Lumateperone (Caplyta) is a second-generation antipsychotic. It is used in the treatment of patients with schizophrenia. Compared to other antipsychotic medications, it has a very low incidence of extrapyramidal symptoms and greater efficacy in treating the negative symptoms of schizophrenia.
Lumateperone (Caplyta) Uses:
-
Schizophrenia:
- It is suggested for the treatment of adult schizophrenia.
Lumateperone (Caplyta) Dose in Adults:
Schizophrenia:
- Oral: Usual dose: 42 mg once a day.
Switching antipsychotics:
- There is no one best method for changing antipsychotic medications.
- Cross-titration is a technique that progressively reduces the first antipsychotic while gradually raising the new antipsychotic. Another is sudden transition (abruptly discontinuing the first antipsychotic and either increasing the new antipsychotic gradually or starting it at a treatment dose).
- Cross-titration therapy should be used in patients with schizophrenia who are at high risk of relapsing; after the new medication is at the therapeutic level, the first medication is gradually reduced and withdrawn over the course of one to two weeks.
- Clinical experience has led some specialists to believe that cross-titration and overlap strategies are preferable than sudden change.
Dosage adjustment for concomitant therapy:
- There are significant medication interactions that call for dose/frequency modification or avoidance.
Discontinuation of therapy:
-
- A cautious tapering of antipsychotics is advised by the American Psychiatric Association, Canadian Psychiatric Association, and World Federation of Societies of Biological Psychiatry guidelines to prevent physical withdrawal symptoms, such as
- anorexia
- Anxiety
- diaphoresis
- diarrhea
- dizziness
- dyskinesia
- headache
- myalgia
- nausea
- paresthesia
- restlessness
- tremulousness
- vomiting.
- Sudden discontinuation of anticholinergic or dopaminergic antipsychotics is at higher risk of withdrawal symptoms.
- Other risk factors include medication half-life, duration, and indication for use.
- There is no surefire sign of relapse in schizophrenia.
- However, studies suggest that 75% of patients who were well-stabilized on medication after withdrawal return within 6–24 months.
- Antipsychotics on indefinite maintenance are typically advised, especially for patients with a history of several prior episodes or two episodes during the previous five years.
- A cautious tapering of antipsychotics is advised by the American Psychiatric Association, Canadian Psychiatric Association, and World Federation of Societies of Biological Psychiatry guidelines to prevent physical withdrawal symptoms, such as
Use in Children:
Not indicated.
Lumateperone Pregnancy Category: N
- Extrapyramidal signals, or aberrant muscle movements in neonates, are more likely to occur after delivery, as are withdrawal symptoms.
- The newborn can experience agitation, feeding disorders, hypotonia and hypertonia as well as tremor, respiratory distress, and somnolence.
- These symptoms could subside on their own or they might necessitate hospitalisation.
- There are no safety data on atypical antipsychotics during pregnancy, and routine use is not advised.
- Continued therapy may be more advantageous than switching to a new medication if the mother was exposed to antipsychotics in an unusual way while she was pregnant.
- Avoid lumateperone if antipsychotics are to be used during pregnancy. Other agents should be preferred.
Use during breastfeeding
- Lumateperone may or may not be found in breast milk.
- Breast milk can be used to give infants anti-psychotic exposure. This can lead to failure to thrive, jitteriness and extrapyramidal symptoms as well as sedation.
- Due to the possibility of major adverse reactions in breastfed infants, the manufacturer does not advise breastfeeding.
- If indicated for breastfeeding women, agents other than lumateperone should not be used.
Dose in Kidney disease:
No dose adjustments.
Lumateperone (Caplyta) Dose in Liver Disease:
- Mild impairment (Child-Pugh class A):
- No dose adjustment necessary.
- Moderate to severe impairment (Child-Pugh class B and C):
- Avoid use.
