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ph-1049

Insomnia Agents Quantity Limit Program Summary

Policy Number: PH-1049

This program applies to Commercial, Blue Partner, GenPlus, NetResults A series, SourceRx and Health Insurance Marketplace

POLICY REVIEW CYCLE

Effective Date	Date of Origin
7/1/2023

FDA APPROVED INDICATIONS AND DOSAGE

Agent(s)	FDA Indication(s)	Notes	Ref#
Ambien® (zolpidem)*^{^}** Tablet	Short-term treatment of insomnia characterized by difficulties with sleep initiation	*- Hypnotics classified as Schedule IV controlled substances ^- Generics available	2
Ambien CR® (zolpidem CR)*^{^}** Tablet	Short-term treatment of insomnia characterized by difficulties with sleep onset and/or sleep maintenance	*- Hypnotics classified as Schedule IV controlled substances ^- Generics available	1
Belsomra® (suvorexant)* Tablet	Treatment of insomnia characterized by difficulties with sleep onset and/or sleep maintenance	*- Hypnotics classified as Schedule IV controlled substances	3
Dayvigo® (lemborexant)^* Tablet	Treatment of adult patients with insomnia, characterized by difficulties with sleep onset and/or sleep maintenance	*- Hypnotics classified as Schedule IV controlled substances	13
Edular® (zolpidem)* Sublingual tablet	Short-term treatment of insomnia characterized by difficulties with sleep initiation	*- Hypnotics classified as Schedule IV controlled substances	4
Intermezzo® (zolpidem)*^ Sublingual tablet	For use as needed for the treatment of insomnia when a middle of the night awakening is followed by difficulty returning to sleep	*- Hypnotics classified as Schedule IV controlled substances ^- Generics available	5
Lunesta® (eszopiclone)*^ Tablet	Treatment of insomnia	*- Hypnotics classified as Schedule IV controlled substances ^- Generics available	6
Quviviq™ (daridorexant)* Tablet	Treatment of adult patients with insomnia characterized by difficulties with sleep onset and/or sleep maintenance	*- Hypnotics classified as Schedule IV controlled substances	14
Rozerem (ramelteon)^ Tablet	Treatment of insomnia characterized by difficulty with sleep onset	^- Generics available	7
Silenor® (doxepin)^{^} Tablet	Treatment of insomnia characterized by difficulty with sleep maintenance	^- Generics available	8
Zolpimist (zolpidem)* Oral spray	Short-term treatment of insomnia characterized by difficulties with sleep initiation	*- Hypnotics classified as Schedule IV controlled substances	9

Agent(s)

FDA Indication(s)

Notes

Ref#

Ambien®

(zolpidem)^{*^}

Tablet

Short-term treatment of insomnia characterized by difficulties with sleep initiation

*- Hypnotics classified as Schedule IV controlled substances

^- Generics available

Ambien CR®

(zolpidem CR)^{*^}

Tablet

Short-term treatment of insomnia characterized by difficulties with sleep onset and/or sleep maintenance

*- Hypnotics classified as Schedule IV controlled substances

^- Generics available

Belsomra®

(suvorexant)*

Tablet

Treatment of insomnia characterized by difficulties with sleep onset and/or sleep maintenance

*- Hypnotics classified as Schedule IV controlled substances

Dayvigo®

(lemborexant)^*

Tablet

Treatment of adult patients with insomnia, characterized by difficulties with sleep onset and/or sleep maintenance

*- Hypnotics classified as Schedule IV controlled substances

Edular®

(zolpidem)*

Sublingual tablet

Short-term treatment of insomnia characterized by difficulties with sleep initiation

*- Hypnotics classified as Schedule IV controlled substances

Intermezzo®

(zolpidem)*^

Sublingual tablet

For use as needed for the treatment of insomnia when a middle of the night awakening is followed by difficulty returning to sleep

*- Hypnotics classified as Schedule IV controlled substances

^- Generics available

Lunesta®

(eszopiclone)*^

Tablet

Treatment of insomnia

*- Hypnotics classified as Schedule IV controlled substances

^- Generics available

Quviviq™

(daridorexant)*

Tablet

Treatment of adult patients with insomnia characterized by difficulties with sleep onset and/or sleep maintenance

