Dosing & Uses
Dosage Forms & Strengths
solution, intranasal: Schedule III
- 28mg/device; each nasal spray device delivers 2 sprays that total 28mg
- Available as a 56mg kit (two 28-mg nasal spray devices) or an 84mg kit (three 28-mg nasal spray devices)
Treatment-resistant Depression
Indicated in conjunction with an oral antidepressant for treatment-resistant depression (TRD)
Adjust dose based on efficacy and tolerability
At the end of the induction phase, evaluate evidence of therapeutic benefit to determine need for continued treatment
Must be administered in healthcare facility under direct supervision
Induction phase
-
Weeks 1-4
- Administer intranasally twice per week
- Day 1 starting dose: 56 mg
- Subsequent doses: 56 mg or 84 mg
Maintenance phase
-
Weeks 5-8
- Administer intranasally once weekly
- 56 mg or 84 mg
-
Week 9 and after
- Administer intranasally q2Week or once weekly; individualize dosing frequency to the least frequent dosing to maintain remission/response
- 56 mg or 84 mg
Major Depressive Disorder
Indicated for depressive symptoms in adults with major depressive disorder (MDD) with acute suicidal ideation or behavior
Administer intranasally in conjunction with an oral antidepressant
Must be administered in healthcare facility under direct supervision
84 mg twice per week x 4 weeks
May reduce dose to 56 mg twice per week based on tolerability
After 4 weeks of treatment, evaluate evidence of therapeutic benefit determine need for continued treatment
Use in conjunction with an oral antidepressant beyond 4 weeks has not been systematically evaluated for treatment of depressive symptoms in patients with MDD with acute suicidal ideation or behavior
Dosage Modifications
Hepatic impairment
- Moderate (Child-Pugh class B): Higher AUC and half-life observed compared with normal hepatic function; may need to be monitored for longer period after dose administration
- Severe (Child-Pugh class C): Not studied, and therefore not recommended
Renal impairment
- Renal dialysis: No clinical experience
Dosing Considerations
Must be administered under direct supervision of a healthcare provider during entire treatment session (ie, nasal administration and postadministration direct observation)
Limitations of use
- Not approved as an anesthetic agent; safety and effectiveness not established
- Effectiveness in preventing suicide or in reducing suicidal ideation or behavior has not been demonstrated; use of esketamine intranasal does not preclude the need for hospitalization if clinically warranted, even if patients experience improvement after an initial dose
Blood pressure monitoring
- Assess blood pressure before administration
- If baseline blood pressure is elevated (eg, >140 mm Hg systolic, >90 mm Hg diastolic), consider the risks of short-term increases in blood pressure and benefit of treatment
- Do not administer if increased blood pressure or intracranial pressure poses serious risk
- After dosing, reassess blood pressure at ~40 minutes (corresponds with peak plasma concentration) and subsequently as clinically warranted
- If blood pressure is decreasing and patient appears clinically stable for at least 2 hr, may discharge patient at the end of the postdose monitoring period; if not, continue to monitor
Food and liquid ingestion
- Some patients may experience nausea and vomiting after administration
- Because of this, advise patients to avoid food for at least 2 hr before administration and to avoid drinking liquids at least 30 minutes before
Nasal corticosteroids or decongestants
- Administer nasal corticosteroid or decongestant at least 1 hr before esketamine
Safety and efficacy not established
In clinical trials, 14% of patients were aged 65 yr or older; no overall differences in safety profile were observed
See adult dosing
Interactions
Interaction Checker
No Results

Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor

Contraindicated (0)
Serious - Use Alternative (3)
- buprenorphine, long-acting injection
buprenorphine, long-acting injection and esketamine intranasal both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate
- metoclopramide intranasal
esketamine intranasal, metoclopramide intranasal. Either increases effects of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: Avoid use of metoclopramide intranasal or interacting drug, depending on importance of drug to patient.
- olopatadine intranasal
esketamine intranasal and olopatadine intranasal both increase sedation. Avoid or Use Alternate Drug. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment.
