Eszopiclone

Brand names: Lunesta, ESZOPICLONE, Eszopiclone

Boxed warning

WARNING: COMPLEX SLEEP BEHAVIORS WARNING: COMPLEX SLEEP BEHAVIORS Complex sleep behaviors including sleep-walking, sleep-driving, and engaging in other activities while not fully awake may occur following use of eszopiclone tablets. Some of these events may result in serious injuries, including death. Discontinue eszopiclone tablets immediately if a patient experiences a complex sleep behavior [ see Contraindications ( 4 ) and Warnings and Precautions (5.1) ]. See full prescribing information for complete boxed warning. Complex sleep behaviors including sleep-walking, sleep-driving, and engaging in other activities while not fully awake may occur following use of eszopiclone tablets. Some of these events may result in serious injuries, including death. Discontinue eszopiclone tablets immediately if a patient experiences a complex sleep behavior (4, 5.1).

Warnings

BOXED WARNING: "Complex sleep behaviors including sleep-walking, sleep-driving, and engaging in other activities while not fully awake may occur following use of LUNESTA. Some of these events may result in serious injuries, including death." The label further warns of CNS depression (worse with alcohol or other depressants), next-day psychomotor/driving impairment, abnormal thinking and behavioral changes including hallucinations, and the need to prescribe the "smallest quantity feasible" for patients with depression given suicide risk.

Contraindications

4 CONTRAINDICATIONS • Eszopiclone tablets are contraindicated in patients who have experienced complex sleep behaviors after taking eszopiclone tablets [ see Warnings and Precautions ( 5.1 ) ]. • Eszopiclone tablets are contraindicated in patients with known hypersensitivity to eszopiclone. Hypersensitivity reactions include anaphylaxis and angioedema [ see Warnings and Precautions ( 5.3 ) ]. • Patients who have experienced complex sleep behaviors after taking eszopiclone ( 4 ) • Known hypersensitivity to eszopiclone ( 4 )

Overdose

10 OVERDOSAGE In clinical trials with eszopiclone, one case of overdose with up to 36 mg of eszopiclone was reported in which the subject fully recovered. Since commercial marketing began, spontaneous cases of eszopiclone overdoses up to 270 mg (90 times the maximum recommended dose of eszopiclone) have been reported, in which patients have recovered. Fatalities related to eszopiclone overdoses were reported only in combination with other CNS drugs or alcohol. 10.1 Signs and Symptoms Signs and symptoms of overdose effects of CNS depressants can be expected to present as exaggerations of the pharmacological effects noted in preclinical testing. Impairment of consciousness ranging from somnolence to coma has been described. Rare individual instances of fatal outcomes following overdose with racemic zopiclone have been reported in European postmarketing reports, most often associated with overdose with other CNS-depressant agents. Methemoglobinemia in association with overdoses of racemic zopiclone has been reported. 10.2 Recommended Treatment General symptomatic and supportive measures should be used along with immediate gastric lavage where appropriate. Intravenous fluids should be administered as needed. Flumazenil may be useful. As in all cases of drug overdose, respiration, pulse, blood pressure, and other appropriate signs should be monitored and general supportive measures employed. Hypotension and CNS depression should be monitored and treated by appropriate medical intervention. Consider monitoring methemoglobin in the setting of high-dose overdosage. The value of dialysis in the treatment of overdosage has not been determined. As with the management of all overdosage, the possibility of multiple drug ingestion should be considered. The physician may wish to consider contacting a poison control center for up-to-date information on the management of hypnotic drug product overdosage.

