Action and Spectrum

Actions and Spectrum 

inotersen is designed to bind to the RNA sequence of the TTR gene, forming a complementary strand. This binding inhibits the translation of TTR messenger RNA (mRNA) into protein, reducing the production of abnormal TTR protein. 

inotersen is used in the treatment of hereditary transthyretin amyloidosis (hATTR), a rare genetic disorder characterized by the buildup of abnormal amyloid proteins in various tissues and organs of the body. 

Drug Interaction

Adverse Reaction

Frequency defined  

1-10% 

Dyspnea (9%) 

Bacterial infection (7%) 

Dry mouth (5%) 

Elevated liver function test (9%) 

Orthostasis (8%) 

Eosinophilia (5%) 

Contusion (7%) 

Influenza like illness (8%) 

Decreased appetite (10%) 

Paresthesia (10%) 

>10% 

Headache (26%) 

Fatigue (25%) 

Fever (20%) 

Chills (18%) 

Vomiting (15%) 

Arthralgia (13%) 

Presyncope or syncope (13%) 

Peripheral edema (19%) 

Anemia (17%) 

Myalgia (15%) 

Arrhythmia (13%) 

Thrombocytopenia (24%) 

Decreased renal function (14%) 

Injection site reactions (49%) 

Nausea (31%) 

Black Box Warning

Black Box Warning 

inotersen can cause thrombocytopenia, which is a decrease in blood platelets that can lead to an increased risk of bleeding. inotersen can cause worsening of renal function, including potentially severe glomerulonephritis.  

inotersen is offered under a restricted distribution programme under a Risk Evaluation and Mitigation Strategy (REMS) due to risks of major bleeding brought on by severe thrombocytopenia and glomerulonephritis, both of which call for regular monitoring. 

Contraindication / Caution

Contraindication/Caution: 

Contraindication: 

• inotersen is contraindicated in individuals who have a known hypersensitivity or have allergic reaction to inotersen or any of its components. 
• inotersen is contraindicated in patients with a platelet count below a certain limit.  

Caution: 

• Inotersen can cause thrombocytopenia, which is a decrease in blood platelets that may increase the risk of bleeding. 
• Patients using inotersen should have their platelet counts regularly checked, and if severe thrombocytopenia develops, treatment should be stopped or terminated. 
• inotersen is injected subcutaneously and may result in adverse injection site reactions. Injection site responses, including pain, swelling, redness, or rash, should be kept an eye out for in the patients. 

Pregnancy / Lactation

Pregnancy consideration: 

Pregnancy category: N/A 

Lactation: Excretion into human milk is unknown  

Pregnancy Categories:         

Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester. 

Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women.  

Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women. 

Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits. 

Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women. 

Category N: There is no data available for the drug under this category. 

Pharmacology

Pharmacology  

Reduced levels of serum TTR protein and tissue TTR protein deposits are the result of the degradation of mutant and wild-type transthyretin (TTR) mRNA caused by the antisense oligonucleotide’s binding to the TTR mRNA. 

Pharmacodynamics 

TTR accumulates in tissues of hereditary transthyretin amyloidosis (hATTR), patients as fibrils, which restricts the tissue’s ability to function normally. 

Pharmacokinetics 

Absorption   

inotersen is readily absorbed into the systemic circulation. 

Distribution 

inotersen distributes throughout the body and the total volume of distribution is approximately 293 L. 

Metabolism 

inotersen metabolized by nucleases to nucleotides of different lengths. 

Elimination and excretion 

The route of elimination for inotersen is through renal excretion.

Adminstartion

Administration 

inotersen is administered through subcutaneous injection. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: inotersen 

Why do we use inotersen? 

inotersen is primarily used for the treatment of hereditary transthyretin amyloidosis (hATTR) polyneuropathy in adult patients.   

inotersen helps to reduce the production of abnormal transthyretin (TTR) protein and slow down the progression of the disease.