Monitor Closely (202)
- acetaminophen/pamabrom/pyrilamine
esketamine intranasal, acetaminophen/pamabrom/pyrilamine. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- acetazolamide
esketamine intranasal, acetazolamide. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- acrivastine
esketamine intranasal, acrivastine. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
acrivastine and esketamine intranasal both increase sedation. Use Caution/Monitor. - alfentanil
esketamine intranasal, alfentanil. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- alprazolam
esketamine intranasal, alprazolam. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- amisulpride
amisulpride and esketamine intranasal both increase sedation. Use Caution/Monitor.
- amitriptyline
esketamine intranasal, amitriptyline. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- amobarbital
esketamine intranasal, amobarbital. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- amoxapine
esketamine intranasal, amoxapine. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- amphetamine
esketamine intranasal, amphetamine. Either increases toxicity of the other by sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor. Closely monitor blood pressure with concomitant use of esketamine nasal with stimulants. .
- amphetamine polistirex
esketamine intranasal, amphetamine polistirex. Either increases toxicity of the other by sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor. Closely monitor blood pressure with concomitant use of esketamine nasal with stimulants. .
- arbaclofen
esketamine intranasal, arbaclofen. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- aripiprazole
esketamine intranasal, aripiprazole. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- armodafinil
esketamine intranasal, armodafinil. Either increases toxicity of the other by sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor. Closely monitor blood pressure with concomitant use of esketamine nasal with stimulants. .
- asenapine
esketamine intranasal, asenapine. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- asenapine transdermal
asenapine transdermal and esketamine intranasal both increase sedation. Use Caution/Monitor.
- atomoxetine
esketamine intranasal, atomoxetine. Either increases toxicity of the other by sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor. Closely monitor blood pressure with concomitant use of esketamine nasal with stimulants. .
- avapritinib
avapritinib and esketamine intranasal both increase sedation. Use Caution/Monitor.
- baclofen
esketamine intranasal, baclofen. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- belladonna and opium
esketamine intranasal, belladonna and opium. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- benperidol
esketamine intranasal, benperidol. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- benzhydrocodone/acetaminophen
esketamine intranasal, benzhydrocodone/acetaminophen. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- brexanolone
brexanolone, esketamine intranasal. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- brexpiprazole
esketamine intranasal, brexpiprazole. Either increases levels of the other by sedation. Modify Therapy/Monitor Closely.
- brimonidine
esketamine intranasal, brimonidine. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- brivaracetam
esketamine intranasal, brivaracetam. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- brompheniramine
esketamine intranasal, brompheniramine. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- buprenorphine
esketamine intranasal, buprenorphine. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- buprenorphine transdermal
esketamine intranasal, buprenorphine transdermal. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- buspirone
esketamine intranasal, buspirone. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- butabarbital
esketamine intranasal, butabarbital. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- butalbital
esketamine intranasal, butalbital. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- butorphanol
esketamine intranasal, butorphanol. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- caffeine
esketamine intranasal, caffeine. Either increases toxicity of the other by sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor. Closely monitor blood pressure with concomitant use of esketamine nasal with stimulants. .
- calcium/magnesium/potassium/sodium oxybates
esketamine intranasal, calcium/magnesium/potassium/sodium oxybates. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- cannabidiol
esketamine intranasal, cannabidiol. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- carbamazepine
esketamine intranasal, carbamazepine. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- carbinoxamine
esketamine intranasal, carbinoxamine. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- cariprazine
esketamine intranasal, cariprazine. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- carisoprodol
esketamine intranasal, carisoprodol. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- cenobamate
cenobamate, esketamine intranasal. Either increases effects of the other by sedation. Use Caution/Monitor.
- cetirizine
esketamine intranasal, cetirizine. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- chlordiazepoxide
esketamine intranasal, chlordiazepoxide. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- chlorpheniramine
esketamine intranasal, chlorpheniramine. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- chlorpromazine
esketamine intranasal, chlorpromazine. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- chlorzoxazone
esketamine intranasal, chlorzoxazone. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- clemastine
esketamine intranasal, clemastine. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- clomipramine
esketamine intranasal, clomipramine. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- clonazepam
esketamine intranasal, clonazepam. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- clonidine
esketamine intranasal, clonidine. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
esketamine intranasal, clonidine. Either increases toxicity of the other by sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor. Closely monitor blood pressure with concomitant use of esketamine nasal with stimulants. . - clorazepate
esketamine intranasal, clorazepate. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- clozapine
esketamine intranasal, clozapine. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- codeine
esketamine intranasal, codeine. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- cyclobenzaprine
esketamine intranasal, cyclobenzaprine. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- cyproheptadine
esketamine intranasal, cyproheptadine. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- dantrolene
esketamine intranasal, dantrolene. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- daridorexant
esketamine intranasal and daridorexant both increase sedation. Modify Therapy/Monitor Closely. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment.
