Drugs List

Therapeutic Indications

Uses

Major depressive episodes in patients with MDD: adjunctive treatment

Treatment of adults with treatment-resistant major depressive disorder, in combination with an SSRI or SNRI, who have not responded to at least two different treatments with antidepressants in the current moderate to severe depressive episode.

Administration

Do not re-administer if sneezing occurs immediately after administration. If administration occurs in the same nostril, do not administer a replacement device.

Contraindications

Children under 18 years
Arterial aneurysm
Breastfeeding
History of cerebrovascular haemorrhage
Pregnancy
Recent myocardial infarction
Renal dialysis
Severe hepatic impairment

Precautions and Warnings

Elderly
Females of childbearing potential
Suicidal ideation
Bipolar disorder
Cardiovascular disorder
Cerebrovascular disorder
History of bipolar disorder
History of drug misuse
History of mania
History of psychosis
Mania
Moderate hepatic impairment
Psychosis
Raised intracranial pressure
Respiratory disease
Uncontrolled hyperthyroidism

Patients at risk of suicide should be closely supervised
Advise patient ability to drive or operate machinery may be impaired
Advise patient not to drive until they know how the medicine affects them
Advise patient this medicine may be subject to driving restrictions
Consider reduced dose in patients of East Asian ancestry
Treatment should be initiated by a psychiatrist
Advise patient to avoid drinking 30 minutes before administration
Advise patient to avoid nasal preparations within 1 hour before treatment
Avoid solid food for at least 2 hours prior to administration
Patient should be closely observed, if possible within an inpatient setting
Treatment to be administered under the supervision of a specialist
Monitor blood pressure pre-treatment and periodically thereafter
Discontinue treatment immediately if pregnancy is suspected
Monitor for signs of suicide ideation or behaviour
Monitor for urinary tract and bladder symptoms
Reassess need for continued treatment at regular intervals
Reduce dose in elderly
Advise patient to avoid alcohol during treatment
Advise that effects are potentiated by CNS depressants (including alcohol)
Advise patient/carers to report signs of suicide ideation or behaviour

Patients with clinically significant or unstable cardiovascular or respiratory conditions should have treatment administered where resuscitation equipment and trained professionals in cardiopulmonary resuscitation are available.

Where an increase in blood pressure or intracranial pressure would put the patient at risk, it should be determined whether the potential benefits of treatment outweighs the risks. Treatment should not be started if an increase in intracranial pressure or blood pressure poses a serious risk. Treatment may also be delayed if blood pressure is elevated due to lifestyle or pharmacological therapies.

Blood pressure should be measured 40 minutes after treatment and regularly thereafter as clinically appropriate. Any treatment sessions with esketamine can cause transient increases in systolic and/or diastolic blood pressure which peaks at approximately 40 minutes and can last 1 to 2 hours. If blood pressure remains elevated for a prolonged period of time, assistance should be sought from practitioners specialised in blood pressure management. Patients experiencing symptoms of a hypertensive crisis should be immediately referred to emergency care.

Prior to treatment the patient should be assessed for the risk of abuse or misuse.

Elderly patients have an increased risk of falls and should be monitored.

Chronic ketamine use has been associated with hepatotoxicity, therefore such an effect cannot be excluded during long term esketamine treatment.

Patients requiring a nasal corticosteroid or nasal decongestant on the day of dosing should not administer the medicinal product 1 hour before treatment administration.

Due to 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.

Depression is associated with an increased risk of suicidal thoughts, self harm and suicide (suicide related events). This risk persists until significant remission occurs. As improvement may not occur during the first few weeks or more of treatment, patients should be closely monitored until such improvement occurs. It is general clinical experience that the risk of self harm is highest shortly after presentation and the risk of suicide may increase again in the early stages of recovery. Furthermore, there is evidence that in children and adolescents, antidepressants may increase the risk of suicidal thoughts and self harm.

Patients with a history of suicide related events, those exhibiting a significant degree of suicidal ideation prior to commencement of treatment, and young adults, are at a greater risk of suicidal thought or suicide attempt, and should receive careful monitoring during treatment.

Patients, (and caregivers of patients) should be alerted about the need to monitor for the emergence of suicidal thoughts and behaviour, and to seek medical advice immediately if these symptoms present.

