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Edluar vs Ambien: Comparing Sublingual and Oral Zolpidem for Insomnia Treatment

by alexxlab

How does sublingual zolpidem (Edluar) compare to oral zolpidem (Ambien) in treating primary insomnia. What are the differences in onset of action and sleep induction between these two formulations. How do the efficacy and safety profiles of sublingual and oral zolpidem compare in clinical studies.

Содержание

Understanding Zolpidem: Sublingual vs Oral Formulations

Zolpidem is a widely prescribed medication for the treatment of insomnia. It belongs to a class of drugs known as sedative-hypnotics, which work by enhancing the effects of GABA, a neurotransmitter that promotes sleep. Two common formulations of zolpidem are available: sublingual (Edluar) and oral (Ambien). While both contain the same active ingredient, their routes of administration and onset of action differ significantly.

What is sublingual zolpidem (Edluar)?

Sublingual zolpidem, marketed under the brand name Edluar, is a tablet designed to be placed under the tongue where it dissolves rapidly. This method of administration allows the drug to be absorbed directly into the bloodstream through the oral mucosa, bypassing the digestive system.

How does oral zolpidem (Ambien) work?

Oral zolpidem, commonly known as Ambien, is a tablet that is swallowed and absorbed through the gastrointestinal tract. It undergoes first-pass metabolism in the liver before reaching the bloodstream, which can affect its onset of action and overall bioavailability.

Clinical Study: Comparing Sublingual and Oral Zolpidem

A randomized, double-blind, two-period, cross-over multi-center study was conducted to compare the hypnotic effects of sublingual zolpidem (Edluar) 10 mg versus oral zolpidem (Ambien) 10 mg in patients with DSM-IV primary insomnia. The study utilized polysomnography (PSG) to measure various sleep parameters.

Study design and objectives

The primary objective of the study was to compare the two formulations on sleep induction, measured by:

  • Latency to persistent sleep (LPS)
  • Sleep onset latency (SOL)
  • Latency to stage 1 (ST1L)

The study involved 70 female and male patients aged 19-64 years. Each participant underwent two successive PSG recording nights for each treatment period, with the medication administered at the start of PSG recordings.

Key Findings: Sublingual Zolpidem Superiority in Sleep Induction

The results of the clinical study revealed significant advantages of sublingual zolpidem over its oral counterpart in terms of sleep induction.

Latency to persistent sleep (LPS)

Sublingual zolpidem significantly shortened LPS by 34% or 10.3 minutes compared to oral zolpidem (95% CI: -4.3 min to -16.2 min, p = 0.001). This indicates a faster onset of persistent sleep with the sublingual formulation.

Sleep onset latency (SOL) and latency to stage 1 (ST1L)

Both SOL and ST1L were also significantly shortened with sublingual zolpidem (p < 0.01). These findings further support the superior sleep-inducing properties of the sublingual formulation.

Sleep Maintenance and Subjective Assessments

While the sublingual formulation showed advantages in sleep induction, other aspects of sleep were comparable between the two formulations.

Total sleep time (TST)

The study found that both sublingual and oral zolpidem were comparable in terms of sleep maintenance properties based on total sleep time (TST). This suggests that once sleep is initiated, both formulations are equally effective in maintaining sleep throughout the night.

Subjective sleep quality and residual effects

Interestingly, the improvement in subjective sleep quality and next-day residual effects did not differ significantly between the two treatments. This indicates that patients’ perceived sleep quality and daytime functioning were similar regardless of the zolpidem formulation used.

Safety and Tolerability Profile

An important aspect of any medication is its safety profile and how well it is tolerated by patients.

Are sublingual and oral zolpidem equally well-tolerated?

The study reported that both routes of administration were well tolerated by the participants. This suggests that the sublingual formulation does not introduce any new safety concerns compared to the well-established oral formulation.

Implications for Insomnia Treatment

The findings of this study have significant implications for the treatment of primary insomnia, particularly for patients who struggle with sleep initiation.

Who might benefit most from sublingual zolpidem?

Patients who have difficulty falling asleep but do not necessarily have problems maintaining sleep throughout the night may benefit most from sublingual zolpidem. The faster onset of action could be particularly advantageous for those who experience anxiety or frustration when trying to fall asleep.

