lumateperone

Absorption: Poorly absorbed (4%) following oral administration.

Distribution: Widely distributed to extravascular tissues.

Protein Binding: 97%.

Metabolism/Excretion: Extensively metabolized in the liver via various enzymes, including UDP-glucuronosyltransferase (UGT), aldoketoreductases, as well as CYP1A2, CYP2C8, and CYP3A4. Excreted in urine (58%) and feces (29%), primarily as metabolites.

Half-Life: 18 hr.

Time/Action Profile ⬆ ⬇

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
PO	unknown	1–2 hr	24 hr

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity.

Use Cautiously in:

Dehydration, use of antihypertensives, cardiovascular disease, or cerebrovascular disease (↑ risk of orthostatic hypotension and/or syncope);
Low white blood cell count or absolute neutrophil count or history of drug-induced leukopenia or neutropenia (↑ risk of leukopenia and/or neutropenia);
Patients at risk for aspiration or falls;
Seizure disorders;
Moderate or severe hepatic impairment (↓ dose);
OB: Neonates at risk for extrapyramidal symptoms and withdrawal after delivery when exposed during the 3rd trimester; use during pregnancy only if potential maternal benefit outweighs potential fetal risk;
Lactation: Use while breastfeeding only if potential maternal benefit outweighs potential risk to infant;
Pedi: May risk of suicide attempt/ideation, especially during early treatment or dose adjustment; risk may be greater in children, adolescents, and young adults taking antidepressants (safety in children/adolescents not established);
Geri: Appears on Beers list. risk of stroke, cognitive decline, and mortality in older adults with dementia. Avoid use in older adults, except for schizophrenia or bipolar disorder.

Adv. Reactions/Side Effects ⬆ ⬇

CV: orthostatic hypotension, syncope, tardive dyskinesia

Endo: hyperglycemia

GI: dry mouth, dysphagia, ↑liver enzymes, nausea, vomiting

GU: ↓fertility

Hemat: leukopenia, neutropenia

Metab: ↓appetite, dyslipidemia, ↑weight

MS: dystonic reactions, ↑creatine kinase

Neuro: drowsiness, dizziness, extrapyramidal reactions, hyperthermia, NEUROLEPTIC MALIGNANT SYNDROME, SEIZURES, SUICIDAL THOUGHTS/BEHAVIORS

Misc: falls, fatigue, hypersensitivity reactions

Interactions ⬆ ⬇

Drug-drug:

Strong CYP3A4 inhibitors, including clarithromycin, itraconazole, nefazodone, nelfinavir, ritonavir, voriconazole, or moderate CYP3A4 inhibitors, including ciprofloxacin, cyclosporine, diltiazem, erythromycin, fluconazole, fluvoxamine, or verapamil, may ↑ levels and risk of toxicity; ↓ lumateperone dose.
CYP3A4 inducers, including aprepitant, armodafinil, bosentan, carbamazepine, efavirenz, etravirine, modafinil, nafcillin, phenytoin, pioglitazone, prednisone, and rifampin, may ↓ levels and effectiveness; avoid concurrent use.

Drug-Natural Products:

St. John's wort may ↓ levels and effectiveness; avoid concurrent use.

Grapefruit juice may ↑ levels and risk of toxicity; avoid concurrent use.

Route/Dosage ⬆ ⬇

PO (Adults ): 42 mg once daily. Concurrent use of strong CYP3A4 inhibitors: 10.5 mg once daily. Concurrent use of moderate CYP3A4 inhibitors: 21 mg once daily.

Hepatic Impairment

PO (Adults ): Moderate or severe hepatic impairment: 21 mg once daily.

Availability ⬆ ⬇

Capsules: 10.5 mg; 21 mg; 42 mg

Assessment ⬆ ⬇

Assess mental status (orientation, mood, behavior) before and periodically during therapy. Assess for suicidal tendencies, especially during early therapy for depression. Risk may be increased in younger adults.
Monitor patient’s mental status (orientation, mood, behavior) before and periodically during therapy.
Assess weight and BMI initially and periodically during therapy. Refer as appropriate for nutritional/weight management and medical management.
Observe patient carefully when administering medication to ensure that medication is actually taken and not hoarded or cheeked.
Lumateperone lowers the seizure threshold. Institute seizure precautions for patients with history of seizure disorder.
Monitor patient for onset of extrapyramidal side effects (akathisia: restlessness; dystonia: muscle spasms and twisting motions; or pseudoparkinsonism: mask-like face, rigidity, tremors, drooling, shuffling gait, dysphagia). Report these symptoms; reduction of dose or discontinuation of medication may be necessary.
Monitor for possible tardive dyskinesia (uncontrolled rhythmic movement of mouth, face, and extremities; lip smacking or puckering; puffing of cheeks; uncontrolled chewing; rapid or worm-like movements of tongue). Report these symptoms immediately; may be irreversible.
Monitor for development of neuroleptic malignant syndrome (fever, muscle rigidity, altered mental status, respiratory distress, tachycardia, seizures, diaphoresis, hypertension or hypotension, pallor, tiredness, loss of bladder control). Notify health care professional immediately if these symptoms occur.
Assess for falls risk. Drowsiness, orthostatic hypotension, and motor and sensory instability increase risk. Institute prevention if indicated.

Lab Test Considerations:

Monitor patients with clinically significant neutropenia for fever or other symptoms or signs of infection and treat promptly if such symptoms or signs occur. Discontinue lumateperone in patients with absolute neutrophil count <1000/mm³ and follow WBC until recovery.
- Assess fasting blood glucose and cholesterol levels before starting and periodically during therapy.
- Monitor liver function tests periodically during therapy or if clinical signs of hepatotoxicity occur.

Implementation ⬆ ⬇

PO: Administer once daily with or without food.

Patient/Family Teaching ⬆ ⬇

Instruct patient to take medication as directed.
Inform patient of possibility of extrapyramidal symptoms and tardive dyskinesia. Instruct patient to report these symptoms immediately.
Instruct patient to avoid grapefruit juice during therapy.
Advise patient to change positions slowly to minimize orthostatic hypotension. Protect from falls.
Inform patient that lumateperone may cause weight gain. Advise patient to monitor weight periodically. Notify health care professional of significant weight gain.
May cause seizures and drowsiness. Caution patient to avoid driving or other activities requiring alertness until response to drug is known.
Advise patient to avoid extremes in temperature and dehydration; this drug impairs body temperature regulation.
Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care professional before taking any other medications, especially St. John's wort. Caution patient to avoid concurrent use of alcohol and other CNS depressants.
Instruct patient to use frequent mouth rinses, good oral hygiene, and sugarless gum or candy to minimize dry mouth.
Advise patient to notify health care professional of medication regimen before treatment or surgery.
Advise patient and family to notify health care professional if thoughts about suicide or dying or attempts to commit suicide occur.
Instruct patient to notify health care professional immediately if signs and symptoms of neuroleptic malignant syndrome occur unexplained fatigue, dyspnea, tachypnea, chest pain, palpitations, sore throat, fever, lethargy, weakness, malaise, or flu-like symptoms occur.
Rep: Advise female patients to notify health care professional if pregnancy is planned or suspected and to avoid breastfeeding. Encourage women who become pregnant while taking lumateperone to enroll in the National Pregnancy Registry for Atypical Antipsychotics at 1-866-961-2388 or visit http://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/. Monitor neonates for extrapyramidal and/or withdrawal symptoms and manage symptoms appropriately. May temporarily cause male and female infertility.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