omaveloxolone

Action and Spectrum

Actions and Spectrum: 

The primary action of omaveloxolone is to activate a transcription factor called Nrf2. Nrf2 regulates the expression of a wide range of genes that are involved in cellular defense mechanisms, including antioxidant and anti-inflammatory pathways. By activating Nrf2, omaveloxolone can increase the expression of these genes and protect cells from damage caused by oxidative stress and inflammation. 

omaveloxolone also has the ability to activate the Keap1-Nrf2-ARE pathway, which is involved in the regulation of oxidative stress response genes. This pathway is critical for maintaining cellular homeostasis and protecting cells from oxidative damage. 

In terms of its spectrum of action, omaveloxolone has been shown to have therapeutic potential in a variety of diseases that involve oxidative stress and inflammation, including mitochondrial myopathies, Friedreich’s ataxia, and diabetic neuropathy. It has also been investigated as a potential treatment for neurodegenerative diseases, such as Alzheimer’s and Parkinson’s diseases. 

Drug Interaction

Adverse Reaction

Frequency Defined  

1-10%   

Rash (10%)  

>10%   

Nausea (33%)  

Headache (37%)  

Abdominal pain (29%)  

Diarrhea (20%)  

AST/ALT increased (37%)  

Fatigue (24%)  

Oropharyngeal pain (18%)  

Vomiting (16%)  

Influenza (16%)  

Muscle spasms (14%)  

Decreased appetite (12%)  

Back pain (13%)  

Black Box Warning

Black Box Warning: 

The U.S. Food and Drug Administration (FDA) has issued a black box warning for omaveloxolone due to the risk of liver injury. According to the warning, omaveloxolone can cause serious and potentially fatal liver injury, including acute liver failure. 

Contraindication / Caution

Contraindication/Caution: 

Contraindications: 

• omaveloxolone is contraindicated in patients with hypersensitivity to the active substance or any of its excipients. 

Cautions: 

• omaveloxolone may cause serious liver injury, and liver function tests should be monitored regularly. 
• omaveloxolone may cause electrolyte imbalances and should be used with caution in patients with electrolyte disturbances or underlying conditions that may lead to electrolyte imbalances. 
• omaveloxolone may interact with certain medications, including drugs that induce or inhibit CYP3A enzymes, and caution should be used when administering omaveloxolone concomitantly with these medications. 
• omaveloxolone has not been studied in pregnant or breastfeeding women, and caution should be used when administering this medication to these populations. 

Pregnancy / Lactation

Pregnancy warnings:     

Pregnancy category: N/A 

Lactation: Excreted into human milk is unknown 

Pregnancy Categories:         

Category A: Studies that were well-controlled and met expectations revealed no risk to the fetus in either the first or second trimester. 

Category B: There were lack of studies on pregnant women and no evidence of risk to the foetus in animal experiments.   

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 available 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:  

omaveloxolone is a small molecule that belongs to a class of compounds known as synthetic triterpenoids. It is being developed as a potential therapeutic agent for the treatment of various diseases, including rare genetic disorders, such as Friedreich’s ataxia and mitochondrial myopathies, as well as for pulmonary arterial hypertension. 

Pharmacodynamics: 

omaveloxolone works by activating a protein called nuclear factor erythroid 2-related factor 2 (Nrf2), which is involved in the body’s response to oxidative stress. Nrf2 regulates the expression of genes that encode antioxidant and detoxification enzymes, as well as other proteins that help to protect cells from damage caused by free radicals and other harmful molecules. 

Pharmacokinetics: 

Absorption  

omaveloxolone is administered orally as a capsule, and its absorption from the gastrointestinal tract is expected to be moderate to high.   

Distribution  

omaveloxolone is expected to be distributed widely throughout the body, as it has a low to moderate plasma protein binding. The volume of distribution of omaveloxolone is not currently known.  

Metabolism  

omaveloxolone is metabolized in the liver by cytochrome P450 enzymes, primarily CYP1A2 and CYP3A4. It undergoes oxidation, hydroxylation, and glucuronidation to form several metabolites, which are excreted in the urine and feces.  

Elimination and Excretion  

The elimination half-life of omaveloxolone is about 17 hours, and it is primarily eliminated through the feces (about 80%) and to a lesser extent in the urine (about 13%).

Adminstartion

Administration:  

omaveloxolone is taken orally, usually with food, and should be swallowed whole. It should not be crushed, chewed, or broken. The dosage and frequency of administration will vary depending on the medical condition being treated, the patient’s age, weight, and overall health, and other factors. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: omaveloxolone 

Why do we use omaveloxolone? 

omaveloxolone is a medication that is used to treat several medical conditions, including Friedreich’s ataxia and mitochondrial myopathy. It works by activating the Nrf2 pathway, which is involved in protecting cells from oxidative stress and inflammation.