Daybue Drug Information

DAYBUE and DAYBUE STIX are indicated for the treatment of Rett syndrome in adults and pediatric patients 2 years of age and older.

Recommended Dosage

The recommended dosage of DAYBUE or DAYBUE STIX is based on patient weight as shown in Table 1. Administer DAYBUE or DAYBUE STIX orally or via gastrostomy (G) tube twice daily, in the morning and evening, with or without food. Doses administered via gastrojejunal (GJ) tubes must be administered through the G-port.

Table 1 Recommended Dosage of DAYBUE or DAYBUE STIX in Patients 2 Years of Age and Older

DAYBUE Oral Solution Preparation Table 2 includes the volume of DAYBUE oral solution to administer for the corresponding recommended dosage. A calibrated measuring device, such as an oral syringe or oral dosing cup, should be obtained from the pharmacy to measure and deliver the prescribed dose accurately. A household measuring cup, teaspoon, or tablespoon is not an adequate measuring device.

Table 2 Recommended Volume of DAYBUE Oral Solution for Administration Dosage DAYBUE Oral Solution Volume 2,500 mg twice daily Dosage for patients with moderate renal impairment Discard any unused DAYBUE oral solution after 14 days of first opening the bottle.

DAYBUE STIX for Oral Solution Preparation Prior to administration, DAYBUE STIX for oral solution powder must be dissolved in a cold to room temperature water or water-based beverage (juice, tea, lemonade, limeade, or liquid hydration). Preparation of DAYBUE STIX Determine the correct dosage as shown in Table 1 or Table 4 (for patients with moderate renal impairment). Select the appropriate packet strength and number of packets required for each dose, as shown in Table 3.

Determine the appropriate volume of liquid within the recommended volume range as shown in Table 3, based on individual patient factors (e.g., age, palatability). Measure the volume of liquid determined in Step 3 by using a calibrated measuring device obtained from the pharmacy. Empty the entire contents of the DAYBUE STIX packet(s) into the measured liquid.

Do not attempt to use partial packets to prepare a dose. Stir until the powder is completely dissolved. Administer the prepared oral solution immediately; do not store for future use.

Discard any prepared oral solution that is not immediately administered. Table 3 Preparation Instructions for DAYBUE STIX for Oral Solution Powder Modification for Diarrhea or Weight Loss Advise patients to stop laxatives before starting DAYBUE or DAYBUE STIX. Interrupt, reduce dose, or discontinue DAYBUE or DAYBUE STIX if severe diarrhea occurs, if dehydration is suspected, or if significant weight loss occurs.

Dose Modification for Vomiting After Administration

If vomiting occurs after DAYBUE or DAYBUE STIX administration, an additional dose should not be taken. Instead, continue with the next scheduled dose. Interrupt, reduce dose, or discontinue DAYBUE or DAYBUE STIX if vomiting is severe or occurs despite medical management.

Dosage Recommendations in Patients with Renal Impairment

No dosage adjustment is recommended for patients with mild renal impairment (estimated glomerular filtration rate 60 to 89 mL/min for adult patients or 60 to 89 mL/min/1.73 m 2 for pediatric patients). DAYBUE and DAYBUE STIX are not recommended for patients with severe renal impairment (eGFR less than 30 mL/min for adult patients or less than 30 mL/min/1.73 m 2 for pediatric patients). For patients with moderate renal impairment who require a dose less than 5,000 mg, DAYBUE oral solution is recommended.

Table 4 Recommended Dosage of DAYBUE or DAYBUE STIX in Patients with Moderate Renal Impairment If a dose of DAYBUE or DAYBUE STIX is missed, the next dose should be taken as scheduled. Doses should not be doubled.

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety of DAYBUE STIX has been established from an adequate, well-controlled study, and open-label studies of DAYBUE. Below is a display of the adverse reactions of DAYBUE in these studies.

Adult and Pediatric Patients with Rett Syndrome 5 Years of Age and Older The safety of DAYBUE was evaluated in a randomized, double-blind, placebo-controlled, 12-week study of patients with Rett syndrome (Study 1). In Study 1, 93 patients received DAYBUE and 94 patients received placebo. Adverse Reactions Leading to Discontinuation of Treatment Eighteen patients (19%) receiving DAYBUE had adverse reactions that led to withdrawal from the study.

The most common adverse reaction leading to discontinuation of treatment with DAYBUE was diarrhea (15%). Common Adverse Reactions Adverse reactions that occurred in Study 1 in at least 5% of patients treated with DAYBUE and were at least 2% more frequent than in patients on placebo are presented in Table 5. Adverse reactions in pediatric patients 2 to 4 years of age treated with DAYBUE were similar to those reported in adult and pediatric patients 5 years of age and older with Rett syndrome in Study 1.

Postmarketing Experience

The following adverse reactions have been identified during postapproval use of DAYBUE. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Aspiration and aspiration pneumonia secondary to vomiting.

Effect of DAYBUE and DAYBUE STIX on Other Drugs

CYP3A and/or P-gp Substrates Closely monitor patients when DAYBUE or DAYBUE STIX is administered concomitantly with sensitive CYP3A and/or P-gp substrates where minimal increases in the plasma concentration of these substrates may lead to serious adverse reactions. Trofinetide, a weak inhibitor of CYP3A and an inhibitor of P-gp, increased the plasma concentrations of CYP3A and/or P-gp substrates, which may increase the risk of adverse reactions associated with these substrates.

Pregnancy Risk Summary There are no adequate data on the developmental risks associated with the use of DAYBUE or DAYBUE STIX in pregnant women. No adverse developmental effects were observed following oral administration of trofinetide to pregnant animals at doses associated with plasma exposures below those used clinically. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown.

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is respectively. Data Animal Data Oral administration of trofinetide mg/kg twice daily; mg/kg/day to pregnant rats during the period of organogenesis resulted in no adverse effects on embryofetal development. At the highest dose tested, plasma exposure (AUC) was less than that in humans at the maximum recommended human dose (MRHD) of 12,000 mg twice daily (24,000 mg/day).

Oral administration of trofinetide mg/kg twice daily; mg/kg/day to rats throughout pregnancy and lactation resulted in no adverse effects on pre- and postnatal development.

Pediatric Use The safety and effectiveness of DAYBUE and DAYBUE STIX for the treatment of Rett syndrome have been established in pediatric patients aged 2 years and older. Safety and effectiveness in pediatric patients less than 2 years of age have not been established. Juvenile Animal Data Oral administration of trofinetide mg/kg twice daily; mg/kg/day to rats from postnatal day (PND) 13-14 through 28 weeks of age resulted in no adverse effects on growth or neurobehavioral function.

Plasma exposures at the highest dose tested were similar to those in pediatric patients at recommended doses. Oral administration of trofinetide mg/kg twice daily; mg/kg/day to juvenile rats for 10 weeks beginning on PND 13-14 resulted in no adverse effects on sexual maturation or reproductive function.