Esketamine Nasal Spray

IMPORTANT WARNING:

Using esketamine nasal spray may cause sedation, fainting, dizziness, anxiety, a spinning sensation, or feeling disconnected from your body, thoughts, emotions, space and time, and breathing problems. You will use esketamine nasal spray by yourself in a medical facility, but your doctor will monitor you before, during, and for at least 2 hours after your treatment. You will need to plan for a caregiver or family member to drive you home after using esketamine. After you use esketamine nasal spray, do not drive a car, operate machinery, or do anything where you need to be completely alert until the next day after a restful night's sleep. Tell your doctor right away if you experience any of the following symptoms: extreme tiredness or sleepiness, dizziness, fainting, or shortness of breath or if you feel anxious or disconnected from your body, thoughts, emotions, space, and time.

Esketamine may be habit-forming. Tell your doctor if you or anyone in your family drinks or has ever drunk large amounts of alcohol, uses or has ever used street drugs, or has overused prescription medications.

A small number of children, teenagers, and young adults (up to 24 years of age) who took antidepressants ('mood elevators') during clinical studies became suicidal (thinking about harming or killing oneself or planning or trying to do so). Children, teenagers, and young adults who take antidepressants to treat depression or other mental illnesses may be more likely to become suicidal than children, teenagers, and young adults who do not take antidepressants to treat these conditions. However, experts are not sure about how great this risk is and how much it should be considered in deciding whether a child or teenager should take an antidepressant. Children should not use esketamine.

You should know that your mental health may change in unexpected ways when you use esketamine or other antidepressants even if you are an adult over age 24. You may become suicidal, especially at the beginning of your treatment and any time that your dose is changed. You, your family, or your caregiver should call your doctor right away if you experience any of the following symptoms: new or worsening depression; thinking about harming or killing yourself, or planning or trying to do so; extreme worry; agitation; panic attacks; difficulty falling asleep or staying asleep; aggressive behavior; irritability; acting without thinking; severe restlessness; and frenzied abnormal excitement. Be sure that your family or caregiver knows which symptoms may be serious so they can call the doctor if you are unable to seek treatment on your own.

No matter your age, before you take an antidepressant, you or your caregiver should talk to your doctor about the risks and benefits of treating your condition with an antidepressant or with other treatments. You should also talk about the risks and benefits of not treating your condition. You should know that having depression or another mental illness greatly increases the risk that you will become suicidal. This risk is higher if you or anyone in your family has or has ever had bipolar disorder (mood that changes from depressed to abnormally excited) or mania (frenzied, abnormally excited mood) or has thought about or attempted suicide. Talk to your doctor about your condition, symptoms, and personal and family medical history. You and your doctor will decide what type of treatment is right for you.

Because of the risks with this medication, esketamine is available only through a special restricted distribution program. A program called Spravato Risk Evaluation and Mitigation Strategies (REMS) program. You, your doctor, and your pharmacy must be enrolled in the Spravato REMS program before you can receive this medication. You will use esketamine nasal spray in a medical facility under the observation of a doctor or other healthcare professional.

Keep all appointments with your doctor and the laboratory.

Your doctor or pharmacist will give you the manufacturer's patient information sheet (Medication Guide) when you begin treatment with esketamine and each time you refill your prescription. Read the information carefully and ask your doctor or pharmacist if you have any questions. You can also visit the Food and Drug Administration (FDA) website or the manufacturer's website to obtain the Medication Guide.

WHY is this medicine prescribed?

Esketamine nasal spray is used along with another antidepressant, taken by mouth, to manage treatment-resistant depression (TRD; depression that does not improve with treatment) in adults. It is also used along with another antidepressant, taken by mouth, to treat depressive symptoms in adults with major depressive disorder (MDD) and suicidal thoughts or actions. Esketamine is in a class of medications called NMDA receptor antagonists. It works by changing the activity of certain natural substances in the brain.

Are there OTHER USES for this medicine?

This medication may be prescribed for other uses; ask your doctor or pharmacist for more information.

HOW should this medicine be used?

Esketamine comes as a solution (liquid) to spray into the nose. For the management of treatment-resistant depression, it is usually sprayed into the nose twice a week during weeks 1–4, once weekly during weeks 5–8, and then once a week or once every 2 weeks during week 9 and beyond. For the treatment of depressive symptoms in adults with major depressive disorder and suicidal thoughts or actions, it is usually sprayed into the nose twice a week for up to 4 weeks. Esketamine must be used in a medical facility.