Pregnancy and Lactation

Pregnancy

Esketamine is contraindicated during pregnancy.

The manufacturer does not recommend using esketamine during pregnancy. At the time of writing there is limited published information regarding the use of esketamine during pregnancy, a potential risk cannot be ruled out. Animal studies have shown neurotoxicity in developing foetuses.

Lactation

Esketamine is contraindicated during breastfeeding.

The manufacturer advises that the patient either discontinues esketamine or discontinues breastfeeding taking into account the benefit of breastfeeding for the infant and the benefit of treatment for the mother. Animal data has shown excretion of esketamine in the breast milk however presence in human breast milk is unknown.

Side Effects

Agitation
Altered temperature sensation
Anxiety
Blurred vision
Derealisation
Desire to micturate
Dissociation
Dizziness
Dry mouth
Dysarthria
Dysgeusia
Dysuria
Euphoria
Feeling abnormal
Feeling drunk
Hallucinations
Headache
Hyperacusis
Hyperhidrosis
Hypertension
Hypoaesthesia
Illusion
Impairment of mental skills
Increased blood pressure
Irritability
Lethargy
Nasal discomfort
Nasal dryness
Nasal pruritus
Nausea
Oral hypoaesthesia
Panic attack
Paraesthesia
Perceptual disturbances
Pollakiuria
Sedation
Somnolence
Tachycardia
Tinnitus
Tremor
Vertigo
Vomiting

Presentation

Nasal spray containing esketamine.

Drugs List

Therapeutic Indications

Uses

Major depressive episodes in patients with MDD: adjunctive treatment

Treatment of adults with treatment-resistant major depressive disorder, in combination with an SSRI or SNRI, who have not responded to at least two different treatments with antidepressants in the current moderate to severe depressive episode.

Dosage

Treatment is recommended for at least 6 months once depressive symptoms improve.

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, esketamine dosing should be individualised to the lowest frequency to maintain remission/response.

Adults

Elderly

Patients with Hepatic Impairment

Additional Dosage Information

Administration

Do not re-administer if sneezing occurs immediately after administration. If administration occurs in the same nostril, do not administer a replacement device.

Contraindications

Children under 18 years
Arterial aneurysm
Breastfeeding
History of cerebrovascular haemorrhage
Pregnancy
Recent myocardial infarction
Renal dialysis
Severe hepatic impairment

Precautions and Warnings

Elderly
Females of childbearing potential
Suicidal ideation
Bipolar disorder
Cardiovascular disorder
Cerebrovascular disorder
History of bipolar disorder
History of drug misuse
History of mania
History of psychosis
Mania
Moderate hepatic impairment
Psychosis
Raised intracranial pressure
Respiratory disease
Uncontrolled hyperthyroidism

Patients at risk of suicide should be closely supervised
Advise patient ability to drive or operate machinery may be impaired
Advise patient not to drive until they know how the medicine affects them
Advise patient this medicine may be subject to driving restrictions
Consider reduced dose in patients of East Asian ancestry
Treatment should be initiated by a psychiatrist
Advise patient to avoid drinking 30 minutes before administration
Advise patient to avoid nasal preparations within 1 hour before treatment
Avoid solid food for at least 2 hours prior to administration
Patient should be closely observed, if possible within an inpatient setting
Treatment to be administered under the supervision of a specialist
Monitor blood pressure pre-treatment and periodically thereafter
Discontinue treatment immediately if pregnancy is suspected
Monitor for signs of suicide ideation or behaviour
Monitor for urinary tract and bladder symptoms
Reassess need for continued treatment at regular intervals
Reduce dose in elderly
Advise patient to avoid alcohol during treatment
Advise that effects are potentiated by CNS depressants (including alcohol)
Advise patient/carers to report signs of suicide ideation or behaviour

Patients with clinically significant or unstable cardiovascular or respiratory conditions should have treatment administered where resuscitation equipment and trained professionals in cardiopulmonary resuscitation are available.

Where an increase in blood pressure or intracranial pressure would put the patient at risk, it should be determined whether the potential benefits of treatment outweighs the risks. Treatment should not be started if an increase in intracranial pressure or blood pressure poses a serious risk. Treatment may also be delayed if blood pressure is elevated due to lifestyle or pharmacological therapies.

