Is there resistance to the sleeping pill Leborex?

drug resistance

There is currently no information on whether leborexan is resistant, so it is not clear whether there is resistance to the sleeping drug leborexan.

Since Leborexen can cause serious side effects such as respiratory depression, drowsiness, depression, suicidal tendencies, etc. during medication, patients should strictly follow the doctor's instructions and are not allowed to take medication or stop medication without permission.

Resistance post-treatment methods

Leborexan is an oral dual orexin receptor (OXR) antagonist. If the drug effect decreases or even disappears during the patient's treatment with leborexan, drug resistance may occur. The patient can switch to other orexin receptor antagonists under the guidance of a doctor, such as Amorent, Suvorexan, etc.

Orexin receptor antagonists, especially dual orexin receptor antagonists (DORAs), have good sedative-hypnotic effects and have been the focus of the research and development of new sedative-hypnotic drugs in the past decade. The more classic DORAs include amorent, suvorexan, leborexan, dalidorexan, etc. Most DORAs drugs are based on the U-shaped molecular skeleton and modify the modules on the skeleton. The core goal of structural modification is to improve the antagonistic activity. In addition, it also includes reducing lipophilicity, reducing time-dependent inhibition of enzymes, reducing drug efflux ratio, increasing brain concentration and reducing susceptibility to P-glycoprotein.

Tolerance

One study characterized lemborexant in adults with insomnia in terms of number needed to treat (NNT), number needed to harm (NNH), and likelihood of helping or harming (LHH) (DSM-5). Lemborexant data come from two Phase 3 trials conducted from 2016 to 2018, using different response classification definitions to assess efficacy and adverse event (ae) rates to assess tolerability.

Direct comparisons were made with zolpidem extended-release (ER) tablets and indirect comparisons with other hypnotic drugs, including suvorexant, doxpin, ramelteon, zolpidem immediate release, eszopiclone, zaleplon, and selected benzodiazepines, using data from published reports and regulatory filings.

Lemborexant had a clinically relevant treatment effect, with an NNT of 3 (95% CI, 2-3) compared with placebo. Generally speaking, NNH values ​​of lemborexant and placebo are ≥10, indicating that lemborexant is relatively tolerable.

Drowsiness was the most common adverse event, with NNH estimates of 28 (95% CI, 18-61) and 15 (95% CI, 11-22) for 5 mg and 10 mg, respectively. The rate of discontinuation of lemborexant due to AEs was low and was lower with lemborexant 5 mg than with placebo.

The above data suggest that the benefit-risk ratio of lemborexant, as measured by NNT, NNH, and LHH, is favorable in the Phase 3 trial.

References

Scott LJ. Lemborexant: First Approval. Drugs. 2020 Mar;80(4):425-432. doi: 10.1007/s40265-020-01276-1. PMID: 32096020.