How does this medication work? What will it do for me?

Esketamine belongs to the class of medications called antidepressants. It is used by adults, in addition to either a selective serotonin reuptake inhibitor (SSRI) or a serotonin-norepinephrine reuptake inhibitor (SNRI), to treat moderate-to-severe depression. It intended for people with major depressive disorder who have tried at least two different antidepressants which did not treat their depression adequately.

Esketamine may also be used in addition to an SSRI or SNRI when the doctor feels that urgent psychiatric treatment for symptoms of depression is needed.

The exact way esketamine works to treat mood disorders has not been fully determined, although it is believed to work by changing the activity of certain natural chemicals in the brain.

This medication may be available under multiple brand names and/or in several different forms. Any specific brand name of this medication may not be available in all of the forms or approved for all of the conditions discussed here. As well, some forms of this medication may not be used for all of the conditions discussed here.

Your doctor may have suggested this medication for conditions other than those listed in these drug information articles. If you have not discussed this with your doctor or are not sure why you are taking this medication, speak to your doctor. Do not stop taking this medication without consulting your doctor.

Do not give this medication to anyone else, even if they have the same symptoms as you do. It can be harmful for people to take this medication if their doctor has not prescribed it.

What form(s) does this medication come in?

Each single-use device contains 0.2 mL of an aqueous solution that delivers 28 mg of esketamine in 2 sprays (one for each nostril). Nonmedicinal ingredients: citric acid monohydrate, sodium edetate, sodium hydroxide, and water for injection.

How should I use this medication?

When esketamine is added to treatment with an SSRI or SNRI that has not been completely effective, the recommended adult starting dose is 56  given intranasally (into the nose) twice a week for 4 weeks. Depending on how you are feeling and how well the medication works, your doctor may adjust the dose. Generally, after 4 weeks, the frequency is decreased to once a week, and then once every 2&mbsp;weeks.

When esketamine is prescribed for urgent psychiatric treatment, the recommended dose is 84 mg given intranasally twice a week for 4 weeks. If side effects are excessive or bothersome, your doctor may decrease the dose.

People with Japanese heritage or people over the age of 65 may require lower doses of this medication. Talk to your doctor if this applies to you.

Each spray device delivers 2 sprays (one in each nostril) for a dose of 28 mg of medication. If your dose is more than 28 mg, wait 5 minutes to allow the medication to be absorbed and then repeat this process with a second device.

This medication is usually taken until 6 months after the symptoms of depression have resolved.

Before using the device, gently blow your nose. Do not prime the device before using it. This will cause medication to be discharged from the device and you will not get the full amount of medication for each dose. Tilt your head back approximately 45 degrees and place the tip of the device into one nostril. Hold the other nostril closed and gently inhale through your nose as you activate the spray. Gently sniff, to keep the medication in your nose. Breathe through your mouth. For the second spray, repeat this process with the other nostril.

Many things can affect the dose of medication that a person needs, such as body weight, other medical conditions, and other medications. If your doctor has recommended a dose different from the ones listed here, do not change the way that you are taking the medication without consulting your doctor.

It is important to take this medication exactly as prescribed by your doctor. Esketamine must be given at the doctor's office or clinic where blood pressure and mental changes can be monitored for at least 2 hours after using the medication. If you miss an appointment to receive esketamine, contact your doctor as soon as possible to reschedule your appointment.

This medication will be stored by your doctor and given to you to use when you arrive for your appointment for treatment.

Do not dispose of medications in wastewater (e.g. down the sink or in the toilet) or in household garbage. Ask your pharmacist how to dispose of medications that are no longer needed or have expired.

Who should NOT take this medication?

Do not take this medication if you:

  • are allergic to esketamine or any ingredients of the medication
  • are allergic to ketamine
  • have a condition in which an increase in blood pressure would be dangerous, including:
    • weakened or widened blood vessels
    • an abnormal connection between veins and arteries
    • a history of bleeding in the brain
    • a previous heart attack, stroke or other serious event in the past 6 weeks

What side effects are possible with this medication?

Many medications can cause side effects. A side effect is an unwanted response to a medication when it is taken in normal doses. Side effects can be mild or severe, temporary or permanent.

