AQNEURSA Granules for oral suspension Ref.[116287] Active ingredients: Levacetylleucine

Anaphylaxis and hypersensitivity reactions

Although no patient experienced anaphylactic or hypersensitivity reaction during the clinical studies, anaphylactic and hypersensitivity reactions may occur after administration of levacetylleucine. Immediate discontinuation of Aqneursa and necessary emergency treatment is required if such reactions occur.

Excipients

Each sachet contains 642.2 mg isomalt. Patients with rare hereditary problems of fructose intolerance should not take this medicinal product.

This medicinal product contains 0.153 mg propylene glycol in each sachet.

No interaction studies have been performed.

Interactions with levacetylleucine

An interaction of levacetylleucine (N-acetyl-L-leucine) with N-acetyl-DL-leucine and N-acetyl-D-leucine has been identified in pharmacology studies indicating that N-acetyl-D-leucine may compete with levacetylleucine for uptake by the monocarboxylate transporters. Concomitant use of levacetylleucine with N-acetyl-DL-leucine and N-acetyl-D-leucine should be avoided.

Interactions with substrates of transporters P-gp, BCRP or BSEP

Levacetylleucine may be an inhibitor of P-glycoprotein (P-gp), breast cancer resistance protein (BCRP) or bile salt export pump (BSEP) (see section 5.2). The relevance to humans is uncertain. A potential interaction of levacetylleucine with other medicinal products that are substrates of P-gp (e.g. digoxin, dabigatran, loperamide, irinotecan, doxorubicin, vinblastine, paclitaxel, fexofenadine, seliciclib, quinidine, talinolol), BCRP (e.g. sulfasalazine, rosuvastatin) or BSEP cannot be excluded.

Caution should be exercised when levacetylleucine is co-administered with BSEP substrates.

The potential inhibitory effect of levacetylleucine on multidrug and toxin extrusion proteins (MATE) transporters is unknown; therefore, caution is advised when co-administering levacetylleucine with substrates of MATE transporters.

Pregnancy

There are no data on the use of levacetylleucine in pregnant women. Studies in animals have shown reproductive toxicity (see section 5.3).

Aqneursa is not recommended during pregnancy and in women of childbearing potential not using contraception.

Breast-feeding

It is unknown whether levacetylleucine or metabolites of levacetylleucine are excreted in human milk. A risk to the newborns and infants cannot be excluded.

A decision must be made as to whether to discontinue breast-feeding or to discontinue/abstain from Aqneursa therapy, taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.

Fertility

No human data on the effect of levacetylleucine on fertility is available. Animal studies indicate no effects of levacetylleucine on male or female fertility (see section 5.3).

Aqneursa has no or negligible influence on the ability to drive and use machines.

Summary of safety profile

The most common adverse reaction, with a frequency of 1.2%, is flatulence.

Tabulated list of adverse reactions

Adverse reactions observed during the placebo-controlled, randomised, crossover clinical study and the open-label, rater-blinded study, including extension phase, in patients with NPC are based on a total of 84 patients with a median treatment duration of 86 days. Within the system organ classes, adverse reactions are listed according to the following frequency categories: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1 000 to <1/100), rare (≥1/10 000 to <1/1 000), very rare (<1/10 000), not known (cannot be estimated from the available data).

Table 2. Adverse reactions in patients with Niemann-Pick Type C treated with levacetylleucine:

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.

Not applicable.