(1)brexanolone, hydromorphone. Either increases toxicity of the other by sedation. Use Caution/Monitor.hydroxyzineMonitor Closely (1)brexanolone, hydroxyzine. Either increases toxicity of the other by sedation. Use Caution/Monitor.iloperidoneMonitor Closely (1)brexanolone, iloperidone. Either increases toxicity of the other by sedation. Use Caution/Monitor.isofluraneMonitor Closely (1)brexanolone, isoflurane. Either increases toxicity of the other by sedation. Use Caution/Monitor.ketamineMonitor Closely (1)brexanolone, ketamine. Either increases toxicity of the other by sedation. Use Caution/Monitor.lamotrigineMonitor Closely (1)brexanolone, lamotrigine. Either increases toxicity of the other by sedation. Use Caution/Monitor.lasmiditanMonitor Closely (1)lasmiditan, brexanolone. Either increases effects of the other by sedation. Use Caution/Monitor. Coadministration of lasmiditan and other CNS depressant drugs, including alcohol have not been evaluated in clinical studies. Lasmiditan may cause sedation, as well as other cognitive and/or neuropsychiatric adverse reactions.lemborexantMonitor Closely (1)lemborexant, brexanolone. Either increases effects of the other by sedation. Modify Therapy/Monitor Closely. Dosage adjustment may be necessary if lemborexant is coadministered with other CNS depressants because of potentially additive effects. .levetiracetamMonitor Closely (1)brexanolone, levetiracetam. Either increases toxicity of the other by sedation. Use Caution/Monitor.levorphanolMonitor Closely (1)brexanolone, levorphanol. Either increases toxicity of the other by sedation. Use Caution/Monitor.lorazepamMonitor Closely (1)brexanolone, lorazepam. Either increases toxicity of the other by sedation. Use Caution/Monitor.loxapineMonitor Closely (1)brexanolone, loxapine. Either increases toxicity of the other by sedation. Use Caution/Monitor.loxapine inhaledMonitor Closely (1)brexanolone, loxapine inhaled. Either increases toxicity of the other by sedation. Use Caution/Monitor.loxicodegolMonitor Closely (1)brexanolone, loxicodegol. Either increases toxicity of the other by sedation. Use Caution/Monitor.lurasidoneMonitor Closely (1)brexanolone, lurasidone. Either increases toxicity of the other by sedation. Use Caution/Monitor.maprotilineMonitor Closely (1)brexanolone, maprotiline. Either increases toxicity of the other by sedation. Use Caution/Monitor.meclizineMonitor Closely (1)brexanolone, meclizine. Either increases toxicity of the other by sedation. Use Caution/Monitor.meperidineMonitor Closely (1)brexanolone, meperidine. Either increases toxicity of the other by sedation. Use Caution/Monitor.meprobamateMonitor Closely (1)brexanolone, meprobamate. Either increases toxicity of the other by sedation. Use Caution/Monitor.metaxaloneMonitor Closely (1)brexanolone, metaxalone. Either increases toxicity of the other by sedation. Use Caution/Monitor.methadoneMonitor Closely (1)brexanolone, methadone. Either increases toxicity of the other by sedation. Use Caution/Monitor.methocarbamolMonitor Closely (1)brexanolone, methocarbamol. Either increases toxicity of the other by sedation. Use Caution/Monitor.methohexitalMonitor Closely (1)brexanolone, methohexital. Either increases toxicity of the other by sedation. Use Caution/Monitor.methsuximideMonitor Closely (1)brexanolone, methsuximide. Either increases toxicity of the other by sedation. Use Caution/Monitor.metoclopramide intranasalSerious - Use Alternative (1)brexanolone, metoclopramide intranasal. Either increases effects of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: Avoid use of metoclopramide intranasal or interacting drug, depending on importance of drug to patient.midazolamMonitor Closely (1)brexanolone, midazolam. Either increases toxicity of the other by sedation. Use Caution/Monitor.midazolam intranasalMonitor Closely (1)midazolam intranasal, brexanolone. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Concomitant use of barbiturates, alcohol, or other CNS depressants may increase the risk of hypoventilation, airway obstruction, desaturation, or apnea and may contribute to profound and/or prolonged drug effect.mirtazapineMonitor Closely (1)brexanolone, mirtazapine. Either increases toxicity of the other by sedation. Use Caution/Monitor.molindoneMonitor Closely (1)brexanolone, molindone. Either increases toxicity of the other by sedation. Use Caution/Monitor.morphineMonitor Closely (1)brexanolone, morphine. Either increases toxicity of the other by sedation. Use Caution/Monitor.nalbuphineMonitor Closely (1)brexanolone, nalbuphine. Either increases toxicity of the other by sedation. Use Caution/Monitor.nitric oxide gasMonitor Closely (1)brexanolone, nitric oxide gas. Either increases toxicity of the other by sedation. Use Caution/Monitor.olanzapineMonitor Closely (1)brexanolone, olanzapine. Either increases toxicity of the other by sedation. Use Caution/Monitor.oliceridineMonitor Closely (1)brexanolone, oliceridine. Either increases toxicity of the other by sedation. Use Caution/Monitor.olopatadine intranasalSerious - Use Alternative (1)brexanolone and olopatadine intranasal both increase sedation. Avoid or Use Alternate Drug. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment. opium tinctureMonitor Closely (1)brexanolone, opium tincture. Either increases toxicity of the other by sedation. Use Caution/Monitor.orphenadrineMonitor Closely (1)brexanolone, orphenadrine. Either increases toxicity of the other by sedation. Use Caution/Monitor.oxazepamMonitor Closely (1)brexanolone, oxazepam. Either increases toxicity of the other by sedation. Use Caution/Monitor.oxycodoneMonitor Closely (1)brexanolone, oxycodone. Either increases toxicity of the other by sedation. Use Caution/Monitor.oxymorphoneMonitor Closely (1)brexanolone, oxymorphone. Either increases toxicity of the other by sedation. Use Caution/Monitor.paliperidoneMonitor Closely (1)brexanolone, paliperidone. Either increases toxicity of the other by sedation. Use Caution/Monitor.pentazocineMonitor Closely (1)brexanolone, pentazocine. Either increases toxicity of the other by sedation. Use Caution/Monitor.pentobarbitalMonitor Closely (1)brexanolone, pentobarbital. Either increases toxicity of the other by sedation. Use Caution/Monitor.perampanelMonitor Closely (1)brexanolone, perampanel. Either increases toxicity of the other by sedation. Use Caution/Monitor.perphenazineMonitor Closely (1)brexanolone, perphenazine. Either increases toxicity of the other by sedation. Use Caution/Monitor.pheniramineMonitor Closely (1)brexanolone, pheniramine. Either increases toxicity of the other by sedation. Use Caution/Monitor.phenobarbitalMonitor Closely (1)brexanolone, phenobarbital. Either increases toxicity of the other by sedation. Use Caution/Monitor.phenytoinMonitor Closely (1)brexanolone, phenytoin. Either increases toxicity of the other by sedation. Use Caution/Monitor.pimavanserinMonitor Closely (1)brexanolone, pimavanserin. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.pimozideMonitor Closely (1)brexanolone, pimozide. Either increases toxicity of the other by sedation. Use Caution/Monitor.pomalidomideMonitor Closely (1)brexanolone, pomalidomide. Either increases toxicity of the other by sedation. Use Caution/Monitor.pregabalinMonitor Closely (2)brexanolone, pregabalin. Either increases toxicity of the other by sedation. Use Caution/Monitor. pregabalin, brexanolone. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation.primidoneMonitor Closely (1)brexanolone, primidone. Either increases toxicity of the other by sedation. Use Caution/Monitor.prochlorperazineMonitor Closely (1)brexanolone, prochlorperazine. Either increases toxicity of the other by sedation. Use Caution/Monitor.promazineMonitor Closely (1)brexanolone, promazine. Either increases toxicity of the other by sedation. Use Caution/Monitor.promethazineMonitor Closely (1)brexanolone, promethazine. Either increases toxicity of the other by sedation. Use Caution/Monitor.quazepamMonitor Closely (1)brexanolone, quazepam. Either increases toxicity of the other by sedation. Use Caution/Monitor.quetiapineMonitor Closely (1)brexanolone, quetiapine. Either increases toxicity of the other by sedation. Use Caution/Monitor.ramelteonMonitor Closely (1)brexanolone, ramelteon. Either increases toxicity of the other by sedation. Use Caution/Monitor.remifentanilMonitor Closely (1)brexanolone, remifentanil. Either increases toxicity of the other by sedation. Use Caution/Monitor.remimazolamMonitor Closely (1)remimazolam, brexanolone. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely. Coadministration may result in profound sedation, respiratory depression, coma, and/or death. Continuously monitor vital signs during sedation and recovery period if coadministered. Carefully titrate remimazolam dose if administered with opioid analgesics and/or sedative/hypnotics.risperidoneMonitor Closely (1)brexanolone, risperidone. Either increases toxicity of the other by sedation. Use Caution/Monitor.scopolamineMonitor Closely (1)brexanolone, scopolamine. Either increases toxicity of the other by sedation. Use Caution/Monitor.secobarbitalMonitor Closely (1)brexanolone, secobarbital. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.selinexorSerious - Use Alternative (1)selinexor, brexanolone. unspecified interaction mechanism. Avoid or Use Alternate Drug. Patients treated with selinexor may experience neurological toxicities. Avoid taking selinexor with other medications that may cause dizziness or confusion.sevofluraneMonitor Closely (1)brexanolone, sevoflurane. Either increases toxicity of the other by sedation. Use Caution/Monitor.sodium oxybateMonitor Closely (1)brexanolone, sodium oxybate. Either increases toxicity of the other by sedation. Use Caution/Monitor.stiripentolMonitor Closely (1)brexanolone, stiripentol. Either increases toxicity of the other by sedation. Use Caution/Monitor.sufentanilMonitor Closely (1)brexanolone, sufentanil. Either increases toxicity of the other by sedation. Use Caution/Monitor.sufentanil SLMonitor Closely (1)brexanolone, sufentanil SL. Either increases toxicity of the other by sedation. Use Caution/Monitor.sulpirideMonitor Closely (1)brexanolone, sulpiride. Either increases toxicity of the other by sedation. Use Caution/Monitor.suvorexantMonitor Closely (1)brexanolone, suvorexant. Either increases toxicity of the other by sedation. Use Caution/Monitor.tapentadolMonitor Closely (1)brexanolone, tapentadol. Either increases toxicity of the other by sedation. Use Caution/Monitor.tasimelteonMonitor Closely (1)brexanolone, tasimelteon. Either increases toxicity of the other by sedation. Use Caution/Monitor.temazepamMonitor Closely (1)brexanolone, temazepam. Either increases toxicity of the other by sedation. Use Caution/Monitor.tetrabenazineMonitor Closely (1)brexanolone, tetrabenazine. Either increases toxicity of the other by sedation. Use Caution/Monitor.thalidomideMonitor Closely (1)brexanolone, thalidomide. Either increases toxicity of the other by sedation. Use Caution/Monitor.thioridazineMonitor Closely (1)brexanolone, thioridazine. Either increases toxicity of the other by sedation. Use Caution/Monitor.thiothixeneMonitor Closely (1)brexanolone, thiothixene. Either increases toxicity of the other by sedation. Use Caution/Monitor.tiagabineMonitor Closely (1)brexanolone, tiagabine. Either increases levels of the other by sedation. Use Caution/Monitor.tizanidineMonitor Closely (1)brexanolone, tizanidine. Either increases toxicity of the other by sedation. Use Caution/Monitor.topiramateMonitor Closely (1)brexanolone, topiramate. Either increases toxicity of the other by sedation. Use Caution/Monitor.tramadolMonitor Closely (1)brexanolone, tramadol. Either increases toxicity of the other by sedation. Use Caution/Monitor.triazolamMonitor Closely (1)brexanolone, triazolam. Either increases toxicity of the other by sedation. Use Caution/Monitor.trifluoperazineMonitor Closely (1)brexanolone, trifluoperazine. Either increases toxicity of the other by sedation. Use Caution/Monitor.triprolidineMonitor Closely (1)brexanolone, triprolidine. Either increases toxicity of the other by sedation. Use Caution/Monitor.valerianMonitor Closely (1)brexanolone, valerian. Either increases toxicity of the other by sedation. Use Caution/Monitor.vigabatrinMonitor Closely (1)brexanolone, vigabatrin. Either increases toxicity of the other by sedation. Use Caution/Monitor.zaleplonMonitor Closely (1)brexanolone, zaleplon. Either increases toxicity of the other by sedation. Use Caution/Monitor.ziconotideMonitor Closely (1)brexanolone, ziconotide. Either increases toxicity of the other by sedation. Use Caution/Monitor.ziprasidoneMonitor Closely (1)brexanolone, ziprasidone. Either increases toxicity of the other by sedation. Use Caution/Monitor.zolpidemMonitor Closely (1)brexanolone, zolpidem. Either