The side effects listed below are not experienced by everyone who takes this medication. If you are concerned about side effects, discuss the risks and benefits of this medication with your doctor.

The following side effects have been reported by at least 1% of people taking this medication. Many of these side effects can be managed, and some may go away on their own over time.

Contact your doctor if you experience these side effects and they are severe or bothersome. Your pharmacist may be able to advise you on managing side effects.

  • abdominal pain or discomfort
  • abnormal dreams
  • changes to sense of taste
  • constipation
  • cough
  • crying
  • decreased interest in sexual activity
  • diarrhea
  • dizziness
  • drowsiness
  • dry mouth
  • ear discomfort
  • faint
  • feeling hot
  • headache
  • hearing loss
  • increased salivation
  • migraine headache
  • muscle stiffness or pain, tremors, or spasms
  • nasal congestion
  • nausea
  • nose bleeds
  • nose or throat discomfort
  • sneezing
  • spinning sensation
  • sweating
  • trouble sleeping
  • trouble speaking
  • very low energy
  • vomiting
  • weakness
  • weight gain

Although most of the side effects listed below don't happen very often, they could lead to serious problems if you do not seek medical attention.

Check with your doctor as soon as possible if any of the following side effects occur:

  • anxiousness
  • decreased feeling or sensitivity, including around the mouth area
  • difficulty thinking (e.g., confusion, disorientation, difficulty paying attention or remembering)
  • euphoria (feeling of extreme well-being)
  • fast or irregular heartbeat
  • feeling "abnormal", "drunk", or "disconnected"
  • feeling disconnected from yourself, thoughts, and things around you
  • hallucinations (seeing or hearing things that aren't there)
  • increased blood pressure (e.g., headache, stronger or faster heartbeat, chest pain, dizziness, excessive tiredness, blurred vision)
  • mood swings
  • restlessness
  • signs of liver problems (e.g., darkening of urine, pale stools, yellow eyes or skin)
  • strong sense of sleepiness
  • symptoms of irregular heartbeat (e.g., chest pain, dizziness, rapid, pounding heartbeat, shortness of breath)
  • symptoms of a urinary tract infection (e.g., pain when urinating, urinating more often than usual, low back or flank pain)
  • tunnel vision
  • uncontrolled eye movement
  • withdrawal symptoms (e.g., anxiety, cravings, shaking, sweating, rapid, pounding heartbeat)

Stop taking the medication and seek immediate medical attention if any of the following occur:

  • signs of respiratory depression (e.g., slow, shallow, or weak breathing; bluish lips fingers, or toes; confusion; headache)
  • signs of a serious allergic reaction (e.g., abdominal cramps, difficulty breathing, nausea and vomiting, or swelling of the face and throat)
  • thoughts of suicide or self-harm

Some people may experience side effects other than those listed. Check with your doctor if you notice any symptom that worries you while you are taking this medication.

Are there any other precautions or warnings for this medication?

Before you begin using a medication, be sure to inform your doctor of any medical conditions or allergies you may have, any medications you are taking, whether you are pregnant or breast-feeding, and any other significant facts about your health. These factors may affect how you should use this medication.

Abuse: People who have a history of misusing drugs or alcohol may be more likely to experience addiction or psychological dependence with this medication. If you have had problems with misusing medications in the past, talk to your doctor about any special monitoring that may be beneficial while you are using this medication.

Alcohol and other medications that cause drowsiness: Do not combine this medication with alcohol or other medications (e.g., antidepressants, sleeping pills, anxiety medications) that cause drowsiness, since additional drowsiness, sedation, coma, and possibly death can occur. Avoid drinking alcohol for at least 24 hours before and after each treatment with esketamine.

Blood pressure: Esketamine can cause severe and potentially dangerous increases in blood pressure. Your doctor will want you to remain at the office or clinic for at least two hours after receiving this medication or until your blood pressure has returned to normal.

Difficulty breathing: Esketamine can cause serious and life-threatening breathing problems. If you experience slowed, shallow, or difficulty breathing, seek immediate medical attention. If you are taking other medications that can slow breathing (e.g., anxiety medications, sleeping pills) are a senior, have chronic bronchitis or emphysema that is not severe, or are obese and have sleep apnea you are more at risk of experiencing these symptoms.

