imetelstat

Action and Spectrum

Actions and Spectrum:  

Actions:  

Tumor cells are known to exhibit high levels of telomerase activity, which is necessary to divide and replicate cells indefinitely and maintain telomere size and structure.  

Imetelstat interferes with this process by inhibiting telomerase, leading to progressive shortening of telomeres, cellular aging, and cell death with a focus on the affected malignant cells. 

Drug Interaction

Adverse Reaction

Frequency defined 

>10% 

All grades 

PTT prolonged (26%) 

Fatigue (29%) 

ALT increased (43%) 

ALP increased (48%) 

AST increased (53%) 

Neutrophil count decreased (92%) 

WBC count decreased (94%) 

Platelet count decreased (97%) 

Grades 3-4 

Neutrophil count decreased (72%) 

WBC count decreased (53%) 

Platelet count decreased (65%) 

1-10% 

All grades 

Pruritus (6%) 

Hematoma (6%) 

Epistaxis (7%) 

Syncope (7%) 

Infusion-related reactions (8%) 

Urinary tract infection (9%) 

Grades 3-4 

Urinary tract infection (2.5%) 

Arthralgia/myalgia (2.5%) 

Fractures (3.4%) 

ALT increased (3.4%) 

Other clinically relevant adverse reactions (<5%) 

Sepsis 

Hypertension 

Gastrointestinal hemorrhage 

Febrile neutropenia 

<1% 

Grades 3-4 

Headache (0.8%) 

AST increased (0.8%) 

Black Box Warning

Black Box Warning  

None  

Contraindication / Caution

Contraindication/Caution:  

Contraindication: 

None

Caution: 

Embryo-fetal toxicity 

Infusion-related reactions 

Neutropenia 

Thrombocytopenia 

Pregnancy / Lactation

Pregnancy & breastfeeding: 

Pregnancy consideration:   

No data is available regarding the administration of the drug during pregnancy.  

Breastfeeding warnings:   

No data is available regarding the excretion of drugs in breast milk.  

Pregnancy category:  

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: No data for the drug under this category is available.  

Pharmacology

Pharmacology:  

Imetelstat is a selective small-molecule inhibitor of telomerase. 

Pharmacodynamics:  

The pharmacodynamics profile reveals imetelstat’s ability to reduce telomere length and telomerase activity, contributing to anticancer attributes. Based on this mechanism, imetelstat maybe a useful therapy for several types of hematologic malignancies including myelofibrosis and several subtypes of MDS. 

Pharmacokinetics:  

Absorption 

The drug has a peak plasma concentration of 18.3 μM. 

Distribution 

Imetelstat is highly bound to proteins in the blood (>94%). The volume of distribution of the drug is 14.1 L. 

Metabolism 

Anticipated to be broken down into nucleotides of different lengths by nucleases 

Excretion and elimination 

The elimination half-life of the drug is 4.9 hr. 

Adminstartion

Administration:  

The route of administration is intravenous. 

Patient Information Leaflet

Patient information leaflet  

Generic Name: imetelstat 

Why do we use imetelstat?  

Based on the current evaluations, the use of imetelstat has been considered effective as it relieves symptoms through shrinking the size of the spleen in patients diagnosed with myelofibrosis.
It is currently explored in its ability to enhance the hematologic outcomes, as well as decrease the frequency of RBC transfusions for myelodysplastic syndromes; especially in lower risk MDS.