Subject: Insomnia Post Limit PA 201-J P01-2025

Drug

Insomnia Agents

AMBIEN  (zolpidem)

AMBIEN CR  (zolpidem extended-release)

DORAL  (quazepam)

estazolam (brand unavailable)  (estazolam)

flurazepam (brand unavailable)  (flurazepam)

HALCION  (triazolam)

LUNESTA  (eszopiclone)

RESTORIL  (temazepam)

ROZEREM  (ramelteon)

zaleplon (brand unavailable)  (zaleplon)

ZOLPIDEM TARTATE  (zolpidem tartrate)

Note: Products Referenced by this Document Drugs that are listed in the following table include both brand and generic and all dosage forms and strengths unless otherwise stated. Over-the-counter (OTC) products are not included unless otherwise stated. Edluar, zolpidem tartrate sublingual tablets (generic Intermezzo), ZolpiMist, Belsomra, Dayvigo, and Quviviq are not included in these criteria. Refer to Insomnia (zolpidem sublingual, oral spray) or Insomnia (Belsomra, Dayvigo, Quviviq) Prior Authorization criteria.

Policy:

Indications

FDA-approved Indications

Ambien

Ambien (zolpidem tartrate) is indicated for the short-term treatment of insomnia characterized by difficulties with sleep initiation. Ambien has been shown to decrease sleep latency for up to 35 days in controlled clinical studies.

The clinical trials performed in support of efficacy were 4-5 weeks in duration with the final formal assessments of sleep latency performed at the end of treatment.

Ambien CR

Ambien CR (zolpidem tartrate extended-release tablets) is indicated for the short-term treatment of insomnia characterized by difficulties with sleep onset and/or sleep maintenance (as measured by wake time after sleep onset).

The clinical trials performed in support of efficacy were up to 3 weeks (using polysomnography measurement up to 2 weeks in both adult and elderly patients) and 24 weeks (using patient-reported assessment in adult patients only) in duration.

Doral

Doral is indicated for the treatment of insomnia characterized by difficulty in falling asleep, frequent nocturnal awakenings, and/or early morning awakenings. The effectiveness of Doral has been established in placebo-controlled clinical studies of 5 nights duration in acute and chronic insomnia. The sustained effectiveness of Doral has been established in chronic insomnia in a sleep lab (polysomnographic) study of 28 nights duration. Because insomnia is often transient and intermittent, the prolonged administration of Doral Tablets is generally not necessary or recommended. Since insomnia may be a symptom of several other disorders, the possibility that the complaint may be related to a condition for which there is a more specific treatment should be considered.

Estazolam

Estazolam is indicated for the short-term management of insomnia characterized by difficulty in falling asleep, frequent nocturnal awakenings, and/or early morning awakenings. Both outpatient studies and a sleep laboratory study have shown that estazolam administered at bedtime improved sleep induction and sleep maintenance.

Because insomnia is often transient and intermittent, the prolonged administration of estazolam is generally neither necessary nor recommended. Since insomnia may be a symptom of several other disorders, the possibility that the complaint may be related to a condition for which there is a more specific treatment should be considered.

There is evidence to support the ability of estazolam to enhance the duration and quality of sleep for intervals up to 12 weeks.

Flurazepam

Flurazepam hydrochloride capsules are indicated for the treatment of insomnia characterized by difficulty in falling asleep, frequent nocturnal awakenings, and/or early morning awakenings.

Since insomnia is often transient and intermittent, short-term use is usually sufficient. Prolonged use of hypnotics is usually not indicated and should only be undertaken concomitantly with appropriate evaluation of the patient.

Halcion

Halcion is indicated for the short-term treatment of insomnia (generally 7 to 10 days) in adults.

Lunesta

Lunesta (eszopiclone) is indicated for the treatment of insomnia. In controlled outpatient and sleep laboratory studies, Lunesta administered at bedtime decreased sleep latency and improved sleep maintenance.

The clinical trials performed in support of efficacy were up to 6 months in duration. The final formal assessments of sleep latency and maintenance were performed at 4 weeks in the 6-week study (adults only), at the end of both 2-week studies (elderly only) and at the end of the 6-month study (adults only).

Restoril

Restoril (temazepam) is indicated for the short-term treatment of insomnia (generally 7 to 10 days).

For patients with short-term insomnia, instructions in the prescription should indicate that Restoril (temazepam) should be used for short periods of time (7 to 10 days).

The clinical trials performed in support of efficacy were 2 weeks in duration with the final formal assessment of sleep latency performed at the end of treatment.

Rozerem

Rozerem is indicated for the treatment of insomnia characterized by difficulty with sleep onset.

The clinical trials performed in support of efficacy were up to six months in duration. The final formal assessments of sleep latency were performed after two days of treatment during the crossover study (elderly only), at five weeks in the six week studies (adults and elderly), and at the end of the six month study (adults and elderly).

Zaleplon

Zaleplon capsules are indicated for the short-term treatment of insomnia. Zaleplon capsules have been shown to decrease the time to sleep onset for up to 30 days in controlled clinical studies. It has not been shown to increase total sleep time or decrease the number of awakenings.

