From the Guidelines
Zolpidem requires a lower dose in women compared to men due to pharmacokinetic differences, with recommended doses of 5 mg for women and 10 mg for men for immediate-release formulations, and 6.25 mg for women and 12.5 mg for men for extended-release formulations. This dosing difference exists because women metabolize zolpidem more slowly than men, resulting in higher blood concentrations and longer duration of action when given the same dose, as noted in a study published in the Journal of Clinical Sleep Medicine in 2018 1. The slower clearance in women is primarily due to differences in body composition, lower activity of certain liver enzymes, and hormonal influences on drug metabolism. These higher blood levels can lead to increased morning drowsiness and impaired driving performance the next day if women take the same doses as men. The FDA recommends lower doses of zolpidem in women, as well as in older or debilitated adults, to minimize the risk of adverse effects, including next-day impairment 1.
Some key points to consider when prescribing zolpidem include:
- Women should take lower doses of zolpidem due to pharmacokinetic differences
- Immediate-release zolpidem should be taken at a dose of 5 mg in women and 10 mg in men
- Extended-release zolpidem should be taken at a dose of 6.25 mg in women and 12.5 mg in men
- The FDA recommends short-term use of zolpidem, although many patients may continue their use for extended periods
- Other medications, such as alcohol, certain antidepressants, and some cardiovascular medications, may also require sex-specific dosing, although zolpidem is the clearest example where official dosing guidelines specifically recommend different doses based on sex.
From the FDA Drug Label
The recommended initial dose is 5 mg for women and either 5 or 10 mg for men, taken only once per night immediately before bedtime with at least 7 to 8 hours remaining before the planned time of awakening. The recommended initial doses for women and men are different because zolpidem clearance is lower in women. Women clear zolpidem tartrate from the body at a lower rate than men. Cmax and AUC parameters of zolpidem were approximately 45% higher at the same dose in female subjects compared with male subjects Given the higher blood levels of zolpidem tartrate in women compared to men at a given dose, the recommended initial dose of zolpidem tartrate for adult women is 5 mg, and the recommended dose for adult men is 5 or 10 mg.
The medication that requires a lower dose in women compared to men due to pharmacokinetic differences is Zolpidem 2 2.
- The main reason for this difference is that zolpidem clearance is lower in women.
- As a result, women have higher blood levels of zolpidem compared to men at the same dose.
- The recommended initial dose for adult women is 5 mg, while the recommended dose for adult men is 5 or 10 mg.
From the Research
Medication Requiring Lower Dose in Women
- The medication that requires a lower dose in women compared to men due to pharmacokinetic differences is:
- D Zolpidem
Rationale
- Studies have shown that women have a lower apparent clearance of zolpidem compared to men, resulting in higher plasma concentrations and increased risk of adverse effects 3, 4, 5.
- The FDA has recommended a lower dose of zolpidem for women (50% of the dose for men) due to these pharmacokinetic differences 3.
- Other studies have also found that women have higher exposure to zolpidem and delayed recovery compared to men, which may be related to higher zolpidem concentrations 4, 5.
- While some studies suggest that sex differences in pharmacokinetics may be clinically insignificant, others argue that further research is needed to determine the clinical importance of these differences 6, 7.