Due to challenges with completion of required laboratory testing or imaging studies for REMS drugs because of self-isolation or quarantine during the COVID-19 public health emergency, the FDA is recommending health care providers prescribing and/or dispensing REMS drugs consider whether there are compelling reasons or not to complete these requirements during this public health emergency and weigh with the patient the benefits and risks of continuing treatment in the absence of the laboratory testing and imaging studies. The FDA will not take action against sponsors and others during the public health emergency for failing to adhere to REMS requirements.
Further information may be found at https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-provides-update-patient-access-certain-rems-drugs-during-covid-19.
Patients are at risk for sedation and for dissociative or perceptual changes after administration of esketamine. Because of the risks of sedation and dissociation, patients must be monitored for at least 2 hours at each treatment session, followed by an assessment to determine when the patient is considered clinically stable and ready to leave the health care setting.
Esketamine has the potential to be abused and misused. Consider the risks and benefits of prescribing esketamine prior to use in patients at higher risk of abuse. Monitor patients for signs and symptoms of abuse and misuse.
Because of the risks of serious adverse outcomes resulting from sedation, dissociation, and abuse and misuse, esketamine is only available through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the SPRAVATO REMS.
Antidepressants increased the risk of suicidal thoughts and behavior in pediatric and young adult patients 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.
Note: Administer in conjunction with an oral antidepressant. Must be administered under the direct supervision of a health care provider with patients monitored for adverse effects for at least 2 hours following administration. In those who respond to short-term esketamine treatment (eg, 1 to 4 weeks), some experts recommend transitioning to maintenance treatment with antidepressants and/or psychotherapy instead of prolonged esketamine treatment (Schreiber 2021; Thase 2021).
Depression, treatment-resistant: Intranasal:
Induction: 56 mg twice weekly; may increase dose (after first dose) based on response and tolerability to 84 mg twice weekly. After 4 weeks, evaluate for evidence of therapeutic benefit to determine need for continued treatment.
Maintenance: Beginning on week 5, using the previously established dose (56 or 84 mg) decrease the dosing frequency to once weekly. At week 9 and onward, continue effective dose (56 or 84 mg) once weekly or decrease to every 2 weeks.
Major depressive disorder (unipolar), with suicidality: Intranasal: Initial: 84 mg twice weekly for 4 weeks; may reduce dosage to 56 mg twice weekly based on tolerability. After 4 weeks, evaluate for evidence of therapeutic benefit to determine need for continued treatment; use beyond 4 weeks has not been evaluated.
Missed treatment sessions:
Treatment-resistant depression:
Missed treatment sessions and no worsening of symptoms: Continue current dosing schedule.
Missed treatment sessions during maintenance treatment and worsening of symptoms: Consider returning to patient's previous dosing schedule (eg, every 2 weeks to once weekly or weekly to twice weekly).
Major depressive disorder (unipolar) with suicidality:
Missed treatment sessions and no worsening of symptoms: Continue current dosing schedule.
There are no dosage adjustments provided in the manufacturer labeling (has not been studied).
Mild to moderate impairment (Child-Pugh classes A and B): There are no dosage adjustments provided in the manufacturer labeling (has not been studied); patients with moderate impairment may need to be monitored for adverse effects for a longer period of time.
Severe impairment (Child-Pugh class C): Use is not recommended (has not been studied).
Refer to adult dosing.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Therapy Pack, Nasal, as hydrochloride:
Spravato (56 MG Dose): 28 mg/device (dose pack of 2) (1 ea) [contains edetate (edta) disodium]
Spravato (84 MG Dose): 28 mg/device (dose pack of 3) (1 ea) [contains edetate (edta) disodium]
No
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Therapy Pack, Nasal:
Spravato: 28 mg (1 ea) [contains edetate (edta) disodium]
C-III
In Canada, Spravato is only available through the JANSSEN JOURNEY Program. Patients, pharmacists, and physicians must all be enrolled in the program prior to prescribing and dispensing. More information can be obtained by contacting the JANSSEN JOURNEY Program at 1-833-257-7191 or https://www.JanssenJourneyHCP.ca.
