esketamine hydrochloride: clinical use

Prescribing considerations

• Nasal treatment should be initiated by a psychiatrist and delivered with direct supervision and post-administration observation.
• Assess cardiovascular, cerebrovascular and respiratory stability, psychiatric history, hepatic impairment and misuse or diversion risk.
• Improvement in depressive symptoms does not establish suicide prevention and must not delay clinically necessary hospitalisation or other care.
• Injectable esketamine is restricted to hospital or pre-hospital emergency use under anaesthetic-specialist supervision.
• Review persistent urinary symptoms and consider hepatic assessment where clinically indicated, especially with prolonged exposure.

Contraindications and cautions

• Hypersensitivity to esketamine; nasal esketamine is also contraindicated with ketamine hypersensitivity.
• Any condition in which increased blood pressure or intracranial pressure creates a serious risk.
• Nasal formulation: aneurysmal vascular disease, previous intracerebral haemorrhage or a recent cardiovascular event.
• Injectable formulation: use as sole anaesthetic in manifest ischaemic cardiac disease, eclampsia or pre-eclampsia, and combination with xanthines or ergometrine.

Monitoring

• For nasal use, assess blood pressure before administration and afterwards until clinically appropriate.
• Observe consciousness, dissociation, respiratory status, haemodynamic stability and readiness to leave.
• Monitor depressive deterioration, suicidality, misuse or drug-seeking behaviour.
• During anaesthesia, continuously monitor vital functions and ensure airway and resuscitation equipment is available.
• Consider falls risk in older adults and monitor persistent bladder or urinary symptoms during ongoing nasal treatment.

Clinical pharmacology

Esketamine is the S-enantiomer of ketamine and a non-selective, non-competitive NMDA-receptor antagonist. Nasal administration is rapidly absorbed and undergoes hepatic metabolism, mainly through CYP2B6 and CYP3A4. Sympathomimetic effects can raise blood pressure and heart rate; at anaesthetic exposure it causes dissociative anaesthesia and analgesia.

Formulation and product differences

• The nasal spray is a single-use, patient-operated device used under direct healthcare supervision for licensed depressive disorders.
• The injection or infusion is administered intravenously or intramuscularly by trained clinicians for anaesthetic and emergency indications.
• The formulations have different indications, contraindications, breastfeeding wording, monitoring requirements and driving restrictions; they are not interchangeable.

Nasal preparation

Route: Nasal

Strengths: 28 mg

Injection

Route: Parenteral

Strengths: 5 mg/mL, 25 mg/mL