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Spravato is a brand name for Esketamine. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: Spravato, in combination with a SSRI or SNRI, is indicated for adults with treatment-resistant Major Depressive Disorder, who have not responded to at least two different treatments with antidepressants in the current moderate to severe depressive episode. Spravato, co-administered with oral antidepressant therapy, is…
Verbatim from this product's EMA label. Tap a section to expand.
The decision to prescribe this medicinal product should be determined by a psychiatrist. It is intended to be self-administered by the patient under the direct supervision of a healthcare professional. A treatment session consists of nasal administration and a post-administration observation period.
Both administration and post-administration observation should be carried out in an appropriate clinical setting. Assessment before treatment Prior to dosing with Spravato blood pressure should be assessed. 4). 3). Patients with clinically significant or unstable cardiovascular or respiratory conditions require additional precautions.
4). 4). 4). Posology Treatment-resistant Major Depressive Disorder The dose recommendations for treatment-resistant Major Depressive Disorder are shown in Table 1 and Table 2 (adults ≥65 years). It is recommended to maintain the dose the patient receives at the end of the induction phase in the maintenance phase.
Dose adjustments should be made based on efficacy and tolerability to the previous dose. During the maintenance phase, dosing should be individualised to the lowest frequency to maintain remission/response.
Table 1:
Recommended dosing for Spravato in adults <65 years with treatment-resistant Major Depressive Disorder Induction phase Maintenance phase Weeks 1-4: Starting day 1 dose: 56 mg Subsequent doses: 56 mg or 84 mg twice a week Weeks 5-8: 56 mg or 84 mg once weekly From Week 9: 56 mg or 84 mg every 2 weeks or once weekly Evidence of therapeutic benefit should be evaluated at the end of induction phase to determine need for continued treatment.
The need for continued treatment should be re-examined periodically.
Table 2:
Recommended dosing for Spravato in adults ≥65 years with treatment-resistant Major Depressive Disorder Induction phase Maintenance phase Weeks 1-4: Starting day 1 dose: 28 mg Subsequent doses: 28 mg, 56 mg or 84 mg twice a week, all dose changes should be in 28 mg increments Weeks 5-8: 28 mg, 56 mg or 84 mg once weekly, all dose changes should be in 28 mg increments From Week 9: 28 mg, 56 mg or 84 mg every 2 weeks or once weekly, all dose changes should be in 28 mg increments Evidence of therapeutic benefit should be evaluated at the end of induction phase to determine need for continued treatment.
Summary of the safety profile The most commonly observed adverse reactions in patients treated with Spravato were dizziness (31%), dissociation (27%), nausea (27%), headache (23%), somnolence (18%), dysgeusia (18%), vertigo (16%), hypoaesthesia (11%), vomiting (11%), and blood pressure increased (10%).
Tabulated list of adverse reactions Adverse reactions reported with esketamine are listed in Table 3. Within the designated system organ classes, adverse reactions are listed under headings of frequency, using the following convention: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1 000 to < 1/100); rare (≥ 1/10 000 to < 1/1 000); very rare (< 1/10 000); not known (cannot be estimated from the available data).
Table 3:
List of adverse reactions System Organ Class Adverse Drug Reaction Frequency Very common Common Uncommon Rare Psychiatric disorders dissociation anxiety, euphoric mood, confusional state, derealisation, irritability, hallucination including visual hallucination, agitation, illusion, panic attack, time perception altered psychomotor retardation, emotional distress, dysphoria 9 Nervous system disorders dizziness, headache, somnolence, dysgeusia, hypoaesthesia paraesthesia, sedation, tremor, mental impairment, lethargy, dysarthria, disturbance in attention nystagmus, psychomotor hyperactivity seizure Eye disorders vision blurred Ear and labyrinth disorders vertigo tinnitus, hyperacusis Cardiac disorders tachycardia bradycardia Vascular disorders hypertension hypotension Respiratory, thoracic and mediastinal disorders nasal discomfort, throat irritation, oropharyngeal pain, nasal dryness including nasal crusting, nasal pruritus respiratory depression Gastrointestinal disorders nausea, vomiting hypoaesthesia oral, dry mouth salivary hypersecretion Skin and subcutaneous tissue disorders hyperhidrosis cold sweat Renal and urinary disorders pollakiuria, dysuria, micturition urgency General disorders and administration site conditions feeling abnormal, feeling drunk, asthenia, crying, feeling of body temperature change gait disturbance Investigations blood pressure increased Long-term safety Long-term safety was assessed in a Phase 3, multicentre, open-label extension study (TRD3008) in 1 148 adult patients with treatment-resistant Major Depressive Disorder representing 3 777 patient-years of exposure.
