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Oxazepam

Classification: A

Drug products: Oxascand, Sobril®

ATC code: N05BA04

Substances: oxazepam

Summary

Oxazepam has effect in both men and women. Sex differences in adverse effects have been described but it’s unclear what is directly associated with the drug. The reported pharmacokinetic differences are conflicting and of doubtful clinical relevance.
 
The present evidence concerning differences between men and women is limited and do not motivate differentiation in dosing or treatment.

Additional information

Pharmacokinetics and dosing

Studies show conflicting results whether there are sex differences in oxazepam pharmacokinetics or not. In a single-dose pharmacokinetic study 30 mg oxazepam tablets were given to healthy volunteers (18 men, 20 women). Elimination half-life was 20% shorter, and total clearance was 29% higher in men than in women [1]. However, no  differences in kinetics between men and women were found in a study using similar methods (22 men, 9 women) [5]. Despite the pharmacokinetic differences of oxazepam, the clinical studies have shown effect with similar doses in men and women and no sex differentiation in dosing has been suggested [6].

An in vitro analysis of human liver samples (38 men, 16 women) has shown higher activity in oxazepam glucuronidation in male than female samples [7] .

Effects

A randomized double-blind study on insomnia in hospitalized patients (29 men, 30 women) comparing midazolam and oxazepam with placebo found no differences in sleep onset latency or sleep duration between men and women [8].

Adverse effects

The frequency of adverse effects of benzodiazepines experienced in psychiatric outpatients has been evaluated in a questionnaire (60 men, 19 women). All women and 91% of men had at least one adverse effect. The mean number of adverse events was 4.8 in both men and women. The most commonly reported adverse effects in both men and women were sleepiness, slowness and fatigue. The most evident sex difference was the higher prevalence of dizziness in women (31%) than men (6%) [2].The risk of falls when using benzodiazepines was studied in a registry study (124009 men, 197413 women). Higher age and female sex was associated with a higher incidence of falls among benzodiazepine users and controls. The risk of falling was higher among benzodiazepine users, more pronouncedly so in men. A history of treatment of alcohol abuse was an important risk factor for falls in this group with an odds ratio of 10.7 in men and 4.3 in women. The benzodiazepines showing the highest increase in risk of falls were flurazepam and triazolam followed by, oxazepam, lorazepam and diazepam in falling order [3].

Reproductive health issues

Regarding teratogenic aspects, please consult the Drugs and Birth Defects Database (in Swedish, Janusmed fosterpåverkan).

Other information

A Swedish register-based study conducted on a geriatric population (280623 men, 450482 women, age ≥75) has shown a higher probability for women to use  benzodiazepines/benzodiazepine related drugs [4].

Updated: 2019-02-26

Date of litterature search: 2015-04-21

References

  1. Greenblatt DJ, Divoll M, Harmatz JS, Shader RI. Oxazepam kinetics: effects of age and sex. J Pharmacol Exp Ther. 1980;215:86-91. PubMed
  2. Arbanas G, Arbanas D, Dujam K. Adverse effects of benzodiazepines in psychiatric outpatients. Psychiatr Danub. 2009;21:103-7. PubMed
  3. Neutel CI, Hirdes JP, Maxwell CJ, Patten SB. New evidence on benzodiazepine use and falls: the time factor. Age Ageing. 1996;25:273-8. PubMed
  4. Johnell K, Fastbom J. The use of benzodiazpines and related drugs amongst older people in Sweden: associated factors and concomitant use of other psychotropics. Int J Geriatr Psychiatry. 2009;24:731-8. PubMed
  5. Ochs HR, Greenblatt DJ, Otten H. Disposition of oxazepam in relation to age, sex, and cigarette smoking. Klin Wochenschr. 1981;59:899-903. PubMed
  6. Sobril (oxazepam). Summary of Product Characteristics. Medical Products Agency Sweden; 2014.
  7. Court MH, Hao Q, Krishnaswamy S, Bekaii-Saab T, Al-Rohaimi A, von Moltke LL et al. UDP-glucuronosyltransferase (UGT) 2B15 pharmacogenetics: UGT2B15 D85Y genotype and gender are major determinants of oxazepam glucuronidation by human liver. J Pharmacol Exp Ther. 2004;310:656-65. PubMed
  8. Gallais H, Casanova P, Fabregat H. Midazolam and oxazepam in the treatment of insomnia in hospitalized patients. Br J Clin Pharmacol. 1983;16 Suppl 1:145S-149S. PubMed
  9. Läkemedelsstatistik. Stockholm: Socialstyrelsen. 2015 [cited 2016-04-29] länk

Authors: Anna Garmén, Desirée Loikas

Reviewed by: Mia von Euler

Approved by: Karin Schenck-Gustafsson