serious allergic reactions, which can be life-threatening and require immediate medical attention. Tell your doctor right away if you have a rash, itching, hoarseness, trouble breathing, trouble swallowing, or any swelling of your hands, face, or mouth after using this medicine.

This medicine may lower the vitamin A levels in your body, which may cause eye or vision problems (eg, night blindness, blurred vision, difficulty with reading, or any other change in vision). Your doctor may want your eyes to be checked by an ophthalmologist (eye doctor).

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal or vitamin supplements.

Side Effects of This Medicine:

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

More common

Black, tarry stools

bleeding gums

blood in the urine or stools

bruise

burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings

chest tightness

chills

cough

decreased frequency or amount of urine

diarrhea

difficulty in moving

dizziness or lightheadedness when getting up suddenly from a lying or sitting position

fainting

fast, slow, or irregular heartbeat

fever

general feeling of discomfort or illness

headache

hoarseness

increased blood pressure

increased thirst

joint pain

loss of appetite

lower back or side pain

muscle pain or stiffness

nausea

painful or difficult urination

pale skin

pinpoint red spots on the skin

runny nose

shivering

sore throat

sweating

swelling of the face, fingers, arms, or lower legs

trouble breathing

trouble sleeping

unusual bleeding or bruising

unusual tiredness or weakness

vomiting

weight gain

Less common

Chest pain

sores, ulcers, or white spots on the lips or in the mouth

swollen glands

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common

Bleeding, blistering, burning, coldness, discoloration of skin, feeling of pressure, hives, infection, inflammation, itching, lumps, numbness, pain, rash, redness, scarring, soreness, stinging, swelling, tenderness, tingling, ulceration, or warmth at the injection site

swollen joints

Less common

Dry mouth

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.