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Zolpidem

Klassificering: C!

Preparat: Edluar, Stilnoct, Stilnox, Zolpidem Actavis, Zolpidem Aurobindo, Zolpidem HEXAL, Zolpidem Mylan, Zolpidem Orifarm, Zolpidem ratiopharm, Zolpidem Sandoz, Zolpidem STADA, Zolpidem Winthrop, Zolpidem Vitabalans

ATC kod: N05CF02

Substanser: zolpidem, zolpidemtartrat

Sammanfattning

Kvinnor metaboliserar zolpidem långsammare än män. Studier visar ingen entydig skillnad i effekt mellan män och kvinnor men det finns rapporter om ökad dåsighet dagen efter hos kvinnor men inte hos män. Eftersom kvinnor metaboliserar zolpidem långsammare bör dosen reduceras, i synnerhet till äldre kvinnor.

Additional information

Pharmacokinetics and dosing

Zolpidem has a short half-life, 2.4 h. No significant effects of race or sex on the pharmacokinetics of zolpidem have been found [5]. However, women appear to eliminate zolpidem slower than men and the U.S. Food and Drug Administration (FDA) recommends a 50% lower dose of zolpidem to women [6, 7]. One explanation for this sex difference could be that testosterone increase the activity of CYP3A4 catalyzed metabolism of zolpidem [8]. As men have higher testosterone levels, they will eliminate zolpidem faster. This was examined in another study (10 men, 8 women) where the pharmacokinetics of a single-dose of 10 mg zolpidem was studied. Zolpidem clearance showed a non-significant tendency to be lower in women [9].

Effects

The pharmacodynamics of a single-dose 10 mg zolpidem of was studied in healthy volunteers in a double-blind study (10 men, 8 women). No differences between men and women were seen; except for the higher “self-rated sedation” reported in women [9].

Zolpidem increases sleep spindle activity and reduces low frequency EEG activity. A randomized, double-blind, placebo-controlled trial recorded brain activity after intake of 10 mg zolpidem in healthy volunteers (45 women, 36 men) using electroencephalogram (EEG). Women had a greater increase in sleep spindle activity in Non Rapid Eye Movement sleep (stage 2 sleep), but no sex differences were seen in the suppression of delta and theta activity (deep or slow-wave sleep, stage 3 sleep) [10].

Adverse effects

A review article discussing sex differences in driving performance showed that 4 hours after middle-of-the-night administration of 10 mg zolpidem, women drove worse than men. [11] After the 20 mg dose, three of the 15 women were not able to fulfill the driving test due to dizziness and vomiting. Zolpidem blood levels > 50 ng/ml has been associated with increased risk of driving impairment. Eight hours after the administration of a 10 mg zolpidem tablet, an estimated 15% of the women and 3% of the men will have zolpidem blood concentration levels that could affect their driving [12].In a study of driving capacity after medication with sleeping pills (9 men, 14 women) zopiclone 7.5 mg, but not zolpidem 10 mg, was found to increase the number of collisions in a driving simulator compared to placebo. No analysis based on sex was performed [1]. Also another study showed that zopiclone 7.5 mg, but not zolpidem 3.5 mg, impaired next-day driving, but with no differences between men and women [2].

Reproductive health issues

Zolpidem might interact with oral contraceptive preparations, but it is not likely to be of clinical importance. Regarding drug-drug interactions aspects, please consult Janusmed Interactions (in Swedish, Janusmed interaktioner).

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

Other information

Two Swedish register-based studies [13, 14] showed that more women were dispensed zolpidem. The first study (280,623 men, 450,482 women) analyzed all dispensed prescriptions to people aged ≥75 years during a 3-month period in 2005. The adjusted odds ratio for use of zolpidem in women versus men was 1.07 [13]. In the second study (645,429 men, 105,007 women), all dispensed prescriptions to patients between 75-89 years during a 4-month period in 2005 were analyzed. The adjusted odds ratio for use of zolpidem in women compared with men was 1.18 [14].Also, studies from other countries show similar patterns. In a Danish register-based study in patients ≥65 years (5000 men, 5000 women), women redeemed more prescriptions of zopiclone, zolpidem and zaleplon than men (treatment ≥4 weeks: adjusted OR 1.36; treatment ≥6 months: adjusted OR 1.34) [3]. In a Norwegian register study in patients 18-69 years (73,144 men, 135,400 women), the incidence rates for zolpidem and zopiclone were also higher for women. The incidence rate was calculated as the number of incident users divided by the population at risk in Norway on January 1, 2006 [4].

