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Eszopiclone


General


Pronunciation

(es zoe PIK lone)


Brand Names: U.S.

  • Lunesta

Indications


Use: Labeled Indications

Insomnia: Treatment of insomnia


Contraindications


Hypersensitivity to eszopiclone or any component of the formulation.


Dosing and Administration


Dosing: Adult

Insomnia: Oral: Note: The lowest effective dose should be used.

Initial: 1 mg immediately before bedtime; dosing may be increased to 2 mg or 3 mg if clinically necessary (maximum dose: 3 mg daily)

Debilitated patients: Initial: 1 mg immediately before bedtime (maximum dose: 2 mg)

Concurrent use with strong CYP3A4 inhibitor: Initial: 1 mg immediately before bedtime (maximum dose: 2 mg)


Dosing: Geriatric

Initial: 1 mg immediately before bedtime (maximum dose: 2 mg)


Dosing: Renal Impairment

No dosage adjustment necessary.


Dosing: Hepatic Impairment

Mild to moderate impairment: No dosage adjustment necessary.

Severe impairment: Initial: 1 mg immediately before bedtime (maximum dose: 2 mg); use with caution; systemic exposure is doubled in severe impairment.


Administration

Because of the rapid onset of action, eszopiclone should be administered immediately prior to bedtime or after the patient has gone to bed and is having difficulty falling asleep. Do not take with, or immediately following, a high-fat meal (may delay onset).


Dietary Considerations

Avoid taking after a heavy meal; may delay onset.


Storage

Store at 25 ‚ °C (77 ‚ °F); excursions permitted to 15 ‚ °C to 30 ‚ °C (59 ‚ °F to 86 ‚ °F).


Dosage Forms/Strengths


Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Lunesta: 1 mg [contains fd&c blue #2 (indigotine)]

Lunesta: 2 mg

Lunesta: 3 mg [contains fd&c blue #2 (indigotine)]

Generic: 1 mg, 2 mg, 3 mg


Drug Interactions

Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Monitor therapy

Aprepitant: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Azelastine (Nasal): CNS Depressants may enhance the CNS depressant effect of Azelastine (Nasal). Avoid combination

Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Consider therapy modification

Bosentan: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Buprenorphine: CNS Depressants may enhance the CNS depressant effect of Buprenorphine. Management: Consider reduced doses of other CNS depressants, and avoiding such drugs in patients at high risk of buprenorphine overuse/self-injection. Initiate buprenorphine patches (Butrans brand) at 5 mcg/hr in adults when used with other CNS depressants. Consider therapy modification

Cannabis: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Monitor therapy

Conivaptan: May increase the serum concentration of CYP3A4 Substrates. Avoid combination

CYP3A4 Inducers (Moderate): May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates. Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification

CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates. Monitor therapy

CYP3A4 Inhibitors (Strong): May increase the serum concentration of Eszopiclone. Management: Limit the eszopiclone dose to 2 mg daily when combined with strong CYP3A4 inhibitors and monitor for increased eszopiclone effects and toxicities (eg, somnolence, drowsiness, CNS depression). Consider therapy modification

Dabrafenib: May decrease the serum concentration of CYP3A4 Substrates. Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Consider therapy modification

Dasatinib: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Deferasirox: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

Dimethindene: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Doxylamine: May enhance the CNS depressant effect of CNS Depressants. Management: The manufacturer of Diclegis (doxylamine/pyridoxine), intended for use in pregnancy, specifically states that use with other CNS depressants is not recommended. Monitor therapy

Dronabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Droperidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (e.g., opioids, barbiturates) with concomitant use. Consider therapy modification

Enzalutamide: May decrease the serum concentration of CYP3A4 Substrates. Management: Concurrent use of enzalutamide with CYP3A4 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP3A4 substrate should be performed with caution and close monitoring. Consider therapy modification

Flumazenil: May diminish the sedative effect of Hypnotics (Nonbenzodiazepine). Monitor therapy

Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Consider therapy modification

Fosaprepitant: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates. Avoid combination

HYDROcodone: CNS Depressants may enhance the CNS depressant effect of HYDROcodone. Management: Consider starting with a 20% to 30% lower hydrocodone dose when using together with any other CNS depressant. Dose reductions in the other CNS depressant may also be warranted. Consider therapy modification

HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Idelalisib: May increase the serum concentration of CYP3A4 Substrates. Avoid combination

Ivacaftor: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Kava Kava: May enhance the adverse/toxic effect of CNS Depressants. Monitor therapy

Luliconazole: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Methotrimeprazine: CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce adult dose of CNS depressant agents by 50% with initiation of concomitant methotrimeprazine therapy. Further CNS depressant dosage adjustments should be initiated only after clinically effective methotrimeprazine dose is established. Consider therapy modification

MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Monitor therapy

MiFEPRIStone: May increase the serum concentration of CYP3A4 Substrates. Management: Minimize doses of CYP3A4 substrates, and monitor for increased concentrations/toxicity, during and 2 weeks following treatment with mifepristone. Avoid cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, and tacrolimus. Consider therapy modification

