In the year-long study, Spravato also improved depression symptoms. Spravato isn’t available for you to purchase at a pharmacy. After the four-week trial, some people enrolled in a year-long study. However, it’s also taken as a “party drug” that’s referred to as “Special K” and can be misused. Your doctor will determine the best dosage to suit your needs. Depression symptoms were measured on a scale of zero to 60 (with higher scores meaning worse depression symptoms). Esketamine (the active drug in Spravato) and ketamine are not the same drug, but they are similar chemicals. Spravato is for nasal use only. (SPRAH VAH' TOE) CIII Your doctor may recommend that you take Spravato on a long-term basis if it’s safe, effective, and necessary for you. Clinical studies of Spravato in pediatric patients have not been conducted. medical offices and clinics) must be enrolled in the program. This can affect the body’s ability to function properly. The European Commission (EC) has approved the expanded use of Janssen’s Spravato for the rapid reduction of depressive symptoms in a psychiatric emergency, for adult patients with a moderate-to-severe episode of major depressive disorder (MDD). People who were younger. Healthcare providers will monitor you for side effects during and after your treatment. If you take a nasal corticosteroid or nasal decongestant medicine, take these medicines at least 1 hour before taking Spravato. Moods and mental well-being can be affected by imbalance in neurotransmitter levels. Spravato is available in the following presentations: Within each kit, each 28 mg device is individually packaged in a sealed blister (NDC 50458-028-00). This list does not include all possible side effects. Patients in stable remission who continued treatment with Spravato plus oral AD experienced a statistically significantly longer time to relapse of depressive symptoms than did patients on placebo nasal spray plus an oral AD (see Figure 5). Check indicator again to confirm device is empty. Tell your healthcare provider right away if you or your family member have any of the following symptoms, especially if they are new, worse, or worry you: Tell your healthcare provider about all the medicines that you take, Especially tell your healthcare provider if you take, under supervision of a healthcare professional. Ketamine isn’t approved to treat depression at this time. There are no data on pregnancy exposures in primates corresponding to periods prior to the third trimester in humans [see Use in Specific Populations (8.2)]. Nasal corticosteroids or nasal decongestants. These complications include heart attack, stroke, or swelling in your brain. Increases in BP peak approximately 40 minutes after Spravato administration and last approximately 4 hours [see Adverse Reactions (6.1)]. In patients whose BP is elevated prior to Spravato administration (as a general guide: >140/90 mmHg) a decision to delay Spravato therapy should take into account the balance of benefit and risk in individual patients. Spravato® During week 9 and after, you’ll take Spravato either once weekly or twice weekly. Talk with your doctor about whether Spravato is safe for you. It’s often described as having an “out-of-body” experience. Spravato is also contraindicated in people with aneurysmal vascular disease, arteriovenous malformation, or history of intracerebral hemorrhage. This could make the drug less effective for you. Abilify contains the drug aripiprazole. Spravato is approved to treat a form of depression called treatment-resistant depression (TRD) in adults. The 112 mg dose of intranasal Spravato was associated with significantly higher scores for "Hallucinating," "Floating," "Detached," and "Spaced Out" than the 84 mg dose of intranasal Spravato and the intravenous ketamine dose. Table 4 shows the incidence of adverse reactions that occurred in patients treated with Spravato plus oral AD and greater than patients treated with placebo nasal spray plus oral AD. During the postweaning period, a decrease in motor activity was observed at doses ≥ 15 mg/kg which is 0.5-times the human exposure at the MRHD of 84 mg/day. Tell your healthcare provider right away if you have any new or sudden changes in mood, behavior, thoughts, or feelings. If you need financial support to pay for Spravato, or if you need help understanding your insurance coverage, help is available. Spravato comes as a nasal spray. During this study, people were taking an oral antidepressant with either Spravato or a placebo nasal spray. It’s taken once daily, in the evening. Spravato-treated patients with moderate hepatic impairment may need to be monitored for adverse reactions for a longer period of time. If you are not sure if you have any of the above conditions, talk to your healthcare provider before taking Spravato. There are no data on the effects of Spravato