An FDA-approved patient medication guide, which is available with the product information and at https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/211243s004lbl.pdf#page=42, must be dispensed with this medication.
Intranasal: To reduce risk of nausea and vomiting, avoid food for at least 2 hours before administration and avoid drinking liquids at least 30 minutes prior to administration. If patient requires a nasal corticosteroid or nasal decongestant on a dosing day, administer at least 1 hour prior to administration of esketamine. Do not prime the device prior to use to avoid medication loss; device indicator will show 2 green dots indicating ready for use (get a new device if dots are not present). Each nasal spray device contains 2 sprays (1 spray for each nostril) and delivers a total of 28 mg; spray once into each nostril per device. Use 2 devices for 56 mg dose or 3 devices for 84 mg dose, with a 5-minute rest between use of each device to allow for absorption. Gently blow nose to clear nostrils before the first device only. Instruct patient to recline head about 45 degrees. Instruct patient to close opposite nostril and breathe in through the nose while pushing plunger all way up the nose until it stops. Instruct patient to sniff gently after spraying into the nose. Dab any excess liquid with a tissue; do not blow nose. Dispose of used devices according to procedure for a schedule III drug and according to federal, state, and local regulations.
Depression, treatment-resistant: Treatment of treatment-resistant depression in adults, in conjunction with an oral antidepressant.
Major depressive disorder (unipolar) with suicidality: Treatment of depressive symptoms in adults with major depressive disorder with suicidal ideation or behavior.
Limitations of use: Not approved as an anesthetic agent. The safety and effectiveness of esketamine as an anesthetic agent have not been established. Additionally, esketamine treats depressive symptoms; effectiveness of esketamine in preventing suicide or decreasing suicidal ideation has not been shown.
Spravato may be confused with Steglatro
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Cardiovascular: Increased diastolic blood pressure (4% to 14%), increased systolic blood pressure (3% to 17%)
Gastrointestinal: Dysgeusia (19% to 20%), nausea (27% to 32%; severe nausea: 3%), vomiting (6% to 12%; severe vomiting: 3%)
Nervous system: Anxiety (13% to 15%), depersonalization, derealization, dissociative reaction (41% to 48%), dizziness (29% to 45%), headache (20%), hypoesthesia (13% to 18%), lethargy (4% to 11%), sedated state (23% to 61%), vertigo (6% to 23%)
1% to 10%:
Cardiovascular: Tachycardia (2% to 4%)
Dermatologic: Hyperhidrosis (4% to 5%)
Gastrointestinal: Constipation (3% to 10%), diarrhea (7%), xerostomia (4% to 5%)
Genitourinary: Pollakiuria (2% to 3%)
Nervous system: Confusion (2%), dysarthria (4%), dysphoria (2%), euphoria (4% to 7%), feeling abnormal (3%), insomnia (8%), intoxicated feeling (4% to 5%), mental deficiency (3%), relaxation (2%)
Neuromuscular & skeletal: Myalgia (2%), tremor (3%)
Respiratory: Nasal discomfort (7%), oropharyngeal pain (3% to 4%), throat irritation (4% to 7%)
<1%: Nervous system: Loss of consciousness
Frequency not defined:
Genitourinary: Cystitis (ulcerative and interstitial)
Nervous system: Cognitive dysfunction, drug abuse, suicidal ideation (in young adults ≤24 years), suicidal tendencies (in young adults ≤24 years)
Postmarketing:
Nervous system: Akathisia (Gastaldon 2021), ataxia (Gastaldon 2021), depression (Gastaldon 2021), mania (Gastaldon 2021), panic attack (Gastaldon 2021), paranoid ideation (Gastaldon 2021), talkativeness (logorrhea) (Gastaldon 2021)
Miscellaneous: Crying (Gastaldon 2021)
Hypersensitivity to esketamine, ketamine, or any component of the formulation; aneurysmal vascular disease (including thoracic and abdominal aorta, intracranial, and peripheral arterial vessels) or arteriovenous malformation; history of intracerebral hemorrhage.