- desflurane
esketamine intranasal, desflurane. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- desipramine
esketamine intranasal, desipramine. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- desloratadine
esketamine intranasal, desloratadine. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- deutetrabenazine
esketamine intranasal, deutetrabenazine. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- dexbrompheniramine
esketamine intranasal, dexbrompheniramine. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- dexchlorpheniramine
esketamine intranasal, dexchlorpheniramine. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- dexmethylphenidate
esketamine intranasal, dexmethylphenidate. Either increases toxicity of the other by sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor. Closely monitor blood pressure with concomitant use of esketamine nasal with stimulants. .
- dextroamphetamine
esketamine intranasal, dextroamphetamine. Either increases toxicity of the other by sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor. Closely monitor blood pressure with concomitant use of esketamine nasal with stimulants. .
- diazepam
esketamine intranasal, diazepam. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- diazepam intranasal
diazepam intranasal, esketamine intranasal. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration may potentiate the CNS-depressant effects of each drug.
- diethylpropion
esketamine intranasal, diethylpropion. Either increases toxicity of the other by sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor. Closely monitor blood pressure with concomitant use of esketamine nasal with stimulants. .
- difelikefalin
difelikefalin and esketamine intranasal both increase sedation. Use Caution/Monitor.
- dimenhydrinate
esketamine intranasal, dimenhydrinate. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- diphenhydramine
esketamine intranasal, diphenhydramine. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- diphenoxylate hcl
esketamine intranasal, diphenoxylate hcl. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- dosulepin
esketamine intranasal, dosulepin. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- doxepin
esketamine intranasal, doxepin. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- doxylamine
esketamine intranasal, doxylamine. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- droperidol
esketamine intranasal, droperidol. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- efavirenz
esketamine intranasal, efavirenz. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- emedastine
esketamine intranasal, emedastine. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- estazolam
esketamine intranasal, estazolam. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- eszopiclone
esketamine intranasal, eszopiclone. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- ethanol
esketamine intranasal, ethanol. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- ethosuximide
esketamine intranasal, ethosuximide. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- ethotoin
esketamine intranasal, ethotoin. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- ezogabine
esketamine intranasal, ezogabine. Either increases levels of the other by sedation. Use Caution/Monitor.
- felbamate
esketamine intranasal, felbamate. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- fenfluramine
fenfluramine, esketamine intranasal. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration with drugs that increase serotoninergic effects may increase the risk of serotonin syndrome.
- fentanyl
esketamine intranasal, fentanyl. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- fentanyl intranasal
esketamine intranasal, fentanyl intranasal. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- fentanyl transdermal
esketamine intranasal, fentanyl transdermal. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- fentanyl transmucosal
esketamine intranasal, fentanyl transmucosal. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- fexofenadine
esketamine intranasal, fexofenadine. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- flibanserin
esketamine intranasal, flibanserin. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- fluphenazine
esketamine intranasal, fluphenazine. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- flurazepam
esketamine intranasal, flurazepam. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- fosphenytoin
esketamine intranasal, fosphenytoin. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- gabapentin
esketamine intranasal, gabapentin. Either increases toxicity of the other by sedation. Use Caution/Monitor.
gabapentin, esketamine intranasal. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation. - gabapentin enacarbil
esketamine intranasal, gabapentin enacarbil. Either increases toxicity of the other by sedation. Use Caution/Monitor.
gabapentin enacarbil, esketamine intranasal. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation. - ganaxolone
esketamine intranasal and ganaxolone both increase sedation. Use Caution/Monitor.
