SPRAVATO Dosage & Rx Info | Uses, Side Effects

Spravato Generic Name & Formulations

Legal Class

CIII

General Description

Esketamine 28mg; per nasal spray device (delivers total of 2 sprays).

Pharmacological Class

NMDA receptor antagonist.

How Supplied

Dose Kit 56mg—2; 84mg—3

Manufacturer

Janssen Pharmaceuticals, Inc.

Generic Availability

Mechanism of Action

The mechanism by which esketamine exerts its antidepressant effect is unknown. Esketamine is the S-enantiomer of racemic ketamine, which inhibits the N-methyl-D-aspartate (NMDA) receptor, an ionotropic glutamate receptor.

Spravato Indications

Indications

In conjunction with an oral antidepressant, for treatment-resistant depression (TRD) or depressive symptoms with major depressive disorder (MDD) with acute suicidal ideation or behavior in adults.

Limitations of Use

The effectiveness in preventing suicide or reducing suicidal ideation or behavior has not been demonstrated. Not approved as an anesthetic.

Spravato Dosage and Administration

Adult

See full labeling. Avoid food (≥2hrs) and liquids (≥30mins) prior to use. Wait 5mins between use of each device. ≥18yrs: TRD: Induction phase (Weeks 1–4): Day 1 starting dose: 56mg; subsequent doses: 56mg or 84mg twice weekly. Evaluate for continued treatment after the induction phase. Maintenance phase (Weeks 5–8): 56mg or 84mg once weekly; (Weeks 9 and after): 56mg or 84mg every 2 weeks or once weekly (frequency should be individualized). MDD: 84mg twice weekly for 4 weeks; may reduce to 56mg twice weekly based on tolerability. Evaluate for continued treatment after 4 weeks (treatment >4 weeks has not been systematically evaluated).

Children

<18yrs: not established.

Spravato Contraindications

Contraindications

Aneurysmal vascular disease (including thoracic and abdominal aorta, intracranial and peripheral arterial vessels) or arteriovenous malformation. History of intracerebral hemorrhage. Hypersensitivity to ketamine.

Spravato Boxed Warnings

Boxed Warning

Sedation. Dissociation. Respiratory depression. Abuse and misuse. Suicidal thoughts and behaviors.

Spravato Warnings/Precautions

Warnings/Precautions

Must be administered under supervision of a healthcare provider. Risk of sedation, dissociation, respiratory depression; monitor for ≥2hrs at each treatment session and until clinically stable. Assess benefit/risk in those with psychosis prior to initiation. History of substance use disorder including alcohol; monitor for abuse or dependence. Monitor all patients for clinical worsening and emergence of suicidal thoughts and behaviors. Cardiovascular and cerebrovascular conditions. Assess BP prior to initiation; consider delaying therapy if >140/90mmHg. History of hypertensive encephalopathy; monitor frequently. Cognitive impairment. Impaired ability to drive. Ulcerative/interstitial cystitis: monitor for urinary tract and bladder symptoms during therapy. Hepatic impairment (moderate): monitor for longer time; (severe): not recommended. Embryo-fetal toxicity. Advise females of reproductive potential to consider pregnancy planning and prevention. Pregnancy, nursing mothers: not recommended.

REMS

YES

Spravato Pharmacokinetics

Absorption

Mean absolute bioavailability: ~48%. Time to reach maximum plasma concentration: 20–40 minutes.

Distribution

Mean steady-state volume of distribution: 709 L. Plasma protein bound: ~43–45%.

Metabolism

Primarily (CYP2B6, CYP3A4); and lesser extent (CYP2C9, CYP2C19).

Elimination

Renal (≥78%), fecal (≤2%). Half-life: 7–12 hours. Mean clearance: ~89 L/hr.

Spravato Interactions

Interactions

Concomitant CNS depressants (eg, benzodiazepines, opioids, alcohol) may increase sedation; monitor closely. Concomitant psychostimulants (eg, amphetamines, methylphenidate, modafanil, armodafinil) or MAOIs may increase blood pressure; monitor BP closely. Give concomitant nasal corticosteroid or decongestant ≥1hr before Spravato.

Spravato Adverse Reactions

Adverse Reactions

Dissociation, dizziness, nausea, sedation, vertigo, hypoesthesia, anxiety, lethargy, increased blood pressure, vomiting, feeling drunk, euphoric mood.

Spravato Clinical Trials

See Literature

Spravato Note

Notes

Spravato Patient Counseling