Spravato

In conjunction w/ oral antidepressant therapy for treatment-resistant depression (major depressive disorder in adults who have not responded adequately to at least 2 different antidepressants of adequate dose & duration to treat the current depressive episode) & for the rapid reduction of depressive symptoms in adults w/ major depressive disorder who have acute suicidal ideation or behavior.

Treatment-resistant depression Adult Induction phase: Initially 56 mg on day 1, then 56 mg or 84 mg subsequent doses for wk 1-4 (2 treatment sessions wkly). Maintenance phase: 56 mg or 84 mg once wkly for wk 5-8, then 56 mg or 84 mg every 2 wk or once wkly from wk 9. Elderly ≥65 yr Induction phase: Initially 28 mg on day 1, then 56 mg or 84 mg subsequent doses for wk 1-4 (2 treatment sessions wkly). Subsequent doses should be increased in increments of 28 mg up to 56 mg or 84 mg based on efficacy & tolerability. Maintenance phase: 56 mg or 84 mg once wkly for wk 5-8, then 56 mg or 84 mg every 2 wk or once wkly from wk 9. Major depressive disorder w/ acute suicidal ideation or behavior 84 mg twice wkly for 4 wk, may be reduced to 56 mg based on tolerability. After 4 wk, continue oral antidepressant therapy per clinical judgment.

Hypersensitivity to esketamine or ketamine. Patients for whom an increase in BP or ICP poses a serious risk eg, those w/ known aneurysmal vascular disease (including intracranial, thoracic or abdominal aorta, or peripheral arterial vessels) or history of intracerebral hemorrhage.

For nasal use only. Effectiveness in preventing suicide or reducing suicidal ideation or behavior has not been demonstrated. Does not preclude need for hospitalization, if clinically warranted, even if patients experience improvement after initial dose. Closely monitor patients for clinical worsening or emergence of suicidal thoughts & behaviors, especially during initial few mth of therapy & at times of dosage changes. Greater risk of suicidal thoughts or attempts in patients w/ history of suicide related events or those exhibiting a significant degree of suicidal ideation prior to commencement of treatment. Carefully assess patients w/ CV & cerebrovascular conditions prior to prescribing including those w/ unstable or poorly controlled HTN, history (w/in 6 wk) of CV event including MI, history (w/in 6 mth) of ischemic stroke or transient ischemic attack, hemodynamically significant valvular heart disease (eg, mitral regurgitation, aortic stenosis or aortic regurgitation), NYHA class III-IV heart failure of any etiology. Administration can temporarily raise BP lasting approx 1-2 hr; assess BP prior to dosing. Closely monitor BP in concomitant use w/ psychostimulants or MAOIs. Potential for cognitive (short- & long-term) & motor impairment. Reports of dependence & tolerance w/ prolonged use. Patients w/ history of drug abuse or dependence; history of substance use disorder including alcohol; presence or history of psychosis, mania or bipolar disorder; hyperthyroidism that has not been sufficiently treated; significant pulmonary insufficiency; known uncontrolled brady- or tachyarrhythmias that lead to hemodynamic instability; history of brain injury, hypertensive encephalopathy, intrathecal therapy w/ ventricular shunts, or any other condition associated w/ increased ICP. Advise patients not to eat for at least 2 hr & not to drink liqd at least 30 min prior to administration. Monitor patients for resp depression. Major influence on the ability to drive & use machines. Do not engage in potentially hazardous activities requiring complete mental alertness & motor coordination (eg, driving motor vehicle or operating machinery) until the next day following a restful sleep. Not recommended in severe hepatic impairment (Child-Pugh class C). Women of reproductive potential should use highly effective contraception during & up to 6 wk after last treatment. Not recommended during pregnancy & lactation. Safety & efficacy have not been established in childn ≤17 yr. Efficacy in Japanese & Chinese patients has not been established.

Dissociation, dizziness, nausea, sedation, headache, dysgeusia, hypoesthesia, vertigo, anxiety, increased BP & vomiting. Euphoric mood, emotional distress; lethargy, mental impairment, dysarthria, tremor, nystagmus; tachycardia; throat irritation, nasal discomfort; dry mouth, salivary hypersecretion; hyperhidrosis; pollakiuria; dysuria; feeling drunk & abnormal, asthenia, gait disturbance; increased BP.

May increase sedation w/ CNS depressants eg, benzodiazepines, opioids, alcohol. May increase BP w/ psychostimulants (eg, amphetamines, methylphenidate, modafinil, armodafinil) & MAOIs (eg, tranylcypromine, selegiline, phenelzine). Increased AUC_∞ w/ oral ticlopidine (CYP2B6 inhibitor). Increased mean C_max & AUC_∞ w/ oral clarithromycin (CYP3A4 inhibitor). Decreased mean C_max & AUC_∞ w/ oral rifampicin (CYP3A4 & CYP2B6 inducer). Minor pharmacokinetic effects w/ other nasal spray products (eg, oxymetazoline & mometasone furoate). Reduced mean plasma AUC_∞ of oral midazolam (CYP3A4 substrate).

Antidepressants

N06AX27 - esketamine ; Belongs to the class of other antidepressants.

EDD, Rx