9 (3%) --- 2 (3%) 1 (2%)
≥40 mmHg increase 29 (8%) 1 (0.5%) 12 (17%) 1 (2%)
Diastolic blood pressure
≥110 mmHg 13 (4%) 1 (0.5%) --- ---
≥25 mmHg increase 46 (13%) 6 (3%) 10 (14%) 2 (3%)
Nausea and Vomiting
SPRAVATO can cause nausea and vomiting (Table 7). Most of these events occurred on the dayof dosing and resolved the same day, with the median duration not exceeding 1 hour in mostsubjects across dosing sessions. Rates of reported nausea and vomiting decreased over timeacross dosing sessions from the first week of treatment in the short-term studies, as well as overtime with long-term treatment (Table 7).
Table 7: Incidence and Severity of Nausea and Vomiting in Double-blind, Randomized-controlled Fixeddose
Study
Nausea Vomiting
Treatment (+ Oral AD)
N All Severe All Severe
SPRAVATO 56 mg 115 31 (27%) 0 7 (6%) 0
SPRAVATO 84 mg 116 37 (32%) 4 (3%) 14 (12%) 3 (3%)
Placebo Nasal Spray 113 12 (11%) 0 2 (2%) 0
Sense of Smell
Sense of smell was assessed over time; no difference was observed between patients treated withSPRAVATO plus oral AD and those treated with placebo nasal spray plus oral AD during thedouble-blind maintenance phase of Study 2 [see Clinical Studies (14.2)].
7 DRUG INTERACTIONS
7.1 Central Nervous System DepressantsConcomitant use with CNS depressants (e.g., benzodiazepines, opioids, alcohol) may increasesedation [see Warnings and Precautions (5.1)]. Closely monitor for sedation with concomitantuse of SPRAVATO with CNS depressants.
7.2 PsychostimulantsConcomitant use with psychostimulants (e.g., amphetamines, methylphenidate, modafanil,armodafinil) may increase blood pressure [see Warnings and Precautions (5.6)]. Closelymonitor blood pressure with concomitant use of SPRAVATO with psychostimulants.
7.3 Monoamine Oxidase Inhibitors (MAOIs)Concomitant use with monoamine oxidase inhibitors (MAOIs) may increase blood pressure [seeWarnings and Precautions (5.6)]. Closely monitor blood pressure with concomitant use ofSPRAVATO with MAOIs.
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Pregnancy Exposure RegistryThere is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed toantidepressants, including SPRAVATO, during pregnancy. Healthcare providers are encouragedto register patients by contacting the National Pregnancy Registry for Antidepressants at1-844-405-6185 or online at https://womensmentalhealth.org/clinical-and-researchprograms/pregnancyregistry/antidepressants/.
Risk Summary
SPRAVATO is not recommended during pregnancy. There are insufficient data on SPRAVATOuse in pregnant women to draw conclusions about any drug-associated risk of major birthdefects, miscarriage, or adverse maternal or fetal outcomes. Based on published findings frompregnant animals treated with ketamine, the racemic mixture of arketamine and esketamine,SPRAVATO may cause fetal harm when administered to pregnant women (see Data).
Advisepregnant women of the potential risk to an infant exposed to SPRAVATO in utero. There arerisks to the mother associated with untreated depression in pregnancy(see ClinicalConsiderations). If a woman becomes pregnant while being treated with SPRAVATO, treatmentwith esketamine should be discontinued and the patient should be counseled about the potentialrisk to the fetus.
Published studies in pregnant primates demonstrate that the administration of drugs that blockN-methyl-D-aspartate (NMDA) receptors during th |
