THERAPEUTICS

Brands

• Hetlioz

Generic?

• No

Class

• Melatonin receptor agonist

Commonly Prescribed for

(FDA approved in bold)

• Treatment of non-24-hour sleep–wake disorder (non-24)

• Circadian rhythm disorders (shift work disorder, jet-lag)

• Sundowning associated with Alzheimer’s disease

• Insomnia

How the Drug Works

• Selectively binds to melatonin receptors (MT1, MT2) in the suprachiasmatic nuclei (SCN). It increases the activity of MT1 receptors (inhibits arousal from SCN) for sleep onset and stimulates MT2 receptors (synchronizes the circadian clock to day–night cycle) for circadian phase shifting. It has greater affinity for MT2 than MT1, supporting its use for non-24

• No affinity for GABA, dopamine, norepinephrine, acetylcholine, opiate receptors

How Long Until It Works

• Onset in less than 2 hours. Optimal improvement may take weeks or months

If It Works

• Continue to use

If It Doesn't Work

• Increase dose or combine with other antiinsomnia agents. Re-evaluate underlying conditions

Best Augmenting Combos for Partial Response or Treatment-Resistance

• Non-pharmacological treatment using phototherapy can be beneficial in those with light perception

• For insomnia, may use low dose of antihistamine, TCAs, benzodiazepines, or antipsychotics

Tests

• Not necessary

ADVERSE EFFECTS (AEs)

How the Drug Causes AEs

• CNS depressant

Notable AEs

• Most common: headache, nightmares, increased alanine aminotransferase, upper respiratory or urinary tract infection

Life-Threatening or Dangerous AEs

• Decreased hemoglobin

Weight Gain

• Unusual

Sedation

• Problematic

What to Do About AEs

• Discontinue if severe AEs

Best Augmenting Agents to Reduce AEs

• Most AEs cannot be reduced by use of augmenting agent

DOSING AND USE

Usual Dosage Range

• 20mg

Dosage Forms

• Capsules: 20mg

How to Dose

• 20mg prior to bedtime, at same time every night

Dosing Tips

• Do not take with high-fat meal, which delays its absorption

Overdose

• As with the management of any overdose, general symptomatic and supportive measures should be used, along with immediate gastric lavage where appropriate. IV fluids should be administered as needed. Respiration, pulse, blood pressure, and other appropriate vital signs should be monitored. No antidote available