This page was last updated on June 17, 2022.
Lumateperone (US brand name Caplyta®) is a second-generation (“atypical”) antipsychotic that was approved by the FDA in 2019 and became available in the US in 2020.
On this page, we will provide basic information about this medication. Other articles on this website with more advanced information and tips related to this medication and related medications are linked to under Related Pages below.
1. Schizophrenia (in adults).
2. Bipolar depression (Depressive episodes associated with bipolar I or II disorder. in adults):
- As monotherapy, and
- As adjunctive therapy with lithium or valproate.
What are the receptor effects of lumateperone?
Lumateperone blocks the following two receptors in the brain:
1. Postsynaptic D2 dopamine receptors, for which it has moderate binding affinity
2. 5-HT2A serotonin receptors, for which it has a high binding affinity.
It has low affinities for some receptors that are well-known to be associated with specific side effects that can occur with some antipsychotics. These receptors are alpha-1, muscarinic, and histaminergic.
Everything mentioned so far in this section could apply to several other second-generation antipsychotics. How are lumateperone’s receptor effects different from the others? We’ll discuss this in another article on this website
And, do these differences in pharmacological effects translate into clinically important differences in the incidence of side effects? We’ll discuss this in other articles on this website; please see Related Pages below.
Lumateperone is metabolized by many different enzymes including:
– UGT 1A1, 1A4, and 2B15
– Aldoketoreductase (AKR) 1C1, 1B10, and 1C4
– Cytochrome P450 (CYP) 3A4, 2C8, and 1A2.
Peak plasma concentration (Cmax)
After it is taken orally, the peak plasma concentration of lumateperone is reached approximately 1 to 2 hours later.
Ingestion of a high-fat meal with lumateperone may lower lumateperone peak plasma concentration by about 33%.
About 97% of lumateperone is protein bound.
Half-life and steady-state
The terminal half-life of lumateperone is about 18 hours. This is why:
– It did not need to be manufactured as a sustained-release preparation
– It is given once a day.
– It reaches steady-state concentration after about 5 days. This is to be expected since, in general, drugs reach steady-state concentrations in about 5 times their half-life.
1. Lumateperone should be avoided in patients who are on medication that is a strong CYP3A4 inducer, for example (alphabetically):
carbamazepine, phenytoin, St. John’s Wort.
2. Lumateperone is, obviously, contraindicated in patients who have had an allergic reaction to it.
Lumateperone carries two boxed warnings (often wrongly called “black box warnings”) both of which are generic “class warnings”.
1. In common with other antipsychotics: “Increased Mortality in Elderly Patients with Dementia-Related Psychosis”
2. In common with antidepressants (since it has an FDA indication related to depressive episodes): Suicidal Thoughts and Behaviors
Warnings and Precautions
Every single one of the “Warnings and Precautions” listed in the Prescribing Information for lumateperone is a “class warning” that it has in common with the other second-generation antipsychotics.
Just FYI, these Warnings and Precautions are related to:
– Cerebrovascular Adverse Reactions in Elderly Patients with Dementia-Related Psychosis
– Neuroleptic Malignant Syndrome
– Tardive Dyskinesia
– Metabolic Changes
– Leukopenia, Neutropenia, and Agranulocytosis
– Orthostatic Hypotension and Syncope
– Potential for Cognitive and Motor Impairment
– Body Temperature Dysregulation
Potential side effects
Considering monotherapy clinical trials in either schizophrenia or bipolar depression, the most common side effects of lumateperone are the 4 D”s and nausea:
– Drowsiness (described as “somnolence/ sedation”; drug-placebo difference about 14%)
– Dizziness (drug-placebo difference about 4%)
– Dry mouth (drug-placebo difference about 4%)
– Diarrhea (drug-placebo difference about 2%)
– Nausea (drug-placebo difference:about 5%)
Other potential side effects of lumateperone include:
– Increase in creatine phosphokinase
– Increase in hepatic transaminases
– Decreased appetite.
The Prescribing Information for lumateperone notes that “Based on findings from animal studies, lumateperone may impair male and female fertility“.
There are potential risks of lumateperone during pregnancy that are not discussed here. Prescribing clinicians should consult the most up-to-date information on this topic before prescribing lumateperone to a pregnant woman. For resources related to potential risks of medications during pregnancy, please see the following article on this website:
Note: The Prescribing Information for lumateperone notes that it “May cause extrapyramidal and/or withdrawal symptoms in neonates with third trimester exposure”. But when we read the details, we realize that this is just a generic statement applying to all antipsychotics and not based on specific information about lumateperone.
Please see THIS PAGE for a handout listing both the common and less common side effects of this medication along with the percentages of patients who report them.
How should lumateperone be taken?
– Lumateperone can be taken with or without food
– Though the Prescribing Information does not comment on when in the day lumateperone should be taken, since somnolence/ sedation can occur in some patients, it may be best to ask patients to take it at bedtime (at least when they first start taking it).
– No dose titration is required; lumateperone can directly be started at the target doses given below.
– Usual dose for adults: 42 mg once daily. Note for those reading lumateperone clinical trials—42 mg of lumateperone is equivalent to 60 mg of lumateperone tosylate.
– Moderate/ severe liver impairment: 21 mg once daily
– If the patient is on a moderate CYP3A4 inhibitor: 21 mg once daily
– If the patient is on a strong CYP3A4 inhibitor: 10.5 mg once daily
Dosage forms and strengths
Capsules: 42 mg, 21 mg, 10.5 mg
These 3 tablet strengths cover the majority of adult patients as well as the special situations discussed above under Dosage and Administration.
As of June 2022, 30 capsules (a one-month supply) of lumateperone 42 mg cost about $1500 (source: goodrx.com).
Here is a link to the manufacturer’s cost savings program to reduce copays for the first few months in commercially insured patients: https://www.caplyta.com/schizophrenia/cost-savings
Editor: I strongly believe that prescribing clinicians should keep the cost of medication in mind even if the health insurance is paying. Remember: There are no free lunches. The costs of expensive treatments simply end up being distributed among other persons who have that insurance plan.
So, we have to ask ourselves: How is lumateperone different from second-generation antipsychotics that are available as inexpensive generics?
Important! Please refer to the full Prescribing Information (see link below) before prescribing this medication.
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