1). Use of esketamine does not preclude the need for hospitalisation if clinically warranted, even if patients experience improvement after an initial dose of esketamine. Close supervision of patients and in particular those at high risk should accompany treatment especially in early treatment and following dose changes.
Patients (and caregivers of patients) should be alerted to the need to monitor for any clinical worsening, suicidal behaviour or thoughts and unusual changes in behaviour 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.
8). These effects may impair attention, judgment, thinking, reaction speed and motor skills. 7). Respiratory depression Respiratory depression may occur at high doses following rapid intravenous injection of esketamine or ketamine when used for anaesthesia.
Rare cases of deep sedation have been reported. 5). During post- marketing use, rare cases of respiratory depression have been observed. The majority of these cases have been reported with concomitant use of 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. Close monitoring is required for sedation and respiratory depression. 8). A substantial increase in blood pressure could occur after any treatment session.
1. 8): - Patients with aneurysmal vascular disease (including intracranial, thoracic, or abdominal aorta, or peripheral arterial vessels). - Patients with history of intracerebral haemorrhage. - Recent (within 6 weeks) cardiovascular event, including myocardial infarction (MI).
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The need for continued treatment should be re-examined periodically. After depressive symptoms improve, treatment is recommended for at least 6 months. Acute short-term treatment of psychiatric emergency due to Major Depressive Disorder The recommended dosage for adult patients (<65 years) is 84 mg twice per week for 4 weeks.
Dosage reduction to 56 mg should be made based on tolerability. After 4 weeks of treatment with Spravato, the oral antidepressant (AD) therapy should be continued, per clinical judgement. In these patients, treatment with Spravato should be part of the comprehensive clinical care plan.
8). Nasal corticosteroid or nasal decongestant Patients who require a nasal corticosteroid or nasal decongestant on a dosing day should be advised not to administer these medicinal products within 1 hour before administration. Missed treatment session(s) Patients who have missed treatment session(s) during the first 4 weeks of treatment should continue with their current dosing schedule.
For patients with treatment-resistant Major Depressive Disorder who miss treatment session(s) during maintenance phase and have worsening of depression symptoms, per clinical judgement, consider returning to the previous dosing schedule (see Tables 1 and 2).
Special populations Elderly (65 years of age and older) In elderly patients the initial Spravato dose for treatment-resistant Major Depressive Disorder is 28 mg esketamine (day 1, starting dose, see Table 2 above). Subsequent doses should be increased in increments of 28 mg up to 56 mg or 84 mg, based on efficacy and tolerability.
Spravato has not been studied in elderly patients as acute short-term treatment of psychiatric emergency due to Major Depressive Disorder. Hepatic impairment No dose adjustment is necessary in patients with mild (Child-Pugh class A) or moderate (Child-Pugh class B) hepatic impairment.
However, the maximum dose of 84 mg should be used with caution in patients with moderate hepatic impairment. Spravato has not been studied in patients with severe hepatic impairment (Child-Pugh class C). 2). Renal impairment No dose adjustment is necessary in patients with mild to severe renal impairment.
