lurasidone

Contraindicated in:

Hypersensitivity;
Concurrent use of strong CYP3A4 inhibitors or inducers.

Use Cautiously in:

Moderate or severe renal impairment (dose adjustment recommended);
Moderate or severe hepatic impairment (dose adjustment recommended);
May ↑ risk of suicide attempt/ideation especially during early treatment or dose adjustment; this risk appears to be greater in adolescents or children
;
Diabetes mellitus;
Overheating/dehydration (may ↑ risk of serious adverse reactions);
Patients at risk for falls;
History of leukopenia or previous drug-induced leukopenia/neutropenia;
History of breast cancer;
OB: Use in pregnancy only if potential maternal benefit justifies potential fetal risk;
Lactation: Use while breastfeeding only if potential maternal benefit justifies potential risk to infant;
Pedi: Children <10 yr (safety and effectiveness 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: bradycardia, orthostatic hypotension, syncope, tachycardia

Derm: pruritus, rash

EENT: blurred vision

Endo: hyperglycemia, hyperprolactinemia

GI: nausea, esophageal dysmotility

Hemat: AGRANULOCYTOSIS, anemia, leukopenia

Metab: dyslipidemia, weight gain

Neuro: akathisia, drowsiness, parkinsonism, agitation, anxiety, cognitive/motor impairment, dizziness, dystonia, NEUROLEPTIC MALIGNANT SYNDROME (NMS), SEIZURES, SUICIDAL THOUGHTS/BEHAVIORS, tardive dyskinesia

Interactions ⬆ ⬇

Drug-drug:

Strong CYP3A4 inhibitors, including ketoconazole, clarithromycin, ritonavir, and voriconazole, significantly ↑ levels and risk of toxicity; concurrent use contraindicated.
Strong CYP3A4 inducers, including rifampin, phenytoin, and carbamazepine, significantly ↓ levels and effectiveness; concurrent use contraindicated.
Moderate CYP3A4 inhibitors, including diltiazem, atazanavir, erythromycin, fluconazole, and verapamil, ↑ levels and risk of toxicity; if used concurrently, lurasidone dose should not exceed 40 mg/day.
↑sedation may occur with other CNS depressants, including alcohol, sedative/hypnotics, opioids, and some antidepressants and antihistamines.

Drug-Natural Products:

St. John's wort significantly ↓ levels and effectiveness; concurrent use contraindicated.

Drug-Food:

Grapefruit juice significantly ↑ levels and risk of toxicity; concurrent use contraindicated.

Availability ⬆ ⬇

(Generic available)

Tablets: 20 mg; 40 mg; 60 mg; 80 mg; 120 mg

Route/Dosage ⬆ ⬇

Schizophrenia

PO (Adults ): 40 mg once daily (not to exceed 160 mg once daily); Addition of moderate CYP3A4 inhibitor to existing lurasidone therapy:↓ lurasidone dose by 50%; Addition of lurasidone to existing moderate CYP3A4 inhibitor therapy: 20 mg once daily (not to exceed 80 mg once daily).
PO (Children 13–17 yr): 40 mg once daily (not to exceed 80 mg once daily); Addition of moderate CYP3A4 inhibitor to existing lurasidone therapy:↓ lurasidone dose by 50%; Addition of lurasidone to existing moderate CYP3A4 inhibitor therapy: 20 mg once daily (not to exceed 80 mg once daily).

Renal Impairment

PO (Adults and Children 13–17 yr): CCr <50 mL/min: 20 mg once daily (not to exceed 80 mg once daily).

Hepatic Impairment

(Adults and Children 13–17 yr): Moderate hepatic impairment: 20 mg once daily (not to exceed 80 mg once daily); Severe hepatic impairment: 20 mg once daily (not to exceed 40 mg once daily).

Depressive Episodes Associated With Bipolar I Disorder

PO (Adults ): 20 mg once daily (not to exceed 120 mg once daily); Addition of moderate CYP3A4 inhibitor to existing lurasidone therapy:↓ lurasidone dose by 50%; Addition of lurasidone to existing moderate CYP3A4 inhibitor therapy: 20 mg once daily (not to exceed 80 mg once daily).
PO (Children 10–17 yr): 20 mg once daily (not to exceed 80 mg once daily); Addition of moderate CYP3A4 inhibitor to existing lurasidone therapy:↓ lurasidone dose by 50%; Addition of lurasidone to existing moderate CYP3A4 inhibitor therapy: 20 mg once daily (not to exceed 80 mg once daily).

