Lumateperone (Caplyta): New Antipsychotic Approved for Schizophrenia

FDA has approved this new antipsychotic CAPLYTA (lumateperone) for the treatment of schizophrenia.

This post will summarize the important clinically relevant facts regarding this medication, in following sections:

Indication:

  • Schizophrenia in adults

Mechanism of Action:

  • Serotonin 5-HT2A receptors antagonism: high binding affinity for serotonin 5-HT2A receptors.
  • Postsynaptic Dopamine D2 receptors antagonism: moderate binding affinity for dopamine D2.
  • Serotonin reuptake inhibitor: moderate binding affinity for serotonin transporters.

Dosage and Titration:

  • Available as: 42 mg strength.
  • Recommended Dose: 42 mg administered orally once daily with food.
  • No need for titration.

Dosage Adjustment with Hepatic Impairment:

  • Mild hepatic impairment (Child-Pugh class A): No dosage adjustment.
  • Moderate hepatic impairment (Child-Pugh class B): AVOID 
  • Severe hepatic impairment (Child-Pugh class C): AVOID

When to Discontinue: 

  • Discontinue in patients with absolute neutrophil count < 1000/mm3.

Important Drug-Drug Interactions:

CYP3A4:

(a) AVOID with Moderate or Strong CYP3A4 Inhibitors:

  • increases lumateperone exposure.
  • Moderate 3A4 inhibitors: fluvoxamine, ciprofloxacin, erythromycin, fluconazole.
  • Strong 3A4 inhibitors: nefazodone, Clarithromycin, grapefruit juice, ritonavir, nelfinavir

(b) AVOID with CYP3A4 inducers:

  • decreases lumateperone exposure.
  • 3A4 inducers: Carbamazepine, phenytoin, rifampin, St. John’s wort.

UGT INHIBITORS:

  • increases lumateperone exposure.
  • UGT inhibitors: valproic acid.

Most Common Adverse Reactions:

(defined as incidence of at least 5% of patients exposed to CAPLYTA and greater than twice the rate of placebo)

  • somnolence/sedation 
  • dry mouth

NOTE: no single adverse reaction leading to discontinuation that occurred at a rate of >2% in CAPLYTA-treated patients

Metabolic Adverse Events:

(A) Weight Gain: 

  • (In pooled data from placebo-controlled trials): mean changes in body weight is similar with CAPLYTA and placebo. 
  • (In uncontrolled open-label trial): mean changes in body weight -2 kg (SD 5.6) at Day 175 and approximately – 3.2 kg (SD 7.4) at Day 350

(B) Hyperglycemia:

  • (In pooled data from placebo-controlled trials): mean changes in fasting glucose is similar with CAPLYTA and placebo. 
  • (In uncontrolled open-label trial): 4.7% of patients with normal hemoglobin A1c (<6.5%) at baseline developed elevated levels (≥6.5%) post-baseline.

References:

  1. CAPLYTA (lumateperone) package insert (PDF)
  2. Lieberman JA, Davis RE, Correll CU, Goff DC, Kane JM, Tamminga CA, Mates S, Vanover KE. ITI-007 for the Treatment of Schizophrenia: A 4-Week Randomized, Double-Blind, Controlled Trial. Biol Psychiatry. 2016 Jun 15;79(12):952-61. (pubmed)
  3. NCT02282761 (clinical trial)

Dr. Harvinder Singh

Admin, Psychiatry Education Forum

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