Sleep3

Drug overview for SLEEP3 (melatonin/theanine/valerian rt/lemon balm/chamomile/lavender):

Generic name: melatonin/theanine/valerian rt/lemon balm/chamomile/lavender
Drug class: Antianxiety Agents
Therapeutic class: Central Nervous System Agents

No enhanced Introduction information available for this drug.

No enhanced Uses information available for this drug.

DRUG IMAGES

No Image Available

The following indications for SLEEP3 (melatonin/theanine/valerian rt/lemon balm/chamomile/lavender) have been approved by the FDA:

Indications:
None.

Professional Synonyms:
None.

The following drug interaction information is available for SLEEP3 (melatonin/theanine/valerian rt/lemon balm/chamomile/lavender):

Contraindicated
Severe
Moderate

There are 0 contraindications.

There are 1 severe interactions. These drug interactions can produce serious consequences in most patients. Actions required for severe interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration scheduling, and providing additional patient monitoring. Review the full interaction monograph for more information.

Drug Interaction	Drug Names
Melatonin/Strong CYP1A2 Inhibitors SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Strong CYP1A2 inhibitors may significantly increase the area-under-curve (AUC) of melatonin by inhibiting CYP1A2.(1,2) Fluvoxamine, a strong CYP1A2 inhibitor, has also been shown to increase endogenous melatonin levels. CLINICAL EFFECTS: The concurrent administration of melatonin and strong CYP1A2 inhibitors may result in significantly increased melatonin levels and subsequent side effects.(1-3) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The UK manufacturer of melatonin recommends against the concurrent use of melatonin and CYP1A2 inhibitors.(1) The Australian manufacturer of melatonin states concurrent use of melatonin and CYP1A2 inhibitors should be avoided.(2) Patients should be monitored for increased effects of melatonin when melatonin and CYP1A2 inhibitors are used concurrently. DISCUSSION: In a study, fluvoxamine increased the area-under-curve (AUC) and concentration maximum (Cmax) of melatonin by 17-fold and 12-fold, respectively.(2) In a case report, a 51 year old female with chronic primary insomnia who received 5 mg melatonin at bedtime and 75 mg fluvoxamine in the afternoon experienced increased nocturnal sleep, from 2.5 hours (drug free) to 4.2 hours (melatonin alone) up to 5.5 hours per night (melatonin with fluvoxamine). Both melatonin and fluvoxamine alone increased melatonin levels; however administration of melatonin alone increased melatonin levels more than fluvoxamine alone. Concurrent use of melatonin and fluvoxamine increased melatonin levels 20-fold when compared to the administration of melatonin alone.(3) In a study involving five males, 5 mg of melatonin daily was given for one week, then 50 mg of fluvoxamine was added (administered three hours apart. The AUC of melatonin increased at least nine-fold (p<0.05). The Cmax increased at least six-fold in melatonin (p<0.01), versus the Cmax in patients who received melatonin alone.(4) Strong CYP1A2 inhibitors include: enasidenib, fluvoxamine, and viloxazine.(5)	FLUVOXAMINE MALEATE, FLUVOXAMINE MALEATE ER, IDHIFA, QELBREE

Drug Interaction

Drug Names

Melatonin/Strong CYP1A2 Inhibitors

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Strong CYP1A2 inhibitors may significantly increase the area-under-curve (AUC) of melatonin by inhibiting CYP1A2.(1,2) Fluvoxamine, a strong CYP1A2 inhibitor, has also been shown to increase endogenous melatonin levels.

CLINICAL EFFECTS: The concurrent administration of melatonin and strong CYP1A2 inhibitors may result in significantly increased melatonin levels and subsequent side effects.(1-3)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The UK manufacturer of melatonin recommends against the concurrent use of melatonin and CYP1A2 inhibitors.(1) The Australian manufacturer of melatonin states concurrent use of melatonin and CYP1A2 inhibitors should be avoided.(2) Patients should be monitored for increased effects of melatonin when melatonin and CYP1A2 inhibitors are used concurrently.

DISCUSSION: In a study, fluvoxamine increased the area-under-curve (AUC) and concentration maximum (Cmax) of melatonin by 17-fold and 12-fold, respectively.(2) In a case report, a 51 year old female with chronic primary insomnia who received 5 mg melatonin at bedtime and 75 mg fluvoxamine in the afternoon experienced increased nocturnal sleep, from 2.5 hours (drug free) to 4.2

hours (melatonin alone) up to 5.5 hours per night (melatonin with fluvoxamine). Both melatonin and fluvoxamine alone increased melatonin levels; however administration of melatonin alone increased melatonin levels more than fluvoxamine alone.

Concurrent use of melatonin and fluvoxamine increased melatonin levels 20-fold when compared to the administration of melatonin alone.(3) In a study involving five males, 5 mg of melatonin daily was given for one week, then 50 mg of fluvoxamine was added (administered three hours apart. The AUC of melatonin increased at least nine-fold (p<0.05). The Cmax increased at least six-fold in melatonin (p<0.01), versus the Cmax in patients who received melatonin alone.(4) Strong CYP1A2 inhibitors include: enasidenib, fluvoxamine, and viloxazine.(5)

FLUVOXAMINE MALEATE, FLUVOXAMINE MALEATE ER, IDHIFA, QELBREE

There are 0 moderate interactions.

Severe List
Autoimmune disease
Systemic lupus erythematosus

The following adverse reaction information is available for SLEEP3 (melatonin/theanine/valerian rt/lemon balm/chamomile/lavender):

Overview
Severe
Less Severe

Adverse reaction overview.

No enhanced Common Adverse Effects information available for this drug.

There are 2 severe adverse reactions.

More Frequent	Less Frequent
None.	None.

Rare/Very Rare
Hallucinations Hepatitis

There are 37 less severe adverse reactions.

More Frequent	Less Frequent
Dizziness Headache disorder Sedation hangover effect	Abdominal pain with cramps Acute cognitive impairment CNS depression Concentration difficulty Depression Hypotension Irritability Nausea Symptoms of anxiety Tremor Vomiting

Rare/Very Rare
Accidental fall Agitation Ataxia Blurred vision Dizziness Dream disorder Drowsy Dyspepsia Excitement Fatigue Headache disorder Hypersensitivity drug reaction Hypothermia Insomnia Muscle relaxation Nausea Nervousness Palpitations Panic disorder Paresthesia Sedation Skin rash Xerostomia

The following precautions are available for SLEEP3 (melatonin/theanine/valerian rt/lemon balm/chamomile/lavender):

Pediatric
Pregnant
Lactation
Geriatric

No enhanced Pediatric Use information available for this drug.

Contraindicated

None

Severe Precaution

None

Management or Monitoring Precaution

None

No enhanced Pregnancy information available for this drug.

No enhanced Lactation information available for this drug.

No enhanced Geriatric Use information available for this drug.