Drug interactions

7 DRUG INTERACTIONS • CNS Depressants: Additive CNS-depressant effects with combination use. Use with ethanol causes additive psychomotor impairment ( 7.1 ) • Rifampicin: Combination use may decrease exposure and effects of eszopiclone ( 7.2 ) • Ketoconazole: Combination use increases exposure and effect of eszopiclone. Dose reduction of eszopiclone is needed ( 7.2 ) 7.1 CNS Active Drugs Ethanol: An additive effect on psychomotor performance was seen with coadministration of eszopiclone and ethanol [see Warnings and Precautions ( 5.1 , 5.2 )]. Olanzapine: Coadministration of eszopiclone and olanzapine produced a decrease in DSST scores. The interaction was pharmacodynamic; there was no alteration in the pharmacokinetics of either drug. 7.2 Drugs that Inhibit or Induce CYP3A4 Drugs that Inhibit CYP3A4 (Ketoconazole) CYP3A4 is a major metabolic pathway for elimination of eszopiclone. The exposure of eszopiclone was increased by coadministration of ketoconazole, a potent inhibitor of CYP3A4. Other strong inhibitors of CYP3A4 (e.g., itraconazole, clarithromycin, nefazodone, troleandomycin, ritonavir, nelfinavir) would be expected to behave similarly. Dose reduction of eszopiclone is needed for patient co-administered eszopiclone with potent CYP3A4 inhibitors [see Dosage and Administration ( 2.3 )]. Drugs that Induce CYP3A4 (Rifampicin) Racemic zopiclone exposure was decreased 80% by concomitant use of rifampicin, a potent inducer of CYP3A4. A similar effect would be expected with eszopiclone. Combination use with CYP3A4 inducer may decrease the exposure and effects of eszopiclone.

Uses

"LUNESTA is indicated for the treatment of insomnia," decreasing sleep latency and improving sleep maintenance, as shown in controlled outpatient and sleep laboratory studies.

Dosage forms & strengths

Tablet Tablet, Coated Tablet, Film Coated TABLET, FILM COATED TABLET, COATED POWDER

ESZOPICLONE 1 mg ESZOPICLONE 2 mg ESZOPICLONE 3 mg eszopiclone 2 mg eszopiclone 3 mg ESZOPICLONE 1 mg/1 ESZOPICLONE 2 mg/1 ESZOPICLONE 1 kg/kg ESZOPICLONE 3 mg/1 ESZOPICLONE 15 kg/15kg ESZOPICLONE 100 kg/100kg

2 DOSAGE & ADMINISTRATION Use the lowest effective dose for the patient. · Use the lowest dose effective for the patient ( 2 ) · Recommended initial dose is 1 mg, immediately before bedtime, with at least 7-8 hours remaining before the planned time of awakening. May increase dose if clinically indicated, to a maximum of 3 mg ( 2.1 ) · Geriatric or debilitated patients: Dose should not exceed 2 mg ( 2.2 ) · Patients with severe hepatic impairment, or taking potent CYP3A4 inhibitors: Dose should not exceed 2 mg ( 2.3 ) · Do not take with or immediately after a meal ( 2.5 ) 2.1 Dosage in Adults The recommended starting dose is 1 mg. Dosing can be raised to 2 mg or 3 mg if clinically indicated. In some patients, the higher morning blood levels of eszopiclone tablets following use of the 2 mg or 3 mg dose increase the risk of next day impairment of driving and other activities that require full alertness [ see Warnings and Precautions ( 5.1 ) ]. The total dose of eszopiclone tablets should not exceed 3 mg, once daily immediately before bedtime [ see Warnings and Precautions ( 5.6 ) ]. 2.2 Geriatric or Debilitated Patients The total dose of eszopiclone tablets should not exceed 2 mg in elderly or debilitated patients. 2.3 Patients with Severe Hepatic Impairment, or Taking Potent CYP3A4 Inhibitors In patients with severe hepatic impairment, or in patients coadministered eszopiclone with potent CYP3A4 inhibitors, the total dose of eszopiclone tablets should not exceed 2 mg [ see Warnings and Precautions ( 5.7 ) ]. 2.4 Use with CNS Depressants Dosage adjustments may be necessary when eszopiclone tablets are combined with other central nervous system (CNS) depressant drugs because of the potentially additive effects [see Warnings and Precautions ( 5.1 )]. 2.5 Administration with Food Taking eszopiclone tablets with or immediately after a heavy, high-fat meal results in slower absorption and would be expected to reduce the effect of eszopiclone tablets on sleep latency [see Clinical Pharmacology ( 12.3 )] .