Flurazepam

Source: Wikipedia, the free encyclopedia.
Flurazepam
Clinical data
Trade namesDalmane, Dalmadorm, Fluzepam
AHFS/Drugs.comMonograph
MedlinePlusa682051
Pregnancy
category
  • X (Contraindicated in pregnancy)
Addiction
liability		Moderate
Routes of
administration		By mouth
Drug classBenzodiazepine
ATC code
Legal status
Legal status
N-desalkylflurazepam (active metabolite)
Elimination half-life2.3 hours
N-desalkylflurazepam: 47–100 hours
ExcretionKidney
Identifiers
  • 7-Chloro-1-[2-(diethylamino)ethyl]-5-(2-fluorophenyl)-1,3-dihydro-2H-1,4-benzodiazepin-2-one
JSmol)
Melting point79.5 °C (175.1 °F)
  • FC1=CC=CC=C1C2=NCC(N(CCN(CC)CC)C3=C2C=C(C=C3)Cl)=O
  • InChI=1S/C21H23ClFN3O/c1-3-25(4-2)11-12-26-19-10-9-15(22)13-17(19)21(24-14-20(26)27)16-7-5-6-8-18(16)23/h5-10,13H,3-4,11-12,14H2,1-2H3 checkY
  • Key:SAADBVWGJQAEFS-UHFFFAOYSA-N checkY
  (verify)

Flurazepam

skeletal muscle relaxant properties. It produces a metabolite with a long half-life, which may stay in the bloodstream for days.[3]
Flurazepam was patented in 1968 and came into medical use the same year.[4] Flurazepam, developed by Roche Pharmaceuticals, was one of the first benzodiazepine hypnotic medications to be marketed.[5]

Medical uses

Two Dalmane (flurazepam) capsules

Flurazepam is officially indicated for mild to moderate insomnia and as such it is used for short-term treatment of patients with mild to moderate insomnia such as difficulty falling asleep, frequent awakening, early awakenings or a combination of each. Flurazepam is a long-acting benzodiazepine and is sometimes used in patients who have difficulty in maintaining sleep, though benzodiazepines with intermediate half-lives such as loprazolam, lormetazepam, and temazepam are also indicated for patients with difficulty maintaining sleep.

Flurazepam was temporarily unavailable in the United States when its sole producer, Mylan Pharmaceuticals, discontinued making it in January 2019.[citation needed] In October 2019, the FDA informed pharmacies that they could expect to be resupplied by manufacturers in early to mid December 2019. As of this date,[when?] flurazepam is now again available in the United States.

Side effects

The most common adverse effects are dizziness, drowsiness, light-headedness, and ataxia. Flurazepam has abuse potential and should never be used with alcoholic beverages or any other substance that can cause drowsiness. Addictive and possibly fatal results may occur. Flurazepam users should only take this drug strictly as prescribed, and should only be taken directly before the user plans on sleeping a full night. Next day drowsiness is common and may increase during the initial phase of treatment as accumulation occurs until steady-state plasma levels are attained.

A 2009 meta-analysis found a 44% higher rate of mild infections, such as pharyngitis or sinusitis, in people taking hypnotic drugs compared to those taking a placebo.[6]

In September 2020, the U.S. Food and Drug Administration (FDA) required the boxed warning be updated for all benzodiazepine medicines to describe the risks of abuse, misuse, addiction, physical dependence, and withdrawal reactions consistently across all the medicines in the class.[7]

Tolerance, dependence and withdrawal

Main article: Benzodiazepine withdrawal syndrome

A review paper found that long-term use of flurazepam is associated with

barbiturates can easily be substituted by flurazepam in those who are habituated to barbiturate sedative hypnotics.[10]

After discontinuation of flurazepam a rebound effect or benzodiazepine withdrawal syndrome may occur about four days after discontinuation of medication.[11]

Contraindications and special caution

Benzodiazepines require special precaution if used in the elderly, during pregnancy, in children, alcohol- or drug-dependent individuals and individuals with

psychiatric disorders.[12]