Renal Impairment

PO (Adults and Children 10–17 yr): CCr <50 mL/min: 20 mg once daily (not to exceed 80 mg once daily).

Hepatic Impairment

PO (Adults and Children 10–17 yr): Moderate hepatic impairment: 20 mg once daily (not to exceed 80 mg once daily); Severe hepatic impairment: 20 mg once daily (not to exceed 40 mg once daily).

US Brand Names ⬆ ⬇

Action ⬆ ⬇

Effect may be mediated via effects on central dopamine type 2 (D₂) and serotonin Type 2 (5HT_2A) receptor antagonism.

Therapeutic effects:

Reduction in schizophrenic behavior.
Reduction in depressive episodes in bipolar I disorder.

Classifications ⬆ ⬇

Therapeutic Classification: antipsychotics

Pharmacologic Classification: benzoisothiazole

Pharmacokinetics ⬆ ⬇

Absorption: 9–19% absorbed following oral administration.

Distribution: Unknown.

Protein Binding: >99%.

Metabolism/Excretion: Primarily metabolized by the liver via the CYP3A4 isoenzyme. Two metabolites are pharmacologically active; 80% eliminated in feces, 8% in urine primarily as metabolites.

Half-Life: 18 hr.

Time/Action Profile ⬆ ⬇

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
PO	unknown	1–3 hr	24 hr

Patient/Family Teaching ⬆ ⬇

Explain the purpose and side effects of lurasidone. Instruct patient to take as directed. Emphasize the caloric food needs for taking medication. Caution patient to consult health care provider before discontinuing. Advise patient to read Medication Guide before starting and with each Rx refill in case of changes.
Emphasize the importance of follow-up exams to monitor progress. Laboratory tests may be needed to detect side effects.
Inform patient of the possibility of extrapyramidal symptoms. Instruct patient to report these symptoms immediately to health care provider.
Advise patient to change positions slowly to minimize orthostatic hypotension. Protect from falls.
May cause drowsiness and cognitive and motor impairment. Caution patient to avoid driving or other activities requiring alertness until response to medication is known.
Advise patient, family, and caregivers to watch for suicidality, especially during early therapy or dose changes. Notify health care provider immediately if thoughts about suicide or dying, attempts to commit suicide, new or worse depression or anxiety, agitation or restlessness, panic attacks, insomnia, new or worse irritability, aggressiveness, acting on dangerous impulses, mania, or other changes in mood or behavior occur.
Advise patient and family to notify health care provider if new or worse depression, new or worse anxiety, feeling very agitated or restless, panic attacks, trouble sleeping, new or worse irritability, acting aggressive, being angry or violent, acting on dangerous impulses, an extreme ↑ in activity and talking, or other unusual changes in behavior or mood occur.
Advise patient to avoid extremes in temperature; this drug impairs body temperature regulation.
Advise patient to tell health care provider what medications they are taking and to avoid taking new Rx, OTC, vitamins, or herbal products without consulting health care provider, especially alcohol and other CNS depressants. Instruct patient to avoid grapefruit and grapefruit juice.
Advise patient to notify health care provider of medication regimen before treatment or surgery.
Instruct patient to notify health care provider promptly if sore throat, fever, unusual bleeding or bruising, rash, or tremors occur.
Rep: Advise women of reproductive potential to notify health care provider if pregnancy is planned or suspected or if breastfeeding. Monitor neonates exposed to lurasidone during the 3rd trimester of pregnancy for extrapyramidal and/or withdrawal symptoms following delivery. There have been reports of agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, and feeding disorder in these neonates. Monitor breastfed infants for excessive drowsiness, lethargy, and developmental delays. Encourage women who become pregnant while taking lurasidone 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/.

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Indications ⬇

Contraind./Precautions ⬆ ⬇