Source: European Medicines Agency (EU) Revision Year: 2025 Publisher: Janssen-Cilag International NV, Turnhoutseweg 30, B-2340 Beerse, Belgium
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 indicated in adults with a moderate to severe episode of Major Depressive Disorder, as acute short-term treatment, for the rapid reduction of depressive symptoms, which according to clinical judgement constitute a psychiatric emergency.
See section 5.1 for a description of the populations studied.
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.
Prior to dosing with Spravato blood pressure should be assessed.
If baseline blood pressure is elevated the risks of short-term increases in blood pressure and benefit of the treatment should be considered (see section 4.4). The medicinal product should not be administered if an increase in blood pressure or intracranial pressure poses a serious risk (see section 4.3).
Patients with clinically significant or unstable cardiovascular or respiratory conditions require additional precautions. In these patients, the medicinal product should be administered in a setting where appropriate resuscitation equipment and healthcare professionals with training in cardiopulmonary resuscitation are available (see section 4.4).
After dosing with Spravato, blood pressure should be reassessed at approximately 40 minutes and subsequently as clinically warranted (see section 4.4).
Because of the possibility of sedation, dissociation and elevated blood pressure, patients must be monitored by a healthcare professional until the patient is considered clinically stable and ready to leave the healthcare setting (see section 4.4).
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. | The need for continued treatment should be re-examined periodically. |
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.
Since some patients may experience nausea and vomiting after administration of the medicinal product, patients should be advised not to eat for at least 2 hours before administration and not to drink liquids at least 30 minutes prior to administration (see section 4.8).
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.
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).
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.
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). Use in this population is not recommended (see sections 4.4 and 5.2).
No dose adjustment is necessary in patients with mild to severe renal impairment. Patients on dialysis were not studied.
The safety and efficacy of Spravato in paediatric patients aged 17 years and younger have not been established. There is no relevant use of Spravato in children less than 7 years of age.
This medicinal product is for nasal use only. The nasal spray device is a single-use device that delivers a total of 28 mg of esketamine, in two sprays (one spray per nostril). To prevent loss of medicinal product, the device should not be primed before use. It is intended for administration by the patient under the supervision of a healthcare professional, using 1 device (for a 28 mg dose), 2 devices (for a 56 mg dose) or 3 devices (for an 84 mg dose), with a 5-minute rest between use of each device.
If sneezing occurs immediately after administration, a replacement device should not be used.
If administration in the same nostril occurs, a replacement device should not be used.
Treatment discontinuation does not require tapering off; based on data from clinical trials the risk of withdrawal symptoms is low.
The potential for overdose of Spravato by the patient is minimised due to the product’s design and the administration taking place under the supervision of a healthcare professional (see section 4.2).
The maximum single esketamine nasal spray dose tested in healthy volunteers was 112 mg which showed no evidence of toxicity and/or adverse clinical outcomes. However, compared to the recommended dose range, the 112 mg esketamine nasal spray dose was associated with higher rates of adverse reactions, including dizziness, hyperhidrosis, somnolence, hypoaesthesia, feeling abnormal, nausea and vomiting.
Life-threatening symptoms are expected based on experience with ketamine given at 25-fold the usual anaesthetic dose. Clinical symptoms are described as convulsions, cardiac arrhythmias, and respiratory arrest. Administration of a comparable supratherapeutic dose of esketamine by the intranasal route is unlikely to be feasible.
There is no specific antidote for esketamine overdose. In the case of overdose, the possibility of multiple medicinal products involvement should be considered. Management of Spravato overdose should consist of treating clinical symptoms and relevant monitoring. Close supervision and monitoring should continue until the patient recovers.
4 years.
This medicinal product does not require any special storage conditions.
Type-I glass vial with a chlorobutyl rubber stopper. The filled and stoppered vial is assembled into a manually-activated nasal spray device. The device dispenses two sprays.
Within each pack, each device is individually packaged in a sealed blister.
Pack sizes of 1, 2, 3, or 6 nasal spray devices and in multipacks containing 12 (4 packs of 3) or 24 (8 packs of 3) nasal spray devices.
Not all pack sizes may be marketed.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
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