Buy Daridorexant ( Quviviq) Cas 1505484-82-1.

Daridorexant, sold under the brand name Quviviq, is an orexin antagonist medication which is used for the treatment of insomnia.^{[1][5][7][8][9]} Daridorexant is taken by mouth.^[1][5][8]

Side effects of daridorexant include headache, somnolence, and fatigue.^[1][8] The medication is a dual orexin receptor antagonist (DORA).^{[10][8][11][9]} It acts as a selective dual antagonist of the orexin receptors OX₁ and OX₂.^[10][11][9] Compared to other marketed OX antagonists, daridorexant has a relatively short elimination half-life of 8 hours and a time to peak of about 1 to 2 hours.^[1][8][6] It is not a benzodiazepine or Z-drug and does not interact with GABA receptors, instead having a distinct mechanism of action.^[9][8]

Daridorexant was approved for medical use in the United States in January 2022^[1][12] and became available in May 2022.^[13] It was approved in the European Union in April 2022, and is the first orexin receptor antagonist to become available in European Union.^[14] The medication is a schedule IV controlled substance in the United States and may have a modest potential for misuse.^[1][15][16] Besides daridorexant, other orexin receptor antagonists, like suvorexant and lemborexant, have also been introduced.^[17][18]

Daridorexant is indicated for the treatment of adults with insomnia characterized by difficulties with sleep onset and/or sleep maintenance.^[1] The medication has been found to significantly improve latency to persistent sleep (LPS), wake after sleep onset (WASO), and subjective total sleep time (TST) in regulatory clinical trials.^[1] At doses of 25 to 50 mg and in terms of treatment–placebo difference, it reduces LPS by 6 to 12 minutes, reduces WASO by 10 to 23 minutes, and increases subjective TST by 10 to 22 minutes.^[1][19] Daridorexant has also been found to improve daytime functioning at a dose of 50 mg but not at 25 mg.^[18]

Network meta-analyses have assessed the sleep-promoting effects of orexin receptor antagonists and have compared them between one another as well as to other sleep aids including benzodiazepines, Z-drugs, antihistamines, sedative antidepressants (e.g., trazodone, doxepin, amitriptyline, mirtazapine), and melatonin receptor agonists.^{[20][21][22][23]} A major systematic review and network meta-analysis of insomnia medications published in 2022 found that daridorexant had an effect size (standardized mean difference (SMD)) against placebo for treatment of insomnia at 4 weeks of 0.23 (95% CITooltip confidence interval –0.01 to 0.48).^[20] This was similar to but numerically lower than the effect sizes at 4 weeks for suvorexant (SMD 0.31, 95% CI 0.01 to 0.62) and lemborexant (SMD 0.36, 95% CI 0.08 to 0.63).^[20] Benzodiazepines and Z-drugs generally showed larger effect sizes than orexin receptor antagonists (e.g., SMDs of 0.45 to 0.83).^[20] The review concluded on the basis of daridorexant’s small effect size that it did not show an overall material benefit in the treatment of insomnia.^[20] Conversely, it concluded that lemborexant—as well as the Z-drug eszopiclone—had the best profiles overall in terms of efficacy, tolerability, and acceptability among all of the assessed insomnia medications.^[20]

Orexin receptor antagonists are not used as first-line treatments for insomnia due to their costs and concerns about possible misuse liability.^[21]

Population pharmacokinetic modeling indicates that differences between subjects do not require dose adjustments, and that lean body weight and fat mass effect the pharmacokinetics of daridorexant better than other body size descriptors.^[24]

Treatment with daridorexant is generally safe and well tolerated for up to one year, with improvements in sleep and daytime functioning persisting throughout treatment.^[25]

The Department of Defense (DOD) is testing the effectiveness of daridorexant in patients with post-traumatic stress disorder (PTSD) as the link between insomnia and PTSD is well established.^[26]

In the United States and Canada, daridorexant is available in the form of 25 and 50 mg oral tablets.^[1] It is provided as the salt daridorexant hydrochloride, with each tablet containing 27 or 54 mg of this substance (equivalent to 25 or 50 mg daridorexant).^[1]

Daridorexant is contraindicated in people with narcolepsy.^[1] It is not recommended in people with severe hepatic impairment, whereas a lower maximum dose is recommended in people with moderate hepatic impairment.^[1] Concomitant use of daridorexant with strong CYP3A4 inhibitors and moderate to strong CYP3A4 inducers is not recommended and should be avoided due to unfavorable modification of daridorexant exposure.^[1]

Side effects of daridorexant include headache (6% at 25 mg vs. 7% at 50 mg vs. 5% for placebo), somnolence or fatigue (includes somnolence, sedation, fatigue, hypersomnia, and lethargy) (6% at 25 mg vs. 5% at 50 mg vs. 4% for placebo), dizziness (2% at 25 mg vs. 3% at 50 mg vs. 2% for placebo), and nausea (0% at 25 mg vs. 3% at 50 mg vs. 2% for placebo).^[1] No residual effects have been found after administration of 25 mg daridorexant in the evening to either young or elderly individuals.^[6] However, daridorexant may cause next-morning driving impairment at the start of treatment or in some individuals.^[1] Orexin receptor antagonists like daridorexant may have less or no propensity for causing tolerance compared to other sedatives and hypnotics based on animal studies.^[9][1] Daridorexant did not produce signs of withdrawal or dependence upon discontinuation in animal studies and clinical trials, and orexin receptor antagonists are not associated with rebound insomnia.^[1][6] Loss of sleep-promoting effectiveness occurs rapidly upon discontinuation of daridorexant.^[1] Preclinical research has suggested that orexin antagonists may reduce appetite, but daridorexant and other orexin antagonists have not been associated with weight loss in clinical trials.^[17] Daridorexant may have a small risk of suicidal ideation.^[27]

Orexin receptor antagonists can affect the reward system and produce drug-liking responses in humans.^[28][17] Daridorexant at a dose of 50 mg (the maximum recommended dose) showed significantly greater drug liking than placebo but significantly less drug liking than zolpidem (30 mg) and suvorexant (150 mg) in recreational sedative drug users.^[1][29] At higher doses of 100 and 150 mg (greater than the recommended maximum dose), drug liking with daridorexant was similar to that with zolpidem (30 mg) and suvorexant (150 mg).^[1][29] In other studies, suvorexant showed similar drug liking compared to zolpidem but lower misuse potential on other measures (e.g., overall rate of misuse potential adverse events of 58% for zolpidem and 31% for suvorexant in recreational drug users).^[30] No reports indicative of misuse liability were observed in clinical trials with daridorexant, although these studies excluded participants with history of drug or alcohol misuse.^[1][31][29]

There is limited clinical experience with overdose of daridorexant.^[1] Overdose of the medication at a dose of up to four times the maximum recommended dose may result in adverse effects including somnolence, muscle weakness, cataplexy-like symptoms, sleep paralysis, attention disturbances, fatigue, headache, and constipation.^[1] There is no specific antidote to overdose of daridorexant.^[1]