Milsaperidone
BYSANTI
“Mill-sap (can’t) Buy sanity”
Antipsychotics are represented with spooky mascots
Polka dots on pink → α1 blocker → syncope if titrated too quickly (hit the floor)
Money → patent-extender bioequivalent to iloperidone
What it isD2 and 5-HT2A antagonist with alpha-1 and hERG blockade; schizophrenia and bipolar mania.
Why it mattersIt rapidly interconverts with iloperidone and has closely similar efficacy and safety, leaving little clinical differentiation.
What it changesOrthostatic hypotension and QT prolongation shape titration and interaction review; sedation and weight gain also occur.
FDA-approved for
- schizophrenia (2026)
- bipolar mania (2026)
FDA label
Read the full label on DailyMed ↗
| FDA dosing | Population | Start | Target | Max |
|---|---|---|---|---|
| Schizophrenia | Adult | 1 mg BID (Day 1) | 6–12 mg BID | 12 mg BID |
| Bipolar I (manic/mixed episodes) | Adult | 1 mg BID (Day 1) | 12 mg BID | 12 mg BID |
| Schizophrenia | CYP2D6 poor metabolizer | 1 mg BID (Day 1) | 3–6 mg BID | 6 mg BID |
| Bipolar I (manic/mixed episodes) | CYP2D6 poor metabolizer | 1 mg BID (Day 1) | 6 mg BID | 6 mg BID |
Titration Titrate daily per schedule (schizophrenia through Day 7; bipolar through Day 5) to reduce risk of orthostatic hypotension
Renal Undefined
Hepatic Mild: same as normal; moderate: consider lower maintenance dose; severe: not recommended
Restart titration if more than 3 days of treatment are missed
Instructions
- Take orally twice daily with or without food
- If >3 days of doses missed, restart the titration schedule
- With a strong CYP2D6 and/or CYP3A4 inhibitor, reduce dose by one-half; consider CYP2D6 genotyping
Available strengths
- tab 1, 2, 4, 6, 8, 10, 12 mg
Cautions
- Cerebrovascular reactions/stroke in elderly with dementia-related psychosis
- QTc prolongation — avoid other QT-prolonging drugs; monitor K+/Mg2+
- Neuroleptic malignant syndrome
- Tardive dyskinesia
- Metabolic changes (hyperglycemia, dyslipidemia, weight gain)
- Orthostatic hypotension and syncope
- Seizures
- Leukopenia/neutropenia/agranulocytosis
- Hyperprolactinemia
- Priapism
- Cognitive/motor impairment
- Intraoperative floppy iris syndrome
Adverse reactions
- Schizophrenia: dizziness, dry mouth, fatigue, nasal congestion, orthostatic hypotension, somnolence, tachycardia, weight increased
- Bipolar mania: tachycardia, dizziness, dry mouth, increased hepatic enzymes, nasal congestion, weight increased, hypotension, somnolence
Pregnancy Third-trimester antipsychotic exposure risks neonatal extrapyramidal/withdrawal symptoms; pregnancy exposure registry available
Lactation No human data; advise not to breastfeed during treatment and for 6 days (CYP2D6 normal) / 8 days (poor metabolizers) after last dose
Cost
| Strength | #/mo | generic $/mo | CostPlus | |
|---|---|---|---|---|
| 1 mg | tab | 60 BID | not offered | |
| 2 mg | tab | 60 BID | not offered | |
| 4 mg | tab | 60 BID | not offered | |
| 6 mg | tab | 60 BID | not offered | |
| 8 mg | tab | 60 BID | not offered | |
| 10 mg | tab | 60 BID | not offered | |
| 12 mg | tab | 60 BID | not offered |
Generic entry2040 est.
⚠ BOXED WARNING
- Increased mortality in elderly patients with dementia-related psychosis
Principal riskCYP2D6 poor metabolizers accumulate it, which is why iloperidone dosing is halved in that group
Classes and tags
Clinical profile
Legacy pregnancy categoryNot assigned — PLLR-era drug
Defining liabilityMetabolic effects, extrapyramidal symptoms/tardive dyskinesia and agent-specific QT or orthostatic risk.
Active metabolites
Open Milsaperidone in the interactive console ↗
