Pronunciation:

es-KET-a-meen

Brand Names:

• Spravato

Dosage Forms:

• Spray

Warnings:

Warning: Sedation; Dissociation; Respiratory Dissociation; Abuse and Misuse; and Suicidal Thoughts and BehaviorsRisk for sedation, dissociation, and respiratory depression after administration. Monitor patients for at least 2 hours after administration.Potential for abuse and misuse. Consider the risks and benefits of prescribing esketamine prior to using in patients at higher risk of abuse. Monitor patients for signs and symptoms of abuse and misuse.Esketamine is only available through a restricted program call the SPRAVATO(TM) REMS.Increased risk of suicidal thoughts and behaviors in pediatric and young adult patients taking antidepressants. Closely monitor all antidepressant-treated patients for clinical worsening and emergence of suicidal thoughts and behaviors. Esketamine is not approved for use in pediatric patients .

Classifications:

Therapeutic—

Antidepressant

Pharmacologic—

N-Methyl-D-Aspartate Receptor Antagonist

Uses of This Medicine:

Esketamine nasal spray is used together with an antidepressant taken by mouth, to treat patients with depression who have previously received at least 2 antidepressant treatments that did not work well (treatment-resistant depression).

Esketamine nasal spray is also used together with an antidepressant taken by mouth, to treat depressive symptoms in patients with major depressive disorder (MDD) with suicidal ideation or behavior.

This medicine is available only under a restricted distribution program called Spravato™ REMS (Risk Evaluation and Mitigation Strategy) Program.

Before Using This Medicine:

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies—

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Children—

Appropriate studies have not been performed on the relationship of age to the effects of esketamine nasal spray in the pediatric population. Safety and efficacy have not been established.

Older adults—

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of esketamine nasal spray in the elderly.

Breast-feeding—

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Other medicines—

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Acepromazine
• Alfentanil
• Alprazolam
• Amobarbital
• Anileridine
• Aripiprazole
• Asenapine
• Baclofen
• Benperidol
• Benzhydrocodone
• Bromazepam
• Buprenorphine
• Buspirone
• Butalbital
• Butorphanol
• Calcium Oxybate
• Cannabidiol
• Cannabis
• Carbamazepine
• Carbidopa
• Carbinoxamine
• Carisoprodol
• Carphenazine
• Cetirizine
• Chloral Hydrate
• Chlordiazepoxide
• Chlorpromazine
• Chlorzoxazone
• Clobazam
• Clonazepam
• Clorazepate
• Clozapine
• Codeine
• Cyclobenzaprine
• Cyproheptadine
• Daridorexant
• Dexmedetomidine
• Diacetylmorphine
• Diazepam
• Dichloralphenazone
• Difenoxin
• Dihydrocodeine
• Diphenhydramine
• Diphenoxylate
• Doxylamine
• Droperidol
• Enflurane
• Estazolam
• Eszopiclone
• Ethchlorvynol
• Ethopropazine
• Ethylmorphine
• Fentanyl
• Flibanserin
• Fluphenazine
• Flurazepam
• Fluspirilene
• Foscarbidopa
• Foslevodopa
• Fospropofol
• Gabapentin
• Gabapentin Enacarbil
• Halazepam
• Haloperidol
• Halothane
• Hexobarbital
• Hydrocodone
• Hydromorphone
• Hydroxyzine
• Isoflurane
• Ketamine
• Ketazolam
• Ketobemidone
• Lacosamide
• Lemborexant
• Levocetirizine
• Levodopa
• Levorphanol
• Lorazepam
• Loxapine
• Magnesium Oxybate
• Meclizine
• Melperone
• Meperidine
• Mephobarbital
• Meprobamate
• Meptazinol
• Mesoridazine
• Metaxalone
• Methadone
• Methdilazine
• Methocarbamol
• Methohexital
• Methotrimeprazine
• Methylene Blue
• Midazolam
• Molindone
• Moricizine
• Morphine
• Morphine Sulfate Liposome
• Nalbuphine
• Nicomorphine
• Nitrazepam
• Nitrous Oxide
• Olanzapine
• Oliceridine
• Opium
• Opium Alkaloids
• Orphenadrine
• Oxazepam
• Oxycodone
• Oxymorphone
• Paliperidone
• Papaveretum
• Paregoric
• Pentazocine
• Pentobarbital
• Perampanel
• Perazine
• Periciazine
• Perphenazine
• Phenobarbital
• Pimozide
• Piperacetazine
• Pipotiazine
• Piritramide
• Potassium Oxybate
• Prazepam
• Pregabalin
• Primidone
• Prochlorperazine
• Promazine
• Promethazine
• Propofol
• Quazepam
• Quetiapine
• Ramelteon
• Remifentanil
• Remimazolam
• Remoxipride
• Ropeginterferon Alfa-2b-njft
• Secobarbital
• Sertindole
• Sodium Oxybate
• Sufentanil
• Sulpiride
• Suvorexant
• Tapentadol
• Temazepam
• Thiethylperazine
• Thiopental
• Thiopropazate
• Thioridazine
• Tilidine
• Tizanidine
• Tolonium Chloride
• Topiramate
• Tramadol
• Trazodone
• Triazolam
• Trifluoperazine
• Trifluperidol
• Triflupromazine
• Trimeprazine
• Zaleplon
• Zolpidem
• Zopiclone
• Zotepine
• Zuranolone