Considerations for prescribing

Healthcare providers should consider the individual needs of each patient when deciding between sublingual and oral zolpidem. Factors to consider include:

  • The patient’s specific sleep complaints (e.g., difficulty falling asleep vs. staying asleep)
  • Any history of delayed gastric emptying or absorption issues
  • Patient preference for route of administration
  • Cost and insurance coverage for different formulations

Future Research Directions

While this study provides valuable insights into the comparative efficacy of sublingual and oral zolpidem, several areas warrant further investigation.

Long-term efficacy and safety

Further research is needed to assess the long-term efficacy and safety of sublingual zolpidem compared to oral formulations. This could include:

  1. Extended-duration studies to evaluate the potential for tolerance or dependence
  2. Investigation of the impact on cognitive function and next-day performance over prolonged use
  3. Assessment of the risk of rebound insomnia upon discontinuation

Subpopulation studies

Additional research could focus on specific subpopulations to determine if certain groups might benefit more from sublingual zolpidem:

  • Elderly patients, who may have altered drug metabolism
  • Individuals with comorbid conditions such as depression or anxiety
  • Shift workers or those with jet lag, who may require more rapid sleep onset

The comparative study of sublingual zolpidem (Edluar) and oral zolpidem (Ambien) has revealed significant advantages of the sublingual formulation in terms of sleep induction. Sublingual zolpidem demonstrated faster onset of action, shorter latency to persistent sleep, and reduced sleep onset latency compared to its oral counterpart. These findings suggest that sublingual zolpidem may be particularly beneficial for patients who struggle with falling asleep.

However, it’s important to note that both formulations were comparable in terms of sleep maintenance, subjective sleep quality, and next-day residual effects. This indicates that the choice between sublingual and oral zolpidem should be tailored to individual patient needs and preferences.

The safety and tolerability profiles of both formulations were similar, which is reassuring for patients and healthcare providers considering the sublingual option. Nonetheless, as with any medication, the potential risks and benefits should be carefully weighed for each individual patient.

Future research should focus on long-term efficacy and safety, as well as the potential benefits of sublingual zolpidem in specific patient populations. As our understanding of sleep disorders and their treatments continues to evolve, medications like sublingual zolpidem offer promising options for improving sleep quality and overall quality of life for those suffering from insomnia.

In conclusion, the introduction of sublingual zolpidem represents an important advancement in the treatment of primary insomnia, particularly for those who struggle with sleep initiation. By offering a faster onset of action without compromising safety or overall sleep quality, sublingual zolpidem provides healthcare providers with an additional tool to address the diverse needs of patients with sleep disorders.

As research in this field progresses, it is likely that we will gain even more insights into the optimal use of different zolpidem formulations, leading to more personalized and effective treatment strategies for insomnia. Patients and healthcare providers alike should stay informed about these developments to ensure the best possible outcomes in the management of sleep disorders.

Sublingual zolpidem in early onset of sleep compared to oral zolpidem: polysomnographic study in patients with primary insomnia

Randomized Controlled Trial

. 2010 Jun;26(6):1423-31.

doi: 10.1185/03007991003788225.

Corinne Staner 
1
, Frédéric Joly, Nathalie Jacquot, Irina D Vlasova, Maria Nehlin, Thomas Lundqvist, Charlotte Edenius, Luc Staner

Affiliations

Affiliation

  • 1 Forenap Pharma, Rouffach, France.

  • PMID:

    20397964

  • DOI:

    10.1185/03007991003788225

Randomized Controlled Trial

Corinne Staner et al.

Curr Med Res Opin.

2010 Jun.

. 2010 Jun;26(6):1423-31.

doi: 10.1185/03007991003788225.

Authors

Corinne Staner 
1
, Frédéric Joly, Nathalie Jacquot, Irina D Vlasova, Maria Nehlin, Thomas Lundqvist, Charlotte Edenius, Luc Staner

Affiliation

  • 1 Forenap Pharma, Rouffach, France.

  • PMID:

    20397964

  • DOI:

    10.1185/03007991003788225

Abstract


Objective:

To compare the hypnotic effects of a single dose of a sublingual formulation of zolpidem (Edluar*) 10 mg vs oral formulation (Ambien dagger ) 10 mg by polysomnography (PSG) in DSM-IV primary insomnia patients. Primary objective was to compare the two formulations on sleep induction, measured by latency to persistent sleep (LPS), sleep onset latency (SOL) and latency to stage 1 (ST1L).


