Impact of a US Food and Drug Administration Drug Safety Communication on Zolpidem Dosing

Harward, J.; Clinard, Valerie B.; Jiroutek, Michael R.; Lingerfeldt, B.; Muzyk, Andrew J.

doi:10.4088/pcc.14m01728

Cited by 9 publications

(8 citation statements)

References 4 publications

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“…The resulting mixture was placed in a freezer (at −14 • C) overnight, and the next day, 3 mL of diethyl ether was added, and the precipitate was washed with a small amount of diethyl ether (2 mL) to give I with 73% of yield (90 mg). The spectral data matched those previously reported [36]; white solid, mp 195-197 • C; 1 Sample preparation for microscope imagining: 1mg of zolpidem tartrate I was placed on a microscope plate, dissolved in a drop of methanol and evaporated directly on the microscope plate. The images were taken immediately after the solvent was evaporated using polarized light microscope Hund Wetzlar type H600/12 (Helmut Hund GmbH, Wetzlar, Germany).…”

Section: General Methodssupporting

confidence: 79%

“…Zolpidem 1 is one of the most widely prescribed hypnotic medications in the United States, with an annual prescription rate of nearly 39 million [1,2]. It was developed in the late 1980s [3] and 1990s as a subtle alternative to benzodiazepines, which could rapidly promote sleep, while retaining the negligible risk of impaired daily functioning [4].…”

Section: Introductionmentioning

confidence: 99%

“…The mixture was irradiated at 110 • C for 40 min in CEM-Discover system, operating at a frequency of 2.445 GHz, with continuous irradiation power from 0 to 200 W. After that time, the reaction mixture was extracted with EtOAc, dried over Na 2 SO 4 and concentrated under reduced pressure. Purification by column chromatography using (Hex:EtOAc 7:3) as eluent, gave 4 (585 mg, 90%) as a light yellow powder mp 200.8-203.7 • C, Rf = 0.31 (Hex:EtOAc 7:3);1 H NMR (500 MHz, CDCl 3 ) δ = 7.89 (s, 1 H), 7.85-7.82 (m, 2 H), 7.74 (s, 1 H), 7.54 (d, J = 9.2 Hz, 1 H), 7.24 (d, J = 8.0 Hz, 2 H), 7.01 (dd, J = 1.7, 9.2 Hz, 1 H), 2.39 (s, 3 H), 2.31 (d, J = 1.1 Hz, 3 H); 13 C NMR (126MHz, CDCl 3 ) δ = 145.6, 144.7, 137.7, 131.0, 129.5, 127.9, 125.9, 123.4, 122.1, 116.8, 107.6, 21.4, 18.2; EI MS m/z: 223.0 [M + H + ]. Alternatively, the reaction performed using 5 mL of toluene afforded the product 4 with 71% yield.2-(4-fluorophenyl)-6-methylimidazo[1,2-a]pyridine(5).…”

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confidence: 99%

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Study on a Three-Step Rapid Assembly of Zolpidem and Its Fluorinated Analogues Employing Microwave-Assisted Chemistry

et al. 2020

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We developed an efficient microwave-assisted three-step synthesis of zolpidem and its fluorinated analogues 1–3. The procedure relays on the utilization of easily accessible and inexpensive starting materials. Our protocol shows superior performance in terms of yield and purity of products, compared to conventional heating systems. Notably, the total time needed for reaction accomplishment is significantly lower comparing to oil bath heating systems. Finally, we have performed a detailed study on the preparation of zolpidem tartrate salt I, and we assessed its particle-sizes using a polarizing microscope. Our goal was to select the appropriate method that generates the acceptable particle-size, since the solid-size directly influences solubility in biological fluids and further bioavailability. We believe that the disclosed procedure will help to produce a lab-scale quantity of zolpidem and its fluorinated derivatives 1–3, as well as zolpidem tartrate salt I, with suitable fine-particle size for further biological experimentation.

