INSOMNIA MEDICATIONS









Eszopiclone (Lunesta®)

Dosage forms

Tablet
  • 1 mg
  • 2 mg
  • 3 mg

Dosing

Insomnia
  • Starting: 1 mg at bedtime
  • Maintenance: 1 - 3 mg at bedtime
  • Elderly patients: do not exceed 2 mg
  • When taken with CYP3A4 strong inhibitors, do not exceed 2 mg

Generic / Price

- YES/$

Other

  • Eszopiclone is a CIV controlled substance
  • High fat meals slow absorption and may decrease effect
  • Abuse and dependence may occur in susceptible patients

Pharmacokinetics

  • Peak concentration: 1 hour
  • Half-life: 6 hours

Mechanism of action

  • Exact mechanism is not known
  • Eszopiclone interacts with GABA-receptor complexes at binding domains located close to or allosterically coupled to benzodiazepine receptors

FDA-approved indications

  • Insomnia - In controlled outpatient and sleep laboratory studies, eszopiclone 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

Side effects



Side effect Eszopiclone Placebo
Unpleasant taste 17% (2 mg dose)
34% (3 mg dose)
3%
Headache 21% 13%
Somnolence 10% 3%
Dry mouth 5% 3%
Nervousness 5% 3%
Respiratory infection 5% 3%
Depression 4% 0%
Painful menses 3% 0%
Gynecomastia 3% 0%
Anxiety 3% 0%
Vomiting 3% 1%
Rash 3% 1%


Drug interactions

  • CYP3A4 inducers and inhibitors - eszopiclone is a CYP3A4 sensitive substrate. CYP3A4 inhibitors and inducers may affect eszopiclone levels. The dose of eszopiclone should not exceed 2 mg when taken with CYP3A4 strong inhibitors.
  • CNS active drugs - medications that have central nervous system activity may interact with eszopiclone. Use caution.

Contraindications / Precautions

  • Angioedema - rare cases of angioedema have occurred with eszopiclone
  • Compromised respiratory function - use caution
  • Abnormal thinking and behavioral changes - a wide range of psychiatric side effects have been reported by patients taking eszopiclone. These effects are generally rare.
  • Withdrawal side effects - anxiety, abnormal dreams, nausea, and upset stomach may occur in patients who stop eszopiclone abruptly. Withdrawal side effects are rare (< 2% of patients).
  • Decreased mental alertness - eszopiclone should not be taken before activities that require mental alertness (ex. driving)
  • Worsening depression - worsening of depression may occur in some patients
  • Liver disease
    • Mild-moderate (Child-Pugh A/B) - no dose adjustment necessary
    • Severe (Child-Pugh C) - do not exceed 2 mg
  • Kidney disease - no dose adjustment is necessary

Ramelteon (Rozerem®)

Dosage forms

Tablet
  • 8 mg tablet

Dosing

Insomnia
  • Dosing: 8 mg within 30 minutes of going to bed
  • Max: 8 mg a day

Generic / Price

- YES/$$

Other

  • A high-fat meal may slow absorption and decrease effect
  • Do not take immediately after a high-fat meal

Pharmacokinetics

  • Peak concentration: 45 minutes
  • Half-life (ramelteon): 1 - 2.6 hours
  • Half-life (major metabolite): 2 - 5 hours

Mechanism of action

  • Ramelteon is a melatonin receptor agonist with both high affinity for melatonin MT₁ and MT₂ receptors and selectivity over the MT₃ receptor
  • The activity of ramelteon at the MT₁ and MT₂ receptors is believed to contribute to its sleep-promoting properties, as these receptors, acted upon by endogenous melatonin, are thought to be involved in the maintenance of the circadian rhythm underlying the normal sleep-wake cycle

FDA-approved indications

  • Insomnia - ramelteon is indicated for the treatment of insomnia characterized by difficulty with sleep onset
  • The clinical trials performed in support of efficacy were up to 6 months in duration