Research and methods:

This was a randomized, double-blind, two-period, cross-over multi-centre study in which each period comprised two successive PSG recording nights. Treatment was administered when PSG recordings started. Subjective sleep and residual effects were assessed the next morning.


Results:

Seventy female and male patients aged 19-64 were analysed. Sublingual zolpidem significantly shortened LPS by 34% or 10.3 minutes as compared to oral zolpidem (95% CI: -4.3 min to -16.2 min, p = 0.001). SOL and ST1L were also significantly shortened (p < 0.01). Furthermore the two formulations were comparable in terms of sleep maintenance properties based on total sleep time (TST). The improvement in subjective sleep and next-day residual effects did not differ between the two treatments. Both routes of administration were well tolerated.


Conclusions:

The results demonstrate that sublingual zolpidem is superior to an equivalent dose of oral zolpidem in terms of sleep inducing properties in a carefully selected sample of primary insomnia patients.

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Zolpidem (Ambien®, Ambien CR®, Edluar®, Intermezzo®, Zolpimist®): Basic Information

Zolpidem (Ambien® and generic, Ambien CR® and generic, Edluar®, Intermezzo® and generic, and Zolpimist) is a gamma-aminobutyric acid (GABA) A agonist that is used as a hypnotic. Here is basic information about this medication.

FDA-approved indications

A. Short-term treatment of insomnia characterized by difficulty in sleep initiation

Oral tablet (Ambien® and generic), sublingual tablet (Edluar®), or oral spray (Zolpimist®) may be indicated

B. Treatment of insomnia when a middle-of-the-night awakening is followed by difficulty returning to sleep

Low-dose zolpidem sublingual tablet (Intermezzo® and generic) may be indicated

C. Treatment of insomnia characterized by difficulties with sleep initiation and/or sleep maintenance

Extended-release oral tablet (Ambien CR® and generic) may be indicated

Dosage

1. Short-term treatment of insomnia characterized by difficulty in sleep initiation

a. Oral tablet (Ambien®) or sublingual tablet (Edluar®)

Initial: 5 mg (women), 5 or 10 mg (men) once daily at bed time
Maximum: 10 mg once daily at bed time

b. Oral Spray (Zolpimist®)

Initial: 10 mg (2 sprays) once daily at bedtime
Maximum: 10 mg once daily at bedtime

2. Treatment of insomnia when a middle-of-the-night awakening is followed by difficulty returning to sleep

Low-dose sublingual tablet (Intermezzo®): 1.75 mg (women), 3.5 mg (men)

Note: Indicated only if more than four hours remain before the planned time of waking

3. Treatment of insomnia characterized by difficulties with sleep maintenance and/or sleep initiation

Extended-release tablet (Ambien CR®)

Initial: 6.25 mg (women), 6.25 mg or 12.5 mg (men) once daily at bed time
Maximum: 12.5 mg once daily at bedtime

Special Considerations: In elderly, debilitated, and patients with hepatic impairment start with the lowest dose (refer to prescribing information for details)

Dosage forms and strengths

Oral tablet (Ambien®): 5 mg, 10 mg

Sublingual tablet (Edluar®): 5 mg, 10 mg

Extended-release tablet (Ambien CR®): 6.25 mg, 12.5 mg

Oral Spray (Zolpimist®): Each spray (metered actuation) delivers 5 mg zolpidem in 0. 1 mL

Low-dose sublingual tablet (Intermezzo®): 1.75 mg and 3.5 mg

Please refer to Prescribing Information (see link below) for complete discussion of dosage, administration, warnings and precautions, contraindications, etc.

Related Pages
Practical tips on using hypnotics: the Z drugs
Practical tips on using hypnotics: benzodiazepines
Three important pieces of information about benzodiazepines
Relaxation Practice: A Simple and Powerful Tool for Anxiety, Tension, and Insomnia
Sleep Hygiene worksheets-Part 1 and Part 2
Sleep log: Ten important questions about the person’s sleep
References
Zolpidem oral tablet prescribing information
Zolpidem sublingual tablet prescribing information
Zolpidem extended-release oral tablet prescribing information
Zolpidem oral spray prescribing information
Zolpidem low-dose sublingual tablet prescribing information

Copyright 2016, Rajnish Mago, MD.