INTRODUCTION:

ISpravato (esketamine) nasal spray is a non-competitive N-methyl D-aspartate (NMDA) receptor antagonist approved in March 2019. Spravato is specifically indicated for use, in conjunction with an oral antidepressant, for the treatment of treatment-resistant depression (TRD) in adults (Bahr, 2019). Spravato is supplied as a spray for intranasal administration.

Class:

NMDA Antagonists, Antidepressants.

Dosage:

Induction Phase: Weeks 1 to 4: Administer twice per week; Day 1 starting dose: 56 mg followed by subsequent doses of 56 mg or 84 mg. (Popov, 2019)

Maintenance Phase: Weeks 5 to 8: Administer once weekly at 56mg or 84mg. Week 9 and after: Administer every 2 weeks or once weekly at 56mg or 84mg.

Dosing frequency should be individualized to the least frequent dosing to maintain remission/response.

Pharmacodynamics:

Absorption: The mean absolute bioavailability is about 48%. The Peak plasma time is 20-40 minutes after last nasal spray of treatment session. (Jonkman, 2017)

Distribution: The mean steady-state volume of distribution of esketamine administered by the intravenous route is 709 L. Protein binding of esketamine was approximately 43% to 45%. The brain-to-plasma ratio of noresketamine, the primary metabolite of esketamine, is 4- to 6-times lower than that of esketamine.

Metabolism:

Primarily metabolized to noresketamine by cytochrome (CYP) enzymes. Noresketamine is metabolized by CYP-dependent pathways, and certain subsequent metabolites undergo glucuronidation.

Elimination:

The Half-life is about7-12 hours. The mean clearance (IV) is approximately 89 L/hr.

Excretion:

Urine: (<1%) as unchanged drug, metabolites: (≥78%), Feces: (≤2%)

Drug interactions:

· Central Nervous System Depressants: Increase sedation.

· Psychostimulants: Increase blood pressure.

· Monoamine Oxidase Inhibitors: Increase blood pressure.

Indications:

Treatment Resistant Depression.

Mechanism of action:

Spravato targets the N-methyl-D-aspartate (NMDA) receptor in the brain. The mechanism by which esketamine exerts its antidepressant effect is unknown. The major circulating metabolite of esketamine demonstrated activity at the same receptor with less affinity. (Regi, 2022)

Contraindications:

· Aneurysmal vascular disease (including thoracic and abdominal aorta, intracranial and peripheral arterial vessels) or arteriovenous malformation.

· History of intracerebral hemorrhage.

· Hypersensitivity to ketamine.

Adverse Effects:

Dissociation, Dizziness, Nausea and vomiting, Vertigo, Sedation, Headache, Dysgeusia Hypoesthesia, Anxiety, Lethargy, Sedation, Increased Blood pressure, Insomnia, Diarrhea, Nasal discomfort, Throat irritation, Dry mouth, Feeling drunk Dysarthria, Euphoric mood, Hyperhidrosis, Constipation, Feeling abnormal, Mental impairment, Tremor, Pollakiuria, Oropharyngeal pain, Tachycardia.

Patient Preparation:

a) Measure blood pressure before dose; if elevated, a decision to delay therapy should take into account benefit and risk to patient.

b) Instruct patient to blow nose before first device only.

c) Have patient hold device and recline head to 45° to keep medication inside nose.

d) See prescribing information for detailed regarding administration technique.

e) Food and liquid ingestion

f) Food: Do not eat for at least 2 hr before administration

g) Liquids: Do not drink liquids for at least 30 min before administration

Nurses Responsibilities:

· 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 severeheadache, visual disturbances, seizures, diminished consciousness, or focal neurological deficits) immediately for emergency care

· Closely monitor blood pressure with concomitant use of psychostimulants or MAOIs.

· Instruct patients not to engage in potentially hazardous activities (eg, driving a motor vehicle, operating machinery).

· Patients with history of hypertensive encephalopathy require more intensive and frequent blood pressure monitoring.

· Missed treatment sessions

Consider returning to previous dosing schedule (ie, 2Weeks to once weekly or weekly to twice weekly) if treatment sessions are missed and there is worsening of depression symptoms

Additional information:

The Spravato drug label comes with the following

Black Box Warning: Risk for sedation and dissociation after administration. Monitor patients for at least two hours after administration.

· Potential for abuse and misuse.

Consider the risks and benefits of prescribing Spravato prior to using in patients at higher risk of abuse. Monitor patients for signs and symptoms of abuse and misuse.

· Spravato is only available through a restricted program called the Spravato REMS.

· Increased risk of suicidal thoughts and behaviors in pediatric and young adult patients taking antidepressants.

Closely monitor all antidepressant-treated patients for clinical worsening and emergence of suicidal thoughts and behaviors. Spravato is not approved for use in pediatric patients.

REFERENCES:

1. https://www.spravato.com/

2. https://reference.medscape.com/drug/spravato-esketamine-intranasal-1000325

3. https://www.empr.com/drug/spravato/

4. https://www.centerwatch.com/drug-information/fda-approved-drugs/drug/100357/spravato-esketamine-nasal-spray

5. https://www.pharmaceutical-technology.com/news/fda-janssen-depression-drug-spravato/

Received on 10.04.2023 Modified on 29.04.2023

Asian J. Nursing Education and Research. 2023; 13(3):226-227.

DOI: 10.52711/2349-2996.2023.00048