Caplyta
Caplyta
Generic Name
Caplyta
Mechanism
Caplyta (generic *lumateperone*) is a novel, *selective dopamine D₂/D₃ receptor antagonist* and *5‑HT₂A receptor antagonist* with *partial agonist* activity at *5‑HT₂C* receptors. Its unique profile also modulates glutamatergic neurotransmission by influencing neuronal calcium‑dependent signaling, thereby providing antipsychotic efficacy with a low risk of extrapyramidal symptoms (EPS).
Pharmacokinetics
| Parameter | Typical Value | Notes |
| Absorption | Rapid, peak concentration (Cmax) ~2 h post‑dose. | Food may slightly delay absorption but not reduce AUC. |
| Distribution | ~90 % protein binding (primarily to albumin). | Volume of distribution = 200 L. |
| Metabolism | Majorly via CYP3A4 (also minor CYP2D6). | Metabolites inactive; no major drug‑drug interactions via CYP2D6. |
| Elimination | Renal excretion of unchanged drug and metabolites; terminal half‑life ~17 h. | Dose adjustment not routinely required for mild‑moderate renal impairment. |
| Drug‑Drug Interactions | Inhibitors/inducers of CYP3A4 alter serum levels. | Eg,ketoconazole ↑ → ↑AUC; rifampin ↓ → ↓AUC. |
Indications
*Treatment‑emergent schizophrenia* (both acute and maintenance phases) in adults.
Contraindications
- Contraindicated in patients with hypersensitivity to lumateperone or formulation excipients.
- Warnings:
- *Neuroleptic malignant syndrome (NMS)* – low incidence but monitor for rigidity, hyperthermia, autonomic instability.
- *Weight gain & metabolic dysregulation* – monitor weight, fasting glucose, lipids.
- *Cardiac arrhythmias*: not QT‑prolonging; still monitor baseline ECG in patients with pre‑existing conduction disease.
- *Pregnancy*: Category C; use only if benefits outweigh risks.
Dosing
- Initial dose: 41.5 mg orally once daily (usually taken in the evening).
- Maintenance: May titrate up to a maximum of 83 mg once daily based on efficacy and tolerability.
- Administration: Administer with or without food.
- Short‑term discontinuation: No benzodiazepine or rapid dose taper required.
Adverse Effects
**Common (10 % of baseline body weight
• New onset or worsening diabetes mellitus
• Orthostatic hypotension
• Seizure (rare)
Monitoring
| Parameter | Frequency | Rationale |
| Weight & BMI | Every visit (≥3 mo) | Detect weight gain |
| Fasting glucose & HbA1c | Baseline, then every 3–6 mo | Metabolic monitoring |
| Lipid profile | Baseline, then annually | Hyperlipidemia risk |
| Blood pressure | At each visit | Orthostatic hypotension |
| ECG (QTc) | Baseline if cardiac risk factors | Rare arrhythmias |
| CBC & LFTs | Baseline, then annually | General safety profile |
Clinical Pearls
- Low EPS risk vs. traditional antipsychotics: Ideal for patients with Parkinsonian side‑effects or those intolerant to high‑dose typical agents.
- Minimal CYP3A4 overlap: Allows safe co‑administration with many antidepressants and benzodiazepines without clinically significant drug interactions.
- Rapid onset of action: Peak plasma levels within 2 h; consider this when managing acute psychotic exacerbations.
- Dosing simplicity: Fixed once‑daily dose simplifies adherence in outpatient settings.
- Weight management counseling: Although weight gain is lower than first‑generation antipsychotics, proactive lifestyle advice remains essential.
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• *Caplyta* delivers effective antipsychotic control with a favorable side‑effect profile, making it a valuable option for modern psychiatric practice.