Side effects



Side effect Ramelteon Placebo
Dizziness 4% 3%
Somnolence 3% 2%
Fatigue 3% 2%
Nausea 3% 2%
Insomnia exacerbated 3% 2%


Drug interactions

  • Fluvoxamine - DO NOT COMBINE
  • CYP1A2 inducers and inhibitors - ramelteon is a CYP1A2 sensitive substrate. CYP1A2 inhibitors and inducers may affect ramelteon levels. Use caution.
  • CYP3A4 strong inhibitors - ramelteon is a minor CYP3A4 substrate. CYP3A4 strong inhibitors may affect ramelteon levels. Use caution.
  • CYP2C9 strong inhibitors - ramelteon is a minor CYP2C9 substrate. CYP2C9 strong inhibitors may affect ramelteon levels. Use caution.
  • CNS active drugs - medications that have central nervous system activity may interact with ramelteon. Use caution.

Contraindications / Precautions

  • Severe liver disease - DO NOT USE
  • Severe sleep apnea - not recommended
  • Compromised respiratory function - use caution
  • Increased prolactin levels - ramelteon can raise prolactin levels. In one study, ramelteon 16 mg a day raised prolactin levels in women by an average of 4.9 mcg/L.
  • Decreased testosterone levels - ramelteon can lower testosterone levels. This effect is not well-defined.
  • Angioedema - rare cases of angioedema have occurred with ramelteon
  • Abnormal thinking and behavioral changes - a wide range of psychiatric side effects have been reported by patients taking ramelteon. These effects are generally rare.
  • Decreased mental alertness - ramelteon should not be taken before activities that require mental alertness (ex. driving)
  • Worsening depression - worsening of depression may occur in some patients
  • Liver disease
    • Mild-moderate (Child-Pugh A/B) - use caution
    • Severe (Child-Pugh C) - DO NOT USE
  • Kidney disease - no dose adjustment is necessary

Suvorexant (Belsomra®)

Dosage forms

Tablet
  • 5 mg
  • 10 mg
  • 15 mg
  • 20 mg

Dosing

Insomnia
  • Starting: 10 mg at bedtime
  • Maintenance: 10 - 20 mg at bedtime
  • Maximum dose: 20 mg at bedtime
  • Take within 30 minutes of going to bed
  • When taken with CYP3A4 moderate inhibitors, starting dose is 5 mg. Do not exceed 10 mg.
  • Do not take with CYP3A4 strong inhibitors
  • Exposure is increased in obese patients and women. Use caution in obese women

Generic / Price

- NO/$$$$

Other

  • Belsomra® is a CIV controlled substance
  • Time to effect may be delayed if taken with or soon after a meal
  • Only take with at least 7 hours remaining before the planned time of awakening

Pharmacokinetics

  • Peak concentration: 2 hours
  • Half-life: 12 hours

Mechanism of action

  • The mechanism by which suvorexant exerts its therapeutic effect in insomnia is presumed to be through antagonism of orexin receptors
  • The orexin neuropeptide signaling system is a central promoter of wakefulness
  • Blocking the binding of wake-promoting neuropeptides orexin A and orexin B to receptors OX1R and OX2R is thought to suppress wake drive

FDA-approved indications

  • Insomnia - characterized by difficulties with sleep onset and/or sleep maintenance

Side effects



Side effect Suvorexant Placebo
Headache 7% 6%
Somnolence 7% 3%
Dizziness 3% 2%
Abnormal dreams 2% 1%


Drug interactions

  • CYP3A4 strong inhibitors - DO NOT COMBINE
  • CYP3A4 moderate inhibitors - starting dose should be 5 mg when taken with CYP3A4 moderate inhibitors. Do not exceed 10 mg a day.
  • CYP3A4 strong inducers - suvorexant blood levels may be decreased
  • P-glycoprotein substrates - in vitro studies show that suvorexant is a p-glycoprotein inhibitor. Suvorexant may affect levels of p-glycoprotein substrates.
  • Digoxin - may increase digoxin levels
  • CNS active drugs - medications that have central nervous system activity may interact with suvorexant. Use caution.