*- Hypnotics classified as Schedule IV controlled substances

Rozerem

(ramelteon)^

Tablet

Treatment of insomnia characterized by difficulty with sleep onset

^- Generics available

Silenor®

(doxepin)^{^}

Tablet

Treatment of insomnia characterized by difficulty with sleep maintenance

^- Generics available

Zolpimist

(zolpidem)*

Oral spray

Short-term treatment of insomnia characterized by difficulties with sleep initiation

*- Hypnotics classified as Schedule IV controlled substances

See package insert for FDA prescribing information: https://dailymed.nlm.nih.gov/dailymed/index.cfm

CLINICAL RATIONALE

Insomnia

Insomnia is the most prevalent sleep disorder and can be associated with numerous adverse effects on function, health, and quality of life. (10,11) The American Academy of Sleep Medicine and the American College of Physicians created clinical guidelines for the management (psychological/behavioral and pharmacological).(10,11,15) The guidelines indicate psychological/behavioral interventions are first line and as effective as pharmacologic therapies. Initial approaches to treatment should include at least one behavioral intervention such as stimulus control therapy or relaxation therapy, or the combination of cognitive therapy, stimulus control therapy, sleep restriction therapy with or without relaxation therapy—otherwise known as cognitive behavioral therapy for insomnia (CBT-I). Short-term hypnotic therapy should be supplemented with behavioral and cognitive therapies.(10,15)

The guidelines recommend these general sequence of medication trials for patients with primary insomnia:(15)

Short-intermediate acting benzodiazepine receptor agonists (BZD or newer BzRAs) or ramelteon: examples of these medications include zolpidem, eszopiclone, zaleplon, and temazepam
Alternate short-intermediate acting BzRAs or ramelteon if the initial agent has been unsuccessful
Sedating antidepressants, especially when used in conjunction with treating comorbid depression/anxiety: examples of these include trazodone, amitriptyline, doxepin, and mirtazapine
Combined BzRA or ramelteon and sedating antidepressant
Other sedating agents: examples include anti-epilepsy medications (gabapentin, tiagabine) and atypical antipsychotics (quetiapine and olanzapine)

The guidelines also provide recommendations regarding the management of chronic insomnia with all prescription medications:(15)

Pharmacological treatment should be accompanied by patient education regarding:
1. treatment goals and expectations
2. safety concerns
3. potential side effects and drug interactions
4. other treatment modalities (cognitive and behavioral treatments)
5. potential for dosage escalation
6. rebound insomnia
Patients should be followed on a regular basis, every few weeks in the initial period of treatment when possible, to assess for effectiveness, possible side effects, and the need for ongoing medication.
Efforts should be made to employ the lowest effective maintenance dosage of medication and to taper medication when conditions allow.
- Medication tapering and discontinuation are facilitated by cognitive behavioral therapy for insomnia.
Chronic hypnotic medication may be indicated for long-term use in those with severe or refractory insomnia or chronic comorbid illness. Whenever possible, patients should receive an adequate trial of cognitive behavioral treatment during long-term pharmacotherapy.
- Long-term prescribing should be accompanied by consistent follow-up, ongoing assessment of effectiveness, monitoring for adverse effects, and evaluation for new onset or exacerbation of existing comorbid disorders
- Long-term administration may be nightly, intermittent (e.g., three nights per week), or as needed.

Over-the-counter antihistamine or antihistamine/analgesic type drugs (OTC “sleep aids”) as well as herbal and nutritional substances (e.g., valerian and melatonin) are not recommended in the treatment of chronic insomnia due to the relative lack of efficacy and safety data.(15)

Safety(1-9,13,14)

Ambien, Ambien CR, Edluar, Intermezzo, and Zolpimist are contraindicated in the following:

Patient who have experienced complex sleep behaviors taking zolpidem
Known hypersensitivity to zolpidem

Belsomra, Dayvigo, and Quviviq are contraindicated in patients with narcolepsy

Lunesta is contraindicated in the following:

Patient who have experienced complex sleep behaviors taking eszopiclone
Known hypersensitivity to eszopiclone

Rozerem is contraindicated in the following:

Patient who develop angioedema after treatment with ramelteon
In combination with fluvoxamine

Silenor is contraindication in the following:

Known hypersensitivity to doxepin, any of the inactive ingredients, or other dibenzoxepines
Coadministration or use within the past 14 days with a monoamine oxidase inhibitor (MAOI)
In patients with untreated narrow angle glaucoma or severe urinary retention

