Daybue
(trofinetide)Dosage & Administration
| Patient Weight | DAYBUE Dosage | DAYBUE Volume |
|---|---|---|
| 9 kg to less than 12 kg | 5,000 mg twice daily | 25 mL twice daily |
| 12 kg to less than 20 kg | 6,000 mg twice daily | 30 mL twice daily |
| 20 kg to less than 35 kg | 8,000 mg twice daily | 40 mL twice daily |
| 35 kg to less than 50 kg | 10,000 mg twice daily | 50 mL twice daily |
| 50 kg or more | 12,000 mg twice daily | 60 mL twice daily |
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Daybue Prescribing Information
DAYBUE is indicated for the treatment of Rett syndrome in adults and pediatric patients 2 years of age and older.
Dosing Information
Administer DAYBUE orally twice daily, in the morning and evening, according to patient weight as shown in Table 1. DAYBUE can be taken with or without food.
| Patient Weight | DAYBUE Dosage | DAYBUE Volume |
|---|---|---|
| 9 kg to less than 12 kg | 5,000 mg twice daily | 25 mL twice daily |
| 12 kg to less than 20 kg | 6,000 mg twice daily | 30 mL twice daily |
| 20 kg to less than 35 kg | 8,000 mg twice daily | 40 mL twice daily |
| 35 kg to less than 50 kg | 10,000 mg twice daily | 50 mL twice daily |
| 50 kg or more | 12,000 mg twice daily | 60 mL twice daily |
Administration Information
Administer DAYBUE orally or via gastrostomy (G) tube; doses administered via gastrojejunal (GJ) tubes must be administered through the G-port.
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 is not an adequate measuring device.
Discard any unused DAYBUE oral solution after 14 days of first opening the bottle [see How Supplied/Storage and Handling (16.2)].
Dose Modification for Diarrhea or Weight Loss
Advise patients to stop laxatives before starting DAYBUE. Interrupt, reduce the dosage, or discontinue DAYBUE if severe diarrhea occurs, if dehydration is suspected, or if significant weight loss occurs [see Warnings and Precautions (5.1, 5.2)].
Dose Modification for Vomiting After Administration
If vomiting occurs after DAYBUE administration, an additional dose should not be taken. Instead, continue with the next scheduled dose. Interrupt, reduce dose, or discontinue DAYBUE if vomiting is severe or occurs despite medical management [see Warnings and Precautions (5.3)].
Dosage Recommendations in Patients With Renal Impairment
No dosage adjustment is recommended for patients with mild renal impairment (estimated glomerular filtration rate [eGFR] 60 to 89 mL/min for adult patients or 60 to 89 mL/min/1.73 m2 for pediatric patients). The recommended dosage of DAYBUE for patients with moderate renal impairment (eGFR 30 to 59 mL/min for adult patients or 30 to 59 mL/min/1.73 m2 for pediatric patients) is described in Table 2 [see Use in Specific Populations (8.6), Clinical Pharmacology (12.3)]. DAYBUE is 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 m2 for pediatric patients).
| Patient Weight | DAYBUE Dosage | DAYBUE Volume |
|---|---|---|
| 9 kg to less than 12 kg | 2,500 mg twice daily | 12.5 mL twice daily |
| 12 kg to less than 20 kg | 3,000 mg twice daily | 15 mL twice daily |
| 20 kg to less than 35 kg | 4,000 mg twice daily | 20 mL twice daily |
| 35 kg to less than 50 kg | 5,000 mg twice daily | 25 mL twice daily |
| 50 kg or more | 6,000 mg twice daily | 30 mL twice daily |
Missed Dose
If a dose of DAYBUE is missed, the next dose should be taken as scheduled. Doses should not be doubled.
Trofinetide oral solution: 200 mg/mL of a pink to red, strawberry flavored solution.
Pregnancy
Risk Summary
There are no adequate data on the developmental risks associated with the use of DAYBUE 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 [see Animal Data].
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 2 to 4% and 15 to 20%, respectively.
Data
Animal Data
Oral administration of trofinetide (0, 150, 450, or 1000 mg/kg twice daily; 0, 300, 900, or 2000 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 (0, 75, 150, or 300 mg/kg twice daily; 0, 150, 300, or 600 mg/kg/day) to pregnant rabbits 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 MRHD.