Other interactions—

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following is usually not recommended, but may be unavoidable in some cases. If used together, your doctor may change the dose or how often you use this medicine, or give you special instructions about the use of food, alcohol, or tobacco.

• Ethanol

Other medical problems—

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

• Allergy to ketamine, history of or
• Aneurysmal vascular disease (blood vessel disease in the brain, chest, abdominal aorta, arms, and legs) or
• Arteriovenous malformation (abnormal connection between your veins and arteries) or
• Intracerebral hemorrhage (bleeding in the brain), history of—Should not be used in patients with these conditions.

• Cardiovascular (heart or blood vessel) disease or
• Cerebrovascular (brain or blood vessel) disease or
• Heart failure or
• Psychosis (mental illness)—Use with caution. May increase risk for more side effects.

• Drug abuse, history of or
• Heart attack, history of or
• Hypertension (high blood pressure) or
• Stroke, history of—Use with caution. May make these conditions worse.

• Hypertensive encephalopathy (brain problem caused by high blood pressure), history of—Use with caution. May increase risk for encephalopathy.

• Liver disease, moderate—Use with caution. The effects may be increased because of the slower removal of the medicine from the body.

• Liver disease, severe—Use is not recommended in patients with this condition.

Proper Use of This Medicine:

You will need to take a dose of this medicine under your doctor's supervision in a medical facility.

It is very important that you understand the requirements of the Spravato™ REMS program, and become familiar with the Spravato™ medication guide and patient instructions. Read and follow these instructions carefully to avoid misuse and abuse of this medicine. Ask your doctor if you have any questions. Ask your pharmacist for the medication guide and patient instructions f you do not have one.

Each device contains 2 sprays. Your doctor will tell you how many devices to use depending on your dose.

Do not eat for at least 2 hours and do not drink at least 30 minutes before using this medicine.

To use the nasal device:

• This medicine is for use only inside the nose. Do not get any of it into your eyes or on your skin. If it does get on these areas, rinse it off right away.
• Gently blow your nose to clear the nostrils before you use the first device only.
• Hold the device upright between your thumb and first 2 fingers. Do not press the plunger.
• Tilt your head back slightly.
• Insert the device tip into the first nostril. The nose rest should touch the skin between the nostrils.
• Close the other nostril, then firmly press the plunger all the way up as you slowly breathe through your nose. Sniff gently after spraying.
• Repeat the steps for the other nostril.
• If you need to use another device, wait 5 minutes after each device to allow the medicine to be absorbed.
• If liquid drips down from your nose, dab it with a tissue. Do not blow your nose.

Your doctor may also want you to stay in the medical facility for at least 2 hours to check for unwanted effects.

