From the Guidelines
Zolpidem requires a lower dose in women compared to men due to pharmacokinetic differences. Women should take 5 mg of immediate-release zolpidem at bedtime, while men typically take 10 mg. For extended-release formulations, women should take 6.25 mg versus 12.5 mg for men. 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. The primary reason for this difference is that women have lower activity of specific liver enzymes (particularly CYP3A4) that metabolize the drug. Additionally, women generally have a higher percentage of body fat, which can affect drug distribution. These pharmacokinetic differences can lead to increased morning drowsiness, impaired driving, and higher risk of side effects in women if the dose is not appropriately reduced. The FDA mandated these sex-specific dosing recommendations for zolpidem in 2013 after recognizing these important differences, as noted in a study published in the Journal of Clinical Sleep Medicine 1.
Some key points to consider when prescribing zolpidem include:
- Women have a higher risk of next-day impairment due to the slower metabolism of the drug
- The FDA recommends lower doses of zolpidem for women, with a maximum dose of 5 mg for immediate-release formulations and 6.25 mg for extended-release formulations
- Men can typically take higher doses of zolpidem, with a maximum dose of 10 mg for immediate-release formulations and 12.5 mg for extended-release formulations
- These dosing recommendations are based on pharmacokinetic differences between men and women, as well as the risk of adverse effects such as morning drowsiness and impaired driving, as discussed in guidelines for the management of chronic insomnia disorder in adults 1.
Overall, the correct answer is D, Zolpidem, which requires a lower dose in women compared to men due to pharmacokinetic differences.
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.