Levacetylleucine

Levacetylleucine
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Parth Vikram Singh, MBBS[2]

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Overview

Levacetylleucine is {{{aOrAn}}} {{{drugClass}}} that is FDA approved for the treatment of AQNEURSA is FDA approved for the treatment of neurological manifestations of Niemann-Pick disease type C (NPC) in adults and pediatric patients weighing ≥15 kg.. Common adverse reactions include Most common adverse reactions (incidence ≥5% and greater than placebo) are abdominal pain, dysphagia, upper respiratory tract infections, and vomiting..

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

AQNEURSA is indicated for the treatment of neurological manifestations of Niemann-Pick disease type C (NPC) in adults.

• Important Recommendation Prior to AQNEURSA Treatment Initiation
  • For females of reproductive potential, verify that the patient is not pregnant.
• 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.
  • AQNEURSA can be taken with or without food. For 2 gram levacetylleucine doses, prepare two AQNEURSA packets individually.

    

    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.

• 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.

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Levacetylleucine in adult patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Levacetylleucine in adult patients.

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

There is limited information regarding Levacetylleucine FDA-Labeled Indications and Dosage (Pediatric) in the drug label.

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Levacetylleucine in pediatric patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Levacetylleucine in pediatric patients.

Contraindications

None.

Warnings

• 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.

Adverse Reactions

Clinical Trials Experience

• 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 AQNEURSA was evaluated in Trial 1, which included a total of 60 patients with Niemann-Pick disease Type C (NPC), in a placebo-controlled, randomized, crossover trial. The mean (SD) treatment duration of AQNEURSA was 86.2 (4.7) days (69 min, 97 max); the mean (SD) treatment duration on placebo was 87.3 (4.8) days (78 min, 113 max). TABLE 2

    

    summarizes adverse reactions that occurred in patients who were treated with AQNEURSA in Treatment Period I of Trial 1

• Rosacea
  • One patient experienced an exacerbation of rosacea during Trial 1 that responded to treatment. AQNEURSA was not discontinued.
• Laboratory Findings
  • Thrombocytopenia with platelets < 100 10^3 cells/µL was observed in four patients during Treatment Period 1, all of whom were receiving miglustat for 42 days or longer at the time of enrollment. In two of these patients, the thrombocytopenia was present at baseline. In the other two patients, the thrombocytopenia developed during the trial.

Postmarketing Experience

There is limited information regarding Levacetylleucine Postmarketing Experience in the drug label.

Drug Interactions

• Effect of Other Drugs on AQNEURSA
  • N-acetyl-DL-leucine and N-acetyl-D-leucine

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

• Effect of AQNEURSA on Other Drugs
  • P-glycoprotein (P-gp) Transporter Substrates

Monitor more frequently for P-gp substrate related adverse reactions when used concomitantly with AQNEURSA.**Levacetylleucine inhibits P-gp.However, the clinical significance of this finding has not been fully characterized.

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA):

• Risk Summary
  • Based on findings from animal reproduction studies, AQNEURSA may cause embryo-fetal harm when administered during pregnancy. In animal reproduction studies, an increase in embryo-fetal death (post implantation loss/resorption), decrease in fetal body weight, and increase in external and skeletal malformations were observed in rats and rabbits when levacetylleucine was administered in pregnant rats and rabbits during the period of organogenesis. These effects were observed in rats and rabbits at the doses that were approximately 1.4-fold and 6-fold, respectively, the maximum recommended human dose (MRHD) in patients taking 4 grams of AQNEURSA per day.
  • There are no available data on AQNEURSA use in pregnant females to evaluate a drug-associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes. Advise a pregnant female of the potential risk to the fetus. 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.
  • The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, miscarriage, or other adverse outcomes. 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
    • In a dose-range finding rat embryo-fetal development study, doses of up to 1000 mg/kg/day oral levacetylleucine were administered daily to pregnant females during organogenesis (Gestation Day [GD] 6 through GD 17). Increases in the mean number of resorptions, mean post-implantation losses and skeletal malformations (thoracic arch of the vertebra-fused thoracic arch, misaligned thoracic arch, hemicentric thoracic centrum, and misaligned thoracic centrum; vertebral column-scoliosis, and ribs-absent costal cartilage and short rib) were observed at a dose of 600 mg/kg/day, which is 1.4-fold the 4 g/day MRHD of levacetylleucine based on body surface area.
    • In a dose-range finding rabbit embryo-fetal development study, doses of up to 2500 mg/kg/day oral levacetylleucine were administered daily to pregnant females during organogenesis (GD 7 through GD 19). Increased embryo-fetal death (post-implantation loss/resorption), decreased fetal body weight, and increase in external (open or partially open eyes, hyperflexion of limbs) and skeletal malformations (misshapen maxillae and premaxillae, and small interparietal bones) were observed at the dose of 1250 mg/kg/day, which is 6-fold the MRHD of levacetylleucine based on body surface area.

