Prospect: information for the patient

Spravato 28 mg nasal spray solution

esketamine

This medicine is subject to additional monitoring, which will expedite the detection of new information about its safety. You may contribute by reporting any adverse effects you experience. The final part of section 4 includes information on how to report these adverse effects.

Read this prospect carefully before starting to use this medicine, because it contains important information for you.

• Keep this prospect, as you may need to read it again.
• If you have any doubts, consult your doctor or pharmacist.
• If you experience adverse effects, consult your doctor or pharmacist, even if they are not listed in this prospect. See section 4.

What is Spravato

Spravato contains the active ingredient esketamine. This belongs to a group of medicines called antidepressants and has been prescribed for you to treat your depression.

How is Spravato used

Spravato is used in adults to reduce symptoms of depression, such as feeling sad, anxious, or useless, difficulty sleeping, changes in appetite, loss of interest in favorite activities, feeling slowed down. It is administered in conjunction with another antidepressant, if you have tried at least two other antidepressants but they have not helped.

Spravato is also used in adults to rapidly reduce symptoms of depression in a situation that requires immediate treatment (also known as psychiatric emergency).

Do not use Spravato

• if you are allergic to esketamine, a similar medication called ketamine used for anesthesia, or any of the other ingredients in this medication (listed in section 6).
• if you have ever had certain conditions such as:

• a weakened blood vessel wall (aneurysm) that has bulged or ballooned
• brain hemorrhage

• if you have had a heart attack in the past 6 weeks

The reason is that Spravato can cause a temporary increase in blood pressure that can lead to serious complications in these conditions.

Do not use Spravato if you are in any of the above circumstances. If you are unsure, talk to your doctor before using Spravato; your doctor will decide if you can or cannot use this medication.

Warnings and precautions

Consult your doctor before starting to use Spravato if:

• you have an uncontrolled heart condition such as poor blood flow to the heart often with chest pain (angina), high blood pressure, heart valve disease, or heart failure
• you have ever had problems with blood supply to the brain (such as a stroke)
• you have ever had problems with substance abuse (prescribed medications or illegal drugs)
• you have ever had a condition called psychosis, where you believe things that are not true (delusions) or see, feel, or hear things that do not exist (hallucinations)
• you have ever had a condition called bipolar disorder, or symptoms of mania (where the person is hyperactive or overexcited)
• you have ever had an overactive thyroid gland that has not been properly treated (hyperthyroidism)
• you have ever had lung problems that cause difficulty breathing (pulmonary insufficiency), including chronic obstructive pulmonary disease (COPD)
• you have extreme obesity and sleep apnea
• you have ever had slow or rapid heartbeats that cause difficulty breathing, palpitations, or chest discomfort, dizziness, or fainting
• you have had a severe head or brain injury or have had serious problems that affect the brain, especially if there is an increase in brain pressure
• you have severe liver problems

If you meet any of the above conditions (or are unsure), consult your doctor before starting to use Spravato. Your doctor will decide if you should use this medication.

Worsening of depression

Inform your doctor or go to the nearest hospital immediately if you ever think about harming yourself or committing suicide.

It may be helpful to talk to a family member or close friend if you are depressed and ask them if they think your depression is getting worse or if they are concerned about your behavior. You can ask them to read this leaflet.

Blood pressure

Spravato can increase your blood pressure for about 1 to 2 hours after using it, so your blood pressure will be measured before you start using Spravato and after using it.

If your blood pressure is high before using this medication, your doctor will decide if you should start using it or wait until your blood pressure is lower. If your blood pressure increases after using this medication and remains high for more than a few hours, you may need to undergo further tests.

This medication can cause a temporary increase in blood pressure after administering a dose. Your blood pressure will be measured before and after using this medication. Inform your doctor immediately if you experience chest pain, difficulty breathing, severe headache, changes in vision, or seizures (convulsions) after using this medication.

Inform your doctor if you experience any of the following symptoms while using Spravato

• difficulty with attention, judgment, and thought (see also "Driving and operating machinery" and "Possible side effects"). During and after each use of this medication, your doctor will check your condition and decide how long you should be monitored.
• drowsiness (sedation), fainting, dizziness, feeling of spinning, anxiety, or feeling disconnected from yourself, your thoughts, sensations, space, and time (disconnection), difficulty breathing (respiratory depression). Inform your doctor immediately if you feel you cannot stay awake or feel like you are going to faint.
• painful urination or blood in your urine; these may be signs of bladder problems. These can occur with high doses of a similar medication (called ketamine) used for a prolonged period.