Drowsiness/reduced alertness: Esketamine is likely to cause drowsiness, dizziness, and reduced awareness, affecting your ability to drive or operate machinery safely. It is important to avoid driving or operating machinery after using esketamine until the next day. Arrange to have someone pick you up from your appointment to receive this medication.

Food and drink: Nausea and vomiting are possible side effects of nasal esketamine. It is important to avoid eating anything for at least 2 hours before receiving esketamine. Avoid drinking anything for at least 30 minutes before receiving your dose of esketamine.

Heart problems: This medication may cause increased blood pressure and heart rate which can worsen symptoms of heart disease. If you have heart disease such as angina, congestive heart failure, or arrhythmia, discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed. Contact your doctor as soon as possible if you develop symptoms of heart problems such as shortness of breath, chest pain, rapid heartbeat, or swollen ankles.

Liver function:  Liver disease or reduced liver function may cause this medication to build up in the body, causing side effects. If you have liver problems, discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed. If you experience symptoms of liver problems such as fatigue, feeling unwell, loss of appetite, nausea, yellowing of the skin or whites of the eyes, dark urine, pale stools, abdominal pain or swelling, and itchy skin, contact your doctor immediately.

Mania: Esketamine may cause activation of mania. This means that people who are prone to mania may be more likely to have their mania start up again. If you have a history of mania or bipolar disorder, your doctor should closely monitor your condition while you are taking this medication.

Other nasal sprays: If you use prescription or non-prescription nasal sprays, use them at least 1 hour before receiving esketamine.

Perception changes: Esketamine can cause your perception of yourself and your surroundings to change temporarily. This can lead to behaving in ways that are dangerous or not normal for you. Your doctor will have you rest at the office or clinic to monitor your feelings of drowsiness or perception until your thinking has returned to normal.

Suicidal or self-harm behaviour: People with depression are more likely to experience thoughts and behaviour associated with suicide. This is more likely to occur in the early stages of recovery from depression and may be further increased by using this medication. These symptoms may occur within several weeks after starting this medication. If you experience these side effects or notice them in a family member who is taking this medication, contact your doctor immediately. You should be closely monitored by your doctor for emotional and behaviour changes while taking this medication.

Thyroid disease: The safety and effectiveness of this medication when used by people with an overactive thyroid gland have not been determined. Esketamine may cause increased symptoms of an overactive thyroid gland, such as increased blood pressure and heart rate. If you have thyroid problems, discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed.

Urinary tract problems: Esketamine may cause inflammation of the bladder and may cause ulcers to form in the bladder. If you have bladder problems, discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed.

Symptoms of bladder inflammation include painful urination, increased urgency to urinate and increased urination at night. If you experience these symptoms or blood in the urine, contact your doctor as soon as possible.

Pregnancy: This medication should not be used during pregnancy unless the benefits outweigh the risks. People who may become pregnant should use effective birth control while using this medication and for 6 weeks after stopping the esketamine. If you become pregnant while taking this medication, contact your doctor immediately.

Breast-feeding: It is not known if esketamine passes into breast milk. If you are breast-feeding and taking this medication, it may affect your baby. Talk to your doctor about whether you should continue breast-feeding.

Children: The safety and effectiveness of using this medication have not been established for children and adolescents less than 17 years of age.

Seniors: The safety and effectiveness of this medication have not been determined for people over the age of 65. Seniors may be more sensitive to the effects of this medication and it is generally not recommended for people in this age group.

What other drugs could interact with this medication?

For a full list of interactions, use the Drug Interaction Checker available on the website.

If you are taking other medications, speak with your doctor or pharmacist. Depending on your specific circumstances, your doctor may want you to:

  • stop taking one of the medications,
  • change one of the medications to another,
  • change how you are taking one or both of the medications, or
  • leave everything as is.

An interaction between two medications does not always mean that you must stop taking one of them. Speak to your doctor about how any drug interactions are being managed or should be managed.

Tell your doctor or prescriber about all prescription, over-the-counter (non-prescription), and herbal medications you are taking. Also tell them about any supplements you take. Since caffeine, alcohol, the nicotine from cigarettes, or street drugs can affect the action of many medications, you should let your prescriber know if you use them.

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