ganaxolone

Action and Spectrum

Actions and Spectrum: 

While the precise mode of action of ganaxolone is yet unknown, it is believed to increase the activity of the neurotransmitter GABA (gamma-aminobutyric acid), which oversees reducing brain nerve activity. This causes the brain to calm down, which can lessen anxiety and stop seizures. 

In preclinical and clinical research, ganaxolone has demonstrated efficacy for a variety of illnesses across its spectrum, including: 

Patients with various kinds of epilepsy, including those with the illness that is treatment-resistant, have proven that ganaxolone is beneficial in lowering the frequency of their seizures. 

A potential treatment for postpartum depression, which affects some women after giving birth. ganaxolone is also being investigated as a potential therapy for this genetic disorder, which produces symptoms like intellectual incapacity, behavioural issues, and emotional issues. 

Drug Interaction

Adverse Reaction

Frequency Defined  

1-10% 

Upper respiratory tract infection (10%) 

Seasonal allergy (6%) 

Sedation (6%) 

Salivary hypersecretion (6%) 

Gail disturbance (4%) 

Nasal congestion (4%) 

Bronchitis (4%) 

Influenza (4%) 

>10% 

Pyrexia (18%) 

Somnolence (38%) 

Black Box Warning

Contraindication / Caution

Contraindication/Caution: 

Contraindication: 

• Those with a history of hypersensitivity to ganaxolone or its ingredients should not use it. 

Caution: 

• ganaxolone should not be taken during pregnancy unless the advantages outweigh the dangers since it may provide a risk to the growing baby. 
• Care should be used when giving ganaxolone to individuals with compromised liver or kidney function because the drug is processed in the liver and eliminated via the kidneys. 
• Cognitive and motor performance may be hampered by the CNS depression that ganaxolone can produce. 

Pregnancy / Lactation

Pregnancy warnings:     

Pregnancy category: N/A 

Lactation: Excretion into human milk is known 

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 

It is an artificial neurosteroid (ganaxolone), that works as a positive allosteric modulator of the GABA-A receptor. It is being researched as a possible therapy for several illnesses, including postpartum depression, epilepsy and fragile X syndrome. It possesses both anxiolytic (anti-anxiety) and anticonvulsant characteristics. 

Pharmacodynamics 

As a positive allosteric modulator of the GABA-A receptor, ganaxolone increases GABA’s activity at the receptor site. When ganaxolone binds to a particular region of the GABA-A receptor, channel opening frequency and chloride ion inflow increase.

This causes the neuron to become hyperpolarized and reduces neuronal excitability, which calms the brain. These effects are comparable to benzodiazepines and barbiturates, two drugs that increase GABAergic transmission. 

Pharmacokinetics 

Absorption   

When taken orally as a solution, ganaxolone is quickly absorbed from the digestive tract. Peak plasma concentrations of ganaxolone are reached after 1 to 2 hours of administration, and its absolute bioavailability is around 12%. 

Distribution 

With a volume of distribution of around 3.8 L/kg, ganaxolone is widely dispersed throughout the body. Around 99% of the medication can bind to plasma proteins, indicating strong binding. The blood-brain barrier is crossed by ganaxolone, which also has good central nervous system penetration. 

Metabolism 

The CYP2D6 and CYP3A4 enzymes are primarily responsible for the liver’s metabolism of ganaxolone. Three-beta-methyl-dihydro deoxycorticosterone (3-beta-MDHC) and three-beta, twenty-one-dihydroxy-5-alpha-pregnant-20-one are ganaxolone’s principal metabolites. These metabolites help the drug’s overall effects by being pharmacologically active. 

Elimination and excretion 

Around 75% of the dosage of ganaxolone and its metabolites are discharged in the urine after 24 hours of administration. ganaxolone has a half-life of around 6-7 hours, and after dosage, steady-state concentrations are reached in about 2-3 days. The kidneys do not significantly metabolize ganaxolone, so patients with renal impairment do not require dosage adjustments. 

Adminstartion

Administration:  

ganaxolone is given orally and is authorised for use as an oral solution. Depending on the indication being treated, the dose schedule may change, and this should be decided by a healthcare professional. 

The beginning dose of ganaxolone for treating postpartum depression is 1,320 mg twice daily for the first two weeks, and then a maintenance dose of 1,980 mg twice daily for the following two weeks. Four weeks are allotted for the course of therapy. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: ganaxolone  

Why do we use ganaxolone? 

A few disorders involving the central nervous system are treated using the medication ganaxolone. 

For treating postpartum depression (PPD) in adults, ganaxolone has received approval. PPD, a kind of depression that follows delivery, can manifest as mood swings, anxiety, and trouble sleeping. 

Adults with focal onset seizures may be treated with ganaxolone, according to official guidelines. Status epilepticus is a medical emergency characterised by continuous or frequent seizures that can cause brain damage or death.