Elderly

Flurazepam, similar to other benzodiazepines and nonbenzodiazepine hypnotic drugs causes impairments in body balance and standing steadiness in individuals who wake up at night or the next morning. Falls and hip fractures are frequently reported. The combination with alcohol increases these impairments. Partial, but incomplete tolerance develops to these impairments.[13] An extensive review of the medical literature regarding the management of insomnia and the elderly found that there is considerable evidence of the effectiveness and durability of non-drug treatments for insomnia in adults of all ages and that these interventions are underutilized. Compared with the benzodiazepines including flurazepam, the nonbenzodiazepine sedative-hypnotics appeared to offer few, if any, significant clinical advantages in efficacy in elderly persons. Tolerability in elderly patients, however, is improved marginally in that benzodiazepines have moderately higher risks of falls, memory problems, and disinhibition ("paradoxical agitation") when compared to non-benzodiazepine sedatives. It was found that newer agents with novel mechanisms of action and improved safety profiles, such as the melatonin agonists, hold promise for the management of chronic insomnia in elderly people. Chronic use of sedative-hypnotic drugs for the management of insomnia does not have an evidence base and has been discouraged due to concerns including potential adverse drug effects as cognitive impairment (anterograde amnesia), daytime sedation, motor incoordination, and increased risk of motor vehicle accidents and falls. In addition, the effectiveness and safety of long-term use of sedative hypnotics has been determined to be no better than placebo after 3 months of therapy and worse than placebo after 6 months of therapy.[14][15]

Pharmacology

Flurazepam is a "classical" benzodiazepine; some other classical benzodiazepines include

hip fractures.[17]

Flurazepam is

lipophilic, is metabolized hepatically via oxidative pathways. The main pharmacological effect of flurazepam is to increase the effect of GABA at the GABAA receptor via binding to the benzodiazepine site on the GABAA receptor causing an increase influx of chloride ions into the GABAA neuron.[18][19]

Flurazepam is contraindicated in pregnancy. It is recommended to withdraw flurazepam during breast feeding, as flurazepam is excreted in breast milk.[20]

Misuse

See also:
Benzodiazepine drug misuse

Flurazepam is a drug with potential for misuse. Two types of drug misuse can occur, either recreational misuse where the drug is taken to achieve a high, or when the drug is continued long term against medical advice.[21]

Legal status

Flurazepam is a Schedule IV drug under the Convention on Psychotropic Substances.[22]

See also

  • Long-term effects of benzodiazepines

References

  1. ^ Anvisa (2023-03-31). "RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial" [Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control] (in Brazilian Portuguese). Diário Oficial da União (published 2023-04-04). Archived from the original on 2023-08-03. Retrieved 2023-08-16.
  2. ^ BE 629005 
  3. ^ a b "FLURAZEPAM HCl CAPSULES, USP". dailymed.nlm.nih.gov.
  4. ISBN 9783527607495
    .
  5. ISBN 978-0-19-029201-0
    .
  6. PMID 19968019
    .
  7. ^ "FDA expands Boxed Warning to improve safe use of benzodiazepine drug". U.S. Food and Drug Administration (FDA). 23 September 2020. Retrieved 23 September 2020. Public Domain This article incorporates text from this source, which is in the public domain.
  8. PMID 10533351
    .
  9. S2CID 23137060
    .
  10. S2CID 23780461
    .
  11. S2CID 38591190
    .
  12. PMID 19900604
    .
  13. PMID 20171127
    .
  14. ^ NEJM, 1983, 1994, et seq. [full citation needed]
  15. PMID 16860264
    .
  16. PMID 639854
    .
  17. S2CID 25592318
    .
  18. PMID 2570451
    .
  19. PMID 3034628
    .
  20. PMID 851373
    .
  21. PMID 16336040
    .
  22. ^ "green-lists". incb.org. Archived from the original on 2015-12-08. Retrieved 2015-12-03.

External links

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