Oral administration of trofinetide (0, 150, 450, or 1000 mg/kg twice daily; 0, 300, 900, or 2000 mg/kg/day) to rats throughout pregnancy and lactation resulted in no adverse effects on pre- and postnatal development. At the highest dose tested, plasma exposure (AUC) was less than that in humans at the MRHD.
Lactation
Risk Summary
There is no information regarding the presence of trofinetide or its metabolites in human milk, the effects on the breastfed infant, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for DAYBUE and any potential adverse effects on the breastfed infant from DAYBUE or from the underlying maternal condition.
Pediatric Use
The safety and effectiveness of DAYBUE for the treatment of Rett syndrome have been established in pediatric patients aged 2 years and older. The safety and effectiveness of DAYBUE for the treatment of Rett syndrome in pediatric patients 5 years of age and older was established in a randomized, double-blind, placebo-controlled, 12-week study (Study 1), which included 108 pediatric patients age 5 to less than 12 years of age and 47 pediatric patients age 12 to less than 17 years of age [see Adverse Reactions (6.1) and Clinical Studies (14)]. Use of DAYBUE in patients 2 to 4 years of age is supported by evidence from Study 1 and pharmacokinetic and safety data in 13 pediatric patients 2 to 4 years of age treated with DAYBUE for 12 weeks [see Dosage and Administration (2.1), Adverse Reactions (6.1), Clinical Pharmacology (12.3), and Clinical Studies (14)].
Safety and effectiveness in pediatric patients less than 2 years of age have not been established.
Juvenile Animal Data
Oral administration of trofinetide (0, 150, 300, or 1000 mg/kg twice daily; 0, 300, 600, or 2000 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 (0, 150, 300, or 1000 mg/kg twice daily; 0, 300, 600, or 2000 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. Plasma exposures at the highest dose tested were similar to those in pediatric patients at recommended doses.
Geriatric Use
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. This drug is known to be substantially excreted by the kidney. Because elderly patients are more likely to have decreased renal function, it may be useful to monitor renal function.
Renal Impairment
Mild renal impairment is not expected to impact the exposure of trofinetide; therefore, dosage adjustment is not necessary. Dosage adjustment of DAYBUE is recommended in patients with moderate renal impairment (adult: eGFR 30 to 59 mL/min; pediatric: eGFR 30 to 59 mL/min/1.73 m2) [see Dosage and Administration (2.5), Clinical Pharmacology (12.3)]. Administration of DAYBUE to patients with severe renal impairment (eGFR less than 30 mL/min for adults or less than 30 mL/min/1.73 m2 for pediatrics) is not recommended.
None.
Diarrhea
In Study 1 [see Clinical Studies (14)] and in long-term studies, 85% of patients treated with DAYBUE experienced diarrhea. In those treated with DAYBUE, 49% either had persistent diarrhea or recurrence after resolution despite dose interruptions, reductions, or concomitant antidiarrheal therapy. Diarrhea severity was of mild or moderate severity in 96% of cases. In Study 1, antidiarrheal medication was used in 51% of patients treated with DAYBUE.
Advise patients to stop laxatives before starting DAYBUE. If diarrhea occurs, patients should notify their healthcare provider, consider starting antidiarrheal treatment, and monitor hydration status and increase oral fluids, if needed. Interrupt, reduce dose, or discontinue DAYBUE if severe diarrhea occurs or if dehydration is suspected [see Dosage and Administration (2.3)].
Weight Loss
In Study 1, 12% of patients treated with DAYBUE experienced weight loss of greater than 7% from baseline, compared to 4% of patients who received placebo. In long-term studies, 2.2% of patients discontinued treatment with DAYBUE due to weight loss.
Monitor weight and interrupt, reduce dose, or discontinue DAYBUE if significant weight loss occurs [see Dosage and Administration (2.3)].
Vomiting
In Study 1, vomiting occurred in 29% of patients treated with DAYBUE and in 12% of patients who received placebo [see Adverse Reactions (6.1)].
Patients with Rett syndrome are at risk for aspiration and aspiration pneumonia. Aspiration and aspiration pneumonia have been reported following vomiting in patients being treated with DAYBUE. Interrupt, reduce dose, or discontinue DAYBUE if vomiting is severe or occurs despite medical management [see Dosage and Administration (2.4)].