levacetylleucine 1000 MG Granules for Oral Suspension

INDICATIONS AND USAGE AQNEURSA™ is indicated for the treatment of neurological manifestations of Niemann-Pick disease type C (NPC) in adults and pediatric patients weighing ≥15 kg. AQNEURSA is indicated for the treatment of neurological manifestations of Niemann-Pick disease type C (NPC) in adults and pediatric patients weighing ≥15 kg. ( 1 )

DOSAGE AND ADMINISTRATION • For females of reproductive potential, verify that the patient is not pregnant prior to initiating treatment. ( 2.1 ) • Recommended dosage ( 2.2 ) Patient Body Weight Morning Dose Afternoon Dose Evening Dose 15 to <25 kg 1 g No Dose 1 g 25 to <35 kg 1 g 1 g 1 g 35 kg or more 2 g 1 g 1 g • See the full prescribing information for administration instructions. ( 2.3 ) 2.1 Important Recommendation Prior to AQNEURSA Treatment Initiation For females of reproductive potential, verify that the patient is not pregnant [see Use in Specific Populations ( 8.1 , 8.3 )]. 2.2 Recommended Dosage The recommended dosage of AQNEURSA is based on the patient’s actual body weight (kg) to be administered orally up to three times daily. See Table 1 . AQNEURSA can be taken with or without food [see Clinical Studies ( 14 )] . For 2 gram levacetylleucine doses, prepare two AQNEURSA packets individually [see Dosage and Administration ( 2.3 )] . Table 1 Recommended Dosage of Levacetylleucine Based on Body Weight (kg) Patient’s Body Weight Morning Dose Afternoon Dose Evening Dose 15 kg to less than 25 kg 1 gram No Dose 1 gram 25 kg to less than 35 kg 1 gram 1 gram 1 gram 35 kg or more 2 gram 1 gram 1 gram One AQNEURSA packet contains 1 gram levacetylleucine. Missed Dose If a dose of AQNEURSA is missed, skip the missed dose and take the next dose at the scheduled time. Do not take 2 doses at the same time to make up for a missed dose. 2.3 Preparation and Administration Instructions Oral Administration For oral administration, administer AQNEURSA as follows: 1. Obtain the required number of AQNEURSA packets for the prescribed dose (one or two packets). 2. Open and empty the entire contents of one AQNEURSA packet into a container with 40 mL of water, orange juice, or almond milk. Do not use hot liquid. 3. Stir to form a suspension. 4. Swallow the suspension immediately (within 30 minutes). 5. For doses requiring two AQNEURSA packets, repeat steps 2 to 4. 6. Discard unused AQNEURSA suspension if not administered within 30 minutes. Use of Gastrostomy Tube (G-Tube) for Feeding Tube Administration For patients who have a G-tube (French size 18 or larger) in place, administer AQNEURSA as follows: 1. Prepare AQNEURSA suspension immediately before administration via gastrostomy tube. 2. Obtain the required number of AQNEURSA packets for the prescribed dose (one or two packets). 3. Open and empty the entire contents of one AQNEURSA packet into a container with 40 mL of water ONLY. Do not use hot liquid. 4. Stir to form a suspension. 5. Draw up the suspension into a catheter tip syringe. 6. Administer the suspension immediately through the G-tube. 7. Flush any residual suspension in the catheter tip syringe with an additional 20 mL of water. 8. Flush the G-tube again, as needed, until no residual suspension is left in the syringe or feeding tube. 9. For doses requiring two AQNEURSA packets, repeat steps 3 to 8. 10. Discard unused AQNEURSA suspension if not administered immediately.

WARNINGS AND PRECAUTIONS Embryo-Fetal Toxicity : May cause fetal harm. Advise females of reproductive potential to use effective contraception during treatment and for 7 days after the last dose if AQNEURSA is discontinued. ( 5.1 ) 5.1 Embryo-Fetal Toxicity Based on findings from animal reproduction studies, AQNEURSA may cause embryo-fetal harm when administered during pregnancy. Administration of levacetylleucine to pregnant rats and rabbits during the period of organogenesis caused an increase in embryo-fetal death (post implantation loss/resorption) and skeletal malformations at a dose that was approximately 1.4-fold and 6-fold, respectively, the maximum recommended human dose (MRHD) of 4 g/day of levacetylleucine (based on body surface area). The decision to continue or discontinue AQNEURSA treatment during pregnancy should consider the female’s need for AQNEURSA, the potential drug-related risks to the fetus, and the potential adverse outcomes from untreated maternal disease. For females of reproductive potential, verify that the patient is not pregnant prior to initiating treatment with AQNEURSA. Advise females of reproductive potential to use effective contraception during treatment with AQNEURSA and for 7 days after the last dose if AQNEURSA is discontinued [see Use in Specific Populations ( 8.1 , 8.3 )].

CONTRAINDICATIONS None. None. ( 4 )

Mechanism of Action The distinct molecular target for levacetylleucine in the treatment of NPC is unknown.