Fitusiran

Action and Spectrum

Actions and Spectrum

RNA interference degrades antithrombin mRNA to lower plasma antithrombin levels.

Fitusiran targets antithrombin mRNA in liver cells using siRNA.

Degradation of AT mRNA reduces antithrombin protein levels.

Drug Interaction

Adverse Reaction

Frequency defined:

>10%

Nasopharyngitis

Viral infection

Bacterial infection

1-10%

Hepatic injury

Headache

Cough

Arthralgia

Injection site reactions

Gallbladder events

Thrombotic events

Dyspepsia

Abdominal pain

Black Box Warning

Black Box Warning 

Serious thrombotic events occurred in patients with thromboembolism risk factors, including low antithrombin activity, fitusiran use, indwelling catheters, and non-adherence to bleed management.

Monitor signs of acute gallbladder disease to consider discontinuing fitusiran and explore alternative hemophilia treatment if symptoms arise.

Contraindication / Caution

Contraindication / Caution

Contraindication:

None

Caution:

Risk of Thrombosis

Liver Function Monitoring

Hepatotoxicity

Pregnancy / Lactation

Pregnancy / Lactation

Pregnancy Warnings:

Pregnancy category: N/A

Lactation: Excretion of the drug into the human breast milk is unknown

Pregnancy categories:

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

Category B: No evidence of risk to fetus found in animal reproduction studies and there are not enough studies on pregnant women.

Category C: Adverse effects on the fetus found with evidence in animal reproduction studies and no adequate evidence for an effect in humans, care must be taken for potential risks in pregnant women.

Category D: There is adequate data available with sufficient evidence of human fetal risk from various platforms, but despite potential risks may be used only in emergency cases for potential benefits.

Category X: Drugs listed in this category clearly outweigh risks over benefits. These category drugs should be prohibited for pregnant women.

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

Pharmacology

Pharmacology

Hemophilia patients lack clotting factors to cause impaired blood coagulation.

It reduced thrombin activity to enhance clot formation and decreasing bleeding.

Antithrombin inhibits thrombin and Factor Xa to prevent clotting.

Pharmacodynamics

Fitusiran increases thrombin production by reducing antithrombin in hemophilia.

It decreased antithrombin translation reduces plasma levels and improving blood clot formation in hemophilia patients.

The effects last weeks because of siRNA’s long half-life.

Pharmacokinetics

Absorption:

Peak plasma levels are reached within for fitusiran 20 mg: 2.88 hours and for 50 mg: 3.78 hours.

Area of curve for fitusiran 20 mg: 491 ng⋅hr/ml

And for 50 mg: 1,290 ng⋅hr/ml.

Distribution:

It has high protein binding up to 96.6%

Metabolism:

Endo- and exo-nucleases metabolize to oligonucleotides of progressively shorter lengths.

Elimination and excretion:

Half-life shows of fitusiran for 20 mg: 5.57 hours and for 50 mg: 7.98 hours.

Clearance shows of fitusiran for 20 mg: 41.9 L

and for 50 mg: 50.8 L.

Adminstartion

Administration

Administer through subcutaneous route in thigh or abdomen region but avoid around navel region.

Caregiver injects in outer upper arm area.

Avoid injecting into tender, damaged, or bruised skin.

Avoid administering into a vein.

Patient Information Leaflet

Patient information leaflet

Generic Name: fitusiran

Why do we use fitusiran?

Fitusiran is an investigational RNA interference (RNAi) therapy drug used in treatment of hemophilia A and B.