Zopilone

Uses

Zopilone is used for the treatment of insomnia, including difficulty falling asleep and difficulty maintaining sleep through the night. Zopilone is the first sedative approved long-term use.

Zopilone is also used to associated treatment for these conditions: Insomnia

How Zopilone works

The exact mechanism of action of eszopiclone is unknown at this time but is thought to occur via binding with the GABA receptor complexes at binding sites located near benzodiazepine receptors, possibly explaining its hypnotic and sedative effects. It has particular affinity for GABA-A (or GABAA) receptor subunits 1, 3 and 5. Zopilone increases GABA-A channel currents significantly. GABA-A channels are major inhibitory channels that cause CNS depression when their receptors are activated.

Dosage

Zopilone dosage

The usual dose to improve or maintain sleep in most adults is 2 or 3 mg. Persons over the age of 65 years usually are treated with 1 or 2 mg. Zopilone should be taken immediately before going to bed since the onset of sedation may occur as rapidly as 10 minutes. It should be taken only by individuals who intend to sleep for at least 8 hours since its effects may last up to six hours.

Side Effects

Zopilone is generally well tolerated. However few side effects like fatigue, anorexia, nausea, unpleasant taste in the mouth, mood problems, abdominal pain, dyspepsia, asthenia, nervousness, dizziness and confusion have been reported.

Toxicity

The oral LD50 of eszopiclone in rats is 980 mg/kg and 3200 mg/kg in rabbits. Symptoms of overdose may include mental status changes and somnolence, demonstrating general exaggeration of the drug's pharmacological effects. Perform gastric lavage and offer supportive treatment if an overdose is suspected, including intravenous fluids as required. Flumazenil may be used. Vital signs should be closely monitored in addition to patient symptoms. Appropriate medical interventions should be employed. The possibility of an overdose with multiple drugs should be considered. Ensure to contact the local poison control center for the most updated management of hypnotic drug overdose.

Precaution

Zopilone like all sedatives should be taken immediately before bedtime to avoid short-term memory impairment, hallucinations, impaired coordination, dizziness and lightheadedness.

Interaction

Alcohol (which causes sedation) and drugs that have sedating effects should not be used with Zopilone since their sedating effects, when added to those of Zopilone, may cause excessive sedation.

Food Interaction

• Avoid alcohol.
• Do not take with or immediately after a high-fat meal. This decreases the absorption of eszopiclone.

[Moderate] GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of zopiclone and eszopiclone.

Use in combination may result in additive central nervous system depression and
ADJUST DOSING INTERVAL: Administration of eszopiclone (the S-enantiomer of zopiclone) with or immediately after a high-fat

In healthy adults, administration of a 3 mg dose of eszopiclone after a high-fat meal decreased the mean peak plasma drug concentration (Cmax) by 21% and delayed the time to reach peak plasma drug concentration (Tmax) by approximately 1 hour.

Theoretically, this interaction should also affect racemic zopiclone.

MANAGEMENT: Patients receiving zopiclone or eszopiclone should be advised to avoid consumption of alcohol.

For faster sleep onset, eszopiclone and zopiclone should not be administered with or immediately after a high-fat

Zopilone Drug Interaction

Moderate: lorazepam, lorazepam, duloxetine, duloxetine, pregabalin, pregabalin, quetiapine, quetiapine, bupropion, bupropionUnknown: acetaminophen, acetaminophen, levothyroxine, levothyroxine, cyanocobalamin, cyanocobalamin, ascorbic acid, ascorbic acid, cholecalciferol, cholecalciferol

Zopilone Disease Interaction

Major: depressionModerate: glaucoma, liver disease

Volume of Distribution

The volume of distribution of eszopiclone is estimated at 89.9L

Elimination Route

Zopilone is rapidly absorbed and the peak concentration is reached within about 1 hour after oral administration. The mean AUC after a 3 mg dose of eszopiclone was 278 ng/mL × h. The consumption of a high-fat has been shown to slow absorption. Steady-state concentrations of eszopiclone are reached within 24-48 hours.

Half Life

The half-life is 6.1 hours in healthy patients but is prolonged in various patients, including those with hepatic impairment, elderly patients, in addition to those taking CYP3A enzyme inhibiting drugs.

Clearance

The mean clearance of eszopiclone in young, healthy volunteers was 184 mL/min in one pharmacokinetic study.

Elimination Route

Only about 10% of an eszopiclone dose is found excreted in the urine as the parent drug. As much as 75% of an orally administered dose of racemic zopiclone as is found to be excreted in the urine in the form of metabolites. Zopilone, the S-isomer of racemic zopiclone, would likely show the same excretion pattern.

Pregnancy & Breastfeeding use

Pregnancy: Category C. There is no adequate and well-controlled studies in pregnant women. This drug should be used during pregnancy only if clearly needed.

Nursing Mothers: It is not known whether the drug is excreted in breast milk. As many drugs are excreted in breast milk, caution should be exercised when Zopilone is administered to a nursing mother.

Contraindication

Depression, Severe Chronic Obstructive Lung Disease, Severe Liver Disease, Weakened Patient, Having thoughts of Suicide.

Acute Overdose

There is limited clinical experience with the overdose of Zopilone. In clinical trials one case of overdose with up to 36 mg of Zopilone has been reported in which the subject fully recovered. Intravenous fluids should be administered as needed & Flumazenil may be useful.

Storage Condition

Store at 25°C.

Innovators Monograph

You find simplified version here Zopilone