Trofinetide for Rett Syndrome: How It Works, Benefits, and Side Effects

When a child starts to lose skills they once had — like using their hands, speaking, or walking steadily — it can be a frightening time for families. In people with Rett syndrome, these changes are caused by a rare genetic condition that affects movement, speech, breathing, and daily life. For years, no targeted treatments were designed for Rett syndrome. That changed in 2023 with trofinetide (Daybue), the first drug approved by the U.S. Food and Drug Administration (FDA) specifically for this condition.

In more than 95 percent of classic cases, Rett syndrome is caused by a mutation in a gene called MECP2. This gene helps control how the brain develops and how brain cells communicate. When the MECP2 gene doesn’t work properly, these connections are disrupted. Rett syndrome mostly affects females, though a small number of males also develop the condition, according to the FDA.

This article explains how trofinetide works, who it may help, and what research shows. It also discusses side effects and drug interactions families should understand.

How Trofinetide Works

Here’s what trofinetide is, how it may work in the brain, and how it’s taken each day.

What Trofinetide Is

Trofinetide is a lab-made version of a small protein fragment related to insulin-like growth factor 1 (IGF-1). In 2023, the FDA approved trofinetide as an oral solution for people 2 years and older with Rett syndrome.

How It May Help

Researchers believe trofinetide may help brain cells communicate more smoothly and reduce inflammation in the brain. Exactly how it works is still not fully understood, but it’s clear that trofinetide doesn’t fix the MECP2 gene itself. Instead, it may help the brain function better despite the gene change, so it helps manage symptoms but isn’t a cure.

How It’s Taken

Trofinetide is taken by mouth twice daily, and the dose is based on body weight. In 2025, the FDA approved a powder form (Daybue Stix) that’s mixed with water. This allows families to adjust volume and taste, which can help people who are sensitive to tastes and textures.

People who have trouble swallowing can take trofinetide through a gastrostomy tube (G-tube). If a gastrojejunal (GJ) tube is used, the dose is given through the G-port, not the J-port. People taking trofinetide are usually advised to stop laxatives before starting trofinetide. Diarrhea is the most common side effect, and laxatives can make it worse.

Who It’s For

Not every person with Rett syndrome will be able to take trofinetide. A healthcare provider will consider overall health, body weight, nutrition, and digestive health before starting treatment.

Kidney function also matters because the body clears most of the medicine through the kidneys. People with mild kidney problems can take the standard dose. Those with moderate kidney problems may need a lower dose, and some lower doses are available only as the liquid form. People with severe kidney disease should not take trofinetide. A simple blood test can check kidney function before starting treatment.

Recognizing the Benefits

Both clinical trials and real-world studies help families understand what trofinetide can realistically do.

What Studies Found

In the main study behind trofinetide’s approval, one group took trofinetide and another took a placebo (a liquid with no active drug). After 12 weeks, the trofinetide group showed greater improvement in overall Rett symptoms, including hand movements, balance, breathing patterns, and communication. Healthcare providers also rated participants in this group as improved overall.

Benefits continued in people who stayed on the drug longer. Follow-up studies found that improvements held steady for up to 32 months, with no new safety concerns. Another study found the drug was generally well tolerated in children ages 2 to 4.

What Real-World Data Showed

A real-world study followed people taking trofinetide for 12 months. Caregivers often reported improvements in nonverbal communication, alertness, and social interaction, with many noting positive changes over time. They also reported some improvement in quality of life, including physical health, independence, and positive emotions.

Keeping Expectations Grounded

Trofinetide helps manage symptoms but doesn’t cure Rett syndrome. Some people may see clear improvements, while others may see smaller ones. Benefits often take weeks to months to appear, and they may fade if the drug is stopped. Any decision to pause or stop trofinetide should be made with a healthcare provider.

Managing Side Effects and Staying Safe

Understanding the effects of trofinetide — both benefits and side effects — can help families know what to watch for and when to act. Some side effects require close attention, so staying in contact with the care team is essential.

Vomiting and Aspiration Risk

Many people with Rett syndrome already have trouble swallowing and a weak cough reflex. In one study, trofinetide caused vomiting in nearly 30 percent of participants (compared to 12 percent on placebo). Together, these factors raise the risk of aspiration — when stomach contents enter the lungs. Vomiting during treatment can lead to aspiration and can cause aspiration pneumonia, a serious lung infection.

After any vomiting episode, caregivers should watch for breathing problems, fever, or sudden changes in alertness. If these symptoms develop, contact the care team right away.

Other Common Side Effects

Diarrhea, the most common side effect, affected about 4 in 5 people taking trofinetide in clinical studies. Most cases were mild, but diarrhea can be ongoing and require dose changes or antidiarrheal medication. The FDA advises reducing the dose, pausing, or stopping the drug if diarrhea is severe.

Other side effects of trofinetide include fever, seizures, anxiety, fatigue, and decreased appetite. Because epilepsy is common in Rett syndrome, any change in seizure activity after starting trofinetide should be reported to a doctor right away.

Responses to side effects can vary. In a clinical trial, about 17 percent of people taking trofinetide stopped treatment due to side effects, compared with 2 percent on placebo. Diarrhea was the most common reason. This doesn’t mean the drug won’t work, but it does mean doctors need to monitor people using it and treat any problems quickly.

Tracking Fluids, Food, and Weight

Diarrhea and vomiting can lead to fluid loss and weight loss, so good hydration is important. A study found that 12 percent of people taking trofinetide lost more than 7 percent of their body weight, compared with 4 percent of those on placebo. If significant weight loss occurs, the FDA recommends reducing, pausing, or stopping the dose under a doctor’s guidance. Caregivers can take these steps to help manage this risk:

• Track the frequency of bowel movements and consistency of stools.
• Monitor daily fluid intake.
• Check weight regularly and record the results.
• Reach out to a dietitian if nutrition becomes a concern.

Watching for Drug Interactions

Trofinetide can affect how the body processes certain medications, causing them to build up and increase the risk of side effects.

One important interaction involves loperamide, a common over-the-counter antidiarrheal. Because many people taking trofinetide develop diarrhea — and more than half may need antidiarrheal treatment — loperamide is often used with trofinetide. Research shows that combining the two can nearly double the peak level of loperamide in the blood, which may affect heart rhythm. For this reason, a doctor or a pharmacist should review all medications before starting treatment.

Taking the Next Step

Studies suggest that trofinetide may improve communication, hand movements, alertness, and overall function — and benefits may remain over time for many people. The drug can also cause side effects that need active management, but with careful monitoring and support, many families are able to continue treatment.

Families can prepare for the next step by writing down all current medications, including doses and timing, to share at the next doctor visit. You and the doctor may discuss kidney function, seizure history, and diarrhea management.

Every person with Rett syndrome is different, and a healthcare team can help build a plan that fits individual needs.

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