Contraindications / Precautions

  • CYP3A4 strong inhibitors - DO NOT COMBINE
  • Narcolepsy - DO NOT USE
  • Obese patients - exposure to suvorexant is increased compared to non-obese
  • Women - exposure to suvorexant is increased compared to men
  • Impairment of daytime wakefulness - suvorexant can impair daytime wakefulness even when used as prescribed. Elderly patients are at greater risk.
  • Decreased mental alertness - suvorexant should not be taken before activities that require mental alertness (ex. driving)
  • Cataplexy/sleep paralysis - weakness or inability to move during transition from sleep to wakefulness has been reported in some patients
  • Abnormal thinking and behavioral changes - a wide range of psychiatric side effects have been reported by patients taking suvorexant. These effects are generally rare.
  • Amnesia - cases of amnesia and not remembering complex behaviors such as driving have been reported with hypnotics like suvorexant. Discontinue suvorexant if patients report such events.
  • Worsening depression - worsening of depression may occur in some patients
  • Compromised respiratory function - has not been studied; use caution
  • Severe sleep apnea - has not been studied; use caution
  • Liver disease
    • Mild-moderate (Child-Pugh A/B) - no dose adjustment necessary
    • Severe (Child-Pugh C) - has not been studied, not recommended
  • Kidney disease - no dose adjustment is necessary

Zaleplon (Sonata®)

Dosage forms

Capsule
  • 5 mg
  • 10 mg

Dosing

Insomnia
  • Starting: 10 mg at bedtime
  • Maintenance: 10 - 20 mg at bedtime
  • Max: 20 mg at bedtime
  • Elderly patients: starting dose should be 5 mg. Do not exceed 10 mg.
  • Low weight individuals may want to start with 5 mg
  • A high-fat meal may slow absorption and decrease effect
  • Do not take immediately after a high-fat meal

Generic / Price

- YES/$

Other

  • Zaleplon is a CIV controlled substance
  • Abuse and dependence may occur in susceptible patients

Pharmacokinetics

  • Peak concentration: 1 hour
  • Half-life: 1 hour

Mechanism of action

  • Zaleplon interacts with the gamma-aminobutyric acid-benzodiazepine (GABA-BZ) receptor complex
  • Subunit modulation of the GABA-BZ receptor chloride channel macromolecular complex is hypothesized to be responsible for some of the pharmacological properties of benzodiazepines, which include sedative, anxiolytic, muscle relaxant, and anticonvulsant effects in animal models

FDA-approved indications

  • Insomnia - zaleplon is indicated for the short-term treatment of insomnia
  • Zaleplon has 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

Side effects



Side effect Zaleplon Placebo
Abdominal pain 6% 3%
Somnolence 5% 4%
Eye pain 4% 2%
Paresthesia 3% 1%
Painful menses 3% 2%
Amnesia 2% 1%
Tremor 2% 1%


Drug interactions

  • Cimetidine - cimetidine inhibits aldehyde oxidase and CYP3A4. Zaleplon is a substrate for both of these enzymes. Cimetidine may increase zaleplon levels. Initial zaleplon dose should be 5 mg when given with cimetidine.
  • Promethazine - promethazine may decrease zaleplon levels
  • Aldehyde oxidase inhibitors - aldehyde oxidase is the primary enzyme that metabolizes zaleplon. Aldehyde oxidase and its inducers/inhibitors/substrates have not been studied extensively.
  • CYP3A4 strong inhibitors and inducers - zaleplon is a minor CYP3A4 substrate. CYP3A4 strong inhibitors and inducers may affect zaleplon levels. Use caution.
  • CNS active drugs - medications that have central nervous system activity may interact with zaleplon. Use caution.

