Spravato 56mg Nasal Spray Dose Kit
WARNING: This drug may make you feel sleepy or dizzy, pass out, or cause anxiety. This drug may also cause a spinning feeling or an out-of-body feeling (like you are separated from your thoughts, feelings, surroundings, yourself, or time). These effects happened on the day of treatment and have gone away. Tell your doctor right away if you feel like you cannot stay awake or if you feel like passing out.This drug may cause breathing problems. Rarely, these problems were severe or life- threatening. Call your doctor right away if you have slow, shallow, or trouble breathing.You will be watched closely while you receive this drug and for some time after your dose. Talk with your doctor.Drugs like this one have raised the chance of suicidal thoughts or actions in children and young adults. The risk may be greater in people who have had these thoughts or actions in the past. All people who take this drug need to be watched closely. Call the doctor right away if signs like depression, nervousness, restlessness, grouchiness, panic attacks, or changes in mood or actions are new or worse. Call the doctor right away if any thoughts or actions of suicide occur.This drug has a risk of misuse. Use this drug only as you were told by your doctor. Tell your doctor if you have ever had alcohol or drug use disorder. @ COMMON USES: It is used to treat certain types of depression.
Drug Class
Antidepressant
Pharmacologic Class
N-methyl-D-aspartate (NMDA) receptor antagonist
Pregnancy Category
Not assigned (Risk Summary available)
FDA Approved
Mar 2019
DEA Schedule
Schedule III
Overview
What is this medicine?
Spravato is a nasal spray used to treat severe depression, especially when other antidepressants haven't worked (treatment-resistant depression) or for people with major depression who have suicidal thoughts. It works differently from other antidepressants and is given in a doctor's office or clinic because it can cause temporary side effects like feeling disconnected or sleepy, and your blood pressure needs to be monitored.
How to Use This Medicine
Taking Your Medication Correctly
To use this medication safely and effectively, follow your doctor's instructions carefully. Read all the information provided to you and adhere to the guidelines.
Administration
This medication is for nasal use only and will be administered in a healthcare setting where you can be closely monitored. Your doctor will instruct you on how to use the medication, and you should follow their guidance.
Each nasal spray device contains two sprays. Your doctor will determine the number of devices you need to use for your prescribed dose. Before using the first nasal spray device, blow your nose to clear your nasal passages. If any liquid drips out after use, gently dab your nose with a tissue. Avoid blowing your nose after using the medication.
Pre-Administration Precautions
Do not consume food for at least 2 hours before using this medication. Additionally, refrain from drinking liquids for at least 30 minutes before administration. If you use other nasal medications on the same day, use them at least 1 hour before using this medication.
Storage and Disposal
If you need to store this medication at home, consult with your doctor, nurse, or pharmacist for guidance on proper storage.
Missed Dose
If you miss a dose, contact your doctor to determine the best course of action.
To use this medication safely and effectively, follow your doctor's instructions carefully. Read all the information provided to you and adhere to the guidelines.
Administration
This medication is for nasal use only and will be administered in a healthcare setting where you can be closely monitored. Your doctor will instruct you on how to use the medication, and you should follow their guidance.
Each nasal spray device contains two sprays. Your doctor will determine the number of devices you need to use for your prescribed dose. Before using the first nasal spray device, blow your nose to clear your nasal passages. If any liquid drips out after use, gently dab your nose with a tissue. Avoid blowing your nose after using the medication.
Pre-Administration Precautions
Do not consume food for at least 2 hours before using this medication. Additionally, refrain from drinking liquids for at least 30 minutes before administration. If you use other nasal medications on the same day, use them at least 1 hour before using this medication.
Storage and Disposal
If you need to store this medication at home, consult with your doctor, nurse, or pharmacist for guidance on proper storage.
Missed Dose
If you miss a dose, contact your doctor to determine the best course of action.
Lifestyle & Tips
- Do not drive or operate machinery until the next day after a restful sleep, or until sedation and dissociation have resolved.
- Avoid alcohol and other CNS depressants on treatment days.
- Inform your doctor about all medications, supplements, and herbal products you are taking.
- Adhere strictly to the supervised administration schedule and monitoring requirements.