Use in the Elderly

Zolpidem, zaleplon, and eszopiclone are all included in the list of Potentially Inappropriate Medications (for use in the elderly) in the Beers List published by the American Geriatrics Society.(12) Benzodiazepine-receptor agonist hypnotics (i.e., Z drugs) have adverse events similar to those of benzodiazepines in older adults (e.g., delirium, falls, fractures); increased emergency room visits and hospitalizations; motor vehicle crashes; minimal improvement in sleep latency and duration. Beers provides a strong recommendation that these drugs be avoided in the elderly.(12)

REFERENCES

Number	Reference
1	Ambien CR prescribing information. Sanofi-Aventis U.S. LLC. February 2022.
2	Ambien prescribing information. Sanofi-Aventis U.S. LLC. February 2022.
3	Belsomra prescribing information. Merck & Co., Inc. May 2022.
4	Edluar prescribing information. Meda Pharmaceuticals Inc. August 2019.
5	Intermezzo prescribing information. Transcept Pharmaceuticals, Inc. August 2019.
6	Lunesta prescribing information. Sunovian Pharmaceuticals, Inc. August 2019.
7	Rozerem prescribing information. Takeda Pharmaceuticals America, Inc. November 2021.
8	Silenor prescribing information. Pernix Therapeutics, Inc. October 2020.
9	Zolpimist prescribing information. Magna Pharmaceuticals. August 2019.
10	Qaseem A, Kansagara D, Forciea MA, Cooke M, Denberg TD, for the Clinical Guidelines Committee of the American College of Physicians. Management of Chronic Insomnia Disorder in Adults: A Clinical Practice Guideline From the American College of Physicians. Ann Intern Med. 2016;165:125-133. doi: 10.7326/M15-2175
11	Sateia, Michael J, MD, et al. Clinical Practice Guidelines for the Pharmacologic Treatment of Chronic Insomnia in Adults: An American Academy of Sleep Medicine Clinical Practice Guideline. Journal of Clinical Sleep Medicine. 2017. 13 (2): 307-349.
12	American Geriatrics Society 2019 Updated Beers Criteria for Potentially Inappropriate Medication Use in Older Adults. J Am Geriatr Soc 2019:1-21.
13	Dayvigo prescribing information. Eisai Inc. June 2022.
14	Quviviq prescribing information. Idorsia Pharmaceuticals LTD. October 2022.
15	Schutte-Rodin S, Broch L, Buysse D, et al. Clinical guideline for the evaluation and management of chronic insomnia in adults. J Clin Sleep Med. 2008;4(5): 487-504.

POLICY AGENT SUMMARY QUANTITY LIMIT

Target Brand Agent Name(s)	Target Generic Agent Name(s)	Strength	QL Amount	Dose Form	Day Supply	Duration	Addtl QL Info	Allowed Exceptions	Targeted NDCs When Exclusions Exist

	zaleplon cap	10 MG ; 5 MG	30	Capsules	30	DAYS
	Zolpidem Tartrate SL Tab 1.75 MG	1.75 MG	30	Tablets	30	DAYS
	Zolpidem Tartrate SL Tab 3.5 MG	3.5 MG	30	Tablets	30	DAYS
Ambien	zolpidem tartrate tab	10 ; 10 MG ; 5 MG	30	Tablets	30	DAYS
Ambien cr	zolpidem tartrate tab er	12.5 MG ; 6.25 MG	30	Tablets	30	DAYS
Belsomra	suvorexant tab	10 MG ; 15 MG ; 20 MG ; 5 MG	30	Tablets	30	DAYS
Dayvigo	lemborexant tab	10 MG ; 5 MG	30	Tablets	30	DAYS
Edluar	Zolpidem Tartrate SL Tab 10 MG	10 MG	30	Tablets	30	DAYS
Edluar	Zolpidem Tartrate SL Tab 5 MG	5 MG	30	Tablets	30	DAYS
Lunesta	Eszopiclone Tab ; eszopiclone tab	1 MG ; 2 ; 2 MG ; 3 ; 3 MG	30	Tablets	30	DAYS
Quviviq	daridorexant hcl tab	25 MG ; 50 MG	30	Tablets	30	DAYS
Rozerem	ramelteon tab	8 MG	30	Tablets	30	DAYS
Silenor	doxepin hcl (sleep) tab	3 MG ; 6 MG	30	Tablets	30	DAYS
Zolpimist	zolpidem tartrate oral spray	5 MG/ACT	1	Inhaler	30	DAYS