Contraindications / Precautions

  • Severe liver disease - DO NOT USE
  • Compromised respiratory function - use caution
  • Angioedema - rare cases of angioedema have occurred with zaleplon
  • Abnormal thinking and behavioral changes - a wide range of psychiatric side effects have been reported by patients taking zaleplon. These effects are generally rare.
  • Decreased mental alertness - zaleplon should not be taken before activities that require mental alertness (ex. driving)
  • Worsening depression - worsening of depression may occur in some patients
  • Liver disease
    • Mild-moderate (Child-Pugh A/B) - use 5 mg dose
    • Severe (Child-Pugh C) - DO NOT USE
  • Kidney disease
    • Mild-moderate (CrCl > 30 ml/min) - no dose adjustment is necessary
    • Severe (CrCl < 30 ml/min) - has not been studied

Zolpidem | Ambien® | Ambien CR® | Edluar® | Intermezzo® | Zolpimist®

Dosage forms

Tablet (Ambien®)
  • 5 mg
  • 10 mg
Tablet, extended-release (Ambien CR®)
  • 6.25 mg
  • 12.5 mg
Sublingual tablet (Edluar®)
  • 5 mg
  • 10 mg
Sublingual tablet (Intermezzo®)
  • 1.75 mg
  • 3.5 mg
Oral spray (Zolpimist®)
  • 5 mg per spray

Dosing - insomnia

Ambien®, Edluar®, and Zolpimist®
  • Starting (women): 5 mg at bedtime
  • Starting (men): 5 - 10 mg at bedtime
  • Starting (elderly and liver disease): 5 mg at bedtime
  • Max dose: 10 mg
  • Only take when at least 7 – 8 hours are remaining before planned awakening
  • Food decreases absorption and may decrease effect
Ambien CR®
  • Starting (women): 6.25 mg at bedtime
  • Starting (men): 6.25 - 12.5 mg at bedtime
  • Starting (elderly and liver disease): 6.25 mg at bedtime
  • Max dose: 12.5 mg
  • Only take when at least 7 – 8 hours are remaining before planned awakening
  • Food decreases absorption and may decrease effect
Intermezzo®
  • Dose (women): 1.75 mg
  • Dose (men): 3.5 mg
  • Dose (elderly and liver disease): 1.75 mg
  • Intermezzo® is to be taken in bed when a patient wakes in the middle of the night and has difficulty returning to sleep
  • Intermezzo® should only be taken if the patient has at least 4 hours of bedtime remaining before the planned time of waking
  • Intermezzo® should only be taken once
  • Food decreases absorption and may decrease effect

Generic / Price

  • Ambien® - YES/$
  • Ambien CR® - YES/$
  • Edluar® - NO/$$$$
  • Intermezzo® - YES/$$
  • Zolpimist® - NO/$$$$

Other

All
  • Zolpidem is a CIV controlled substance
  • Abuse and dependence may occur in susceptible patients
Ambien CR®
  • Do not crush, cut, or chew tablet
Edluar® and Intermezzo®
  • Place under tongue and allow to dissolve
  • Do not swallow tablet or take with water
Zolpimist®
  • Prime before first use with 5 sprays
  • If not used for 14 days, re-prime with 1 spray
  • Spray directly into mouth over tongue

Pharmacokinetics

Ambien
  • Peak concentration: 1.6 hours
  • Half-life: 2.6 hours

Mechanism of action

  • Zolpidem interacts with a GABA-BZ receptor complex and shares some of the pharmacological properties of the benzodiazepines
  • In contrast to the benzodiazepines, which non-selectively bind to and activate all BZ receptor subtypes, zolpidem in vitro binds the BZ₁ receptor preferentially with a high affinity ratio of the α₁/α₅ subunits
  • This selective binding of zolpidem on the BZ₁ receptor is not absolute, but it may explain the relative absence of myorelaxant and anticonvulsant effects in animal studies as well as the preservation of deep sleep (stages 3 and 4) in human studies of zolpidem tartrate at hypnotic doses

