Milsaperidone
Looking up MedlinePlus…
From MedlinePlus, U.S. National Library of Medicine
Boxed warning
WARNING: INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. BYSANTI is not approved for the treatment of patients with dementia-related psychosis [see Warnings and Precautions (5.1) ] . WARNING: INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS See full prescribing information for complete boxed warning. Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. BYSANTI is not approved for use in patients with dementia-related psychosis. ( 5.1 )
Dosing in kidney impairment
Clinical manifestations of NMS include hyperpyrexia, muscle rigidity, altered mental status (including catatonic signs), and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis, and cardiac dysrhythmia). Additional signs may include elevated creatine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure.
Dosing in liver impairment
Dosage Recommendations in Patients with Hepatic Impairment The recommended BYSANTI dosage in patients with mild hepatic impairment (HI) is the same as those with normal hepatic function. Consider a lower maintenance dosage in patients with moderate HI. BYSANTI is not recommended in patients with severe HI [see Use in Specific Populations , Clinical Pharmacology ] .
Preparation and administration
Dosage Modifications for Drug Interactions Concomitant Administration with a Strong CYP2D6 Inhibitor In patients receiving a: Stable dosage of a strong CYP2D6 inhibitor, when initiating BYSANTI, the recommended BYSANTI titration schedule is the same as that in Table 2 . Maintenance BYSANTI dosage, when initiating a strong CYP2D6 inhibitor, reduce the BYSANTI dosage by one-half.
When the strong CYP2D6 inhibitor is stopped in BYSANTI-treated patients, titrate to the recommended dosage as described in Table 1 [see Drug Interactions ] . Concomitant Administration with a Strong CYP3A4 Inhibitor In patients receiving a: Stable dosage of a strong CYP3A4 inhibitor, when initiating BYSANTI, the recommended BYSANTI titration schedule is the same as that in Table 2 .
Maintenance BYSANTI dosage, when initiating a strong CYP3A4 inhibitor, reduce the BYSANTI dosage by one-half. When the CYP3A4 inhibitor is stopped in BYSANTI-treated patients, titrate to the recommended dosage as described in Table 1 [see Drug Interactions ] . Concomitant Administration with a Strong CYP2D6 Inhibitor and a Strong CYP3A4 Inhibitor In patients receiving a: Stable dosage of a strong CYP2D6 inhibitor and a strong CYP3A4 inhibitor, when initiating BYSANTI, the recommended BYSANTI titration schedule is the same as that in Table 2 .
Maintenance BYSANTI dosage, when initiating a strong CYP2D6 inhibitor and a strong CYP3A4 inhibitor, reduce the BYSANTI dosage by one-half. When the strong CYP2D6 inhibitor and CYP3A4 inhibitor are both stopped in BYSANTI-treated patients, titrate to the recommended dosage as described in Table 1 . [see Drug Interactions ] .
Drug interactions
Check milsaperidone against a medication listLabel text (7 paragraphs)
Strong CYP2D6 Inhibitors: Reduce the dosage of BYSANTI when administered with a strong CYP2D6 inhibitor ( 7.1 ) Strong CYP3A4 Inhibitors: Reduce the dosage of BYSANTI when administered with a strong CYP3A4 inhibitor ( 7.1 ) Strong CYP2D6 and Strong CYP3A4 Inhibitors: Reduce the dosage of BYSANTI if administered concomitantly with both a CYP2D6 and a CYP3A4 inhibitor ( 7.1 ). Drugs that Lower Blood Pressure: Avoid concomitant administration of BYSANTI with alpha-adrenergic blocking agents and consider lowering the dosage of other drugs that lower blood pressure ( 7.3 )
7.1 Effects of Other Drugs on BYSANTI Table 7 presents clinically significant drug interactions where concomitant use of another drug affects BYSANTI. Table 7: Clinically Significant Drug Interactions: Concomitant Use of Other Drugs Affect the Use of BYSANTI Strong CYP2D6 Inhibitors Prevention or Management Reduce the dosage of BYSANTI when administered with a strong CYP2D6 inhibitor [see Dosage and Administration (2.4) ] . When the strong CYP2D6 inhibitor is stopped in BYSANTI-treated patients, gradually increase the BYSANTI dosage to the pre-inhibitor dosage.
Mechanism and Clinical Effect(s) Milsaperidone and iloperidone are CYP2D6 substrates (iloperidone and milsaperidone rapidly interconvert in vivo). Strong CYP2D6 inhibitors increased exposure of milsaperidone and iloperidone [see Clinical Pharmacology (12.3, 12.5) ] , which may increase the risk of BYSANTI-associated adverse reactions. Strong CYP3A4 Inhibitors Prevention or Management Reduce the dosage of BYSANTI when administered with a strong CYP3A4 inhibitor [see Dosage and Administration (2.4) ] . When the strong CYP3A4 inhibitor is stopped in BYSANTI-treated patients, gradually increase the BYSANTI dosage to the pre-inhibitor dosage.