- guanfacine
esketamine intranasal, guanfacine. Either increases toxicity of the other by sedation. Use Caution/Monitor.
esketamine intranasal, guanfacine. Either increases toxicity of the other by sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor. Closely monitor blood pressure with concomitant use of esketamine nasal with stimulants. . - haloperidol
esketamine intranasal, haloperidol. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- hydrocodone
esketamine intranasal, hydrocodone. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- hydromorphone
esketamine intranasal, hydromorphone. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- hydroxyzine
esketamine intranasal, hydroxyzine. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- iloperidone
esketamine intranasal, iloperidone. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- imipramine
esketamine intranasal, imipramine. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- isocarboxazid
esketamine intranasal, isocarboxazid. Either increases toxicity of the other by sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor. Closely monitor blood pressure with concomitant use of esketamine nasal with MAO-Is. .
- isoflurane
esketamine intranasal, isoflurane. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- ketamine
esketamine intranasal, ketamine. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- lamotrigine
esketamine intranasal, lamotrigine. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- lasmiditan
lasmiditan, esketamine intranasal. Either increases effects of the other by sedation. Use Caution/Monitor. Coadministration of lasmiditan and other CNS depressant drugs, including alcohol have not been evaluated in clinical studies. Lasmiditan may cause sedation, as well as other cognitive and/or neuropsychiatric adverse reactions.
- levetiracetam
esketamine intranasal, levetiracetam. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- levocetirizine
esketamine intranasal, levocetirizine. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- levorphanol
esketamine intranasal, levorphanol. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- lisdexamfetamine
esketamine intranasal, lisdexamfetamine. Either increases toxicity of the other by sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor. Closely monitor blood pressure with concomitant use of esketamine nasal with stimulants. .
- loratadine
esketamine intranasal, loratadine. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- lorazepam
esketamine intranasal, lorazepam. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- loxapine
esketamine intranasal, loxapine. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- lurasidone
esketamine intranasal, lurasidone. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- maprotiline
esketamine intranasal, maprotiline. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- meclizine
esketamine intranasal, meclizine. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- meperidine
esketamine intranasal, meperidine. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- metaxalone
esketamine intranasal, metaxalone. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- methadone
esketamine intranasal, methadone. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- methamphetamine
esketamine intranasal, methamphetamine. Either increases toxicity of the other by sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor. Closely monitor blood pressure with concomitant use of esketamine nasal with stimulants. .
- methocarbamol
esketamine intranasal, methocarbamol. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- methylphenidate
esketamine intranasal, methylphenidate. Either increases toxicity of the other by sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor. Closely monitor blood pressure with concomitant use of esketamine nasal with stimulants. .
- midazolam
esketamine intranasal, midazolam. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- midazolam intranasal
midazolam intranasal, esketamine intranasal. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Concomitant use of barbiturates, alcohol, or other CNS depressants may increase the risk of hypoventilation, airway obstruction, desaturation, or apnea and may contribute to profound and/or prolonged drug effect.
- modafinil
esketamine intranasal, modafinil. Either increases toxicity of the other by sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor. Closely monitor blood pressure with concomitant use of esketamine nasal with stimulants. .
- morphine
esketamine intranasal, morphine. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- nalbuphine
esketamine intranasal, nalbuphine. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- nicotine gum
esketamine intranasal, nicotine gum. Either increases toxicity of the other by sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor. Closely monitor blood pressure with concomitant use of esketamine nasal with stimulants. .
- nicotine inhaled
esketamine intranasal, nicotine inhaled. Either increases toxicity of the other by sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor. Closely monitor blood pressure with concomitant use of esketamine nasal with stimulants. .
- nicotine intranasal
esketamine intranasal, nicotine intranasal. Either increases toxicity of the other by sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor. Closely monitor blood pressure with concomitant use of esketamine nasal with stimulants. .
- nicotine lozenge
esketamine intranasal, nicotine lozenge. Either increases toxicity of the other by sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor. Closely monitor blood pressure with concomitant use of esketamine nasal with stimulants. .
- nicotine transdermal
esketamine intranasal, nicotine transdermal. Either increases toxicity of the other by sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor. Closely monitor blood pressure with concomitant use of esketamine nasal with stimulants. .
