Inotersen

Inotersen is a prescription medication used for the treatment of polyneuropathy of hereditary transthyretin amyloidosis (hATTR-PN) in adults.

• Inotersen is available under the following different brand names: Tegsedi

Common side effects of Inotersen include:

• bruising
• redness
• a hard lump
• inflammation
• swelling
• pain
• itching
• rash
• hives

Serious side effects of Inotersen include:

• hives
• trouble breathing
• swelling of the face, lips, tongue, or throat
• sudden numbness or weakness (especially on one side of the body)
• slurred speech
• drooping eyelids
• problems with vision or balance
• puffy eyes
• swelling in the hands or feet
• shortness of breath
• vomiting
• weight loss
• back pain
• muscle weakness
• easy bruising
• unusual bleeding (nose, gums, or a cut)
• purple or red spots under your skin
• heavy menstrual bleeding
• severe headache
• neck stiffness
• bleeding in the whites of the eyes
• black or bloody stools
• pink or brown urine
• coughing up blood
• vomit that looks like coffee grounds
• loss of appetite
• stomach pain (upper stomach right side)
• yellowing of the skin or eyes (jaundice)
• dark urine
• chest pain
• flu-like symptoms
• warmth or chills
• redness on the palms of hands
• muscle or joint pain
• uncontrolled muscle movements

Rare side effects of Inotersen include:

• none

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, loss of coordination, feeling unsteady, very stiff muscles, high fever, profuse sweating, or tremors;
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights;
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out.

This is not a complete list of side effects and other serious side effects or health problems that may occur as a result of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult dosage

Injectable solution

• 284 mg/1.5 mL single-dose prefilled syringe

Hereditary transthyretin amyloidosis

Adult dosage

• 284 mg SC once weekly; administer on the same day each week

Dosage Considerations – Should be Given as Follows:

• See “Dosages”

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, healthcare provider, or pharmacist first.

• Inotersen has severe interactions with no other drugs
• Inotersen has serious interactions with no other drugs
• Inotersen has moderate interactions with the following drugs:
  • voclosporin
  • warfarin
• Inotersen has minor interactions with no other drugs

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all the products you use. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional or doctor for additional medical advice, or if you have health questions or concerns.

Contraindications

• Platelet count less than 100*10^9/L
• History of acute glomerulonephritis caused by Inotersen
• Hypersensitivity

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Inotersen?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Inotersen?”

Cautions

• Causes platelet count reduction that may result in sudden and unpredictable thrombocytopenia that can be life-threatening; monitoring required
• Uninterpretable platelet counts may occur owing to platelet clumping that occurs between antiplatelet antibodies and EDTA; if EDTA-mediated platelet clumping is suspected, repeat platelet count using a different anticoagulant (e.g., sodium citrate, heparin) in the blood collection tube
• Can cause glomerulonephritis that may result in dialysis-dependent renal failure; monitoring required; treatment for glomerulonephritis is immunosuppressive therapy; avoid use in patients for whom immunosuppressive treatment is not advised
• Prescribers must be certified to prescribe inotersen by enrolling in and completing the REMS training program; patients must enroll in the program and comply with ongoing monitoring requirements
• May cause stroke and cervicocephalic arterial dissection (rare) within 2 days of the first dose; patients may also have symptoms of cytokine release (eg, nausea, vomiting, muscular pain, weakness) and a high-sensitivity C-reactive protein level of more than 100 mg/L during this time
• Vitamin A levels may decrease; supplementation with recommended daily allowance advised; refer to an ophthalmologist if ocular symptoms suggestive of vitamin A deficiency occur (eg, night blindness)
• Inflammatory and immune effects
  • May cause inflammatory and immune changes, including immune thrombocytopenia, glomerulonephritis, or rarely, antineutrophil cytoplasmic autoantibody (ANCA)-positive systemic vasculitis
  • One patient developed gait changes that progressed over 6 months to paraparesis, in the absence of radiologic evidence of spinal cord compression
  • Another patient developed progressive lumbar pain, weight loss, headache, vomiting, and impaired speech 7 months after starting inotersen; cerebrospinal fluid (CSF) analysis findings included elevated protein, lymphocyte-predominant pleocytosis, and testing that was negative for infection; recovery occurred after empiric therapy (ie, high-dose steroids, antibiotics) and the patient resumed inotersen without recurrence of symptoms
  • The liver accumulates antisense oligonucleotides; monitor ALT, AST, and total bilirubin
  • Cases of liver transplant rejection reported 2 to 4 months after starting therapy in patients whose liver allografts had previously been clinically stable (for over 10 years) prior to starting therapy; patients clinically improved and transaminase levels normalized after glucocorticoid administration and cessation of therapy; in patients with a history of liver transplant, monitor ALT, AST, and total bilirubin monthly; discontinue therapy in patients who develop signs of liver transplant rejection
  • Hypersensitivity may occur; discontinue treatment and do not reinitiate
• Drug interaction overview
  • Owing to thrombocytopenia risk, caution if inotersen is coadministered with antiplatelets or anticoagulants
  • Caution if coadministered with other drugs that may impair renal function

Pregnancy and Lactation

• There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to the drug during pregnancy; healthcare providers are encouraged to register patients and pregnant women are encouraged to register themselves by calling: 1-877-465-7510, emailing: [email protected], or visiting online at www.tegsedipregnancystudy.com
• There are no available data regarding use in pregnant women
• Inotersen treatment leads to a decrease in serum vitamin A levels and vitamin A supplementation is advised for patients taking inotersen; vitamin A is essential for normal embryofetal development; however, excessive levels of vitamin A are associated with adverse developmental effects
• Effects on the fetus of maternal serum transthyretin (TTR) reduction caused by inotersen and vitamin A supplementation are unknown
• Lactation
  • Unknown if distributed in human milk
  • The development and health benefits of breastfeeding should be considered along with the mother’s clinical need for the drug and any potential adverse effects on the breastfed child or from the underlying maternal condition