Spravato Special Precautions

Suicide/suicidal thoughts or clinical worsening: The effectiveness of Esketamine (Spravato) in preventing suicide or in reducing suicidal ideation or behavior has not been demonstrated.
Use of Esketamine (Spravato) for the rapid reduction of depressive symptoms in adult patients with Major Depressive Disorder who have acute suicidal ideation or behavior does not preclude the need for hospitalization, if clinically warranted, even if patients experience improvement after an initial dose of Esketamine (Spravato).
Closely monitor all antidepressant treated patients including patients treated with Esketamine (Spravato) for clinical worsening or emergence of suicidal thoughts and behaviors, especially during the initial few months of drug therapy and at times of dosage changes. Patients (and caregivers of patients) should be alerted to the need to monitor for any clinical worsening, suicidal behavior or thoughts and unusual changes in behavior and to seek medical advice immediately if these symptoms present.
Depression is associated with an increased risk of suicidal thoughts, self harm and suicide (suicide related events). This risk persists until significant remission occurs, therefore, patients should be closely monitored. It is general clinical experience that the risk of suicide may increase in the early stages of recovery.
Patients with a history of suicide related events or those exhibiting a significant degree of suicidal ideation prior to commencement of treatment are known to be at greater risk of suicidal thoughts or suicide attempts and should receive careful monitoring during treatment.
Effect on blood pressure: Esketamine (Spravato) can cause transient increases in systolic and/or diastolic blood pressure which peak at approximately 40 minutes after drug administration and last approximately 1‑2 hours (see Adverse Reactions). Patients with cardiovascular and cerebrovascular conditions should be carefully assessed before prescribing Esketamine (Spravato) and treatment initiated only if the benefit outweighs the risk (see Contraindications). Examples of conditions which should be carefully considered include: Unstable or poorly controlled hypertension.
History (within 6 weeks) of cardiovascular event, including myocardial infarction (MI). Patients with a history of an MI should be clinically stable and cardiac symptom free prior to dosage administration.
History (within 6 months) of ischemic stroke or transient ischemic attack.
Hemodynamically significant valvular heart disease such as mitral regurgitation, aortic stenosis, or aortic regurgitation.
New York Heart Association (NYHA) Class III‑IV heart failure of any etiology.
Administration of Esketamine (Spravato) can temporarily raise blood pressure lasting approximately 1‑2 hours. Blood pressure should be assessed prior to dosing with Esketamine (Spravato). In patients whose blood pressures prior to dose administration are judged to be elevated (as a general guide: >140/90 mmHg for patients <65 years of age and >150/90 mmHg for patients ≥65 years of age), it is appropriate to consider lifestyle and/or pharmacologic therapies to reduce blood pressure before starting treatment with Esketamine (Spravato). The decision whether or not to delay Esketamine (Spravato) therapy should take into account the balance of benefit and risk in individual patients.
Blood pressure should be monitored after dose administration until blood pressure returns to acceptable levels. If blood pressure remains too high, assistance should promptly be sought from practitioners experienced in blood pressure management. Patients who experience symptoms of a hypertensive crisis should be referred immediately for emergency care.
Closely monitor blood pressure with concomitant use of Esketamine (Spravato) with psychostimulants or monoamine oxidase inhibitors (MAOIs) (see Interactions).
Respiratory depression: During postmarketing use, rare cases of respiratory depression have been observed (see Postmarketing data under Adverse Reactions). The majority of these cases have been reported with the use of Esketamine (Spravato) in combination with other CNS depressants and/or in patients with comorbidities such as obesity, anxiety, cardiovascular and respiratory conditions. These events were transient in nature and resolved after verbal/tactile stimulation or supplemental oxygen. Patients should be monitored for respiratory depression.
Potential for Cognitive and Motor Impairment: Esketamine (Spravato) has been reported to cause somnolence, sedation, dissociative symptoms, perception disturbances, dizziness, vertigo and anxiety during the clinical trials (see Adverse Reactions).
These effects may impair attention, judgment, thinking, reaction speed and motor skills. Tolerance to the previously mentioned effects may develop after a few treatment sessions. At each treatment session, patients should be monitored by a healthcare professional to assess when the patient is considered clinically stable (see Post‑administration observation under Dosage & Administration).
