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Lumateperone (CAPLYTA)

Updated: Nov 20, 2021

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“’Luminated Cap lighter”


luma TEP er ohn / cap LIE ta 

Year of US release: 2020 ❖ Antipsychotic (SGA)

❖ D2 antagonist - ⇩DA

❖ 5-HT2A antagonist - ⇧DA

❖ Glutamate modulator

FDA-approved for:

 ❖ Schizophrenia

Antipsychotics are represented with spooky mascots.

Lumateperone is a new antipsychotic that purportedly modulates glutamate in addition to the usual SGA mechanism of blocking D2 and 5-HT2A receptors. However, the official prescribing information does not mention glutamate, suggesting the FDA saw insufficient evidence for lumateperone being a first-in-class novel antipsychotic. It appears to be equally effective as risperidone (Risperdal) with fewer side effects other than sedation (Citrome, 2016).

Lumateperone’s D2 receptor occupancy is lower than most other antipsychotics. This means extrapyramidal side effects are unlikely. The other antipsychotics with low D2 occupancy are quetiapine (Seroquel) and clozapine (Clozaril). 

Lumateperone is also a weak D2 receptor partial agonist. The stronger D2 partial agonists are aripiprazole (Abilify), brexpiprazole (Rexulti), and cariprazine (Vraylar). 

Lumateperone has a favorable side effect profile. In clinical trials no single adverse effect led to discontinuation. The main side effects are somnolence/sedation (24% vs 10% placebo) and dry mouth (6% vs 2% placebo). At one year, lumateperone caused a modest weight loss of 3.2 kg (7 pounds) but a modest elevation in A1c and lipids. It does not appear to cause hypotension, prolactin elevation, or QT prolongation.

Lumateperone is associated with a loss of 3.2 kg (7 pounds) at one year.

Lumateperone is extensively metabolized, resulting in more than twenty metabolites. It is a highly susceptible 3A4 substrate, making it contraindicated concomitantly with the medications listed below.

Because lumateperone can be highly sedating, it is typically administered at night. Taking lumateperone with food improves tolerability by delaying peak blood levels. This is more relevant if dosed during the day. Unlike ziprasidone (Geodon) and lurasidone (Latuda), taking lumateperone with food is not required for GI absorption. 

Dosing: 42 mg is the only recommended dose, typically given at bedtime; Titration is not necessary (nor possible); No dose adjustment is required for renal impairment; Avoid with moderate/severe hepatic insufficiency.

On Jackie Robinson Day (April 15), all players in Major League Baseball wear Robinson's uniform number, 42. For lumateperone, 42 mg is the only recommended dose.

Dynamic interactions:

 ❖ Antidopaminergic

 ❖ EPS (high for an SGA)

 ❖ Sedation (moderate)

 ❖ Hypotensive effects 

 ❖ Prolactin elevation (mild)

Kinetic interactions:

 ❖ 3A4 substrate

 ❖ UGT substrate

The fish (our symbol for a 3A4 substrate) is big because with lumateperone 3A4 interactions are a very big deal. 

Lumateperone is contraindicated with 3A4 inDucers due to rapid clearance. Levels will be decreased up to 20-fold, rendering lumateperone useless when given concomitantly with:

  • Carbamazepine (Tegretol)

  • Modafinil (Provigil)

  • Phenytoin (Dilantin)

  • Phenobarbital (Luminal)

  • Oxcarbazepine (Trileptal)

  • St. John’s wort

  • Rifampin (20-fold decrease)

Lumateperone should also be avoided with moderate-to-strong 3A4 inHibitors due to increased exposure to lurasidone. Strong 3A4 inhibitors include:

  • Fluconazole (antifungal) and other -azole antifungals

  • Clarithromycin (antibacterial)

  • Ritonavir (antiretroviral, HIV)

Lumateperone is a UGT substrate, which should not be combined with valproic acid (Depakote, Depakene)—a UGT inHibitor that increases exposure to lumateperone.

Download 5-page PDF with lumateperone monograph, 2nd Gen Antipsychotic comparison chart, and visual mnemonics relevant to lumateperone:

Download PDF • 2.47MB

Copyright 2020, CaferMed LLC

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