INSOMNIA MEDICATIONS

All dosing is for ADULTS unless otherwise specified
PRICING INFO



Drug Dosage form Dosage Generic/Price Other / Pharmacokinetics Mechanism of Action FDA-approved indications Side Effects Drug Interactions Precautions / Contraindications
Eszopiclone

Lunesta®
Tablet
  • 1 mg
  • 2 mg
  • 3 mg
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
YES/$ Other
  • High fat meals slow absorption and may decrease effect
  • Eszopiclone is a CIV controlled substance
  • Abuse and dependence may occur in susceptible patients

Pharmacokinetics
  • Peak concentration: 1 hour
  • Half-life: 6 hours
  • Exact mechanism is not known

  • Eszopiclone interacts with GABA-receptor complexes at binding domains located close to or allosterically coupled to benzodiazepine receptors
  • 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
NOTE: P = % of patients on placebo who reported side effect

  • Unpleasant taste - 17% (2 mg dose), 34% (3 mg dose), P - 3%
  • Headache - 21%, P - 13%
  • Somnolence - 10%, P - 3%
  • Dry mouth - 5%, P - 3%
  • Nervousness - 5%, P - 3%
  • Respiratory infection - 5%, P - 3%
  • Depression - 4%, P - 0%
  • Painful menses - 3%, P - 0%
  • Gynecomastia - 3%, P - 0%
  • Anxiety - 3%, P - 0%
  • Vomiting - 3%, P - 1%
  • Rash - 3%, P - 1%
  • 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.
  • 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
Drug Dosage form Dosage Generic/Price Other / Pharmacokinetics Mechanism of Action FDA-approved indications Side Effects Drug Interactions Precautions / Contraindications
Ramelteon

Rozerem®
Tablet
  • 8 mg tablet
Insomnia
  • Dosing: 8 mg within 30 minutes of going to bed
  • Max: 8 mg a day
NO/$$$$ 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
  • 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
  • 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
NOTE: P = % of patients on placebo who reported side effect

  • Dizziness - 4%, P - 3%
  • Somnolence - 3%, P - 2%
  • Fatigue - 3%, P - 2%
  • Nausea - 3%, P - 2%
  • Insomnia exacerbated - 3%, P - 2%
  • 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.
  • 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
Drug Dosage form Dosage Generic/Price Other / Pharmacokinetics Mechanism of Action FDA-approved indications Side Effects Drug Interactions Precautions / Contraindications
Suvorexant

Belsomra®
Tablet
  • 5 mg
  • 10 mg
  • 15 mg
  • 20 mg
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
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
  • 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
  • Insomnia - characterized by difficulties with sleep onset and/or sleep maintenance
NOTE: P = % of patients on placebo who reported side effect

  • Headache - 7%, P - 6%
  • Somnolence - 7%, P - 3%
  • Dizziness - 3%, P - 2%
  • Abnormal dreams - 2%, P - 1%
  • CYP3A4 strong inhibitors - DO NOT COMBINE
  • CYP3A4 moderate inhibitors - starting dose should be 5 mg; may increase to 10 mg if tolerated
  • 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.
  • 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
  • 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.
  • 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
Drug Dosage form Dosage Generic/Price Other / Pharmacokinetics Mechanism of Action FDA-approved indications Side Effects Drug Interactions Precautions / Contraindications
Zaleplon

Sonata®
Capsule
  • 5 mg
  • 10 mg
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
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
  • 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
  • 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
NOTE: P = % of patients on placebo who reported side effect

  • Abdominal pain - 6%, P - 3%
  • Somnolence - 5%, P - 4%
  • Eye pain - 4%, P - 2%
  • Paresthesia - 3%, P - 1%
  • Painful menses - 3%, P - 2%
  • Amnesia - 2%, P - 1%
  • Tremor - 2%, P - 1%
  • 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.
  • 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
Drug Dosage form Dosage Generic/Price Other / Pharmacokinetics Mechanism of Action FDA-approved indications Side Effects Drug Interactions Precautions / Contraindications
Zolpidem

Ambien®
Ambien CR®
Edluar®
Intermezzo®
Zolpimist®
Ambien® - tablet
  • 5 mg
  • 10 mg

Ambien CR®
extended-release tablet
  • 6.25 mg
  • 12.5 mg

Edluar®
sublingual tablet
  • 5 mg
  • 10 mg

Intermezzo®
sublingual tablet
  • 1.75 mg
  • 3.5 mg

Zolpimist® - spray
  • 5 mg per spray

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
  • Ambien® - YES/$

  • Ambien CR® - YES/$-$$

  • Edluar® - NO/$$$$

  • Intermezzo® - NO/$$$$

  • Zolpimist® - NO/$$$$
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
  • 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
    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
NOTE: P = % of patients on placebo who reported side effect Only side effects that occurred at an incidence > 1% more than placebo are listed. Data is from Ambien PI.

  • Drowsiness - 8%, P - 5%
  • Dizziness - 5%, P - 1%
  • Allergy - 4%, P - 1%
  • Sinusitis - 4%, P - 2%
  • Drugged feeling - 3%, P - 0%
  • Pharyngitis - 3%, P - 1%
  • Lethargy - 3%, P - 1%
  • Dry mouth - 3%, P - 1%
  • Palpitations - 2%, P - 0%
  • 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.
  • 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