Available Forms & Alternatives
Available Strengths:
Dosing & Administration
Adult Dosing
Standard Dose:
Treatment-Resistant Depression (TRD): Initial phase: 56 mg or 84 mg twice weekly for 4 weeks. Maintenance phase: 56 mg or 84 mg once weekly or every two weeks. Major Depressive Disorder with Acute Suicidal Ideation or Behavior (MDD-ASI): 84 mg twice weekly for 4 weeks. Administered under direct supervision in a certified healthcare setting.
Dose Range:
56 - 84 mg
Condition-Specific Dosing:
TRD_initial:
56 mg or 84 mg twice weekly for 4 weeks
TRD_maintenance:
56 mg or 84 mg once weekly or every two weeks
MDD_ASI:
84 mg twice weekly for 4 weeks
Pediatric Dosing
Neonatal:
Not established
Infant:
Not established
Child:
Not established
Adolescent:
Not established (Safety and efficacy not established in patients <18 years of age)
Dose Adjustments
Renal Impairment:
Mild:
No dosage adjustment recommended
Moderate:
No dosage adjustment recommended
Severe:
No dosage adjustment recommended (Limited data, caution advised)
Dialysis:
No specific recommendations; caution advised due to limited data.
Hepatic Impairment:
Mild:
No dosage adjustment recommended (Child-Pugh Class A)
Moderate:
Consider dose reduction (e.g., 56 mg) for TRD, avoid for MDD-ASI (Child-Pugh Class B)
Severe:
Not recommended (Child-Pugh Class C)
Pharmacology
Mechanism of Action
Esketamine is the S-enantiomer of ketamine. It is an N-methyl-D-aspartate (NMDA) receptor antagonist. The exact antidepressant mechanism is not fully understood but is thought to involve modulation of glutamatergic neurotransmission, leading to increased synaptic plasticity and restoration of synaptic function in brain regions implicated in mood regulation.
Pharmacokinetics
Absorption:
Bioavailability:
Approximately 48% (nasal)
Tmax:
20-40 minutes
FoodEffect:
Not applicable (nasal administration)
Distribution:
Vd:
2.9 L/kg
ProteinBinding:
43-45%
CnssPenetration:
Yes (readily crosses blood-brain barrier)
Elimination:
HalfLife:
4-7 hours (terminal elimination half-life)
Clearance:
Not readily quantifiable due to nasal administration and extensive metabolism
ExcretionRoute:
Urine (78%), Feces (2%)
Unchanged:
<1% (urine)
Pharmacodynamics
OnsetOfAction:
Rapid (within hours for antidepressant effect, dissociation/sedation within minutes)
PeakEffect:
Dissociation/sedation: 40 minutes post-dose; Antidepressant effect: within 24 hours for some patients
DurationOfAction:
Dissociation/sedation: typically resolves within 1.5 hours; Antidepressant effect: sustained with continued treatment
Safety & Warnings
BLACK BOX WARNING
SPRAVATO has a Boxed Warning for sedation, dissociation, abuse and misuse, and suicidal thoughts and behaviors. Patients must be monitored by a healthcare professional for at least 2 hours after administration. SPRAVATO is only available through a restricted program called the SPRAVATO REMS program.
