SPRAVATO (esketamine) Nasal Spray

SPRAVATO is a nasal spray available as a prescription and is used along with an antidepressant taken by mouth to treat:

• adults with treatment-resistant depression (TRD)

• depressive symptoms in adults with MDD or major depressive disorder with suicidal thoughts or actions

SPRAVATO cannot be used as a medicine to prevent or relieve pain (anesthetic). It is not known if SPRAVATO is safe to use as an anesthetic medicine.

It is not known if SPRAVATO is safe and effective for use in preventing or reducing suicidal thoughts or actions. SPRAVATO should not be replaced with that of a hospital or your healthcare provider even if the improvement is experienced after the first dose of SPRAVATO.

It is not known if SPRAVATO is safe to use in children

Do not take SPRAVATO if you:

• have aneurysmal vascular disease or blood vessel disease (including in the brain, chest, abdominal aorta, arms, and legs)

• have an arteriovenous malformation (an abnormal connection between your veins and arteries)

• have a history of bleeding in the brain

• are allergic to ketamine, esketamine, or any of the other ingredients in SPRAVATO.

Before you take SPRAVATO, tell your doctor about all of your medical conditions, including if you:

• have heart or brain problems

• high blood pressure (hypertension)

• slow or fast heartbeats that cause chest pain, shortness of breath, lightheadedness, or fainting

• history of heart attack

• history of stroke

• heart valve disease or heart failure

• have a history of brain injury or any condition where there is increased pressure in the brain

• have liver problems

• have ever had a condition called “psychosis”.

• are pregnant or planning to become pregnant. SPRAVATO may harm your unborn baby. You should not take SPRAVATO if you are pregnant. Tell your doctor if you become pregnant during treatment with SPRAVATO.

• are breastfeeding or planning to breastfeed. It is not known if SPRAVATO can pass into your breast milk.

• Tell your doctor about all the medicines, prescriptions, over-the-counter medicines, vitamins, and herbal supplements that you take.

Especially tell your doctor if you take psychostimulants, central nervous system (CNS) depressants, or monoamine oxidase inhibitors (MAOIs) medicines. Ask your doctor if you are not sure if you take these medicines.

• You will have to take SPRAVATO nasal spray yourself, under the supervision of a doctor in a healthcare setting. Your doctor will show you how to use the SPRAVATO nasal spray device.

• Your doctor will tell you how much SPRAVATO you will need to take and when you will take it.

• Follow your SPRAVATO treatment schedule exactly as your doctor tells you to.

• During and after each use of the SPRAVATO nasal spray device, you will be checked by a doctor who will decide when you are ready to leave the healthcare setting.

• You will need a family member or anyone to drive you home after taking SPRAVATO.

• If you miss a SPRAVATO treatment, your doctor may change your dose and treatment schedule.

• Some people taking SPRAVATO may get nausea and vomiting. You should not eat (at least 2 hours) and drink liquids (at least 30 minutes) before taking SPRAVATO.

• If you take a nasal decongestant or nasal corticosteroid medicine, take these medicines at least 1 hour before taking SPRAVATO.

Nasal Spray: 28 mg of esketamine per device. Each nasal spray device delivers two sprays containing a total of 28 mg of esketamine.

SPRAVATO is contraindicated in patients with:

• Aneurysmal vascular disease (including intracranial, and peripheral arterial vessels, thoracic and abdominal aorta) or arteriovenous malformation

• History of intracerebral hemorrhage

• Hypersensitivity to esketamine, ketamine, or any of the excipients.

Do not drive, operate machinery, or do anything where you need to be completely alert after taking SPRAVATO. Take part in these activities the next day after a restful sleep.

The common side effects of SPRAVATO when used along with an antidepressant taken by mouth include:

• feeling disconnected from yourself, your thoughts, feelings, and things around you

• dizziness

• nausea

• feeling sleepy

• spinning sensation

• decreased feeling of sensitivity (numbness)

• feeling anxious

• lack of energy

• increased blood pressure

• vomiting

• feeling drunk

• feeling very happy or excited

• Increased blood pressure: SPRAVATO can cause a temporary increase in your blood pressure that may last for about 4 hours after taking a dose. Your doctor will check your blood pressure before taking SPRAVATO and for at least 2 hours after you take SPRAVATO. Tell your doctor right away if you get chest pain, sudden severe headache, change in vision shortness of breath, or seizures after taking SPRAVATO.

• Sedation and dissociation: SPRAVATO may cause fainting, dizziness, sleepiness, spinning sensation, anxiety, or feeling disconnected from yourself, feelings, your thoughts, space, and time. Tell your doctor right away if you feel like you cannot stay awake or if you feel like you are going to pass out. Your doctor should monitor you for serious side effects for at least 2 hours after taking SPRAVATO. Your doctor will then decide when you are ready to leave

• Abuse and misuse: There is a risk for abuse, physical, and psychological dependence with SPRAVATO treatment. Your doctor should check you for signs of abuse and dependence before and during treatment with SPRAVATO. Tell your doctor if you have ever abused or been dependent on prescription medicines, alcohol, or street drugs. Your doctor can tell you more about the differences between drug addiction, physical and psychological dependence

• SPRAVATO Risk Evaluation and Mitigation Strategy (REMS): Because of the risks of dissociation, sedation, abuse, and misuse, SPRAVATO is only available through a restricted program called the SPRAVATO Risk Evaluation and Mitigation Strategy.

• (REMS) Program: SPRAVATO can only be administered in healthcare settings certified in the SPRAVATO REMS Program. Patients treated in outpatient healthcare settings must be enrolled in the program.

• Increased risk of suicidal thoughts and actions: Antidepressant medicines may increase suicidal thoughts and actions in some people 24 years of age and younger, especially within the first few months of treatment or when the dose is changed. Depression and other serious mental illnesses are the causes of suicidal thoughts and actions.

• Problems with thinking clearly: Tell your doctor if you have problems thinking or remembering.
• Bladder problems: Tell your doctor if you develop trouble urinating, such as pain when urinating, a frequent need to urinate, or urinating frequently at night.

• Pay close attention to any change in thoughts, feelings, mood, behavior, or if you develop suicidal thoughts or actions.

• Tell your doctor right away if you have a sudden change in mood, thoughts, behavior, or feelings.

• Keep all follow-up visits with your doctor as scheduled. Call your doctor between visits as needed, especially if you have concerns about symptoms.

• Tell your doctor right away if you or your family member have any of the following symptoms, especially if they are new, worse, or worry you:
  • suicide attempts
  • worsening depression
  • thoughts about suicide or dying
  • other unusual changes in behavior or mood

Active ingredient: esketamine hydrochloride
Inactive ingredients: citric acid monohydrate, edetate disodium, sodium hydroxide, and water for injection