Pregnancy Category (AUS): There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Levacetylleucine in women who are pregnant.

Labor and Delivery

There is no FDA guidance on use of Levacetylleucine during labor and delivery.

Nursing Mothers

• Risk Summary
  • There are no data on the presence of levacetylleucine or its metabolites in either human or animal 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 AQNEURSA and any potential adverse effects on the breastfed infant from levacetylleucine or from the underlying maternal condition.

Pediatric Use

The safety and effectiveness of AQNEURSA for the treatment of NPC have been established in 23 pediatric patients weighing ≥15 kg in Trial 1. Use of AQNEURSA for this indication is supported by evidence from one adequate and well-controlled study in adults and pediatric patients weighing ≥15 kg with additional pharmacokinetic data from 40 adults and 17 pediatric patients who participated in two open-label studies.The safety and effectiveness of AQNEURSA have not been established in pediatric patients weighing <15 kg.

Geriatic Use

NPC is largely a disease of pediatric and young adult patients. Clinical studies of AQNEURSA did not include sufficient numbers of patients 65 years of age and older to determine whether they respond differently from younger adult patients.

Gender

There is no FDA guidance on the use of Levacetylleucine with respect to specific gender populations.

Race

There is no FDA guidance on the use of Levacetylleucine with respect to specific racial populations.

Renal Impairment

There is no FDA guidance on the use of Levacetylleucine in patients with renal impairment.

Hepatic Impairment

There is no FDA guidance on the use of Levacetylleucine in patients with hepatic impairment.

Females of Reproductive Potential and Males

• AQNEURSA may cause embryo-fetal harm when administered to a pregnant female.
  • Pregnancy Testing

For a female of reproductive potential, verify that the patient is not pregnant prior to initiating treatment with AQNEURSA.

• • Contraception
    • Females

Advise a female of reproductive potential to use effective contraception during treatment and for 7 days after the last dose if AQNEURSA is discontinued.

Immunocompromised Patients

There is no FDA guidance one the use of Levacetylleucine in patients who are immunocompromised.

Administration and Monitoring

Administration

There is limited information regarding Levacetylleucine Administration in the drug label.

Monitoring

There is limited information regarding Levacetylleucine Monitoring in the drug label.

IV Compatibility

There is limited information regarding the compatibility of Levacetylleucine and IV administrations.

Overdosage

There is limited information regarding Levacetylleucine overdosage. If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.

Pharmacology

There is limited information regarding Levacetylleucine Pharmacology in the drug label.

Mechanism of Action

There is limited information regarding Levacetylleucine Mechanism of Action in the drug label.

Structure

AQNEURSA ( levacetylleucine ) for oral suspension contains the drug substance levacetylleucine, a modified amino acid. Levacetylleucine is slightly soluble in aqueous solutions. The chemical name is 2-acetamido-4-methylpentanoic acid. The empirical formula is C8H15NO3 and the molecular weight is 173.21. The chemical structure is

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Each packet of AQNEURSA granules contains 1 gram levacetylleucine and the inactive ingredients hypromellose, isomalt and strawberry flavor.

Pharmacodynamics

There is limited information regarding Levacetylleucine Pharmacodynamics in the drug label.

Pharmacokinetics

There is limited information regarding Levacetylleucine Pharmacokinetics in the drug label.

Nonclinical Toxicology

There is limited information regarding Levacetylleucine Nonclinical Toxicology in the drug label.

Clinical Studies

There is limited information regarding Levacetylleucine Clinical Studies in the drug label.

How Supplied

There is limited information regarding Levacetylleucine How Supplied in the drug label.

Storage

There is limited information regarding Levacetylleucine Storage in the drug label.

Images

Drug Images

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Package and Label Display Panel

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Patient Counseling Information

There is limited information regarding Levacetylleucine Patient Counseling Information in the drug label.

Precautions with Alcohol

Alcohol-Levacetylleucine interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

Brand Names

There is limited information regarding Levacetylleucine Brand Names in the drug label.

Look-Alike Drug Names

There is limited information regarding Levacetylleucine Look-Alike Drug Names in the drug label.

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.