Side Effects
Serious Side Effects: Seek Medical Attention Immediately
Although rare, some people may experience severe and potentially life-threatening side effects while taking this medication. If you notice any of the following symptoms, contact your doctor or seek medical help right away:
Signs of an allergic reaction, such as:
+ Rash
+ Hives
+ Itching
+ Red, swollen, blistered, or peeling skin with or without fever
+ Wheezing
+ Tightness in the chest or throat
+ Trouble breathing, swallowing, or talking
+ Unusual hoarseness
+ Swelling of the mouth, face, lips, tongue, or throat
Signs of high blood pressure, including:
+ Severe headache or dizziness
+ Passing out
+ Changes in eyesight
Chest pain
Shortness of breath
Seizures
Confusion or memory problems
Anxiety
Frequent or urgent need to urinate, pain while urinating, or increased nighttime urination
Other Possible Side Effects
Like all medications, this drug can cause side effects. However, many people do not experience any side effects or only have mild ones. If you are bothered by any of the following side effects or if they do not go away, contact your doctor or seek medical help:
Dizziness or drowsiness
Feeling sluggish, disoriented, or unwell
Excessive happiness or excitement
Upset stomach or vomiting
Changes in taste
Headache
Numbness or tingling in the mouth
Sore throat
Reporting Side Effects
This list is not exhaustive, and you may experience other side effects. If you have questions or concerns about side effects, contact your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
Although rare, some people may experience severe and potentially life-threatening side effects while taking this medication. If you notice any of the following symptoms, contact your doctor or seek medical help right away:
Signs of an allergic reaction, such as:
+ Rash
+ Hives
+ Itching
+ Red, swollen, blistered, or peeling skin with or without fever
+ Wheezing
+ Tightness in the chest or throat
+ Trouble breathing, swallowing, or talking
+ Unusual hoarseness
+ Swelling of the mouth, face, lips, tongue, or throat
Signs of high blood pressure, including:
+ Severe headache or dizziness
+ Passing out
+ Changes in eyesight
Chest pain
Shortness of breath
Seizures
Confusion or memory problems
Anxiety
Frequent or urgent need to urinate, pain while urinating, or increased nighttime urination
Other Possible Side Effects
Like all medications, this drug can cause side effects. However, many people do not experience any side effects or only have mild ones. If you are bothered by any of the following side effects or if they do not go away, contact your doctor or seek medical help:
Dizziness or drowsiness
Feeling sluggish, disoriented, or unwell
Excessive happiness or excitement
Upset stomach or vomiting
Changes in taste
Headache
Numbness or tingling in the mouth
Sore throat
Reporting Side Effects
This list is not exhaustive, and you may experience other side effects. If you have questions or concerns about side effects, contact your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
Seek Immediate Medical Attention If You Experience:
- Severe dizziness or lightheadedness
- Difficulty breathing
- Chest pain
- Severe confusion or hallucinations
- Loss of consciousness
- Worsening depression or suicidal thoughts
- New or worsening urinary problems (e.g., frequent urination, painful urination, blood in urine)
Before Using This Medicine
Before Taking This Medication: Important Information to Share with Your Doctor
It is essential to inform your doctor about the following:
Any allergies you have, including allergies to this medication, its components, or other substances, such as foods or drugs. Be sure to describe the symptoms you experienced.
Certain health conditions, including:
+ Aneurysm (a type of blood vessel disease) in the brain, chest, abdomen, arms, or legs
+ Arteriovenous malformation
+ High blood pressure
+ Liver problems
If you have a history of bleeding in the brain
If you are pregnant or think you might be pregnant. Do not take this medication if you are pregnant.
* If you are breastfeeding. You should not breastfeed while taking this medication.
Additionally, it is crucial to discuss all of your medications, including prescription and over-the-counter drugs, natural products, and vitamins, with your doctor and pharmacist. This will help ensure that it is safe to take this medication with your other medications and health conditions. Never start, stop, or change the dose of any medication without first consulting your doctor.
It is essential to inform your doctor about the following:
Any allergies you have, including allergies to this medication, its components, or other substances, such as foods or drugs. Be sure to describe the symptoms you experienced.
Certain health conditions, including:
+ Aneurysm (a type of blood vessel disease) in the brain, chest, abdomen, arms, or legs
+ Arteriovenous malformation
+ High blood pressure
+ Liver problems
If you have a history of bleeding in the brain
If you are pregnant or think you might be pregnant. Do not take this medication if you are pregnant.
* If you are breastfeeding. You should not breastfeed while taking this medication.
Additionally, it is crucial to discuss all of your medications, including prescription and over-the-counter drugs, natural products, and vitamins, with your doctor and pharmacist. This will help ensure that it is safe to take this medication with your other medications and health conditions. Never start, stop, or change the dose of any medication without first consulting your doctor.
Precautions & Cautions
It is essential to inform all your healthcare providers, including doctors, nurses, pharmacists, and dentists, that you are taking this medication. After taking a dose, avoid operating a vehicle or engaging in any activities that require alertness until the following day, after you have had sufficient sleep. You will need someone to drive you home after each dose.
