SPRAVATO Nasal spray, solution (2020)

Βιβλιογραφική αναφορά

Συγγραφείς

Janssen Pharmaceuticals Inc.

Λέξεις κλειδιά

50458-028

Για την προβολή της πλήρους καταχώρησης απαιτείται συνδρομή σε ισχύ.
Αποκτήστε πρόσβαση σε όλες τις πληροφορίες και τα εργαλεία του Galinos.gr δωρεάν για έναν μήνα απλά κάνοντας εγγραφή.
Δωρεάν εγγραφή

BOXED WARNING SECTION

WARNING: SEDATION; DISSOCIATION; ABUSE AND MISUSE; and SUICIDAL THOUGHTS AND BEHAVIORS Sedation: Patients are at risk for sedation after administration of SPRAVATO [see Warnings ...

1. Indications and Usage

SPRAVATO is indicated, in conjunction with an oral antidepressant, for the treatment of: Treatment-resistant depression (TRD) in adults Depressive symptoms in adults with major depressive disorder (MDD) ...

2. Dosage and Administration

2.1 Important Considerations Prior to Initiating and During Therapy SPRAVATO must be administered under the direct supervision of a healthcare provider. A treatment session consists of nasal administration ...

3. Dosage Forms and Strengths

Nasal Spray: 28 mg of esketamine per device. Each nasal spray device delivers two sprays containing a total of 28 mg esketamine.

4. Contraindications

SPRAVATO is contraindicated in patients with: Aneurysmal vascular disease (including thoracic and abdominal aorta, intracranial, and peripheral arterial vessels) or arteriovenous malformation [see ...

5. Warnings and Precautions

5.1 Sedation In clinical trials, 48% to 61% of SPRAVATO-treated patients developed sedation based on the Modified Observers Assessment of Alertness/Sedation scale (MOAA/S) [see Adverse Reactions (6.1)] ...

6. Adverse Reactions

The following adverse reactions are discussed in more detail in other sections of the labeling: Sedation [see Warnings and Precautions (5.1)] Dissociation [see Warnings and Precautions (5.2)] ...

6.1. Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another ...

7. Drug Interactions

7.1 Central Nervous System Depressants Concomitant use with CNS depressants (e.g., benzodiazepines, opioids, alcohol) may increase sedation [see Warnings and Precautions (5.1)]. Closely monitor ...

8.1. Pregnancy

Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antidepressants, including SPRAVATO, during pregnancy. Healthcare providers are encouraged ...

8.2. Lactation

Risk Summary Esketamine is present in human milk. There are no data on the effects of SPRAVATO on the breastfed infant or on milk production. Published studies in juvenile animals report neurotoxicity ...

8.3. Females and Males of Reproductive Potential

Contraception Based on published animal reproduction studies, SPRAVATO may cause embryo-fetal harm when administered to a pregnant woman [see Warnings and Precautions (5.10) and Use in Specific Populations ...

8.4. Pediatric Use

The safety and effectiveness of SPRAVATO in pediatric patients have not been established. Clinical studies of SPRAVATO in pediatric patients have not been conducted.

8.5. Geriatric Use

Of the total number of patients in Phase 3 clinical studies exposed to SPRAVATO, (N=1601), 194 (12%) were 65 years of age and older, and 25 (2%) were 75 years of age and older. No overall differences in ...

8.6. Hepatic Impairment

The mean esketamine AUC and t1/2 values were higher in patients with moderate hepatic impairment compared to those with normal hepatic function [see Clinical Pharmacology (12.3)]. SPRAVATO-treated ...

9.1. Controlled Substance

SPRAVATO contains esketamine hydrochloride, the (S)-enantiomer of ketamine and a Schedule III controlled substance under the Controlled Substances Act.

9.2. Abuse

Individuals with a history of drug abuse or dependence may be at greater risk for abuse and misuse of SPRAVATO. Abuse is the intentional, non-therapeutic use of a drug, even once, for its psychological ...

9.3. Dependence

Physical dependence has been reported with prolonged use of ketamine. Physical dependence is a state that develops as a result of physiological adaptation in response to repeated drug use, manifested by ...

10. Overdosage

Management of Overdosage There is no specific antidote for esketamine overdose. In the case of overdose, the possibility of multiple drug involvement should be considered. Contact a Certified Poison Control ...

11. Description

SPRAVATO contains esketamine hydrochloride, a non-competitive NmethylD-aspartate (NMDA) receptor antagonist. Esketamine is the S-enantiomer of racemic ketamine. The chemical name is ...

12.1. Mechanism of Action

Esketamine, the S-enantiomer of racemic ketamine, is a non-selective, non-competitive antagonist of the NmethylD-aspartate (NMDA) receptor, an ionotropic glutamate receptor. The mechanism ...

12.2. Pharmacodynamics

Cardiac Electrophysiology The effect of SPRAVATO (84 mg nasal spray and 0.8 mg/kg esketamine intravenously infused over 40 minutes) on the QTc interval was evaluated in a randomized, double-blind, placebo-, ...

12.3. Pharmacokinetics

Esketamine exposure increases with dose from 28 mg to 84 mg. The increase in Cmax and AUC values was less than dose-proportional between 28 mg and 56 mg or 84 mg, but it was nearly dose proportional ...

13.1. Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenesis Once-daily intranasal administration of esketamine at doses equivalent to 4.5, 15, and 45 mg/kg/day (based on a 200-gram rat) did not increase the incidence of tumors in a 2-year rat carcinogenicity ...

13.2. Animal Toxicology and/or Pharmacology

Neurotoxicity In a single-dose neuronal toxicity study where esketamine was administered intranasally to adult female rats, there were no findings of neuronal vacuolation in the brain up to an estimated ...

14. Clinical Studies

14.1 Treatment-Resistant Depression Short-Term Study SPRAVATO was evaluated in a randomized, placebo-controlled, double-blind, multicenter, short-term (4-week), Phase 3 study (Study 1; NCT02418585) in ...

16.1. How Supplied

SPRAVATO nasal spray is available as an aqueous solution of esketamine hydrochloride in a stoppered glass vial within a nasal spray device. Each nasal spray device delivers two sprays containing a total ...

16.2. Storage and Handling

Storage Store at 20° to 25°C (68° to 77°F); excursions permitted from 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. Disposal SPRAVATO nasal spray devices must be handled with ...

17. Patient Counseling Information

Advise the patient to read the FDA-approved patient labeling (Medication Guide). Sedation and Dissociation Inform patients that SPRAVATO has potential to cause sedation, dissociative symptoms, perception ...