trofinetide

Action and Spectrum

Actions and Spectrum: 

• trofinetide is a synthetic peptide developed to treat Rett syndrome, a rare genetic disorder affecting girls’ brain development. The mechanism of action of trofinetide has yet to be fully understood. Still, it is thought to work by modulating the activity of the neurotrophic factors brain-derived neurotrophic factor (BDNF) and insulin-like growth factor 1 (IGF-1), which play essential roles in brain development, plasticity, and function. 

• trofinetide has a broad spectrum of activity, affecting multiple systems in the brain and improving neuronal function and communication. It has been shown to increase synaptic and dendritic spine density, which is essential for neural communication and plasticity. It also enhances neuroprotection, reduces neuroinflammation, and regulates the brain’s excitatory and inhibitory neurotransmitter balance. 

Drug Interaction

Adverse Reaction

Frequency defined 

>10% 

Diarrhea (82%) 

Vomiting (29%) 

Persistent or recurrent diarrhea after dosage pauses, dose reductions, or concurrent antidiarrheal treatment (49%) 

1-10% 

Seizure (9%) 

Decreased appetite (8%) 

Nasopharyngitis (5%) 

Fever (9%) 

Anxiety (8%) 

Fatigue (8%) 

Black Box Warning

Contraindication / Caution

Contraindications/caution: 

Contraindications: 

None 

Caution: 

• Adverse effects: trofinetide has been generally well-tolerated in clinical trials, but some adverse effects have been reported, including diarrhea, vomiting, and injection site reactions. 
• Interactions with other drugs: The potential for interactions with other drugs have not been extensively studied. Therefore, caution is advised when trofinetide is used concomitantly with other drugs. 
• Long-term effects: The long-term safety and efficacy of trofinetide still need to be fully understood, as the drug is still in clinical development 
• Cost: As with many novel drugs, the cost of trofinetide is likely to be high, which may limit its accessibility to patients. 
• Limited availability: trofinetide still needs to be approved for use by regulatory agencies in most countries, so access to the drug may be limited to clinical trial participants or through compassionate use programs. 

Pregnancy / Lactation

Pregnancy consideration: The pregnancy category of trofinetide is not currently established. The drug is still in clinical development and has not yet been approved by regulatory agencies for use in any indication. 

Lactation:  

• The safety and efficacy of trofinetide during lactation have not been established. The drug is still in clinical development and has not yet been approved for use in any indication. 
• Limited information is available on the extent of trofinetide excretion in human milk, and it is unknown whether trofinetide can cause harm to a nursing infant. 

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

Pharmacology

Pharmacology: 

• Modulation of neurotrophic factors: trofinetide is thought to modulate the activity of the neurotrophic factors brain-derived neurotrophic factor (BDNF) and insulin-like growth factor 1 (IGF-1), which play essential roles in brain development, plasticity, and function. 

• Enhancement of synaptic density: trofinetide has been shown to increase synaptic density, which is essential for neural communication and plasticity. 

• Regulation of neurotransmitters: trofinetide appears to regulate the balance of excitatory and inhibitory neurotransmitters in the brain, which is critical for maintaining normal brain function. 

• Reduction of neuroinflammation: trofinetide has been shown to reduce neuroinflammation, a pathological process that can damage neurons and impair brain function. 

• Improve cognitive function: trofinetide has been shown to improve cognitive function in preclinical and clinical studies, with improvements in social communication, behavior, and cognition observed in patients with Rett syndrome. 

Pharmacodynamics: 

The pharmacodynamics of trofinetide, a synthetic peptide being developed for treating Rett syndrome, are complex and not yet fully understood. 

Pharmacokinetics: 

Absorption 

trofinetide is administered by subcutaneous injection and is rapidly absorbed into the bloodstream. Peak plasma concentration is achieved within 2-3 hours after administration. The bioavailability of trofinetide is ≥84%, indicating that most of the administered dose reaches systemic circulation.  

Distribution 

trofinetide has a low degree of plasma protein binding (<6%) and a large volume of distribution (~80 L), indicating that it distributes widely into the tissues.  

Metabolism 

trofinetide is not significantly metabolized by the cytochrome P450 (CYP450) enzyme system or other metabolic pathways.Hepatic metabolism is not a significant route of elimination.  

Elimination and Excretion 

trofinetide has a relatively short elimination half-life of approximately 1.5 hours. Approximately 80% of the dose is eliminated unchanged in the urine, indicating that renal excretion is the primary route of elimination. A minor amount of trofinetide is eliminated in the feces. 

Adminstartion

Administration: 

Oral administration: 

• It may be consumed with or without food 
• Administer orally or through a gastrostomy (G) tube; gastrojejunal (GJ) tube dosages must be supplied via the G-port. 
• Use calibrated measurement equipment (e.g., oral syringe or oral dosing cup) to measure and provide the required amount correctly; The domestic measuring cup is insufficient as a measuring instrument. 

Storage 

• Refrigerate the bottle vertically at 2-8°C (36-46°F). 
• Do not freeze 
• Keep the child-resistant cap firmly closed. 
• Within 14 days after opening the bottle, discard any unused oral solution. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: trofinetide 

Why do we use trofinetide? 

trofinetide is a synthetic peptide currently being developed as a potential treatment for Rett syndrome, a rare genetic disorder affecting brain development and function, primarily in girls. Rett syndrome is caused by mutations in the MECP2 gene, which regulates the expression of other genes in the brain.