on the breastfed infant or on milk production. In studies for the treatment of depressive symptoms in adults with MDD with acute suicidal ideation or behavior, there was a higher incidence of sedation (MOAA/S score <5) in patients treated with Spravato plus oral AD compared to patients treated with placebo plus oral AD, similar to the TRD study results in Table 5. Abilify is usually taken once per day by mouth when used to treat depression. Each device delivers two sprays In studies for the treatment of depressive symptoms in adults with MDD with acute suicidal ideation or behavior, patients treated with Spravato plus oral AD also demonstrated a higher number (84%) with dissociation (CADSS total score >4 and change >0) compared to patients treated with placebo plus oral AD (16%). Each device delivers two sprays of the medication. Use in this population is not recommended [see Clinical Pharmacology (12.3)]. If you take a nasal corticosteroid or nasal decongestant medicine take these medicines at least 1 hour before taking Spravato. The MADRS is a ten-item, clinician-rated scale used to assess severity of depressive symptoms. Hold device as shown with the thumb gently supporting the plunger. It’s approved for use in combination with at least one other antidepressant medication that’s taken by mouth. Symptoms of sedation include extreme sleepiness, having trouble thinking, and a decreased ability to respond. Spravato was initiated at 28 mg twice weekly and could be titrated to 56 mg or 84 mg administered twice-weekly. Spravato must be administered under the direct observation of a healthcare provider. Monitoring for signs of abuse and misuse is recommended. Learn…, Solitary confinement is associated with significant increases in anxiety, suicidal thoughts, and physical health conditions, such as vision loss…. Driving performance was assessed at 8 hours after Spravato or mirtazapine administration. In a second single-dose neurotoxicity study conducted with intranasally administered esketamine to adult female rats, there were no findings of neuronal necrosis up to a dose equivalent of 270 mg/kg for a 200-gram rat which has a safety margin of 18-fold and 23-fold, respectively, to AUC and Cmax exposures at the MRHD of 84 mg/day. These imbalances may also be related to depression. Advise patients that they will need to be observed by a healthcare provider until these effects resolve [see Boxed Warning, Warnings and Precautions (5.1, 5.2)]. However, it is known that the drug passes into human breast milk. In addition, a dose-dependent delay in the age of attainment of Preyer response reflex was observed in pups at all doses during the preweaning period. It’s thought that ketamine and esketamine work differently because of their different structures. Spravato and Abilify contain very different drugs. It depends. No significant differences in the pharmacokinetics of Spravato nasal spray were observed for sex and total body weight (>39 to 170 kg) based on population PK analysis. The actual price you would pay for either drug depends on your dose, your insurance plan, your location, and the pharmacy you use. Spravato is available only through a restricted program called the Spravato REMS [see Warnings and Precautions (5.4)]. Your healthcare provider will show you how to use the Spravato nasal spray device. Risks can include serious side effects such as sedation (sleepiness, trouble thinking clearly, or inability to drive or use heavy machinery) and dissociation (an “out-of-body” experience). Healthcare providers are encouraged to register patients by contacting the National Pregnancy Registry for Antidepressants at 1-844-405-6185 or online at https://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/antidepressants/. Spravato hasn’t been FDA-approved to treat the conditions described below. They may recommend that you skip your sleep medication on the night before your Spravato dose. Spravato causes increases in systolic and/or diastolic blood pressure (BP) at all recommended doses. Scores on the MADRS range from 0 to 60, with higher scores indicating more severe depression. Among stable responders, 34% received every-other-week dosing and 55% received weekly dosing the majority of time during the maintenance phase. However, it is not clear how these animal findings relate to females of reproductive potential treated with the recommended clinical dose. Spravato and Symbyax are both brand-name drugs. Spravato and opioids can both cause sedation. Call your doctor for medical advice about side effects. Some people may have a higher risk of having suicidal thoughts and actions. One group was given Spravato and an oral antidepressant. Spravato can cause nausea and vomiting. Closely monitor all antidepressant-treated patients for clinical worsening, and for emergence of suicidal thoughts and behaviors. If a woman