Melatonin

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NOTE: Most over the counter (OTC) are not reviewed and approved by the FDA. However, they may be marketed if they comply with applicable regulations and policies. FDA has not evaluated whether this product complies.

# Overview
Melatonin is a hormone that is FDA approved for the treatment of sleep cycle support.   Common adverse reactions include hypothermia, somnolence, fatigue.

# Adult Indications and Dosage

## FDA-Labeled Indications and Dosage (Adult)
- Sleep cycle support.

## Off-Label Use and Dosage (Adult)

### Guideline-Supported Use
- Cancer: 20 mg ORALLY once daily has been used in clinical trials
- Cancer: up to 40 years, immediate-release, 1.5 mg ORALLY daily
- Cancer: 40 to 60 years, immediate-release, 1.5 to 3 mg ORALLY daily
- Cancer: older than 60 years, immediate-release, 3 to 6 mg ORALLY daily
- Jet lag: 1.5 to 3 mg ORALLY at 11 PM (local time in the destination country) on day 1, 10:30 PM on day 2, and 10 PM on day 3
- Sleep disorder: immediate-release, 5 mg ORALLY 30 minutes prior to time of sleep ; up to 10 mg ORALLY daily
- Sleep disorder: extended-release, 2 mg ORALLY 1 to 2 hours before bedtime 

### NonGuideline-Supported Use
There is limited information regarding Off-Label NonGuideline-Supported Use of Melatonin in adult patients.

# Pediatric Indications and Dosage

## FDA-Labeled Indications and Dosage (Pediatric)
There is limited information regarding FDA-Labeled Use of Melatonin in pediatric patients.

## Off-Label Use and Dosage (Pediatric)

### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Melatonin in pediatric patients.

### NonGuideline-Supported Use
There is limited information regarding Off-Label NonGuideline-Supported Use of Melatonin in pediatric patients.

# Contraindications
- Specific contraindications have not been determined.

# Warnings
Stop use and seek medical attention if symptoms worsen or persist more than 5 days

# Adverse Reactions

## Clinical Trials Experience
- Erythema
- Fixed drug eruption
- Fixed-drug eruptions on the glans was described as burning, itching, and sharply marginated, erythematous, vesicular plaques and well-demarcated erosions on the shaft in 2 adult males, occurring within 6 to 8 hours after taking melatonin for jet lag. Lesions dissipated within 10 days.
- Flushing
- Occasional vasodilation has been reported in patients with Parkinson disease treated with a maximum of melatonin 1000 mg/day.
- Pruritus
- Pruritus was reported in 1 of 12 elderly subjects with insomnia during therapy with sustained-release melatonin in one study.
- Gynaecomastia
- Hypothermia

## Postmarketing Experience
There is limited information regarding Postmarketing Experience of Melatonin in the drug label.

# Drug Interactions
Drug interactions have been reported with the following drugs.
Concomitant use can cause central nervous depression.
Concomitant use can cause increased blood pressure.
Increased risk of bleeding has been noted with concomitant use of warfarin.

# Use in Specific Populations

### Pregnancy
Pregnancy Category (FDA):
- Pregnancy Category
Pregnancy Category (AUS):
- Australian Drug Evaluation Committee (ADEC) Pregnancy Category
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Melatonin in women who are pregnant.

### Labor and Delivery
There is no FDA guidance on use of Melatonin during labor and delivery.

### Nursing Mothers
There is no FDA guidance on the use of Melatonin with respect to nursing mothers.

### Pediatric Use
There is no FDA guidance on the use of Melatonin with respect to pediatric patients.

### Geriatic Use
There is no FDA guidance on the use of Melatonin with respect to geriatric patients.

### Gender
There is no FDA guidance on the use of Melatonin with respect to specific gender populations.

### Race
There is no FDA guidance on the use of Melatonin with respect to specific racial populations.

### Renal Impairment
There is no FDA guidance on the use of Melatonin in patients with renal impairment.

### Hepatic Impairment
There is no FDA guidance on the use of Melatonin in patients with hepatic impairment.

### Females of Reproductive Potential and Males
There is no FDA guidance on the use of Melatonin in women of reproductive potentials and males.