- nortriptyline
esketamine intranasal, nortriptyline. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- olanzapine
esketamine intranasal, olanzapine. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- oliceridine
esketamine intranasal, oliceridine. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- orphenadrine
esketamine intranasal, orphenadrine. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- oxazepam
esketamine intranasal, oxazepam. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- oxycodone
esketamine intranasal, oxycodone. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- oxymorphone
esketamine intranasal, oxymorphone. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- paliperidone
esketamine intranasal, paliperidone. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- pentazocine
esketamine intranasal, pentazocine. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- pentobarbital
esketamine intranasal, pentobarbital. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- phendimetrazine
esketamine intranasal, phendimetrazine. Either increases toxicity of the other by sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor. Closely monitor blood pressure with concomitant use of esketamine nasal with stimulants. .
- phenelzine
esketamine intranasal, phenelzine. Either increases toxicity of the other by sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor. Closely monitor blood pressure with concomitant use of esketamine nasal with MAO-Is. .
- phentermine
esketamine intranasal, phentermine. Either increases toxicity of the other by sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor. Closely monitor blood pressure with concomitant use of esketamine nasal with stimulants. .
- phenylephrine PO
esketamine intranasal, phenylephrine PO. Either increases toxicity of the other by sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor. Closely monitor blood pressure with concomitant use of esketamine nasal with stimulants. .
- phenytoin
esketamine intranasal, phenytoin. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- pimavanserin
esketamine intranasal, pimavanserin. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- pimozide
esketamine intranasal, pimozide. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- pomalidomide
esketamine intranasal, pomalidomide. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- pregabalin
esketamine intranasal, pregabalin. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
pregabalin, esketamine intranasal. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation. - primidone
esketamine intranasal, primidone. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- promethazine
esketamine intranasal, promethazine. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- propofol
esketamine intranasal, propofol. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- protriptyline
esketamine intranasal, protriptyline. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- pseudoephedrine
esketamine intranasal, pseudoephedrine. Either increases toxicity of the other by sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor. Closely monitor blood pressure with concomitant use of esketamine nasal with stimulants. .
- quazepam
esketamine intranasal, quazepam. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- quetiapine
esketamine intranasal, quetiapine. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- ramelteon
esketamine intranasal, ramelteon. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- remifentanil
esketamine intranasal, remifentanil. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- remimazolam
remimazolam, esketamine intranasal. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely. Coadministration may result in profound sedation, respiratory depression, coma, and/or death. Continuously monitor vital signs during sedation and recovery period if coadministered. Carefully titrate remimazolam dose if administered with opioid analgesics and/or sedative/hypnotics.
- reserpine
esketamine intranasal, reserpine. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- risperidone
esketamine intranasal, risperidone. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- rufinamide
esketamine intranasal, rufinamide. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- scopolamine
esketamine intranasal, scopolamine. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- secobarbital
esketamine intranasal, secobarbital. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- serdexmethylphenidate/dexmethylphenidate
esketamine intranasal, serdexmethylphenidate/dexmethylphenidate. Either increases toxicity of the other by sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor. Closely monitor blood pressure with concomitant use of esketamine nasal with stimulants. .
- sevoflurane
esketamine intranasal, sevoflurane. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- sodium oxybate
esketamine intranasal, sodium oxybate. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- stiripentol
esketamine intranasal, stiripentol. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- sufentanil
esketamine intranasal, sufentanil. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- sufentanil SL
esketamine intranasal, sufentanil SL. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- sulpiride
esketamine intranasal, sulpiride. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- suvorexant
esketamine intranasal, suvorexant. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- tapentadol
esketamine intranasal, tapentadol. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- tasimelteon
esketamine intranasal, tasimelteon. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- temazepam
esketamine intranasal, temazepam. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- tetrabenazine
esketamine intranasal, tetrabenazine. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- thalidomide
esketamine intranasal, thalidomide. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- thioridazine
esketamine intranasal, thioridazine. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- thiothixene
esketamine intranasal, thiothixene. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- tiagabine
esketamine intranasal, tiagabine. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- tizanidine
esketamine intranasal, tizanidine. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- topiramate
esketamine intranasal, topiramate. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- tramadol
esketamine intranasal, tramadol. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- tranylcypromine
esketamine intranasal, tranylcypromine. Either increases toxicity of the other by sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor. Closely monitor blood pressure with concomitant use of esketamine nasal with MAO-Is. .