becomes pregnant while being treated with Spravato, treatment with esketamine should be discontinued and the patient should be counseled about the potential risk to the fetus. In a clinical study lasting four weeks, Spravato improved symptoms of depression in people taking the drug. Such withdrawal symptoms are likely to occur if esketamine were similarly abused. Esketamine is primarily metabolized to noresketamine metabolite via cytochrome P450 (CYP) enzymes CYP2B6 and CYP3A4 and to a lesser extent CYP2C9 and CYP2C19. No adverse effects of Spravato nasal spray on cognitive functioning were observed in a one-year open-label safety study; however, the long-term cognitive effects of Spravato have not been evaluated beyond one year. Spravato and Abilify are both brand-name drugs. Hypersensitivity to esketamine, ketamine, or any of the excipients. Reported symptoms of withdrawal associated with daily intake of large doses of ketamine include craving, fatigue, poor appetite, and anxiety. Use 2 devices (for a 56 mg dose) or 3 devices (for an 84 mg dose), with a 5-minute rest between use of each device. To enter and activate the submenu links, hit the down arrow. medical offices and clinics) must be enrolled in the Spravato REMS Program prior to administration. It’s approved for use in adults, in combination with at least one other antidepressant that’s taken by mouth. Results in these studies were conflicting. Of all Spravato-treated patients in the completed Phase 3 studies, 184 (81%) received all eight doses over a 4-week treatment period. The number of devices you’ll use depends on your specific dose. Measure blood pressure around 40 minutes post-dose and subsequently as clinically warranted until values decline. Spravato is available only as a brand-name medication. Brand name: Spravato® Nasal spray: 56 mg, 84 mg dose kit; Generic name: esketamine (es KET ah meen) All FDA black box warnings are at the end of this fact sheet. Because Spravato has these serious side effects, the FDA has placed restrictions on its use. In a single-dose neuronal toxicity study in adult rats, subcutaneously administered racemic ketamine caused neuronal vacuolation in layer I of the retrosplenial cortex of the brain without neuronal necrosis at a dose of 60 mg/kg. It’s approved for use in adults, in combination with at least one other antidepressant drug that’s taken by mouth. These studies have had promising short-term results. Dissociation was evaluated by adverse event reports and the Clinician-Administered Dissociative States Scale (CADSS). Sense of smell was assessed over time; no difference was observed between patients treated with Spravato plus oral AD and those treated with placebo nasal spray plus oral AD during the double-blind maintenance phase of Study 2 [see Clinical Studies (14.1)]. If a patient misses treatment session(s), provided there is no worsening of their depressive symptoms, the patient should continue the current dosing schedule. The Food and Drug Administration (FDA) approves prescription drugs such as Spravato to treat certain conditions. The inter-subject variability of esketamine ranges from 27% to 66% for Cmax and 18% to 45% for AUC∞. Spravato may cause serious side effects, including: The most common side effects of Spravato when used along with an antidepressant taken by mouth include: If these common side effects occur, they usually happen right after taking Spravato and go away the same day. The first dose of Spravato is 56 mg. Each dose after that is either 56 mg or 84 mg. The mean esketamine Cmax and AUC values were higher in elderly patients compared with younger adult patients [see Clinical Pharmacology (12.3)]. Advise the patient to read the FDA-approved patient labeling (Medication Guide). Your healthcare provider will show you how to use the SPRAVATO ® nasal spray device. Your healthcare provider will show you how to use the SPRAVATO™ nasal spray device. Counsel family members or caregivers of patients to monitor for changes in behavior and to alert the healthcare provider. Symptoms of a mild allergic reaction can include: A more severe allergic reaction is rare but possible. Generic Name: esketamine hydrochloride Brand Name: Spravato Manufacturer: Janssen Inc. Spravato starts working very quickly. In studies for the treatment of depressive symptoms in adults with MDD with acute suicidal ideation or behavior, patients demonstrated similar incidence and severity of reported nausea and vomiting compared to the TRD study results described above. Keep all follow-up visits with your healthcare provider as scheduled. It’s used in combination with other antidepressant medications taken by mouth. Two placebo-controlled studies were conducted to assess the effects of Spravato on the ability to drive [see Clinical Studies (14.3)]. TRD is a type of depression that hasn’t improved after you’ve tried