Version July 2025
Rett syndrome:
Weight 35 to <50 kg: Oral: 10 g (50 mL) twice daily.
Weight ≥50 kg: Oral: 12 g (60 mL) twice daily.
Missed doses: If a dose is missed or if vomiting occurs after administration, take the next dose as scheduled (eg, do not administer an extra or double dose).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
eGFR ≥60 mL/minute: No dosage adjustment necessary.
eGFR 30 to 59 mL/minute:
Weight 35 to <50 kg: 5 g (25 mL) twice daily.
Weight ≥50 kg: 6 g (30 mL) twice daily.
eGFR <30 mL/minute: Use is not recommended.
There are no dosage adjustments provided in the manufacturer's labeling; however, hepatic impairment is not expected to affect trofinetide exposure.
Diarrhea, dehydration, vomiting:
Diarrhea, mild or moderate : Consider antidiarrheal therapy; monitor hydration status and increase oral fluids as appropriate.
Diarrhea, severe; dehydration; vomiting, severe : Interrupt therapy, reduce dose, or discontinue therapy.
Weight loss, significant: Monitor weight and interrupt therapy, reduce dose, or discontinue therapy.
Refer to adult dosing.
(For additional information see "Trofinetide: Pediatric drug information")
Rett syndrome:
Note: Manufacturer recommends discontinuation of laxatives prior to initiation due to significant incidence of diarrhea in clinical trials.
Children ≥2 years and Adolescents:
9 to <12 kg: Oral: 5,000 mg twice daily.
12 to <20 kg: Oral: 6,000 mg twice daily.
20 to <35 kg: Oral: 8,000 mg twice daily.
35 to <50 kg: Oral: 10,000 mg twice daily.
≥50 kg: Oral: 12,000 mg twice daily.
Dosing adjustment for toxicity:
Diarrhea, dehydration:
Diarrhea, mild or moderate : Consider antidiarrheal therapy; monitor hydration status and increase oral fluids as appropriate.
Diarrhea, severe; dehydration : Interrupt, reduce dose, or discontinue therapy.
Weight loss, significant: Monitor weight and interrupt, reduce dose, or discontinue therapy.
Vomiting, severe or despite medical management: Interrupt, reduce dose, or discontinue therapy.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Altered kidney function:
Children ≥2 years and Adolescents:
eGFR ≥60 mL/minute/1.73 m2: No dosage adjustment necessary.
eGFR 30 to <60 mL/minute/1.73 m2: Reduce dose based on weight:
9 to <12 kg: Oral: 2,500 mg twice daily.
12 to <20 kg: Oral: 3,000 mg twice daily.
20 to <35 kg: Oral: 4,000 mg twice daily.
35 to <50 kg: Oral: 5,000 mg twice daily.
≥50 kg: Oral: 6,000 mg twice daily.
eGFR <30 mL/min/1.73 m2: Use not recommended.
There are no dosage adjustments provided in the manufacturer's labeling; liver metabolism is not a significant route of elimination.
Gastrointestinal effects, including diarrhea, vomiting, and weight loss, have been reported with trofinetide and may lead to treatment discontinuation. Diarrhea was reported as mild to moderate in a majority of cases; however, persistent diarrhea or recurrence after resolution despite dose interruptions, reductions, or concomitant antidiarrheal therapy has been reported.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Reported adverse reactions are for adults and pediatrics.
>10%:
Endocrine & metabolic: Weight loss (12%; weight loss of >7% from baseline) (table 1)
|
Drug (Trofinetide) |
Placebo |
Population |
Number of Patients (Trofinetide) |
Number of Patients (Placebo) |
Comments |
|---|---|---|---|---|---|
|
12% |
4% |
Children, adolescents, and adults |
93 |
94 |
Weight loss of >7% from baseline |
Gastrointestinal: Diarrhea (82%) (table 2), vomiting (29%) (table 3)
|
Drug (Trofinetide) |
Placebo |
Population |
Number of Patients (Trofinetide) |
Number of Patients (Placebo) |
|---|---|---|---|---|
|
82% |
20% |
Children, adolescents, and adults |
93 |
94 |
|
Drug (Trofinetide) |
Placebo |
Population |
Number of Patients (Trofinetide) |
Number of Patients (Placebo) |
|---|---|---|---|---|
|
29% |
12% |
Children, adolescents, and adults |
93 |
94 |
1% to 10%:
Gastrointestinal: Decreased appetite (8%)
Nervous system: Anxiety (8%), fatigue (8%), seizure (9%)
Respiratory: Nasopharyngitis (5%)
Miscellaneous: Fever (9%)
There are no contraindications listed in the manufacturer's US labeling.
Canadian labeling: Hypersensitivity to trofinetide or any component of the formulation.
There are no warnings listed in the manufacturer's labeling.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Oral:
Daybue: 200 mg/mL (450 mL) [contains fd&c red #40 (allura red ac dye), methylparaben sodium, propylparaben sodium; strawberry flavor]
No
Solution (Daybue Oral)
200 mg/mL (per mL): $28.39
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Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Oral:
Daybue: 200 mg/mL (500 mL) [contains fd&c red #40 (allura red ac dye), methylparaben sodium, propylparaben sodium]
Oral: May administer without regard to food. Administer with a calibrated measuring device (eg, oral syringe or oral dosing cup obtained from pharmacy); do not use a household measuring cup. May also be administered via gastrostomy (G) tube; doses administered via gastrojejunal tubes must be administered through the G port.
Oral:
Oral solution (commercially available): May administer without regard to food. Administer with a calibrated measuring device (eg, oral syringe or dosing cup); do not use a household measuring device (eg, measuring cup).
Administration via feeding tube:
Gastric (eg, G-tube) tubes: Draw up dose into an enteral dosing syringe and administer via feeding tube. If administering via gastrojejunal (GJ) tube, administer only through G-port.
Missed dose: If a dose is missed or vomiting occurs after administration, resume dosing at next scheduled time; do not administer an additional dose.
Rett syndrome: Treatment of Rett syndrome in adults and pediatric patients ≥2 years of age.
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
CYP3A4 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors): Trofinetide may increase serum concentration of CYP3A4 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor
OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors): Trofinetide may increase serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Management: Avoid concurrent use with OATP1B1/1B3 substrates for which small changes in exposure may be associated with serious toxicities. Monitor for evidence of an altered response to any OATP1B1/1B3 substrate if used together with trofinetide. Risk D: Consider Therapy Modification
Adverse events were not observed in animal reproduction studies; studies were conducted using doses lower than the maximum recommended human dose.
It is not known if trofinetide is present in breast milk.
According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother.
Hydration status (if diarrhea occurs); weight (if significant weight loss occurs).
Trofinetide is a synthetic analog of glycine-proline-glutamate, a naturally occurring peptide. The exact mechanism by which trofinetide exerts therapeutic effects is unknown; trofinetide may exhibit anti-inflammatory and trophic effects (Darwish 2022; Glaze 2019).
Distribution: Vd: ~80 L.
Protein binding: <6%.
Metabolism: Not significantly metabolized via CYP450 enzymes or other hepatic mechanisms of metabolism.
Half-life elimination: Children ≥5 years and Adolescents ≤15 years: Geometric mean range: 5.3 to 6.1 hours (Glaze 2019); Adults: 1.5 hours.
Time to peak: ~2 to 3 hours.
Excretion: Urine (~80% as unchanged drug); feces (minor excretion as unchanged drug).
Altered kidney function: In patients with moderate (eGFR 30 to 59 mL/minute) impairment, AUC increased by ~80% compared to patients with normal kidney function.
