Overview
11 DESCRIPTION DAYBUE oral solution and DAYBUE STIX for oral solution contain the active moiety trofinetide. The chemical name of trofinetide is (2S)-2-{[(2S)-1-(2-aminoacetyl)-2-methylpyrrolidine-2-carbonyl]amino}pentanedioic acid (IUPAC). The molecular formula of trofinetide is C 13 H 21 N 3 O 6 and its molecular weight is 315.33 g/mol. The chemical structure is shown below.
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action The mechanism by which trofinetide exerts therapeutic effects in patients with Rett syndrome is unknown. 12.2 Pharmacodynamics Cardiac Electrophysiology At the maximum recommended dose in healthy adult subjects, trofinetide does not prolong the QT interval to any clinically relevant extent . 12.3 Pharmacokinetics DAYBUE STIX for oral solution demonstrated comparable bioavailability to DAYBUE oral solution in adult healthy subjects under fasted state. Trofinetide exhibits linear kinetics with no time- or dose-dependent effect on pharmacokinetic parameters. Systemic exposure to trofinetide was dose-proportional across the studied dose range. Minimal to no accumulation was observed following multiple-dose administration.
Indications
- 1 INDICATIONS AND USAGE DAYBUE and DAYBUE STIX are indicated for the treatment of Rett syndrome in adults and pediatric patients 2 years of age and older. DAYBUE and DAYBUE STIX are indicated for the treatment of Rett syndrome in adults and pediatric patients 2 years of age and older. ( 1 )
Common Doses
- 000 mg
- 500 mg
- 12.5 mL
- 15 mL
Dosage
2 DOSAGE AND ADMINISTRATION Recommended dosage is twice daily, morning and evening, according to patient weight. DAYBUE or DAYBUE STIX can be given with or without food. ( 2.1 ) Patient Weight Recommended Dosage 9 kg to less than 12 kg 5,000 mg twice daily 12 kg to less than 20 kg 6,000 mg twice daily 20 kg to less than 35 kg 8,000 mg twice daily 35 kg to less than 50 kg 10,000 mg twice daily 50 kg or more 12,000 mg twice daily Can be given orally or via gastrostomy (G) tube; doses administered via gastrojejunal (GJ) tubes must be administered through the G-port. ( 2.
Contraindications
- 4 CONTRAINDICATIONS None. None. ( 4 )
Side Effects
- 6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in labeling: Diarrhea [see Warnings and Precautions (5.1) ] Weight Loss [see Warnings and Precautions (5.2) ] Vomiting [see Warnings and Precautions (5.3) ] The most common adverse reactions (that occurred in at least 10% of DAYBUE-treated patients and at least 2% greater than in placebo) were diarrhea and vomiting. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Acadia Pharmaceuticals Inc. at 1-844-422-2342 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.
Interactions
- 7 DRUG INTERACTIONS Orally administered CYP3A and/or P-gp sensitive substrates for which a small change in substrate plasma concentration may lead to serious adverse reactions: closely monitor for adverse reactions with concomitant use. ( 7.1 ) 7.1 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.