Minocycline: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Mirtazapine: CNS Depressants may enhance the CNS depressant effect of Mirtazapine. Monitor therapy

Mitotane: May decrease the serum concentration of CYP3A4 Substrates. Management: Doses of CYP3A4 substrates may need to be adjusted substantially when used in patients being treated with mitotane. Consider therapy modification

Nabilone: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Netupitant: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Avoid combination

Osimertinib: May increase the serum concentration of CYP3A4 Substrates. Osimertinib may decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

OxyCODONE: CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: When oxycodone is combined with another CNS depressant, a dose reduction of one or both agents should be considered. The extended release oxycodone starting dose should be reduced 50% to 67% when initiated in patients already receiving CNS depressants. Consider therapy modification

Palbociclib: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Avoid combination

Perampanel: May enhance the CNS depressant effect of CNS Depressants. Management: Patients taking perampanel with any other drug that has CNS depressant activities should avoid complex and high-risk activities, particularly those such as driving that require alertness and coordination, until they have experience using the combination. Consider therapy modification

Piribedil [INT]: CNS Depressants may enhance the CNS depressant effect of Piribedil [INT]. Monitor therapy

Pramipexole: CNS Depressants may enhance the sedative effect of Pramipexole. Monitor therapy

ROPINIRole: CNS Depressants may enhance the sedative effect of ROPINIRole. Monitor therapy

Rotigotine: CNS Depressants may enhance the sedative effect of Rotigotine. Monitor therapy

Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Monitor therapy

Selective Serotonin Reuptake Inhibitors: CNS Depressants may enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced. Monitor therapy

Siltuximab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

Simeprevir: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Sodium Oxybate: Hypnotics (Nonbenzodiazepine) may enhance the CNS depressant effect of Sodium Oxybate. Avoid combination

St Johns Wort: May decrease the serum concentration of CYP3A4 Substrates. Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification

Stiripentol: May increase the serum concentration of CYP3A4 Substrates. Management: Use of stiripentol with CYP3A4 substrates that are considered to have a narrow therapeutic index should be avoided due to the increased risk for adverse effects and toxicity. Any CYP3A4 substrate used with stiripentol requires closer monitoring. Consider therapy modification

Suvorexant: CNS Depressants may enhance the CNS depressant effect of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. Consider therapy modification

Tapentadol: May enhance the CNS depressant effect of CNS Depressants. Management: Start tapentadol at a dose of one-third to one-half of the normal dose if being initiated in a patient who is taking another drug with CNS depressant effects. Monitor closely for evidence of excessive CNS depression. Consider therapy modification

Tetrahydrocannabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Avoid combination

Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

Trimeprazine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Zolpidem: CNS Depressants may enhance the CNS depressant effect of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. Consider therapy modification


Adverse Reactions


>10%:

Central nervous system: Headache (15% to 21%)

Gastrointestinal: Dysgeusia (8% to 34%)

1% to 10%:

Cardiovascular: Chest pain ( ≥1%), peripheral edema ( ≥1%)

Central nervous system: Drowsiness (8% to 10%), dizziness (5% to 7%), pain (4% to 5%), nervousness ( ≤5%), depression (1% to 4%), confusion ( ≤3%), neuralgia ( ≤3%), abnormal dreams (1% to 3%), anxiety (1% to 3%), hallucination (1% to 3%), migraine

Dermatologic: Skin rash (3% to 4%), pruritus (1% to 4%)

Endocrine & metabolic: Decreased libido ( ≤3%), gynecomastia ( ≤3%)

Gastrointestinal: Xerostomia (3% to 7%), dyspepsia (2% to 6%), nausea (4% to 5%), diarrhea (2% to 4%), vomiting ( ≤3%)

Genitourinary: Dysmenorrhea ( ≤3%), urinary tract infection ( ≤3%)

Infection: Infection (5% to 10%), viral infection (3%)

Miscellaneous: Accidental injury ( ≤3%)

<1% (Limited to important or life-threatening): Abnormality in thinking, alopecia, amenorrhea, anaphylaxis, anemia, angioedema, anorexia, aphthous stomatitis, asthma, ataxia, blepharoptosis, breast hypertrophy, breast neoplasm, bronchitis, bursitis, cholelithiasis, colitis, conjunctivitis, contact dermatitis, cystitis, dehydration, dysphagia, dyspnea, emotional lability, epistaxis, erythema multiforme, facial edema, gastric ulcer, gastritis, gout, halitosis, heatstroke, hematuria, hepatitis, hepatomegaly, herpes zoster, hypercholesterolemia, hypermenorrhea, hypersensitivity reaction, hypertension, hypokalemia, hyporeflexia, insomnia, laryngitis, lymphadenopathy, mastalgia, melena, memory impairment, myasthenia, mydriasis, myopathy, neck stiffness, nephrolithiasis, neuritis, neuropathy, nystagmus, oliguria, pyelonephritis, rectal hemorrhage, reflexes decreased, renal pain, skin discoloration, skin photosensitivity, sleep disorder (complex sleep-related behavior, including cooking or eating food, making phone calls, sleep driving), thrombophlebitis, tongue edema, urethritis, urinary incontinence, uterine hemorrhage, vaginal hemorrhage, vaginitis, vesiculobullous dermatitis, vestibular disturbance


Warnings/Precautions


Special Populations: Hepatic Function Impairment

Systemic exposure is doubled in severe hepatic impairment with no change in Cmax or Tmax


Special Populations: Elderly

Subjects ≥65 years of age had a 41% increase in total exposure (AUC) and a 50% increase in elimination half-life.