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Section: General Methodssupporting

confidence: 79%

Section: Introductionmentioning

confidence: 99%

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confidence: 99%

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Study on a Three-Step Rapid Assembly of Zolpidem and Its Fluorinated Analogues Employing Microwave-Assisted Chemistry

et al. 2020

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“…We are aware that patients treated with benzodiazepine receptor agonists could be treated with benzodiazepines, and believe our findings with benzodiazepine hypnotics also apply to benzodiazepine receptor agonists registered as hypnotics such as zolpidem. The SAMHSA reported that the visits to emergency departments due to overmedication with zolpidem doubled from 2005-2006 to 2009-2010 in the USA [46] , leading to a warning from the US Food and Drug Administration to decrease the recommended dose by 50% in women [52] .…”

Section: Discussionmentioning

confidence: 99%

Hypnotics and Triazolobenzodiazepines - Best Predictors of High-Dose Benzodiazepine Use: Results from the Luxembourg National Health Insurance Registry

Cloos¹,

Bocquet

Rolland-Portal³

et al. 2015

Psychother Psychosom

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Background: Benzodiazepines are not all the same concerning their risk of high-dose use. Methods: We studied benzodiazepine use from the Luxembourg national records of all insured. We calculated the 12-year prevalence from 1995 to 2007. Benzodiazepine users were divided into 3 groups, short-term with no longer than 3-month intake, intermediate with multiple administration with at least a 1-year interruption, and continuous who never stopped. A high-dose user (HDU) was defined as a patient who received a higher dose than the yearly maximum usual therapeutic dose. Results: An average of 16.0% of the adult insured population received at least 1 benzodiazepine annually, 42.9% were older than 50, 55.9% were women, and 5.4% were HDUs. We found that 32.6% were short-term users, 49.0% intermediate and 18.4% continuous. Compared to diazepam, hypnotics had higher risks for high-dose use in at least 1 age group at first-benzodiazepine intake, the risks being greater in elderly subjects and women, the highest risks being with triazolam (adjusted odds ratio = 215.85; 95% confidence interval = 133.75-348.35) in the 69- to 105-year-old group at first-benzodiazepine intake. Anxiolytics had a low risk except for alprazolam and prazepam in the 69- to 105-year-old group at first-benzodiazepine intake, clonazepam and clobazam had the lowest risk in 18- to 43-year-olds at first-benzodiazepine intake. Alprazolam had dispensed volumes increased by threefold over the 12-year period. Conclusion: All hypnotics had higher risks for high-dose use compared to diazepam in continuous users. Two anxiolytics, clonazepam and clobazam, had the lowest risks. Hypnotics and the triazolobenzodiazepines alprazolam and triazolam were most problematic. Elderly subjects and women are at greater risks.

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“…Although the FDA now recommends dosing women with only 5 mg or 6.25 mg of zolpidem, at least to begin with, only 5% of women and 10% of elderly were prescribed these low doses in 2012 153 . Apparently, there was little change in dosing for women and elderly after the FDA recommended the low doses in 2013 153 , 156 . Moreover, 23% of patients with sustained use took another drug targeting the same receptors.…”

Section: Contributory Factors Combined With Hypnotics Could Cause Covmentioning

confidence: 99%

Hypnotic drug risks of mortality, infection, depression, and cancer: but lack of benefit

Kripke

2018

F1000Res

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This is a review of hypnotic drug risks and benefits. Almost every month, new information appears about the risks of hypnotics (sleeping pills). The most important risks of hypnotics include excess mortality (especially overdose deaths, quiet deaths at night, and suicides), infections, cancer, depression, automobile crashes, falls, other accidents, and hypnotic-withdrawal insomnia. Short-term use of one-two prescriptions is associated with even greater risk per dose than long-term use. Hypnotics have usually been prescribed without approved indication, most often with specific contraindications, but even when indicated, there is little or no benefit. The recommended doses objectively increase sleep little if at all, daytime performance is often made worse (not better) and the lack of general health benefits is commonly misrepresented in advertising. Treatments such as the cognitive behavioral treatment of insomnia and bright light treatment of circadian rhythm disorders offer safer and more effective alternative approaches to insomnia.

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Impact of a US Food and Drug Administration Drug Safety Communication on Zolpidem Dosing

Cited by 9 publications

References 4 publications

Study on a Three-Step Rapid Assembly of Zolpidem and Its Fluorinated Analogues Employing Microwave-Assisted Chemistry

Study on a Three-Step Rapid Assembly of Zolpidem and Its Fluorinated Analogues Employing Microwave-Assisted Chemistry

Hypnotics and Triazolobenzodiazepines - Best Predictors of High-Dose Benzodiazepine Use: Results from the Luxembourg National Health Insurance Registry

Hypnotic drug risks of mortality, infection, depression, and cancer: but lack of benefit

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