Brand name: Aqneursa
Drug class: Other Miscellaneous Therapeutic Agents

Introduction

Modified amino acid.

Uses for Levacetylleucine

Niemann-Pick Disease

Treatment of neurological manifestations of Niemann-Pick type C disease (NPC) in adults and pediatric patients weighing ≥15 kg.

Clinical studies were conducted mainly in patients who were receiving concomitant miglustat.

Designated an orphan drug by FDA for treatment of NPC.

Management of NPC includes supportive therapy and disease modifying agents. A consensus guideline recommends that miglustat be considered in all patients with confirmed diagnosis of NPC (not an FDA-labeled use for miglustat in the US); levacetylleucine is not discussed as the guideline predates approval of the drug.

Levacetylleucine Dosage and Administration

General

Pretreatment Screening

• Verify pregnancy status in females of reproductive potential.

Administration

Oral Administration

Administer orally as a suspension, with or without food.

Available in individual unit-dose packets containing granules that must be reconstituted prior to administration. One packet contains 1 g levacetylleucine.

May administer by mouth or via gastrostomy tube (G-tube).

Oral Administration

Obtain required number of packets for prescribed dose (1 or 2 packets). Open and empty entire contents of 1 packet into container with 40 mL of water, orange juice, or almond milk; do not use hot liquid. Stir to form suspension.

Swallow suspension immediately (within 30 minutes); discard unused suspension if not used within 30 minutes.

For doses requiring 2 packets, repeat above steps.

Administration via Gastrostomy Tube

Prepare suspension immediately before administration.

Obtain required number of packets for prescribed dose (1 or 2 packets). Open and empty entire contents of 1 packet into container with 40 mL of water only; do not use hot liquid. Stir to form suspension.

Draw up suspension into catheter tip syringe; administer immediately through G-tube. Flush G-tube with additional 20 mL of water. Flush G-tube again as needed until no suspension is left in syringe or feeding tube.

For doses requiring 2 packets, repeat above steps.

Discard any unused suspension if not used immediately.

Dosage

Pediatric Patients

Niemann-Pick Disease

Oral

Pediatric patients ≥15 kg: Dosage based on actual body weight (kg); administered 2 or 3 times a day depending on weight (see Table 1).

If a dose is missed, skip missed dose and take next dose at scheduled time; do not take 2 doses at same time.

Adults

Niemann-Pick Disease

Oral

Dosage based on actual body weight (kg); administered 2 or 3 times a day depending on weight (see Table 1).

If a dose is missed, skip missed dose and take next dose at scheduled time; do not take 2 doses at same time.

Special Populations

Hepatic Impairment

No specific population dosage recommendations at this time.

Renal Impairment

No specific population dosage recommendations at this time.

Geriatric Patients

No specific population dosage recommendations at this time.

Cautions for Levacetylleucine

Contraindications

• None.

Warnings/Precautions

Fetal/Neonatal Morbidity and Mortality

May cause fetal harm.

Verify pregnancy status in females of reproductive potential prior to initiating therapy. Advise women of reproductive potential to use effective contraception during treatment and for 7 days after last dose if levacetylleucine is discontinued.

Specific Populations

Pregnancy

No data available on use during pregnancy. Based on animal studies, may cause embryo-fetal harm.

Decision to continue or discontinue during pregnancy should consider patient’s need for drug, potential drug-related risk to fetus, and potential adverse outcomes from untreated disease.

Lactation

Not known whether levacetylleucine is distributed into human milk, or if drug has any effects on the breastfed infant or milk production. Consider developmental and health benefits of breastfeeding along with mother’s clinical need for levacetylleucine and any potential adverse effects on the breastfed infant from drug or underlying maternal condition.

Females and Males of Reproductive Potential

Verify pregnancy status in females of reproductive potential prior to initiating therapy; advise patients to use effective contraception during treatment and for 7 days after last dose is discontinued.

Pediatric Use

Safety and efficacy established in pediatric patients weighing ≥15 kg.

Geriatric Use

No experience in geriatric population because Niemann-Pick type C disease (NPC) is largely a disease of pediatric and young adult patients.

Hepatic Impairment

Safety and efficacy not studied in hepatic impairment.

Renal Impairment

Safety and efficacy not studied in renal impairment.

Common Adverse Effects

Most common adverse reactions (≥5%): abdominal pain, dysphagia, upper respiratory tract infections, vomiting.

Drug Interactions

CYP enzymes not involved in metabolism.

Does not inhibit CYP1A2, 2B6, 2C8, 2C9, 2C19, 2D6, or 3A4 and does not induce CYP 1A2, 2B6, or 3A4.

Substrate of organic anion transporter (OAT)1 and OAT3; not substrate of organic cation transporter (OCT)2, breast cancer resistance protein (BCRP), or P-glycoprotein (P-gp).

Inhibits P-gp; however, the clinical significance of this not fully characterized. Also inhibits BCRP, bile salt export pump (BSEP), OAT1 and OAT3, but does not inhibit organic anion transporting polypeptide (OATP)1B1 and OATP1B3.

Drugs Affecting or Affected by Transport Systems

Monitor more frequently for adverse effects of P-gp substrates when used concomitantly with levacetylleucine.

Effect of Other Drugs on Levacetylleucine

Avoid concomitant use with N-acetyl-DL-leucine and N-acetyl-D-leucine. D-enantiomer, N-acetyl-D-leucine, competes with levacetylleucine for monocarboxylate transporter uptake, which may reduce efficacy of levacetylleucine.

Levacetylleucine Pharmacokinetics

Absorption

Plasma Concentrations

Time to peak plasma concentration 1 hour (range 0.5-2.5 hours).

Elimination

Metabolism

Metabolized into acetate and L-leucine by ubiquitously expressed enzymes.

Not metabolized by CYP enzymes.

Half-life

Approximately 1 hour.

Stability

Storage

Oral

Granules, for oral suspension

Store at room temperature (20–25°C).

Discard unused reconstituted suspension for oral administration if not used within 30 minutes.

Discard unused suspension for G tube administration if not administered immediately.

Actions

• Modified amino acid; slightly soluble in aqueous solution.

• Animal studies suggest potential mechanism related to reduction of stored intracellular lipids; however, molecular target and mechanism of action not known.

Advice to Patients

• Advise the patient and/or caregiver to read the FDA-approved patient labeling (Instructions for Use).

• Levacetylleucine may cause embryo-fetal harm. Advise patients of the potential risk to a fetus and instruct females of reproductive potential to use effective contraception during treatment and for 7 days after the last dose.

• Advise patients to inform their clinician if they are or plan to breast-feed.

• Advise patients to inform their clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.

• Inform patients of other important precautionary information.

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Levacetylleucine is available through the manufacturer. Contact the manufacturer or consult the levacetylleucine website ([Web]) for more information.

Reload page with references included

Medical Disclaimer