Canadian labeling: Additional contraindications (not in US labeling): Recent (within 6 weeks) major cardiovascular event (such as myocardial infarction or cerebrovascular accident).
Concerns related to adverse effects:
• Abuse and misuse: [US Boxed Warning]: Esketamine has the potential to be abused and misused. Consider the risks and benefits of prescribing esketamine prior to use in patients at higher risk of abuse. Monitor patients for signs and symptoms of abuse and misuse including drug-seeking behavior, while on therapy. Individuals with a history of drug abuse or dependence are at greater risk; use careful consideration prior to treatment and monitor for signs of abuse or dependence.
• CNS depression: [US Boxed Warning]: Patients are at risk for sedation after administration of esketamine. Because of the risks of sedation, patients must be monitored for at least 2 hours at each treatment session, followed by an assessment to determine when the patient is considered clinically stable and ready to leave the health care setting. CNS depression may impair physical or mental abilities; patients must be cautioned about performing tasks that require mental alertness (eg, operating machinery or driving) until the next day after a restful sleep. Manufacturer labeling recommends patients arrange transportation home following treatment. No adverse effects of esketamine nasal spray on cognitive functioning were observed in a one-year open-label safety study; long-term cognitive and memory impairment have been reported with repeated ketamine misuse or abuse. Closely monitor sedation with concomitant CNS depressants.
• Dissociation: [US Boxed Warning]: Patients are at risk for dissociative or perceptual changes after administration of esketamine. Because of the risks of dissociation, patients must be monitored for at least 2 hours at each treatment session, followed by an assessment to determine when the patient is considered clinically stable and ready to leave the health care setting. Given its potential to induce dissociative or perceptual changes (including distortion of time, space, and illusions), derealization and depersonalization, assess patients with psychosis carefully before esketamine administration; treatment should only be initiated if benefit outweighs risk.
• Blood pressure: Increases in systolic and/or diastolic BP (occurring ~40 minutes after administration and lasting ~4 hours) have been observed at all recommended doses. Substantial BP increases may occur after any dose even if smaller effects were observed with previous administrations. Esketamine is contraindicated in patients for whom an increase in BP or intracranial pressure poses a serious risk (eg, aneurysmal vascular disease, arteriovenous malformation, history of intracerebral hemorrhage). Carefully assess patients with other cardiovascular and cerebrovascular conditions prior to esketamine use to determine whether the potential benefits outweigh the risks. Assess BP prior to administration; if elevated (>140/90 mm Hg) consider the benefits and risks of delaying therapy. Measure BP ~40 minutes post-dose and subsequently as clinically indicated for at least 2 hours after administration of last dose or 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 disturbance, seizures, diminished consciousness or focal neurological deficits) immediately for emergency care. Closely monitor blood pressure with concomitant use of esketamine with psychostimulants or monoamine oxidase inhibitors. In patients with a history of hypertensive encephalopathy, more intensive monitoring, including more frequent BP and symptom assessment is warranted because these patients are at increased risk for developing encephalopathy with even small increases in BP.
• Suicidal thoughts and behaviors: [US Boxed Warning]: Antidepressants increased the risk of suicidal thoughts and behavior in pediatric and young adult patients in short-term studies. Short-term studies did not show an increased risk in patients >24 years of age and showed a decreased risk in patients ≥65 years. Closely monitor all patients for clinical worsening, suicidality, or unusual changes in behavior, particularly during the initial 1 to 2 months of therapy or during periods of dosage adjustments (increases or decreases); the patient's family or caregiver should be instructed to closely observe the patient and communicate condition with health care provider. The possibility of a suicide attempt is inherent in major depression and may persist until remission occurs. Worsening depression and severe abrupt suicidality that are not part of the presenting symptoms may require discontinuation or modification of drug therapy. Esketamine is not approved in pediatric patients.