This medication may cause an increase in blood pressure, and your doctor will closely monitor your blood pressure levels. Before consuming alcohol, using marijuana or other cannabis products, or taking prescription or over-the-counter medications that may impair your reactions, consult with your doctor.
If you need to discontinue treatment with this medication, be aware that you may experience withdrawal symptoms. Report any adverse effects to your doctor, and do not hesitate to reach out if you have questions or concerns.
If you are of childbearing potential, discuss effective birth control methods with your doctor to prevent pregnancy while taking this medication. This drug may pose a risk to the unborn baby if taken during pregnancy. If you become pregnant or suspect you may be pregnant while taking this medication, contact your doctor immediately.
This medication may cause an increase in blood pressure, and your doctor will closely monitor your blood pressure levels. Before consuming alcohol, using marijuana or other cannabis products, or taking prescription or over-the-counter medications that may impair your reactions, consult with your doctor.
If you need to discontinue treatment with this medication, be aware that you may experience withdrawal symptoms. Report any adverse effects to your doctor, and do not hesitate to reach out if you have questions or concerns.
If you are of childbearing potential, discuss effective birth control methods with your doctor to prevent pregnancy while taking this medication. This drug may pose a risk to the unborn baby if taken during pregnancy. If you become pregnant or suspect you may be pregnant while taking this medication, contact your doctor immediately.
Overdose Information
Overdose Symptoms:
- Severe sedation
- Dissociation (out-of-body experience, feeling unreal)
- Respiratory depression
- Coma
- Severe hypertension
What to Do:
Seek immediate medical attention. Call 911 or Poison Control (1-800-222-1222). Management is supportive, including airway management, oxygenation, and cardiovascular support.
Drug Interactions
Major Interactions
- CNS depressants (e.g., benzodiazepines, opioids, alcohol): Increased sedation and dissociation.
- Psychostimulants (e.g., amphetamines, methylphenidate): Increased blood pressure and heart rate.
- MAOIs (Monoamine Oxidase Inhibitors): Potential for increased blood pressure and heart rate (caution advised, monitor BP).
Moderate Interactions
- CYP3A4 inducers (e.g., rifampin, carbamazepine, phenytoin): May decrease esketamine plasma concentrations.
- CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin, grapefruit juice): May increase esketamine plasma concentrations.
- Other drugs that increase blood pressure/heart rate (e.g., thyroid hormones, decongestants): Additive effects.
Monitoring
Baseline Monitoring
Blood Pressure (BP) and Heart Rate (HR)
Rationale: Risk of transient increases in BP and HR, especially post-dose.
Timing: Prior to administration
Mental Status Examination (MSE)
Rationale: Assess baseline psychiatric state, including suicidal ideation and history of psychosis.
Timing: Prior to administration
Dissociation/Sedation Assessment
Rationale: Establish baseline and prepare for post-dose monitoring.
Timing: Prior to administration
Routine Monitoring
Blood Pressure (BP) and Heart Rate (HR)
Frequency: At 40 minutes and 1.5 hours post-dose, and as clinically indicated
Target: Individualized, but monitor for significant increases (e.g., >40 mmHg systolic, >25 mmHg diastolic)
Action Threshold: Sustained clinically significant increases in BP/HR; consider delaying treatment or medical intervention.
Dissociation (e.g., CADSS score)
Frequency: At 40 minutes and 1.5 hours post-dose, and as clinically indicated
Target: Resolution of symptoms within 1.5-2 hours
Action Threshold: Persistent or severe dissociation requiring intervention or extended observation.
Sedation (e.g., RASS score)
Frequency: At 40 minutes and 1.5 hours post-dose, and as clinically indicated
Target: Resolution of symptoms within 1.5-2 hours
Action Threshold: Persistent or severe sedation requiring intervention or extended observation.
Suicidal Ideation/Behavior
Frequency: Regularly throughout treatment, especially at each visit
Target: Reduction or absence of suicidal thoughts
Action Threshold: Worsening suicidal ideation or emergence of new suicidal behaviors; requires immediate clinical assessment and intervention.