Patients on dialysis were not studied. Paediatric population The safety and efficacy of Spravato in paediatric patients aged 17 years and younger have not been […]
9 months (up to 79 months) with 63% and 28% of patients receiving treatment at least 3 years and 5 years, respectively. The safety profile of esketamine was consistent with the known safety profile observed in the pivotal clinical trials.
No new safety concerns were identified. Description of selected adverse reactions Dissociation Dissociation (27%) was one of the most common psychological effects of esketamine. 2%). These adverse reactions were reported as transient and self-limited and occurred on the day of dosing.
Dissociation was reported as severe in intensity at the incidence of less than 4% across studies. 5 hours post-dose and the severity tended to reduce over time with repeated treatments. 2%) were primarily mild or moderate in severity, occurred on the day of dosing and resolved spontaneously the same day.
5 hours post-dose. Rates of somnolence were relatively stable over time during long-term treatment. In the cases of sedation, no symptoms of respiratory distress were observed, and haemodynamic parameters (including vital signs and oxygen saturation) remained within normal ranges.
4). 4). The frequency of markedly abnormal blood pressure elevations of SBP (≥40 mmHg increase) ranged from 8% (<65 years) to 17% (≥65 years) and DBP (≥25 mmHg increase) ranged from 13% (<65 years) to 14% (≥65 years) in patients receiving esketamine plus oral antidepressant.
The incidence of increased SBP (≥ 180 mmHg) was 3% and DBP (≥ 110 mmHg) was 4%. Cognitive and memory impairment 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.
9 months (up to 79 months), the effect of esketamine nasal spray on cognitive functioning was evaluated over time and performance remained stable. Urinary tract symptoms Cases of interstitial cystitis have been reported with daily and long-term ketamine use at high doses.
In clinical studies with esketamine, there were no cases of interstitial cystitis, however a higher rate of lower urinary tract symptoms was observed (pollakiuria, dysuria, micturition urgency, nocturia, and cystitis) in esketamine-treated patients compared with placebo-treated patients.
9 months (up to 79 months), no cases of interstitial cystitis were observed. Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk […]
3). Before prescribing esketamine, patients with other cardiovascular and cerebrovascular conditions should be carefully assessed to determine whether the potential benefits of esketamine outweigh its risks. In patients whose blood pressure prior to dose administration is 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 adjust lifestyle and/or pharmacologic therapies to reduce blood pressure before starting treatment with esketamine.
If blood pressure is elevated prior to esketamine administration a decision to delay esketamine therapy should take into account the balance of benefit and risk in individual patients. Blood pressure should be monitored after dose administration.
Blood pressure should be measured around 40 minutes post-dose and subsequently as clinically warranted until values decline. If blood pressure remains elevated for a prolonged period of time, 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. Patients with clinically significant or unstable cardiovascular or respiratory conditions Only initiate treatment with esketamine in patients with clinically significant or unstable cardiovascular or respiratory conditions if the benefit outweighs the risk.
In these patients, esketamine should be administered in a setting where appropriate resuscitation equipment and healthcare professionals with training in cardiopulmonary resuscitation are available. Examples of conditions which should be considered include, but are not limited to: Significant pulmonary insufficiency, including COPD; Sleep apnoea with morbid obesity (BMI ≥35); Patients with uncontrolled brady- or tachyarrhythmias that lead to haemodynamic instability; Patients with a history of an MI.
These patients should be clinically stable and cardiac symptom free prior to administration; Haemodynamically significant valvular heart disease or heart failure (NYHA Class III-IV). Drug abuse, dependence, withdrawal Individuals with a history of drug abuse or dependence may be at greater risk for abuse and misuse of esketamine.
Prior to prescribing esketamine, each patient’s risk for abuse or misuse should be assessed and patients receiving esketamine should be monitored for the development of behaviours or conditions of abuse or misuse, including drug seeking behaviour, while on therapy.
Dependence and tolerance have been reported with prolonged use of ketamine. In individuals who were dependent on ketamine, withdrawal symptoms of cravings, anxiety, shaking, sweating and palpitations have been reported upon discontinuing ketamine.
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