Zaleplon

Uses

Zaleplon is used 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 trials.

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

How Zaleplon works

Zaleplon exerts its action through subunit modulation of the GABA_BZ receptor chloride channel macromolecular complex. Zaleplon also binds selectively to the brain omega-1 receptor located on the alpha subunit of the GABA-A/chloride ion channel receptor complex and potentiates t-butyl-bicyclophosphorothionate (TBPS) binding.

Dosage

Zaleplon dosage

The dose of Zaleplon should be individualized. The recommended dose of Zaleplon for most non elderly adults is 10 mg. For certain low weight individuals, 5 mg may be a sufficient dose. Although the risk of certain adverse events associated with the use of Zaleplon appears to be dose dependent, the 20 mg dose has been shown to be adequately tolerated and may be considered for occasional patient who does not benefit from a trial of lower dose. Dosage above 20 mg has not been adequately evaluated and is not recommended.Zaleplon should be taken immediately before bedtime. Taking Zaleplon with or immediately after a heavy, high fat meal results in slower absorption and would be expected to reduce the effect of Zaleplon on sleep latency. Elderly patients and debilitated patients appear to be more sensitive to the effects of hypnotic, and respond to 5 mg of Zaleplon. The recommended dose for these patients is therefore 5 mg, doses over 10 mg are not recommended. For patients with mild to moderate renal impairment no dose adjustment is necessary.An initial dose of 5 mg should be given to patients concomitantly taking Cimetidine because ZalZaleplon clearance is reduced in this population.

Side Effects

Side effects of Zaleplon appear to be dose related. So, it is important to use the lowest possible effective dose, specially in the elderly. The side effects are usually mild and transient, the most common are diarrhoea, nausea, vomiting, vertigo, headache, asthenia, nightmare etc.

Toxicity

Side effects include abdominal pain, amnesia, dizziness, drowsiness, eye pain, headache, memory loss, menstrual pain, nausea, sleepiness, tingling, weakness

Precaution

Timing of drug administration: Zaleplon should be taken immediately before bedtime or after the patient has gone to bed.Use in the elderly and/or debilitated patients: Impaired motor and/or cognitive performance after repeated exposure or unusual sensitivity to sedative/hypnotic drugs is a concern in the treatment of elderly and/or debilitated patients. A dose of 5 mg is recommended for elderly patients to decrease the possibility of side effects. Elderly and/or debilitated patients should be monitored closely.Use in patients with concomitant illness: Zaleplon should be used with caution in patients with diseases or conditions that could affect metabolism or haemodynamic responses. Although preliminary studies did not reveal respiratory depressant effects at hypnotic doses of Zaleplon in normal subjects, caution should be observed if Zaleplon is prescribed to patients with compromised respiratory function, because sedative/hypnotic have the capacity to depress respiratory drive. However, patients with compromised respiration due to preexisting illness should be monitored carefully. The dose of Zaleplon should be reduced to 5 mg in patients with mild to moderate hepatic impairment. It is not recommended for use in patients with severe hepatic impairment.Renal impairment patients: No dose adjustment is necessary in patients with mild to moderate renal impairment. Zaleplon has not been adequately studied in patients with severe renal impairment.Use in patients with depression: As with other sedative or hypnotic drugs, Zaleplon should be administered with caution to patients exhibiting signs or symptoms of depression

Interaction

Zaleplon has been shown to have minimal effects on the kinetic of Warfarin, Imipramine, Ethanol, Ibuprofen, Diphenhydramine, Thioridazine, and Digoxin.

Food Interaction

• Avoid alcohol. Ingesting alcohol may increase the CNS depressant effects of zaleplon.
• Do not take with or immediately after a high-fat meal. The effects of zaleplon are reduced when taken with a high-fat meal.

[Moderate] GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of zaleplon.

Use in combination may result in additive central nervous system depression and
ADJUST DOSING INTERVAL: Administration of zaleplon with a high-fat or heavy meal may delay the onset of hypnotic effects.

In healthy adult subjects, administration of zaleplon with a high-fat meal resulted in a 2-hour delay in the time to reach peak plasma drug concentration (Tmax) and a 35% reduction in the peak plasma drug concentration (Cmax) compared to fasting.

Zaleplon systemic exposure (AUC) and elimination half-life were not significantly affected.

MANAGEMENT: Patients receiving zaleplon should be advised to avoid the consumption of alcohol.

For faster sleep onset, zaleplon should not be administered with or immediately after a high-fat or heavy meal.

Zaleplon Drug Interaction

Moderate: aripiprazole, duloxetine, escitalopram, eszopiclone, pregabalin, alprazolam, cetirizineUnknown: amphetamine / dextroamphetamine, zolpidem, ubiquinone, omega-3 polyunsaturated fatty acids, metoprolol, esomeprazole, albuterol, montelukast, cyanocobalamin, ascorbic acid, ergocalciferol, cholecalciferol, lisdexamfetamine

Zaleplon Disease Interaction

Major: alcohol intox, depression, drug dependence, liver diseaseModerate: glaucoma, liver disease, resp depression, renal dysfunction

Volume of Distribution

• 1.4 L/kg

Elimination Route

Absorption Zaleplon is rapidly and almost completely absorbed following oral administration.

Half Life

Approximately 1 hour

Clearance

• 1 L/h/kg

Elimination Route

Zaleplon is metabolized primarily by the liver and undergoes significant presystemic metabolism. After oral administration, zaleplon is extensively metabolized, with less than 1% of the dose excreted unchanged in urine. Renal excretion of unchanged zaleplon accounts for less than 1% of the administered dose.

Pregnancy & Breastfeeding use

Pregnancy: There are no studies of Zaleplon in pregnant women; therefore, it is not recommended for use in women during pregnancy. Zaleplon has no established use in labour and delivery.Lactation: A study in lactating mothers indicated that the clearance and half-life of Zaleplon is similar to that in young normal subjects. A small amount of Zaleplon is excreted in breast milk, with the highest excreted amount occurring during a feeding at approximately 1 hour after Zaleplon administration. Since the small amount of the drug from breast milk may result in potentially important concentrations in infants, and because the effects of Zaleplon on a nursing infant are not known, it is not recommended in nursing mothers.

Contraindication

Zaleplon is contraindicated in patients with known hypersensitivity to any of its components.

Special Warning

Special Patient Group: Patients on cimetidine should receive initial dose of 5 mg at bedtime.Hepatic Impairment:

• Mild to moderate: 5 mg at bedtime.
• Severe: Contraindicated.

Paediatric use

: The safety and effectiveness of Zaleplon in paediatric patients have not been established.

Innovators Monograph

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