Symptom Monitoring
- Sedation
- Dissociation (feeling detached from self, surroundings, or thoughts)
- Dizziness
- Nausea
- Vomiting
- Vertigo
- Anxiety
- Increased blood pressure
- Increased heart rate
- Urinary tract symptoms (e.g., frequency, urgency, pain, hematuria) - rare but serious with chronic high-dose ketamine use
Special Patient Groups
Pregnancy
Use during pregnancy is generally not recommended unless the potential benefit justifies the potential risk to the fetus. There are no adequate and well-controlled studies in pregnant women. Animal studies show developmental toxicity (embryo-fetal lethality, skeletal abnormalities) at doses higher than human therapeutic doses.
Trimester-Specific Risks:
First Trimester:
Potential for embryo-fetal toxicity based on animal data.
Second Trimester:
Potential for embryo-fetal toxicity based on animal data.
Third Trimester:
Potential for neurotoxicity in developing brain based on animal data with other NMDA antagonists.
Lactation
It is not known if esketamine is excreted in human milk. Due to the potential for serious adverse reactions in breastfed infants, including neurotoxicity, a decision should be made whether to discontinue breastfeeding or to discontinue the drug, taking into account the importance of the drug to the mother.
Infant Risk:
Potential for sedation, neurodevelopmental effects; unknown.
Pediatric Use
Safety and efficacy have not been established in pediatric patients (under 18 years of age). Not approved for use in this population.
Geriatric Use
No overall differences in safety or effectiveness were observed between elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. Caution is advised due to potential for increased risk of falls, cardiovascular events, and cognitive impairment. Dose adjustments are not routinely needed based on age alone.
Clinical Information
Clinical Pearls
- Spravato is part of a REMS (Risk Evaluation and Mitigation Strategy) program due to risks of sedation, dissociation, and abuse/misuse. It must be administered in a certified healthcare setting under direct supervision.
- Patients must be monitored for at least 2 hours after each administration for adverse effects, particularly sedation and dissociation, and for blood pressure changes.
- Patients should not drive or operate machinery until the next day after a restful sleep, or until the effects of sedation and dissociation have fully resolved.
- Spravato is typically used in conjunction with an oral antidepressant.
- The nasal spray device delivers a fixed dose; patients should not attempt to use more than prescribed or administer it themselves outside of the supervised setting.
- Monitor for urinary tract symptoms with long-term use, as chronic high-dose ketamine use has been associated with urological issues.
Alternative Therapies
- Electroconvulsive Therapy (ECT)
- Transcranial Magnetic Stimulation (TMS)
- Vagus Nerve Stimulation (VNS)
- Ketamine (racemic, IV infusion, off-label for TRD)
- Other investigational rapid-acting antidepressants
Cost & Coverage
Average Cost:
Highly variable, typically several thousand dollars per month per treatment course
Insurance Coverage:
Specialty Tier (requires prior authorization, often limited to specific diagnoses and treatment failures)
General Drug Facts
If your symptoms or health problems persist or worsen, it is essential to contact your doctor promptly. To ensure safe use, do not share your medication with others, and never take someone else's medication. Store all medications in a secure location, out of reach of children and pets, to prevent accidental ingestion. Dispose of unused or expired medications properly. Unless instructed to do so by a healthcare professional, do not flush medications down the toilet or pour them down the drain. If you are unsure about the proper disposal method, consult your pharmacist, who can also inform you about potential drug take-back programs in your area.
This medication is accompanied by a Medication Guide, which is a comprehensive patient fact sheet. It is crucial to read this guide carefully and review it again each time your prescription is refilled. If you have any questions or concerns about this medication, discuss them with your doctor, pharmacist, or other healthcare provider. In the event of a suspected overdose, immediately contact your local poison control center or seek emergency medical attention. Be prepared to provide information about the medication taken, the amount, and the time it happened, as this will aid in prompt and effective treatment.
This medication is accompanied by a Medication Guide, which is a comprehensive patient fact sheet. It is crucial to read this guide carefully and review it again each time your prescription is refilled. If you have any questions or concerns about this medication, discuss them with your doctor, pharmacist, or other healthcare provider. In the event of a suspected overdose, immediately contact your local poison control center or seek emergency medical attention. Be prepared to provide information about the medication taken, the amount, and the time it happened, as this will aid in prompt and effective treatment.