Inform your doctor if you experience any of the above symptoms while using Spravato.

Patients over 65 years old

If you are over 65 years old, you will be closely monitored, as you may have a higher risk of falling when you start moving after treatment.

Children and adolescents

Do not administer this medication to children or adolescents under 18 years of age. This is because Spravato has not been studied in treatment-resistant depression in this age group.

Other medications and Spravato

Inform your doctor if you are taking, have taken recently, or may need to take any other medication.

The use of Spravato with certain medications can cause side effects. Inform your doctor especially if you take:

• medications used to treat nervous system disorders or intense pain (e.g., benzodiazepines, opioids), or medications or beverages that contain alcohol
• stimulants used to treat conditions such as narcolepsy or attention deficit hyperactivity disorder (ADHD) (e.g., amphetamines, methylphenidate, modafinil, armodafinil)
• medications that can increase your blood pressure, such as thyroid hormones, asthma medications like xanthine derivatives, medications for postpartum hemorrhage (ergometrine), and heart medications like vasopressin
• medications for depression or Parkinson's disease called monoamine oxidase inhibitors (MAOIs) (e.g., tranilcipromina, selegilina, fenelzina)

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, or think you may be pregnant, consult your doctor before using this medication.

Contraception

If you can become pregnant, you should use contraception during treatment. Talk to your doctor about the appropriate contraceptive methods.

Pregnancy

Do not use Spravato if you are pregnant.

If you become pregnant while receiving treatment with Spravato, talk to your doctor immediately to decide if you should stop treatment and explore other treatment options.

Breastfeeding

Do not use Spravato if you are breastfeeding. Talk to your doctor before using Spravato if you are breastfeeding. Your doctor will discuss with you whether you should stop breastfeeding or stop using this medication. Your doctor will consider the benefits of breastfeeding for you and your child and the benefits of treatment for you.

Driving and operating machinery

Spravato can make you feel drowsy, dizzy, and experience other side effects that can temporarily affect your ability to drive vehicles or use machines and perform activities that require being fully alert. After receiving treatment with this medication, do not perform these activities until the next day after a restful sleep.

Follow exactly the administration instructions for this medication as indicated by your doctor.

In case of doubt, consult your doctor.

You will use the nasal spray of Spravato under the supervision of a doctor, or another healthcare professional in a healthcare setting, such as the doctor's office or clinic.

Your doctor or another healthcare professional will teach you how to use the nasal spray (see also Usage Instructions).

Recommended Dose

Your doctor will decide if you need 1, 2, or 3 nasal sprays and how often you should visit the doctor's office or clinic to receive the medication.

• One nasal spray administers two sprays (one per nostril)
• Spravato is used twice a week for the first 4 weeks

If your treatment is continued:

• Spravato is usually used once a week for the next 4 weeks
• Subsequently, Spravato is usually used once a week or once every 2 weeks.

Your doctor will review and decide how long you should be monitored during and after each use of this medication.

Foods and Beverages

Some patients using Spravato may experience nausea or vomiting. You should avoid eating for 2 hours before treatment and not drink liquids for 30 minutes before using this medication.

Nasal Sprays

If you need medications with steroids or decongestants in the form of a nasal spray, avoid using them during the hour prior to treatment with Spravato.

If You Use More Spravato Than You Should

You will use this medication under the supervision of a doctor in the doctor's office or clinic. Consequently, it is unlikely that you will use an excessive amount.

If you use too much Spravato, you are more likely to experience side effects (see "Possible Adverse Effects").

If You Discontinue Treatment with Spravato

It is essential that you attend scheduled appointments so that this medication can be effective for you.

If you have any other questions about using this medication, ask your doctor.

Like all medicines, this medicine may cause side effects, although not everyone will experience them.

Inform your doctor if you observe any of the following side effects.

Very common(may affect more than 1 in 10 people)

• sensation of being disconnected from oneself, one's thoughts, feelings, and surroundings
• sensation of dizziness
• headache
• drowsiness
• alteration of taste
• decreased sensation or sensitivity, including around the mouth area
• sensation of everything spinning (“dizziness”)
• vomiting
• nausea
• increased blood pressure

Common(may affect up to 1 in 10 people)