at least two different antidepressant medications. Individuals with a history of drug abuse or dependence may be at greater risk for abuse and misuse of Spravato. You should always consult your doctor or other healthcare professional before taking any medication. The most common psychological effects of Spravato were dissociative or perceptual changes (including distortion of time, space and illusions), derealization and depersonalization (61% to 84% of Spravato-treated patients developed dissociative or perceptual changes based on the Clinician-Administered Dissociative States Scale) [see Adverse Reactions (6.1)]. Misuse is the intentional use, for therapeutic purposes, of a drug by an individual in a way other than prescribed by a healthcare provider or for whom it was not prescribed. The blood pressure changes seen within 1.5 hours of taking Spravato included: Your doctor will check your blood pressure before you take Spravato. It was also more common in people taking higher doses than in people taking lower doses of the drug. The mean absolute bioavailability is approximately 48% following nasal spray administration. Drug class: miscellaneous antidepressants, SD=standard deviation; SE=standard error; LS Mean=least-squares mean; CI=confidence interval; AD=antidepressant. If BP remains high, promptly seek assistance from practitioners experienced in BP management. 56 mg Dose Kit: Unit-dose carton containing two 28 mg nasal spray devices (56 mg total dose) (NDC 50458-028-02). This will depend on your specific insurance plan. Patients in this study were responders in one of two short-term controlled trials (Study 1 and another 4-week study) or in an open-label direct-enrollment study in which they received flexibly-dosed Spravato (56 mg or 84 mg twice weekly) plus daily oral AD in an initial 4-week phase. Serious side effects and their symptoms can include the following: * These effects can also occur in children. Ketamine contains a mixture of enantiomers, which are two chemicals that are mirror images of each other. Estimating 50% of the exposure to be from esketamine, the NOAEL for neuronal vacuolation is 1.6-times and 4.5-times and the NOAEL for neuronal necrosis is 10-times and 16-times exposures, respectively, for AUC and Cmax to the clinical exposure at the MRHD of 84 mg/day. Spravato can cause mild or serious side effects. It may be related to how Spravato interacts with neurotransmitters. Spravato is classified by the DEA as a Schedule III controlled substance, indicating a potential for misuse and dependence. Spravato contains the drug esketamine. These lists contain examples of serious side effects that can occur with Spravato, with Symbyax, or with both drugs (when taken individually). This monitoring is done to make sure that you have no serious side effects after your treatment. Consider the risk of untreated depression when discontinuing or changing treatment with antidepressant medication during pregnancy and postpartum. Increased blood pressure could cause serious complications with blood vessels in your heart or brain. Spravato contains the drug esketamine. What are the effects of solitary confinement on health? Spravato should be stored at room temperature (68°F to 77°F/20°C to 25°C). Refer patients experiencing symptoms of a hypertensive crisis (e.g., chest pain, shortness of breath) or hypertensive encephalopathy (e.g., sudden severe headache, visual disturbances, seizures, diminished consciousness or focal neurological deficits) immediately for emergency care. It’s taken under the supervision of a healthcare provider at a certified medical facility. Its molecular formula is C13H16ClNO.HCl and its molecular weight is 274.2. Yes, Spravato is a controlled substance. These medications belong to different drug classes, but they’re both used to treat depression. You may need to be monitored for a longer time after taking Spravato to make sure that you don’t feel sedated after treatment. Out of scope information includes radiopharmaceuticals, contrast media, herbals, homeopathics, and food. especially within the first few months of treatment or when the dose is changed. In both Study 3 and Study 4, Spravato's treatment difference compared to placebo was observed starting at 4 hours. What is esketamine and what does it treat? Below are lists of medications that can interact with Spravato. Each nasal spray device delivers two sprays containing a total of 28 mg esketamine. After the first dose, a one-time dose reduction to Spravato 56 mg was allowed for patients unable to tolerate the 84 mg dose. Before taking Spravato, talk with your doctor about your health history. This can help you avoid an increased risk of sedation. 