The clinical trials performed in support of efficacy ranged from a single night to 5 weeks in duration. The final formal assessments of sleep latency were performed at the end of treatment.

Zolpidem Tartrate Capsules

Zolpidem Tartrate Capsules are indicated for the short-term treatment of transient insomnia characterized by difficulties with sleep initiation in adults younger than 65 years of age.

Coverage Criteria

Insomnia

Authorization may be granted when the requested drug is being prescribed for insomnia when the following criteria is met:

• Potential factors contributing to sleep disturbances have been addressed or are currently being addressed (e.g., inappropriate sleep hygiene and sleep environment issues) as well as treatable medical/psychiatric disorders that are co-morbid with insomnia.

Continuation of Therapy

Insomnia

Authorization may be granted when the requested drug is being prescribed for insomnia and ALL of the following criteria are met:

• The patient has achieved or maintained a positive response to treatment from baseline.
• The patient’s need for continued therapy has been assessed.
• Potential factors contributing to sleep disturbances continue to be addressed (e.g., inappropriate sleep hygiene, sleep environment issues, treatable medical/psychiatric comorbid disorders).

Quantity Limits Apply

Ambien, Ambien CR, Lunesta, Rozerem: 30 tablets per 25 days or 90 tablets per 75 days

Zolpidem tartrate capsules: 30 capsules per 25 days or 90 capsules per 75 days

Zaleplon: 60 capsules per 25 days or 180 capsules per 75 days

The duration of 25 days is used for a 30-day fill period and 75 days is used for a 90-day fill period to allow time for refill processing.

There is a lack of data supporting benzodiazepines for long-term management of insomnia; therefore, no post limit quantities will be available for Doral, estazolam, flurazepam, Halcion, and Restoril.

Duration of Approval (DOA)

201-J: Initial therapy DOA: 6 months; Continuation of therapy DOA: 12 months

Place of Service:

Outpatient

The above policy is based on the following references:

1. Ambien [package insert]. Bridgewater, NJ: sanofi-aventis U.S. LLC; February 2022.
2. Ambien CR [package insert]. Bridgewater, NJ: sanofi-aventis U.S. LLC; February 2022.
3. Doral [package insert]. Atlanta, GA: Galt Pharmaceuticals, LLC.; January 2023.
4. Estazolam [package insert]. Princeton, NJ: Dr. Reddy’s Laboratories Inc.; August 2023.
5. Flurazepam Hydrochloride [package insert]. Congers, NY: Chartwell RX, LLC.; December 2023.
6. Halcion [package insert]. New York, NY: Pharmacia & Upjohn Company LLC; July 2024.
7. Lunesta [package insert]. Wixom, MI: Waylis Therapeutics LLC; July 2023.
8. Restoril [package insert]. Webster Groves, MO: SpecGx LLC; January 2023.
9. Rozerem [package insert]. Lexington, MA: Takeda Pharmaceuticals America, Inc.; November 2021.
10. Zaleplon [package insert]. Princeton, NJ: Bionpharma Inc.; June 2023.
11. Zolpidem Tartrate Capsules [package insert]. Morristown, NJ: Almatica Pharma LLC; May 2023.
12. Lexicomp Online, AHFS DI (Adult and Pediatric) Online. Waltham, MA: UpToDate, Inc.; 2024. https://online.lexi.com. Accessed November 27, 2024.
13. Micromedex® (electronic version). Merative, Ann Arbor, Michigan, USA. Available at: https://www.micromedexsolutions.com/ (cited: 11/26/2024).
14. Sateia MJ, Buysse DJ, Krystal AD, et al. Clinical practice guideline for the pharmacologic treatment of chronic insomnia in adults: An American Academy of Sleep Medicine clinical practice guideline. J Clin Sleep Med. 2017;13(2):307-349.
15. American Academy of Sleep Medicine. International Classification of Sleep Disorders, Third Edition, Text Revision. American Academy of Sleep Medicine, 2023.
16. Edinger JD, Arnedt JT, Bertisch SM, et al. Behavioral and psychological treatments for chronic insomnia disorder in adults: an American Academy of Sleep Medicine clinical practice guideline. J Clin Sleep Med. 2021;17(2):255-262.
17. Crescenzo FD, D’Alo GL, Ostinelli EG, et al. Comparative effects of pharmacological interventions for the acute and long-term management of insomnia disorder in adults: a systematic review and network meta-analysis. Lancet. 2022;400:170-184.

Copyright Aetna Inc. All rights reserved. Pharmacy Clinical Policy Bulletins are developed by Aetna to assist in administering plan benefits and constitute neither offers of coverage nor medical advice. This Clinical Policy Bulletin contains only a partial, general description of plan or program benefits and does not constitute a contract. Aetna does not provide health care services and, therefore, cannot guarantee any results or outcomes. Participating providers are independent contractors in private practice and are neither employees nor agents of Aetna or its affiliates. Treating providers are solely responsible for medical advice and treatment of members. This Clinical Policy Bulletin may be updated and therefore is subject to change.

June 06, 2025