increases toxicity of the other by sedation. Use Caution/Monitor. >10% Sedation, somnolence (13-21%) Dizziness, presyncope, vertigo (12-13%) Dry mouth (3-11%) 1-10% Loss of consciousness (3-5%) Flushing, hot flush (2-5%) Tachycardia (3%) Diarrhea (2-3%) Oropharyngeal pain (2-3%) Dyspepsia (2%) Black Box Warnings Excessive sedation and sudden loss of consciousness Patients treated with brexanolone are at risk of excessive sedation or sudden loss of consciousness during administration Owing to the risk of serious harm, monitor for excessive sedation and sudden loss of consciousness and have continuous pulse oximetry monitoring Patients must be accompanied during interactions with their child(ren) Brexanolone is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the Zulresso REMS Patient must enroll in REMS before receiving drug; healthcare facilities and pharmacies must be registered and certified in the REMS program Contraindications None Cautions Sedation and sudden loss of consciousness Sedation and somnolence occurred during clinical trials that required dose interruption or reduction in some patients during infusion There was no clear association between loss or altered consciousness and pattern or timing of dose Not all patients who experienced a loss of or altered consciousness reported sedation or somnolence before the episode Caution against engaging in potentially hazardous activities requiring mental alertness (eg, driving) after infusion until sedative effects dissipate Monitor oxygenation with continuous pulse oximetry Suicidal thoughts and behaviors In pooled analyses of placebo-controlled trials of long-term administration of antidepressant drugs (SSRIs and other antidepressants) that included ~77,000 adults and 4,500 pediatric patients, the incidence of suicidal thoughts and behaviors in antidepressant-treated patients aged ≤24 yr was greater than in placebo-treated patients Brexanolone does not directly affect monoaminergic systems; because of this and the comparatively low number of exposures to brexanolone, risk of developing suicidal thoughts and behaviors is unknown Drug interaction overview Coadministration with CNS depressants (eg, opioids, benzodiazepines) may increase the likelihood or severity of adverse reactions related to sedation In the placebo-controlled studies, a higher percentage of brexanolone-treated patients who used concomitant antidepressants reported sedation-related events Pregnancy Available data from case reports use in pregnant women are insufficient to establish a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes Based on findings in animals of other drugs that enhance GABAergic inhibition, brexanolone may cause fetal harm Antidepressant pregnancy registry Pregnancy exposure registry monitors pregnancy outcomes in women exposed to antidepressants during pregnancy Clinicians are encouraged to register patients by calling the National Pregnancy Registry for Antidepressants at 1-844-405-6185, OR Online at: https://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/antidepressants Animal studies Malformations were not seen in rats or rabbits at plasma levels up to 5 and 6 times the maximum recommended human dose (MRHD), respectively Developmental toxicities were seen in the fetuses of rats and rabbits at 5 and ≥3 times the plasma levels at the MRHD, respectively Brexanolone administered to pregnant rats during pregnancy and lactation resulted in lower pup survival at doses associated with ≥2 times the plasma levels at the MRHD and a neurobehavioral deficit in female offspring at 5 times the plasma levels at the MRHD Lactation Data from a lactation study in 12 women indicate that brexanolone is transferred to breastmilk in nursing mothers; however, the relative infant dose (RID) is low, 1-2% of the maternal weight-adjusted dosage Available data do not suggest a significant risk of adverse reactions to breastfed infants from exposure The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for the drug and any potential adverse effects on the breastfed child from the drug or from the underlying maternal conditionPregnancy Categories A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk. B: May be acceptable. Either animal studies show no risk but human studies not available or