Common Side Effects of Lumateperone (Caplyta):
-
Central nervous system:
- Sedated state
- Drowsiness
Less Common Side Effects of Lumateperone (Caplyta):
-
Central nervous system:
- Dizziness
- Fatigue
- Extrapyramidal reaction
-
Gastrointestinal:
- Vomiting
- Decreased appetite
- Nausea Xerostomia
-
Hepatic:
- Increased serum transaminases
-
Neuromuscular & skeletal:
- Increased creatine phosphokinase in blood specimen
Frequency of Side effects not defined:
-
Central nervous system:
- Dystonia
-
Endocrine & metabolic:
- Increased serum cholesterol
- Increased serum triglyceride
- Increased LDL cholesterol
-
Hematologic & oncologic:
- Elevated glycosylated hemoglobin
Contraindications to Lumateperone (Caplyta):
- Hypersensitivity.
ALERT: US Boxed Warning
- Patients with dementia-related psychosis are at greater risk of dying:
- For dementia-related psychosis, lumateperone should not be used
Warnings and precautions
-
Anticholinergic effects
- It is possible to experience confusion, agitation and constipation.
- In cases of decreased GI motility or urinary retention, BPH and xerostomia, caution is advised.
-
Blood dyscrasias:
- Clinical trials and post-marketing reports have shown Leukopenia and Neutropenia in combination with antipsychotics.
- Pre-existing low WBC/ANC or history of drug-induced neutropenia/neutropenia.
- If you have signs of blood disorder or an acute neutrophil count below 1,000/mm 3, discontinue use.
-
Effects on the cerebrovascular system:
- One placebo-controlled study of some atypical antipsychotics in dementia-related psychosis showed an increase in cerebrovascular effects (eg stroke, TIA).
-
Depression in the CNS:
- It may result in CNS depression, which may impede both mental and physical function.
- It is preferable to avoid activities that call for mental attentiveness, such as operating machinery or operating a vehicle, if there are signs of CNS depression.
-
Dyslipidemia:
- Antipsychotics that are not typical may cause an increase in total cholesterol or triglyceride levels. Different products may have different incidence rates.
-
Aspiration/ oesophageal dysmotility:
- Antipsychotics may lead to oesophageal dysmotility or aspiration.
- Old age and conditions that increase the chance of aspiration pneumonia (eg Alzheimer disease) are risk factors.
-
Extrapyramidal symptoms
- Extrapyramidal symptoms can be caused by antipsychotics.
- These symptoms include tardive dyskinesia, acute dystonic reactions and pseudoparkinsonism.
- The incidence of EPS is much lower in antipsychotics than those that are more common or traditional.
- The use of conventional antipsychotics in men who are younger than those under their care may raise the risk of dystonia and other EPS.
- These are some of the factors that increase vulnerability to tardive dyskinesia.
- Old age
- Females who are postmenopausal
- Pseudoparkinsonism and Parkinson disease symptoms
- Affective disorders, especially major depressive disorder.
- Diabetes, prior brain injuries, alcoholism, and inadequate care are examples of concurrent medical disorders.
-
Falls
- It can cause motor or sensory instability, somnolence, orthostatic hypertension, and even falls.
-
Hyperglycemia
- Hyperglycemia can result from antipsychotics that are not typical. Diabetes can also be caused by hyperosmolar or ketoacidosis.
- It is not recommended for diabetic patients, or any other disorder of glucose regulation. Monitor blood sugar levels
-
Orthostatic hypotension
- Orthostatic hypotension can occur; be cautious in patients at greater risk, such as those who have been taking medication that could cause hypotension/bradycardia/hypovolemia.
- If you have a history of cardiovascular or cerebrovascular disease, use caution (myocardial Infarction, heart failure, conduction abnormalities, or myocardial infarction).
-
Neuroleptic malignant Syndrome:
- It can lead to neuroleptic malignant symptoms. Signs and symptoms include mental state changes, fever, rigidity of the muscles, and/or instability. NMS Monitor
-
Temperature regulation
- An antipsychotic may cause an impaired regulation of the core body temperature.
