SPRAVATO

What it is

SPRAVATO is a single use nasal spray device containing an intranasal solution with esketamine hydrochloride equivalent to esketamine 28 mg/0.2 mL as the active ingredient. The nasal spray device is a single-use device that delivers a total of 28 mg of esketamine in two actuations (one actuation per nostril). Esketamine, the S-enantiomer of racemic ketamine, is an antidepressant with a novel mechanism of action. It is a non-selective, non-competitive antagonist of the N-methyl-D-aspartate (NMDA) receptor, an ionotropic glutamate receptor. This medicinal product is subject to additional monitoring in Australia. This will allow quick identification of new safety information.

Approved indications

— Treatment resistant depression (Major Depressive Disorder in adults who have not responded adequately to at least two different antidepressants of adequate dose and duration to treat the current moderate to severe depressive episode).

Dosing overview

SPRAVATO is to be initiated in conjunction with a newly initiated oral antidepressant. The device 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. For adults aged less than 65 years, the starting dose on Day 1 is 56 mg, with subsequent doses of 28 mg (for patients aged 65 years or older), 56 mg or 84 mg administered twice weekly during weeks 1–4 (induction phase), then 28 mg, 56 mg or 84 mg once weekly during weeks 5–8 (maintenance phase), and then 28 mg, 56 mg or 84 mg every 2 weeks or once weekly from week 9 onwards. In elderly patients the initial SPRAVATO dose is 28 mg (Day 1), with subsequent doses increased in increments of 28 mg, up to 56 mg or 84 mg, based on efficacy and tolerability. After depressive symptoms improve, treatment should continue for at least 6 months.

Key safety warnings

SPRAVATO can cause transient increases in systolic and/or diastolic blood pressure which peak at approximately 40 minutes after drug administration and last approximately 1–2 hours. Blood pressure should be assessed prior to dosing with SPRAVATO. If baseline blood pressure is elevated (for example, >140 mmHg systolic, >90 mmHg diastolic), consider the risks of short term increases in blood pressure and benefit of SPRAVATO treatment in patients with treatment resistant depression. During and after SPRAVATO administration at each treatment session, patients should be monitored until the patient is stable based on clinical judgment. Due to the possibility of sedation, dissociation, elevated blood pressure, changes to pulse rate, and rarely seizures, patients must be monitored by a healthcare professional until the patient is considered clinically stable and ready to leave the healthcare setting. SPRAVATO has been reported to cause somnolence, sedation, dissociative symptoms, perception disturbances, dizziness, vertigo and anxiety during the clinical trials. These effects may impair attention, judgment, thinking, reaction speed and motor skills. Patients should be instructed not to drive or operate machinery until next day. During post-marketing use, rare cases of respiratory depression have been observed. The majority of these cases have been reported with the use of SPRAVATO in combination with other 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. Depression is associated with an increased risk of suicidal thoughts, self-harm and suicide. This risk persists until significant remission occurs. 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. Close supervision of patients and in particular those at high risk should accompany treatment especially in early treatment and following dose changes.

Contraindications

SPRAVATO is contraindicated in patients for whom an increase in blood pressure or intracranial pressure poses a serious risk, including patients with known aneurysmal vascular disease (including intracranial, thoracic, or abdominal aorta, or peripheral arterial vessels) and patients with known history of intracerebral haemorrhage. SPRAVATO is contraindicated in patients with a known hypersensitivity to esketamine, ketamine, or to any of the excipients.

PBS listing

SPRAVATO nasal spray device 28 mg in 2 actuations is listed on the PBS with 18 items, restriction type authority required, and ex-manufacturer price of A$882.48.

Regulatory history

SPRAVATO esketamine hydrochloride 28 mg per 2 actuations nasal spray solution was first registered on the ARTG on 9 March 2021. The PBAC initially did not recommend SPRAVATO for treatment resistant depression in July 2021, with not recommended outcomes repeated in July 2022 and July 2023. In July 2024, the matter was deferred. In December 2024, SPRAVATO was recommended (new) for treatment-resistant major depression in patients who have failed at least two prior oral anti-depressant drugs. The recommendation was for General Schedule and Section 100 (Highly Specialised Drugs Program – Public and Private Hospitals) listings with authority required access, based on additional changes to restriction and financial estimates adequately addressing previous concerns.