Trofinetide
{{DrugProjectFormSinglePage |authorTag=Alen Antony Pathil, M.D.[1] |genericName=trofinetide |aOrAn=a |drugClass=drug |indicationType=treatment |indication=Rett syndrome in adults and pediatric patients of age 2 years and older |adverseReactions=diarrhea and vomiting. |fdaLIADAdult=DAYBUE (trofinetide) is used for the treatment of Rett syndrome in adults and pediatric patients 2 years of age and older.
DAYBUE is administered orally or via gastrostomy tube twice daily, in the morning and evening, according to patient weight and can be taken with or without food.
- 9-12 kg - 5000 mg twice daily (25ml twice daily)
- 12-20 kg - 6000 mg twice daily (30ml twice daily)
- 20-35 kg - 8000 mg twice daily (40ml twice daily)
- 35-50 kg - 10000 mg twice daily (50ml twice daily)
- 50 kg or more - 12,000 mg twice daily (60 mL twice daily)
If a dose of DAYBUE is missed, the next dose should be taken as scheduled and doses should not be doubled.
An additional dose should not be taken if vomiting occurs after DAYBUE administration and instead, continue with the next scheduled dose.
Patients are advised to discontinue laxatives prior to starting DAYBUE. The DAYBUE dosage is interrupted or reduced if patients develops severe diarrhea, dehydration or significant weight loss. |contraindications=none |warnings=1. Diarrhea In a clinical study, it was observed 85% of patients treated with DAYBUE experienced diarrhea and in those, 49% either had persistent diarrhea or recurrence after resolution despite dose interruptions, reductions, or concomitant antidiarrheal therapy.
Patients are advised to discontinue any laxatives prior to starting DAYBUE. Healthcare providers are informed and appropriate management with antidiarrheal agents and fluids are initiated if the patients develop diarrhea during the DAYBUE treatment course. Interrupt, reduce dose, or discontinue DAYBUE, if severe diarrhea occurs or if dehydration is suspected.
2. Weight loss In a clinical study, 12% of patients on DAYBUE developed weight loss greater than 7% from the baseline compared to the 4% of the placebo.
Patients are advised to monitor their weight during the treatment course and interrupt, reduce dose, or discontinue DAYBUE if significant weight loss occurs. |clinicalTrials=A randomized, double-blind, placebo-controlled, 12-week study of patients with Rett syndrome was performed to evaluate the safety of the drug. The study consisted of 93 patients receiving DAYBUE and other 94 patients receiving placebo, among which all were female with 92% white and age ranging from 5to 20 years.
The results showed at least 5% of patients treated with DAYBUE had adverse effects and was 2% more frequent than the patients treated with placebo. Among which the most common adverse effects were diarrhea (82%) and vomiting (29%). Others were Fever (9%), Seizure (9%), anxiety (8%), decreased appetite (8%), fatigue (8%), and nasopharyngitis (5%). |drugInteractions=Trofinetide is a weak CYP3A4 inhibitor; therefore, plasma concentrations of CYP3A4 substrates may be increased if given concomitantly with DAYBUE. Hence, patients are closely monitored when DAYBUE is used along with orally administered CYP3A4 sensitive substrates. |FDAPregCat=B |useInPregnancyFDA=No adverse developmental effects were observed following oral administration of trofinetide to pregnant animals at doses associated with plasma exposures below those used clinically.
No sufficient data is available regarding the developmental risk associated with the DAYBUE usage in pregnant women. |useInNursing=There is no data regarding the presence of trofinetide or its metabolites in human milk, the effects on the breastfed infant, or the effects on milk production. |useInPed=The safety and effectiveness of DAYBUE for the treatment of Rett syndrome have been established in pediatric patients aged 2 years and older. |useInGeri=Clinical studies of DAYBUE did not include patients 65 years of age and older to determine whether or not they respond differently from younger patients. |administration=DAYBUE is administered orally or via gastrostomy tube as a solution, and tge recommended dosage is determined as per the weight of the body.
DAYBUE is administered twice daily, in the morning and evening, according to patient weight and can be taken with or without food. |monitoring=Monitor the patient for diarrhea, vomiting, dehydration or significat weight loss during the treatment course with DAYBUE.
The DAYBUE dosage is interrupted, reduced or discontinued if they develop severe diarrhea, dehydration or significant weight loss. |mechAction=The exact mechanism of action through which DAYBUE produced its therapeutic effects on Rett syndrome is unknown. |structure=Trofinetide is designated chemically as (2S)-2-{[(2S)-1-(2-aminoacetyl)-2-methylpyrrolidine-2-carbonyl]amino}pentanedioic acid (IUPAC). Its empirical formula is C13H21N3O6 and its molecular weight is 315.33 g/mol. |PK=*The time to attain maximum drug concentration (Tmax) is about 2 to 3 hours after administration. Coadministration of DAYBUE with a high-fat meal had no impact on the total exposure (AUC0-inf) of trofinetide and reduced the peak plasma concentration (Cmax) by approximately 20%.
- Following oral administration, the apparent volume of distribution of trofinetide in healthy adult subjects was approximately 80 L and the protein binding in human plasma is less than 6%.
- The effective elimination half-life of orally administered trofinetide in healthy subjects is about 1.5 hours.
- Trofinetide is not significantly metabolized by CYP450 enzymes.
- Trofinetide is primarily excreted unchanged (approximately 80% of the dose) in urine, with minor excretion in feces.
|howSupplied=Trofinetide (DAYBUE) is available as an oral solution 200 mg/mL of a pink to red, strawberry flavored solution.
It is upplied in a nominal 500 mL round high-density polyethylene (HDPE) multi-dose bottle with a child-resistant closure containing 450 mL of oral solution |storage=Store DAYBUE in an upright position refrigerated at 2°C to 8°C (36°F to 46°F)and do not freeze.
Discard any unused DAYBUE oral solution after 14 days of first opening the bottle. |brandNames=DAYBUE }}