Invega
Invega
Generic Name
Invega
Mechanism
- Primary action: Potent, high‑affinity antagonist at dopamine D₂ and serotonin 5‑HT₂A receptors, producing antipsychotic effects while minimizing dopamine blockade in the nigrostriatal pathway.
- Secondary receptor activity:
- Moderate affinity for D₃, D₄, and 5‑HT₂C receptors (modulates mood and cognition)
- Antagonism at α₁‑ and α₂‑adrenergic receptors (contributes to orthostatic hypotension)
- No activity at muscarinic or histamine H₁ receptors, explaining lower sedation relative to other atypicals.
Pharmacokinetics
| Feature | Details |
| Absorption | Oral bioavailability ~ 30 %, prolonged by pH‑dependent precipitation; dose delayed 4–5 h. |
| Distribution | Vd ≈ 1.0 L/kg; protein binding 90 % (mainly to α‑1‑acid glycoprotein). |
| Metabolism | Minimal hepatic metabolism. Primarily excreted unchanged via kidneys. Enzyme: CYP2D6 (minor). |
| Half‑life | 23–43 h (oral); 22–45 h (LAI). |
| Excretion | 70–80 % unchanged in urine. |
| Special Populations | Renal impairment: Dose reduction required (see dosing). Hepatic impairment: No clinically significant adjustments. |
Indications
- Adults & adolescents (≥13 yrs): Acute schizophrenia, schizophrenia maintenance, and schizoaffective disorder (positive/negative symptom control).
- Pediatric (≥6 yrs): Short‑term acute psychotic episodes in acute settings.
- LAI formulations: Chronic schizophrenia requiring adherence support.
Contraindications
| Category | Key Points |
| Contraindications | Hypersensitivity to paliperidone or any excipient. |
| Warnings |
• Metabolic syndrome – monitor weight, glucose, lipids. • QT prolongation – caution in patients with congenital long QT, electrolyte disturbances, or concurrent QT‑prolonging drugs. • Neuroleptic malignant syndrome (NMS) – rare but life‑threatening; watch for hyperthermia, rigidity. • Tardive dyskinesia – risk increases with cumulative dose; periodic screening. • Renal dysfunction – dose adjustment essential. • Seizures – rare; contraindicated in uncontrolled seizures. |
Dosing
| Form | Starting Dose | Titration | Maintenance | Max Dose | Notes |
| Oral XR (25 mg/18 mg) | 6 mg once daily (25 mg/18 mg tablets) | 2–3 mg increments every 2–4 weeks | 8–12 mg daily (usually 10–12 mg) | 12 mg | Take with minimal food. |
| LAI (Sustenna 150 mg IM) | 150 mg IM q2 mo | Dose adjustment after 2 mo if needed | 150 mg IM q2 mo | 180 mg IM (max) | Rapid‑release equivalent to ~10 mg/day. |
| LAI (Trinza 400 mg IM) | 400 mg IM q3 mo | Adjust after 3 mo | 400 mg IM q3 mo | 500 mg IM | Equivalent to ~12 mg/day. |
| Renal impairment | CKD G3: 4 mg daily; CKD G4–5: 2 mg daily | Slow titration, avoid >8 mg | ≤8 mg (or 4 mg if severe) | 8 mg | Monitor creatinine clearance every 4–6 weeks. |
> Tip: Use the 25 mg/18 mg tablet split in half for lower initial doses (6–8 mg).
Adverse Effects
| Class | Common | Serious |
| Extrapyramidal (EPS) | Akathisia, mild tremor | Neuroleptic malignant syndrome, tardive dyskinesia |
| Metabolic | Weight gain, hyperglycemia, dyslipidemia | Diabetes mellitus, cardiovascular events |
| Cardiovascular | Orthostatic hypotension, QTc >450 ms | Arrhythmias, sudden cardiac death |
| Endocrine | Elevated prolactin (variable) | Gynecomastia, galactorrhea |
| Other | Somnolence, dry mouth, blurred vision | Seizures (rare), agranulocytosis (very rare) |
Monitoring
- Baseline: CBC (rare), fasting glucose, HbA1c, lipid profile, weight, BMI, waist circumference, BP, ECG (if QT risk).
- Ongoing:
- Every 3–6 months: weight, BMI, fasting glucose, lipids.
- Every 6–12 months: ECG if QTc >450 ms or on QT‑prolonging meds.
- Renal function: Every 2–3 months (or sooner if significant change).
- Clinical: Monitor for EPS, akathisia, mood changes, suicidality.
Clinical Pearls
- Depot Advantage: Invega LAI delivers steady plasma levels, reducing peak‑trough fluctuations that drive EPS and medication non‑adherence.
- Renal Dosing: Paliperidone’s renal excretion means even mild CKD (CrCl 30–49 mL/min) necessitates a 50 % dose reduction; in severe CKD, the LAI form is not recommended.
- Psychosis Rescue: Because of its low sedative profile, paliperidone can be initiated in an acute psychotic setting without high risk of overdose‑related respiratory depression.
- Metabolic Monitoring: Despite being less lipogenic than clozapine or olanzapine, paliperidone still contributes to weight gain; early lifestyle interventions are key.
- Drug Interaction Alert: Co‑administration with strong CYP2D6 inhibitors (e.g., fluoxetine) has minimal impact; however, high doses of strong CYP1A2 inducers (e.g., carbamazepine) can lower paliperidone levels – adjust dose accordingly.
- Patient Education: Emphasize the importance of taking the oral drug the same time every day to maintain therapeutic trough levels.
Invega remains a reliable choice for both acute and maintenance therapy in schizophrenia, offering a favorable balance between efficacy and tolerability when used with vigilant monitoring and individualized dose adjustments.