• Ulcerative or interstitial cystitis: Cases of ulcerative or interstitial cystitis have been reported in individuals with long-term off-label use or misuse/abuse of ketamine. In clinical trials there was a higher rate of lower urinary tract symptoms (pollakiuria, dysuria, micturition urgency, nocturia, and cystitis) in esketamine-treated patients; however, no cases of esketamine-related interstitial cystitis were observed in patients treated for up to a year. Monitor for urinary tract and bladder symptoms during the course of treatment and refer to an appropriate health care provider as clinically indicated.
Disease-related concerns:
• Hepatic impairment: Patients with moderate hepatic impairment may need to be monitored for adverse reactions for a longer period of time. Esketamine is not recommended in patients with severe hepatic impairment.
Concurrent drug therapy issues:
• Drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
Other warnings/precautions:
• Appropriate use: Use of esketamine does not preclude the need for hospitalization if clinically needed, even if improvement is seen after initial dose. Additionally, esketamine treats depressive symptoms; the safety and effectiveness of esketamine in the prevention of suicide or reducing suicidal ideation or behavior has not been established.
• REMS program: [US Boxed Warning]: Because of the risks of serious adverse outcomes resulting from sedation, dissociation, and abuse and misuse, esketamine is only available through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the SPRAVATO REMS. Under the esketamine REMS program, only certified health care settings and pharmacies may administer and dispense esketamine. Esketamine may only be administered to patients who are enrolled in the program and under the direct observation of a health care provider (during administration) with monitoring for at least 2 hours following the last dose. Call 855-382-6022 or visit www.spravatorems.com for further information.
Substrate of CYP2B6 (major), CYP2C19 (minor), CYP2C9 (minor), CYP3A4 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Risk C: Monitor therapy
Alizapride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Androgens: Hypertension-Associated Agents may enhance the hypertensive effect of Androgens. Risk C: Monitor therapy
Azelastine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Management: Use caution if coadministering blonanserin and CNS depressants; dose reduction of the other CNS depressant may be required. Strong CNS depressants should not be coadministered with blonanserin. Risk D: Consider therapy modification
Brexanolone: CNS Depressants may enhance the CNS depressant effect of Brexanolone. Risk C: Monitor therapy
Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Bromopride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Bromperidol: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Buprenorphine: CNS Depressants may enhance the CNS depressant effect of Buprenorphine. Management: Consider reduced doses of other CNS depressants, and avoiding such drugs in patients at high risk of buprenorphine overuse/self-injection. Initiate buprenorphine at lower doses in patients already receiving CNS depressants. Risk D: Consider therapy modification
Cannabinoid-Containing Products: CNS Depressants may enhance the CNS depressant effect of Cannabinoid-Containing Products. Risk C: Monitor therapy
Chlormethiazole: May enhance the CNS depressant effect of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used. Risk D: Consider therapy modification
Chlorphenesin Carbamate: May enhance the adverse/toxic effect of CNS Depressants. Risk C: Monitor therapy
CNS Depressants: Esketamine may enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
CNS Stimulants: Esketamine may enhance the hypertensive effect of CNS Stimulants. Risk C: Monitor therapy
Corticosteroids (Nasal): May diminish the therapeutic effect of Esketamine. Management: Patients who require a nasal corticosteroid on an esketamine dosing day should administer the nasal corticosteroid at least 1 hour before esketamine. Risk D: Consider therapy modification
Daridorexant: May enhance the CNS depressant effect of CNS Depressants. Management: Dose reduction of daridorexant and/or any other CNS depressant may be necessary. Use of daridorexant with alcohol is not recommended, and the use of daridorexant with any other drug to treat insomnia is not recommended. Risk D: Consider therapy modification
Decongestants (Nasally Administered): May diminish the therapeutic effect of Esketamine. Management: Patients who require a nasal decongestant on an esketamine dosing day should administer the nasal decongestant at least 1 hour before esketamine. Risk D: Consider therapy modification
DexmedeTOMIDine: CNS Depressants may enhance the CNS depressant effect of DexmedeTOMIDine. Management: Monitor for increased CNS depression during coadministration of dexmedetomidine and CNS depressants, and consider dose reductions of either agent to avoid excessive CNS depression. Risk D: Consider therapy modification
Difelikefalin: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Dimethindene (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Doxylamine: May enhance the CNS depressant effect of CNS Depressants. Management: The manufacturer of Diclegis (doxylamine/pyridoxine), intended for use in pregnancy, specifically states that use with other CNS depressants is not recommended. Risk C: Monitor therapy
Droperidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (eg, opioids, barbiturates) with concomitant use. Risk D: Consider therapy modification
Flunarizine: CNS Depressants may enhance the CNS depressant effect of Flunarizine. Risk X: Avoid combination
Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Management: Reduce the dose of CNS depressants when combined with flunitrazepam and monitor patients for evidence of CNS depression (eg, sedation, respiratory depression). Use non-CNS depressant alternatives when available. Risk D: Consider therapy modification
HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Management: Consider a decrease in the CNS depressant dose, as appropriate, when used together with hydroxyzine. Increase monitoring of signs/symptoms of CNS depression in any patient receiving hydroxyzine together with another CNS depressant. Risk D: Consider therapy modification
Kava Kava: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Kratom: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Lemborexant: May enhance the CNS depressant effect of CNS Depressants. Management: Dosage adjustments of lemborexant and of concomitant CNS depressants may be necessary when administered together because of potentially additive CNS depressant effects. Close monitoring for CNS depressant effects is necessary. Risk D: Consider therapy modification
Lisuride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Lofexidine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Memantine: NMDA Receptor Antagonists may enhance the adverse/toxic effect of Memantine. Risk C: Monitor therapy
Methotrimeprazine: CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce the usual dose of CNS depressants by 50% if starting methotrimeprazine until the dose of methotrimeprazine is stable. Monitor patient closely for evidence of CNS depression. Risk D: Consider therapy modification
Metoclopramide: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Risk C: Monitor therapy
MiFEPRIStone: May increase the serum concentration of CYP2B6 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
Minocycline (Systemic): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Monoamine Oxidase Inhibitors: Esketamine may enhance the hypertensive effect of Monoamine Oxidase Inhibitors. Risk C: Monitor therapy
Olopatadine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Opioid Agonists: CNS Depressants may enhance the CNS depressant effect of Opioid Agonists. Management: Avoid concomitant use of opioid agonists and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider therapy modification
Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Risk X: Avoid combination
Oxomemazine: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Oxybate Salt Products: CNS Depressants may enhance the CNS depressant effect of Oxybate Salt Products. Management: Consider alternatives to this combination when possible. If combined, dose reduction or discontinuation of one or more CNS depressants (including the oxybate salt product) should be considered. Interrupt oxybate salt treatment during short-term opioid use Risk D: Consider therapy modification
OxyCODONE: CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider therapy modification
Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Risk X: Avoid combination
Perampanel: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Piribedil: CNS Depressants may enhance the CNS depressant effect of Piribedil. Risk C: Monitor therapy
Pramipexole: CNS Depressants may enhance the sedative effect of Pramipexole. Risk C: Monitor therapy
Procarbazine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Ropeginterferon Alfa-2b: CNS Depressants may enhance the adverse/toxic effect of Ropeginterferon Alfa-2b. Specifically, the risk of neuropsychiatric adverse effects may be increased. Management: Avoid coadministration of ropeginterferon alfa-2b and other CNS depressants. If this combination cannot be avoided, monitor patients for neuropsychiatric adverse effects (eg, depression, suicidal ideation, aggression, mania). Risk D: Consider therapy modification
ROPINIRole: CNS Depressants may enhance the sedative effect of ROPINIRole. Risk C: Monitor therapy
Rotigotine: CNS Depressants may enhance the sedative effect of Rotigotine. Risk C: Monitor therapy
Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Risk C: Monitor therapy
Solriamfetol: May enhance the hypertensive effect of Hypertension-Associated Agents. Risk C: Monitor therapy
Suvorexant: CNS Depressants may enhance the CNS depressant effect of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. Risk D: Consider therapy modification
Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Risk X: Avoid combination
Thiotepa: May increase the serum concentration of CYP2B6 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
Trimeprazine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Valerian: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Zolpidem: CNS Depressants may enhance the CNS depressant effect of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. Risk D: Consider therapy modification
Based on adverse events observed in animal reproduction studies, the manufacturer recommends females of reproductive potential consider pregnancy planning and prevention during esketamine therapy.