Do not eat for at least 2 hours or drink liquids for at least 30 minutes before using esketamine nasal spray.

Each nasal spray device provides 2 sprays (one spray for each nostril). Two green dots on the device tells you that the nasal spray is full, one green dot tells you that one spray was used, and no green dots indicates that the full dose of 2 sprays was used.

What SPECIAL PRECAUTIONS should I follow?

Before using esketamine nasal spray,

• tell your doctor and pharmacist if you are allergic to esketamine, ketamine, any other medications, or any of the ingredients in esketamine nasal spray. Ask your pharmacist or check the Medication Guide for a list of the ingredients.

• tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take. Your doctor may need to change the doses of your medications or monitor you carefully for side effects.

• if you are using a nasal corticosteroid such as budesonide (Rhinocort), ciclesonide (Alvesco), flunisolide, fluticasone (Flonase), and mometasone (Nasonex) or a nasal decongestant such as oxymetazoline (Afrin, others) and phenylephrine (Neosynephrine), use it at least 1 hour before using esketamine nasal spray.

• tell your doctor if you have a blood vessel disease in the brain, chest, stomach area, arms or legs; have arteriovenous malformation (an abnormal connection between your veins and arteries); or have a history of bleeding in your brain. Your doctor will probably tell you not to use esketamine nasal spray.

• tell your doctor if you have ever had a stroke, heart attack, brain injury, or any condition that causes increased brain pressure. Tell your doctor if you see, feel, or hear things that are not there; or believe in things that are not true. Also, tell your doctor if you have or have ever had heart valve disease, heart failure, hypertension (high blood pressure), a slow or irregular heartbeat, shortness of breath, chest pain, or liver or heart disease.

• tell your doctor if you are pregnant or plan to become pregnant. If you become pregnant while using esketamine nasal spray, call your doctor immediately. Esketamine nasal spray may harm the fetus.

• tell your doctor if you are breast-feeding or plan to breast-feed. You should not breastfeed while using esketamine nasal spray.

• you should know that esketamine nasal spray may temporarily increase your blood pressure, which may last for about 4 hours. Your doctor will check your blood pressure before and for at least 2 hours after you use esketamine nasal spray. Tell your doctor right away if you experience any of the following symptoms after using the medication: chest pain, shortness of breath, sudden severe headache, change in vision, or seizures.

What SPECIAL DIETARY instructions should I follow?

Unless your doctor tells you otherwise, continue your normal diet.

What should I do IF I FORGET to take a dose?

If you miss a treatment session contact your doctor right away to schedule an appointment. If you miss a treatment and your depression becomes worse, your doctor may have to change your dose or treatment schedule.

What SIDE EFFECTS can this medicine cause?

Esketamine nasal spray may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:

• constipation
• diarrhea
• dry mouth
• nausea
• vomiting
• feeling drunk
• headache
• unusual or metallic taste in the mouth
• nasal discomfort
• throat irritation or pain
• toothache
• increased sweating
• muscle pain
• numbness or change in your ability to feel light touch, pain, heat, or cold
• difficulty speaking
• difficulty falling asleep or staying asleep
• abnormally happy or excited mood

Some side effects can be serious. If you experience any of the symptoms listed in the IMPORTANT WARNING or SPECIAL PRECAUTIONS sections, call your doctor immediately or get emergency medical treatment.

• frequent, urgent, burning, or painful urination
• difficulty thinking or remembering
• increased or rapid heart rate

Esketamine nasal spray may cause other side effects. Call your doctor if you have any unusual problems while using this medication.

If you experience a serious side effect, you or your doctor may send a report to the Food and Drug Administration's (FDA) MedWatch Adverse Event Reporting program online (http://www.fda.gov/Safety/MedWatch) or by phone (1-800-332-1088).

What should I do in case of OVERDOSE?

In case of overdose, call the poison control helpline at 1-800-222-1222. Information is also available online at https://www.poisonhelp.org/help. If the victim has collapsed, had a seizure, has trouble breathing, or can't be awakened, immediately call emergency services at 911.

What OTHER INFORMATION should I know?

It is important for you to keep a written list of all of the prescription and nonprescription (over-the-counter) medicines you are taking, as well as any products such as vitamins, minerals, or other dietary supplements. You should bring this list with you each time you visit a doctor or if you are admitted to a hospital. It is also important information to carry with you in case of emergencies.