Warnings/Precautions

Concerns related to adverse effects:

- Abnormal thinking/behavioral changes: Hypnotics/sedatives have been associated with abnormal thinking and behavior changes including decreased inhibition, aggression, bizarre behavior, agitation, hallucinations, and depersonalization. These changes may occur unpredictably and may indicate previously unrecognized psychiatric disorders; evaluate appropriately.

- CNS depression: Daytime function may be impaired in patients taking higher doses (2 mg or 3 mg) even if used as prescribed; patients taking 3 mg must be cautioned about performing tasks which require mental alertness (operating machinery or driving) the day after use. An increased risk of next-day psychomotor impairment may occur if taken with less than a full night of sleep (7 to 8 hours); if a higher than recommended dose is taken; if co-administered with other CNS depressants or other drugs that increase blood concentrations of eszopiclone. Dose adjustment may be necessary if taking concomitant CNS depressants; the use of concomitant sedative-hypnotics at bedtime or in the middle of the night is not recommended.

- Hypersensitivity reactions: Hypersensitivity reactions including anaphylaxis as well as angioedema have been reported, in some cases following initial dosing. Patients who develop severe reactions should not be rechallenged.

- Sleep-related activities: An increased risk for hazardous sleep-related activities such as sleep-driving, cooking and eating food, and making phone calls while asleep has also been noted; amnesia may also occur. The use of alcohol, other CNS depressants, and exceeding the recommended maximum dose may increase the risk of these activities. Discontinue treatment in patients who report any sleep-related episodes.

Disease-related concerns:

- Depression: Use with caution in patients with depression; worsening of depression, including suicidal ideation has been reported with the use of hypnotics. Intentional overdose may be an issue in this population. The minimum dose that will effectively treat the individual patient should be used. Prescriptions should be written for the smallest quantity consistent with good patient care.

- Drug abuse: Use with caution in patients with a history of drug dependence.

- Hepatic impairment: Use with caution in patients with hepatic impairment; dosage adjustment required with severe impairment.

- Respiratory disease: Use with caution in patients with respiratory compromise, COPD or sleep apnea.

Concurrent drug therapy issues:

- Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

- Debilitated/Elderly: Use with caution in debilitated and elderly patients; dose adjustment recommended. Closely monitor for impaired cognitive and/or motor performance, confusion, and potential for falling.

Other warnings/precautions:

- Appropriate use: Symptomatic treatment of insomnia should be initiated only after careful evaluation of potential causes of sleep disturbance. Failure of sleep disturbance to resolve after 7-10 days may indicate psychiatric and/or medical illness.

- Duration of therapy: Tolerance, as assessed by sleep measurement, did not develop over 6 months of use.

- Rapid onset: Because of the rapid onset of action, administer immediately prior to bedtime or after the patient has gone to bed and is having difficulty falling asleep.

- Withdrawal: Abrupt discontinuance or rapid dose decreases may lead to withdrawal symptoms.


Pregnancy Risk Factor

C


Pregnancy Considerations

Adverse effects were observed in animal reproduction studies. Eszopiclone is the S-isomer of the racemic derivative zopiclone. Available data related to zopiclone (not available in the United States) and similar medications note the potential for preterm birth, low birth weight, and/or small for gestational age infants following maternal use. Long-term use of medications in this class is not recommended during pregnancy and a planned discontinuation should be done to prevent rebound insomnia (Okun 2015).


Actions


Pharmacology

May interact with GABA-receptor complexes at binding domains located close to or allosterically coupled to benzodiazepine receptors.


Absorption

Rapid; high-fat/heavy meal may delay absorption


Metabolism

Hepatic via oxidation and demethylation (CYP2E1, 3A4); (S)-N-desmethyl zopiclone metabolite has less activity than parent compound


Excretion

Urine (up to 75%, primarily as metabolites; <10% as parent drug)


Time to Peak

~1 hour


Half-Life Elimination

~6 hours; Elderly ( ≥65 years): ~9 hours


Protein Binding

52% to 59%


Patient and Family Education


Patient Education

- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

- Patient may experience bad taste, dry mouth, headache, common cold symptoms, or fatigue. Have patient report immediately to prescriber signs of depression (suicidal ideation, anxiety, emotional instability, or illogical thinking), behavioral changes, hallucinations, memory impairment, severe dizziness, change in balance, confusion, severe loss of strength and energy, severe vomiting, or severe nausea (HCAHPS).

- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

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