- Be careful with heat exposure, strenuous exercise, dehydration, heat exposure, and any concomitant anticholinergic medication.
-
Weight loss
- An antipsychotic could cause weight gain. Be sure to monitor your waist circumference, and your BMI.
-
Dementia:[US Boxed Warning]
- Antipsychotics have a higher death rate than placebo for dementia-related psychosis in the elderly.
- In the event of either severe or mild hepatic impairment, it should not be used.
- Patients suffering from Lewy body dementia and Parkinson's disease are more at risk for adverse effects.
- There is an increased sensitivity to extrapyramidal side effects. This can lead to irreversible cognitive decline or even death.
- Lumateperone is not approved to treat dementia-related psychosis.
-
Hepatic impairment
- Patients who are at high risk for seizures should receive cautious care.
-
Seizures
- Patients over 65 can be more vulnerable.
Lumateperone: Drug Interaction
|
Acetylcholinesterase Inhibitors (Central) |
Antipsychotic Agents' neurotoxic (central) effects might be amplified. In some cases, severe extrapyramidal symptoms have manifested. |
|
Alcohol (Ethyl) |
Alcohol's CNS depressing effect may be amplified by CNS depressants (Ethyl). |
|
Alizapride |
CNS depressants may have an enhanced CNS depressant impact. |
|
Amphetamines |
Antipsychotic Agents may diminish the stimulatory effect of Amphetamines. |
|
Antidiabetic Agents |
Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents. |
|
Armodafinil |
|
|
Blood Pressure Lowering Agents |
Could make antipsychotic drugs' hypotensive effects stronger. |
|
Brexanolone |
CNS Depressants may enhance the CNS depressant effect of Brexanolone. |
|
Brimonidine (Topical) |
May enhance the CNS depressant effect of CNS Depressants. |
|
Cannabidiol |
May enhance the CNS depressant effect of CNS Depressants. |
|
Cannabis |
May enhance the CNS depressant effect of CNS Depressants. |
|
Chlorphenesin Carbamate |
May enhance the adverse/toxic effect of CNS Depressants. |
|
Ciprofloxacin (Systemic) |
May increase the serum concentration of Lumateperone. |
|
Clofazimine |
May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). |
|
CNS Depressants |
Other CNS depressants' harmful or toxic effects might be exacerbated. |
|
CycloSPORINE (Systemic) |
May raise the level of Lumateperone in the serum. |
|
Deferasirox |
May lower the serum level of CYP3A4 substrates (High risk with Inducers). |
|
Deutetrabenazine |
Could intensify the negative or hazardous effects of antipsychotic drugs. Particularly, there may be a higher chance of developing akathisia, parkinsonism, or neuroleptic malignant syndrome. |
|
Dimethindene (Topical) |
Other CNS depressants' harmful or toxic effects might be exacerbated. |
|
Doxylamine |
CNS depressants may have an enhanced CNS depressant impact. Management: The producer of the pregnancy-safe drug Diclegis (doxylamine/pyridoxine) particularly advises against combining it with other CNS depressants. |
|
Dronabinol |
Other CNS depressants' harmful or toxic effects might be exacerbated. |
|
Erdafitinib |
May lower the serum level of CYP3A4 substrates (High risk with Inducers). |
|
Erdafitinib |
May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors). |
|
Esketamine |
Other CNS depressants' harmful or toxic effects might be exacerbated. |
|
FluvoxaMINE |
May raise the level of Lumateperone in the serum. |
|
Fosaprepitant |
May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors). |
|
Guanethidine |
Guanethidine's therapeutic impact may be diminished by antipsychotic medications. |
|
HydrOXYzine |
May enhance the CNS depressant effect of CNS Depressants. |
|
Ivosidenib |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). |
|
Kava Kava |
May enhance the adverse/toxic effect of CNS Depressants. |
|
Larotrectinib |
May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). |
|
Lithium |
Antipsychotic Agents' neurotoxic effects might be amplified. Lithium may lower the level of antipsychotic agents in the blood. Particularly relevant with chlorpromazine. |
|
Lofexidine |
CNS depressants may have an enhanced CNS depressant impact. Management: Separate drug interaction monographs go into further detail about the medications indicated as exceptions to this book. |
|
Magnesium Sulfate |
May enhance the CNS depressant effect of CNS Depressants. |
|
Methylphenidate |