• sensation of anxiety
• sensation of extreme happiness (“euphoria”)
• sensation of confusion
• sensation of detachment from reality
• sensation of irritability
• seeing, feeling, hearing, or smelling things that are not there (hallucinations)
• sensation of agitation
• eyes, ears, or sense of touch are confused or deceived in some way (something is not what it seems)
• panic attack
• change in perception of time
• unusual sensation in the mouth (like tingling or prickling)
• muscle tremors
• difficulty thinking
• sensation of great drowsiness with little energy
• difficulty speaking
• difficulty concentrating
• blurred vision
• persistent ringing in the ears (tinnitus)
• increased sensitivity to noise or sounds
• rapid heart rate
• high blood pressure
• nasal congestion
• throat irritation
• sore throat
• dryness of the nose including dry crusts in the nose
• itching in the nose
• decreased sensation or sensitivity in the mouth
• dry mouth
• excessive sweating
• need to urinate frequently
• pain while urinating
• urgent need to urinate
• abnormal sensation
• sensation of intoxication
• sensation of weakness
• crying
• sensation of change in body temperature

Uncommon(may affect up to 1 in 100 people)

• slowing of thoughts, speech, and physical movements
• emotional stress
• sensation of restlessness or tension
• rapid eye movements that cannot be controlled
• hyperactivity
• increased saliva
• chills
• difficulty walking

Rare(may affect up to 1 in 1,000 people)

• difficulty breathing (respiratory depression)

Reporting of side effects

If you experience any type of side effect, consult your doctor or pharmacist, even if it is a possible side effect that does not appear in this prospectus. You can also report them directly through thenational notification system included in theAppendix V.By reporting side effects, you can contribute to providing more information about the safety of this medicine.

Keep this medication out of the sight and reach of children.

Do not use this medication after the expiration date that appears on the box and on the label.

The expiration date is the last day of the month indicated.

This medication does not require special storage conditions.

Medicines should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the containers and medications that you no longer need. This will help protect the environment.

Composition of Spravato

The active ingredient is esketamine.

Each nasal spray contains esketamine hydrochloride corresponding to 28 mg of esketamine.

The other components are:

Citric acid monohydrate

Edetate disodium

Sodium hydroxide (for pH adjustment)

Water for injection

Appearance of the product and contents of the package

Spravato is a nasal spray solution. This medication is a transparent and colorless solution presented in a single-use nasal spray.

Spravato is available in packages containing 1, 2, 3, or 6 nasal sprays and as a multiple-pack containing 24 (8 packages of 3) nasal sprays.

Each nasal spray is individually packaged in a sealed blister.

Only some package sizes may be marketed.

Marketing Authorization Holder

Janssen-Cilag International NV

Turnhoutseweg 30

B-2340 Beerse

Belgium

Responsible for Manufacturing

Janssen Pharmaceutica NV

Turnhoutseweg 30

B-2340 Beerse

Belgium

For more information about this medication, please contact the local representative of the marketing authorization holder:

Last update of this leaflet:{MM/AAAA} {month YYYY}.

For detailed information about this medication, please visit the website of the European Medicines Agency:http://www.ema.europa.eu/.

The following information is intended for healthcare professionals only:

Instructions for Use

SPRAVATO

(esketamine)

Nasal spray

28 mg per device

Each nasal spray device delivers

28 mg of esketamine in two sprays.

Important

This device is intended for patient use,under the supervision of a healthcare professional. Read these Instructions for Use carefully before training and supervising the patient.

Do you need help?

For more help or to share your opinion, see the contact information of the local representative of the marketing authorization holder in the leaflet.

Nasal spray

Only before the first device:

• Check the expiration date (‘CAD’). If it has expired, obtain a new device.
• Open the blister and remove the device.

• Do not prepare (prime) the device.This will result in medication loss.
• Check that the indicator shows2 green dots. If not, discard the device and obtain a new one.
• Hand the device to the patient.

Inform the patient to:

• Hold the device as shown, with the thumb lightly resting on the plunger.
• Do not press the plunger.

Inform the patient to:

• Tilt their head back to an angle of about45 degreesduring administration to keep the medication inside the nose.

Inform the patient to:

• Insert the tip directly into thefirst nasal passage.
• The nasal support should touch theskin between the nasal passages.

Inform the patient to:

• Close the opposite nasal passage.
• Breathe in through the nosewhile pushing the plunger up to the top.

Inform the patient to:

• Breathe in slowlyafter the spray to keep the medication inside the nose.

Inform the patient to:

• Switch hands to insert the tip into thesecond nasal passage.
• Repeat step 4 to administer the second spray.

• Collect the device from the patient.
• Check the indicator to confirm that the device is empty.

Inform the patient to:

• Rest in a comfortable position (preferably semi-reclined) for5 minutes after each device.
• If dripping occurs, clean the nose with a tissue.

Do not blow the nose.

• Repeat steps 2-5if more than one device is needed.

Reviewed: {month YYYY}