lurasidone

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

Contraind./Precautions ⬆ ⬇

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);
History of suicide attempt;
Diabetes mellitus;
Overheating/dehydration (may ↑ risk of serious adverse reactions);
Patients at risk for falls;
History of leukopenia or previous drug-induced leukopenia/neutropenia;
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: May risk of suicide attempt/ideation especially during dose early treatment or dose adjustment; risk may be greater in children, adolescents, and young adults taking antidepressants; safety and effectiveness not established in children 10 yr;
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, SEIZURES, SUICIDAL THOUGHTS, tardive dyskinesia

Interactions ⬆ ⬇

Drug-drug:

Strong CYP3A4 inhibitors, including ketoconazole, clarithromycin, ritonavir, and voriconazole↑ levels and risk of toxicity; concurrent use contraindicated.
Strong CYP3A4 inducers, including rifampin, phenytoin, and carbamazepine↓ 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, some antidepressants and antihistamines.

Drug-Natural Products:

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

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

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).

Availability ⬆ ⬇

(Generic available)

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

Assessment ⬆ ⬇

Monitor patient’s mental status (orientation, mood, behavior) before and periodically during therapy.
Assess weight and BMI initially and during therapy. Refer as appropriate for nutritional/weight and medical management.
Monitor mood changes. Assess for suicidal tendencies, especially during early therapy. Restrict amount of drug available to patient.
Monitor BP (sitting, standing, lying down) and pulse before and frequently during initial dose titration. May cause tachycardia and orthostatic hypotension. If hypotension occurs, dose may need to be ↓.
Observe patient when administering medication to ensure medication is swallowed and not hoarded or cheeked.
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 may be necessary. Trihexyphenidyl or benztropine may be used to control symptoms.
Monitor for tardive dyskinesia (involuntary rhythmic movement of mouth, face, and extremities). Report immediately; may be irreversible.
Monitor for symptoms related to hyperprolactinemia (menstrual abnormalities, galactorrhea, sexual dysfunction).
Monitor for development of neuroleptic malignant syndrome (fever, respiratory distress, tachycardia, seizures, diaphoresis, hypertension or hypotension, pallor, tiredness). Notify health care professional immediately if these symptoms occur.
Monitor for symptoms of hyperglycemia (polydipsia, polyuria, polyphagia, weakness) periodically during therapy.
Assess for falls risk. Drowsiness, orthostatic hypotension, and motor and sensory instability increase risk. Institute prevention if indicated.

Lab Test Considerations:

May cause ↑ serum prolactin levels.
- May cause ↑ CK.
- Obtain fasting blood glucose and cholesterol levels initially and periodically during therapy.
- Monitor CBC frequently during initial mo of therapy in patients with pre-existing or history of low WBC. May cause leukopenia, neutropenia, or agranulocytosis. Discontinue therapy if this occurs.

Implementation ⬆ ⬇

Do not confuse Latuda with Lantus.
PO: Administer once daily with food of at least 350 calories. Use beyond 6 wk has not been studied.

Patient/Family Teaching ⬆ ⬇

Instruct patient to take medication as directed. Emphasize the caloric food needs for taking medication.
Inform patient of the possibility of extrapyramidal symptoms. Instruct patient to report these symptoms immediately to health care professional.
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 and family to notify health care professional if thoughts about suicide or dying, attempts to commit suicide; 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, 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 professional what medications they are taking and to avoid taking new Rx, OTC, vitamins, or herbal products without consulting health care professional, especially alcohol and other CNS depressants.
Advise patient to notify health care professional of medication regimen before treatment or surgery.
Instruct patient to notify health care professional promptly if sore throat, fever, unusual bleeding or bruising, rash, or tremors occur.
Rep: Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected, and to avoid breastfeeding during therapy. Monitor neonates exposed to lurasidone during the third 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/. Monitor neonates for extrapyramidal and/or withdrawal symptoms and manage symptoms appropriately.
Emphasize the importance of routine follow up exams to monitor side effects.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