Antipsychotic Agents may enhance the adverse/toxic effect of Methylphenidate. Methylphenidate may enhance the adverse/toxic effect of Antipsychotic Agents. |
|
MetyroSINE |
CNS Depressants may enhance the sedative effect of MetyroSINE. |
|
MetyroSINE |
May enhance the adverse/toxic effect of Antipsychotic Agents. |
|
Minocycline (Systemic) |
May enhance the CNS depressant effect of CNS Depressants. |
|
Nabilone |
May enhance the CNS depressant effect of CNS Depressants. |
|
Palbociclib |
May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors). |
|
Quinagolide |
Quinagolide's therapeutic effects may be diminished by antipsychotic drugs. |
|
Rufinamide |
CNS depressants' harmful or toxic effects could be increased. Particularly, drowsiness and lightheadedness could be worsened. |
|
Sarilumab |
May lower the serum level of CYP3A4 substrates (High risk with Inducers). |
|
Selective Serotonin Reuptake Inhibitors |
Selective serotonin reuptake inhibitors may have a worsened or more hazardous effect when taken with CNS depressants. Particularly, there may be an increased risk of psychomotor impairment. |
|
Serotonergic Agents (High Risk) |
Could intensify the negative or hazardous effects of antipsychotic drugs. Particularly, serotonergic drugs may intensify the effects of dopamine blocking, thus raising the danger of neuroleptic malignant syndrome. Serotonergic agents' serotonergic action may be enhanced by antipsychotic drugs (High Risk). Serotonin syndrome might occur from this. |
|
Siltuximab |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). |
|
Simeprevir |
May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). |
|
Tetrabenazine |
May enhance the adverse/toxic effect of Antipsychotic Agents. |
|
Tetrahydrocannabinol |
May enhance the CNS depressant effect of CNS Depressants. |
|
Tetrahydrocannabinol and Cannabidiol |
May enhance the CNS depressant effect of CNS Depressants. |
|
Tocilizumab |
May lower the serum level of CYP3A4 substrates (High risk with Inducers). |
|
Trimeprazine |
CNS depressants may have an enhanced CNS depressant impact. |
|
Risk Factor D (Consider therapy modification) |
|
|
Anti-Parkinson Agents (Dopamine Agonist |
The therapeutic benefit of second-generation [atypical] antipsychotic agents may be reduced (Dopamine Agonist). When possible, alternative antipsychotic medications should be used with Parkinson disease patients. If an atypical antipsychotic is required, clozapine or quetiapine may provide the lowest risk of interactions. |
|
Blonanserin |
CNS Depressants may enhance the CNS depressant effect of Blonanserin. |
|
Buprenorphine |
CNS Depressants may enhance the CNS depressant effect of Buprenorphine. Management: Consider reduced doses of other CNS depressants, and avoiding such drugs in patients at high risk of buprenorphine overuse/self-injection. Initiate buprenorphine at lower doses in patients already receiving CNS depressants. |
|
Chlormethiazole |
May enhance the CNS depressant effect of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used. |
|
Droperidol |
May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (eg, opioids, barbiturates) with concomitant use. Exceptions to this monograph are discussed in further detail in separate drug interaction monographs. |
|
Flunitrazepam |
CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. |
|
HYDROcodone |
CNS Depressants may enhance the CNS depressant effect of HYDROcodone. Management: Avoid concomitant use of hydrocodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. |
|
Lemborexan |
CNS depressants may have an enhanced CNS depressant impact. Management: Due to the possibility of additive CNS depressant effects when lemborexant and concurrent CNS depressants are administered concurrently, dosage modifications may be required. Effects of CNS depressants must be closely monitored. |
|
Mequitazine |
Mequitazine's arrhythmogenic action may be enhanced by antipsychotic medications. Management: When possible, look into alternatives to one of these agents. Despite the fact that this combination is not clearly contraindicated, mequitazine labelling states that it should be avoided. |
|
Methotrimeprazine |