Blood pressure should be measured 40 minutes after treatment and regularly thereafter as clinically appropriate. Any treatment sessions with esketamine can cause transient increases in systolic and/or diastolic blood pressure which peaks at approximately 40 minutes and can last 1 to 2 hours. If blood pressure remains elevated for a prolonged period of time, assistance should be sought from practitioners specialised in blood pressure management. Patients experiencing symptoms of a hypertensive crisis should be immediately referred to emergency care.

Prior to treatment the patient should be assessed for the risk of abuse or misuse.

Elderly patients have an increased risk of falls and should be monitored.

Chronic ketamine use has been associated with hepatotoxicity, therefore such an effect cannot be excluded during long term esketamine treatment.

Patients requiring a nasal corticosteroid or nasal decongestant on the day of dosing should not administer the medicinal product 1 hour before treatment administration.

Due to 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.

Depression is associated with an increased risk of suicidal thoughts, self harm and suicide (suicide related events). This risk persists until significant remission occurs. As improvement may not occur during the first few weeks or more of treatment, patients should be closely monitored until such improvement occurs. It is general clinical experience that the risk of self harm is highest shortly after presentation and the risk of suicide may increase again in the early stages of recovery. Furthermore, there is evidence that in children and adolescents, antidepressants may increase the risk of suicidal thoughts and self harm.

Patients with a history of suicide related events, those exhibiting a significant degree of suicidal ideation prior to commencement of treatment, and young adults, are at a greater risk of suicidal thought or suicide attempt, and should receive careful monitoring during treatment.

Patients, (and caregivers of patients) should be alerted about the need to monitor for the emergence of suicidal thoughts and behaviour, and to seek medical advice immediately if these symptoms present.

Pregnancy and Lactation

Pregnancy

Esketamine is contraindicated during pregnancy.

The manufacturer does not recommend using esketamine during pregnancy. At the time of writing there is limited published information regarding the use of esketamine during pregnancy, a potential risk cannot be ruled out. Animal studies have shown neurotoxicity in developing foetuses.

Lactation

Esketamine is contraindicated during breastfeeding.

The manufacturer advises that the patient either discontinues esketamine or discontinues breastfeeding taking into account the benefit of breastfeeding for the infant and the benefit of treatment for the mother. Animal data has shown excretion of esketamine in the breast milk however presence in human breast milk is unknown.

Effects on Ability to Drive and Operate Machinery

This class of medicine is in the list of drugs included in regulations under 5a of the Road Traffic Act 1988 (England and Wales). When prescribing this medicine: Advise patient the medicine can affect cognitive function and is likely to affect ability to drive. Advise patient not to drive until they know how the medicine affects them.

Side Effects

Agitation
Altered temperature sensation
Anxiety
Blurred vision
Derealisation
Desire to micturate
Dissociation
Dizziness
Dry mouth
Dysarthria
Dysgeusia
Dysuria
Euphoria
Feeling abnormal
Feeling drunk
Hallucinations
Headache
Hyperacusis
Hyperhidrosis
Hypertension
Hypoaesthesia
Illusion
Impairment of mental skills
Increased blood pressure
Irritability
Lethargy
Nasal discomfort
Nasal dryness
Nasal pruritus
Nausea
Oral hypoaesthesia
Panic attack
Paraesthesia
Perceptual disturbances
Pollakiuria
Sedation
Somnolence
Tachycardia
Tinnitus
Tremor
Vertigo
Vomiting

Overdosage

It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

The following number will direct the caller to the relevant local centre (0844) 892 0111

Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Further Information

Last Full Review Date: 20 October 2020

Reference Sources

Summary of Product Characteristics: Spravato 28mg nasal spray. Janssen Cilag Ltd. Revised July 2020.

Gov.uk. Government departments. Department for Transport. Publications. Drug driving and medicine: Advice for healthcare professionals. Drug driving: Guidance for healthcare professionals on drug driving. Available at: https://www.gov.uk/
Last accessed: 20 October 2020

New drug driving offence: implications for medicines packaging. Medicines Regulatory News. 10 December 2013. Available at: https://www.mhra.gov.uk Last accessed: 20 October 2020