Based on animal data, use of medications that block N-methyl-D-aspartate (NMDA) receptors and/or potentiate gamma-aminobutyric acid (GABA) activity, may affect brain development.
The ACOG recommends treatment of depression during pregnancy should be individualized and incorporate the clinical expertise of the mental health clinician, obstetrician, primary health care provider, and pediatrician. According to the American Psychiatric Association (APA), the risks of medication treatment should be weighed against other treatment options and untreated depression. For women who discontinue antidepressant medications during pregnancy and who may be at high risk for postpartum depression, the medications can be restarted following delivery. Treatment algorithms have been developed by the ACOG and the APA for the management of depression in women prior to conception and during pregnancy (ACOG 2008; APA 2010; Yonkers 2009)
Pregnant females exposed to antidepressants during pregnancy are encouraged to enroll in the National Pregnancy Registry for Antidepressants (NPRAD). Females 18 to 45 years of age or their health care providers may contact the registry by calling 1-844-405-6185 or online at https://womensmentalhealth.org/clinical-and-researchprograms/ pregnancyregistry/antidepressants/. Enrollment should be done as early in pregnancy as possible.
Esketamine is present in breast milk
Based on animal data, use of medications that block N-methyl-D-aspartate (NMDA) receptors and/or potentiate gamma-aminobutyric acid (GABA) activity, may affect brain development. Infants may be most vulnerable during the first several months of life and possibly until ~3 years of age. Due to the potential for adverse events in a nursing infant, breastfeeding is not recommended by the manufacturer.
Monitor all patients for adverse effects in a health care setting for at least 2 hours following administration of the last dose.
Blood pressure (prior to dose; repeat ~40 minutes post-dose, and then as clinically indicated for at least 2 hours post-dose); suicidal ideation (especially at the beginning of therapy or when doses are increased or decreased)
Prior to administration, assess patient risk for abuse or misuse, psychosis, and cardiovascular and cerebrovascular conditions.
Closely monitor all patients for clinical worsening of depression and emergence of suicidal thoughts and behaviors, especially during the initial few months of therapy and at times of dosage changes; assess for evidence of therapeutic benefit at the end of the induction phase to determine need for continued treatment; closely monitor patients for signs/symptoms of abuse and misuse during therapy; monitor for sedation with use of concomitant CNS depressants; monitor for urinary tract or bladder symptoms during the course of treatment.
Esketamine (S-enantiomer of racemic ketamine) is a nonselective, noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist. The mechanism by which it exerts its antidepressant effect is unknown. The major circulating metabolite noresketamine demonstrated activity at the same receptor with less affinity.
Distribution: Vd: 709 L
Protein binding: ~43% to 45%
Metabolism: Primarily metabolized to the active metabolite noresketamine via cytochrome P450 (CYP) enzymes CYP2B6 and CYP3A4 and to a lesser extent CYP2C9 and CYP2C19. Noresketamine is metabolized via CYP-dependent pathways and certain subsequent metabolites undergo glucuronidation.
Bioavailability: ~48%
Half-life elimination: Esketamine: 7 to 12 hours; Noresketamine (active metabolite): ~8 hours
Time to peak, plasma: 20 to 40 minutes
Excretion: Urine (<1% as unchanged drug)
Hepatic function impairment: Mean esketamine AUC and t1/2 values were higher in patients with moderate hepatic impairment.
Older adult: Mean esketamine Cmax and AUC values were higher in elderly patients compared with younger adult patients.
Soln Therapy Pack (Spravato (56 MG Dose) Nasal)
28MG/DEVICE% (per each): $410.20
Soln Therapy Pack (Spravato (84 MG Dose) Nasal)
28MG/DEVICE% (per each): $410.20
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