The CNS depressing action of methotrimeprazine may be enhanced by CNS depressants. The CNS depressant action of CNS Depressants may be strengthened by methotrimeprazine. Management: Start concurrent methotrimeprazine therapy while reducing the adult dose of CNS depressants by 50%. Only once a clinically effective dose of methotrimeprazine has been established should additional CNS depressant dosage modifications be made. |
|
Opioid Agonists |
Opioid agonists' CNS depressing effects may be amplified by CNS depressants. Management: When at all possible, refrain from using benzodiazepines or other CNS depressants concurrently with opioid agonists. Only in the event that other treatment choices are insufficient should these medications be combined. Limit the duration and dosage of each medicine when used together. |
|
OxyCODONE |
CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. |
|
Perampanel |
May enhance the CNS depressant effect of CNS Depressants. Management: Patients taking perampanel with any other drug that has CNS depressant activities should avoid complex and high-risk activities, particularly those such as driving that require alertness and coordination, until they have experience using the combination. |
|
Sodium Oxybate |
May enhance the CNS depressant effect of CNS Depressants. Management: Take into account substitutes for combined use. Reduce the doses of one or more medications when simultaneous use is necessary. It is not advised to use sodium oxybate with alcoholic beverages or hypnotic sedatives. |
|
Stiripentol |
May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Use of stiripentol with CYP3A4 substrates that are considered to have a narrow therapeutic index should be avoided due to the increased risk for adverse effects and toxicity. Any CYP3A4 substrate used with stiripentol requires closer monitoring. |
|
Suvorexant |
CNS Depressants may enhance the CNS depressant effect of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. |
|
Tapentadol |
May enhance the CNS depressant effect of CNS Depressants. Management: Avoid concomitant use of tapentadol and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. |
|
Zolpidem |
CNS Depressants may enhance the CNS depressant effect of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. |
|
Risk Factor X (Avoid combination) |
|
|
Amisulpride |
Antipsychotic drugs may intensify Amisulpride's harmful or hazardous effects. Management: Separate drug interaction monographs go into further detail about the medications indicated as exceptions to this book. |
|
Azelastine (Nasal) |
CNS Depressants may enhance the CNS depressant effect of Azelastine (Nasal). |
|
Bromopride |
May enhance the adverse/toxic effect of Antipsychotic Agents. |
|
Bromperidol |
May enhance the CNS depressant effect of CNS Depressants. |
|
Conivaptan |
May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). |
|
CYP3A4 Inducers (Moderate) |
May lower the level of Lumateperone in the serum. |
|
CYP3A4 Inducers (Strong) |
May lower the level of Lumateperone in the serum. |
|
CYP3A4 Inhibitors (Moderate) |
May raise the level of Lumateperone in the serum. |
|
CYP3A4 Inhibitors (Strong) |
May raise the level of Lumateperone in the serum. |
|
Fusidic Acid (Systemic) |
May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors). |
|
Idelalisib |
May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors). |
|
Metoclopramide |
May enhance the adverse/toxic effect of Antipsychotic Agents. |
|
Orphenadrine |
CNS Depressants may enhance the CNS depressant effect of Orphenadrine. |
|
Oxomemazine |
May enhance the CNS depressant effect of CNS Depressants. |
|
Paraldehyde |
CNS Depressants may enhance the CNS depressant effect of Paraldehyde. |
|
Piribedil |
Piribedil's therapeutic effects may be diminished by antipsychotic drugs. Piribedil may lessen an antipsychotic agent's therapeutic impact. Treatment: Piribedil should not be used in combination with antiemetic neuroleptics and is not advised to be used with antipsychotic neuroleptics, with the exception of clozapine. |
|
Probenecid |
May raise the level of Lumateperone in the serum. |
|
Sulpiride |
Antipsychotic drugs may intensify the hazardous or harmful effects of sulpiride. |
|
Thalidomide |
CNS Depressants may enhance the CNS depressant effect of Thalidomide. |
|
Valproate Products |
May increase the serum concentration of Lumateperone. |
Monitoring Parameters:
- Mental health
- Vital signs:
- Clinically indicated
- BP:
-
Repeat the procedure three months after starting antipsychotics at baseline then every year.
