Indicated, in conjunction with an oral antidepressant, for the treatment of:

• Treatment-resistant depression (TRD) in adults
• Depressive symptoms in adults with major depressive disorder (MDD) with acute suicidal ideation or behavior

The effectiveness of SPRAVATO in preventing suicide or in reducing suicidal ideation or behavior has not been demonstrated.

Use of SPRAVATO does not preclude the need for hospitalization if clinically warranted, even if patients experience improvement after an initial dose of SPRAVATO.

SPRAVATO is not approved as an anesthetic agent. The safety and effectiveness of SPRAVATO as an anesthetic agent have not been established.

Patients are at risk for sedation after administration of SPRAVATO.

Patients are at risk for dissociative or perceptual changes after administration of SPRAVATO.

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 healthcare setting.

SPRAVATO has the potential to be abused and misused. Consider the risks and benefits of prescribing SPRAVATO 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, SPRAVATO 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. SPRAVATO is not approved for use in pediatric patients.

SPRAVATO must be administered under the direct supervision of a healthcare provider. A treatment session consists of nasal administration of SPRAVATO and post-administration observation under supervision.

Assess blood pressure prior to dosing with SPRAVATO.

If baseline blood pressure is elevated (e.g., >140 mmHg systolic, >90 mmHg diastolic), consider the risks of short term increases in blood pressure and benefit of SPRAVATO treatment.

Do not administer SPRAVATO if an increase in blood pressure or intracranial pressure poses a serious risk.

After dosing with SPRAVATO, reassess blood pressure at approximately 40 minutes (which corresponds with the Cmax) and subsequently as clinically warranted.

If blood pressure is decreasing and the patient appears clinically stable for at least two hours, the patient may be discharged at the end of the post-dose monitoring period; if not, continue to monitor.

Because some patients may experience nausea and vomiting after administration of SPRAVATO, advise patients to avoid food for at least 2 hours before administration and to avoid drinking liquids at least 30 minutes prior to administration.

Patients who require a nasal corticosteroid or nasal decongestant on a dosing day should administer these medications at least 1 hour before SPRAVATO.

Before SPRAVATO administration, instruct patients not to engage in potentially hazardous activities, such as driving a motor vehicle or operating machinery, until the next day after a restful sleep.

SPRAVATO is contraindicated in patients with:

• 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 of the excipients

SPRAVATO has not been studied in patients with severe hepatic impairment (Child-Pugh class C). Use in this population is not recommended.

The most common psychological effects of SPRAVATO were dissociative or perceptual changes (including distortion of time, space and illusions), derealization and depersonalization. Given its potential to induce dissociative effects, carefully assess patients with psychosis before administering SPRAVATO; treatment should be initiated only if the benefit outweighs the risk.

SPRAVATO contains esketamine, a Schedule III controlled substance (CIII), and may be subject to abuse and diversion. Assess each patient’s risk for abuse or misuse prior to prescribing SPRAVATO and monitor all patients receiving SPRAVATO for the development of these behaviors or conditions, including drug-seeking behavior, while on therapy.

In a study in healthy volunteers, a single dose of SPRAVATO caused cognitive performance decline 40 minutes post-dose.

Cases of ulcerative or interstitial cystitis have been reported in individuals with long-term off-label use or misuse/abuse of ketamine.

Tolerance has been reported with prolonged use of ketamine. Tolerance is a physiological state characterized by a reduced response to a drug after repeated administration (i.e., a higher dose of a drug is required to produce the same effect that was once obtained at a lower dose). Similar tolerance would be expected with prolonged use of esketamine.

Concomitant use with psychostimulants (e.g., amphetamines, methylphenidate, modafinil, armodafinil) may increase blood pressure.

Concomitant use with CNS depressants (e.g., benzodiazepines, opioids, alcohol) may increase sedation.

Concomitant use with monoamine oxidase inhibitors (MAOIs) may increase blood pressure.

SPRAVATO is not recommended during pregnancy. Based on published findings from pregnant animals treated with ketamine, the racemic mixture of arketamine and esketamine, SPRAVATO may cause fetal harm when administered to pregnant women.

Esketamine is present in human milk. Because of the potential for neurotoxicity, advise patients that breastfeeding is not recommended during treatment with SPRAVATO.

GoToSource

• Use in patients under 18 years of age. GoToSource 

• Pain. GoToSource

• Anxiety disorders and post-traumatic stress disorder. GoToSource

Cystitis (bladder inflammation), suicidal ideation, interstitial cystitis (chronic bladder pain) and embryo-fetal toxicity. GoToSource

Hypothermia (drop in body temperature), lacunar stroke and seizures. GoToSource

Impaired attention, judgment, thinking, reaction speed and motor skills. GoToSource

Cognitive impairment. GoToSource

Sedation, dissociation, abuse and misuse, suicidal behavior, dysgeusia (altered sense of taste), hypoesthesia (numbness), vertigo (sensation of motion), vomiting, upper respiratory tract infections, hallucinations, euphoria, increased blood pressure and heart rate. GoToSource

Lawsuits filed for death, strokes and severe hypertension.