Esketamine

Source: UK SPC (eMC) for Spravato 28 mg nasal spray, solution, §4.2 (https://www.medicines.org.uk/emc/product/10977/smpc). PRESCRIBING AND SETTING: the decision to prescribe 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 plus a post-administration observation period, both carried out in an appropriate clinical setting. ASSESSMENT BEFORE TREATMENT: assess blood pressure before dosing; if baseline blood pressure is elevated, weigh the risks of short-term increases against the benefit of treatment. Do not administer if an increase in blood pressure or intracranial pressure poses a serious risk (see contraindications). Patients with clinically significant or unstable cardiovascular or respiratory conditions require additional precautions and should be dosed where appropriate resuscitation equipment and healthcare professionals trained in cardiopulmonary resuscitation are available. POST-ADMINISTRATION OBSERVATION: reassess blood pressure at approximately 40 minutes and subsequently as clinically warranted; because of the possibility of sedation, dissociation and elevated blood pressure, patients must be monitored by a healthcare professional until considered clinically stable and ready to leave the healthcare setting. (The US label specifies observing the patient for at least 2 hours, with monitoring of respiratory status including pulse oximetry for at least 2 hours at each session.) MAINTENANCE PRINCIPLE: it is recommended to maintain the dose the patient receives at the end of the induction phase; dose adjustments should be based on efficacy and tolerability of the previous dose; during maintenance, dosing should be individualised to the lowest frequency that maintains remission/response. Evidence of therapeutic benefit should be evaluated at the end of the induction phase to determine the need for continued treatment, and re-examined periodically. After depressive symptoms improve, treatment is recommended for at least 6 months. SECOND INDICATION — 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, with dosage reduction to 56 mg based on tolerability; after 4 weeks the oral antidepressant therapy should be continued per clinical judgement, and treatment should be part of a comprehensive clinical care plan. ELDERLY (>= 65 years, treatment-resistant MDD): starting day 1 dose 28 mg; subsequent doses 28 mg, 56 mg or 84 mg twice a week during weeks 1–4, then 28 mg, 56 mg or 84 mg once weekly during weeks 5–8, then 28 mg, 56 mg or 84 mg every 2 weeks or once weekly from week 9 — all dose changes should be in 28 mg increments. Spravato has not been studied in elderly patients for acute short-term treatment of psychiatric emergency. FOOD AND LIQUID: advise patients not to eat for at least 2 hours before administration and not to drink liquids for at least 30 minutes before administration. NASAL CORTICOSTEROID OR DECONGESTANT: patients who require these on a dosing day should not administer them within 1 hour before Spravato. MISSED SESSIONS: patients who miss session(s) during the first 4 weeks should continue their current dosing schedule; for treatment-resistant MDD patients who miss session(s) during maintenance and have worsening depressive symptoms, consider returning to the previous dosing schedule per clinical judgement. DEVICE: each single-use device delivers a total of 28 mg of esketamine in two sprays (one spray per nostril) — use 1 device for 28 mg, 2 devices for 56 mg, 3 devices for 84 mg, with a 5-minute rest between devices. Do not prime the device before use. If sneezing occurs immediately after administration, or if 2 consecutive sprays are given into the same nostril, a replacement device should NOT be used. HEPATIC IMPAIRMENT: no dose adjustment in mild (Child-Pugh A) or moderate (Child-Pugh B), but use the 84 mg maximum dose with caution in moderate impairment; not studied in severe (Child-Pugh C) and use is not recommended. PAEDIATRIC: safety and efficacy in patients aged 17 years and younger have not been established; there is no relevant use in children less than 7 years of age — no paediatric dose is stated and none should be inferred; verify any under-18 use against a children's formulary. DISCONTINUATION does not require tapering; based on clinical trial data the risk of withdrawal symptoms is low. §4.4 was truncated at the source-fetch limit and §4.5 was not retrieved in this bundle — verify the complete interactions section (interactions listed below are from the US label, as marked).