If you need to take a nasal steroid medicine or decongestant, take these at least 1 hour before using this medicine.

Dosing—

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For nasal dosage form (solution):
  • For depressive symptoms in patients with major depressive disorder (MDD) with suicidal ideation or behavior:
    • Adults—84 milligrams (mg) 2 times per week for 4 weeks. Your doctor may adjust your dose as needed and tolerated.
    • Children—Use and dose must be determined by your doctor.
  • For treatment-resistant depression (TRD):
    • Adults—The starting dose is 56 milligrams (mg) on Day 1, followed by 56 or 84 mg taken 2 times per week on Weeks 1 to 4. Then, 56 or 84 mg taken once a week on Weeks 5 to 8, followed by 56 or 84 mg taken every 2 weeks or once a week on Week 9 and after. Your doctor may adjust your dose as needed and tolerated.
    • Children—Use and dose must be determined by your doctor.

Missed dose—

This medicine needs to be given on a fixed schedule. If you miss a dose or forget to use your medicine, call your doctor or pharmacist for instructions.

Storage—

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

Precautions While Using This Medicine:

It is very important that your doctor check your progress at regular visits to make sure this medicine is working properly. Blood tests may be needed to check for unwanted effects.

This medicine may cause prolonged drowsiness, loss of consciousness, mental changes (eg, confusion about identity, place, and time, feeling of unreality, sense of detachment from self or body), or high blood pressure. Your doctor will check for these effects for at least 2 hours after each treatment session.

This medicine may cause lung or breathing problems, including respiratory depression. Check with your doctor right away if you have irregular, fast or slow, or shallow breathing, pale or blue lips, fingernails, or skin, or trouble breathing. Your doctor will check for these effects for at least 2 hours after each treatment session.

Esketamine nasal spray may cause some people to be agitated, irritable, or display other abnormal behaviors. It may also cause some people to have suicidal thoughts and tendencies or to become more depressed. Also tell your doctor if you have sudden or strong feelings, such as feeling nervous, angry, restless, violent, or scared. If you or your caregiver notice any of these side effects, tell your doctor right away.

This medicine may make you drowsy, confused, or have problems with thinking clearly. Do not drive or do anything else that could be dangerous until the next day after a restful sleep or until you know how this medicine affects you. You may also need someone to drive you home after treatment with this medicine.

This medicine may cause bladder problems, including ulcerative or interstitial cystitis. Check with your doctor right away if you have bloody or cloudy urine, difficult, burning, or painful urination, or a frequent urge to urinate.

Using this medicine while you are pregnant can harm your unborn baby. Use an effective form of birth control to keep from getting pregnant during treatment with this medicine. If you think you have become pregnant while using this medicine, tell your doctor right away.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal or vitamin supplements.

Side Effects of This Medicine:

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

More common

Anxiety

blurred vision

confusion about identity, time, and place

dizziness

drowsiness

feeling of constant movement of self or surroundings

feeling of unreality

headache

lightheadedness

nervousness

pounding in the ears

relaxed and calm feeling

sensation of spinning

sense of detachment from self or body

sleepiness

slow or fast heartbeat

unusual drowsiness, dullness, tiredness, weakness, or feeling of sluggishness

Less common

Changes in patterns and rhythms of speech

excitement

false or unusual sense of well-being

fast, pounding, or irregular heartbeat or pulse

feeling abnormal or drunk

frequent daytime urination

nightmares or unusually vivid dreams

slurred speech

tremor

trouble in speaking

urinating small amounts of urine at a time

Rare

Changes in behavior

chest pain or discomfort

discouragement

fast or pounding heartbeat

feeling sad or empty

irritability

lack of appetite

loss of interest or pleasure

sweating

thoughts of killing oneself

trouble concentrating

trouble sleeping

Incidence not known

Irregular, fast or slow, or shallow breathing

pale or blue lips, fingernails, or skin

trouble breathing

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common

Burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings

change in or loss of taste

diarrhea

nasal itching, burning, or irritation

nausea

throat irritation

vomiting

Less common

Constipation

dry mouth

mouth or throat pain

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.