- triazolam
esketamine intranasal, triazolam. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- trifluoperazine
esketamine intranasal, trifluoperazine. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- trimipramine
esketamine intranasal, trimipramine. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- triprolidine
esketamine intranasal, triprolidine. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- valerian
esketamine intranasal, valerian. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- valproic acid
esketamine intranasal, valproic acid. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- vigabatrin
esketamine intranasal, vigabatrin. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- zaleplon
esketamine intranasal, zaleplon. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- ziconotide
esketamine intranasal, ziconotide. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- ziprasidone
esketamine intranasal, ziprasidone. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- zolpidem
esketamine intranasal, zolpidem. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- zonisamide
esketamine intranasal, zonisamide. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
Minor (0)
Adverse Effects
>10% (TRD)
Dissociation (41%)
Dizziness (29%)
Nausea (28%)
Vertigo (23%)
Sedation (23%)
Headache (20%)
Dysgeusia (19%)
Hypoesthesia (18%)
Anxiety (13%)
Lethargy (11%)
Sedation
- Aged <65 yr, 84 mg (61%)
- Aged <65 yr, 56 mg (50%)
- Aged ≥65 yr, 28-84 mg (49%)
Dissociation or perceptual changes
- Aged ≥65 yr, 28-84 mg (75%)
- Aged <65 yr, 84 mg (69%)
- Aged <65 yr, 56 mg (61%)
Blood pressure
-
Aged <65 yr
Diastolic BP ≥25 mm Hg increase (13%)
-
Aged ≥65 yr
- Systolic BP ≥40 mm Hg increase (17%)
- Diastolic BP ≥25 mm Hg increase (14%)
Nausea and vomiting
-
56 mg
- Nausea (27%)
-
84 mg
- Nausea (32%)
- Vomiting (12%)
>10% (MDD)
Dissociation (48%)
Dizziness (45%)
Sedation (29%)
Nausea (27%)
Dysgeusia (20%)
Increased blood pressure (15%)
Anxiety (15%)
Hypoesthesia (13%)
Vomiting (11%)
1-10% (TRD)
Increased blood pressure (10%)
Vomiting (9%)
Insomnia (8%)
Diarrhea (7%)
Nasal discomfort (7%)
Throat irritation (7%)
Dry mouth (5%)
Feeling drunk (5%)
Dysarthria (4%)
Euphoric mood (4%)
Hyperhidrosis (4%)
Constipation (3%)
Feeling abnormal (3%)
Mental impairment (3%)
Tremor (3%)
Pollakiuria (3%)
Oropharyngeal pain (3%)
Tachycardia (2%)
Blood pressure
-
Aged <65 yr
- Systolic BP ≥40 mm Hg increase (8%)
- Diastolic BP ≥110 mm Hg (4%)
- Systolic BP ≥180 mm Hg (3%)
-
Aged ≥65 yr
- Systolic BP ≥180 mm Hg (3%)
Nausea and vomiting
-
56 mg
- Vomiting (6%)
-
84 mg
- Nausea, severe (3%)
- Vomiting, severe (3%)
1-10% (MDD)
Constipation (10%)
Euphoric mood (7%)
Vertigo (6%)
Hyperhidrosis (5%)
Tachycardia (4%)
Dry mouth (4%)
Lethargy (4%)
Oropharyngeal pain (4%)
Throat irritation (4%)
Intentional self-injury (3%)
Toothache (2%)
Felling of relaxation (2%)
Myalgia (2%)
Confusion (2%)
Dysphoria (2%)
Pollakiuria (2%)
Warnings
Black Box Warnings
Sedation and dissociation
- Risk for sedation and dissociation after administration
- Because of these risks, monitor for at least 2 hr at each treatment session, followed by an assessment to determine when the patient is considered clinically stable and ready to leave the healthcare setting
Abuse and misuse
- Potential for drug abuse and misuse
- Consider risks and benefits of prescribing esketamine in patients at higher risk of abuse
- Monitor for signs and symptoms of abuse and misuse
Suicidal thoughts and behaviors
- Antidepressants increased the risk of suicidal thoughts and behavior in children and young adults in short-term studies
- Closely monitor all antidepressant-treated patients for clinical worsening, and for emergence of suicidal thoughts and behaviors
- Esketamine is not approved in pediatric patients
REMS
- Owing to serious adverse outcomes resulting from sedation, dissociation, abuse, and misuse, esketamine is only available through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS)
- Patients treated in outpatient settings (e.g. medical offices and clinics) must be enrolled in the program
- Pharmacies must be certified and only dispense esketamine to healthcare settings that are certified
- More information is available at www.spravatorems.com or 1-855-382-6022
-
Healthcare setting must be certified
- Only dispensed and administered in healthcare settings
- Patients treated in outpatient settings must be enrolled in the program