Försäljning på recept

Fler kvinnor än män hämtade ut tabletter innehållande zolpidem (ATC-kod N05CF02) på recept i Sverige år 2015, totalt 155 594 kvinnor och 77 793 män. Det motsvarar 32 respektive 16 personer per tusen invånare. Andelen som hämtat ut läkemedel ökade med stigande ålder hos båda könen. I genomsnitt var tabletter innehållande zolpidem 1,7 gånger vanligare hos kvinnor [15].

Uppdaterat: 2017-03-31

Litteratursökningsdatum: 2013-04-05

Referenser

  1. Staner L, Ertlé S, Boeijinga P, Rinaudo G, Arnal MA, Muzet A et al. Next-day residual effects of hypnotics in DSM-IV primary insomnia: a driving simulator study with simultaneous electroencephalogram monitoring. Psychopharmacology (Berl). 2005;181:790-8. PubMed
  2. Vermeeren A, Vuurman EF, Leufkens TR, Van Leeuwen CJ, Van Oers AC, Laska E et al. Residual effects of low-dose sublingual zolpidem on highway driving performance the morning after middle-of-the-night use. Sleep. 2014;37:489-96. PubMed
  3. Andersen AB, Frydenberg M. Long-term use of zopiclone, zolpidem and zaleplon among Danish elderly and the association with sociodemographic factors and use of other drugs. Pharmacoepidemiol Drug Saf. 2011;20:378-85. PubMed
  4. Hausken AM, Furu K, Skurtveit S, Engeland A, Bramness JG. Starting insomnia treatment: the use of benzodiazepines versus z-hypnotics A prescription database study of predictors. Eur J Clin Pharmacol. 2009;65:295-301. PubMed
  5. Dollery C Sir, editor. Therapeutic drugs. 2nd ed. Edinburgh: Churchill Livingstone; 1999
  6. FDA. FDA Drug Safety Communication: Risk of next-morning impairment after use of insomnia Drugs; FDA requires lower recommended doses for certain drugs containing zolpidem (Ambien, Ambien CR, Edluar and Zolpimist). 2013-01-10.
  7. Ambien (zolpidem) . DailyMed [www]. US National Library of Medicine. [updated 2013-06-01, cited 2013-07-04]. länk
  8. Olubodun JO, Ochs HR, von Moltke LL, Roubenoff R, Hesse LM, Harmatz JS et al. Pharmacokinetic properties of zolpidem in elderly and young adults: possible modulation by testosterone in men. Br J Clin Pharmacol. 2003;56:297-304. PubMed
  9. Greenblatt DJ, Harmatz JS, von Moltke LL, Wright CE, Durol AL, Harrel-Joseph LM et al. Comparative kinetics and response to the benzodiazepine agonists triazolam and zolpidem: evaluation of sex-dependent differences. J Pharmacol Exp Ther. 2000;293:435-43. PubMed
  10. Dijk DJ, James LM, Peters S, Walsh JK, Deacon S. Sex differences and the effect of gaboxadol and zolpidem on EEG power spectra in NREM and REM sleep. J Psychopharmacol. 2010;24:1613-8. PubMed
  11. Verster JC, Roth T. Gender differences in highway driving performance after administration of sleep medication: a review of the literature. Traffic Inj Prev. 2012;13:286-92. PubMed
  12. Medical Letter on Drugs and Therapeutics. FDA Requires Lower Dosing of Zolpidem. 2013-01-21.
  13. Johnell K, Fastbom J. Gender and use of hypnotics or sedatives in old age: a nationwide register-based study. Int J Clin Pharm. 2011;33:788-93. PubMed
  14. 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
  15. Läkemedelsstatistik. Stockholm: Socialstyrelsen. 2015 [cited 2016-04-29] länk

Författare: Fadiea Al-Aieshy, Desirée Loikas

Faktagranskat av: Expertrådet för psykiatriska sjukdomar, Expertrådet för geriatriska sjukdomar, Ellen Vinge, Lars Lööf, Mia von Euler

Godkänt av: Karin Schenck-Gustafsson