3. The demographic and baseline disease characteristics of the two groups were similar. Time to relapse was also significantly delayed in the stable responder population. However, this article should not be used as a substitute for the knowledge and expertise of a licensed healthcare professional. Scores for people taking Spravato improved by 4 points more than scores for people taking the placebo. More studies are needed to know whether Spravato or ketamine are safe or effective for OCD treatment. This allows the healthcare provider to monitor you for any side effects, including hallucinations. You will take Spravato nasal spray yourself, under the supervision of a healthcare provider in a healthcare setting. The following information describes dosages that are commonly used or recommended. Esketamine exposure increases with dose from 28 mg to 84 mg. Trump had high praise of Spravato (he called the results "incredible"), but it isn't clear if Johnson & Johnson can benefit from the president's desire to get Spravato … The use of Spravato, in conjunction with an oral antidepressant, beyond 4 weeks has not been systematically evaluated in the treatment of depressive symptoms in patients with MDD with acute suicidal ideation or behavior. Esketamine was administered intranasally to both male and female rats before mating, throughout the mating period, and up to day 7 of gestation at doses equivalent to 4.5, 15, and 45 mg/kg/day (based on a 200-gram rat), which are approximately 0.05, 0.3, and 0.6-times the maximum recommended human dose (MRHD) of 84 mg/day based on mean AUC exposures, respectively. After Cmax was reached following intranasal administration, the decline in plasma esketamine concentrations was biphasic, with rapid decline for the initial 2 to 4 hours and a mean terminal half-life (t1/2) that ranged from 7 to 12 hours. A treatment session consists of nasal administration of Spravato and post-administration observation under supervision.Blood Pressure Assessment Before and After Treatment 1. Exposures of esketamine in specific populations are summarized in Figure 1. Some may be better suited for you than others. Both Spravato and alcohol can cause sedation (sleepiness, trouble thinking clearly, inability to drive or use heavy machinery). Follow these administration instructions and read the Instructions for Use before administration: During and after Spravato administration at each treatment session, observe the patient for at least 2 hours until the patient is safe to leave [see Warnings and Precautions (5.1, 5.2, 5.6, 5.8)]. Adverse reactions leading to Spravato discontinuation in more than 1 patient were (in order of frequency): dissociation-related events (2.6%), blood pressure increased (0.9%), dizziness-related events (0.9%), nausea (0.9%), and sedation-related events (0.9%). The actual price you would pay for either drug depends on your dose, your insurance plan, your location, and the pharmacy you use. This Medication Guide has been approved by the U.S. Food and Drug Administration. The greatest improvement in symptoms was seen in the first 24 hours after people took Spravato. Mirtazapine (30 mg) was used as a positive control. These drugs interact in different ways with nerves in your brain. Your doctor or pharmacist can tell you more about these laws. Your doctor will advise when you can safely leave the clinic. Approximately 19% of patients had reduction in Spravato dosage from 84 mg to 56 mg twice weekly. Maximum concentration is reached within 20 to 40 minutes after the dose. Examples of neurotransmitters include serotonin and dopamine. A delusion is a belief based on an inaccurate interpretation of reality. Your doctor will show you how to use the nasal spray device. According to estimates from GoodRx.com, Spravato may cost more than Symbyax. Drugs.com provides accurate and independent information on more than 24,000 prescription drugs, over-the-counter medicines and natural products. Table 5 presents the incidence of sedation (MOAA/S score <5) in a fixed-dose study with adult patients <65 years of age with TRD and a flexible-dose study with patients ≥65 years of age with TRD. This helps the medication stay inside your nose so that your body can absorb it. There are many different medications available to treat depression. Taking Spravato with monoamine oxidase inhibitors (MAOIs) can cause an increase in blood pressure. * Note: In Study 3, after the first dose, a one-time dose reduction to Spravato 56 mg was allowed for patients unable to tolerate the 84 mg dose. Because of the possibility of delayed or prolonged sedation, patients must be monitored by a healthcare provider for at least 2 hours at each treatment session, followed by an assessment to determine when the patient is considered clinically stable and ready to leave the healthcare setting [see Dosage and Administration (2.4)]. Approximately 8% to 19% of Spravato-treated patients and 1% to 4% of placebo-treated patients experienced an increase of greater than or equal to 40 mmHg in