-
- Weighing, height, BMI and waist circumference
-
Repeat at baseline, 4, 8, and 12 weeks after starting or modifying therapy then once a year.
- If you suffer a weight gain of greater than 5% from your starting weight, think about switching to another antipsychotic.
-
- CBC:
- Clinically indicated
- For the first several months, patients who have low WBC or a history of drug-induced neutropenia or nephenia should be closely watched.
- Liver function and electrolytes:
- Annually and as clinically indicated
- HbA 1c fasting blood sugar levels
- Baseline, follow-up three months after starting an antipsychotic, and then annually
- Fasting lipid profile
- Baseline, repeat after three months, and if your low-density lipoprotein levels are normal, repeat as often as every two to five years or more, as clinically necessary.
- Changes in menstruation and libido.
- Annual
- Parkinsonian signs or abnormal involuntary movements
- Baseline, weekly for at least two weeks after introduction, and for no more than two weeks after any large dose increases, until dose stabilisation is attained.
- Tardive dyskinesia
- Every 12 months; High-Risk Patients every 6 months
- Ocular examination
- Younger patients may attend once every two years; people over the age of 40 may visit annually.
- Fall risk
- Baseline and regularly during therapy, particularly if there are any conditions or concurrent drugs that could make a patient more likely to fall.
How to administer Lumateperone (Caplyta)?
Oral: take with food (calorie or fat content not specified).
Lumateperone (Caplyta) Mechanism of action:
- There is also lumateperone, a second-generation antipsychotic.
- Both the central 5-HT2A and D2 dopamine receptors are blocked by it.
- With a high binding affinity to serotonin 5-HT2A receptors and a moderate binding affinity to dopamine D2 receptors, lumateperone is a variable binding agent.
- Although lumateperone has a low affinity for muscarinic or histaminergic receptors, it has a considerable affinity for dopamine D1 and D4 receptors as well as adrenergic beta1A and alpha1B receptors.
Absorption
- High-fat meals increase the AUC by 9% while decreasing the mean C maximum by 33%.
- The median T max delay in the presence of food is 1 hour (from 1 to 2 hours fasted).
Protein binding
- Plasma: 97.4%
Metabolism
- It is subject to extensive metabolism and can be converted by more than 20 enzymes to a variety of metabolites.
- These enzymes include cytochrome P450 3A4, 2C8, 1A2, uridine 5-diphosphoglucuronosyl-transferases, UDP-glucuronosyltransferases 1A1, U4, and 2B15, aldoketoreductases 1C1 and 1B10, and a few more.
Bioavailability:
- 4.4%.
Half-life elimination:
- ~18 hours after intravenous administration;
- with the oral route, steady-state is reached in ~5 days.
Time to peak:
- 1 - 2 hours.
Excretion:
- Urine: 58% (<1% as unchanged drug)
- feces: 29%.
International Brand Names of Lumateperone:
- Caplyta
Lumateperone Brand Names in Pakistan:
No Brands Available in Pakistan.
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