Short-Term Cognitive Impairment: In a study in healthy volunteers, a single dose of Esketamine (Spravato) caused cognitive performance decline 40 minutes post-dose. Compared to placebo-treated subjects, Esketamine (Spravato)-treated subjects required a greater effort to complete cognitive tests at 40 minutes post-dose. Cognitive performance and mental effort were comparable between Esketamine (Spravato) and placebo at 2 hours post-dose. Sleepiness was comparable after 4 hours post-dose.
Long-Term Cognitive Impairment: Long‑term cognitive and memory impairment have been reported with long‑term ketamine use or drug abuse. These effects did not increase over time and were reversible after discontinuing ketamine. In the clinical trials, the effect of esketamine nasal spray on cognitive functioning was evaluated over time and performance remained stable.
Effect on Driving: Two studies were conducted to assess the effects of Esketamine (Spravato) on the ability to drive (see Pharmacology: Pharmacodynamics: Clinical Studies: Effects on driving under Actions). Before Esketamine (Spravato) administration, instruct patients not to engage in potentially hazardous activities requiring complete mental alertness and motor coordination, such as driving a motor vehicle or operating machinery, until the next day following a restful sleep (see Potential for Cognitive and Motor Impairment as previously mentioned).
Bladder Effects: Cases of interstitial cystitis have been reported in subjects using ketamine for recreational use or for treatment of chronic pain at high doses with long‑term use. In clinical studies with esketamine nasal spray, subjects were assessed for symptoms of cystitis, bladder pain and interstitial cystitis. No cases of esketamine‑related interstitial cystitis were observed in any of the studies, which involved treatment for up to a year (see Pharmacology: Pharmacodynamics: Clinical Studies under Actions).
Drug abuse and dependence: Abuse: Individuals with a history of drug abuse or dependence may be at greater risk for abuse and misuse of Esketamine (Spravato). Careful consideration is advised prior to treatment of individuals with a history of substance use disorder, including alcohol. Monitoring for signs of abuse or dependence is recommended.
The potential for abuse, misuse and diversion of Esketamine (Spravato) is minimized due to the product's design and the administration taking place under the supervision of a healthcare professional.
Ketamine, the racemic mixture of arketamine and esketamine, has been reported as a drug of abuse. In a study of abuse potential conducted in recreational polydrug users (n=41), single doses of esketamine nasal spray (84 mg and 112 mg) and the positive control drug intravenous ketamine (0.5 mg/kg infused over 40 minutes) produced significantly greater scores than placebo on subjective ratings of "drug liking" and on other measures of subjective drug effects.
Dependence: Dependence and tolerance have been reported with prolonged use of ketamine. Individuals who were dependent on ketamine reported withdrawal symptoms of cravings, anxiety, shaking, sweating and palpitations. Monitoring for signs of dependence is recommended.
Other Populations at Risk: Esketamine (Spravato) should be used with caution in patients with the following conditions. These patients should be carefully assessed before prescribing Esketamine (Spravato) and treatment initiated only if the benefit outweighs the risk: Presence or history of psychosis.
Presence or history of mania or bipolar disorder.
Hyperthyroidism that has not been sufficiently treated.
Significant pulmonary insufficiency.
Patients with known uncontrolled brady‑ or tachyarrhythmias that lead to hemodynamic instability.
History of brain injury, hypertensive encephalopathy, intrathecal therapy with ventricular shunts, or any other condition associated with increased intracranial pressure.
Effects on Ability to Drive and Use Machines: Esketamine (Spravato) has a major influence on the ability to drive and use machines. In clinical studies, Esketamine (Spravato) has been reported to cause somnolence, sedation, dissociative symptoms, perception disturbances, dizziness, vertigo and anxiety (see Adverse Reactions). Before Esketamine (Spravato) administration, instruct patients not to engage in potentially hazardous activities requiring complete mental alertness and motor coordination, such as driving a motor vehicle or operating machinery, until the next day following a restful sleep (see Effects on Driving as previously mentioned and Pharmacology: Pharmacodynamics: Clinical Studies under Actions).