systolic BP and/or 25 mmHg in diastolic BP in the first 1.5 hours after administration at least once during the first 4 weeks of treatment. If you have a history of psychosis, you may be at increased risk. Spravato was evaluated in two identical Phase 3 short-term (4-week) randomized, double-blind, multicenter, placebo-controlled studies, Study 3 (NCT03039192) and Study 4 (NCT03097133), in adults with moderate-to-severe MDD (MADRS total score >28) who had active suicidal ideation and intent. This material is provided for educational purposes only and is not intended for medical advice, diagnosis or treatment. Enantiomers look similar to each other but have different effects inside the body. After at least 16 initial weeks of treatment with Spravato and an oral AD, stable remitters and stable responders were randomized separately to continue intranasal treatment with Spravato or switch to placebo nasal spray, in both cases with continuation of their oral AD. SD=standard deviation; SE=standard error; LS Mean=least-squares mean; CI=confidence interval; SOC=standard of care. You shouldn’t drive after taking the drug. Based on comparisons across species, the window of vulnerability to these changes is believed to correlate with exposures in the third trimester of gestation through the first several months of life, but this window may extend out to approximately 3 years of age in humans. Table 6 presents the incidence of dissociation (CADSS total score >4 and change >0) in a fixed-dose study with adult patients <65 years of age with TRD and a flexible-dose study with patients ≥65 years of age with TRD. The elimination of the major metabolite, noresketamine, from plasma is slower than esketamine. (esketamine) If you’re taking Spravato, you’ll need to sign an enrollment form stating that you understand the following: Additional information about the REMS requirements for Spravato can be found on the FDA’s website. Rates of reported nausea and vomiting decreased over time across dosing sessions from the first week of treatment in the short-term studies, as well as over time with long-term treatment. Your healthcare provider will let you know when they feel you can safely go home. Your doctor will determine if you have TRD based on your use of other antidepressants. Table 8 presents the incidence and severity of nausea and vomiting in a short-term study with patients with TRD. A single-blind, placebo-controlled study in 25 adult patients with major depressive disorder evaluated the effects of a single 84 mg dose of intranasal Spravato on next day driving and the effect of repeated administration of 84 mg of intranasal Spravato on same-day driving performance (Study 5). Taking a nasal corticosteroid or nasal decongestant around the time of your Spravato dose may reduce how much Spravato your body absorbs. This is the story of Amelia D., a … Tell your healthcare provider if you have ever abused or been dependent on alcohol, prescription medicines, or street drugs. The efficacy of Spravato for the treatment of TRD in geriatric patients was evaluated in a 4-week, randomized, double-blind study comparing flexibly-dosed intranasal Spravato plus a newly initiated oral antidepressant compared to intranasal placebo plus a newly initiated oral antidepressant in patients ≥ 65 years of age. A person with delusional disorder repeatedly has delusional thoughts. There were differences in absolute risk of suicidal thoughts and behaviors across the different indications, with the highest incidence in patients with major depressive disorder (MDD). A prospective, longitudinal study followed 201 pregnant women with a history of major depressive disorder who were euthymic and taking antidepressants at the beginning of pregnancy. Sedation was a common side effect seen in clinical studies of Spravato. Neurotransmitter levels can become imbalanced if they increase or decrease in activity. Esketamine exposure is dose-proportional between 56 mg and 84 mg. In these studies, patients received treatment with Spravato 84 mg or placebo nasal spray twice-weekly for 4 weeks. You will be asked to blow your nose before you take the first spray of Spravato. Patients in Study 1 met DSM-5 criteria for major depressive disorder (MDD) and in the current depressive episode, had not responded adequately to at least two different antidepressants of adequate dose and duration. Because of the risks of serious adverse outcomes resulting from sedation, dissociation, and abuse and misuse, Spravato is only available through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the Spravato REMS [see Warnings and Precautions (5.4)]. The inactive ingredients are citric acid monohydrate, edetate disodium, sodium hydroxide, and water for injection. Esketamine and its major metabolites do not induce CYP1A2. 2 fruit and 3 vegetable servings: The key to a longer life?