- Administered by patients under the direct observation of a healthcare provider and monitored by a healthcare provider for at least 2 hr after administration
Contraindications
Aneurysmal vascular disease (including thoracic and abdominal aorta, intracranial, and peripheral arterial vessels) or arteriovenous malformation
History of intracerebral hemorrhage
Hypersensitivity to esketamine, ketamine, or any excipients
Cautions
Available only through a restricted access program (REMS)
Sedation is likely to occur
Dissociative or perceptual changes (including distortion of time, space and illusions), derealization and depersonalization reported
The most common psychological effects are dissociative or perceptual changes (including distortion of time, space, and illusions), derealization, and depersonalization; carefully assess patients with psychosis before administering to determine if benefit outweighs risk
Because of risk of sedation, dissociation, and increased blood pressure, patients must be monitored for at least 2 hr after each treatment session; carefully assess to determine if the patient is clinically stable and ready to leave the healthcare setting
Esketamine is a schedule III controlled substance and may be subject to abuse and diversion; assess risk for each patient before prescribing
Pooled analyses of placebo-controlled trials of antidepressant drugs have shown an increased risk for suicidality in patients aged ≤24 yr; monitor all patients receiving antidepressants, especially during the initial phase of treatment, for clinical worsening and emergence of suicidal thoughts and behaviors
Ulcerative or interstitial cystitis reported with long-term, off-label use or misuse/abuse of ketamine; esketamine intranasal showed a higher rate of lower urinary tract symptoms compared with placebo; however, no cases of interstitial cystitis observed
May cause fetal harm when administered to pregnant women
Cognitive impairment
-
Short-term
- After single dose in healthy volunteers, esketamine caused cognitive performance decline 40 minutes postdose compared with placebo
- Cognitive performance, mental effort, and sleepiness were comparable at 2 hr postdose
-
Long-term
- Long-term cognitive and memory impairment reported with repeated ketamine misuse or abuse
- No adverse effects were observed esketamine intranasal on cognitive functioning in a 1-year open-label safety study
- Long-term cognitive effects have not been evaluated beyond 1 yr
Drug interaction overview
- No clinically significant interactions were observed when esketamine intranasal was coadministered with CYP inducers, CYP3A inhibitors, CYP2B6 inhibitors, or substrates of CYP3A or CYP2B6
- Coadministration with other CNS depressants may cause additive risk for sedation
- Coadministration with psychostimulants or MAOIs may add to risk of increased blood pressure
Pregnancy
Pregnancy
Not recommended during pregnancy
Based on published findings from pregnant animals treated with ketamine (racemic mixture of arketamine and esketamine), may cause fetal harm when administered to pregnant women
Antidepressant registry: Healthcare providers are encouraged to register patients exposed to antidepressants during pregnancy at 1-844-405-6185 or https://womensmentalhealth.org/clinical-and-researchprograms/pregnancyregistry/antidepressants/
Animal data
- N-methyl-D-aspartate (NMDA) receptors blockers administered during the period of peak brain development in pregnant primates increased neuronal apoptosis in the developing brain of the offspring
- Embryo-fetal reproduction studies in rabbits showed skeletal malformations at maternally toxic doses when ketamine was intranasally administered with a No Observed Adverse Effect Level (NOAEL) at estimated esketamine exposures 0.3 times the exposures at the maximum recommended human dose (MRHD) of 84 mg/day
- Additionally, intranasal administration of esketamine to pregnant rats during pregnancy and lactation at exposures that were similar to those at the MRHD resulted in a delay in sensorimotor development in pups during the preweaning period and a decrease in motor activity in the postweaning period
Clinical considerations
- A prospective, longitudinal study followed 201 pregnant women with a history of major depressive disorder who were euthymic and taking antidepressants at the beginning of pregnancy
