Action and Spectrum

Actions and Spectrum: 

• Anticonvulsant activity: stiripentol is effective in reducing the prevalence and severity of seizures in people with Dravet syndrome, which is characterized by frequent and often life-threatening seizures. 
• Anxiolytic activity: Some studies suggest that stiripentol may have anxiolytic (anti-anxiety) effects, although more research is needed to confirm this. 
• Sedative activity: stiripentol has been shown to have sedative effects in some people, although the extent of these effects can vary widely depending on the individual. 
• Anti-tumor activity: stiripentol has been investigated for its potential to inhibit the growth of cancer cells, although the results of these studies have been mixed. 

Drug Interaction

Adverse Reaction

Frequency defined 

>10% 

• Hypotonia (18%) 
• Ataxia (27%) 
• Tremor (15%) 
• Somnolence (67%) 
• Decreased weight (27%) 
• Agitation (27%) 
• Nausea (15%) 
• Dysarthria (12%) 
• Decreased appetite (46%) 

1-10% 

• Salivary hypersecretion (6%) 
• Aggression (9%) 
• Nasopharyngitis (6%) 
• Vomiting (9%) 
• Fatigue (9%) 
• Increased weight (6%) 
• Bronchitis (6%) 
• Pyrexia (6%) 

Black Box Warning

Black Box Warning: 

stiripentol carries a black box warning for the risk of potentially fatal or major skin reactions, together with Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN).

SJS and TEN are rare but severe allergic reactions that can cause widespread blistering and detachment of the skin and mucous membranes, and can be life-threatening. 

Patients should be advised to stop taking stiripentol immediately and seek medical attention if they develop a skin rash or other signs of an allergic reaction while taking the medication.

Contraindication / Caution

Contraindication/Caution: 

Contraindication 

stiripentol is contraindicated in patients with a history of hypersensitivity to stiripentol or any of its components.stiripentol should be avoided in patients who have a history of Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN) due to an increased risk of developing these conditions while taking the medication. 

Caution 

stiripentol may interact with other medications, including other anticonvulsants, and caution should be exercised when using it in combination with other drugs. Patients should inform their healthcare provider of all medications they are taking, including prescription drugs, over-the-counter medications, and dietary supplements, before starting treatment with stiripentol. 

stiripentol should be used with caution in patients with a previous history of liver or kidney disease, as it may affect the function of these organs. It may also cause drowsiness or dizziness, which can affect a patient’s ability to drive or operate machinery, and patients should be advised to avoid these activities until they know how stiripentol affects them. 

As with any medication, patients should discuss the potential benefits and risks of stiripentol with their healthcare provider before starting treatment, especially if they have any root medical conditions or are taking other medications. 

Pregnancy / Lactation

Pregnancy consideration:  

AU TGA pregnancy category B3:   

These are drugs that have been administered to a small number of pregnant women and women of childbearing age, and there has been no indication of an increase in malformation frequency or other direct or indirect dangerous effects on the human fetus. 

US FDA pregnancy category: Not assigned 

Pregnancy category: 

• Category A: well-controlled and Satisfactory studies do not show risk to the fetus in the first/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 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: 

stiripentol is an anticonvulsant medication that is primarily used in the treatment of definite types of seizures. Its precise mechanism of action is not totally understood, but it is believed to enhance the activity of inhibitory neurotransmitter gamma-aminobutyric acid (GABA) in the brain. 

stiripentol has been shown to increase the synthesis and release of GABA, and also to reduce its breakdown in the brain, leading to an overall increase in GABAergic activity. This increased activity of GABA in turn leads to an overall reduction in neuronal excitability, helping to prevent seizures from occurring. 

Pharmacodynamics: 

Although the mechanisms of action are uncertain, it is suggested that the anticonvulsant effect in humans could be attributed to both direct effects on the gamma-aminobutyric acid (GABA) A receptor, as well as indirect effects involving inhibition of cytochrome P450 activity, which could result in elevated blood levels of clobazam and its active metabolite. 

Pharmacokinetics: 

Absorption 

The time to reach peak plasma concentration is typically between 2 to 3 hours. 

Distribution 

The drug has a protein binding capacity of 99%. 

Metabolism 

The drug undergoes hepatic metabolism primarily by the enzymes CYP1A2, CYP2C19, and CYP3A4. 

Elimination and Excretion 

In healthy adults, the drug has a half-life that ranges from 4.5 to 13 hours, which increases with doses of 500 mg, 1000 mg, and 2000 mg. 

For children (median age 7.3 years) with Dravet syndrome, the drug has a half-life of 8.5 hours in a 10-kg patient and 23.5 hours in a 60-kg patient. 

Adminstartion

Administration: 

Oral Administration 

Capsules 

It is recommended to swallow the capsule whole with a glass of water during a meal. Breaking or opening the capsule is not advised. 

Powder for oral suspension 

To administer the medication, mix it in a glass of water (100 mL) and consume it immediately after mixing, preferably during a meal. It is recommended to add a small amount of water (25 mL) to the drinking cup to ensure that no medicine is left in the glass, and to drink all of the mixture. 

Please note that the mixture should not be stored after it is mixed and must be administered immediately after preparation. 

Missed Dose 

If a dose is missed, it is recommended to take it as soon as possible. However, if the next scheduled dose is missed, it should be skipped and the following dose should be taken at the appropriate time. It is important to avoid taking a double dose of the medication to compensate for the missed dose. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: stiripentol 

Pronounced: [ STIR-i-PEN-tol ] 

Why do we use stiripentol? 

stiripentol is a medication used in the treatment of seizures associated with Dravet syndrome, a rare genetic disorder that causes severe epilepsy in children. It is usually prescribed as an add-on treatment for patients who have not responded well to other anti-epileptic medications. 

stiripentol works by enhancing the effects of the neurotransmitter GABA, which helps to calm overactive brain activity and reduce seizures. It is typically taken orally in capsule form, usually in combination with other anti-epileptic drugs. 

Aside from its use in the treatment of Dravet syndrome, stiripentol is also being studied for its potential use in other forms of epilepsy, such as Lennox-Gastaut syndrome and refractory epilepsy.