Mechanism and Clinical Effect(s) Milsaperidone and iloperidone are CYP3A4 substrates. Strong CYP3A4 inhibitors increased the exposure of milsaperidone, iloperidone and P95 [see Clinical Pharmacology (12.3) ] , which may increase the risk of BYSANTI-associated adverse reactions. Strong CYP2D6 and Strong CYP3A4 Inhibitors Prevention or Management Reduce the dosage of BYSANTI if administered concomitantly with both a strong CYP2D6 inhibitor and a strong CYP3A4 inhibitor.
Mechanism and Clinical Effect(s) Concomitant administration with a strong CYP2D6 inhibitor and a strong CYP3A4 inhibitor resulted in an increase in steady-state exposure of milsaperidone and iloperidone [see Clinical Pharmacology (12.3) ] , which may increase the risk of BYSANTI-associated adverse reactions.
7.2 Drugs that Prolong the QTc Interval Avoid concomitant use of BYSANTI with other drugs that prolong the QTc interval [see Warnings and Precautions (5.3) ] . Iloperidone causes QTc interval prolongation [see Clinical Pharmacology (12.2) ] . Concomitant use of BYSANTI with other drugs that prolong the QTc interval may result in a greater increase in the QTc interval and adverse reactions associated with QTc interval prolongation, including arrhythmias.
7.3 Drugs that Lower Blood Pressure Concomitant use of BYSANTI with drugs that lower blood pressure could potentially cause symptomatic hypotension. Avoid concomitant administration of BYSANTI with alpha-adrenergic blocking agents and consider lowering the dosage of other drugs that lower blood pressure [see Warnings and Precautions (5.7) ] .
Contraindications
4 CONTRAINDICATIONS BYSANTI is contraindicated in individuals with a known hypersensitivity reaction to milsaperidone or the inactive ingredients in BYSANTI. Anaphylaxis, angioedema, and other hypersensitivity reactions have been reported [see Adverse Reactions (6.2) ] . Known hypersensitivity to milsaperidone or the inactive ingredients in BYSANTI. ( 4 , 6.2 )
Pregnancy and lactation
Pregnancy
8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to BYSANTI during pregnancy. For more information contact the National Pregnancy Registry for Atypical Antipsychotics at 1-866-961-2388 or visit http://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/ . Risk Summary Neonates exposed to antipsychotic drugs, including BYSANTI, during the third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms following delivery (see Clinical Considerations ) .
There are no available data with BYSANTI use during pregnancy and available data from pharmacovigilance reports with iloperidone (iloperidone and milsaperidone rapidly interconvert in vivo) use during pregnancy are insufficient to inform a drug-associated risk for major birth defects and miscarriage. There are risks to the mother associated with untreated schizophrenia or bipolar I disorder (see Clinical Considerations ).
When iloperidone) was administered orally to pregnant rats during organogenesis at doses up to 26 times the maximum recommended human dose (MRHD) of 24 mg/day on mg/m 2 basis it prolonged the duration of pregnancy and parturition, increased still births, early intrauterine deaths, increased incidence of developmental delays, and decreased post-partum pup survival. When iloperidone was administered orally to pregnant rabbits during organogenesis at doses up to 20-times the MRHD on mg/m 2 basis it increased early intrauterine deaths and decreased fetal viability at term at the highest dose which was also a maternally toxic dose (see Data ) .
The safety margins for milsaperidone are expected to be the same as those seen with iloperidone because exposures to iloperidone, milsaperidone, and their major metabolites are similar when either iloperidone tablets or BYSANTI (milsaperidone) tablets are administered in humans. The background risk of major birth defects and miscarriage in patients with schizophrenia or bipolar disorder is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.
Clinical Considerations Disease-Associated Maternal and/or Embryo/Fetal Risk: There is a risk to the mother from untreated schizophrenia or bipolar I disorder, including increased risk of relapse, hospitalization, and suicide. Schizophrenia and bipolar I disorder are associated with increased adverse perinatal outcomes, including preterm birth. It is not known…
For breastfeeding, also see LactMed (National Library of Medicine), which summarizes milk levels and infant effects.
Supply and cost
Drug shortage status
Recalls (last 24 months)
Therapeutic equivalence (Orange Book)
Price ladder
Not the price at the counterThese are not what a patient pays at the pharmacy counter. They are what pharmacies, health plans, and government buyers pay, before manufacturer rebates. A patient's cost depends on their insurance (copay, coinsurance, or deductible) or the pharmacy's cash price.