### Immunocompromised Patients
There is no FDA guidance one the use of Melatonin in patients who are immunocompromised.

# Administration and Monitoring

### Administration
- Oral

### Monitoring
- Improvement of sleep in insomnia (eg, reduced sleep latency, longer sleep duration, improved quality of sleep) may indicate efficacy.
- Alleviation of symptoms in jet lag (eg, correction of disturbed sleep, reduced daytime tiredness) may indicate efficacy.

# IV Compatibility
There is limited information regarding IV Compatibility of Melatonin in the drug label.

# Overdosage
There is limited information regarding Chronic Overdose of Melatonin in the drug label.

# Pharmacology

## Mechanism of Action
- The binding of melatonin to melatonin receptors activates a few signaling pathways.
- MT1 receptor activation inhibits the adenylyl cyclase and its inhibition causes a rippling effect of non activation; starting with decreasing formation of cyclic adenosine monophosphate (cAMP), and then progressing to less protein kinase A (PKA) activity, which in turn hinders the phosphorylation of cAMP responsive element-binding protein (CREB binding protein) into P-CREB. MT1 receptors also activate phospholipase C (PLC), affect ion channels and regulate ion flux inside the cell.The binding of melatonin to MT2 receptors inhibits adenylyl cyclase which decreases the formation of cAMP.
- As well it hinders guanylyl cyclase and therefore the forming of cyclic guanosine monophosphate (cGMP). Binding to MT2 receptors probably affects PLC which increases protein kinase C (PKC) activity. Activation of the receptor can lead to ion flux inside the cell.
- When melatonin receptor agonists activate their receptors it causes numerous physiological processes.
- MT1 and MT2 receptors may be a target for the treatment of circadian and non circadian sleep disorders because of their differences in pharmacology and function within the SCN. The SCN is responsible for maintaining the 24 hour cycle which regulates many different body functions ranging from sleep to immune functions.
- Melatonin receptors have been identified in the cardiovascular system. Evidence from animal studies points to a dual role of melatonin in the vasculature.
- Activation of MT1 receptors mediates vasoconstriction and the activation of MT2 receptors mediates vasodilation. Melatonin is involved in regulating immune responses in both human and animals through activation of both MT1 and MT2 receptors.
- MT1 and MT2 receptors are widespread in the eye and are involved in regulating aqueous humor secretion, which is important for glaucoma, and in phototransduction. This is not a complete list since many of the possible processes need further confirmation

## Structure
There is limited information regarding Melatonin Structure in the drug label.

## Pharmacodynamics
There is limited information regarding Pharmacodynamics of Melatonin in the drug label.

## Pharmacokinetics
There is limited information regarding Pharmacokinetics of Melatonin in the drug label.

## Nonclinical Toxicology
There is limited information regarding Nonclinical Toxicology of Melatonin in the drug label.

# Clinical Studies
There is limited information regarding Clinical Studies of Melatonin in the drug label.

# How Supplied
There is limited information regarding Melatonin How Supplied in the drug label.

## Storage
There is limited information regarding Melatonin Storage in the drug label.

# Images

## Drug Images

## Package and Label Display Panel

# Patient Counseling Information
Take 15 minutes before meals.
- Adults and children 12 years and older 20 drops twice a day in a little water. Hold in the mouth for about 30 seconds then swallow.
- Children  between 12 years and 6 years of age    10 drops twice a day in a little water. Hold in the mouth for about 30 seconds then swallow.
- Children under 6 years

# Precautions with Alcohol
- Alcohol-Melatonin interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

# Brand Names
- GUNA-MELATONIN  

# Look-Alike Drug Names
There is limited information regarding Melatonin Look-Alike Drug Names in the drug label.

# Drug Shortage Status

# Price