CLIENT SUMMARY – QUANTITY LIMITS

Target Brand Agent Name(s)	Target Generic Agent Name(s)	Strength	Client Formulary
	zaleplon cap	10 MG ; 5 MG	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx
	Zolpidem Tartrate SL Tab 1.75 MG	1.75 MG	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx
	Zolpidem Tartrate SL Tab 3.5 MG	3.5 MG	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx
Ambien	zolpidem tartrate tab	10 ; 10 MG ; 5 MG	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx
Ambien cr	zolpidem tartrate tab er	12.5 MG ; 6.25 MG	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx
Belsomra	suvorexant tab	10 MG ; 15 MG ; 20 MG ; 5 MG	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx
Dayvigo	lemborexant tab	10 MG ; 5 MG	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx
Edluar	Zolpidem Tartrate SL Tab 10 MG	10 MG	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx
Edluar	Zolpidem Tartrate SL Tab 5 MG	5 MG	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx
Lunesta	Eszopiclone Tab ; eszopiclone tab	1 MG ; 2 ; 2 MG ; 3 ; 3 MG	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx
Quviviq	daridorexant hcl tab	25 MG ; 50 MG	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx
Rozerem	ramelteon tab	8 MG	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx
Silenor	doxepin hcl (sleep) tab	3 MG ; 6 MG	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx
Zolpimist	zolpidem tartrate oral spray	5 MG/ACT	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

QUANTITY LIMIT CLINICAL CRITERIA FOR APPROVAL

Module	Clinical Criteria for Approval
	Quantity Limit for the Target Agent(s) will be approved when ONE of the following is met: The requested quantity (dose) does NOT exceed the program quantity limit OR The requested quantity (dose) is greater than the program quantity limit AND ONE of the following: BOTH of the following: The requested agent does NOT have a maximum FDA labeled dose for the requested indication AND Information has been provided to support therapy with a higher dose for the requested indication OR BOTH of the following: The requested quantity (dose) does NOT exceed the maximum FDA labeled dose for the requested indication AND Information has been provided to support why the requested quantity (dose) cannot be achieved with a lower quantity of a higher strength that does NOT exceed the program quantity limit OR BOTH of the following: The requested quantity (dose) is greater than the maximum FDA labeled dose for the requested indication AND Information has been provided to support therapy with a higher dose for the requested indication Length of Approval: up to 12 months

Module

Clinical Criteria for Approval

Quantity Limit for the Target Agent(s) will be approved when ONE of the following is met:

The requested quantity (dose) does NOT exceed the program quantity limit OR
The requested quantity (dose) is greater than the program quantity limit AND ONE of the following:
1. BOTH of the following:
  1. The requested agent does NOT have a maximum FDA labeled dose for the requested indication AND
  2. Information has been provided to support therapy with a higher dose for the requested indication OR
2. BOTH of the following:
  1. The requested quantity (dose) does NOT exceed the maximum FDA labeled dose for the requested indication AND
  2. Information has been provided to support why the requested quantity (dose) cannot be achieved with a lower quantity of a higher strength that does NOT exceed the program quantity limit OR
3. BOTH of the following:
  1. The requested quantity (dose) is greater than the maximum FDA labeled dose for the requested indication AND
  2. Information has been provided to support therapy with a higher dose for the requested indication

Length of Approval: up to 12 months

This pharmacy policy is not an authorization, certification, explanation of benefits or a contract. Eligibility and benefits are determined on a case-by-case basis according to the terms of the member’s plan in effect as of the date services are rendered. All pharmacy policies are based on (i) information in FDA approved package inserts (and black box warning, alerts, or other information disseminated by the FDA as applicable); (ii) research of current medical and pharmacy literature; and/or (iii) review of common medical practices in the treatment and diagnosis of disease as of the date hereof. Physicians and other providers are solely responsible for all aspects of medical care and treatment, including the type, quality, and levels of care and treatment.

The purpose of Blue Cross and Blue Shield of Alabama’s pharmacy policies are to provide a guide to coverage. Pharmacy policies are not intended to dictate to physicians how to practice medicine. Physicians should exercise their medical judgment in providing the care they feel is most appropriate for their patients.

Neither this policy, nor the successful adjudication of a pharmacy claim, is guarantee of payment.

Commercial _ PS _ Insomnia Agents Quantity Limit _ProgSum_ 7/1/2023