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Esketamine (Spravato)

Dissociativeprescriptioninhalation · predicted

S-enantiomer of ketamine; intranasal formulation approved for treatment-resistant depression (with oral antidepressant) and MDD with acute suicidal ideation/behavior. Administered 56 or 84 mg in-clinic under REMS with 2-hour observation. Plasma half-life ~7-12h. Intranasal bioavailability ~48%. NMDA antagonist with rapid-onset antidepressant effect (hours to days).

Projected serum levels — 56 mg, custom (shown daily)

Esketamine (Spravato)
Esketamine (Spravato) modeled serum levels, 56 mg custom (shown daily) over 15 days Population-based pharmacokinetic estimate. Steady state reached after approximately 1 days. 0 6.3 12.5 18.8 25 Day 0 Day 4 Day 8 Day 11 Day 15 Time on a regular schedule ≈ steady state · day 1

Maintenance schedule: 56 mg custom (shown daily) (inhalation).

Modeled steady state after ~1 days: peak ≈ 22.2 mg, trough ≈ 0.17 mg body load. Population-based estimate over 15 days for a 56 mg dose at a 70 kg reference body mass — the interactive app scales curves to your doses, timing, and body mass.

Key facts

Category
Dissociative
Route modeled
Inhalation
Model confidence
predicted
Half-life
9 h
Common dose
56 mg
Suggested maximum
84 mg/day
Reference dose range
28–84 mg (single dose)
Suggested cadence
custom (shown daily)
Validated against
84 mg inhalation — Cmax 0.090 mg/L at 0.50 h

Documented interactions

  • danger
    Carbamazepine (Tegretol) + Esketamine (Spravato) CYP induction

    Carbamazepine (Tegretol) inducer of CYP3A4 predicted to change Esketamine (Spravato) AUC by ~0.32x

  • danger
    Dextromethorphan (DXM) + Esketamine (Spravato) Stacked effects

    Dextromethorphan (DXM) and Esketamine (Spravato) both push the mu opioid, nmda, and sigma 1 in the same direction.

  • danger
    Efavirenz (Sustiva) + Esketamine (Spravato) CYP induction

    Efavirenz (Sustiva) inducer of CYP3A4 predicted to change Esketamine (Spravato) AUC by ~0.21x

  • danger
    Ketamine + Esketamine (Spravato) Stacked effects

    Esketamine (Spravato) and Ketamine both push the mu opioid, nmda, and sigma 1 in the same direction.

  • danger
    Phenobarbital + Esketamine (Spravato) CYP induction

    Phenobarbital inducer of CYP3A4 predicted to change Esketamine (Spravato) AUC by ~0.49x

  • danger
    Phenytoin (Dilantin) + Esketamine (Spravato) CYP induction

    Phenytoin (Dilantin) inducer of CYP3A4 predicted to change Esketamine (Spravato) AUC by ~0.49x

Serum checks 107 modeled interaction pairings for esketamine (spravato) across your whole stack — absorption conflicts, enzyme inhibition, and nutrient depletion included.

Research behind this entry

  1. Population pharmacokinetics of intranasal esketamine in patients with treatment-resistant depression Perez-Ruixo C et al. · Clinical Pharmacokinetics, 2021 DOI

    Population PK analysis characterizing intranasal esketamine's ~48% bioavailability, ~7-12h half-life, and exposure in TRD.

  2. Efficacy and safety of intranasal esketamine adjunctive to oral antidepressant therapy in treatment-resistant depression Daly EJ et al. · JAMA Psychiatry, 2018 DOI

    Pivotal phase 2 trial demonstrating rapid and sustained antidepressant effect of intranasal esketamine added to oral AD in TRD.

2 published studies referenced in the app, each with a plain-language summary.