FDA-approved indications

Ambien®
  • Insomnia - Ambien® 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
Ambien CR®
  • Insomnia - Ambien CR® is indicated for the 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 24 weeks (using patient-reported assessment in adult patients only) in duration
Edluar®
  • Insomnia - Edluar® is indicated for the short-term treatment of insomnia characterized by difficulties with sleep initiation
  • The clinical trials performed with Edluar® in support of efficacy were 4-5 weeks in duration
Intermezzo®
  • Insomnia - Intermezzo® is indicated for use as needed for the treatment of insomnia when a middle-of-the-night awakening is followed by difficulty returning to sleep
  • Limitations of Use: Intermezzo® is not indicated for the treatment of middle-of-the-night insomnia when the patient has fewer than 4 hours of bedtime remaining before the planned time of waking
Zolpimist®
  • Insomnia - Zolpimist® is indicated for the short-term treatment of insomnia characterized by difficulties with sleep initiation
  • Zolpimist® has been shown to decrease sleep latency for up to 35 days in controlled clinical studies

Side effects



Side effect Ambien tablet Placebo
Drowsiness 8% 5%
Dizziness 5% 1%
Allergy 4% 1%
Sinusitis 4% 2%
Drugged feeling 3% 0%
Pharyngitis 3% 1%
Lethargy 3% 1%
Dry mouth 3% 1%
Palpitations 2% 0%


Drug interactions

  • CYP3A4 strong inhibitors and inducers - zolpidem is a CYP3A4 substrate. CYP3A4 strong inhibitors and inducers may affect zolpidem levels. Use caution.
  • Ciprofloxacin - ciprofloxacin may inhibit zolpidem metabolism and increase zolpidem blood levels. Concurrent use is not recommended.
  • Imipramine - zolpidem may decrease imipramine levels
  • Sertraline - sertraline may increase zolpidem levels
  • Fluoxetine - fluoxetine may increase the zolpidem half-life
  • Fluvoxamine - fluvoxamine may inhibit zolpidem metabolism and increase zolpidem blood levels
  • CNS active drugs - medications that have central nervous system activity may interact with zolpidem. Use caution.

Contraindications / Precautions

  • Compromised respiratory function - use caution
  • Angioedema - rare cases of angioedema have occurred with zolpidem
  • Abnormal thinking and behavioral changes - a wide range of psychiatric side effects have been reported by patients taking zolpidem. These effects are generally rare.
  • Next-day impairment - next-day psychomotor impairment may occur in the following circumstances: if zolpidem is taken with less than 7 - 8 hours of sleep remaining; if higher than normal doses are taken; if co-administered with other CNS depressants; if co-administered with other drugs that increase the blood levels of zolpidem (CYP3A4 inhibitors)
  • Withdrawal side effects - fatigue, nausea, flushing, lightheadedness, uncontrolled crying, emesis, stomach cramps, panic attack, nervousness, and abdominal discomfort have been reported in patients who stop zolpidem abruptly. Withdrawal side effects are rare (≤ 1% of patients).
  • Decreased mental alertness - zolpidem should not be taken before activities that require mental alertness (ex. driving)
  • Worsening depression - worsening of depression may occur in some patients
  • Hepatic encephalopathy - zolpidem may precipitate hepatic encephalopathy in patients with significant liver disease. Do not use in severe liver disease.
  • Kidney disease - no dose adjustment is necessary
  • Liver disease
    • Mild to moderate (Child-Pugh A/B) - recommended dose is 5 mg once daily (6.25 mg for Ambien CR)
    • Severe (Child-Pugh C) - DO NOT USE






Pricing legend
  • $ = 0 - $50
  • $$ = $51 - $100
  • $$$ = $101 - $150
  • $$$$ = > $151
  • Pricing based on one month of therapy at standard dosing in an adult
  • Pricing based on information from GoodRX.com®
  • Pricing may vary by region and availability