- The women who discontinued antidepressants during pregnancy were more likely to experience a relapse of major depression than women who continued antidepressants
- Consider the risk of untreated depression when discontinuing or changing treatment with antidepressants during pregnancy and postpartum
Contraception
- Based on published animal reproduction studies, esketamine may cause embryo-fetal harm when administered to a pregnant woman
- However, it is not clear how these animal findings relate to females of reproductive potential treated with the recommended clinical dose
- Consider pregnancy planning and prevention for females of reproductive potential during treatment
Lactation
Esketamine is present in human milk; there are no data on the effects on the breastfed infant or on milk production
Published studies in juvenile animals report neurotoxicity; because of the potential for neurotoxicity, advise patients that breastfeeding is not recommended during treatment
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
Esketamine, the S-enantiomer of racemic ketamine, is a nonselective, noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist (NMDA is an ionotropic glutamate receptor)
The mechanism by which esketamine exerts its antidepressant effect is unknown
Absorption
Bioavailability: 48%
Peak plasma time: 20-40 minutes after last nasal spray of treatment session
Distribution
Vd (IV): 709 L
Protein bound: 43-45%
Metabolism
Primarily metabolized to noresketamine by CYP2B and 3A4, and to a lesser extent by CYP2C9/2C19
Noresketamine is metabolized by CYP-dependent pathways, and certain subsequent metabolites undergo glucuronidation
Noresketamine demonstrated activity at the NMDA receptor with less affinity
Elimination
Half-life: 7-12 hr; 8 hr (noresketamine)
Clearance (IV): 89 L/hr
Excretion
- Urine: <1% unchanged; ≥78% metabolites
- Feces: ≤2% metabolites
Administration
Intranasal Administration
For nasal use only
To prevent loss of medication, do not prime the device before use
Use 2 devices (for 56-mg dose) or 3 devices (for 84-mg dose), with a 5-minute rest between use of each device
See prescribing information for detailed pictures and diagrams
Patient preparation
- Measure blood pressure before dose; if elevated, a decision to delay therapy should take into account benefit and risk to patient
- Instruct patient to blow nose before first device only
- Have patient hold device and recline head to 45° to keep medication inside nose
- See prescribing information for detailed pictures regarding administration technique
-
Food and liquid ingestion
- Food: Do not eat for at least 2 hr before administration
- Liquids: Do not drink liquids for at least 30 min before administration
Postadministration observation
- During and after administration at each treatment session, observe patient for at least 2 hr until the patient is safe to leave
- Measure blood pressure 40 minutes postdose and subsequently as clinically warranted until values decline
- Refer patients experiencing symptoms of a hypertensive crisis (eg, chest pain, shortness of breath) or hypertensive encephalopathy (eg, sudden severe headache, visual disturbances, seizures, diminished consciousness, or focal neurological deficits) immediately for emergency care
- Closely monitor blood pressure with concomitant use of psychostimulants or MAOIs
- Patients with history of hypertensive encephalopathy require more intensive and frequent blood pressure monitoring
- Before administration, instruct patients not to engage in potentially hazardous activities (eg, driving a motor vehicle, operating machinery) until the next day after a restful sleep
Missed treatment sessions
Treatment session(s) missed resulting in worsening symptoms: Consider returning to previous dosing schedule
Treatment session(s) missed with no worsening symptoms: Continue current dosing schedule
Storage
Store at 20-25°C (68-77°F); excursion permitted from 15-30°C (59-86°F)
Security and disposal
- Nasal spray devices must be handled with adequate security, accountability, and proper disposal, per facility procedure for a Schedule III drug product, and per applicable federal, state, and local regulations
Images
BRAND | FORM. | UNIT PRICE | PILL IMAGE |
---|---|---|---|
Spravato nasal - | 56 mg (28 mg x 2) liquid | ![]() | |
Spravato nasal - | 28 mg liquid | ![]() | |
Spravato nasal - | 84 mg (28 mg x 3) liquid | ![]() |
Copyright © 2010 First DataBank, Inc.
Formulary
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